Panel Session II: Foundation Support for CAM Research
MS. CHANG: We are going to go ahead and move on to the next session for this agenda. Dr. Bridget Duffy, Dr. Doriane Miller, Susan Braun, and I think we have a substitution for Ron Chez, Susan Samueli speaking for Ron Chez. DR. GORDON: Welcome. We will begin with Bridget Duffy.Presenter: M. Bridget Duffy, M.D.
DR. DUFFY: Thank you for inviting me. I enjoyed meeting some of you in Minnesota. Was it a month ago when you were there for the Town Forum? It was great to get here today, because it is 99 degrees in Minnesota this morning. Today, in Minnesota, the nurses vote whether to strike, and I bring this up because it is very pertinent to what I want to talk about today with you. Most believe that they will strike, and if they strike, they will walk on May 31st. I was asked a few months ago to come and speak to the nurses at the largest hospital in Minnesota, on May 31st coincidentally, and they called me yesterday to confirm my title and to ask me what my objectives would be. In lieu of this potential strike and walkout on the day that I am speaking to them, I changed my title. The original title was, "The Use of Complementary and Alternative Therapies in the Nursing Practice," and I changed my title to read, "Restoring Healing to Health Care: The Crucial Role of Nurses". Now, I think what is at the core of the writ, of the issue that they have in health care today, and the reason they may strike, is not what the papers would have you believe, just money, but it is about the loss of their profession as a healing profession. It is the loss of a relationship with themselves, with their patients, with the ability to provide the healing services and care that they know impacts their patients. So, their issues form the basis of my comments and my recommendations to you today, and I believe that the interest and the use of complementary alternative therapies is a symptom of a much deeper issue in medicine, and through my work, through the Medtronic Foundation, and in my collaboration with other foundations and philanthropists, we are seeking to change this. So, what I would like to do in the few minutes that I have with you is talk about four things. I would like to tell you what we are seeking to do to change medicine, how we will do it, what are the obstacles we have encountered, and what are our recommendations to you. So, what are we seeking to do? We are seeking -- and as you asked me in the first question, which is included in your handout -- is our foundation funding complementary alternative medicine research, and my answer was that we are not supporting the study of specific CAM modalities, rather, we are seeking to support research efforts that are identifying the best clinical care models to improve the lives of people with chronic disease. Now, Medtronic, for those of you who don't know who the company is, is the world's largest device company, makes implants for the brain and for the heart. There are 22,000 employees worldwide, and we make devices for Parkinson's, for every aspect of heart disease. So, the people that we serve are quite large. As you know, heart disease is the number one killer in the United States with neurologic conditions expected to surpass that in 10 years. So, our goal is to transform the way we care for people with chronic disease. Medtronic believes and due to an enlightened founder and CEO that it is not enough to just crack a chest, put in a valve, and send a person home in four days, or to put a burr whole in the brain and put an implant in to stop the tremor and send him home in two days. We believe that there is much more to healing and that we, as a device company, needs to play a role in shaping what that model looks like. So, how will we do it? Point No. 2. We could wait for government and academia to redesign or overhaul the medicine, but we decided we would find those who we felt could just go build it. So, through philanthropy, we are seeking people that have vision and leadership in place to build these models of care, and that is because I am impatient and so is the founder of my company and the current CEO. In fact, Earl Bakken, who invented the pacemaker 50 years ago, said to me, "Bridget, 25 years ago I wrote a paper called Vision 2010: The Hospital and Health Care of the Future," and it was about the incorporation of alternative therapies and creating a healing environment, and he said, "It took me 20 years to get them to even start listening to me." I said to him, "Earl, I don't have 20 years, we are going to do this much more quickly." So, how we are seeking to do that is that Medtronic's main customers are heart patients and brain patients, so our customers are neurosurgeons and heart surgeons that implant these devices. So, I decided to target these folks. We know that nurses and family docs and internists usually get this, they usually know what it takes to heal. We decided to go to this group of individuals to have them help us build the models. Hierarchically and financially within the institutions, these people run the hospital. So, we realized that if we could get and identify some champions in these fields, that we could ask them to build these models, and we would have a ripple effect across the country. So, we have identified some of the top academic centers and clinical centers across the country, and we are supporting several of them, and the number will be growing, as David Eisenberg alluded to. Now, how do we identify them? We had institutional and programmatic criteria. I will tell you briefly some of the criteria, that we really wanted them to have a strong research infrastructure because we believe without the data, people will not adopt these behaviors. Secondly, they had to have the ability to implement and apply these therapies in a clinical setting. So, we targeted specific cardiac and neurologic diseases, so that some of the centers to date that we have funded are Duke, Harvard, Stanford, Scripps, Alina Health Care Systems, St. Barnabas, Beth Israel, New York, with several others that we are investigating. The first year and a half we focused on cardiovascular disease. This year we are focusing on neurologic, and we specifically are looking at pain. So, as an example of the way we are using our dollars in philanthropy is at Beth Israel in New York, they have the top pain guru who sits within the Beth Israel campus and 20 blocks away they have the leader in integrative healing within the same health care system, and with our dollars we have asked them to work together and to build an integrative model of pain management. My ultimate goal is across the country, through our support, we will build integrative centers of excellence around specific disease and device entities, so that you could look on the Internet or a patient could find the integrative center of excellence for pain, the integrative center of excellence for coronary artery disease, et cetera. So, through, as Dr. Eisenberg alluded to, I think the most important thing about our funding of these centers is that all of them have said to us we are not just interested in your dollars, we are interested in true collaboration among the centers, because there is nothing more frustrating to me than to see 10 different spirituality surveys or 30 different proposals on whether guided imagery works, and 10 different ways to measure pain and anxiety, and there is no ability to pool the data at these different centers. So, they have agreed to do three things - to share a common database, to share common assessment tools, and to share in the dissemination of the findings, so that others might learn. Lastly, and most importantly, they have agreed to collaborate in the training of future leaders on healing. By this, I don't mean setting a medical school curriculum on how you teach people which herb works, how it works, sort of like memorizing the Kreb's cycle or the mechanism of action, but rather how do you teach people what the core principles and values are around healing and how you apply these therapies. As an example, to demonstrate how we are hoping to disseminate these findings, this is not anything I am pushing, but this is the brochure that I will leave behind from the American College of Cardiology, the first conference ever on the integration of complementary medicine in a traditional cardiology practice. One of the participants here said to me he never thought in his lifetime he would see the ACC sponsor a meeting on this subject. So, in this program, the CEO of Medtronic will be the keynoter and then I will have a panel where we profile the centers that we have funded to date, but I think that's miraculous. We have a long way to go, though. Third, what are our obstacles? My greatest obstacle is not the absence of data, and personally and professionally, inside Medtronic, my greatest obstacle is the perception that I am about building alternative clinics. I believe that what I have found is the greatest obstacle as I talk around the country to people who have built these models or are trying to build them, I ask them, what is your greatest obstacle, and they tell me it's, number one, the physicians -- and I am one -- and number two, the administrative leaders. So, I could not agree more with what Dr. Eisenberg said about the need to have an institution or an entity that can train current faculty and future leaders and administrators of these health care systems that can help us get the adoption of these models into place. So, what are our recommendations to you? I have five brief recommendations. The first would be to broaden your mission and your focus to include study of the delivery mechanism or the context in which this care can be delivered. First is just the safety, efficacy, licensure. We are trying to do that through the centers that we are working with, and I will talk about further, we would like to figure out a way to collaborate with the work that you are doing. Secondly, I would eliminate terminology that will exclude or delay the adoption of these healing practices. I believe those words are alternative and complementary. When I work with these cardiologists, these neurosurgeons, and they hear that I am coming to a committee like this or hear these terms, they run for the hills. So, I think that there is a need to establish something like an academy for health and healing, and under that are boards and panels that look at the safety and efficacy, licensure, et cetera. Third, I would create a vehicle or a mechanism to keep informed of the work that philanthropy is supporting. There has got to be a way that we can communicate and relay the information of the best practices or the findings that we know about. Fourth, I would establish an entity, a committee or academy, that then takes these findings and proactively works to shape policy and reimbursement. Lastly, I would recommend that you seek and support educational initiatives that foster a new breed of leaders who can drive the adoption of these best practices, thereby allowing patients access to the best that medicine has to offer. Thank you for your time and thank you for the invitation to be here. DR. GORDON: Thank you. Thank you for your precision and concision. Doriane Miller, welcome back.Presenter: Doriane Miller, M.D.
DR. MILLER: Thank you, Dr. Gordon. Yesterday, I had the opportunity to talk with you a little bit about minority and under- and uninsured issues regarding CAM, and today, I would like to put on a slightly different hat, and that is the role that I serve at the Robert Wood Johnson Foundation as Director of the Program Development and Grantmaking in the area of clinical care management. For those of you who are unfamiliar with the Foundation, the Robert Wood Johnson Foundation was established as a national philanthropy in 1972, and is dedicated to the health and health care of people in the United States. We fund programs in three major areas - increasing access to health care services, providing care and support for people with chronic health conditions, and reducing the harm from substance use. From an asset base of approximately $8 billion, we will fund about $400 million in grants this year only in the area of health and health care. In preparation for my testimony today, I reviewed the Robert Wood Johnson Foundation's grantmaking in the area of CAM for the committee. You will find in your packets a summary of selection of those grants, which I think actually range pretty much across the board in terms of the area. However, for the purposes of the discussion today, I think that it would be helpful for the Commission to hear a little bit about how our philanthropy and actually many other health philanthropies think about strategic decisionmaking when making decisions about what projects to fund. In my opening comments, I mentioned many areas of Robert Wood Johnson Foundation, but within these broad goals, narrower focused areas help Foundation staff to direct their programmatic development and grantmaking, and also helps grant applicants to understand our strategic priorities. Within these areas, staff link program development and grantmaking to measurable strategic objectives. We based our program development and funding decisions on a specific project's ability to contribute to achieving the strategic objectives. The Foundation funds projects that use the tools of research and policy analysis, demonstration, education, and training, communications and evaluations to achieve those strategic objectives. The area that I am responsible for is the clinical care management area at the Foundation, which is designed to narrow the gap between what is known and what is practiced in health delivery systems today for people with chronic medical conditions. We attempt to effect change in three strategic areas - change in purchaser behavior to support the delivery of evidence-based medicine, improving delivery system capacity to provide evidence-based medicine, and also engaging people both as consumers and also as patients to become more involved in evidence-based medical care. The projects that we funded are both cross-cutting in terms of those strategic elements that I mentioned, but also disease specific. Some examples of these projects include a project in Adina, Minnesota, that has developed a protocol for depression screening in an adult day center, a project in Lafayette, Colorado, that is working to improve community resources to support chronic illness self-management within a low-income, Spanish-speaking population, and a project at the Medical University of South Carolina that is testing the benefit of group visits for low-income people with Type 2 diabetes. The focus that I want to make here is that we have not a basic science focus or even looking at best practices, but much more of a translational agenda, and that is looking at ways in which we can take evidence-based and translate it into implementation on a widespread basis. How does this translational agenda affect our view of funding CAM research? If there were sufficient evidence that a particular CAM approach to treatment could positively affect the outcome of a treatment of a condition we are targeting, we would consider funding CAM as a part of a total program or system of care. CAM is not currently an area of strategic funding for the Robert Wood Johnson Foundation, nor are we considering making it a funding priority for the Foundation. To the extent that current and future CAM research and implementation could help to make improvements in our strategic funding areas, however, we would consider funding CAM on a case-by-case basis. The Robert Wood Johnson Foundation has tremendous experience in the area of convening, training, and demonstrations in the health field. We had the opportunity to collaborate with the Medtronic Foundation just this summer on a project that looked at issues around patient empowerment and consumer activation. If we chose to become more active in the area of CAM, we would draw upon these experiences to help stimulate more activity and interest in CAM, and we would also welcome public and private funding partners in this endeavor. Thank you for your time. DR. GORDON: Thank you very much. Susan Braun, nice to see you.Presenter: Susan Braun
MS. BRAUN: Good morning. Thank you for inviting us to speak. I am Susan Braun. I am CEO of the Susan G. Komen Breast Cancer Foundation, which was started in 1982 by Nancy Brinker in honor of the memory of her sister who was Susan Komen, who died of breast cancer at the age of 36. Since that time, we have grown from just a group of a few people who have an interest in what breast cancer does to men and women with the disease, into a network now of 115 affiliates in the United States, in 45 of our 50 states, and we have three international affiliates. We have about 70,000 active volunteers, and to date we have raised more than $400 million towards our mission, which is to eradicate breast cancer through research, education, screening, and treatment. I will talk a little bit about our own approaches to CAM and what we are looking towards in the future, but I also want to point out one way in which our foundation model is perhaps uniquely suited to address some of the questions that we are needing to address here, and that is because our primary base, our primary group of constituents are the public. For example, our Race for the Cure events, which are our major fundraiser, although by no means our sole fundraiser, will have more than a million participants this year, and our corporate sponsors are million dollar council members are Kelloggs and G.E. and Lee Jeans and American Airlines, Ford, a lot of large corporations like that, and yet we are the largest private funder of breast cancer research. We fund a great deal of basic clinical and translational research, to date more than $68 million we have put into those programs, and pretty much following the model that Dr. Eisenberg put forth and which you all are familiar with within the academic institutions of the United States and around the world. So, we really bridge that gap between who the public is, what the public wants, and then research that have followed those interests of the public, so much of our determination as to what we will be funding comes from the public interest, although it is driven certainly in terms of which proposals are accepted by peer-reviewed processes and by the scientific community. Our choices as to what we will fund are very, very much driven by the public, and they are driven by an interest in filling gaps, in doing what isn't being done by someone else out there and doing things that we are particularly well suited to do. Another thing, too, about Komen is we really didn't get to where we are today by following the status quo. Although somehow we have become a real major player in grantmaking, it wasn't because that is what we sought to do, but it was really because we followed the emotions, the needs, and the demands of the public, and the public is not accepting that breast cancer doesn't have answers yet, just as they aren't accepting that cancer doesn't have answers yet, and that is what continues to fuel what we do. So, we plan to continue to ask all of the difficult questions, both those inside and outside of the proverbial box. We also are pretty aware of most of the statistics and surveys that have been done and particularly one that looked at cancer patients, finding that 50 percent of those patients who were surveyed did combine complementary and alternative modes of care with their conventional care, but also that breast cancer patients are more likely than other cancer patients to use complementary and alternative medicines and/or therapies, and we find again and again and again without constituency base this interest and this need in continuing with these therapies, but also in understanding them better scientifically. So, I believe that one of the things that we need to help do, and will do, is identify the dichotomy that was pointed out between people, the public wanting to have proven therapies, wanting to have data, but yet also interestingly a willingness to continue along with something that has not been proven, and I think we are in a good place to help identify and understand that dichotomy. You had asked about our specific endeavors within the field of complementary and alternative medicine, and we do have now in last year's portfolio, which was $19.2 million in grants, and this is just within our structured grant programs. We also have thousands and thousands of community programs that we fund that are educational and outreach programs. We funded over a million dollars in complementary and alternative, within that part of the portfolio, and then also programs within the community, such as wellness and improvement in quality of life. One of the things, for example, that I wanted to highlight within our portfolio is research that is being done on black cohosh. I think many of you are familiar with some of the recent reports that identify that this substance might have estrogenic properties. Breast cancer survivors and those who are either at risk of breast cancer or who fear breast cancer, whether they are truly at higher risk than the average or not, are increasingly reluctant about taking estrogen replacement therapies although a definitive link to breast cancer is still debated. So, we find, for example, not only in patients, but in well women who either fear or are at high risk for the disease are not going to take estrogen, so they will look to alternatives. Well, we have also begun to recognize, for example, that with black cohosh, there is a concern about is it tumorigenic or does it cause the lining of the uterus, for example, to expand, and so we are funding a study that is being done by Vicky Davis at Cedars-Sinai Medical Center that will look at black cohosh, and that will look at its activity particularly in the breast and whether or not it does accelerate breast tumor development. We are also, though, looking more and more, not only in our funding, but also in the programs that we are a part of or that we fund in the community, at areas such as spirituality and other forms of healing that are not necessarily invasive. We have recently had Larry Daucy [ph] come and speak to a group of us in Dallas as a part of a lecture series that we helped to fund, and I think what is so fascinating -- and I sat in as he spoke to the medical staff at Baylor, and he spoke to our folks, so he spoke to a number of audiences -- and what is fascinating to me in this, and as I have spoken about his visit since then -- I do a lot of public speaking -- how it grabs the attention of everyone there. I spoke to a large group in Little Rock late last week, and when I began to talk about that and what Larry Daucy had done, the room was perfectly silent, and afterwards -- and I had talked about many things, I spoke for almost 45 minutes -- and that is what people came up to, wanted to share their stories and talk to me about. So, there is this huge groundswell clearly of interest, and rather than go on too much further with all of this, because you have my remarks, a couple of recommendations that I would like to make specific to what we have been finding and to the public interest that we are seeing around us is working with patients, and it is something that we will be funding more to, talking to patients and talking to consumers who have a high health care interest, about that dichotomy that was pointed out earlier and what it is that we need to find out in that, not necessarily just how do we close that gap, but what is that telling us. I think, too, especially as we talk to cancer doctors, I was at the American Society of Clinical Oncology meeting that is taking place this week in San Francisco, 28,000 very mainstream cancer professionals, and one of the areas that they are most concerned with, of course, is medical interactions, what is going on with the things that patients ingest as they are having chemotherapy, radiotherapy, for example. So, we would like to suggest a strong differentiation between those things that are ingested or at least that -- can I finish my sentence -- DR. GORDON: Go ahead. MS. BRAUN: -- but that have a potential for a toxic effect compared to those that have a more complementary or a potential for a healing effect in a different way, so the differentiation. Also, I think as I sit here with, in the world of not-for-profit funding, a funder's consortium, bringing together funders to say what are you doing compared to what are you doing, what are you doing, so that we are doing things in ways that work together as opposed to reinventing wheels. Then, I think, very importantly, when we talk about what isn't there in basic science, there has been no question from our experience in the funding of breast cancer research, both our own and then what has happened at the National Institutes of Health, the Department of Defense, and other funders, that the basic scientists really do, as they choose their career, look at where they are going to be able to be funded, so that they continue the science that they want so desperately to study. Our Young Investigators program and our Fellowship programs have demonstrated that in spades, so I think it would be very important if we want to see more basic research, to fund young scientists who are interested in the field. Thank you very much. DR. GORDON: Thank you very much. Susan Samueli. Welcome.Presenter: Susan Samueli
MS. SAMUELI: Thank you very much, and I am very honored to be here today. After spending 20 years of studying homeopathy and nutrition, I am very excited that the government is beginning to focus much more in this area. I would like to spend my time today before you to share with you the vision and the history of the Samueli Foundation and the Samueli Institute for Information Biology. The Samueli Foundation was created by my husband and myself as a way to express our philanthropic interest. My husband, Dr. Henry Samueli, while a Professor of Electrical Engineering at UCLA, was successful in creating broadband technology, which eventuated in his co-founding the company Broadcom, Inc. The success of this company has brought us great wealth, and it is our privilege to return a good portion of this to our community in the forms of grants and gifts. Through our foundation, we have funded various projects and programs in the areas of education, religion, social services, and fine arts, but because of my passion for the study of alternative and complementary medicine, we are committed to support scientific research that will affirm the credibility that this field so deserves. Much of the public is utilizing various modalities and interventions that are placed under the complementary medicine umbrella. Current documentation and evidence support that not only is this happening in the United States, but in Europe, as well. We believe there is a critical need to obtain valid, accurate, clinical information for the public's decisionmaking. In my opinion, there are two problems. The first is a lack of acceptance by most physicians towards the research and use of complementary medicine, and the other is the lack of basic and clinical research in this country. Researchers are not responding to the public who are utilizing complementary medicine without benefiting from clinical and scientific studies. Because we feel this is so important, the Samueli Foundation has funded two major programs. The first, we created the Susan Samueli Center for Complementary Medicine at the University of California in Irvine. The center status was awarded in December 1999, and we are presently in the second full year of operation. The mission of the center is twofold. One is to focus on high quality scientific research, and the other is the education of medical students, health care professionals, and the community about complementary medicine. There are two key approaches to the research component. One is the awarding of competitive grants in basic research and complementary and alternative medicine to members of the faculty of the College of Medicine. These projects are expected to be focused on integrative biology and outcomes research that have direct clinical applicability. Amounts of up to $100,000 can be awarded and thereby serve as seed money. The intent is to help the investigator develop enough preliminary data to strengthen subsequent proposals submitted to other research-funding agencies, such as the NIH. The response of the faculty to this opportunity has been impressive. Nineteen applications were received in February 2000, of which the peer review committee awarded 6. This calendar year, 14 grants were submitted, and 5 were awarded. The other key approach is the research component in the creation of an analysis unit team. This group conducts systematic reviews of the literature, assessing all of the various media now available for the purpose of identifying and writing a variety of complementary and alternative therapies. Their findings are archived with the potential for dissemination to both health professionals and the public. The education aspect of the center also has both a public and a health professional purpose. The latter includes a commitment to curriculum development for medical students, integration of complementary and alternative medicine skills and knowledge into the appropriate primary care residency programs and an annual symposium for the medical and nursing community. The public education programs provide information through a combination of community forums, a website, and position papers, which analyze research reports. Now to our second major effort. This has been our creation of the Samueli Institute for Information Biology. This institute is currently being created as a free-standing entity without direct or indirect affiliation with any other academic or other nonprofit organization or facility. We anticipate it will be operational July 1st of this year, and you have in your notebooks a single-page handout, which is the current vision statement of the Samueli Institute. As you know, Dr. Wayne Jonas, a member of this commission, will be the director of the institute, and Dr. Ronald Chez, who is here with me today, will be the deputy director. At the present time, these two physicians serve as consultants while completing their tenure and full-time academic positions in their respective medical schools. Per the handout, we are using the term "information biology" to refer to the interaction of biological systems with non-molecular signals, particularly those signals which are separated from their molecular and electromagnetic carriers. The five bullets indicate the major categories under that definition. We will not be exclusively focusing on supporting research only in complementary medicine, rather, research in these categories lend themselves to overlapping between complementary and conventional basic science. For instance, conventional science research could include biophysics, cell signaling, and neuroscience. The primary purpose of the institute will be to support basic research in the four areas noted under the heading of Science and Discoveries. We are particularly interested in supporting the work of senior authoritative investigators who have a proven track record in their respective areas of research. We believe these grants could be as long as three to five years and be designed in such a way that they investigators can enjoy a relative freedom of exploration as a research evolves. Initially, we will be soliciting grant applications from a number of colleagues with whose work we are familiar. These applications will be reviewed by a Scientific Advisory Council in the fall of this year. The Scientific Advisory Council will be composed of individuals with outstanding credentials in research and scientific method, although they may not necessarily be identified primarily with complementary and alternative medicine. Similar to the NIH system of study sections, each application will be critiqued by a primary and a secondary reviewer, and this information will be presented to the entire council. In some instances, because of the area and the need for specific expertise, the primary reviewer may not be a member of the Scientific Advisory Council. Different from the NIH system, the principal investigator will be invited to his or her portion of the meeting for the purpose of making a presentation and to respond to questions. If the grant is approved, we will assign a experienced investigator in the same field to be the primary reviewer of the investigator's progress reports. The Scientific Advisory Council will review each grant on a yearly basis for the purpose of deciding on continuation of financial support. We are designing a plan that extends over a 10-year framework. Our dominant goal is to grow the number of investigators over that time frame. One of our long-term goals is a translate the information obtained from this funded research to human applications. This will most likely involve the field of biosensors, digital pharmacology, conditioned healing spaces, and perhaps electromagnetic and homeopathic treatments. The ultimate focus of the Samueli Institute is not only to advance knowledge, but also to enhance patients' quality of life, support their wellness, and treat their illness. In addition, the other activities of the Samueli Institute will include the implementation and/or co-sponsorship of annual or semiannual meetings of relatively small groups of scientists, visionaries, and philosophers, and just plain thinkers to explore various topics. As you see listed in your one-page handout, these topics may include aspects of causation, placebo effect, homeopathic action, spirituality, and multidimensional spaces. There were several other questions in your invitation that I would like to address at this time. I believe there are several real and potential obstacles in achieving our goals. Access to money is always a primary one. But second to money is the ability for productive investigators to publish their research in peer-reviewed journals. I have been told that extremely competent, world class experts in complementary and alternative medicine have repeatedly had their data and even their analysis and reviews of the literature rejected by peer-reviewed journals whose primary readers are allopathic physicians. Therefore, I am delighted to see on your agenda a commitment of time and thought to this fundamental issue. At the Samueli Institute, we have every intention of working together with other foundations in our areas of research interest. We anticipate most of the senior investigators, who will be applying for funds from us, are already supported by other sources. We, ourselves, will be seeking partnerships with other foundations to pursue specific projects of mutual interest. Our approach to working with the federal government is a proactive one, and we will engage in specific liaison activity. We know that aspects of information biology have specific interests for various branches of our government, and we want to ensure awareness of our efforts and potential. In closing, please allow me to thank you for this opportunity to present this information, and thank you all for the important work you are doing.Panel Discussion
DR. GORDON: Great. Thank you very much. It is wonderful to feel the energy, feminine energy, sort of moving out ahead, and not waiting for others, including the government, to lead. So, I really appreciate that tremendously. I wanted to ask one question to begin with and then open it up, and that is, Susan Braun, you raised the issue of collaboration, and I know Bridget Duffy is very interested. I wonder if the four of you could talk a little bit about how you would see foundations working together to set agendas and help move the whole field ahead. MS. BRAUN: With what we do, for example, in breast cancer research, we are a part of a couple of different consortia of funders where we get together on a formal and an informal basis to discuss priorities in funding, for example, criteria for review. I think there are certainly those possibilities that are somewhat conventional. I think there are opportunities, though, that might even be a little bit less conventional, for us to talk about, what the various areas of research themselves really need to be, and specifically, who, by virtue of their mission and to whom they might be answerable, would be able to fund such things. As I talk about the Komen Foundation, we are fairly unencumbered in a remarkable way in what we can fund because we answer to the public primarily. We don't have government funds, and we aren't funded by any particular industry, and I think that is a type of collaboration that we could look at within these groups to say, okay, what does the whole puzzle look like or as much of it as we can define, and who is best suited to pose certain questions and/or fund the answering of those questions. DR. MILLER: When you take a look at the field of health philanthropy, you will find organizations that have varied agendas, some that focus just on health, some that focus on community organizations, et cetera, but I think that there is an opportunity for the Commission to look at ways in which they can provide education for the field of health philanthropy through an affinity organization called Grantmakers in Health. It is an organization that the Robert Wood Johnson Foundation has been very active in, Medtronic, as well, and also Susan G. Komen. They have a series of policy and issue briefings that take place three to four times a year, usually based here in Washington, that give the opportunity for committees or commissions, such as yourselves, to sit down and to talk with health philanthropies about interest, evidence based, so that there can be an educational process there, so that we can I think develop more interest in CAM, and I would take a look at that recommendation. DR. GORDON: I would right now, on behalf of the Commission, like to say we would welcome that opportunity for all of us or a small group of us to come. DR. DUFFY: We are already working to put a panel together on this subject soon. DR. MILLER: Yes, and I am on the board of directors for Grantmakers in Health, if anyone would like to have any individual discussions about that. DR. GORDON: That would be great. Thank you. DR. DUFFY: In answer to your question, I think there is great opportunity for philanthropy to collaborate, and I am just struck by the number of philanthropists, large organizations, small organizations. I think that there is a need for a clearinghouse, so that we know who we are and where we are, and can identify our specific areas of interest, and then divide and conquer. Several of us here in the room had an opportunity to participate in something like that three weeks ago, where one philanthropist in particular, a woman, Penny George, was frustrated, she felt like Sisyphus holding the boulder at the side of the hill with her grant dollars, and she said I want to do more and I want to make it happen more quickly in health care. So, we convened 15 philanthropists and 15 leaders in health care to have a conversation about that very question, how could this collaboration help move this faster. So, I think there is a need for that and we need to do something about it. MS. SAMUELI: We are the new kids on the block, so I think we are hoping because of what we are doing is so innovative and creative that we are going to be able to draw from other foundations to collaborate with us. DR. GORDON: Great. Thank you very much. Dean. DR. ORNISH: My first comment is just one of appreciation, how exciting it is for me, and I think for most of us here, just to hear of the work you are doing, and just acknowledge it, how important it is and what a difference you are making. So, thank you. I was also going to ask about this issue about the consortia. Bridget and I talked about this briefly before, but if there is any kind of forum, whether it is Grantmakers in Health or in any other format, it would be wonderful if it could be both experiential, as well as didactic, because I think that one of the things that is the most influential in getting people motivated and understanding some of the power of these simple techniques is to experience them themselves, and I would just ask you to consider that. DR. DUFFY: Dean, my greatest obstacle in building this was really internal, and so for a year and a half I tried to get this big device company on-board, and it wasn't until we did a site visit to a center where, instead of sitting in a boardroom all day looking at slides on integrative medicine, these enlightened physicians had my board lay on the table. They came out that afternoon, they are in the back of the limo on the way to the airport, and their ties are to the side, and they said to me, "Bridget, we finally get what you are doing and what this is about," and I was like yes. So, that is when I realized it has to be experiential. You know, in an airport Hilton, I can't inform 200 sales guys from Medtronic about what it is their patients are seeking. I think people have to experience what it is that their patients are seeking and paying a lot of money for. DR. GORDON: Thank you. Joe. DR. PIZZORNO: I would like to ask for your help. I think what you are doing is laudable, and I think all of us in this room want to see medicine advance and see conventional medicine regain some of its soul. The reality is that 600 million visits to complementary and alternative medicine care providers is being provided by CAM providers, over 200,000 of them in the United States, and they are the ones who are experts in this, they are the ones who have kept this medicine alive for a century and a half, when conventional medicine has done everything it could to destroy it. Now, we have talked about integrative care clinics. That is a great idea, but in reality, this care can be provided within communities, integrated within communities, which means conventional practitioners working with CAM practitioners and physicians. We need your foundations to pay attention to the CAM professionals and the CAM institutions, as well, because we need to advance these healing arts. Again, the majority of the care will be provided by us CAM professionals. We need your assistance also. How can that happen? I am speaking from experience as the Founding President of Bastyr University that foundations have virtually always said no to every request that we have made. This has to change. How can we do that? MS. BRAUN: I realize that is probably a rhetorical question, but one comment about that, again, as we look at our mission, it is to fund those issues of science, but that are of most pressing concern and need to our lay constituents, and within the world of cancer and within the world of breast cancer that we specifically operate in, we know that some of the most pressing questions are what else is there in my healing. I understand a bit about chemotherapy, a patient might say, and chemotherapy is perhaps one of the most toxic of all of the kinds of medicine, traditional medicine that are employed, so they seek to have, not only an understanding of their healing, but how do they deal with the traditional healing. So, we know that these are people, we know from studies and we know from anecdote, these are people who make a great deal of use of complementary and alternative providers. So, we are pushed by them, and I think what we can do is tap into what is truly a public demand if we are going to then embrace and wrap the science around it, so that we come at it from both sides. DR. DUFFY: We have to fund some pilots that work, and there is one we are trying to build in Minneapolis. There is a Powder Horn Community Clinic that I think is probably one of the best models in the world, and it is the only one that doesn't require you to see a physician, it is not just a bunch of CAM practitioners with a bunch of M.D.'s all put in a box together and trying to alter reimbursement, which is what a lot of the models are. So, I think what the goal is, is how do we connect individuals to the community of healers that they need to heal, and it may not be that we have to open a clinic that has an M.D., an acupuncturist, chiropractor all in the same place. It may be a way that we connect them in different ways and we have to figure that out. I can't agree with you more, and I don't know the answer to your question, but we need to try. DR. MILLER: I think from the perspective of Robert Wood Johnson, as I said, we have a translational agenda in terms of our programmatic funding where the evidence base exists. We are very interested in funding projects that will help in widespread implementation. If you take a look at the projects that are in your appendix in terms of both mind-body and other areas where an evidence base exists, that we have done some work in that area, but I think that you pose a very important challenge and possibly we need to do more. DR. GORDON: Wayne. DR. JONAS: I want to echo Dean and other's sentiments, thanking you all for the spirit in which you operate, one of philanthropy and generosity. I think the quality of the resources has somehow changed by having that spirit and may, in fact, go farther than other types of resources in getting towards understanding healing and having healing as a fundamental concept. I was glad to hear that I heard at least four times the word "healing" and focusing on healing to help us understand what it is all the way from the basic science level up to the actual application level in terms of personal interactions because I think if anything is going to help us in our current chronic illness, it will be supplementing our current medical system with the practice of healing as a way of approaching and treating chronic disease. My question to you is how is your effort any different than what goes on from the government, or how does it relate to what goes on from the government. We are primarily involved in making policy that comes from the government. Are you in some sense supplementing what the government can't provide, but going along the same lines, or are you doing something fundamentally different, or is your process in some way fundamentally different that makes it more likely that there will be breakthroughs or utility? Any, all? MS. BRAUN: Two things. One is at the Komen Foundation we follow and we are one of the NIH-accredited, I guess, grantmaking organizations, so we do follow the model with respect to our basic peer reviewed grant program, but in addition to that, we have a couple of other mechanisms for grantmaking, so it may be that that is one differential. We have an ability also to change topics, not on a whim by any means, by certainly in keeping with the demand of the public. So, I believe that that is a little bit different is that ability to change direction perhaps a bit more quickly. Then, the other thing again, as I have said, is our funds are for the most part unrestricted, so that we can work in the precise needs that have been identified, and I guess complementary to what the government does, at least in our model, we work with especially the National Cancer Institute and the Department of Defense in our case because they are both the major funders of breast cancer research, and work them to see what they are doing, and not to be duplicative. There are also some things that they will forthrightly say to us we can't fund this, can you, because it is not something as a government agency we can do, but we feel it is important to be done. So, we work in that way collaboratively. But I think back to the community and the question that was raised. We also fund a huge number of programs within the 115 communities where we exist, and I think that is also something that is remarkably different from the government model, is that reach within the community and the way that things bubble up, as well as filter down, so perhaps that is a mechanism. I think you will see that most philanthropic organizations do have that strong reach into the community. DR. GORDON: I wanted to say just a couple of words about that. As I chaired the Committee on Research Grants and CAM last year, I think that is precisely a group that CAM practitioners should apply to. We looked at the grants, there was no particular discrimination or prejudice because of the degrees, it was simply the expertise of the participants. So, I think part of the issue is making more widely available some of the information about foundations that is out there, so that a dialogue can start about some of these issues, and some of the misconceptions can be cleared up. The other thing that I want to say about Komen is that your turnaround time is about 1/50th of the government's. MS. BRAUN: I didn't really want to raise that. [Laughter.] DR. GORDON: So, it is very effective. You apply, you either take the grant or you don't take the grant, and you know in a few weeks. I think that is a great blessing especially in this field where things are moving very fast and we are really trying to go with what is important at that time. So, I just wanted to mention that. George, you had a question. DR. BERNIER: Yes. I would like to comment that it is very striking that three of the four of the presenters really deal with fairly narrow, potentially solvable problems, and I am sure that is part of the attraction. I do wonder, though, if down the road, you would consider, and I guess, Dr. Duffy, you would be the most likely one, that you have gone from a one area of interest to two areas in the relatively recent past. Do you see this as an evolving process whereby you may well start touching territory in areas outside neurosciences or cardiology? DR. DUFFY: I think most likely not, because the core mission of the company is to provide life-long solutions for people with heart and brain disease, so our foundation tries to do things complementary to what the corporate side does, however, I think the volume of people that we impact with heart disease and neurologic conditions is so large that I don't see that we can hardly make a dent in it, so we have got a lot to do. So, it is frustrating for me because I do see people within the community and a lot of grass-roots efforts who I believe are really making a difference in building the model, but because of the people we serve, I tend to have to go with cardiovascular centers and neurologic centers because it is in line with our mission. But I believe that through collaboration with other foundations and philanthropy that we could identify some key next partners or projects to fund that would be complementary to what we are doing, so I would see a role within a hub of people that looked at exploring, reaching out more broadly. DR. BERNIER: I would like very much to compliment you and thank you for your contributions today. MS. BRAUN: May I just add one comment to that, as well, that we found because the interest in breast cancer, I guess, has remained so strong, and we do focus exclusively on breast cancer, but because we have been relatively successful in garnering public interest and support, that it is also incumbent upon us to, as we do things within the world of breast cancer, structure them such that they can either serve as models for other diseases or for other cancers, and pave the way for others to hopefully, as they go along, whether it is within research of community outreach, to have to do less work, and we have actually structured our organization such that the core competencies that we have will be made available to other organizations, so that they will not have to reinvent wheels as they go along, but can focus upon their mission. So, I think that may be a way rather than reaching out specifically into other diseases or areas that you will see foundations working, is to trying to provide what they have learned to those entrepreneurs who are coming into other areas. DR. GORDON: Wayne. DR. JONAS: I was hoping some of the others would comment on whether there is any kind of qualitative difference in what you are doing compared to what the government is doing. I mean you often hear from, not just CAM researchers, but a lot of people in research who are trying to do very innovative things that they can't get it from the normal processes because they are rather restricted in terms of what they will fund, not really into high-risk type of innovative areas. I am just wondering, are your foundations addressing this in any way. DR. MILLER: A lot of it depends upon the foundation, and because of my work in GIH, I have got a bit of a scope on what philanthropies do and their approach to grantmaking. At RWJ, 75 percent of the work that we do is through a targeted, solicited authorization, usually programs that have been developed in-house, but we do reserve 25 percent of our annual grantmaking for unsolicited, over-the-transom proposals as long as they fit into one of the general goal areas of access - chronic care or substance abuse. The issue that Commissioner Gordon raised a little while ago regarding flexibility is a very important one in terms of turnaround time for proposals. We are not as fast as Komen, but we are certainly not as slow as the federal government in terms of funding projects. But the other issue that I think is a very important one for health philanthropy is the issue of risk taking, and funding things that the federal government cannot fund. We have done a lot of work and actually at one point were the sole founders in the areas of both tobacco and also end-of-life work at the Robert Wood Johnson Foundation, and I think that if you are able to create that kind of leadership or niche within a particular foundation -- I know that Fetzer was not able to attend the meetings today, but think about that kind of focus and helping to lead a foundation and a foundation's board in a way that can help to promote the field would be very useful. DR. DUFFY: I agree. I think that we target people that take risk and are innovative, and, in fact, I think that what you are doing is really cutting edge, and one center that we are funding couldn't get funding from any other place because they are looking at issues of energy research. I think there is an opportunity, when couched in an organization that there is very conventional treatment and they have visionary people who are looking on the edge, that we can help get them to a place where they can then qualify for funding through the government to take that research to another level. I think that the other thing that we can do is help make inroads to other entities that are doing research in this. For example, I presented on a panel with Dr. Eisenberg and some others at the National Academy of Engineering and Science a month or two ago. There were 400 people in the audience, mostly men, and we were on after the talk on nanoelectrical, microprocessor chip something, and I thought we are going to get laughed off the stage. Our talk was forces driving patients into models of health care, and at the end of our presentation, we were mobbed. I came home with like 20 cards in my pocket from these basic science researchers who are looking at the bioelectrical chemical mechanism of connections between the heart and the brain, and energy, and I was just blown away by what is already going on out there. I think that we can play a role in connecting these people doing the research that can get to a level where the government will support it. MS. SAMUELI: If I could add just one more thing, the creation of the institute was to do just that, we wanted to seed innovative and creative projects, so that the government could see what is out there and that people were willing to seed these projects to add to the credibility of CAM. So, that is exactly what we are trying to do is to be innovative and flexible. DR. JONAS: Dr. Duffy, would you mind giving those cards to Dr. Samueli? [Laughter.] DR. GORDON: I want to thank you all. I want to make a couple of suggestions and ask for your ongoing help. The suggestions are one of the things that is very important to us in reaching out to foundations, and several people have said it or hinted at it, is that if we can be there to share with you, and share the experience, as well as the knowledge, hopefully, the wisdom as well as the knowledge, that that will go a long way, and that can be very important to all of us. Secondly, I think that you are in a wonderful position, all of you, to speak with other foundations, and the foundation people, as you know, trust each other or at least get along with each other in a way that is different from people who are potentially coming for money from you. So, part of what we are doing in a sense is entrusting part of our mission to you, is to reach out and to share with people your experience and the possibilities that you see, and the implications, not only for complementary and alternative medicine, but for informing medicine and health care and healing that you see. Finally, we would love to talk with you further because as we come out with recommendations in the Interim Report and in the Final Report, that is only going to go as far as the people in this country take it, and you are, in various ways, in touch with many people in many different ways. So, we would like to have the opportunity to share with you that information to get your input about it and for all of us to partner in trying to move the field ahead. So, thank you very much for coming and for sharing so much with us. [Applause.] DR. GORDON: We are going to take a 15-minute break and then we will come back with the next panel. [Recess.]Panel Session III: Approaches to Evaluating
Research Literature
Presenter: Donald A. Lindberg, M.D.
DR. LINDBERG: Good afternoon. I am happy to appear before you. If you like, I will make a statement and then take questions. Is that suitable? Okay. In writing, you asked about the policies of the National Library of Medicine with respect to scientific literature on complementary and alternative medicine. At a previous hearing, you already met with Sheldon Kotzin, one of our technical people at the Library, and he has given you a briefing, so I will attempt to go somewhat beyond that in what I say, but I would be happy to take questions on any portion of our work. The National Library of Medicine is the biggest medical library in the world. It actually began its existence in the United States in 1836, so it has been in the business of collecting physical prints and photos and journals and books for all of these many years. It pioneered the use of electronics and indexing that literature starting in 1964, and made those available throughout the world basically starting in 1970. I will say a little bit more about recent advances. But I mention this because it is the mission of the Library to acquire, organize, and disseminate the biomedical knowledge of the world for the benefit of the public health, so we, of course, include the area of your concern along with the other older areas. In fact, I have been there only since 1984, but in those roughly 16 years, a number of new institutes have been created, a number of new fields have been created, a number of regrettable elements like AIDS have been discovered and are being attacked. We are returning to the attack on malaria, an old enemy. So, things have changed and the Library changes with them, and we always ask ourselves two things when we recognize a new field, as we did with complementary and alternative medicine - firstly, what is the status of our collection; secondly, what is the status of the electronic indexing; thirdly, is the terminology we are using to describe this field suitable. So, that is sort of our approach to it. As you, I am sure, realize and would approve, libraries don't write books, they organize them, and we don't write journals, we organize the literature. The literature is pretty big. We add, for instance, the MEDLINE 450,000, say, half a million articles per year, and the terminology to organize those things is roughly 500,000 to a million terms or concepts. In recent times, the advent of Internet and World Wide Web and the electronic technologies have allowed us to include in the list of users, patients, families and the public, so that since starting to make MEDLINE available on Internet in '97, and making it free since 1998 -- Mr. Gore did the first search, as a matter of fact, first free search -- our usage has gone from 7 million a year to, within a year, 75 million, the next year 120 million, the next 240 million searches per year on the database. Mostly, this is the United States, but in areas like molecular medicine, it is half and half, perhaps a little bit larger overseas, but, of course, half the data comes from overseas, too. So, more specifically with respect to the CAM area, at the time that Wayne Jonas was director of the National Center, we offered him the opportunity to talk with our Board of Regents, and in the course of that, he described to us a list of journals, which was then 695 journals that he and his colleagues had felt were important for CAM. So, we sent that list. We did two things. We, first of all, began to examine our own collection, asking the questions that I mentioned to you, do we own these things, and so forth, and then we sent those out to 14 research centers in CAM, in the U.S. and abroad, to get an opinion on which are most important and give us some guidance. Well, it turned out that we already owned 79 percent of all those journals and had since their inception, and it is a big library. Based on consultation from the Centers, we immediately added roughly a dozen journals to the routine collection and reviewed the question of which are to be indexed electronically. In more recent days, of course, Dr. Strauss has taken over the Center, and working with NCCAM and NIH, we have jointly produced a database aimed at the public for the most part, but also practitioners and scientists, of complementary and alternative medicine articles on MEDLINE, so that is to say we are working as partners. This has been very, very helpful to us because we can look to him and his colleagues and consultants and funded centers for guidance as to the quality, if you will, and we know how to do the electronic part. So, I think it is a pretty good result. There are roughly 230,000 citations on that sort of pared-down, high-quality database. Now, questions that, Mr. Chairman, you asked in writing to me had to do with the process for selecting new journals either for the collection or for inclusion in MEDLINE, so perhaps just for the moment I will tell you about that. There is an NIH-chartered committee, that is to say, compliant with the various federal advisory committee rules and regulations, proper committee, in other words, called the Literature Selection Technical Review Committee, LSTRC. It reviews all new journal titles that we undertake to include. They meet three times a year. The skills and backgrounds of the persons vary, but they include a host of medical specialties, medical librarianship, public health, basic science. It isn't, of course, like any study section, necessary to include all knowledge in the heads of a few people around a table or a dozen people around the table, so they will also get collateral reviews whenever a particular journal warrants it. In addition to that, each year we review one or two major fields. So, for instance, last year we did pharmacology, and this year we are doing public health, and I can describe in more detail how that is accomplished. What else would be of interest to you - the success rate. I think I mentioned that they look at roughly 140 new journals each quarter that they meet. I mean it is rather amazing how fast journals come into existence. They don't go out of existence with quite the same speed, so there is an accumulation, but there is a lot to look at, and the success rate is roughly 25 to 30 percent, so it is almost like grants, and we will undertake to include those which are the most important or of highest priority, perhaps I should say. You also asked, Mr. Chairman, in writing, what are the criteria which we would use to judge a journal, and so forth, so I should tell you that the most important one centers on the content of the journal, the scientific content of the journal, and it is desirable, of course, that -- I guess the terminology we would use in our published criteria are we look at the validity, importance, and originality of the contribution. My colleague, George Lindberg, who used to be editor-in-chief of JAMA, said it in a much snappier way. He said when we get a submission of an article, I ask is it new, is it true, is it important, and if it is all three, it might get in JAMA, also won't. So, I suppose we are really looking at much the same criteria. In general, the editorial work on a publication is of some interest, as well. You want it to be well presented, you want it to be on acid-free paper, for example. There is no point in subscribing to and buying stuff that is just a liability. I think I mentioned that 55 percent of the journals themselves in MEDLINE are from outside the United States, so we attempt, as I said, to bring the knowledge of the world to the U.S. In closing, there is an additional effort that NLM is making that you might possibly have an interest in, even though, of course, you didn't ask for this specifically. We have taken a great shine to the idea that we would like to try to do as good a job for the public, for patients, families, and the public as we have historically done for scientists and doctors. I mean it is much more difficult to serve the public. So, we are still learning quite how to do that. Most recently, we have started working with public libraries because there are databases that we produce - MEDLINEplus is aimed at the public, clinicaltrials.gov is aimed at the public, but it is said that only about half of Americans actually have computers and connectivity, so the others we wish to serve, as well, and so partly the public library program is aimed in that direction. In each case, we will have a medical library, a public library, and then a study to see how can we -- we are trying to help both of those -- enhance the ability of members of the public to get biomedical information. There are more public libraries than medical libraries, obviously. So, we have funded I think it is 64 grants in 34 states, thus far with a very encouraging result. While we are not pushing CAM or pushing anything else, we are pushing ourselves to try to increase the likelihood that a user can get what he or she wants in the way of information about science and health from the library system. I think you probably share this goal with us, and I thank you for the chance to be here. DR. GORDON: Thank you very much for your work and for coming here, Dr. Lindberg. Douglas Kamerow.Presenter: Douglas B. Kamerow, M.D., M.P.H.
DR. KAMEROW: Thank you, Mr. Chairman. I am pleased to be here representing the Agency for Healthcare Research and Quality, which is the smallest agency of the Public Health Service. If you look at your list of speakers, you will see that you have listed the old name of the agency, which is the Agency for Health Care Policy and Research, so we have changed our name, and my e-mail address is also wrong in there, so if you want to e-mail me, the correct e-mail address is my name at AHRQ.gov. I have got handout that I think was distributed to you as a set of PowerPoint slides, and I want to go over that very briefly. I will skip around a little bit because I don't think I can cover it all in 10 minutes, and I do want to get to the questions that you asked us. As I said, the agency is the smallest in the Public Health Service, and our job, like NIH's, is to do research, but we focus specifically on health services research. As you can see from the third slide, basically, what we do is support the research that improves access to care, reduces its cost, improves its outcomes, tries to improve its quality, and appropriate use of health care services. There is a cute little water faucet down there a little below that tries to show the pipeline of our research, and if you have good eyes, you can read what is inside of that. If you can't, the idea is that we move through new research on priority health issues, through creating tools and training folks, then translating that research into practice, and the goal coming out of the faucet is improved outcomes, better quality, greater access, and appropriate cost and use. The agency really has focused very little on CAM activities. We have done a bit of research in that area. What we are doing mainly now is two things. One is surveys. That is, we have a large Medical Expenditure Panel Survey that is the biggest health expenditure survey in the country and the most accurate. One of the nice parts of that survey is we ask people about their use of various practitioners, and I have got some slides on that, so if you want to know about that, it is a useful way. As the survey comes out in various iterations, we are now in the '97 survey that is being released, '98 will be out soon, and then followed by '99 as they lag a little bit, but you can find a fair amount about who uses CAM practitioners and for what concerns that they saw them. There is nothing on outcomes of care in that survey. We have done some outcomes research, but not a whole not. It has mainly been in the area of chiropractic, mainly in the area of back pain, looking at acupuncture and chiropractic medicine. The focus of our activities besides those two has been on what we call synthesis here, and the part of the agency that I am in charge of does that kind of synthesis. If you turn over the page to the next one, to the very bottom of that page, that is page 2 in the handout, you can see that it has a little logo and describes our evidence-based practice centers. About four years ago now, we created 12 centers around North America, and their job is to produce systematic reviews. Systematic reviews is not like the kind of general literature review that you see in a journal, at least not the kind that you used to see in journals, and if you go to the middle of page 3, you will see a definition of the word "systematic review." They are concise summaries of the best available evidence addressing sharply defined clinical questions, using explicit and rigorous methods to identify, then appraise, and then synthesize the studies. So, you don't just gather them up. First of all, you systematically gather them up. You have to in a lot of cases -- and CAM is a good example -- really dig around to find things, and I will come back to that in a minute. Then, you have to set up some sort of rating scale to decide how you are going to evaluate those studies. Once you do that, you are going to rate the studies and then come to some sort of conclusion. Sometimes that means using fancy techniques, such as meta-analysis or decision analysis. Sometimes you can't do that for various technical reasons. You basically just display in a series of tables what you have found and try to come to some conclusions. We call these things evidence reports because we don't make recommendations. The agency used to make clinical practice guidelines that had recommendations, but what we do now is try to supply what we think is the front end of these kinds of recommendations, so that organizations, whether they are clinical organizations or states, or whether they are health plans, whether they are groups of practitioners, whoever they are, they can then take the stuff that they ask for, because we do these when we are requested to do them, and they can make their own recommendations. What we do is try to supply to them and to everybody on the web, evidence reports and good syntheses, so what they look like - here are a few that have been done, and I will be glad to pass them around. Here is one on garlic. They come in two versions, the turgid and the brief, the mercifully brief. So, I will pass the two around, and you can take a look. Here is one on milk thistle and it is whether it works to help liver disease, and we have some other ones that are coming out, as well. I will just pass them around. I guess the point that I want to conclude with, and I will be glad to answer your questions after we have finished, are a couple of things. First of all, we have got an agreement with NCCAM at NIH to do this work on selected topics that they are interested in, and you will see on the last page of my slides that we have chosen one of our evidence-based practice centers. This happens to be the one in Southern California, which is a consortium of folks led by Rand, to do a number of topics for NCCAM when they ask for them, and you can see the topics that we are working on now, some of which are done, some of which are in process. They have asked us for these, not so much because they expect to find the answer, that is, they don't really expect that after a systematic review, they are going to find that this particular substance is perfect and should be used for treating that, although that may happen, and occasionally it will. What they are really looking for, and I think in some ways most excited about, is to find areas where more research is needed, the areas where there is good beginnings of evidence, something that lets people know that there is probably something to this idea that people are talking about, whether they are maybe small trials or other kinds of case series that really wouldn't pass the test of very strong evidence, but something that NIH can then turn around and do a carefully done trial, because we don't have the resources at the agency, we don't do many clinical trials. It takes a lot of money to do clinical trials obviously. But we help them, we think, set their research agenda for doing that. The third thing we can help them with is methods and bibliographic research, so that we can try to push forward the ideas of how you go about analyzing data like this, because there is definitely an art, as well as a science, to finding the CAM literature. For instance, we just completed one on Ayurvedic medicine, which is, at least in its origins and still a lot of it is practiced in India, so Rand had to get someone to India and go through libraries there to find language, English language and other kinds of literature about Ayurvedic medicine. They found a lot, and they found more on diabetes than anything else, but still there was no true answer, but there was a lot of interesting indications in a report that is still forthcoming, we are not quite finished with it. But it is an interesting process, it has taken us a little bit of a departure from how we set up this program, but we think it is one that has been useful in NIH and we hope useful to others, as well. So, that is all I wanted to say and I am glad to answer questions when we are done. DR. GORDON: Great. Thank you very much. I certainly understand more now. That is great. Brian Berman is next. Brian is going to assume two different identities or two slightly different identities. He is going to talk both about the Cochrane Collaborative and also about doing research in an academic medical center, so he will have more time than the other presenters. Brian.Presenter: Brian Berman, M.D.
DR. BERMAN: Thank you, Mr. Chairman, members of the Commission. I am honored to be given the opportunity to speak with you today on the evaluation of CAM research literature and the role of the Cochrane Collaboration, and as Jim said, the issues in bringing in research into an academic health center. I am a board-certified family physician and pain management specialist who has been integrating a number of these CAM modalities into my practice over the past 18 years. I am also Director of the University of Maryland's Complementary Medicine Program and principal investigator on an NIH specialized center research in complementary medicine focused on arthritis and principal investigator on one of the large clinical trials in osteoarthritis and acupuncture, so today I will be wearing more of my research hat. One of the main activities of our center is the investigation of the safety, efficacy, and mechanisms of CAM therapies for pain-related problems. We design and conduct original research trials in addition to systematically distilling the best evidence available worldwide and disseminating these also to the public and scientific communities. So, the first half of what I will be talking to you about is the Cochrane Collaboration and evaluation of the literature. Some of you may be familiar with the Cochrane Collaboration. It is an international nonprofit organization that prepares, maintains, and disseminates systematic up-to-date reviews of health care interventions. It started in '93 from a challenge by Archie Cochrane, an epidemiologist in Oxford, England, who recognized that people who want to make more informed decisions about health care do not have access to reliable reviews of the available evidence. So, the Cochrane Collaboration aims for information that is evidence based, easily accessible, internationally developed, quality controlled, clinically useful, and periodically updated. There are a couple of points there. International, we have researchers, clinicians, consumers from all over the world working together in this collaboration. It truly is a collaboration. It is especially important in this area of complementary medicine where about 80 percent of the world uses it as their primary form of care. Evidence based, the reviews, as was mentioned before, they are prepared systematically, and a special feature is that they are kept up to date and to account of the new evidence. I would say that the Cochrane Collaboration has embraced this field's approach to look at what is effective and not effective, and many of the leaders from this group have really taken this on-board. A couple of years ago, in Lancet, it was compared, the Cochrane Collaboration in general compared to the Genome Project. One of the questions was the role of consumers in the Cochrane Collaboration, and I would say they place a high priority on consumer input throughout all levels of activity. There is a consumer network that has been developed based out of Australia, and they have many roles. They make abstracts and reviews more readable and more accessible, so they have developed a way of having a synopsis of these systematic reviews, sort of half-page, and they by now have done about one-third of the thousand systematic reviews that exist in the database. They also have a seat on the Executive Committee. They help research identify important questions to answer, they comment on drafts of reviews, and they help disseminate the results. For the complementary medicine field, the consumer representative is Clara Allen from the U.K., and she has taken a very active role in taking some of these systematic reviews and writing summaries for the public. The products for the Cochrane Collaboration, the main products is the Cochrane Library, and this has in it a database of systematic reviews, as I mentioned, over 1,000 reviews are in it now. In the Controlled Trials Registry, there are over 300,000 randomized controlled trials. This is all aspects of health care, not just complementary medicine. But that is more, as I understand, since he is sitting next to me, more than what is in MEDLINE to date, and not bad for an organization that is only eight years old right now. The complementary medicine field was started in 1996, was registered with the Cochrane Collaboration in part due to Dr. Wayne Jonas' encouragement at the time for our center to really get involved in that, and it has developed a specialized registry of trials in complementary medicine, developed a registry of systematic reviews, and facilitate new systematic reviews, to coordinate the field and work with groups both inside and outside the collaboration, and then disseminate the results. The field is coordinated by our center at the University of Maryland, and we also maintain the CAM registry through the work of Mac Beckner, and we receive funding from the NIH, first, at the Office of Alternative Medicine, and now at NCCAM. One of the first aspects of what we got involved with was to develop the Fields Trial Registry. This registry aims to be inclusive of all randomized controlled trials in complementary medicine, published or unpublished, in any language. The trials and tribulations of finding and developing studies are outlined in the article that I have included for you, the JAMA '98 article and some of those difficulties of capturing all the complementary medicine studies through standard MEDLINE searches and the incomplete search terms up to the early 1990s. There wasn't a MeSH term of alternative medicine, it was actually therapeutic cults. That was then changed in the early 1990s to alternative medicine, and there are, I think, 25 search terms in there. We used 250 search terms. So if you used one of our 25 terms, you would get about a yield of 45,000 articles. If you use the other 250, you would get about 150,000 articles. We also need to identify and search comprehensively the electronic databases worldwide. And then, many of the journals are not indexed in the National Library of Medicine, although it is increasing, as we have heard. There is also the need for hand-searching the journals. We now have 5,300 randomized controlled trials in this registry and another 4,000 possible randomized controlled trials have been identified. One of the questions that you asked was about the criteria for inclusion as complementary medicine, which is a difficult area. What we did was we took the definition of complementary medicine that was developed in the NIH/OAM Methodology Conference back in 1995, which is in your written testimony. We then used this definition as an inclusion criteria, and then developed three exclusion criteria. So, we said that an intervention will be excluded from the registry if it meets two of the following criteria: One. Is the intervention, when practiced in this manner, at this dose, with these patients, almost exclusively practiced by those with conventional medical qualifications. Number two. Is the intervention, when practiced in this manner, at this dose, with these patients, a recommended treatment. In other words, a significant number of standard medical or paramedical references refer to use of therapy as routine. Number three. Does the intervention fail to involve any theoretical divergence with mainstream medicine or science. The search strategy we developed and the list of included the therapies are in the addendum that you have. I would say the value of the search strategy is seen from the graph that you also have in your testimony, where, if you take a MEDLINE alternative medicine MeSH search for randomized controlled trials, you will get a yield of about 2,400. If you take a more comprehensive MEDLINE search of the 182 terms that we tried to take, you get almost double that, 4,700. Then if you take the Cochrane Registry, where there has been some hand-searching and other electronic databases, you get about 5,300. So, how does Cochrane Collaboration assess the quality of the research it includes? That was one of the questions for us. Well, it is accomplished through systematic review, which is the main product of the collaboration. The CAM systematic review registry contains 208 systematic reviews to date, and as we heard, these reviews answer sharply defined questions through a comprehensive search, assess the quality of each trial, and synthesize the data. I have found that they are a powerful way to keep up to date, handle the information overload, give practitioners and consumers answers to what works, what doesn't, what is safe, and tell us where the gaps in the knowledge are. One of the important steps in the systematic review is to critically appraise each study to evaluate the quality of the study's methods. As the computer industry says, garbage in; garbage out. Often a checklist in the scale, such as the Jadad scale, was used. This looks a three main issues. One, is whether the study was randomized, and if so, was the randomization process adequate. Number two, blinding. Was it double-blind, and did they evaluate the success of the blinding? This obviously tends to favor drug trials, but you can always blind the person evaluating the outcomes, as well as the patient. Then there is the third, the attrition rate, was it reported and why did the subjects drop out. The fourth one, has become very important, allocation concealment. After the randomization, how were the groups hidden; was it put up on a board where everybody could see which groups they were going into; was it computer generated; just how was that done. Other features of the study often evaluated are, was the primary endpoint measure defined. For all studies, it is evaluated at 25 percent that that has been done. That is in all conventional, as well as complementary medicine. Very important is the quality of treatment; was there a description of the intervention; and what about the qualifications of the treater. I saw that, recently, in a paper that was submitted to me for acupuncture, looking at rheumatoid arthritis, it was a well-designed study. However, the intervention itself was sorely inadequate, one or two treatments for chronic rheumatoid arthritis. So the adequacy of the treatment. The sample size is important. Was there sufficient statistical power; was the analysis appropriate; did researchers assess compliance; and what about co-interventions to were other things done that maybe made the difference, and then, do the conclusions follow the evidence, or were the hyped up. So, why do all this? Well, we know that poorly executed trials tend to exaggerate treatment effects, and they have important biases. Sometimes they have effects as much as the treatment itself. You asked for some policy recommendations, and I would say that the work of CAM literature evaluation in the Cochrane Collaboration field has just begun. I think the importance is that these systematic reviews are useful to consumers to cohere evidence that may sometimes go in different directions. They are useful for policymakers to define, sometimes, what to fund, as well as for practice guidelines, useful for practitioners to answer specific clinical questions, and for researchers to summarize existing data. The effort in producing systematic review needs to continue, and the scope of the work and its impact needs to be broadened. Specifically, I would recommend that the infrastructure and collaborative work with the Cochrane Collaboration field be allocated ongoing support, allowing for continued maintenance of the registry and coordination of the field. With sufficient support, the field can increase its current work and significantly add to its value in the following ways: Number one, it can set up a working group to further define and broaden the scope of modalities included under alternative medicine, medical subject candidates. Some of our people worked with the National Library of Medicine a few years ago, and I think it still needs to go a lot further than that. Number two, to increase the availability of reviews and their potential value in a number of ways make them available in the offices of policymakers, in public libraries, community health centers, through online subscription of the Cochrane Library; to develop executive summaries of the systematic reviews that clearly and concisely state the results of the reviews; to develop electronic jargon-free versions of systematic reviews with hypertext links to allow readers with various backgrounds to access information at different levels of complexity; to expand the area of the complementary medicine field website to include access to review summaries and to include consumer-friendly information. Then, to identify the need for working with organizations such as NCCAM clearinghouse to find out what are people calling for, on a monthly, basis that is really important to them, and then commission topics for review so that the questions addressed and the information developed are relevant to the users of these treatments. Finally, to develop methodologies to evaluate non-randomized controlled trials, thus broadening the pool of information that can be drawn from them. I think, with support, the field would be able to undertake an ambitious program of generating and disseminating high-quality information to the public. DR. GORDON: Do you want to take a breath and put on the other hat? DR. BERMAN: I actually had a Terps hat and a Ravens hat, but I left them in the car. The second part of the talk, a different subject, is the challenge of integrating CAM research into conventional academic institutions, and the training of CAM practitioners as research investigators. This is really focused around issues ensuring that research in CAM meets the highest scientific standards, and there are a couple points about this. One, it is important to tap into our country's academic institutions for their infrastructure and intellectual wealth, and two, we must make sure those involved in CAM research know about the therapies they are investigating, including their unique paradigms. Our center at Maryland has been in existence now for 10 years, and we are well aware of some of the challenges of bringing CAM research into an academic medical center. I think our taking an evidence-based approach to CAM has been an extremely important part of our developing positive relationships with the institutions and the people therein. We collaborate now with Departments of Epidemiology, Medicine, Pediatrics, as well as Schools of Pharmacy, Dentistry, and Nursing on preclinical and clinical research, as well as other people, both in this country and abroad. Just as important is we have built up trust and respect, and nurture the common curiosity and finding out what works and doesn't, and how this translates into improving our patients' lives. So, I was asked, well, what are some of the challenges in doing this. I would say, number one, the lack of knowledge and understanding of CAM amongst the medical community is one of the first challenges facing any CAM initiative in the medical school or university and with this, a lot of bias can still occur. Number two, sometimes, even if there is a willingness, the interest can be driven more by chasing sources of funding. This can, at times, lead to a highly experienced researcher designing and being funded for a study that isn't sensitive to the way a therapy is practiced. Also, researchers may not have a good understanding of what are the key questions that need to be answered, the sort of big bang questions. Another issue is the importance of a clinical base in order to build a program of clinical research in CAM. At our own center, we have a fully functioning outpatient clinic staffed by practitioners who are duly trained in conventional medicine and complementary medicine, as well as a number of highly qualified CAM practitioners. We found the clinic to be vital as a nurturing ground for research questions that are firmly based in clinical reality, however, establishing a clinic of this sort within an academic medical environment is not always welcomed or readily supported by the institution. I think complementary medicine research has suffered from the lack of CAM practitioners who are knowledgeable about research. The value of an academic-based center is the possibility of developing a team to design and conduct rigorous complementary medicine studies that draws on the expertise of methodologists, clinicians, and CAM practitioners, a critical mass of people. However, the role of the center should also be to train CAM practitioners to become skilled CAM researchers. These researchers, in turn, will ensure the future leadership of the field. So as an example of that, we have recently submitted an application, through the Fogarty, to take people from Beijing University, who are trained in traditional Chinese medicine and now want to become clinical researchers. They will come into our university, they will get trained with a Master's in epidemiology, set courses that are there, and then with a focus, with our people in our own center, to work on particular studies in the area of complementary medicine. But even with the best team and with highly skilled CAM investigators, there are many practical issues common to almost all researchers conducting well-designed studies, and these are the issues of limited funding resources for the type of large randomized, controlled trials that are needed. Some of the many challenges of seeing a research trial through to the conclusion include the usual complaints of space, paperwork, especially now as it get increased with IRB demands and funding bodies, and the difficulties of keeping patients invested in the study, especially if they are randomized into an arm of the study that does not include a CAM intervention. Some recommendations, that good science is a key component to evaluating the role CAM can and should play in the health care of Americans. In turn, education and training are the key components in creating a community dedicated to rigorous evaluation of CAM. So, a number of recommendations for achieving these aims would be, one, to fund a network of centers of excellence at academic institutions dedicated to the investigation of CAM. Some of this work is already going on at the NCCAM, and it is beginning to create the infrastructure necessary to support large and far-reaching research programs, as well as educate and train a growing pool of investigators dedicated to the CAM field. The scope and number of these centers needs to grow. What I have heard here, which you are certainly aware of, is to encourage collaboration between the CAM community, government, industry, philanthropy, and academic health centers through forged partnerships and joint funding. Number 3, to fund career development initiatives that would include research fellowships, including didactic teaching, hands-on training with appropriate mentoring aimed at creating skilled CAM clinical researchers, and also a Masters of Science degree in epidemiology with a CAM clinical research track. The third, would be a critical appraisals training, focused on finding and assessing the scientific literature, and I think that kind of a workshop -- we have had a number of those over the years -- have been very successful, and I think that is the kind of thing you can take as a traveling show, both for the CAM community, as well as the conventional people wanting to get involved with this. Then the CAM tracks at medical schools and residency programs, allowing interested individuals to focus on CAM, which would include experiential elements, as well as the clinical uses, and then methodological issues in CAM research. I would also put in one as the creation of a centralized database of curriculum topics and information material to facilitate the integration of CAM into existing courses, so that people at different universities who actually want to bring this into the courses that exist will have ready material to draw from. I think my time is up, so I thank you very much.Panel Discussion
DR. GORDON: Thank you, and thank you for being so gracious. Brian couldn't be here tomorrow, so his part two would have been, ordinarily, under Training of Conventional and CAM Investigators. So thank you for preparing so well and doing them both at this time. I would like to open with one question, and then the Commissioners may have other questions. You three represent two government and one non-government agency that are very important in providing information and good information about CAM. Do any of you, or all of you together, have any thoughts about how the responsibilities might best be divided up among the various government agencies and non-government? For example, where is the boundary with NCCAM and the National Library, the Agency, and the Cochrane Collaboration? Who do you think best does what? DR. LINDBERG: I think what Dr. Berman was describing is the scholarly production of critical reviews, and that has always been a very, very important part of the scientific literature, very much admired and sought. That, certainly, is what they are doing. That is certainly not what the Library is doing, or will it ever do. On the other hand, we are sort of, I would say, committed to solid information infrastructure, and with respect to these clinical trials, I agree with Dr. Berman, these data are hard to come by, particularly if you go back in the old literature back in the turn of the century. I don't spend much time back there, frankly. We, NLM, and FDA are required under the 1997 FDA Modernization Act to create a database of all clinical trials for, let's say, significant disease in the U.S., and our first step has been to make clinicaltrials.gov, focusing on those that have NIH support. That currently numbers 5,500 trials in 5,500 places. I am only talking about existing ones that patients can call a telephone number and enroll in, or at least consider. That was hard to do. Our next step, of course, is the privately supported ones, drug houses and otherwise, those we will go hand in hand with FDA, because we want to be certain that they are properly described. Beyond that, of course, is overseas. So, there is plenty of work for everybody to do, but our part of it, I would say, is the infrastructure, and it is not writing clinical reviews. DR. GORDON: What about, for example, how evidence reports would relate to systematic analyses? DR. LINDBERG: If they are published in proper journals, they are in there. DR. KAMEROW: The evidence reports that we produce, our systematic reviews, when you compare them to a Cochrane review, what you find in general is that the evidence reports are broader. You might think of them as comprising several different Cochrane reviews. That is a generalization, but it is generally true. We also always have someone who has suggested the topic to us. So it is very important to us to take the review when it is done and give it back to the folks who requested it. It may be a government agency, it may be a group of physicians or other practitioners, it may be a health plan. The hope, then, is that they are going to do something with it, and we generally ask them before they ask us, or as they ask us to do them, what will you do with it, create a guideline coverage decision, some sort of quality improvement program, something to put it into action. Of course, because we are a federal agency, everything we do is in the public domain. So, of course, it is put on the Web, and available, as well. DR. GORDON: Where is the boundary with AHRQ and NCCAM? DR. KAMEROW: Well, they are partners with us. They have asked us, just as we have groups in the private sector who ask us to do topics, we have become in just four years to the point where about almost a half of our budget is contributed by fellow federal agencies, sister, whatever the gender is. DR. GORDON: How much is your budget? DR. KAMEROW: We have about $3 million a year from agency funds that go to fund the evidence-based Practice Centers Program. So a group such as NCCAM will come to us and say, we would like reports on X, Y, and Z, and we talk about trying to get some funding from them, and then we do them. DR. BERMAN: There are some ways that I think they can work together, and are working together as well. With the National Library of Medicine, I think the abstracts of systematic reviews from the Cochrane Collaboration now go into MEDLINE. I think that started about a year ago automatically, and I think they also download the central registry, which is now in New England, to MEDLINE, so they get that way. I know a number of the Cochrane Collaboration have been involved with some advising on the complementary medicine field side within NLM, and the same with AHRQ. When they started, there were evidence-based reports. We know the field, we know the people who are doing it. So some of the people, like Cynthia Murrow [ph], came to us and said, who do we know that could act as either content experts or involved in systematic reviews in there. I think that is one of the ways to work. The Cochrane Collaboration has the ability because they have so many people worldwide, and they are interested in different things. So it depends what they are interested in, but they can do many different systematic reviews. So in the four or five years that it has been receiving funding from NIH, I think we have accomplished about 100 systematic reviews, and I know there are people interested to do a lot more than that. DR. GORDON: What would the next steps be in collaboration, if you could look ahead? DR. BERMAN: I would say, to help with NLM; how do they build an even stronger, finer net to capture the relevant studies might be one way of working together, and then on the systematic review side, I don't think the evidence-based reports are going to be able to do all the systematic reviews that need to be done. DR. GORDON: I'm sorry, Brian. I didn't understand. DR. BERMAN: You might correct me if I'm wrong, but I think these evidence-based reports are in-depth and, as I said, there may be several systematic reviews, as well as, I think, other information. So the evidence isn't really ready for that kind of a report. Yet, it is ready for a systematic review. It is very necessary to do that to find out where the evidence is. DR. KAMEROW: We are trying to find ways to work with the Cochrane Collaboration. We co-located several of our evidence-based practice centers with U.S. Cochrane centers four years ago, and so some of the personnel are the same. We always make sure that we search the Cochrane database as we begin one of our evidence reports because why reinvent the wheel. That is the whole point of this. The Internet, of course, makes that a lot easier to do. So, we are still trying to find a way that we can collaborate better, I think, with the Cochrane Collaboration. DR. LINDBERG: It seems to me the critical reviews are a very good contribution. If it is possible to make nicely written explanations that patients can understand, we link to those kind of things through MEDLINEplus provided that they are from legitimate sources, either agency or voluntary health organizations, that they are kept current, that it is clear what biases are present, but we welcome the opportunity to link patients to good explanations. So, I would say that is a possible area for expansion. NLM has actually been known to ship a little money to you guys, and I haven't seen any checks come back, so I imagine that is a reciprocal arrangement that could be continued. DR. GORDON: Wayne, Joe Fins, and Bill. DR. JONAS: The panel not only represents government and non-government, but it represents the spectrum of data, information, and knowledge. Hopefully, we can take it even further, to wisdom. One thing that Brian didn't mention along the line of what Dr. Lindberg, you just mentioned in terms of public information, is that the Cochrane Collaboration now is actively working on developing lay summaries of their reviews also that will go right along with the evidence reports and the regular summaries specifically working with public input on how to produce those summaries, so that it will be easier for the public and more valuable for the public. Before I ask my question, I want to digress a bit and thank Dr. Lindberg for the support that he gave our initial attempts to try to assess this literature. He had me to the Board of Regents, and began immediately to assess the current journals to look at, where were their quality journals that were not being indexed in MEDLINE. To my great surprise, the vast majority of them were somewhere in the collection of NLM, or many of them already indexed. It was quite a surprise to me because everybody had always said, gee, there is all this stuff out there that is not there, and actually, a lot of it was. Also, in the evidence-based centers, Doug, as those were getting developed, I think we weren't sure exactly what they were going to be able to do in the area of complementary medicine. I am happy to see that you have taken, really, a bold step in looking at something as complicated as Ayurveda because one of the obstacles was, is that literature accessible, and is it any good. The general attitude was that it may not be good, but at least we need to look, I think, and know. My question relates to that now. At the time it didn't appear that it was ready to really launch kind of full blown into the assessment of evidence. We were still trying to develop the methods for doing that including in the Cochrane Collaboration. I am just wondering, do you feel that the field is ready to begin to do kind of an overall assessment of the literature? After all, it really isn't that big in terms of the amount of research literature that is out there relatively speaking, and I know that many of the things that we had talked about here, that people have requested, is if we just had some central authoritative source of the current literature evidence and how it existed, that this would be a useful starting point for a number of activities. I am just wondering, do you feel that the field is ready for that, and would an infusion of support and funding be able to adequately begin to address this? Or, is it even needed at this time? DR. KAMEROW: Is that a question for me? DR. JONAS: It is for all of you, but, yes, I think, Doug, you could certainly start. DR. KAMEROW: I am not an expert in CAM, so I can't really tell you, for sure, the answer, but it seems to us that it is a step-by-step process, that we clearly need to move into some new methodologic areas to be able to do this right, but that we were also able to use the current processes I think to do a pretty good job. Ayurveda was a good example where it was kind of hard for those of us trained in Western medicine to -- I will speak for myself -- to put my mind around the concepts that were put out very carefully and pretty clearly by the Rand Corporation when they did the report, but you have to really shift into frames. Still, though, there is the need to have a defined outcome of some sort, a divine intervention of some sort, and something to compare it to. I don't think that you can get around that. I think that is the question and can you define them and come up with ways to do it. One of the things that Rand is doing is trying to figure out ways to statistically correctly and methodologically provide an overview of non-randomized controlled trials in a way that can be helpful, because a lot of this literature isn't a randomized controlled trial. Some would argue it can never be. There are certainly some interventions for which that is true, but many, that is not true, and so I think that the idea of investing in one of the centers over a period of a few years, giving them a number of topics, getting them familiar with sometimes it is a foreign language or whatever it required, a lot of the language is German, that that may be necessary, can move us along, both in terms of the actual topics, but also the methods that are needed. DR. JONAS: What I am hearing you say is that resources really are not the issue even now, it is really the methodological development. DR. KAMEROW: Oh, NCCAM has provided us most of the resources, it is not coming from AHRQ money, we just don't have that much, so if they are willing to support it, we, I think our centers can provide useful information. DR. JONAS: The assessment of observational data, non-randomized trials, isn't that something, though, that is of interest and is being explored all over in medicine, not just in complementary medicine? DR. KAMEROW: Well, it is an attempt to try to figure out how to combine those data in ways that we already know how to combine in randomized controlled trials, and that is, at least to my knowledge, still an unsolved problem. DR. JONAS: So, the method really isn't developed yet to begin to venture in to do good evaluation using that kind of data. DR. KAMEROW: But it is also one wants to stimulate the kinds of research that we do know how to evaluate. The problem is that is costly research because if you are talking about large trials, they are going to have enough power to be able to come up with the answers to the questions especially if they are relatively close in terms of the outcome, that, you know, it is slightly better, but not a whole lot better, so a large study you need. DR. BERMAN: I would say, Wayne, also, that a little bit of that work is happening, you know, with people like Klause and the Cochrane Group where they have been working for several years on a review of reviews, and I think three of those have been accepted in Biomed Central, you know, one in acupuncture that I am involved with, and one I think in herbs, but it is piecemeal because there, there is a funding issue. You know, it is mainly a volunteer thing, and that would be I think extremely helpful to have those kinds of overviews together. There is also in the Cochrane Collaboration, you know, there is the Methodology Working Group, and there are people that are really interested, not just from the Cochrane's medicine side, but both sides, to see how we can look at some of these observational studies and do it properly. DR. LINDBERG: I don't think that we should be limited by sort of one mental model of what this field is all about. I am reminded, just this morning I was reading an article in Science. It may not have been the latest one, but it was the latest one at hand. It had to do with malaria, because NIH has taken under Harold Varmis' prodding a good interest in malaria in Africa in the application of molecular biology to that, and, Wayne, you probably remember that. So, NLM is involved in it because of our ability to facilitate communication. In any case, what the article described is what no doctor could ever fail to recognize, the power of botanicals. In this case, it is an Artemisia extract, artemisinin, which is active against falciparum malaria. You don't need a big clinical trial and six years of statistical analysis to be excited by that. We now know that you have to use those drugs in combination with others, but I mean this amounts to a spectacular breakthrough, and it apparently has been written about using a Chinese term for the extract for 30 years. So, I mean a lot of I think what this commission is after is sort of an attitudinal change in attitude, keeping an open mind to these matters, so that the benefits will come from a lot of points where we are not expecting them. DR. GORDON: Joe Fins, and then Bill next. DR. FINS: On that attitudinal theme, we have heard from a number of constituencies during our deliberations who just reject the evidence-based approach. They see it, they cast it as their right to choose whatever therapy they want. They will contest the data that you folks would come up with, which I, by the way, endorse your approach. But how do we build trust, how do we achieve an acceptance of these methodologies, as diverse as they may be, consistent with our dissemination mandate, which is in the executive order, and are there any lessons specifically from reactions from the public to any of the studies that maybe the agency has done that disappoint proponents of one modality or treatment or herb or another? I mean what can we do to build a trusting relationship, so that we serve the public health, we promote safety, and we try to bring things that do work down the scientific pipeline, does anybody have any thoughts on that? DR. BERMAN: One way I think is to bring the different groups together when we are looking at some of these questions and when we are looking at the systematic reviews, so there should be some consumers involved with what questions particularly are important to them, and then if they are involved with the whole process, as well as through the dissemination, I think that is going to make all the difference in the world. There is not much point to have somebody in an ivory tower picking out a systematic review of something that really isn't relevant to your average person, but if there are topics that have real value to them, and then the participatory type of research then goes on, I think that will make a big difference. DR. KAMEROW: I would agree. I think that having patients involved on these panels helping to select and refine the topics is useful. There is a bit, of course, always of the keys-under-the-lamppost phenomenon where people who are doing reviews want to go where the evidence is, where the literature is, and people, whether they are physicians, other practitioners, or patients, may have different questions that can't be answered very well by what literature is out there. So, there is always a kind of a conflict there, and it leads to, one hopes, good research agendas in that area. As a family doctor, you know, when I see patients who are interested in these things, nothing substitutes for good information and education on everybody's part, and I think most of us in conventional medicine don't have much education about these substances, treat them with disdain, if not lack of knowledge, and that doesn't help anything. But we still need to have good information available, so I think that is the problem, is trying to get more good research, and it is nice that the Cochrane Collaboration has undertaken the attempt to put into lay language their systematic reviews. That is something we talk about, but haven't done yet. It is not a trivial matter. DR. GORDON: Thank you. Bill. DR. FAIR: On the other end of the spectrum that Wayne mentioned, there was a great deal of experience and knowledge in this area, but it seems to me that this is really very impressive, but many of the CAM practitioners, at least I am associated with, are over the age of 25, and the computer is an intimidating object to them. What I am wondering is do we really need something like finding CAM Information for Dummies or something, because I don't think you will find it here, do we need to go back, or is there such a thing? DR. LINDBERG: We wouldn't use that term, I don't suppose, although it does sell books, but the MEDLINEplus is definitely aimed at patients, families and the public, and it isn't particularly dumbed down, but it is using straightforward terminology and linking to other sources on the web. If we can find Cochrane things to link to that explain this stuff, that is great, we will for sure do it. I don't think anyone quite understands the best way. If I could just mention one other thing, I didn't give you recommendations, but the recommendation clearly from the Library is pay attention to make sure that the public can get good information, can get ready access to good information. I agree with you, not everybody is facile with a computer, so that is why we are trying to work with the public libraries, hoping that, you know, what is whole thousands of other sites that they could go to. Thus far, it has been pretty well received, and the public library people from the American Library Association have embraced the idea. It may seem obvious to you, but I would say 10 years ago, that the medical library and the public library people really didn't have that strong a partnership, but it is emerging from exactly this scheme to get electronic information to the patients. DR. FAIR: I think it is a great idea. Are the locations of those libraries on your website? DR. LINDBERG: Yes, but some are cities, some are little towns. Initially, our questions were, well, will anyone bring medical questions to a public library, and if so, what kind of questions, how good are the answers, and can we help, and it has turned out that, yes, they do. Now, if you bring them to a place -- I visited, for instance, a New York Public, Midtown Branch, 96th Street -- well, those people are fantastic. They are not afraid of medical questions or any other kinds of questions. You will definitely leave with good answers. But on the other hand, and I can't throw this in CAM terms exactly, but when I was there, I tested them by asking about flu shots, and their software was smart and understood "flu" is influenza and "shots" is immunizations. So it gave all the right information. Then I said, well, where do I get a flu shot, and it conjured, and did its searching and all that sort of stuff, and it said Albany, the Public Health Office in Albany. So, I mean that revealed to us the difficulty in linking to local information, which is what the real individual wants, not just crawling around a Web finding out who gives flu shots, but how to package it locally. So, I guess it is just saying that there is a lot for us to learn about how to serve the public properly, and we are trying. DR. GORDON: Joe. DR. PIZZORNO: First, Dr. Lindberg, thank you so much for putting MEDLINE on the Internet. It is an incredibly useful resource. DR. LINDBERG: Thanks. DR. PIZZORNO: I also have a concern. There was an article, I believe it was JAMA December '99, that looked at abstracts and compared what was reported in the abstract to what was in the journal, and looked at the major journals, the New England Journal of Medicine, Lancet, et cetera, and found that about 65 percent of the abstracts contain inaccuracies ranging from important information not reported in the abstract, to the abstracts actually misreporting what was in the journal article. Is there anything that you folks are doing to try to improve the accuracy of abstracts so they could rely on our MEDLINE searches better? DR. LINDBERG: No. I understand what you are saying. Obviously, we don't undertake that level of review. That is what they pay editors for, for heaven's sake, but there has been more than one circumstance, even since I have been there, in which the people entering the stuff into the database have noticed that a drug dose was wrong, a wandering decimal point, or even a change in units, so the abstract didn't match the journal. In that case, we call the editor right away, but in the general case of assuring that they match, I think we would go beyond our limits if we undertook to guarantee that. DR. PIZZORNO: Brian, I would like to ask you a challenging question. The question is, at what point do we decide that the case has been made for CAM therapy? The reason I say that is because I took a careful look at all the CAM reviews in the Cochrane Collaboration, and virtually every one said, "inadequate evidence to support its use." So, I am wondering, where is the threshold, because it is one thing to say it doesn't work, it is another to say there is not enough research for us to be sure about it. Yet, they both appeared to come out the same as, don't use it. DR. BERMAN: That is a hard question of, when is there enough information. We also looked at that, actually, in the Cochrane Library for conventional medicine, and we looked at all the systematic reviews, and did a random sampling. I think it was in three-quarters of the time, it showed that it didn't work -- not that it didn't work, that the conclusions were inconclusive. There are different reasons for that, that when they did trials, the quality has been improving and the standards have been improving. So we are always trying to catch up, I think. I think a lot of things that you can say is, if it was a good review, it will show where the gaps are, and it will show where the flaws are and how we can do things better. Oftentimes, it is not that it doesn't work. I think that is a little bit misleading. It is more that you can't say one way or another, because of, usually, the quality of the trials and that, in what direction to go further. I guess in the Cochrane and evidence-based medicine, they always say, we are looking for the best available evidence, and it may not be the large randomized, controlled trial or the meta-analysis, but we have to know what it is. I am sort of going around in circles because there is no good answer to your question. In a particular therapy, say, for osteoarthritis and acupuncture, practitioners out there say it is great that you guys are doing a very large randomized, controlled trial, but it is not going to really change how we practice one way or the other with that clinical trial. DR. PIZZORNO: Could you give an example of both a definitive positive evaluation of a CAM intervention and a definitive negative evaluation of a CAM intervention, and what the criteria or research was that was adequate to make that decision? DR. BERMAN: Well, definitive negative, I guess, would be the one with acupuncture for smoking cessation. It is used a lot for smoking cessation, but when you looked at all the trials, there really wasn't much evidence to show that it worked beyond any sort of a controlled group in any way. It was a little bit of a caveat to say, well, you could look at it in a different way and do slightly different studies, but basically, you have to look pretty strongly at that to say out of -- I can't remember, maybe it was 9 or 10 -- clinical trials, that there wasn't much there. I think that was useful for that. A positive one, let's see. St. John's wort would be a good example of that, and that was also an example. St. John's wort in '96, really wasn't on anybody's radar screen, and then a systematic review by Klause Linde in Germany was performed. I think most of the studies were non-English. When they looked at the evidence for that, they said there is quite a bit of evidence to show that St. John's wort has real value. That led on to one of the TV shows, "20/20" or one of them. They did something on that, and now all of a sudden, it came on everybody's radar screen. Then the next step, which I think was very appropriate, the NIH, said, we really need to begin to look at this, and they funded a large randomized, controlled trial to look at St. John's wort for depression. DR. GORDON: Thank you. Thank you three very much. We really appreciate it and appreciate the precision of some of the recommendations, as well. We are going to take a five-minute stretch break and then we will come back. In the meantime, the next panel can come forward. [Recess.]Panel Session IV: Concerns about CAM and CAM Research
DR. GORDON: This will be the final panel of the day, and we thank you for coming and for being with us, Dr. London, Dr. Margolis, and Dr. Grollman. We will begin with William London.Presenter: William M. London, Ed.D., M.P.H.
DR. LONDON: Thank you. I am here representing the National Council Against Health Fraud. The Council bases its claim to be a consumer organization on its founding principles derived from consumer protection law and the scientific process. Included are the beliefs that consumer is not a special class, but a role played by all, everyone in the free enterprise society has a stake in maintaining high standards for health products and services. Professionals in the health sciences, academia, law, and business, as well as government agencies, share a responsibility to help consumers protect themselves from deception and exploitation in health-related matters. Scientific process is essential for discovering truths and validating health claims and information, and we also believe that health products and services should be proved safe and effective before marketing with proponents bearing the burden of such proof. Products and services should be accurately labeled and fully described, and they should be truthfully advertised. I want to read you two working definitions of health fraud, which is in the name of our organization. The first one is from The Assembly Republican Task Force on Health Fraud and the Elderly from the New York State Assembly, June 1986. "Health fraud is the promotion, for financial gain, of fraudulent or unproven devices, treatments, services, plans or products (including, but not limited to, diets and nutritional supplements) that alter or claim to alter the human condition." Another definition of health fraud comes from the Compliance Policy Council of the U.S. Food and Drug Administration, that was announced in a letter by M.L. Frazier, Director, State Information Branch, June 18, 1993. "Health fraud is the deceptive promotion, advertisement, distribution or sale of articles, intended for human or animal use, that are represented as being effective to diagnose, prevent, cure, treat, or mitigate disease (or other conditions), or provide a beneficial effect on health, but which have not been scientifically proven safe and effective for such purposes. Such practices may be deliberate, or done without adequate knowledge or understanding of the article. Intent to deceive is not the issue." The keyword in both definitions is "promotion," and that is where the concern is. I wanted to discuss with you my call to oppose health fraud when promoted using words "complementary" and "alternative." According to NCCAM, complementary and alternative medicine cover a broad range of healing philosophies, approaches, and therapies. Generally, it is defined as "those treatments and health care practices not taught widely in medical schools, not generally used in hospitals, and not usually reimbursed by medical insurance companies." The definition has little to do with what the words actually mean, "complementary" and "alternative." To refer to "complementary" and "alternative" methods is to imply that such methods actually complement other methods or serve as alternatives to other methods. To refer to something as "complementary medicine," implies that it completes what some other medicine does not do on its own. However, just because someone refers to a method as "complementary" does not mean it actually complements anything else and providing benefit to health. The claim that a particular method is complementary to anything else is misleading unless the claim can be supported by evidence. If a method doesn't add to the outcome, then, it isn't truly complementary, it just adds to the cost. What about "alternative?" A dictionary definition, American Heritage Dictionary of the English Language, Third Edition, defines alternative in three ways. One is "Allowing or necessitating a choice between two or more things," and definition 2a is, "Existing outside traditional or established institutions or systems," 2b is, "Espousing or reflecting values that are different from those of the establishment." The definition from NCCAM suggests that "alternative" is similar to "alternative" in the sense of dictionary definition 2a, and to some extent this is a fair characterization. However, I point out that "alternative" medicine is largely traditional itself and it has become its own "establishment." Promoters of "alternative" medicine often promote traditional systems of healing. Strong reliance on tradition is one of "alternative" medicine's biggest problems. When I use the term "alternative," I am using it in quotation marks. Tradition-bound systems resist change. Their proponents selectively seek affirming evidence while rejecting disconfirming evidence. Science-based, evidence-based medicine has a different approach. It is one in which practitioners learn to discard unsafe and ineffective methods rather than to cling to them. My big concern is that I am unaware of efforts, first, by the Office of Alternative Medicine, and later by the National Center for Complementary and Alternative Medicine, to identify methods promoted as complementary or alternative that should be discarded. In order to provide reliable and useful information about complementary and alternative medicine, it is necessary to identify methods that should be discarded, and I ask that the Commission make recommendations to accomplish this based on principles of consumer protection and science. I think it is also fair to note that "alternative" is now an establishment. We have many institutions that are part of an alternative medicine establishment, so in that sense, alternative medicine is misleading, as well. According to a usage dictionary, "alternative" may suggest adequacy for some purpose, but questionable and alternative and dubious methods are not adequate for their intended purpose, so calling them "alternative" is misleading. Now, it is unavoidable for practitioners of any sort to use unproven methods. Medicine won't have all the answers. Patients have complex problems. Clinical judgment and innovation will always be important to delivering health care. The question has to do with promotion, the promotion of unproven methods through methods such as advertising and publicity is objectionable because it is deceptive. It violates the ethical principles of veracity and non-maleficence. Everyone wants alternatives, but they want genuine alternatives. Many promoters of "alternative" medicine exploit this by calling for "freedom of choice" for consumers. What these promoters really want is freedom from accountability. They support the concept of caveat emptor, "let the buyer beware," but they have a problem with the concept of caveat vendor, "let the seller beware." Caveat vendor provides a rationale for consumer protection laws to compensate for the disadvantageous bargaining position consumers have in the health marketplace. It is difficult to evaluate claims for health products and services. We are vulnerable to mistaken perception and deception especially when we feel threats to our well-being and when we are desperate for answers. It is important to protect consumers from both intentional and unintentional deception, and it is also important to preserve true freedom of choice. Thus, the model of the National Council Against Health Fraud is enhancing freedom of choice through reliable information. I ask the Commission to enhance freedom of choice by recognizing the need to identify health fraud when it masquerades as complementary and alternative medicine. DR. GORDON: Thank you very much. I am sure we will come back and be asking for some specific suggestions from you. Simeon Margolis.Presenter: Simeon Margolis, M.D., Ph.D.
DR. MARGOLIS: First, let me thank you for the opportunity to testify before the Commission. Let me preface my remarks by stating that as a practicing physician, I would enthusiastically welcome any complementary or alternative product or practice that is proven to be effective. The first question we were asked to address was what were our major concerns about CAM practice, and as you have heard, and will hear, the major problems with CAM, I think are well recognized. Most CAM products and practices are either untested or their use is based on unreliable research. Nonetheless, they are aggressively promoted, usually with guarantees of success, and yet any experienced physician knows that no treatment or procedure is always effective. These promotions and promises mean that patients may not only waste money on unproven measures, but also fail to seek medical attention and obtain effective medications or procedures for illnesses that may have serious consequences. People are urged to use CAM products because they are natural, apparently forgetting that poison ivy, floods, hurricanes, and tornadoes prove that natural isn't necessarily good. Finally, because CAM products are unregulated, patients can be subjected to serious risks, and we all know of studies that have shown that a number of herbal products contain toxic constituents or contaminants. I have chosen to discuss in more detail chelation therapy as one example of CAM. Chelation involves a course of two to three weekly, two-hour long intravenous infusions of EDTA for a total of 30 treatments. Originally, chelation was said to improve atherosclerosis by removing calcium from plaques in the arterial wall. Now, chelation therapy is reputed to improve angina and painful peripheral vascular disease by binding heavy metals that damage tissues and proteins by oxidizing them. However, there is no data to support either the theoretical benefit or any properly controlled study that supports the effectiveness of chelation therapy. By contrast, in two randomized, blinded studies done in Scandinavia and New Zealand on patients with peripheral vascular disease, researchers injected either EDTA or, as a control, saline alone. After treatment, there were no differences between the EDTA group and the control group in how long they could walk on a treadmill before developing leg pain. A recent Canadian study of 80 angina patients reported this March at a meeting of the American College of Cardiology found no differences between the EDTA and control groups and how long they could walk on a treadmill before developing ischemic changes on an electrocardiogram. But in all three studies, patients in both the EDTA and control groups had modest improvements in how long they could walk before they developed either leg pain or angina, and I think these findings emphasize the critical importance of including a control group in studies of chelation or any other CAM or conventional product or procedure. In the Canadian study, at the end of one year of follow up, there were no deaths and one heart attack in the subjects in each group. Nine patients from the EDTA group and 6 from the control group had to be hospitalized for treatment of angina. On questionnaires, patients in both groups reported similar improvements in angina and a better quality of life after they had been treated, and chelation patients often will tell their doctors, and indeed feel, that they have been improved by the treatment, but I really suspect that anyone here, in front of me or behind me in the audience, would tell their doctors that they felt better after they had undergone 30 intravenous, two-hour injections and about $5,000 out-of-pocket expenses. Most distressing to me is a statement that was made in response to this Canadian study by a past president of the American College for the Advancement of Medicine, who was quoted as follows: "I have been doing it for 18 years and have seen some dramatic differences. I have been really impressed with it." He also said that 75 percent of his patients respond and are able to walk further and to have less chest pain. His reaction raises in my mind the terrible concern that CAM practitioners will not accept the negative results of scientifically valid studies, and use those results to alter their practices appropriately. If that is true, then, properly conducted research by either CAM investigators or government-supported investigators at academic institutions will be a tremendous waste of time and money. Quite frankly, I cannot believe how any practitioner who is truly interested in the welfare of his or her patients, given the available evidence about it, can continue to practice chelation therapy. A second question we were asked to address is how can valid research study the complex issues inherent in CAM research. I would like to begin with a quote from an editorial in JAMA a few years ago which stated, "Advocates of alternative medicine argue that many alternative therapies cannot be subjected to the standard scientific methods, and thus, instead, must rely on anecdotes, beliefs, theories, testimonials, and opinions to support effectiveness and justify continue use." Well, I disagree completely with the notion that CAM therapies cannot be subjected to valid testing, and I submit that the problems associated with CAM research are inherently no different than those faced in other areas of clinical research. What is needed is some ingenuity, the design of carefully controlled studies, and the willingness of investigators to roll up their sleeves and go to work. My recommendations to the Commission then. First, CAM research requires large, well-controlled studies which provide scientific evidence that either support or rejects the value of all CAM products, such as herbs and vitamins, as well as procedures like chelation and therapeutic touch. Here, I will echo what has already has been said, and that is, that such studies on safety and efficacy must be done before marketing and before promotion of products, because it would be exorbitantly expensive, indeed impossible, for government agencies to fund such studies on every product or procedure that imaginative and entrepreneurial people can think of to sell to gullible members of the public. I have heard, for example, that the NIH may feel compelled to use, I might even say waste, taxpayer money to fund yet another study on chelation therapy, despite the lack of any evidence to support it and the completion of three studies showing no benefit. The health food industry is doing well and can afford to carry out such studies before products and procedures are promoted and marketed. The failure to carry out such studies means that the public will lose out on two scores. First, the public will continue to waste money using ineffective and possibly risky CAM products largely based on the widespread misinformation in the media and on the Internet. Secondly, equally important, the public will not have widespread access through conventional physicians to products and practices that really are effective. My second recommendation to the Commission is that you urge Congress to revise the Dietary Supplement Act of 1994, so that the Food and Drug Administration has some control over CAM products and procedures. Finally, the Commission and CAM practitioners must accept and act appropriately when the results of sound studies prove that a CAM product or practice is either ineffective or dangerous. Thank you for your attention. DR. GORDON: Thank you very much. Arthur Grollman.Presenter: Arthur P. Grollman, M.D.
DR. GROLLMAN: Thank you for inviting me to appear before the Commission. My background is as follows: I am a physician trained in internal medicine at Johns Hopkins, I have served on the faculty at the Albert Einstein College of Medicine and the State University of New York at Stonybrook. As Chair of the Pharmacology Department for 25 years, I have been responsible for educational programs in pharmacology for medical students, other health professional students, and practicing physicians. I see patients in the role of attending physician in medicine, and I conduct NIH-supported cancer research in the area known as molecular toxicology. You should also know that I have conducted research on the active principles of several herbal medicines, and I have served as a consultant to the Dahli Lama of Tibet regarding the use of Tibetan herbal medicines. Our panel was asked to discuss our concerns regarding CAM and CAM research. I will focus on the former, describing the dangers resulting from the unregulated use of herbal medicines. Many are convinced that this is the Achilles' heel of alternative medicine. Many herbal medicines are safe, others available in health food stores or prescribed by herbalists may be harmful. A serious safety problem is the widespread adulteration of Chinese herbs with drugs and heavy metals, 40 percent in one study by the State of California. Since 1962, when the Harris-Kefauver Amendments were enacted in response to the thalidomide tragedy, the American public has taken FDA surveillance of commercially available medicines for granted. Most are unaware that since 1994, the Dietary Supplement Health and Education Act, DSHEA, allows herbs to be marketed as dietary supplements. Prior testing of dietary supplements is not required by law, and there is no premarketing safety approval by FDA. Understandably, physicians, pharmacists, researchers, and some leaders in the botanical industry have called DSHEA "an accident waiting to happen." Now, in your briefing document, I cite three examples of serious toxic reactions associated with herbal medicines. Additional reports will surely appear before this Commission submits its report to President Bush next spring. Importantly, the incidents I will discuss would not have occurred had the manufacturer been required to provide proof of safety. I will briefly summarize these events as a basis for the discussion, and then offer suggestions as to how such public health tragedies could be avoided in the future. Aristolochia has been used in Europe and Asia for 2,000 years. For five centuries, women in Great Britain were given Aristolochia during childbirth, hence, its common name birthwort. In China, the herb is used to treat symptoms of arthritis. A decade ago in Belgium, about 100 otherwise healthy young women were reported to have developed irreversible renal failure requiring dialysis or transplantation. This group had one thing in common. They had attended the same weight reduction clinic in Brussels where they were given a cocktail containing the usual drugs plus several Chinese herbs including Aristolochia. In addition to permanently losing kidney function, half of these individuals subsequently developed renal cancer. The syndrome, now known as a Chinese herb nephropathy, has been reported in countries throughout the world including the U.S. What can we learn from this unfortunate event? First, that herbs used for centuries in folk medicine can have serious toxic effects including cancer. Aristolochia is hardly unique, comfrey tea, highly toxic to the liver; sassafras, which contains a carcinogen; and many other examples can be cited. Second, the genotoxic properties of the major component of Aristolochia had been established at NIH 20 years before the tragic event in Belgium. Third, stronger laws are needed to protect the American public from toxic substances sold as dietary supplements. Last month, nine years after the initial clinical report, and seven years after the herb was banned in many European countries, the FDA finally sent warning letters to pharmacies, manufacturers, and consumers. Some voluntary recalls have been made. However, Aristolochia remains available. Now, contrast this failure of the FDA to respond to reports of a serious herb-associated toxicity with the situation that occurred with the drug thalidomide in the sixties. Thalidomide, thalidomide, introduced as a sleeping medication, was taken by pregnant women whose children were subsequently born with disfiguring birth defects. FDA was alerted, thalidomide was not marketed in the U.S. The public, however, was alerted and concerned, and major new laws requiring more substantial proof of safety and efficacy were enacted. Regrettably, basic safety regulations that apply to OTC and prescription drugs are not granted to herbal preparations under DSHEA. Ephedra. Again we deal with an herb used in traditional Chinese medicine. Analogs of the active principal of ephedra, ma huang, known as sympathomimetic amines have been subjected to more studies by pharmacologists than any class of drugs in history. These studies have shown that the structure, pharmacology and toxic effects of ephedra alkaloids are essentially similar to those of epinephrine, methamphetamines, speed, and phenylpropanolamine PPA. Now, in the U.S., herbs containing ephedra are rarely used for its time-honored medicinal purpose, that is, to relieve bronchial congestion. Instead, ephedra has been adopted as a mainstay of weight reduction programs and as an energy pill. Over time, tolerance rapidly develops and the toxic effects of higher doses on the cardiovascular system and the central nervous system are both predictable and profound. In recent years, over 1,000 serious toxicities associated with ephedra use were reported to the FDA, far more than any other dietary supplement. Half of these were in individuals under the age of 40. Now, since less than 1 percent of adverse effects resulting from dietary supplements are reported to the FDA, we can estimate that 100,000 individuals had suffered reactions to ephedra including cardiac arrhythmias, hypertension, psychosis, seizures, and death. Now, still focusing on safety, compare the FDA response to the toxicities associated with ephedra, an herb, with those associated with phenylpropalanolamine, a drug, knowing that the pharmacological properties of both agents are essentially the same. In a recent issue of the New England Journal of Medicine, the adverse effects of these agents were independently analyzed. The use of PPA was associated with an increase in the number of strokes in young women. An FDA warning was issued and pharmacies promptly removed OTC drugs containing PPA from their shelves. In contrast, although the simultaneously published study of adverse effects of ephedra confirmed the FDA's earlier analysis of those reports, no action to protect the public was taken. The final example of preventable toxicity has enormous potential for harm. It has been alluded to several times today, but not specifically. I refer to herb-drug interactions as recently reported for St. John's wort, a widely used herb in the U.S. and even more widely used in Europe for symptoms of depression. Essentially everything we take into our bodies including drugs are metabolized and herbal medicines are no exception. The pathway by which St. John's wort is metabolized is shared by approximately half of all drugs used by millions of Americans being treated for hypertension, heart failure, asthma, AIDS, and other chronic diseases. Thus, this herbal remedy, apparently innocuous when taken alone, has ability to inactivate the effects of life-saving drugs on which many patients with chronic diseases depend. You saw the data presented to you by Dr. Eisenberg this morning. Because herbal medicines contain many chemicals, they are much more likely than pure drugs to be involved in drug interactions, and the scope of this problem could be significantly reduced simply by requiring premarketing safety testing. What should the Commission recommend to the President to reduce the clear dangers associated with the unregulated use of herbal medicines? I suggest the following: Echoing Dr. Eisenberg's strong plea and first and foremost as a matter of highest priority, Congress should amend DSHEA, so that manufacturers of dietary supplements, including herbs and other botanicals, would be required to obtain premarketing approval by demonstrating safety to FDA. Two. All recommendations contained in a recent report by the Office of the Inspector General, I sent the executive summary to you, with respect to reporting adverse reactions to dietary supplements should be implemented. Among other things, OIG recommends that the manufacturer should report all adverse drug reactions to FDA. Third. NIH should conduct randomized, double-blind, placebo-controlled clinical trials designed to test, not only efficacy of selected herbal medicines, but also to record their adverse effects. This essential information recently obtained for St. John's wort, will establish the all-important risk-benefit ratio. Finally, if resources are limited, only after the major safety issues have been addressed, basic research on the mechanism of action and toxicities of commonly used herbal medicines should be conducted as this approach can provide leads to new drugs and help to anticipate toxic effects. Thank you.Panel Discussion
DR. GORDON: Thank you. Thank you all for your thoughtful comments and suggestions. Tom. MR. CHAPPELL: Thank you all very much for your concern for consumer safety and good science. I am a manufacturer of herbal-based wellness products that qualify under DSHEA and OTC drugs with the FDA. I share your concern and join you in wanting to bring greater safety to consumers, and the route of doing that is more knowledge, more science. I do want you to be aware, however, of the options that are available to us manufacturers at the present time, because it really gets to my question that I have for Dr. Margolis and Dr. Grollman. We can do a responsible search of available literature on the safety data of a given herb, and that search can provide very clear indication of sufficient clinicals or trials that have been conducted on an herb, and that search will indicate whether there are problems in history. That search can also keep very current with ongoing trials that are going on, so I think the first responsible action is to do a sufficient search of available information. The second responsible action would be test the safety and efficacy. That, too, is a possible course for any of us in this business. Now, having done both steps, a secondary search and specific testing, the options available to us do not change. They are: market under the DSHEA law, marked as an over-the-counter drug, or apply for a new drug application that is a long and expensive process. What I am suggesting is that in the case of plants, such as our herbs, commonly known herbs, that the public wants to have access to, there is very little proprietary data available because there are no patents for such work. The search, the motive to do the research is very limited because it is not patentable, and I am not recommending patentability of these herbal substances, but I am suggesting that there is a far vast open area of a middle ground of simply doing safety and efficacy testing of herbs that does not require a new drug application or does not require hitching the formulation to an over-the-counter drug, monograph-approved item like pseudoephedrine. So, what would you recommend given the options, because all I am saying to you is that for us to do the secondary research, for us to do the clinical research, the options don't change, they are still the same - DSHEA, over-the-counter drug, or new drug application, and it is extremely limiting. So, if you want more evidence, what kind of evidence, and the FDA does not have the time, is not staffed to pass judgment on the tests that are done. That is why postmarket is the best course they have. They have testified here that safety is the best they can keep up with. Efficacy is on, at best, a chance or a crisis basis. So, the middle ground, it seems to me, is just doing, as you say, use some ingenuity, some basic evidence-based research, six-month clinicals, 150,000 bucks or 250,000 bucks, whatever is involved, and those are not small numbers to the people in the health food industry. They are back-breaking numbers to most of them. At the moment, there is no middle ground, and that is why even responsible manufacturers seek the umbrella of either DSHEA or OTC drugs. Now, for me -- DR. GORDON: Tom, excuse me. Do you have -- MR. CHAPPELL: I do have a question, would you put this burden of testing -- but, of course, I had to provide this background information -- [Laughter.] MR. CHAPPELL: Would you put the burden of testing, as you say in Item 3, Dr. Grollman, back to the NIH for these commonly held or these common herbs for the basic research, or would you put the burden on the manufacturers? So, that is my question. We are dealing with publicly available herbs and drugs. You don't need a prescription for these things. So, where do we place the burden of proof of a publicly available plant, with the government or with the manufacturer? DR. GROLLMAN: I am very clear on this. I definitely would place it with the manufacturer, and I would point out -- but I think that some of the special aspects have been taken care of in a document which I am sure you are familiar with, that the FDA put out on advice for botanical products. They allowed you to take information from abroad and from other things. In other words, use this great, wide use and you could bring this. You can't do this with a regular drug. I think this is very important to be able to bring the evidence you have. From every point of view, because of the diversity in your profession, not all of the manufacturers particularly where herbs are brought from abroad, and they can't be checked, they actually can't be checked, they can't be checked as to whether they have the right name on them, et cetera, so the burden must be placed on the person to do that. Dr. Eisenberg put it very well this morning - safety trumps efficacy. Safety is what we all owe the people. It has nothing to do with the size of the industry, the money, and actually a $5 billion herb industry is pretty good and is growing. So, I think that an industry -- MR. CHAPPELL: It is declining at the rate of 25 percent a year currently. DR. GROLLMAN: Last year, yes, but a $5 billion industry can certainly afford to do the testing that the American people expect to have. The FDA obviously can't do the testing, nor do I believe it should be shifted to the taxpayer, which is basically what you have suggested as the other possibility, shifting to the NIH. So, I do feel strongly about that, but I think that accommodations need to be made because of their long history, and that document that I referred to, that you know of, I think tries to do that, and I think they ought to work with industry to further work within that. DR. MARGOLIS: I agree completely that the burden of proof, certainly for safety and hopefully for efficacy, lies with the promoter or the manufacturer. I am really impressed with your statement putting clearly the problems that you face, but you say that these herbs are widely available to the public, but they are only widely available because they are widely promoted. The public would never have heard of these herbs if it weren't for the fact that they are advertised all the time. So, that is what brings the public's desire to have them, but they are unaware of the fact that they either have potential risks or that they are not beneficial. So, I think the burden does have to fall on the manufacturer, but there ought to be, and I would be in favor of -- I am not familiar with the document you mentioned -- but I would be in favor of alternative ways to allow herbs that have proven safety and studies that show efficacy to be marketed. That is the desirable goal, not some rule that has to be passed, but that these products are proven to be safe and effective. MR. CHAPPELL: Well, thank you for your concern and your suggestions. DR. GORDON: Dean. DR. ORNISH: I also want to thank the panel for your thoughtful comments which were very helpful, and I certainly agree with the position for the need for evidence-based approaches. I think most of us on the panel would agree with that. I guess I just wanted to make two points. One is certainly, Dr. Margolis, I share your concerns about chelation and I thought you did a very good job about critiquing that, but particularly I guess with the National Council Against Healthcare Fraud, and so on, why aren't you equally vigilant with conventional therapies in terms of holding them to the same standard. I think there is a concern among many of the people that we have heard testifying that there is a double standard, that the same rigorous scientific evidence-based approach, which we all agree on, certainly I do, isn't applied equally, I mean in the same vein -- or artery I should say -- as chelation, the same standard to angioplasty or radioactive stents. There was an article that was presented to the American College of Cardiology just six or eight weeks ago showing that radioactive stents actually increased complications, atherosclerosis, and yet the use of radioactive stents has increased since that time. I don't see anything in the National Council Against Healthcare Fraud journal -- I guess it's the Scientific Review -- are you affiliated with the Scientific Review of Alternative Medicine? DR. LONDON: We are a separate organization completely. DR. GORDON: I'm sorry, I couldn't hear. DR. LONDON: We are completely separate. DR. ORNISH: But are you also working with that journal, too, or not? DR. LONDON: I think I am a contributing editor. DR. ORNISH: I would say that is some affiliation. DR. LONDON: But that is me personally, and I am a volunteer for both. DR. MARGOLIS: Can I address that first? The reason I would like to is the last thing I did before I came here today was review about six articles on brachiotherapy for stent placements, and there is some disagreement among them, but studies have been done. Sincere efforts have been made to see if they work, to test various doses. They found that the first doses they used didn't work, so they are trying different doses. They are using different radioactive compounds. Some are using beta, some gamma emitters. So, I think the difference is not that there is a double standard, but that there has to be at least an effort, a sincere effort to study things, and there will be disagreements, but at least they must be studied and carefully evaluated, and that is a situation with angioplasty and brachiotherapy. DR. ORNISH: We are all in agreement with that, but the difference is that you are also saying, and certainly the journal is saying, that unless something has been proven to be effective and safe in double-blind, randomized trials, it shouldn't be used, and that is not the case here, and yet it is still being used. I am only making the point that I think that your impact might be greater -- and this is just a personal thing, not speaking so much as a commissioner -- if you applied the same rigorous standards equally to conventional and other approaches, both in terms of evaluation and the standard of what should be out there and what should be made available, and as you say, people may be using supplements because they are being pushed by advertising, but they are using radioactive stents because they are being pushed by people who have other economic incentives, as well as a genuine desire to help. I think you find that mixture of motivations on both sides. I just think that to the degree that those standards could be applied equally, I think there might be a better dialogue. I am also curious why -- just two last points -- why you don't vigorously support increasing the research budget for, say, the National Center for Complementary and Alternative Medicine if the goal is to have more good scientific research, which certainly I think we both agree with. The problem has been that the other double standard is that until recently, it has been very difficult to get those studies funded. You may say, well, industry should be funding supplements, and that is certainly one position, but many of these alternative interventions have no industry as such, and I am just curious to know what your position is. This is directed both to Dr. Margolis and to Dr. London on increasing funding for good quality scientific research, because part of our recommendations are going to be dealing with issues like that. DR. MARGOLIS: Well, having served on several NIH study sections, I can only say that I truly believe that peer review of a well-designed study in alternative medicine would be funded. That was always an opportunity, and I don't remember in the years I was on the study section that there was ever such a proposal made. Secondly, it happens that at Hopkins we have just been given a large amount of money by the NIH to study alternative medicine based on four proposals that I was involved in, in some advisory way, four proposals to carry out what we hope are scientifically valid studies of alternative medicine. DR. ORNISH: I am familiar with that because I reviewed that for the NIH. I was on the study section. But the point is that until this year, that was the first year there was a study section to specifically look at grants in NCCAM. DR. MARGOLIS: I think that there needs to be more provision of funds by the NIH for truly valid studies, but at the same time, as I said earlier, the government cannot possibly study every herb or procedure that is being promoted, there just isn't enough money, so they are going to have to be very selective in picking the ones for which there is at least reasonable evidence that they might be effective. I think St. John's wort is a good example where there was some reasonable evidence that it was helpful in mild to moderate depression, and so they have chosen to support that, and I hope they will continue to pick and choose among the best options to provide support that would give real evidence. DR. GORDON: Joe first, and then Tieraona. DR. FINS: Dr. Grollman, in your role as a toxicologist, could you tell us about the level of preparedness of the poison control centers in the country to handle toxic events and any recommendations that you might make to increase their level of awareness about the toxicities related to supplements that they are encountering as you demonstrate, and also any strategies for tracking these events in a systematic way, so we can understand the extent of the public health issues related to these agents. DR. GROLLMAN: I would be glad on, and you should get from the national head of the Poison Control Center, if you really want, you should have her, Ms. Liebowitz, I think it is, should actually come here, but here is the essence of what she would say. They get calls from people who are taking supplements. There is no way that the individual knows from the label, nor is there any connection with the manufacturer, so they are really operating in the dark. So, they would urge you in the strongest way to make sure the manufacturers, number one, are known and that there is a listing, so that they would be able to do it because you know how a poison control center, they have to act quickly. Now, with other chemicals and things, they have that information. They do not have it. There are 17,000 cases related to dietary supplements this year. They don't break them down into herbs. They have herb homeopathic remedies. They don't break them down up until now. Next year they will break them down. I am sure you are going to find the biggest section is with the herbs, but they don't have the information to do it. That would be a very important thing for you to put into it, and I would suggest that you get a true poison control center, particularly the executive director, who I think can do it. Now, that report that I cited, I hope that you have all taken advantage of it, the Inspector General's Report addresses several of those as to how to do it, and, in fact, the FDA should actually contract with the poison control centers, so they can find out what is going. FDA gets a thousand reports. There is 17,000 of them out there, at least putative ones out there, so they could contract with them, but you don't help the FDA by starving it, and if they don't have the money to even get a trivial contract, to get the information, so you can help this whole process by suggesting that the small amounts that the FDA is requesting -- you know, it is 2/10ths, 3/10ths of a percent that is not receiving attention on the Hill, which would allow them to make contracts with poison control centers, to get adverse drug action, that would be a tremendous help. DR. FINS: Of the people who staff these centers, even if they had that information, you know, in the next iteration, what is their educational preparedness for handling the drug-drug interactions? They know about insecticides and things like that, but how much do they know about the supplements and what kind of educational strategy would you recommend for their CME? DR. GROLLMAN: Well, remember herb-drug interaction would be the kind like I described. You have an older person who is taking, and all of a sudden he goes into heart failure. Well, you really need an internist, a trained family physician who puts it together and says, gee, they are either not taking their digitalis or something was interfering with it, but certainly poison control centers would never, with any education, couldn't handle that. What I would really like to do is cut it off at the beginning and have industry -- we spoke about the cost of doing it. It doesn't cost a lot to test for drug interactions, $10- $15,000. They give them a cocktail and you could test your herbs. That is a very small expense and done as a Phase I thing on volunteers, and that is something the manufacturers could do with an herb, and if you did that, then, maybe the problem would disappear rather than taking care of it after the fact. DR. FINS: Before that happens, we could probably do this before that -- DR. GROLLMAN: Yes. DR. FINS: Thank you very much. DR. GORDON: Thank you. I also wanted to share with you that we have heard a lot of testimony about helping the FDA move ahead with their efforts especially to monitor adverse events, and that is something the Commission feels very strongly about, as well, so we appreciate your recommendations and also about the Office of the Inspector General Report. Thank you. Tieraona. DR. LOW DOG: I want to appreciate all of you. Thank you for all of your comments. Mine are really focused on the botanicals, and it is the Achilles' heel, there is no question, and they range from foods and spices to dilute drugs to potent substances, and so we tend to just talk about them as herbs, and they are just vastly different. You cannot compare comfrey to garlic, I mean, so there is just huge differences there. DSHEA is going to be difficult to overturn. I mean we are seeing that. There is a lot of industry fighting for an overthrow of that bill, of that act. I know that the USP, which I work with, we are in the middle of a pilot program right now that will be available for people who want to participate, it is voluntary, this fall, and it will assure the consumer that that herb company has undergone an GMP inspection meaning that it has shown how it can identify, quarantine, look at the plants, it is free of heavy metals, it is free of pesticides in accordance with the law, that it is the right genus species, et cetera. It is amazing how some support we are getting from the industry and how much also resistance we are getting from the industry for that. The safety data is there for many of these plants - ginseng, ginkgo, St. John's wort. They didn't do mostly drug testing, p450, they didn't do those. The problem that I think we are going to have in this country, though, is that the German companies who spent that money on doing that safety and toxicity research, did it on their particular extract and product, so the ginkgo is free of ginkgolic acid, but if you are doing a different ginkgo, it may have it in there. The black cohosh may not have the estrogenic substance in it, black cohosh, Remifemin, but you might in a product here. So, I am curious, given the state of where we are with DSHEA now, do you believe that the federal government -- I believe the manufacturers need to step up to the plate, too -- but do you believe that the federal government has a role to play from a public health point of view to take the top 20 to 25 herbs that make up 80 percent of the sales in this country and do the safety studies on them? I mean if they are not that expensive and we take the major herbs that are being sold, is that something that we should step up to the plate for as a government or as an agency, one of the agencies from a public health point of view? DR. GROLLMAN: What the government should do is not to overthrow. Overthrow is a word you don't use in Washington. Just amend it. Just make the simple amendment to put the burden on the manufacturers the safety. That's all. So, that's a smaller, smaller change. It addresses the point that was so discussed in the very beginning, but I think that is -- and I think the manufacturers should also attend, and they would, to standardization is what you are bringing out in the difference between the Germans. Now, just being careful and just being standard and having a commission and monograph isn't enough. Look how many Germans have been taking St. John's wort for how long for this, they didn't pick up the drug interaction at all, so remember that just writing a nice monograph never makes up for -- but I think that your specific question was or the option was should the NIH or some government agency take in the testing. I think that would be going down a slippery slope. I don't think they are going to do it, and while the other, I think is a way of professionalizing and actually saving the wonderful things that could be done with herbal medicines is just get Mr. Hatch to let the question be raised, and I think that we should look at it again. DR. GORDON: I just want to ask the Commissioners if you would please focus on questions. We have a significant but limited time with the panel. DR. LOW DOG: The question about the amendment, would you require safety and toxicity data for everything, peppermint, chamomile, and would we take them off the market? I mean I guess my question is, because we have argued with this dilemma, what would the amendment be, have you thought through that and how we would do it? DR. GROLLMAN: Well, I haven't thought through as well as this letter that the FDA -- and they have thought through, and it is treated very differently from a drug. They are open to the information, not just from this country, but it is a big step to say we would take the information from abroad. So, you could provide the information from the -- commission the monographs, so that is going to simplify it a great deal. Simpler, straightforward cellular studies and testing for drug interaction, which have never been done, just need to be done. So, I think that new document offers a real opportunity for a discourse for people who want to make this happen. DR. GORDON: Wayne. DR. JONAS: Thanks. I think we heard from a number of groups including the manufacturing industry, that there should be some modifications of DSHEA, and I, myself, am going to suggest that that be one of our recommendations in some form. Clearly, that needs to be addressed. I am rather saddened actually by the lack of interest there is in evidence. We talk about it, for all the number of times we use the word evidence-based medicine, I don't think people seriously are interested in evidence. The reason evidence-based medicine, the term and the whole process came about, was not because the public wasn't using it, the public wasn't even involved in the discussion, it was because professionals weren't doing it, and every new technology that came up got into practice before -- DR. GORDON: Wayne, could you come to the question, please. DR. JONAS: Yes -- and now we are just adding on top of that the public and the manufacturing. I guess the question is, is there a standard that most reasonable people can agree? For example, would you agree that what was discussed on the last panel, the Cochrane type of work, is the type of evidence evaluation that we need to be doing? Would everybody agree with that, Dr. London, would you agree with that? DR. LONDON: Since I walked in right as that was ending, I am not -- DR. GORDON: Could you come a little closer to the mike, please. DR. LONDON: I didn't get to hear those presentations. DR. JONAS: Any others on the panel? DR. MARGOLIS: I think it is a very good first step. The problem is, as you heard, for most of the studies they have done, they come to the conclusion that they can't reach any conclusion, and that gets back to the point that it is fine to do these literature searches, but if there is no good data, they don't help very much. DR. JONAS: The next question is really what you all are addressing, is all right, let's say we now know what we do know or what we don't know, how do we get that out into actual recommendations and practice, and I think maybe that is where the government has not, and in the past they have gotten into recommendations, but they have pulled back from that, and now most government agencies that I have dealt with are very loath to make recommendations one way or another, positive or negative. AHRQ actually had some trouble because they got into make those kinds of recommendations, and now they no longer do that anymore. So, I am wondering if there are some suggestions from you all as to how evidence can get better disseminated into practice and also to the public, is there anything that we and the government can do to recommend that, are there some suggestions that you have assuming we can come up with agreements on what is good evidence or what is at least a good methodology as to how to really make communication, should there be a center that is sanctioned, if you will, that then disseminates that in some way, or are there any ideas about how to do that? DR. GROLLMAN: The gentleman from the Public Health, working closely with NCCAM, he is developing those, so clearly, people can do that. The German experience is clear. You can get intelligent people working together with information, and you can do that. I think it is very important to do. Now, the public gets it from the Internet, and that is an impossible thing to sort out. I can't sort it out, they certainly can't sort it out. So, I think that that should be a strong recommendation to get the information, but we certainly ought to be able to communicate, and that certainly is a government responsibility. DR. JONAS: I think Bill during the break recommended that what we really should be doing is getting PubMed to work with AOL on line because they actually are the main ones where most people get their information, health information in some way. DR. MARGOLIS: I am not sure I think it is a good idea to have government do this, because if it comes from government, there is always the question in the minds of practitioners whether that is a regulation, a requirement, or a recommendation. So, I think it might be better to come from the various groups, internal medicine groups or others who could take this information and make recommendations to internists, family physicians, surgeons, and so on. But coming from the government, I am a little concerned that it would be suspect. DR. JONAS: [Off mike.] DR. MARGOLIS: Except they don't have any information, and I think the idea would be if these Cochrane Reports or other studies would put together the information, and it were credible, that a product or a procedure should be used, then, I suspect those organizations would recommend their use. DR. JONAS: [Off mike.] DR. MARGOLIS: That would be my thought, to have them make the guidelines. DR. GORDON: Don. DR. WARREN: I was kind of interested in your comment about the $5,000 not being able to speak up. I believe that people, no matter what they spend, if they think they have been done wrong or they think they have been scammed -- DR. GORDON: Don, could you come a little closer. DR. WARREN: -- I think they are going to say something one way or the other. We can differ about that, and that's okay. We talk about a lot of things here with CAM. We also have a problem with drugs in that we have off-label use of drugs. We are talking about having the manufacturers of all CAM products prove their efficacy and safety. Should we then have the drug manufacturers prove the efficacy and safety of the off-label use of their drugs? And then I have got one more thing after that. DR. MARGOLIS: That sounds like a question to be answered by a pharmacologist. DR. GROLLMAN: That is not a bad idea. Certainly, that has not been the case. I think it is a very reasonable proposition to do so. DR. WARREN: And these off-label uses of the drugs are promoted. Does that mean they are fraud? DR. MARGOLIS: No, no, no. DR. GROLLMAN: That is not correct. DR. MARGOLIS: If a pharmaceutical representative is in your room and you mention an off-label drug use, they will say we can't talk about that. They really do not promote that. DR. GROLLMAN: They can't promote the off-label. DR. WARREN: Then, I have one other question. Dr. London, who funds your organization? DR. LONDON: Mostly members and subscribers to our newsletter and people who occasionally buy a book or a T-shirt or something like that. DR. WARREN: Any drug companies? DR. LONDON: No. DR. WARREN: Any medical organizations? DR. LONDON: No. DR. WARREN: I just wanted to know. DR. GORDON: Thank you. I have a question, particularly for Dr. London, but really for any of you. In your recommendations, there is sort of a theme saying that if there is information, if information is gained, that a practice is either ineffective or fraudulent, that information ought to be disseminated, or that some kind of regulation ought to happen. Do you have any thoughts about how that would be implemented? How would we gather the information? And then, who would gather it? And then, how would you suggest getting that information out to the public and practitioners, as well? DR. LONDON: I am not sure how you would do that. My concern is with an imbalance that is set up when methods are studied that don't necessarily have a plausible rationale to support them. Just the fact that things get studied lead reasonable people to think some experts must think there is something there to base that on. I don't know, with all the investment and studying a variety of methods, that might not get funded on the basis of the strengths of its rationale, what we have learned at this point. I am kind of stumped, but I think it all sends a message that raises expectations, and I think something needs to be done to temper them, perhaps messages, clear messages, that, just because something is under investigation doesn't necessarily mean it is something that is promising. DR. GORDON: I think it is a bind because we have to find out, get some answers. I think that what is happening is, for example, the St. John's wort study that was recently published in JAMA showing it was not particularly effective for serious depression is an example of studying an herb and coming out with a negative result, and publishing it and letting people know. So, I think we are in a quandary. We need the information, just as the other two panelists have said, and since we need the information to make recommendations, yes or no, we are really open to figuring out when something is not effective or is dangerous. We would like to know how to better get that information out, just as we would like to get information out if something is beneficial. That is where we are at this point. DR. MARGOLIS: I will reiterate the point that I made, that even if the public isn't informed, then at least the practitioners should be informed and follow appropriately. I would like to cite what was a recommendation. It says, "Resolved, that pending the results of thorough, properly controlled studies, the American Osteopathic Association does not endorse chelation therapy as useful for other than its currently approved and medically accepted uses, which is for heavy metal, like lead poisoning." So, here is a statement made in 1985, again in 1990 and 1995. It apparently has had no effect on the osteopaths or other physicians who do chelation therapy. So, evidently that approach doesn't work. DR. GORDON: Yes. DR. GROLLMAN: Just to sort of tidy up on two points that I wanted to comment. One was the question of the double standard, a very good point being made, but I want to differentiate in terms of my own presentation. I don't think there is -- this is to your question -- a double standard for new chemical agents. There clearly is a double standard for procedures, and they are not controlled, but for new chemical agents, drugs, I think we do have a method that works, and we could apply it to the other. The second was, there has been a lot of speaking about the public, and protecting the public, but the public is pretty smart. My reading of the 25 percent fall -- by the way, I thought it was only 15 percent. That is what I read in Herbalgram, anyway. At any rate, it is leveling off. I think the public is now concerned about the herbal things. They have heard. They are not waiting for the Commission report. They are certainly not waiting to hear from pharmacologists. So I think that they are on to that, and another reason why I think your recommendations will get some urgency, particularly if we can address a safety aspect of herbal medicine. DR. GORDON: I just want to share with you that we have consistently heard, a major concern of public and responsible manufacturers is, that what is said to be in the bottle is not in the bottle in the strength or the appropriate form. So, this clearly, I think, just confirms everything that we have heard over the last nine months of hearing testimony. That is a major concern. Tom. MR. CHAPPELL: Dr. Grollman, I would just to clarify your position and your recommendations. Your third recommendation is that the NIH should conduct randomized, double-blind, placebo-controlled clinical trials. DR. GROLLMAN: On selected herbs, just as they are doing. The NCCAM is doing just what I would like them to do. MR. CHAPPELL: And the object of those tests is what? DR. GROLLMAN: That is for efficacy, and that is for benefit, because if we have something that has a risk, and we know that it has no benefit or the benefit is placebo, we need to know that. We don't have both sides of the equation. We certainly don't have the risk. That is the safety side, and although I didn't address efficacy, others have, it would be nice to have the risk and the benefit. So, doing the proper studies, as has been said over and over again, and having them done under NCCAM with the funding, on those that seem to have promise, is, I am just saying, more of the same. MR. CHAPPELL: So, public dollars. DR. GROLLMAN: Public dollars absolutely. MR. CHAPPELL: Your fourth recommendation is that basic research should be conducted on the mechanisms of action. Now, as you know, that is even more complicated a study than safety studies. DR. GROLLMAN: You have dozens of very excited pharmacologists, like myself, who would love to do these sort of studies, both on the toxic and on the therapeutic things. Don't forget, although there is no published data on this, but those of you who have a connection with industry, the pharmaceutical companies have been exploring botanicals for the last 40 years. Now, they don't publish when they don't work, or when they do work, but there is no better source of an unusual molecule, and there are wonderful screens now that they can put them in. Chemists don't think that way. They still don't think as complicated as that. So, they are a wonderful source, the pharmaceutical industry, academics, to look at their mechanism of action and toxicity. Academics have to get their funding from NIH. The pharmaceutical companies are driven by themselves. I am suggesting more of that. MR. CHAPPELL: That is consistent with what I was saying, as well. DR. GROLLMAN: Yes, absolutely. MR. CHAPPELL: Very good. Thank you. DR. GORDON: Effie. DR. CHOW: I don't have a question. I just really have a comment, that I really appreciate this panel's discussion because it has brought forth and confirmed our discussions in our groups about the safety. We are really concerned about safety. You have brought up some very good suggestions and some ideas, and I just want to say thank you for that. DR. GORDON: Did you want to say something? DR. LONDON: I did want to answer your question again about how to get the information out. It seems to me that if you can call a method "alternative" or "complementary," that is categorizing it in some way, and I have questioned the meaningfulness of those terms. What is to stop characterizing various methods as unproven. If you can label it one way, why not label it in a way that is meaningful. I think, in my remarks, I suggested three ways you can look at alternatives or complements: one, genuine; two, experimental but hopeful. My concern about experimental is that they should be things that have a promising, plausible rationale. The third, was genuine. It seems to me if you can call things complementary and alternative, you can just as easily call them -- DR. GORDON: So, in fact, those categories transcend complementary, alternative, and conventional. DR. LONDON: I don't buy into the notion of categorizing things as alternative and unconventional, or complementary and conventional. I don't buy into it, period. DR. GORDON: I appreciate that. Thank you very much. Thank you all three, and, please, if you have any further thoughts, let us know. [Applause.] DR. GORDON: We will adjourn now and convene again tomorrow morning at 8:00. [Meeting recessed at 5:30 p.m., to reconvene Wednesday, May 16, 2001, at 8:00 a.m.]