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Minutes of the Sixth Meeting - February 5, 2001
National Advisory Council for Complementary and Alternative Medicine (NACCAM)
On this page:
- Call to Order, Introductory Remarks, and Meeting Procedures
- Future Meeting Dates
- Review of Confidentiality and Conflict of Interest
- Inclusion of Women and Minorities in Human Subject Research—Annual Training
- Annual Director's Report
- View from Another NIH Institute
- CAM on PubMed®
- Annual Director's Report (Resumed)
- Public Comment
- Annual Director's Report (Question and Answer)
- Review of NCCAM's Portfolio and Status of Current Initiatives
- Review of the Training Program
- Review of the R21 Program
- Closed Portion
- Review of the Applications
The National Advisory Council For Complementary and Alternative Medicine (NACCAM) convened at 8:30 a.m. on February 5, 2001 at the Neuroscience Office Building in Rockville, Maryland. Richard Nahin, MPH, Ph.D., Executive Secretary, called the meeting to order. The meeting was closed to the public on February 5, 2001 from 3:00 p.m. until adjournment as provided in Sections 552b(c)(4) and 552b(c)(6), Title 5 U.S. Code, and section 10(d) of Public law 92-463, for the review, discussion, and evaluation of grant applications and related information.
NACCAM Members Present (1)
- Dr. Michael Cantwell
- Dr. Haile T. Debas
- Dr. Richard Grimm
- Ms. Susan Holloran
- Dr. Janet Kahn
- Dr. Konrad Kail
- Dr. Ted Kaptchuk
- Dr. Dana Lawrence
- Ms. Diana Manley
- Dr. William Meeker
- Dr. Karen Olness
- Dr. Everett R. Rhoades
- Dr. Marilyn J. Schlitz
- Dr. Leanna Standish
- Dr. Dana Lawrence
- Dr. Anna McIntosh
- Mr. James E. Williams, Jr.
- Ms. Dean Batten
- Ms. Carolyn Bellamy
- Dr. John Chah, NCCAM
- Ms. Linda Engel, NCCAM
- Ms. Marguerite Evans, NCCAM
- Ms. Carol Fitzpatrick, NCCAM
- Dr. Christine Goertz, NCCAM
- Ms. Anita Greene, NCCAM
- Dr. Eugene Hayunga, NCCAM
- Ms. Christine Hollingsworth, NCCAM
- Ms. Camille Hoover, NCCAM
- Dr. Morgan Jackson, NCCAM
- Ms. Kathleen Madden, NCCAM
- Dr. Richard Nahin, NCCAM
- Dr. Mary Ann Richardson, NCCAM
- Mr. Charles Sabatos, NCCAM
- Dr. Allen Spiegel, NIDDK
- Dr. Stephen Straus, NCCAM
- Ms. Shirley Villone, NCCAM
- Dr. Neal West, NCCAM
Dr. Nahin opened the meeting by noting that there was a full agenda. Dr. Straus would be presenting NCCAM's annual report. The Council would also have their mandatory annual training on the inclusion of women, children, and minorities as research subjects. In a continuation of the practice of having directors of other NIH institutes speak to the council, Dr. Allen M. Spiegel, Director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) will discuss NIDDK's CAM-related activities. In the afternoon, there would be an opportunity for public comment. This was to be followed by staff updates on such topics as the extramural training program and R21 activities. Dr. Nahin noted that NCCAM has experienced substantial growth over the last year, with much hiring in the last six months.
Dr. Straus introduced Dr. Marc Blackman, appointed as the new clinical director of the intramural research program. This is an important position within NCCAM and Dr. Blackman's appointment comes after a long search for the right person to fill the job. Dr. Nahin introduced Victoria Carper, the new chief of the grants administration branch, who comes to NCCAM from the National Institute of Allergy and Infectious Diseases. She worked as one of first grants management officers with the Office of Alternative Medicine (OAM), and was the grants management officer for Dr. Leanna Standish's U24 center grant some time ago. NCCAM has also hired Mark Pitts as a grants management specialist. Dr. Joana Rosario has been designated to head the office of international health research once the government hiring freeze ends. She is a neurologist and epidemiologist with more than 20 years of experience in clinical research, mostly in developing countries. Dr. Rosario has worked with public and private international health and research organizations such as World Health Organization. She has first-hand experience in the uses and misuses of CAM. Dr. Nancy Pearson joins NCCAM as a new program officer; her training is in molecular genetics. Finally, Dr. Shan Wong joins the staff; he has a Ph.D. in biochemistry. The NCCAM office of personnel deserves thanks on its efforts during this time of rapid growth.
Dr. Nahin reviewed the ground rules for the council. The meeting is open to the public as required by Public Law 92-409, the Federal Advisory Committee Act, and the Government in the Sunshine Act. The open portion of the meeting consists of reports to public, council, and staff, including the director' report and concept clearances. The closed portion allows the review, discussion, and evaluation of grant applications in accordance with Title 5, U.S. Code 552 (b)(c)(4) and 552 (b)(c)(6), and Section 10 (d) of Public Law 92-463. Attendance at the closed session is limited to council and appropriate NIH and DHHS staff.
Dr. Nahin reminded the council of the dates for the next two meetings—May 31 and August 27. There will be a need for an October-November session. Dr. Nahin asked council members to review the calendar in their folder, which presented potential dates, and to note when they can attend. Also in the folder were a travel voucher form, a copy of the minutes from November Council, a handout for the mandatory training session, and materials relating to other presentations.
Dr. Nahin reviewed conflict of interest and confidentiality requirements. A conflict of interest may occur when any of the following exist: (1) the member has a designated role in the research; (2) the member has a self-interest—professional or financial –- in the research results; (3) there is even an appearance of conflict stemming from participation of a family member or associate of the NACCAM member. Committee members should not be present for reviews in which they or their spouse, minor child, partner (including close professional associates) or employer has a financial interest. In addition, when an institution with which the reviewer is affiliated has an application under review, there is the appearance of conflict of interest even if the reviewer will not benefit financially and knows none of those involved in the proposed project. If any of these conditions is present, the NACCAM member was to withdraw from the discussion to prevent the proceedings from having an appearance of bias. Council members must sign a form indicating no conflict of interest. Members are to refrain from discussing meeting topics outside the forum of NCCAM meetings. The review process should not be discussed with applicants; to do so would be a disservice to them and other applicants. All materials from the closed portion are confidential. Members must leave the confidential materials with staff.
Dr. Gene Hayunga presented the annual training on the inclusion of women and minorities in human subject research. In 1985, it was determined by the Department of Health and Human Services that the lack of research on women's health concerns worked to the detriment of women. It became clear that the dearth of knowledge was due to the widespread exclusion of women from clinical trials. In 1986 and again in 1993, therefore, NIH addressed participation issues. Many of these issues also applied to minority groups. NIH is working from a legislative mandate that women and minorities must be included in clinical trials.
The 1993 NIH guidelines specify that NIH must:
- Ensure that women and minorities, including minority subpopulations, are included in all human subject research;
- Ensure that in Phase III clinical trials, women and minorities and their subpopulations are included in numbers such that valid analyses of differences can be accomplished;
- Not allow cost to be a reason for excluding women or minorities; and, Initiate efforts to recruit women and minorities into clinical trials.
NIH now includes women, minorities, and subpopulations in all NIH-supported research unless compelling data exist that dictate exclusion. For example, women would not be included in studies on prostate cancer. The 1994 guidelines deem that existing gaps must be addressed. NIH considers this an issue of scientific merit.
In order to track gender and minority subjects for purposes of analyses, reviewers assign a gender/minority code to applications under review. NIH may bar funding based on inadequate gender and minority representation, and this extends to applications and proposals that provide insufficient information as to how women and minorities will be included in the study. NIH can lift bars to funding through program staff intervention. The great majority (80-90 percent) of bars are lifted once more information is provided, which can occur with a couple of phone calls. Only a small number of applicants have had to modify their study design in these situations. Other reasons for lifting bars include portfolio balance, coding error, mistakes, etc. After the award is made, program staff monitor the actual enrollment of subjects. Target figures allow evaluators to review recruitment figures. Program staff evaluate demographic data along with other data in progress reports. The intent is not quotas but rather to conduct research so that scientific knowledge will be generalizable to the population of the United States.
Dr. Nahin asked how NIH tracks subject data regarding women and minorities. Dr. Hayunga explained that demographic data are provided by the grantee and put in to a centralized database that NIH uses to monitor whether or not the policy is being successfully implemented. Program staff can look at the database. There seems to be appropriate inclusion on aggregate basis. Since the policy is science-driven, this information will give a good indication of what is happening in human subject research. Dr. Grimm asked for a definition of "subpopulation"? Dr. Hayunga explained that minorities might be made up of several groups defined by geographic or national origins and/or cultural differences. For example, within the Asian minority group, there could be subpopulations of Japanese-American, Chinese-American, etc. Dr. Schlitz said that her understanding of the initial exclusion of women was that it was due to the complexity of hormones, etc. Now, in terms of cost, she wanted to know if inclusion had raised costs to where it becomes an issue to include women. Dr. Hayunga explained that the law and guidelines do not allow cost to be used alone as a reason to exclude women.
Dr. Straus presented the NCCAM annual report. In January 2000, he projected a series of ambitious goals for that year. In most cases, NCCAM has exceeded those goals.
NCCAM has a responsibility to raise the quality of study of CAM research. The hierarchy of evidence moves from anecdotes to case studies, observational studies, uncontrolled trials, small randomized clinical trials (RCTs), and, finally, large RCTs. As NCCAM deals in a vast array of modalities, clearly there must be a system of ranking and a strategic approach.
NCCAM's investments in research have focused on clinical research, the centers, and basic science research, often tied to NIH areas of emphasis and leveraged via collaborations with other NIH Institutes and Centers (ICs). NCCAM's focus on clinical research is due to the fact that these modalities are in public use right now. The centers have helped the community of CAM investigators to matures. The next step is to add depth by providing scientific rationale for treatments through basic and pre-clinical research. Collaboration helps extend NCCAM's scientific reach through work with other NIH institutes.
NCCAM's twelve CAM research centers emphasize a range of areas, including cancer, chiropractic treatment, arthritic patients, addiction, pediatrics, botanicals, cardiovascular disease, aging and cardiovascular disease, aging and women's health, neurological disorders, and craniofacial health. In addition, NCCAM now has botanical centers at Purdue University, the University of Arizona-Tucson, UCLA, and the University of Illinois-Chicago.
NCCAM has funded cancer centers as well. The Johns Hopkins University CAM Cancer Center focuses on prostate and breast cancer. This center is looking at oxidative stress in cells, natural products in rodent pain models, phase 2 study of PC-SPES in prostate cancer, and the use of prayer in women with breast cancer. PC-SPES is a dietary supplement with eight herbs used for advanced prostate cancer. Small phase I and II trials suggest that PC-SPES is safe and effective, resulting in improved quality of life and a reduction of pain; side effects reflect estrogenic activity. The Center is recruiting 100 men, with prostate cancer that is no longer responsive to hormone refractory disease for a double blind RCT comparing PC-SPES with estradiol. The study is being conducted at two sites. End points are disease progression, safety, PSA measurement, and quality of life measurements.
Dr. Kaptchuk's Harvard study of placebo treatments or acupuncture for arm pain illustrates an imaginative approach that answers several key questions. The study looks at placebo approaches in repetitive strain injuries. The trial involves 270 patients, has two placebo-controlled arms, and looks at both a placebo pill versus amitriptyline and sham needling versus acupuncture. Outcomes will be arm strength, mood, and work capacity.
Dr. Abrams at the University of California, San Francisco, is studying the effects of DHEA on HIV load. This small, placebo-controlled trial looks at HIV load, hormone levels, T-cell function, and quality of life. What distinguishes this study is that they are looking both at classic biomarkers and also at quality of life.
Dr. Targ at the California Pacific Medical Center is studying distance healing for glioblastoma, trying to move this research forward from small trials. The study has 150 patients in a double blind RCT in which healers pray for patient recovery. Endpoints include symptoms and functional status.
NCCAM has sponsored five multi-center RCTs. The St. Johns Wort trial is finished and the data are being analyzed; the shark cartilage and Ginkgo trials are active, as are studies of acupuncture and glucosamine for osteoarthritis.
In 2000, results from NCCAM-supported studies were reported in a number of peer-reviewed journals. Dr. Straus reviewed several of these studies for NACCAM; including two on biological mechanisms of acupuncture.
In Fiscal Year (FY) 2000, there were a number of significant organizational developments at NCCAM. These include the development of NCCAM's strategic plan; reorganization and expansion of NCCAM's organizational structure to best meet the plan's objectives; the official recruitment of: 1) Dr. Nahin to direct the NCCAM extramural program; 2) Camille Hoover to be the executive officer; 3) Linda Engel as a special assistant to the Director; 4) Christine Hollingsworth to lead the budget office; 5) Victoria Carper to head the grants management office; 6) Drs. Goertz and Richardson as health science administrators; 7) Dr. Morgan Jackson as Director, Office of Special Populations; and establishment of service center agreements to staff EEO, ethics, contracts, FOIA, and other key responsibilities.
Overall, the total number of personnel grew from 17 to 36. This is significantly more than the projection of 29 people. The estimate for the total number of personnel for the end of FY 2001 is 53. Most growth came in extramural research, administration, and communications and policy. For 2001, NCCAM expects growth in extramural research and intramural research, with some in other areas. Through the practice of responsible stewardship, NCCAM has developed its human resources and infrastructure. In fact, it is now costing less to do more work than it did a year ago.
Program activities for FY 2000 included the issuance or continuation of 13 RFAs/PAs/RFPs; awards for two new specialty research centers in botanicals; and other grant awards. NCCAM issued a total of 57 competing and 98 noncompeting awards.
NCCAM has also had rapid grown in the area of research training. The research training strategy involves individual and institutional awards, mentored and independent research, and basic research through clinical projects.
Organizational developments planned for FY 2001 include completion of NCCAM's strategic plan for health disparities; establishment of a division of intramural research under the direction of NCCAM's first clinical director, Dr. Blackman, who starts April 1; and recruitment of directors for the Review Branch and for the Office of Clinical and Regulatory Affairs.
As noted earlier, NCCAM has designated Dr. Joana Rosario to head the Office of International Research. NCCAM plans to draft a strategic plan for international research; establish offices of international research, science policy, and communications, under their new directors; and increase the number of personnel to 53.
In terms of FY 2001 program activities, NCCAM expects to issue a number of RFAs/PAs/RFPs; establish the intramural program; and award the first frontier medicine program grants, for a projected total of 154 noncompeting and 47 competing awards.
NCCAM has scheduled a number of major meetings for FY 2001, some of which have already occurred. There was a placebo workshop in November, and the Center was involved in organizing a January meeting on integrated medicine with the Royal College of Physicians in London. Still to occur are a meeting of NCCAM research centers in Tucson in March; a co-sponsored NIH workshop on mind-body medicine in March; a second town meeting in Tucson in March; and a colloquium with industry in May.
Dr. Debas represented NACCAM at the meeting in London. After noting differences between the status of specific CAM modalities in the U.K., Dr. Debas said he thought a greater collaboration with the British would be useful. Dr. Straus added that homeopathy is also more developed in the U.K., which may provide some unique research opportunities. This was a very important meeting that gave NCCAM a chance to appear on the international stage to help shape policy.
In looking at the advantages of industry-NIH collaborations, Dr. Straus noted that these advantages include sharing of proprietary reagents and technologies; exploiting complementary interests in defining basic mechanisms and pursuing particular indications; providing optimal study management and oversight; comparing drugs from different companies; affording greater autonomy of study design and conduct; and sharing research costs. The key is leveraging to help the enterprise move forward.
In another development, the electronic magazine Yahoo Internet Life, which is read each day by many thousands of Internet users, designated NCCAM as presenting the best alternative medical information on the web. In December alone, the NCCAM web site had over 526,000 hits. The site (www.nccam.nih.gov) is one of the key elements of NCCAM's outreach strategy, along with the information clearinghouse, the CAM citation index, the NCCAM newsletter, and town meetings.
The organization's funding history shows substantial growth from an initial OAM budget of $2 million in FY 1992 to an NCCAM budget of $89.1 in FY 2001. As part of the overall strategy to eventually double the budget of NIH, Congress gave NIH a 15 percent from FY2000. NCCAM, on the other hand, was given a 29 percent increase, which reflects public enthusiasm and the wishes of Congress.
The priorities within the NCCAM budget have shifted as the budget has grown. For example, the research project grants made up 24 percent of the NCCAM budget in FY1999; this increased to 32 percent in 2000 and should grow to 35 percent in 2001. Funding for Centers has shrunk from 27 percent of the 1999 budget, to 25 percent of the 2000 budget and 23 percent of the budget for 2001. Support for training, career development, and education combined has risen from 2 to 7 to 10 percent. The portion allotted to administration is shrinking. Distribution of the NCCAM budget is beginning to look more like that of other Institutes and Centers. Center grants and management costs remain slightly higher, but are moving toward the NIH average. Intramural programs are low, because that area is just beginning at NCCAM; this item is likely to grow to 5-8 percent, closer to the NIH average of 10 percent.
Dr. Straus said that one of the most gratifying parts of his job is noting the degree to which his colleagues at NIH have been eager to see high-quality CAM research. He then introduced Dr. Allen M. Spiegel, Director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Dr. Spiegel is a renowned investigator of hormonal mechanisms.
Dr. Spiegel began his presentation by saying that he appreciated the opportunity to appear and was having his own council meeting later this week. The mission of NIDDK is to conduct and support research of many of the most severe diseases in society including diabetes, digestive diseases, and kidney diseases. He presented a few vignettes showing NIDDK cooperation with NCCAM and the Office of Dietary Supplements.
In 1999, NIDDK and NCCAM jointly sponsored a meeting on CAM and chronic liver disease, focusing on hepatitis C. The aims of the conference were to review the literature to determine the scope and spectrum of products used; to determine quality control in the manufacture of herbals; to seek evidence of benefits; to set minimum scientific requirements; and to discuss opportunities for clinical research. Milk thistle is one herbal used to treat chronic liver diseases such as hepatitis C. Milk Thistle is the mainstream therapy in some European countries. There is some evidence that it provides protection in vitro, and it may act as an antioxidant and free-radical scavenger. It is also used to treat mushroom poisoning. Good pharmacokinetic studies are needed, as are studies of herbal products in well-defined animal models of liver disease. There is a need to conduct rigorously designed studies of the use of milk thistle in treating chronic hepatitis C and B, while also looking at the herb and its impact on the side effects of conventional drugs.
Another area of mutual concern is benign prostatic hypertrophy. Current treatment options include lifestyle modification, surgery, drugs (finasteride, alpha-blockers), and phytotherapy (herbal supplements). Phytotherapy is more common in Europe, where saw palmetto is most widely used; its use is increasing in the United States. A meta-analysis of RCTs dealing with saw palmetto showed evidence of improvement compared with a placebo and finasteride. However, many of the studies included in the meta-analysis were flawed. Therefore, there should be additional RCTs using standardized urologic measures. A pilot study co-funded by NIDDK and NCCAM is now in progress at the University of California-SF NIDDK would like to expand this study, with NCCAM collaboration, to a multi-center trial.
Diabetes is a major problem, affecting 16 million Americans, 90-95 percent of whom have Type 2 diabetes and many of whom are undiagnosed. The disease results in an estimated $100 billion in annual health care costs. There are suggestions that chromium enhances insulin action and improves glucose tolerance in diabetics. However, a number of questions must be answered before chromium supplementation could be recommended. In this regard, NIDDK plans to partner with ODS and NCCAM for both basic and clinical initiatives to study chromium.
Dr. Pardes asked if NIDDK is emphasizing disorders or interventions. Dr. Spiegel said that they have multiple points of view. In relation to CAM therapies, NCCAM investigates what is already being used, so NCCAM is studying saw palmetto and milk thistle, for example.
Dr. Debas expressed an interest in gastrointestinal diseases for which there are no good treatments. This seems like a possible interface between NCCAM and NIDDK. Dr. Spiegel noted that despite generous budget increases from Congress, they still must set priorities based on need and opportunities. If NCCAM sees agents in wide use in these areas, NIDDK wants to know. Dr. Straus added that NIDDK lets him know when they are assembling the next year's research agenda and asks for NCCAM's input. This era of collaboration is very effective.
Dr. Rhoades asked about collaboration with the Department of Agriculture; Dr. Spiegel said that they have collaborated significantly, for example, in areas of nutrition research coordination. Ms. Holloran raised the issue of putting research results in public domain. She wanted to know how the process could be fast-tracked. Dr. Spiegel said that he is a firm believer that clinical research alone is insufficient. NIDDK has a national diabetes education program. The Institute's partnerships with NCCAM are treated no differently from others the Institute has done. The studies must be done carefully, then the information must get out. For example, a treatment may have symptomatic relief, but may not have the desired effect over the long-term. NIDDK supports long-term studies with these concepts in mind. Dr. Straus agreed, stating that there is nothing unique here in terms of the difficulty of translating science into practice, except in one regard: prescription drugs are driven by profit motive, which does not exist in this field. Therefore, the public sector plays a more important role. He thanked Dr. Spiegel for his presentation.
Dr. Nahin introduced Sheldon Kotzin, Chief, Bibliographic Services Division, National Library of Medicine (NLM). Mr. Kotzin explained that the NLM was established in the 1800s under the Army Surgeon General, and has been publishing the Index Medicus since 1879. In 1971, NLM started MEDLINE, the first remote access database in the world allowing real-time search. It is both the most widely used and largest bibliographic database in the world devoted to a single subject, with more than 11 million citations. Most journals in the database are scholarly titles, but other publications are included. MEDLINE has broadened to cover all the areas needed to care for patients. PUBMED provides a way to access MEDLINE citations, and NLM advocates the use of PUBMED.
An NLM advisory committee advises them on which titles to add to the database; this committee has a wide range of subject expertise. The committee reviews CAM-related journals, and some committee members have experience in CAM. It is hoped that NLM can enhance the expertise in CAM in the near future. NLM periodically reviews subject areas to make sure nothing worthwhile has been omitted from the database. Reviewers make recommendations based on their judgments according to established guidelines. The major criteria are the quality of content, the importance of the data, and whether the work falls into a meaningful niche. Another area evaluated is the editorial work done by the journal, especially how articles are selected and peer reviewed, as well as the prominence of the editors and advisory board members. Also evaluated is production quality, with a focus on readability and lack of disruptive advertising. Ethical issues come into consideration, too. Finally, the committee looks at non-U.S. publications that report on regional health issues. Many users care about these issues, and 59 percent of the journals on MEDLINE are published outside the United States.
CAM has always been in the scope of MEDLINE. Seventy-five journals in the database have significant CAM content with four more journals scheduled for review shortly. MEDLINE does not carry every CAM journal, but that is the case for all biomedical disciplines. NLM consulted with NCCAM staff in expanding the database and found that they needed to add search terms. This was reviewed with NCCAM staff, NLM expert staff, and the NCI office of CAM. NLM will continue to expand and enhance this area. NCCAM has an agreement with NLM that calls for an easier approach to allow NCCAM web site users to go to the CAM subset on PUBMED directly. This carefully developed subset of MEDLINE emphasizes CAM-related terms. This is the first arrangement with another NIH component to create a specific database for that part of NIH.
Ms. Annette Nahin, NLM, worked with NCCAM to develop the database. She discussed how to do a simple search of PUBMED from the NCCAM site, giving examples of a disease search, a treatment modality factoring in an age group and symptoms, and an author search. Examples of these searches can be found on the NCCAM CAM on PubMed® site. Users can also go from the NCCAM site directly to the PUBMED subset. PUBMED includes terms not specifically entered but related to the user's query. PUBMED also provides links supplied by publishers, in some instances going directly to the publisher's web site for full text. Some publishers provide free information on-line journals, although some do not. A popular feature on PUBMED is the link for related articles, which is done in a ranked format. When this feature is used, the first citations listed are most closely related to those from the source.
Dr. Straus said that this has been an extraordinary exercise. NCCAM staff spent a lot of time developing the previous product (CCI), but they asked themselves if they could do better, and decided that while they could, they did not want to reinvent what NLM had already accomplished. This database makes it easier to search for information. Dr. Meeker asked if the subset makes the search more specific to CAM. Ms. Nahin said that it is designed to help restrict retrieval to CAM. Dr. Cantwell asked if Cochrane Library citations are available on PUBMED. Mr. Kotzin said that they are.
Ms. Holloran asked if there had been a discussion about labeling the subset "alternative medicine" rather than Complementary Medicine on the PUBMED search engine. She also wanted to know if there is a feedback mechanism. Ms. Nahin explained that after considerable discussion, term "complementary medicine" was chosen as the name of the CAM subset. Ms. Holloran said that she believed that was a mistake, because many people will search for alternative medicine. She wanted to know if they could include alternative medicine as an option. Dr. Straus suggested that they try the system as it has been developed and see what happens first. Ms. Holloran asked why they had to choose between one term or the other. Mr. Kotzin explained that this is a technical issue. Most subject description terms are one-word terms; at this time, it is not possible to have more than two words. Ms. Holloran asked about feedback mechanisms. Ms. Nahin said that there is a link to the PUBMED help desk and to NCCAM from the NCCAM web-site. In addition, there is an indexing and feedback mechanism on the NCCAM site as a whole. Dr. Nahin said that the webmaster distributed these comments to appropriate staff (like himself), for response. Dr. Rhoades asked what proportion of the NLM budget is devoted to PUBMED. He also wanted to know about the acquisition of books for people coming in off the street. Mr. Kotzin said that a budget of somewhere between $10 and $20 million probably covers the staff and all related costs. There are separate databases for consumer health and for monographs. Dr. Kahn said that she looked forward to using the database. Previously, it had been rather laborious to cover everything in the database that dealt with massage. Ms. Nahin said that much of the PUBMED strategy relies on the ability of the indexers to do a good job in recognizing CAM topics. Dr. Straus asked the council for feedback as they use the system, as it is a work in progress. The goal is to improve this with time and explore further vehicles as well.
Dr. Straus resumed his presentation of the NCCAM annual report with analyses of the grant application process and funding, as compared with the other NIH Institutes and Centers. The Center for Scientific Review shows data on R01 scores, covering more than 10,000 NIH applications per regular receipt date. Applications are scored between 100 and 500; however, the least meritorious applications , about 38 percent, are unscored. The largest cluster is between 140 and 260. In 1999, NCCAM had only 21 scored applications, which were R21s and R01s. NCCAM funded 12, all but one of which scored between 121 and 220, with one in the 261-280 range. In 2000, 92 applications were reviewed, with 48 percent unscored. The distribution was closer to NIH as a whole, clustering in the 181-320 range. NCCAM funding went primarily to applications in the 140 to 260 range, especially those scoring between 181 and 220.
In FY1999, NCCAM received a total of 23 applications (scored and unscored); this increased to 177 in FY2000. Approximately 212 applications are projected for FY2001. The number of new awards funded was 13 in 1999, 44 in 2000, with an estimate of 37 for 2001. The percentages translate to funding success rates of about 56.5 for 1999, 24.8 for 2000, and an estimated 17.5 for 2001.
Much on NCCAM's budget is already committed to projects that cross fiscal years (out-year costs). Typically, IC Portfolios turn over in a four-year cycle. Being a new organization, NCCAM is not yet at the fourth year to turn over those funds, so FY 2002 will present fewer opportunities for new projects. Already, $89 million in out-year costs is committed for 2002. That year, NCCAM will likely be in a position to fund between $4.5 and $10.8 million in new research. A generous budget increase from Congress will allow more new initiatives. The capacity to roll out approved concepts depends on available funds.
Dr. Straus then outlined a number of activities NCCAM will be pursing in the coming year to help meet its strategic goals including: exhibiting at professional meetings; developing grant writing workshops for applicants; increasing investigator-initiated research; developing health disparities and international strategic plans; creating an intramural research program; stimulating collaborations between CAM and conventional investigators; providing training in conducting CAM research; initiating research training programs; working to increase the number of minority trainees; disseminating high-quality CAM information; responding to consumer inquiries in a timely fashion; collaborating broadly to leverage resources; and dialoguing with stakeholders through town meetings, exhibits, and numerous media inquiries.
Richard Pavek, of the Shen Therapy Institute, which deals with emotional disorders, spoke first. He noted that NIH put out a call last August for review committees looking for degreed candidates and people not degreed but experts in their modalities. He has heard nothing since, and wanted to know if that was still in force, and if review panels will include alternative practitioners. Dr. Nahin replied that CSR gets names from NCCAM when they need them. It is not likely that there will ever be a CAM-specific panel at CSR, but the number of applications is going up, so the number of reviewers will as well.
Robert Spiegel spoke next. His experience is in Chirology, science of hand. Mr. Spiegel is in the process of creating an international society for psychological diagnostics. He thinks there is a need to focus more on diagnostic and therapeutic modalities. Mr. Spiegel said that he viewed diagnostic modalities, especially in terms of CAM, as a blind spot in the organization. He has discussed this with panel members from previous councils.
Dr. Meeker asked what NCCAM should do about the weaknesses Dr. Straus noted in epidemiology and outcomes research. Dr. Straus said that NCCAM is funding some studies in epidemiology and is actively pursing others. He reminded Council that they had approved a concept on surveying underserved populations. In talking to those who really do health surveys, NCCAM decided that funding regional surveys would not be broadly relevant. Therefore NCCAM is currently developing a national survey through the National Center for Health Statistics (NCHS), which is part of the CDC. Dr. Nahin added that there are not many investigator-initiated applications in the area of outcomes research. Dr. Meeker said that he would like this to be discussed and developed. Dr. Goertz said that she has had some conversations with the Agency for Health Care Quality and Research regarding setting up outcomes workshops related to CAM.
Dr. Kail asked if the centers meeting will be open to the public. Dr. Nahin answered that there will be a town meeting the next day that is open to the public but that the Centers meeting, itself, is not open. Dr. Schlitz asked if there will be sufficient funds to support the RFAs that NCCAM has put out. Dr. Straus said that there would be, but the Center might not fund everything if the quality is not high enough. Dr. Rhoades suggested that it might help to have data on what CAM research has been supported. Dr. Straus explained that NIH assembles that information regarding what CAM work is being done across NIH, not just at NCCAM. The numbers are now being assembled for 2000. Dr. Grimm asked about the grants funded by NCCAM that have joint support. Dr. Nahin said that there have been very few so far, but many projects are in the pipeline involve co-funding. Dr. Kail said that he is frequently asked about the best way to apply for grant money through NCCAM. He wanted to know if applicants can suggest co-funding where they believe it might be appropriate. He also wanted to know what would occur if an application addresses more than one initiative, such as underserved minority populations and a specific disease. Dr. Nahin said that applicants can suggest in their cover letter the IC(s) they think would be most appropriate. Regarding multiple initiatives, the same application cannot be submitted to two initiatives simultaneously. Program staff are available to guide applicants toward the most appropriate choice. Ms. Holloran noted that there are 13 solicitations out now. She read the integration RFA and thought it was wonderful. She wanted to know about the response to it. Dr. Straus said that that would be addressed shortly.
Dr. Nahin began his presentation by stating the dollar amounts he was about to present have not been confirmed by the NCCAM budget office and are simply best projections. He presented the NCCAM portfolio broken down by clinical trial, basic research, and epidemiological research. Total funding was projected as $40.8 million for clinical trials in FY 2000, with $13.4 million projected for basic research and $1.3 million projected for epidemiological research. Through the first council round in March 2000, these numbers were projected as $24.2, $5.4, $0.3 million respectively, so there has been much growth, especially in clinical trials. Epidemiology is low because of the dearth of appropriate expertise in the CAM research community. Through July 2000, the numbers were $30.4, $8.7, and $0.7 million, respectively. Divided by disease category, the total investment was projected to be $12.3 million for musculoskeletal, $8.8 million for neurology, $7.7 million for cancer, $6.1 million for cardiovascular, $4.3 million for mental health, $3.2 million for women's health, with lesser amounts spent on other categories. This distribution reflects how CAM is actually used. At the bottom of the list, diabetes is last, with a projected $0.4 million allocated. This is of concern, and NCCAM is hoping to work more closely with NIDDK. Gastrointestinal is projected at $0.9 million, and this, too, is an area that NCCAM needs to stimulate. The pulmonary disease category is estimated at $0.6 million, but Dr. Richardson is putting together an RFA that will go out soon regarding magnesium to treat asthma.
Another way to break out the portfolio is by CAM modalities. The biologically based category is projected at $31.6 million; this area covers dietary supplements. Alternative systems is $11.8 million and includes such areas as traditional Chinese medicine; acupuncture is the biggest contributor here. The multiple category is projected at $1.6 million and covers basic science studies. Energy healing doubled from about $1.3 to $2.6 million, largely due to applications from the University of Pennsylvania. Mind-body research is projected at $4.3 million. Manipulation and body-based (such as chiropractic and massage therapy) has projected funding of $3.6 million.
The council had a list of initiatives sorted by the date on which they went to council for concept clearance. Few have finished the review process. The list shows how initiatives spread out across a number of diseases and a number of CAM domains, and emphasizes that NCCAM looks for research opportunities wherever they may occur. The list also gives an idea of staff workload. There were 22 initiatives over an 18-month span, which is quite a bit of work for a small staff. Ms. Holloran asked if staff knew the numbers of applications for the concepts that are closed. Dr. West replied that they had received 13 for frontier medicine and 43 for integrated medicine. Ms. Holloran asked if the differing numbers of responses meant anything. Dr. Nahin replied that applicant cohorts vary according to their ability to respond. For instance, there was a large cohort of health service researchers who were able to respond rapidly to the integrated medicine RFA. Dr. West added that the botanical-drug interaction area has a well-developed community and NCCAM has more than 50 applications in that area.
Dr. Pardes asked how it was determined that an area is worth studying. Dr West replied that the areas are approved by the council. Dr. Nahin added that public use and lack of data on efficacy are major factors. Dr. Pardes asked if frequent use determines study areas. Dr. Nahin said that it is one of several criteria. Also considered are the significance of the public health problem and the total cost. Dr. Kahn noted that while CAM often focuses on wellness, and there is no column for wellness in the table presented by Dr. Nahin.
Dr. West presented a review of the NCCAM training program. NCCAM offers a broad range of training opportunities. A series of charts detailed these opportunities, which include pre- and post-doc fellowships. A number of T32 institutional training grants are available, and there are currently five CAM-related grants through other institutes. Three chiropractic fellows are supported through co-pay arrangements. There are two new T32s that are the first all-NCCAM training grants. These grantees are in the process of selecting fellows. A number of career development awards have been given, with three K01s, four patient-oriented K23s, and two K24s. The latter awards are for mentor support, meaning that they pay for senior investigators to be mentors by buying them time away from their other responsibilities. Two K30 curriculum development awards support development of clinical trial curriculum. A summary showed NCCAM's total training and career development funding to be about $2.4 million. While data across NIH are hard to compare, a summary of NIH competing applications for F32 and T32 awards showed that every year has been remarkably consistent over a decade. The intramural area will provide additional training for CAM researchers. NCCAM research centers have included fellowship training programs that will make a significant contribution to NCCAM's career development program once the centers fill these slots.
Dr. Straus said that Council needs to help determine how much training is enough. The question is, how many more trainees should be funded in what areas and what type, or has NCCAM reached the threshold already? Dr. Kahn said that while the council has seen the number of proposals, they have not seen a ratio of proposals received in the various CAM areas. She will know that they are ready to cut off or stabilize training funds when the proposals coming in reflect high quality across various modalities. Dr. Pardes agreed, but suggested that there is a need to determine where there is more promise in a modality. He would like to focus on those areas showing the most promise. Dr. Nahin observed that much of the NCCAM's portfolio is in the dietary supplement area because most quality trials in CAM thus far have been in that area. The next largest modality in the NCCAM portfolio is acupuncture, which has been funded by NIH since 1975. Acupuncture has a longer research history than any of the other remaining areas, with the possible exception of chiropractic. Dr. Nahin added that four of the five big trials in progress four are based on meta-analysis. Thus, NCCAM is following the evidence. In other, less well research areas, NCCAM is looking at smaller, developmental trials.
Dr. Pardes said that he liked NCCAM's focus on quality applications. He encouraged NCCAM to consider the payoff before beginning large trials. The question of who is best able to determine the most promising areas of research was discussed by the Council. Several members felt this should fall to the PI to argue for relevance. Others suggested that Council must allocate a certain number of dollars according to the best investment of public dollars. For instance, it might be more important to invest in cancer than in something not life threatening. Part of Council's task is to put together a body of information for the public, and in doing that, they will treat certain areas differently.
Dr. Straus said that Council should distinguish areas of research as opposed to training. Research needs to explore a broader range, and can take more risks. NCCAM does not take the same risks with trainees. It is unwise to put a new person on a nebulous area; it is better to give them something they can sink their teeth into and learn from. Dr. Cantwell said it is unlikely that NCCAM will ever be done training CAM practitioners and researchers. Dr. Grimm agreed, and said that NCCAM should put more money into training, which is a good use of funds at this point. Training goes on forever, and there are not that many people who know how to do good clinical research. Ms. Holloran suggested that they do a formal evaluation of training, both quantitative and qualitative, over time, with focus on formulating and answering the right questions. Dr. West said that is NCCAM's intention. Dr. Kail said that while he agreed with most of what had been said, he was concerned about creating a situation of the blind leading blind. There are people who just had training grants and who are now having mentoring grants. Dr. Straus said he would like the Council to recall this discussion when future training applications are considered.
Dr. Goertz explained that it has been historically difficult to receive R01 funding for CAM research at NIH due to the frequent lack of preliminary data and poorly developed research methodology. The R21 program provides investigators with an opportunity to explore the feasibility of CAM projects, develop projects investigating CAM, and generate preliminary data. While preliminary data are not required for an R21, rigor in research methodology is still necessary. Funding under this mechanism is available for up to two years, non-renewable, with a maximum of $125,000 in direct costs.
The funding history of R21s at NCCAM show an upward slope. Last October was the first round for resubmissions, for which NCCAM received nine and funded three. To date, the Center has funded 15 R21s in basic (pre-clinical) research and 15 in clinical studies.
Dr. Straus observed that about 48 percent of R21 applications were unscored in FY2000.
Dr. Standish said she would like to see this change over time. Dr. Straus explained that R21s are not the meat and potatoes of NIH grants. A sign of success will be the proportion that develop into R01s. Dr. Cantwell asked if there was a sense of what percentage involved collaboration between CAM and non-CAM institutions. Dr. Goertz said that the CAM practitioners did not necessarily come from CAM institutes, but rather from organizations that have CAM investigators affiliated with them. Dr. Kail noted that almost every collaborative application was funded.
Dr. Meeker asked if they could track collaboration data, as it seems useful. Dr. Straus agreed, but cautioned that it is also hard to always know who is the CAM practitioner. Dr. Goertz said that they can try to do such a breakdown as long as people understand that definitive, hard numbers might be difficult to develop. Dr. Grimm suggested that they could look more easily by examining the financial data that institutions must file. Dr. Standish said that the R21 issue continues to concern her, regarding the NIH policy of having a cap. Dr. Nahin explained that while the size of the cap varies by NIH institute, only NCI has a higher cap then NCCAM. Dr. Standish responded that her concern is that the research under R21s will be underpowered, resulting in a spate of research that will never turn into R01s. It is hard to squeeze these studies into these caps. Dr. Goertz said that R21s do not need to produce definitive data on treatment effects. In fact, the R21 guidelines specify that this program is not meant for efficacy studies. Their purpose is to develop methodology and establish the feasibility of future studies. Dr. Standish suggested tracking R21s. Dr. Grimm said that review groups do look at power, and there are comments indicating that they will criticize an R21 proposal for not estimating treatment effect, when that cannot be done under an R21. Dr. Kahn noted that comments inappropriate to R21s are being made in R21 reviews. She would like the staff overseeing those review panels to remind them what the R21 criteria are. Dr. Meeker noted that some of the R21s are being penalized for lack of pilot data when the proposed studies are, in fact, pilots. They are also being penalized for being observational. Dr. Nahin said staff would emphasize Council concerns at future study sections.
Dr. Nahin then added that it is necessary to differentiate criticism of applications for not doing something from applicants proposing to do something and not having enough power to do it. If they cannot do what they are proposing, that should be noted in the review. A lot of applicants for R21s are proposing research more appropriate for R01s.
The remainder of the meeting was closed to the public in accordance with the provisions set forth in Section 552b(c)(4) and 552b(c)(6), Title 5, U.S.C. and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2).
Closed session began at 3:30 p.m. A total of 126 applications were assigned to NCCAM. Of these, 85 were reviewed by NCCAM with the rest reviewed by the Center for Scientific Review. Applications that were noncompetitive, unscored, or were not recommended for further consideration by the initial review groups were not considered by Council. Council reviewed 79 applications requesting $31,630,570 in total costs. Council concurred with 79 new research grant applications for a total cost of $31,630,570.
There being no further business, the meeting was adjourned at 6:00 p.m.
We hereby certify that, to the best of our knowledge, the foregoing minutes are accurate and complete.
National Advisory Council for Complementary and Alternative Medicine
National Advisory Council for Complementary and Alternative Medicine
1. Members absent themselves from the meeting when Council discussed applications from their own institutions or when a conflict of interest might occur. The procedure applies only to individual applications discussed, not to en bloc actions.