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Minutes of the Seventh Meeting - May 31, 2001
National Advisory Council for Complementary and Alternative Medicine (NACCAM)
On this page:
- General Statement
- NACCAM Members Present
- NACCAM Ad Hoc Members
- NACCAM Members Absent
- NIH Staff Members Present
- Public Present
- Call to Order
- Future Meeting Dates
- Review of Confidentiality and Conflict of Interest
- NCCAM Director’s Remarks
- NCCAM Intramural Program
- NCCAM Health Disparities Plan
- Overview of Sister Agencies in DHHS
- Concept Clearance
- Public Comment
- IRB Discussion
- CAPCAM/Best Case Series Update
- Closed Session
National Advisory Council for Complementary and Alternative Medicine (NACCAM)
convened at 8:15 a.m. on May 31, 2001, at the NIH Natcher Conference Center
in Bethesda, Maryland. Dr. Richard Nahin, Executive Secretary, called
the meeting to order. The meeting was closed to the public on May 31,
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.
- Dr. Michael Cantwell
- Dr. Haile T. Debas
- Ms. Susan Holloran
- Dr. Janet Kahn
- Dr. Konrad Kail
- Dr. Ted Kaptchuk
- Dr. Dana Lawrence
- Dr. William Meeker
- Dr. Karen Olness
- Dr. Herbert Pardes
- Dr. Everett R. Rhoades
- Dr. Marilyn J. Schlitz
- Dr. Leanna Standish
- Col. James Williams (Ret)
Ad Hoc Members
- Dr. Brian Berman
- Dr. Zang-Hee Cho
- Dr. Murray Goldstein
- Dr. Barbara Timmermann
- Dr. Richard Grimm
- Ms. Diana Manley
- Ms. Dean Batten, NCCAM
- Ms. Carolyn Bellamy, NCCAM
- Dr. Marc Blackman, NCCAM
- Ms. Victoria Carper, NCCAM
- Ms. Linda Engel, NCCAM
- Ms. Carol Fitzpatrick, NCCAM
- Dr. Christine Goertz, NCCAM
- Dr. Martin Goldrosen, NCI
- Dr. Christine Grady, NIH
- Ms. Anita Greene, NCCAM
- Ms. Christine Hollingsworth, NCCAM
- Ms. Camille Hoover, NCCAM
- Dr. Morgan Jackson, NCCAM
- Dr. Jane Kinsel, NCCAM
- Dr. Ruth Kirschstein, Acting
- Dr. Richard Nahin, NCCAM
- Dr. Nancy Pearson, MCCAM
- Dr. Mary Ann Richardson, NCCAM
- Mr. Charles Sabatos, NCCAM
- Dr. Stephen Straus, NCCAM
- Ms. Shirley Villone, NCCAM
- Dr. Neal West, NCCAM
- Dr. Jeff White, NCI
- Dr. Shan Wong, NCCAM
Dr. Ian Coulter, RAND
Dr. Nahin opened the meeting
by reviewing the agenda. In addition to presentations by Dr. Marc Blackman
and Dr. Morgan Jackson of the National Center for Complementary and Alternative
Medicine (NCCAM), NIH, and Dr. Ruth Kirchstein, Acting Director, NIH,
there would be time for public comment and a presentation of two concepts
for initiatives. Additional presentations would address Institutional
Review Board (IRB) issues as they relate to NCCAM, and the Cancer Advisory
Panel on Complementary and Alternative Medicine (CAPCAM) best case series.
The closed session would be held at the end of the day. Dr. Nahin noted
that because the Council had a substantial number of conflicts of interest
with applications under review, NCCAM had brought in four ad hoc Council
members: Drs. Berman, Cho, Goldstein, and Timmermann.
Dr. Nahin reviewed the scheduled
meeting dates. The next meeting will be August 27-28. A meeting scheduled
for October 2 will focus on R01s and R21s. These meetings will take place
in the Neuroscience Office Building. [Note: Since the May meeting, the
October 2 meeting has been canceled. A September conference call is planned.]
III. Review of Confidentiality and Conflict
Dr. Nahin reviewed the rules
under which the Council operates. 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 the public, Council, and staff, including 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 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.
Committee members should not be present for reviews in which they, a spouse,
minor child, or partner (including close professional associates) or organization
with which the Council member is connected 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. Council members are responsible for
ensuring that they meet these conditions. Council members must sign a
form indicating that they did not have a conflict of interest, and this
written certification becomes part of the public record. All Council members
may participate in general discussions. Members must refrain from discussing
review topics outside the forum of NACCAM meetings. The content of review
documents may be disclosed only by staff under the appropriate circumstances
and all questions must be handled by NCCAM staff. All closed session review
materials must be left in the room.
Dr. Kail noted that he was
a consultant on one grant this time, but received a notice disqualifying
him from the review of 11 applications. He asked about the rules governing
this situation. He saw possible difficulties in this. Dr. Nahin explained
that Council members will be in conflict with every application in response
to the same RFA for which they or their affiliation applied. At this meeting,
seven members were in conflict with one or more P20 applications, which
was the reason for having the ad hoc members. Ms. Holloran asked if this
meant that the underlying principle had to do with the mechanism. Dr.
Nahin explained that applications in response to the RFA are competing
for the same limited pool of money. If a Council member recused themselves
only for the specific application on which they were named (i.e., in conflict),
they could still influence whether this application is funded by voting
to lower the priority for all other applications in response to the RFA.
Ms. Holloran had a question
about the confidentiality issue. She thought her own application list
and assignment sheet were her own. Dr. Nahin explained that the assignment
sheet lists which Council member did which review. That key information
that would allow an applicant to link the grant application with an individual
Council member. It is inappropriate to keep these items because if the
list became public knowledge, it would break the confidentiality of peer review.
Dr. Nahin told Council that
three late summary statements and other materials (a special action memo
from staff and copies of letters of appeal) were provided in their folders.
He asked them to read the letters of appeal before the closed session.
Dr. Nahin noted that NCCAM takes all letters of appeal to the Council.
IV. NCCAM Director’s Remarks
Dr. Stephen Straus introduced
Dr. Jane Kinsel. She has years of experience in medicinal chemistry and
pharmacology and served in several senior roles at the National Institute
of Allergy and Infectious Diseases (NIAID) including that of Chief of
the Office of Science Policy before recently joining NCCAM as the Associate
Director for Science Policy and Operations. She will also become the executive
secretary of the Council at the next meeting. NCCAM has designated Dr.
Martin Goldrosen as the new Chief of Review. Dr. Goldrosen, a cancer immunologist
and former Professor at the State University of New York at Buffalo, comes
to NCCAM from the National Cancer Institute where he directed major scientific
Dr. Straus noted that recently
elected President Bush supports NIH and requested the largest NIH budget
increase ever. This request would increase the NCCAM budget to about $100
million in FY 2002 from $89 million this year. Congress seems equally committed.
Regarding funding projections,
Dr. Straus reminded the Council that in 1999, when NCCAM was created,
NCCAM received 23 research applications, and funded 13. In 2000, there
were 177 submissions, 44 of which received funding. In February, Dr. Straus
projected that NCCAM would receive 212 submissions in FY2001, with funding
projected for 37 of those. However, NCCAM has received approximately 400
applications. Depending on the average costs of the grants awarded and
other factors, the Center will be able to fund 10 to 18 percent of all
applications. The Center and Council must make strategic decisions about
what kinds of applications to fund. NCCAM is likely to receive even more
applications in FY2002, which may result in a lower percentage funding.
Dr. Straus added that NIH as a whole finds about 40 percent of applications
to be unscorable, but NCCAM finds 60 percent unscorable. Dr. Kail suggested
that as funding percentages decrease, it will be more difficult for complementary
and alternative medicine (CAM) institutions to compete. He asked if co-funding
with other NIH institutes might help. Dr. Straus explained that some CAM
institutions have been competing successfully and should continue to do
so. To increase co-funding, Dr. Straus is building relationships with
other Institutes. He has commitments for several million dollars in FY 2002.
Dr. Straus introduced Dr. Marc
Blackman, the clinical director of the NCCAM intramural program, and reviewed
his background. Dr. Blackman outlined his goals. The mission of the intramural
program is to explore CAM practices in the context of rigorous science,
train CAM researchers, and disseminate information to the public and professionals.
Among the guiding principles are an unwavering commitment to excellence;
absolute integrity of purpose and actions; and uncompromising respect
for all stakeholders. Dr. Blackman’s objective for FY 2001-2002 is to
establish administrative, scientific, clinical, and training priorities
and infrastructure, while developing a web of intramural and extramural
collaborative relationships. He also intends to establish an extramural
board of scientific counselors to advise and monitor the program, as is
done elsewhere in NIH.
Dr. Blackman explained that
he has a special interest in gerontology. The population of individuals
85 and over is the most rapidly growing segment worldwide. The next 50
years will see a four- to five-fold growth in this group. In that context,
his investigational theme for the NCCAM intramural program will be stressors
and aging: depression/dysphoria; cognitive decline; chronic pain; sleep
disorders; and frailty. Each of these conditions is more problematic in
older people, and each accounts for disproportionate use of CAM modalities,
usually in addition to standard medicine. In addition, these conditions
With this as background, Dr.
Blackman proposed an intramural program with a lab of clinical investigation
(LCI) having six sections: endocrinology, metabolism and nutrition; neurobiology;
clinical immunology and rheumatology; cardiology; oncology; and pharmacology.
Through these sections, he hopes to approach CAM modalities in groupings
of biologically based therapies (such as DHEA and other androgenic dietary
supplements, phytoestrogens, soy, melatonin), mind-body medicine (placebo
effect, meditation, laughter), and alternative medicine systems (acupuncture).
Manipulative and energy systems will be studied later.
Dr. Blackman explained that
there is a drop in DHEA in the human body as a person ages which may contribute
to age-related changes in the body that affect immunological, psychological,
and cardiovascular and body composition aspects of health. DHEA administration
to old rats reverses or attenuates many of these components of aging.
DHEA is now in wide use as a dietary supplement for anti-aging purposes,
although its efficacy and safety in humans are not established. Purity
is uncertain from lot to lot, and it is regulated as a supplement, not
a medicine, by the FDA. Dr. Blackman proposes studies that will: assess
DHEA’s possible clinical utility as a neurosteroid, immunomodulator, and
cardiovascular enhancer in healthy and frail elderly individuals; and
assess the effects of DHEA on gene transcription and the resultant biological
effects in neural, immune, and vascular human cell lines.
To train CAM researchers, Dr.
Blackman plans to stimulate collaborations between CAM practitioners and
conventional investigators; train individuals and practitioners to conduct
broad-based CAM research; increase the number of minority trainees; and
initiate research training programs. In the month he has been with NCCAM,
he accomplished the following: drafted an initial strategic vision; established
the LCI and endocrinology section; and recruited key personnel. He has
also initiated research collaborations with other NIH Institutes and a
number of universities. Finally, he has initiated clinical/educational
collaborations through the NIH inter-institute endocrine fellowship program,
the NIH clinical center pain and palliative care service, and NCI’s Office
of Cancer and CAM.
Among Dr. Blackman’s goals
are to facilitate the coupling of effective CAM and allopathic practices
in the interdisciplinary healthcare system of the NIH clinical center
and to facilitate development of research and clinical training curricula
that include information about safe and effective CAM practices. The longer
term scenario is to establish a clinical program in CAM, form an inter-institute
CAM training program, expand research activities, begin studies in children
and neonates, and establish a lab of cellular and molecular biology to
complement the LCI. Ultimately, he hopes to help establish a scientific
basis for integrative medicine, and to have NCCAM become the leading source
on this kind of information.
Ms. Holloran said that she
was extremely encouraged by this presentation. She has used the modalities
he mentioned, and has used DHEA since 1994. As a patient, she could not
find much information on DHEA, which led to her interest in CAM. Dr. Blackman
noted that there has not been an economic incentive to study DHEA. Dr.
Goldstein asked if the intramural program had assigned clinical space
at NIH. Dr. Blackman replied that NCCAM is negotiating with NIH leadership
to secure lab space. Clinical investigations will take place within the
clinical center. Dr. Kahn noted that she does not consider acupuncture
a system, but rather part of a system. Dr. Blackman said that a growing
body of data indicates that acupuncture has utility, and he wants to start
investigating those CAM modalities with the highest body of evidence.
It is not well-understood how acupuncture achieves its effects; he would
like to examine this.
Health Disparities Plan
Dr. Jackson, Director, NCCAM
Office of Special Populations, presented the draft NCCAM Health Disparities
Plan for Council review and comment. He explained that the DHHS established
an initiative to eliminate racial and ethnic health disparities that focuses
on six priority health areas: cardiovascular disease, cancer, diabetes,
HIV/AIDS, immunization, and infant mortality. As part of the DHHS initiative,
NIH is developing a consolidated plan with the goal of reducing and ultimately
eliminating health disparities (REHD) among racial and ethnic minorities.
Within this goal are three objectives that NIH will address: research,
research infrastructure, and public information and community outreach.
Dr. Jackson outlined the process
for drafting the plan, which involved multiple reviews by NIH staff and
select Council members. A revised plan will be posted on the NCCAM web
site for public comment, updated based on public comment, and presented
to the Council once more. The NCCAM REHD plan reflects the NCCAM mission
to explore CAM healing practices with rigorous science, train CAM researchers,
and disseminate authoritative information.
To address the first NIH priority
for dealing with health disparities, research, the NCCAM plan will advance
our understanding of, and develop new or improved approaches for, treating
diseases and disabilities. These approaches will incorporate research
on CAM systems and interventions for specific diagnoses of concern, while
expanding minority participation in CAM research. To address the second
NIH priority, that of research infrastructure, the NCCAM plan will support
research training and career development and provide support for institutional
resources. The plan will also address the NIH priority of communications
Research initiatives will include
epidemiological studies of CAM in minority populations. There is also
a proposed initiative for outcomes research on CAM in minority populations
and for testing several CAM interventions used to treat or prevent several
of the the six disease areas prioritized by NIH. Coordinated efforts will
be made to increase minority participation, both investigators and patients,
in NCCAM research.
To increase research infrastructure,
NCCAM is supporting research training and career development of minority
scientists. The Center recently received applications for T32 research
training grants at minority serving institutions. The Center will also
support summer internship programs at NIH and will participate in NIH-wide
minority research supplements and DHHS minority youth initiatives targeting
high school students.
NCCAM will collaborate with
other NIH institutes and centers on communication and outreach initiatives,
which will disseminate CAM information to professional organizations and
the general public, and collaborate on a community consultation workshop.
In closing, Dr. Jackson noted
that the NCCAM REHD plan is a dynamic document, and hopes that through
execution of the plan, NCCAM can enhance the cultural competence of the
conventional care system and advance the development of interdisciplinary
Col. Williams and Drs. Rhoades
and Lawrence led the discussion. Dr. Rhoades cautioned that to eliminate
disparities, socioeconomic disparities and stress health education must
be addressed. The clinical conditions discussed in REHD, though identified
by DHHS and NIH, don’t address violent death and intentional and unintentional
injuries, which are epidemic among Native Americans. Dr. Rhoades noted
that these problems do not necessarily fall within NIH’s purview. Dr.
Rhoades added that Native Americans have a different list of conditions
from other minority groups. Alcoholism and lung cancer are third and fourth
on their list. Nonetheless, he liked the draft plan. He thought a workshop
would be a good idea, observing that Native Americans will want their
own breakout sessions. He felt that getting public comment will be critical.
Col. Williams observed that
true integration of CAM will involve elimination of health disparities.
Societal integration is a work in progress, and CAM is facing a parallel
path of integrating into the mainstream. Much of the challenge will be
driven by politics. Many CAM practices attempt to bring balance to our
lives. Col. Williams said that he likes the work NCCAM is doing to collaborate
among agencies. Building research infrastructure in minority institutions
is very important, and release of faculty time is important as well. He
added that NCCAM should not forget the potential of minority investigators
at majority institutions.
Dr. Lawrence said that he was
struck by the fact that it will require economic and educational work
to address health disparities. When he looked at the document, he looked
at it from global and specific perspectives. From the global perspective,
he thought it was very good, dovetailing nicely with the NCCAM strategic
plan. In terms of specifics, a couple of things caught his eye. He is
having more trouble with CAM being discussed in terms of what it is not.
He wants to give greater attention to integrated medicine. In addition,
he thought that in-depth surveys of specific subpopulations are important.
Regarding research training and career development, he wondered about
the level of faculty staffing at CAM institutions in terms of minorities.
Otherwise, he thought the document was very well done.
Dr. Straus asked if there were
other comments. Dr. Debas said that he also liked the plan, but felt it
tried to address too many issues. There should be more focus and some
milestones. Dr. Standish asked about the T32 program. Dr. Jackson said
that applications for T32 programs were due to NCCAM on May 14. Dr. Kaptchuk
said that they should investigate some of the ethnomedical practices in
minority communities. He would like to make sure that minority medicines
and practices are addressed. Dr. Jackson said that this has been discussed
in the plan, including the incomplete picture of minority CAM usage.
of Sister Agencies in DHHS
Dr. Straus invited Dr. Ruth
Kirchstein, Acting Director of NIH, to address how NCCAM relates to its
sister federal agencies. After a general overview of DHHS, Dr. Kirchstein
discussed some of the DHHS agencies that share areas of concern with NIH.
The Agency for Healthcare Research and Quality (AHRQ) supports research
on crosscutting health care issues (health care systems, effectiveness
of medical treatments, health care quality, medical errors, health care
cost) that are often in the news. The Center for Disease Control and Prevention
(CDC) provides a system of health surveillance to monitor and prevent
the outbreak of disease. CDC helps to guard against international disease
transmission, maintains national health statistics, provides for immunization
services, and supports research into disease and injury prevention. The
Food and Drug Administration (FDA) regulates and ensures the safety of
food and cosmetics, and ensures the safety and effectiveness of pharmaceuticals,
biological produce, and medical devices. The Health Resources and Services
Administration (HRSA) provides health resources for medically underserved
populations through the National Health Services Corps, and oversees the
organ transplant system, the Ryan White Services for People with AIDS,
and various local and regional centers. The Indian Health Service (IHS)
provides health care services to 1.5 million Native Americans. This system
encompasses 37 hospitals, 60 health centers, school health centers, health
stations, and urban Indian health centers. Much of what they do is through
contracts with tribes, some of which run their own systems. The Substance
Abuse and Mental Health Services Administration (SAMHSA) works to improve
the quality and availability of substance abuse prevention, addiction
treatment, and mental health services. The Administration for Children
and Families (ACF) provides services and assistance to needy children
and families, usually through block grants. The Administration on Aging
(AOA) works closely with the National Institute on Aging, and administers
block grants to provide for the aging population. Health Care Finance
Agency (HCFA), through Medicare and Medicaid, provides programs that support
health care for the aged and poor. This is not a discretionary budget.
HCFA has recently put together regulations of interest to NIH, allowing
HCFA to provide care for patients who are being studied under research
protocols. This will now allow elderly and needy people to be part of
studies, since they will no longer have to pay for their routine care
Ms. Holloran asked if there
were collaborations among these agencies to focus on disparities issues.
Dr. Kirchstein said that there is a great deal of collaboration. There
are transagency programs on health disparities. There is a close collaboration
between IHS and NIH. In addition, all agencies are developing strategic
plans. One thing to note about the health disparities issue is that these
are not all in the traditional NIH area. Some issues are about access,
for example. As such, NIH Institutes have increased outreach and education
programs. Dr. Debas asked about the selection of the director of NIH.
Dr. Kirchstein explained that this is a presidential appointment. Various
factors go into the selection. In the past, there have been search committees.
Dr. Schlitz asked if the role of prevention is increasing in significance.
Dr. Kirchstein said that it is increasing within all parts of DHS. There
will be an initiative involving all agencies.
Dr. Nahin introduced Dr. Nancy
Pearson of NCCAM, who presented initiative concepts for clearance. Dr.
Pearson provided some general background on two conferences that directly
led to the two concepts for initiatives on placebo: the November 2000
placebo workshop and a conference on mind-body interactions held in March 2001.
The first proposed initiative,
The Placebo Effect in Clinical Practice, is expected
to stimulate investigator-initiated research investigations on how placebos
and placebo effects affect clinical practice, with the goal of understanding
which factors are necessary to elicit a placebo effect in clinical practice.
This will allow practitioners to enhance the benefits of therapeutic intervention
to improve health and promote wellness. The objectives are to solicit
studies: 1) that determine the psychosocial factors in the patient/caregiver
relationship that elicit the placebo effect; 2) on tools that might elicit
the placebo effect; 3) into the role of belief systems and social systems
in eliciting the placebo effect; 4) of ethical questions related to placebo;
and 5) on how different types of caregivers can maximize the placebo effect.
The goal of the second proposed
initiative, An Integrative Approach to Elucidation of the Underlying
Mechanisms of Placebo Effect, is to stimulate research on the
underlying biological mechanisms of placebo that lead to its ultimate
physiological and psychological effects. An integrative research approach
is encouraged, defined as combined use of approaches with several different
scientific disciplines. The idea is that understanding of the underlying
mechanism of placebo effects will elucidate and enhance both conventional
and CAM medical therapies in clinical practice. Expanded placebo research
incorporating the fulle palette of contemporary biomedical techniques
as well as development of better animal models is encouraged.
Dr. Schlitz asked about the
impact on these proposed initiative of the recent meta-analysis published
in JAMA, which suggested that there is no placebo effect. Dr. Pearson
said that the analysis was very provocative, but actually creates a need
for more research. Dr. Schlitz ask what NCCAM would do if the data do
not look compelling. Dr. Berman said that the article questions whether
there is an effect, rather than saying that there is none. Dr. Kaptchuk
added that the meta-analysis was well done, but that the question should
be raised to a higher level. However, one meta-analysis does not negate
numerous research in the area. The controversy makes it that much more
timely for NCCAM to initiate this project. There is much evidence both
ways, which is a reason to do more research.
Dr. Meeker thought the meta-analysis
demonstrated a significant pain effect, which is especially significant
for CAM treatments and modalities. He said that the development of placebos
for testing nonpharmacological treatments is a large issue. Dr. Straus
replied that these types of studies are in the NCCAM portfolio, such as
with acupuncture. Dr. Goldstein added that in the same issue of JAMA,
there was an informative editorial comment that took issue with the conclusions
of the meta-analysis. The commenter noted that questions have now been
raised that demand answers. There was also a recent study on brain injury
in which the placebo group had a substantial long-term benefit.
Dr. Kail said that looking
at the biological reasons for the placebo effect could be complex, and
the proposed funding seemed small in that light. Dr. Straus replied that
NCCAM was seeking additional funds from other NIH Institutes and Centers.
Dr. Cantwell said that regardless of the article, this is the first time
NCCAM has looked at intentionality. This a new direction, and brave. Dr.
Cho said he was glad to see the concepts. He just completed an acupuncture
study in which he saw some of the placebo effect; a sham intervention
found an effect similar to true acupuncture. Dr. Debas noted that even
if there is no placebo effect, there should still be a placebo in trials
to control for investigator bias and the like. Dr. Pearson said that she
would meet soon with interested institutes.
The concepts were approved unanimously.
IX. Public Comment
Dr. Nahin announced the time
for public comment. No members of the public signed up to speak, and no
one came forward when he asked if anyone would like to speak.
X. IRB Discussion
Dr. Christine Grady of the
NIH Department of Clinical Bioethics, spoke about institutional review
boards (IRBs). Dr. Straus explained that the Council had previously raised
issues regarding IRBs and ethical review. There has been concern within
the Council that it might be inappropriately difficult to get a CAM proposal
through an IRB.
Dr. Grady explained that IRBs
are formed to review and monitor research involving human subjects. The
official guidance is under 45CFR46, which applies to all federal agencies
and which protects human subjects. Regulations also address informed consent,
which is the responsibility of the IRB. Non-government-funded research
still must follow FDA regulations (21CFR56) if the researchers want to
take research results to market. FDA regulations for IRBs are different
on very minor points. Most institutions try to comply with both sets of
regulations. The purpose of an IRB is to assure that human subjects are
protected in terms of their rights and welfare. IRBs have authority to
approve, require changes to, and disapprove studies and protocols. Specific
language in 45CFR46 requires that IRBs have at least five members with
varying backgrounds in order to adequately review research activities
commonly conducted by the institution. If an institution has a higher
volume of protocols in alternative medicine, they might want to have CAM
people on the IRB. There are also membership considerations regarding
sex, experience, and diversity, along with considering community sensitivities,
including a nonaffiliated member who is from outside the institution.
IRB membership cannot be concentrated in one profession and must have
at least one scientist and one nonscientist. Membership requirements include
competence in reviewing the specific research activities, and members
must be able to determine that the proposal is appropriate for the institution.
IRBs pay special attention to proposals involving “vulnerable” subjects.
Finally, IRBs may invite ad hoc members with competence in special
areas to assist in the review of issues that require expertise beyond
or in addition to that available on the IRB.
Many IRBs have only one nonscientific
member, but that person must be present in order to proceed. IRBs must
assess whether risks to subjects are minimized by using procedures that
are sound and that do not expose subjects to unnecessary risk. This generates
some disagreement among IRBs with respect to the review of proposed science.
Many institutions have a scientific review that precedes IRB review. Others
argue that IRBs should ensure science of high quality, so that a separate
review process is unnecessary. Another requirement of IRBs is to determine
that risks to subject are reasonable in relation to the benefits. IRBs
judge the balance of risks and benefits, and the value of the knowledge
gained from the proposed study. They must determine that the selection
of subjects is equitable and appropriate, and ensure appropriate consent
and documentation of consent. IRBs have come under much scrutiny in the
last few years. A few studies have looked at their function. Two studies
in 1998, one by NIH and one by the Inspector General, were released in
the same month. They used very different methods of evaluation and came
to contradictory conclusions. One said the IRB system was in jeopardy;
the other said they were doing a good job with minimal resources. The
reality is that there are about 3,000 IRBs. They are variable in how they operate.
Ms. Holloran explained that
some members of Council were concerned with the composition of IRBs and
the familiarity (or lack thereof) that IRBs, especially small ones, might
have with CAM modalities. She asked if it were possible for an IRB to
specialize in CAM, or if it would be better to educate existing IRBs about
CAM. Dr. Grady suggested that efforts should go into providing IRBs the
information they need to evaluate CAM and urging them to use ad hoc consultants.
She has found that IRBs with few qualms about Phase I drug studies have
problems approving surveys, because they do not understand this type of
research as well. As a result, there is disproportionate scrutiny of survey
studies, a situation that might apply to CAM as well. There is an increasing
effort to provide educational materials to IRBs. There are many web sites
that provide IRB members with information. Issues important to NCCAM could
Dr. Meeker asked for a distinction
between local and single project assurances. CAM seems to be in the single
project category, resulting in serious delays. Dr. Grady said that there
is a new mechanism, a federal-wide assurance, that replaces the other
assurances and simplifies the process. There is a grace period in which
institutions can apply for those. NCI has started a pilot project of a
central IRB for its oncology groups. This IRB will review multicenter
protocols in order to circumvent problems inherent when multiple IRB’s
review the same project. This is a pilot and there will be an evaluation
down the road.
Dr. Debas noted that the costs
of running an IRB are large and increasing. Dr. Grady said that there
are almost no data on the costs of IRBs. The business IRBs have their
own data, but institution-level data have not been disaggregated. Members
are usually volunteers. Dr. Debas observed that while this is true, it
is no longer as easy to get volunteer time from faculty. Some are asking
to be paid. Dr. Straus noted that NIH views its indirect payments as covering
IRB costs. NIH no longer requires IRB approval before review, and since
70 percent of proposals do not get funded by NIH, this should decrease
the number of proposals that IRBs review. Dr. Straus added that no NCCAM
proposal approved by Council has failed IRB review. Dr. Straus explained
that research is becoming more administratively burdensome, not just for CAM.
Dr. Pardes observed that mental
health investigators whose proposals were reviewed by non-mental health
people often feel there work is not understood. He believed that investigators
think they are being reviewed by a homogenous group, but this is rarely
the case. He was also concerned that the research oversight structure
is growing cumbersome and may prevent good research. Dr. Grady agreed
with his point, giving an example relating to gene therapy. Dr. Straus
said that he senses a tension in CAM research. The fact that something
has been used by many people for many years seems to provide an inherent
reason to explore. However, unlike work in other areas, there is not much
preclinical work before preceding to clinical trials in CAM, which could
put NCCAM funded projects at a disadvantage.
Dr. Olness presented two examples
where IRB members did not understand what they were reviewing. In one
case, the IRB felt CAM interventions were not legitimate and therefore
dismissed them. In another case, the IRB passed protocols that were done
in error. Dr. Debas asked about the personal liability of IRB members.
Dr. Grady replied that few IRBs have been sued as a body. Individuals
are not usually held accountable, as they make group decisions.
XI. CAPCAM/Best Case Series Update
Dr. Straus introduced Drs.
Jeff White and Ian Coulter, who gave an update on the Cancer Advisory
Panel for Complementary and Alternative Medicine (CAPCAM) and the best
case series (BCS). Dr. White spoke first, about the BCS. He gave a brief
history of the NCI case series reviews, mentioning the laetrile review
of the mid-1970s, a 1989 Vitamin C review, a 1990 Office of Technology
Assessment (OTA) study, and the 1991 NCI BCS program. The laetrile review
involved a solicitation of documentation of cancer responses, with nearly
half a million letters going out to physicians, other health professionals,
and pro-laetrile groups. This resulted in 230 patients with claimed objective
responses from laetrile but only 93 authorized releases of medical records.
Of the 93, only 67 cases provided sufficient information for review.
The 1990 OTA report noted that
the BCS approach could be useful in deciding which alternative treatments
warranted further investigation. The report suggested that key to a successful
BCS was the active participation or support of the practitioner. The NCI
case series reviews were established after the OTA report came out and
involved coordination by the NCI’s cancer therapy evaluation program,
along with internal review of materials. From 1991 to 1998, the program
generated about 30 inquiries, 10 requests for review, 5 reviews, and 4
In 1999, the NCI Office of
Cancer Complementary and Alternative Medicine (OCCAM) began coordinating
the BCS program. The current process is that the practitioner contacts
NCI or NCCAM and receives an information packet from OCCAM. Documentation
of cases goes to OCCAM, with radiology and pathology reviewed at the NIH
Clinical Center. The materials are then summarized and presented to CAPCAM.
The practitioner is invited to present their cases to CAPCAM and answer
questions. CAPCAM advises the NCCAM Director as to whether or not further
research is warranted, and if so, of what nature.
Of those who contacted OCCAM
for information in the first nine months of 1999, eight were from the
U.S and two were foreign. There have been two U.S. best case solicitations
and two submissions. OCCAM began promoting this previously unadvertised
program in December 1999. Over 150 letters were mailed, information was
placed on the OCCAM web site, and there were conference presentations,
journal articles and interviews, and advertisements in six journals. OCCAM
has had more than 125 inquiries since January 1, 2001.
Dr. Nahin explained that NCCAM
is supporting the Agency for Health Research Quality (AHRQ) Southern California
Evidence-based Practice Center (SCEBPC), which includes RAND, in a one-year
pilot project to put together BCS for designated practices. SCEBPC staff
and the practitioner could then present the BCS to CAPCAM.
Dr.Coulter, Principal Investigator
for NCCAM’s contract to the SCEBPC, explained that the SCEBPC is contracted
through AHRQ to provide technical support for NCCAM. Projects include
systematic reviews of: 1) mind-body therapies—gastrointestinal problems;
2) Ayuverdic medicine—diabetes; and 3) SAMe—depression, arthritis, and
chronic liver problems.
Specific aims for the one-year
pilot are to create a BCS for three CAM providers treating cancer, and
to determine if there is sufficient evidence for further study of these
therapies. NCCAM will identify the three CAM providers, of which two have
been chosen so far. The CAM providers will be asked to identify their
best cases, and SCEBPC staff will visit the practice and abstract the
patient files after first obtaining informed consent. Files will be abstracted
from the CAM provider and from mainstream medical providers. This underwent
a rigorous IRB review.
After the CAM provider has
identified the best cases, the provider will contact patients to be included
in the study. Patients will be interviewed regarding health and quality
of life. Where the CAM record in incomplete, they will be asked for permission
to contact their mainstream medical provider. The mainstream medical provider,
in turn, will be asked for a histological report, other documentation
of diagnoses, and documentation of treatment. Inclusion criteria will
be histological confirmation, the starting point for CAM, exclusive CAM
treatment, documented CAM treatment, and a documented end point such as
remission, tumor size, or longevity. Dr. Coulter said it will be difficult
to find patients who have had CAM treatment exclusively.
The first intervention they
are examining, from the Bahamas, is immuno-augmented therapy (IAT). The
premise is that the immune system attacks the cancer cells but also controls
the rate of the attack by blocking protein to prevent toxic damage to
the liver. As immunosuppression and anti-tumor activity occur, the inhibitor
system must be reactivated. There are four factors in the immune system
failure: a blocking protein, a tumor antibody, a tumor complement, and
a deblocking protein. The therapy involves daily injections of human processed
blood based on the patient’s immune system and the four factors.
The SCEBPC is reviewing cases
of cancer patients treated with naltrexone. Naltrexone is an opiate antagonist
used to treat heroin addiction and people with HIV/AIDS. It is also thought
to cause cell death and tumor regression in some instances. The theory
is that a low dose of naltrexone raises levels of beta-endorphins and
met-enkephalin, facilitating immune function.
To contact patients, SCEBPC
staff must go through the provider. The IRB is allowing them to only review
cases where either the patient has given informed consent, or cases where
the unique patient identifiers are removed from the records. The research
team then identifies the cases they wish to include, at which point the
provider contacts the patient to secure their consent. There are three
patient consent forms. The first allows SCEBPC staff to review patient
files, while the second allows SCEBPC staff to interview the patient.
The final consent allows SCEBPC staff to obtain medical records from the
patient’s other health care providers.
XII. Closed Session
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).
The closed session began at
3:00 p.m. A total of 163 applications were assigned to NCCAM. Of these,
134 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 118 applications requesting $117,825,977
in total costs. Council concurred with 108 new research grant applications
for a total cost of $73,089,637. Council recommended deferral of thirteen
(13) (three were noncompetitive, unscored) Frontier Medicine (P20) grant
applications requesting $44,736,368 in total costs.
There being no further business,
the meeting was adjourned at 6:00 p.m.
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.