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Minutes of the Seventh Meeting - May 31, 2001

National Advisory Council for Complementary and Alternative Medicine (NACCAM)

On this page:

  1. Call to Order
  2. Future Meeting Dates
  3. Review of Confidentiality and Conflict of Interest
  4. NCCAM Director’s Remarks
  5. NCCAM Intramural Program
  6. NCCAM Health Disparities Plan
  7. Overview of Sister Agencies in DHHS
  8. Concept Clearance
  9. Public Comment
  10. IRB Discussion
  11. CAPCAM/Best Case Series Update
  12. Closed Session
  13. Adjournment

General Statement

The

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.

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NACCAM Members Present

(1)

  • 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)

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NACCAM

Ad Hoc Members

  • Dr. Brian Berman
  • Dr. Zang-Hee Cho
  • Dr. Murray Goldstein
  • Dr. Barbara Timmermann

NACCAM

Members Absent

  • Dr. Richard Grimm
  • Ms. Diana Manley

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NIH Staff

Members Present

  • 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

    Clinical Center

  • Ms. Anita Greene, NCCAM
  • Ms. Christine Hollingsworth, NCCAM
  • Ms. Camille Hoover, NCCAM
  • Dr. Morgan Jackson, NCCAM
  • Dr. Jane Kinsel, NCCAM
  • Dr. Ruth Kirschstein, Acting

    Director, NIH

  • 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

Public Present

Dr. Ian Coulter, RAND

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I. Call

to Order

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.

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II. Future

Meeting Dates

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.]

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III. Review of Confidentiality and Conflict

of Interest

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.

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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

review activities.

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.

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V. NCCAM

Intramural Program

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

coexist together.

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.

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VI. NCCAM

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

and outreach.

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

health care.

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.

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VII. Overview

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

while participating.

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.

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VIII.

Concept Clearance

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.

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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.

Top

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

be introduced.

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.

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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

response audits.

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.

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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.

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XIII. Adjournment

There being no further business,

the meeting was adjourned at 6:00 p.m.

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.

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