Third Annual Public Interest Organization Meeting

February 6, 2002 - Bethesda, Maryland
Breakout Sessions

The same concurrent sessions were held during the morning and afternoon of the meeting to enable the PIO representatives to attend and contribute to each session. The two topics were: Involving Participants in Clinical Research, and Funding Research.

Involving Participants in Clinical Research

Three presentations by NHLBI staff provided a framework for discussions during this breakout session.

Dr. Lawrence Friedman
Overview of Government and Institutional Considerations
Ms. Eleanor Schron
What Patients Should Know About Participating in Clinical Studies
Dr. Joel Moss
Targeting a Rare Disease
Discussion on Involving Participants in Clinical Research

Overview of Government and Institutional Considerations

Dr. Lawrence Friedman, Assistant Director for Ethics and Clinical Research, NHLBI, reviewed the principles, legal authorities, and policies governing research; and the organization and action of institutional review boards (IRBs; administrative groups that review all research involving human subjects). Interested parties include the Congress, regulatory organizations [e.g., the Food and Drug Administration (FDA), Office for Human Research Protection], research sponsors (e.g., the NIH, Department of Veterans Affairs), advisory groups (e.g., Government Accounting Office, Office of the Inspector General, Institute of Medicine), researchers, and research participants.

Three key documents establish the standards and ethical principles for research:
the Nuremberg Code (which, in 1949, established the concept of voluntary consent),
the Declaration of Helsinki (which put forth the ethical principles for medical research involving human subjects),
and the Belmont Report (which, in 1976, defined the boundaries between practice and research and set forth basic ethical principles).

The Belmont Report led to legal authorities established in the Code of Federal Regulations (45CFR46) and in FDA regulations. Both the Code of Federal Regulations and the FDA require the use of IRBs for the purpose of protecting the rights and welfare of research participants. Additional policies established by the NIH relate to the education of researchers about the protection of human subjects, establishment of data and safety monitoring boards (DSMBs) for all intervention studies, disclosure of any financial conflict of interest among IRB members, and inclusion of women, minorities, and children in clinical trials.

Dr. Friedman noted that all the standards, authorities, and policies ensure:
  • Multiple layers of protection for human subjects in clinical research
  • Full review of study and funding decisions
  • Continuous reporting on safety to various organizations.

What Patients Should Know About Participating in Clinical Studies

Ms. Eleanor B. Schron, Nurse Scientist, Clinical Trials Research Group, NHLBI, summarized ways for patients to find out about clinical research studies, the benefits and risks associated with clinical trials, patients' rights before and after joining a clinical trial, the basic elements of informed consent, and the results of surveys of patients who have participated in clinical studies.

Ms. Schron noted that the NIH Web site ( includes links to (, the most comprehensive central listing of ongoing studies sponsored by the NIH and other public and private organizations. She recommended that the PIOs peruse two resources on the site: "Understanding Clinical Trials" and "Patient Information Publications."

In addition, information on Federally funded trials is available by telephone (at 1-800-411-1222). Other reliable sources of information include the FDA Web site (, national and local organizations, and medical practitioners.

Clinical trials offer patients the opportunity to
take an active role in their health care,
gain access to new treatments not available to the general public,
obtain expert medical care at leading health care facilities, and
help others by contributing to medical research.

Potential risks include side effects or adverse reactions to treatments and ineffective drugs or devices; prospective participants also should be aware of the amount of time that they may be asked to commit.

Before participating in a study, patients should know
the purpose of the research and the study,
the names of the sponsor(s) and reviewers, and
the expected outcomes.
Upon joining a study, patients have the right to
leave it at any time,
ask questions and obtain answers,
receive new information about the treatment,
maintain their privacy, and
be informed about the assigned treatment when the study is completed.
Patients also have a right to be fully informed about all aspects of the study (including risk, benefits, duration, costs) and to talk openly with doctors.

Ms. Schron emphasized that the process of informed consent has been carefully defined and includes a written document, which the patient signs, and continuing explanations and discussion, as needed, throughout the trial. Informed consent pertains to both patients' expectations of a clinical study and the investigators' expectations of the patients. The basic elements are stated in 45CFR46.116, Protection of Human Subjects; the NIH ( Web site includes all consent forms. Ms. Schron noted that patients should be cognizant of their own behaviors (e.g., desperately seeking hope, not asking questions), as well as those of physicians and clinical research professionals, that are potential barriers to chieving informed consent. Reviewers (e.g., IRBs) make every effort to ensure that the risks and benefits are communicated clearly and that patients are not coerced to participate.

Surveys of patients indicate that they choose to participate in clinical trials because they are following their physician's recommendation, desire closer medical monitoring or increased knowledge, and/or want to contribute to medical science. The vast majority say they want to contribute to science and would volunteer again. Some of the inconveniences noted include difficulties with transportation and parking, excessive waiting time in clinics, and turnover among clinic staff.

In summary, Ms. Schron noted the following:
  • Numerous informational resources are available on clinical studies
  • Education of patients participating in these studies is essential
  • Patients should evaluate the benefits, risks, rights, and responsibilities associated with their participation
  • Informed participants are necessary for successful clinical research.

Targeting a Rare Disease

Dr. Joel Moss, Chief, Pulmonary/Critical Care Medicine Branch, NHLBI, described the clinical resources that the NIH intramural program uniquely offers for research on rare diseases. Dr. Moss noted that a primary focus of the NHLBI intramural program is lymphangioleiomyomatosis (LAM) and that more than 50 percent of LAM patients in the United States are enrolled in a clinical trial conducted by this program.

The NIH intramural program is a national resource available to patients in all 50 states. Patients are referred by their physicians to participate in research studies. The NIH pays for their treatment and travel. The NIH program offers many advantages for clinical research. Intramural investigators can

assemble the cohort of patients needed to conduct meaningful clinical studies;
link laboratory research with patient studies to determine the cause(s) of disease and develop effective treatments;
provide ancillary services (e.g., pulmonary rehabilitation, social services, nutrition, complementary and alternative care, community services) to support patients during and after a study;
help educate local physicians, other health care professionals, and social service personnel about a disease and patients' needs; and
facilitate interactions between patients and advocacy groups.
Dr. Moss noted that many patients refer to the intramural program as "club NIH."

All patients at the NIH must be enrolled in an IRB-approved research protocol and must have signed an informed consent document. Dr. Moss reviewed the elements of the consent document and rights of patients, previously summarized by Ms. Schron. He noted the specific risks associated with research on rare diseases, which relate to:

  • Diagnosis of the disease, which may affect patients' future employability or acceptability for insurance
  • Genetic concerns (e.g., insurability of family members, mistaken paternity)
  • Enrollment in a study, which may compromise the privacy and confidentiality of patients' medical records
  • Treatment (e.g., unanticipated effects of experimental therapies).

Some of the most difficult risks to assess are the future use of patients' data, loss of confidentiality, and interpretation of genetic information. Patients may elect to not participate in a study because of elements included in the consent form (e.g., limitations of liability for unanticipated effects), and patients have the right to choose how they will participate in a study (e.g., they may decide not to share their medical information with other research groups).

Dr. Moss said that a basic rule guiding the design of clinical studies in the intramural program is "the 'mom' test"; that is, "given the risk and benefits of the research, would you let your mother participate in the study?" Three objectives are key:

  • Conduct the best science
  • Minimize the risks
  • Protect patients' rights.

He also noted that the PIOs could provide invaluable assistance to intramural researchers. They could:

  • Offer patient referral and support services
  • Disseminate information on diseases and treatments
  • Develop resources (e.g., tissue samples) for research.

The LAM Foundation (, for example, has referred more than 260 patients to the NIH clinical study and has enabled the NIH to obtain tissue samples from patients undergoing transplants. Several other PIOs are also interacting with the NHLBI in similar ways. In closing, Dr. Moss expressed his appreciation for patients' participation in clinical research studies.

Discussion on Involving Participants in Clinical Research

The participants emphasized the need for increased and collaborative efforts to recruit patients for clinical studies. They asked the Institute to consider developing recruitment and education materials. Other issues raised for discussion include the role of PIOs in enhancing clinical research, the design of research protocols, assurances for PIOs and patients, and follow-up support for patients.

Recruitment of Patients

The participants noted that many patients who would be interested in participating in clinical studies do not have access to the Web. NHLBI staff encouraged participants to give the toll-free telephone number, 1-800-411-1222, to anyone who might be interested in a clinical study.

Staff also noted that the NHLBI actively seeks enrollment of minority populations (e.g., African Americans) in clinical studies. Investigators reach out locally to inner-city populations by giving presentations (e.g., at hospitals, churches, mayors' offices), advertising in radio "spots," and talking with individuals one-on-one. The PIOs noted the difficulties in recruiting African Americans in particular, and they encouraged intramural investigators to continue to increase their outreach efforts and to focus on diseases (e.g., lupus, sarcoidosis) that disproportionately affect African Americans.

Public Education and Recruitment Materials

The PIOs commented that one-on-one interactions to educate their constituents about the value of clinical studies are time consuming. They felt a printed brochure that would motivate patients to participate in clinical trials and address the benefits and risks of their participation would be desirable; the brochure's audience would be patients, not physicians, and it would be applicable to all the Institute's constituents, not a specific disease group. They also felt the public needed to be better informed about the nature and need for clinical trials, including differences between the phases or stages of a trial. The NHLBI panel members encouraged the PIOs to "take the leap" and participate in the development of such materials by identifying patients' questions and concerns and communicating this information to the NHLBI.

NHLBI staff noted that the NIH, often in collaboration with professional medical societies, provides informational materials to health practitioners for distribution in their offices to patients. Staff also noted that different types of outreach are needed for the major, common medical illnesses versus rare diseases.

Role of PIOs in Enhancing Clinical Research

The participants agreed that the NIH offers a valuable resource for clinical research at the NIH and in multicenter studies. They suggested that the PIOs could facilitate this research by helping to determine research needs in their areas of interest, identify researchers with expertise in these areas, and stimulate and support the training and development of these researchers. (Also see the discussion on Linking Up With Researchers in the breakout session summarized below.)

Participation in Research Protocols

The PIOs expressed concern about the appropriateness of having narrowly defined inclusion criteria for research protocols that address complex diseases (e.g., sarcoidosis). NHLBI staff noted that determining the eligibility criteria for research on complex diseases is difficult. The number of patients needed is greater than for other studies, but the increased number and variability may affect the possibility of obtaining meaningful results. For any clinical study, patients must meet strictly defined criteria, and investigators can deny participation, for scientific reasons, to any individual.

The PIOs also asked about the inclusion of pregnant women in clinical studies. NHLBI staff noted that various reports have addressed the appropriateness of including pregnant women. For each protocol, researchers determine the appropriateness of including or excluding pregnant women, based on the risk and benefits of the research, and an IRB reviews and approves this determination. Specific rules governing this provision can be obtained from the NIH by calling 301-402-3444.

Assurances for PIOs and Patients

The participants asked about the protections for PIOs that help recruit patients for clinical studies and can be held liable for unanticipated effects. NHLBI staff suggested that the PIOs inform themselves about the review process for a study and obtain the necessary documents of approval and re-approval (e.g., from the IRB, FDA). Staff noted that IRBs differ in composition, function, and activities. It was suggested that each PIO should establish an independent science board to review all consent forms and documents pertaining to studies in which their patients participate.

The participants also noted that the PIOs can obtain information about a study, for their patients, from an IRB and can request interim reports on the progress of a study. Staff suggested that the PIOs identify the sponsors of studies and how the results will be reported, particularly for studies supported by a private company.

Follow-up Support for Patients

The participants asked about follow-up support for patients after a clinical trial has ended. The NHLBI noted that third-party payers cover (at least in part) the costs of follow-up care, which would include new treatments that become the "standard of care" as a result of the trial. There may be a delay between the end of a trial and third-party payers' reimbursement for treatment, although pharmaceutical manufacturers sometimes continue in the interim to provide the drug used in the trial to patients.

Funding Research

Three presentations by NHLBI staff provided a framework for discussions during this breakout session.

Dr. Carl Roth
Research Funding by the NHLBI
Dr. Barbara Alving
Generation of NHLBI-Initiated Activities
Dr. Cage Johnson
The Perspective of an Investigator
Discussion on Funding Research

Research Funding by the NHLBI

Dr. Carl Roth, Associate Director for Scientific Program Operation, NHLBI, presented an overview of the NHLBI's budget and activities. During the past 4 years, annual appropriations for the Institute have increased significantly, as part of the campaign to double the NIH budget in 5 years. In Fiscal Year (FY) 2002, the NHLBI budget of more than $2.5 billion was distributed among extramural research (approximately 91 percent), intramural research (approximately 6 percent), and research management and support (approximately 3 percent). This percentage distribution has remained about the same during the past 10 years.

Extramural activities include:
  • Investigator-initiated research, which is funded from unsolicited grant applications that investigators may submit three times a year
  • Institute-initiated research, which the NHLBI solicits through Requests for Applications (RFAs), Program Announcements (PAs), or Requests for Proposals (RFPs)
  • Research training.

RFAs and RFPs are one-time solicitations and funds are set aside for the awards, whereas PAs are continuing solicitations with no set-aside funds. Applications in response to RFAs and PAs are funded as grants, and applications in response to RFPs are funded as contracts. In FY 2001, the percentage distribution of NHLBI expenditures for extramural activities was approximately 69.2 percent for investigator-initiated research, 27.3 percent for Institute-initiated research, and 3.5 percent for research training. This distribution has remained relatively constant during the past 10 years.

Dr. Roth noted that all research applications are peer reviewed. Unsolicited applications and applications submitted in response to PAs are reviewed by a standing initial review group convened by the NIH Center for Scientific Review, and applications in response to RFAs and RFPs are reviewed by special review groups convened by the NHLBI. The NHLBAC provides secondary review for all research grant applications, approves grant applications for funding, advises the NHLBI on Institute-initiated activities, and approves concepts for RFPs (NHLBI staff provide secondary review of research contract applications submitted in response to RFPs). The NHLBAC also advises the Institute on grantmaking policies and procedures and reviews the work of intramural investigators. The NHLBAC, which consists of 12 health research experts and 6 public interest members, meets four times each year. No grant awards can be made without the NHLBAC's approval. Dr. Roth provided a handout that describes and compares the different review processes in detail.

Generation of NHLBI-Initiated Activities

Dr. Alving elaborated on the process of developing RFAs and RFPs and of obtaining funding for applications submitted in response to these initiatives. She noted that these initiatives, which use set-aside funds, are an important aspect of the Institute's activities. She emphasized that the NHLBI may or may not release initiatives depending on the Institute's portfolio and the availability of funds.

The "birth" of initiatives arises from discussions with basic scientists, clinical investigators, members of PIOs or professional societies, and the Congress. Ideas are transmitted to the NHLBI, which may convene working groups or workshops to further develop ideas in consultation with extramural investigators and others, including patients and representatives of PIOs. Workshop reports are posted on the NHLBI Web site. Staff subsequently prepare the concept of an initiative for consideration by the Institute's Board of Extramural Advisors (BEA). The BEA may suggest modifications and ranks initiatives, which are then presented for further discussion to the NHLBAC and, subsequently, to the staff for further development. For clinical trials, investigators may propose specific initiatives directly to the NHLBI for consideration by an NHLBI review group.

Dr. Alving noted that the BEA, established in September 1999, is a scientific advisory group that meets twice yearly to review initiatives, proposed workshops and conferences, and the results of completed workshops and conferences. Composed of senior investigators with broad expertise, the BEA provides another level of review for the Institute and is the main advisory group to the NHLBAC. Members of the BEA and of the NHLBAC are invited to attend each other's meetings.

Dr. Alving described two examples to illustrate the gestation of an NHLBI initiative: the RFA for Transfusion Medicine/Hemostatis Clinical Research Network (RFA-HL-02-001; and the RFA for Centers for Reducing Asthma Disparities (RFA-HL-02-006; The NHLBI released these RFAs in 2001 and expects to fund awards in 2002 or 2003. The examples demonstrate that gestation, from initial discussion of an idea to the funding of awards, takes 2-3 years.

Dr. Alving also noted that clinical studies take time. She highlighted the "Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)," which involves 600 centers and approximately 42,000 participants in an evaluation to determine the best treatment for hypertension. Begun in 1994, this study will end in 2002, after which the results will be disseminated.

The Perspective of an Investigator

Dr. Cage Johnson, Professor of Medicine, University of Southern California School of Medicine, Los Angeles, commented on the development and review of investigator-initiated research grant applications from the perspective of a researcher and a member of the NHLBAC. He noted that the NHLBI is able to fund about 30 percent of the proposals it receives, and he emphasized that "quality is key." Dr. Johnson described the process of developing a proposal, from generation of an idea to review of prior research findings, organization of a research team, determination of the methodology and protocol, testing of the procedures and capability for conducting the research, and testing of the hypothesis.

At the NIH, proposals for investigator-initiated research are first reviewed by study sections (initial review groups). Dr. Johnson noted that study sections are composed of experts in a scientific area and associated disciplines (e.g., methods, clinical aspects, biostatistics). The study sections review all aspects of the proposals and focus on the importance of the research questions in relation to health and science, the experience and expertise of the research team, and the adequacy of the preliminary data submitted. For clinical studies, reviewers also address the adequacy and appropriateness of the research protocol and methods, the criteria for including or excluding human subjects, protection of human subjects, procedures for obtaining informed consent, and impact on clinical practice.

Based on its review, the study section gives each proposal a priority score, which reflects its overall scientific merit, and forwards the proposal and score to the NHLBAC for secondary review. The NHLBAC, in performing this function (described above in the section on Research Funding by the NHLBI), may advise the Institute on the funding of specific applications, especially those with scores bordering the funding cut-off point, and may assist the Institute in reviewing rebuttal letters from investigators seeking additional review. Dr. Johnson emphasized that the NHLBAC's recommendations for funding are based solely on the quality of applications. The Institute's actual funding of awards reflects the availability of funds and programmatic decisions.

Dr. Johnson also commented on the organization and function of DSMBs (also discussed in Dr. Friedman's presentation). A DSMB is established for each clinical trial and is independent of the investigators and the NHLBI. Composed of basic and clinical scientists, ethicists, statisticians, and others with expertise in clinical studies, the DSMBs meet twice a year to review the adequacy of the informed consent process; monitor enrollment, safety of subjects, and collection and accuracy of data; and review ongoing research. The DSMBs advise the sponsors of the study (e.g., the NHLBI) on problems and potential solutions and recommend continuation or discontinuation of the study.

Discussion on Funding Research

The participants focused on the opportunities and challenges for interaction between the PIOs and researchers and with the NHLBI.

Linking Up With Researchers

The participants noted that small PIOs often do not have funds to support research and need assistance to develop this capability and the grantsmanship required to apply successfully for NIH awards. NHLBI staff noted that the Institute's focus is to fund research and that it may collaborate with PIOs to support research, research training, and scientific conferences. For example, the NHLBI has collaborated successfully with several PIOs, such as the Cystic Fibrosis Foundation, to support quality research on important questions that would not be addressed otherwise.

Drs. Alving and Roth encouraged the PIOs to talk with NHLBI staff, many of whom were present at the meeting, to foster communication and interactions on research needs (e.g., in sarcoidosis). Staff noted, for example, that the NHLBI is supporting both intramural and extramural research studies of sarcoidosis and that PIOs in this area could interact with the NHLBI to publicize the clinical studies and help recruit patients.

Other PIOs commented on the "chicken-and-egg" conundrum of organizing a PIO to support research, and they encouraged smaller PIOs to create a team effort between the PIO and research physicians to "harness the energy" of both in the search for effective treatments. NHLBI staff noted that "start-up" funds provided by PIOs [e.g., the Children's Heart Foundation (] to junior investigators enable these investigators to develop the data and competency needed to compete successfully for NIH grant support. Staff encouraged PIOs that are interested in supporting research or researchers to contact the NHLBI.

Return to Public Involvement
Return to Starting Up a Public Interest Organization
Continue to Questions and Answers and Closing Remarks
Last Modified: 3/19/02

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