Introduction

Return to Top

The National Heart, Lung, and Blood Institute (NHLBI) convened a Public Interest Organization Meeting as an initial step toward developing a process to enhance public input and involvement in its activities. Approximately 100 individuals participated in the 1-day meeting. They included representatives from about 50 public interest organizations as well as universities, professional societies, and the NHLBI. The participants engaged in a dynamic interaction, exchanging views and ideas and learning from each other's experiences. The meeting was so well received that the organizations recommended broader communications, new partnerships, and additional forums.

The agenda included presentations from three perspectives: researchers, constituency groups, and patients. General discussion followed each series of presentations. Speakers commented on the value of research into rare diseases and of contributions from basic research; the various ways in which well-established and "grass-roots" advocacy organizations have effectively influenced the Congress, public, and the NHLBI; the critical and often courageous role that patients play in biomedical research; and opportunities for individuals to participate in NHLBI clinical research protocols. The presentations and discussion provided the framework for six breakout groups which met to identify practical steps that the NHLBI and public interest organizations could take to enhance public input and involvement in NHLBI activities. This report summarizes the presentations, discussions, and suggestions from the meeting.

Dr. Claude Lenfant, Director, NHLBI, welcomed all the participants as "shareholders" who support the work of the NHLBI. He commented that NHLBI staff have met separately with many of the organizations represented and that this was the first collective meeting. He asked everyone to express his or her views candidly and from a broad perspective, with the understanding that research in one area potentially benefits many other areas.

Two intramural researchers described clinical research programs at the NHLBI and the relevance of basic research to prevention, diagnosis, and treatment of disease. The first speaker, Dr. Elizabeth Nabel, Director, Clinical Research Programs, NHLBI, noted that the Institute has an active and robust intramural clinical research program that includes 60 clinical studies involving approximately 12,000 outpatients and 6,000 inpatients at the National Institutes of Health (NIH) Clinical Center. The goals of the program are to engage in clinical research that yields new and innovative insights into heart, lung, and blood diseases that can be translated into new treatments; to provide outstanding care for individuals and families affected by these diseases; and to serve as a national resource for training and education in heart, lung, and blood research.

Focusing on cardiovascular diseases, Dr. Nabel described how patients benefit from "cross-talk" between research focused on understanding common disease processes and research targeted to rare diseases. In the case of Tangier disease, for example, scientists' unraveling of the genetic defect in this rare disorder of high-density lipoprotein metabolism is enhancing understanding of the atherosclerosis process that affects many Americans. The information gained also suggests possibilities for innovative treatments (e.g., drugs) and approaches (e.g., angiogenesis, prevention of blockages) for both the rare and common disease. Dr. Nabel noted that, in this exciting time of medicine, translation of basic research findings into new clinical treatments is becoming increasingly possible. Particularly promising areas of clinical research include genetics, developmental biology, cardiothoracic surgery, bone marrow transplantation, and inflammatory lung diseases. In collaboration with the NHLBI, public interest organizations can help direct and focus this research.

Dr. Robert Balaban, Director, Laboratory Research Programs, NHLBI, described one research effort that has successfully made "the leap" from basic research to clinical application: magnetic resonance imaging (MRI). This technology allows physicians to observe the dynamics of the myocardium in "real-time," as well as water and fat activity in the heart and blood vessels, cross-sections of the heart in three dimensions, and the heart's overall structure and functioning. This technology, based on measurement of radio-frequency signals emitted from water in a magnetic field, provides all the information available from other imaging methods (e.g., echocardiography, coronary angiography, nuclear medicine, positron emission tomography) and more. Major advances in engineering over the past 10 years have made MRI applicable to studies of the heart, and routine use of MRI to provide high-quality, noninvasive coronary angiograms can be expected within 5 years.

Scientists are already using MRI to visualize large and small carotid arteries noninvasively, guide catheters for interventions, quantify cardiac function, measure perfusion and blood flow in the heart and vessels, assess cardiovascular variability and remodeling, and obtain good-quality coronary angiograms of large vessels. Dr. Balaban noted that MRI will have the greatest impact in emergency departments, benefiting patients and reducing health care costs. The NHLBI is supporting an innovative pilot study, in partnership with Suburban Hospital in Bethesda, Maryland, to evaluate use of MRI for assessing chest pain in individuals admitted to the emergency department. Preliminary data indicate that MRI provides detailed information on cardiac function and tissue quickly and efficiently. This technology, first used by the NHLBI for basic research on the heart, is likely to improve clinical medicine dramatically.

The participants expressed concern about patient safety issues (e.g., informed consent, reporting of data) in clinical protocols involving gene therapy. Dr. Nabel noted the need to ensure protection of individuals participating in these studies. The NHLBI Intramural Research Program has instituted a number of mechanisms to ensure adequate protection (e.g., establishment of an Office of Clinical Affairs, data safety monitoring boards, standards for clinical research, and external audits). The participants encouraged the NHLBI to provide models for this activity to constituents supporting research.

Asked to comment on the setting of research priorities and the selection of scientists in the intramural program, Dr. Nabel described the organization of the program and the external review process. Dr. Lenfant said that many factors are considered in making research decisions, including morbidity and mortality from disease, state of knowledge, scientific opportunities, constituents' actions, and congressional legislation and funding. A participant noted that the NHLBI funds the most competitive science through an excellent peer-review process and that public interest organizations can promote both better science and increases in congressional funding.

The participants also addressed the potential availability and costs of MRI. If use of this technology in emergency departments is proven to be cost-effective and to improve patient outcomes, could it be used for early detection of Marfan syndrome or sarcoidosis, for example, and would the costs be reimbursed by third-party payers?

One topic singled out as a major public health problem was obesity. Dr. Lenfant noted that the decline in U.S. mortality from cardiovascular disease over the past 30-40 years is largely due to the availability of new treatments and the control of risk factors. One risk factor that continues to increase, however, is obesity, which the Institute is addressing. A better understanding of the developmental biology and genetics of obesity is needed, as well as targeted prevention and education programs. Dr. Lenfant emphasized that this issue demands public participation, and he encouraged public interest organizations to communicate with him and the NHLBI Office of Prevention, Education, and Control on ways to address the issue more effectively.

Representatives from three constituency groups commented on public input, public-private partnerships, and collaborations with the NHLBI. Dr. Lynn Smaha, President, American Heart Association (AHA), described the mission and activities of the AHA and its approach to providing information and obtaining input from the public on research interests and priorities. He emphasized the importance of partnerships with other groups and the NHLBI to promote understanding of health issues and to apply new knowledge. Hypertension, for example, is a major risk factor for cardiovascular disease and can be prevented, but only one-half of Americans with this condition are being treated.

The AHA recently announced a specific goal to reduce death and disability from cardiovascular disease and stroke by 25 percent over the next 10 years. More than 3,000 staff members and approximately 4 million volunteers are contributing to AHA programs to package and disseminate credible information from scientists and to create partnerships and networks to operationalize programs and obtain input. The budget of approximately $130 million a year is allocated primarily to research and also supports publication of five major journals, as well as position papers, science statements, and consensus guidelines and the training of emergency cardiac care workers. The AHA obtains broad input on its research and program priorities from the scientific community, public, pharmaceutical industry, government agencies, device manufacturers, and donors. Two key issues the AHA has addressed, for example, are barriers to pursuing research careers and barriers to providing care to reduce disability and improve prevention. Many AHA activities already are conducted in tandem with the NHLBI (e.g., development of strategic plans, identification of "hot areas" for research, congressional liaison). Additional opportunities for networking include managing population and behavioral studies and conducting outcomes-based research.

Ms. Doris Tulcin, Executive Director, Cystic Fibrosis Foundation (CFF), commented on how constituent groups such as the CFF can influence the Congress and interact with the NIH. She noted that "every journey begins with several small steps." The foundation's partnership with the NHLBI began in 1976 in response to a congressional mandate to study the state-of-the-art and funding of research for cystic fibrosis. At the time, the disease was perceived as an unsolvable mystery, and the challenge was to develop more innovative research approaches. Ms. Tulcin traced the history of CFF-NHLBI collaboration, from development of a report and recommendations for Congress to establishment and funding of 12 Research Development Partnership Centers, the first network of publicly endorsed, privately funded U.S. research centers. This multidisciplinary center program, initiated in the early 1980s, continues and is complemented by other, similarly conceived programs, including CFF's Gene Transfer Centers and a Therapeutics Development Program.

Factors contributing to CFF's successful partnership with the NIH and Congress include having appreciation for Congress's preference for supporting general basic and clinical research, rather than specific disease-related research; understanding NIH's funding and budgetary processes and the importance of Congress's authorizing language; providing congressional testimony each year to specify research needs and communicate support for the NIH; launching a public-policy alliance of 650 members who receive "alerts" to contact Congress on areas of interest (e.g., patient choice and access, tax credits for orphan drugs, organ transplantation, managed care reform); continuing to encourage legislation on key issues (e.g., privacy of medical information, protection of human subjects); maintaining communications with states about CFF programs; participating in dialogues affecting public policy (e.g., on clinical trials, gene therapy); and collaborating with health coalitions that maintain contact with the Congress (e.g., the Ad Hoc Group for Medical Research Funding). In closing, Ms. Tulcin emphasized that CFF has made a commitment to educate leaders in order to orchestrate political power, knowing that a single letter or telephone call can influence a decision.

Ms. Sue Byrnes, Executive Director, The LAM Foundation, presented a similar perspective, beginning with a quotation from Lao Tzo, "a journey of a thousand miles must begin with a single step." The single step for The LAM Foundation began when Ms. Byrnes' daughter, who had been diagnosed with lymphangioleiomyomatosis (LAM), a rare and fatal lung disease, said to her mother, "you're my best hope." Although LAM was identified 60 years ago, little research had been conducted on it and no cause, cure, or treatment had been determined. Affected individuals were usually undiagnosed or misdiagnosed. As had been recommended previously by physicians, Ms. Byrnes proceeded to developed a registry of LAM patients and then launched a major outreach and public awareness effort involving schoolchildren, educators, and physicians. An NHLBI Working Group Meeting on LAM, held in March 1995, "gave wing" to the Foundation, which was officially established in August 1995 and adopted research as its central mission.

Four years since its inception, and with the guidance of two scientific advisory boards, the foundation has funded 23 investigators, identified more than 500 LAM patients, cosponsored six major meetings on LAM, and undertaken an aggressive support and education program that includes a patient directory, newsletters for patients and the public, and a listserv for patients. The foundation's budget in year 4 is $2 million, of which $1.5 million is allocated to research. Ms. Byrnes reported that investigators have identified important genetic aspects of LAM and a beneficial treatment. Saying "hats off to the NHLBI," she noted that the Institute and the foundation enjoy a mutually beneficial and model collaboration. Together, they are supporting a clinical protocol involving 167 LAM patients. In closing, she shared some "secrets" for other "grass-roots" efforts, including "keep the vision and stick to the mission" of research, raise awareness through Congress, take responsibility for educating and motivating patients, encourage interaction among patients and investigators, develop a broad network of fundraising, and find an advocate in the scientific community.

Dr. Lenfant commented that the presentations depicted three different approaches for constituency groups collaborating with the NHLBI. Whereas the AHA emphasizes a broad outreach program to inform and educate Americans about a disease and many related conditions that affect millions, the CFF supports research centers focused on a disease that affects thousands, and The LAM Foundation is stimulating research to expand knowledge about a disease that affects perhaps 500-600 individuals.

Representatives from other organizations stated that their experience had been similar to that presented. They asked the presenters to comment further on ways of attracting high-quality scientists to investigate a particular illness, establishing a registry of patients, educating physicians about a disease, encouraging interdisciplinary collaborative research within the NIH structure, enhancing the overall pool of researchers, nurturing young scientists, promoting translational and clinical research, presenting public testimony before Congress, and sharing pertinent clinical information to organizations addressing different conditions. The presenters emphasized the importance of several aspects of organizing an effective constituent group: raising sufficient funds to establish a research program that will attract junior and senior scientists, identifying a physician-scientist champion who can enlist the participation of other physicians and scientists, convening meetings of patients and physicians, initially supporting small grants with "seed monies" which could serve to leverage additional funding from the NIH, and providing both written and oral testimony from patients to Congress.

In response to specific inquiries, Dr. Lenfant said that the NHLBI is receiving an increasing number of research grant applications pertaining to sarcoidosis and is prepared to support additional research in this area. He noted that trans-NIH interdisciplinary collaborations are increasingly common and include, for example, a joint initiative for research on autoimmune diseases. In relation to this, the NHLBI is discussing the possibility of establishing a clinical network for blood-related problems, which would include autoimmune and hematological parameters.

Three presenters addressed the participation of patients in research generally and in clinical studies at the NHLBI or sponsored by the NHLBI. Dr. Jane Newburger, Associate Cardiologist, Boston Children's Hospital, described the various ways that patients participate in research. Drawing on examples from cardiology, she emphasized that research is advanced by the courage of these patients and their families. The process of developing new treatments involves a critical step of testing them in patients, initially and in subsequent randomized trials. In initial tests, patients may have a serious and potentially fatal disease for which no treatments are available. One example is hypoplastic left heart syndrome, which used to be fatal within 1 year to all children born with this condition until 1979 when a successful operative technique was developed, which resulted in a 75 percent (and still improving) survival rate at 1 year. In other cases, patients may have a serious disease for which less-than-ideal treatments are available. One example is the 10 percent of otherwise healthy adults who are at risk of stroke because of a patent foramen ovale. A new treatment, transcatheter closure, has been tested in patients and, by eliminating the occurrence of stroke, offers significant benefits over other treatment options.

In randomized trials, patients may contribute to the evaluation of risks and benefits of promising treatments, such as the use of intravenous gamma globulin, which has been shown to be more effective than aspirin for reducing the likelihood of coronary aneurysms in children with Kawasaki disease. In other trials, patients may participate in comparisons of reasonably effective treatments versus potentially better treatments. Such studies have shown, for example, that low-flow bypass offers greater protection to an infant's brain during heart surgery than circulatory arrest. Other studies involve healthy persons willing to test treatments to reduce the risk of cardiovascular disease. In one case, they participated in a randomized, double-blind, placebo-controlled study which showed that lovastatin dramatically lowers cholesterol. In closing, Dr. Newburger emphasized that patients participating in any clinical trial should expect to receive a full explanation of the risks and benefits involved, high-quality care and medical attention, monitoring of safety issues, protection of privacy, and the right to withdraw from the study at any time.

Dr. John Barrett, BMT Unit, Hematology Branch, NHLBI, described clinical research activities in the Hematology Branch of the Institute's Intramural Research Program. This research involves a small number of patients who are participating in early, phase-I studies of experimental approaches to improve treatment. Dr. Barrett focused on bone marrow transplantation (BMT) as a curative treatment for otherwise fatal hematological malignancies resistant to chemotherapy (e.g., acute leukemia). Studies are under way to enhance BMT's powerful immunological effects, optimize treatment outcomes (e.g., by preventing transplantation-related mortality and enhancing antitumor effects), and extend indications for its use to older patients, mismatched donors, and individuals with nonmalignant diseases.

In 1993, the NHLBI initiated an intramural allogeneic stem cell transplant program. This program complements similar extramural efforts and takes advantage of intramural capabilities for sophisticated laboratory research, state-of-the-art cell processing, high-quality patient care and diagnostics, and detailed research investigations with patients and donors. Thus far, the intramural researchers have been able to optimize stem cell doses to achieve profound effects on patients' survival; demonstrate that low-intensity doses reduce transplantation-related mortality; and extend indications for the treatment to other forms of cancer (e.g., chronic myelogeneous leukemia, renal cancer). Dr. Barrett noted that these studies meet the criteria established for all NIH intramural studies (i.e., they are ethically acceptable, offer the best treatment possible, are appropriate for the clinical facility, have a worthwhile goal, address a novel question, and are not feasible outside the NIH).

Dr. Sally Shumaker, Professor, Department of Public Health Sciences, Wake Forest University School of Medicine, described patients' participation in NHLBI-supported extramural research as "being part of the answer." She noted that participation in extramural clinical research offers patients an important opportunity to contribute to current and future medical knowledge and to improvements in medical care. She also noted that participation requires patients' time, dedication, and altruism, even when they may derive no direct benefit. Drawing on her experience with the NIH-supported Women's Health Initiative, she commented on the multiple paths patients may take to enroll in a study, the benefits of participation for patients and others, the duration and population size for studies, and the role of public interest organizations.

Other than participating in large-scale, randomized clinical trials, patients may enroll in community- or clinic-based studies. Community-based enrollment is generally used for large observational studies that yield questions for research or clinical trials, whereas clinic-based enrollment is more common for treatment trials. Although patients derive some benefits (e.g., screening, routine followup), most benefits, by far, accrue to others in the current and future generations (e.g., definitive answers to critical questions, less ambiguous or inappropriate care). The design of each study (e.g., duration, number of patients, expected outcomes) derives from the question(s) to be answered and must accord with statistical principles. For example, large population samples are necessary to establish small, but important, differences in outcomes, and sample sizes must be balanced against the length of followup. Public interest organizations can play an important role in clinical research by helping to frame research questions (e.g., by communicating with constituents, identifying key concerns, informing investigators and funding agencies); by educating investigators and the public about the issue (e.g., helping to enroll hard-to-reach or underrepresented populations, participating on community advisory boards); and by helping to monitor participants over time (e.g., identifying barriers to participation and methods to overcome barriers, educating participants about the importance of "staying with it").

The participants emphasized the need to address ethical issues involved in clinical research. Dr. Lenfant said that these issues are foremost considerations for investigators and the NIH and that many "checks and balances" are in place, such as institutional review boards and data and safety monitoring boards. He noted that clinical research is a complex endeavor, that investigations of new treatments involve some unpredictability, and that the NIH and its grantees are making every effort to minimize any problems and to learn from them and prevent their recurrence.

The participants also expressed concern about the "inflation" of study findings from defined segments of the population to broader population groups. Dr. Lenfant said that the NIH has strict requirements for disseminating information with appropriate caveats, which may be overlooked by the media when reporting results, and that physicians sometimes fail to adopt the recommendations from a study or over-generalize a study's findings. Dr. Shumaker noted that the NIH is funding a series of educational workshops in collaboration with academic health centers to inform the media about research design and reporting of data.

The participants also commented that diagnosis and reporting of cases of rare diseases are complicated by the lack of specific diagnostic criteria and/or an International Classification of Diseases or World Health Organization code. In closing, Dr. Lenfant noted that all clinical studies supported by the NIH, including the NHLBI, are listed on the NIH website (http://www.nih.gov).

The participants divided into six breakout groups which met simultaneously. In presenting their charge, Dr. Lenfant asked them to identify practical and specific ways for facilitating communication and interaction between public interest organizanizations and the NHLBI. The groups met for about 1.5 hours and then reported their findings back in plenary session. Most of the groups organized their suggestions under two headings: What can the NHLBI do for public interest organizations? What can public interest organizations do for the NHLBI?

The participants conceived of a schema of 2-way communication between the NHLBI (and other NIH components) and public interest organizations. These partners, in turn, would interact with broader audiences. For example, the NIH receives direction from the Congress, and the public interest organizations interact closely with health care practitioners, the media, and the general public.

Overall, the participants called for increased communication and sharing of information among the organizations and between the organizations and the NHLBI, strengthening of existing partnerships and development of new partnerships, and continued meetings and followup to address specific topics. Special issues raised by the breakout groups are summarized below.

Communication and Information. The participants suggested that the NHLBI try to increase awareness of its Office of Public Liaison; establish a well-defined route for 2-way communication with different interest organizations (e.g., through meetings, the NHLBI website); designate specific NHLBI staff persons to serve as representatives to public interest organizations; publicize names of NHLBI staff persons to contact; and develop and disseminate an NHLBI "primer" describing what the NHLBI is, how it works, and how organizations can navigate within the NHLBI and NIH to obtain information.

The participants encouraged the NHLBI to enhance its website as a user-friendly presence for public interest organizations (e.g., by highlighting items of interest to public interest organizations; improving accessibility to the site and to NHLBI scientific information; facilitating searches for grants, requests for applications, and research summaries on specific diseases). The participants also encouraged the NHLBI to expand its weblinks to the National Organization for Rare Diseases and other public interest organizations not already included; identify credible health information sites to which the NHLBI could link; develop a listserv or extranet on legislative issues; and offer guidance on accessing PubMed, MEDLINE, and other NIH information sources.

For public interest organizations, the NHLBI could act as a "reservoir" of ongoing research at the NHLBI and NIH; increase the visibility of trans-NIH coordinating committees; and facilitate communication with special interest organizations in vascular diseases. At medical schools, it could continue its efforts to promote translation and delivery of health care advances to help ensure that practitioners use new information as it becomes available.

The participants emphasized the importance of NHLBI efforts to disseminate information and educate the public in cooperation with public interest organizations. The participants expressed particular interest in scientific information (e.g., NHLBI guidelines on asthma, blood pressure, cholesterol) for health care practitioners, patients, and the general public; generic information about ongoing research for the public and public interest organizations; and "NHLBI-reviewed-and-approved" health information that could be disseminated to their constituencies. They also urged the Institute to report on the accuracy of information that is available from other sources; promote timely correction of inaccurate information; advertise scientific meetings; and provide user-friendly reports of NHLBI's Advisory Council and other meetings that could be inserted into organizations' newsletters. The organizations expressed interest in being advised on how to access NHLBI press releases and radio and television "spots" (public service announcements); and in having a contact process for organizations that wish to inquire about possible speakers or commentaries on specific topics.

Partnerships. The participants suggested that the NHLBI could partner with additional public interest organizations to organize disease registries; identify one or two questions that could be added to research studies to address secondary endpoints related to rare diseases; ; develop common themes to support in collaboration with umbrella research organizations (e.g., Research!America); and determine how to meet consumers' needs for credible health and science information.

Meetings and Followup. The participants suggested that the NHLBI convene science-based workshops related to specific conditions and involving individuals affected with rare diseases, NHLBI staff, and research investigators (e.g., to exchange information, "brainstorm" research needs, provide input to the NHLBI's Strategic Plan). Joint scientific meetings focused on specific research themes also would be useful for identifying research gaps and opportunities and promoting cross-fertilization of ideas. The NHLBI could identify organizations with synergy to participate in meetings or provide speakers. To "demystify the Government," the NHLBI could host a seminar for public interest organizations on the functions and missions of Public Health Service agencies.

Communication and Information. The participants suggested that public interest organizations could advertise NHLBI activities and programs among their constituencies; disseminate NHLBI information to their constituencies; and obtain and provide feedback to the NHLBI on the success of its information dissemination programs. Public interest organizations also could inform patient groups about clinical trials and the generic research process (to encourage participation); provide information to the NHLBI on underrepresented groups that could be included in research protocols; and educate patients (e.g., on personal responsibilities for health, ethical issues, accurate diagnoses). The organizations also could communicate to Congress the importance of funding research and develop "grass-roots" support for legislative issues.

Partnerships. The participants suggested that public interest organizations could collaborate with the NHLBI to formulate disease registries (which could be used, for example, to recruit patients for clinical research protocols); define research priorities; problem-solve critical issues (e.g., loan repayment for medical school debts, the declining pool of young researchers); provide access to patients; and promote cooperative funding to leverage the resources of small foundations. Working with the NHLBI, public interest organizations could promote liaison and partnerships with each other, establish umbrella organizations, and provide input to the Institute's decisionmaking processes. They could also conduct "grass-roots" advocacy to generate and stimulate constituencies' discussions with the Congress and state and local legislators.

Meetings and Followup. The public interest organizations expressed strong interest in participating in additional meetings focused on specific problems and solutions. Suggestions related to future meetings included jointly developed agendas, longer (perhaps 2-day) meetings, more time for input from constituency groups, additional breakout sessions (possibly, concurrent), and inclusion of other participants (e.g., staff from other NIH components, including the Office of Rare Diseases, and from Congress).

The participants highlighted three activities for immediate action by the NHLBI: disseminate a summary of the present meeting on the NHLBI website and by mail; create a process for communication and contact among the public interest organizations and with the NHLBI; and establish a committee to follow up and implement the suggestions from this meeting.

Dr. Lenfant thanked the participants for their extremely informative comments and invited them to attend the Institute's Advisory Council meeting the next day. He noted that the NHLBI has jointly funded some research projects with public interest organizations and is interested in exploring other possibilities. He encouraged the participants to forward additional comments to him and said that the NHLBI will follow up and continue its dialogue with public interest organizations.