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Summary of the Fifth Annual Public Interest Organization Meeting

February 11, 2004 - Bethesda, Maryland


Summary Report

The National Heart, Lung, and Blood Institute (NHLBI) convened its fifth annual public interest organization (PIO) meeting to encourage and promote public input and involvement in Institute activities. Approximately 130 individuals participated in the 1-day meeting. They included members of more than 65 public interest organizations, as well as representatives from professional societies, voluntary health agencies, the NHLBI, and the National Heart, Lung, and Blood Advisory Council (NHLBAC). The agenda and format for the meeting were designed to foster interaction among all the individuals and organizations attending. The four previous PIO meetings were held

Two main themes for the fifth annual meeting were fostering collaborations and sharing best practices. The agenda included: The meeting was organized to encourage interaction among all participants and discussion of activities and topics germane to PIOs. Participants contributed to the separate, facilitated discussions of collaborations in:

During the roundtable on sharing best practices, PIOs exchanged ideas and expanded on lessons learned through:

This report summarizes the presentations and discussions at the meeting.

Introductory Remarks

Dr. Barbara Alving, Acting Director, NHLBI, welcomed everyone to the meeting. She noted that participation in the annual PIO meetings has increased every year—evidence of their success. The meetings were initiated under the leadership of the former Director, NHLBI, Dr. Claude Lenfant, who stepped down from his position in September 2003 to pursue interests in international health. Dr. Alving commented that the agenda for the fifth meeting was organized to facilitate exploration of ways for PIOs to collaborate with each other toward achieving their common goals. She invited the representatives of organizations attending to share their expertise with other PIOs, and she encouraged everyone to give feedback about the meeting to the NHLBI.

Dr. Alving remarked that February is “American Heart Month” and that February 6 was National Wear Red Day, a part of The Heart Truth campaign to increase awareness about women and heart disease. The campaign is sponsored by the NHLBI in partnership with the Office on Women’s Health of the U.S. Department of Health and Human Services, the American Heart Association, WomenHeart: the National Coalition for Women with Heart Disease, and others. Dr. Alving noted that the symbol of the campaign is a red dress, and she added that both men and women were wearing their red dress pins.

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Overview of the NIH Roadmap

Dr. Elias Zerhouni, Director, NIH, discussed the themes and initiatives of the NIH Roadmap in the context of trends in disease and research. He emphasized that the PIOs have an important role in supporting the NIH mission, and he thanked the PIOs for their continued advice and wisdom. Dr. Zerhouni noted that approximately 21,000 individuals give advice to the NIH each year through peer review panels and advisory committees and that these individuals “drive NIH’s energy” and are an essential “reality check” for the agency.

The NIH consists of 27 institutes and centers (ICs). It has experienced rapid growth, with a doubling of its budget in 5 years, and is challenged by an even greater expansion in the complexity of scientific and research issues. In this new era, key questions for the NIH are:

Dr. Zerhouni noted that much attention is being given to achieving a balance between conducting basic research and translating research findings into practice. He compared the interconnected wholeness of basic and translational research to a hand—with the palm representing basic research and the fingers representing translational research—and he noted that the need to balance these endeavors reflects the changing landscape of disease and research over the past 30 years.

From a public health perspective, the focus shifted over that same period from acute disease to chronic disease. In heart disease and cancer, for example, scientists have made great progress in preventing and treating acute events (e.g., stroke). While these advances have increased life expectancy, they also have led to the emergence of chronic conditions (e.g., congestive heart failure) that diminish quality of life. Other problems that require attention include health disparities, the health effects of aging, and disabling conditions such as musculoskeletal disease.

From a research perspective, scientists now have tools and techniques for exploring complex biological systems in ways not possible 30 years—or even 5 years—ago. With the completed sequencing of the human genome in 2003 and the emergence of high-throughput computer capabilities for analyzing tissue and generating biological data, scientists can now rapidly identify genes associated with a disease and probe questions about their function. Through this research, for example, we now know that cancer is not caused by a “magic bullet,” as was thought in 1973, but is the result of complex interactions involving many, many genes and environmental factors as well.

Dr. Zerhouni noted that, with these perspectives in mind, the NIH launched in September 2003 the NIH Roadmap. The NIH views the Roadmap as an investment portfolio to transform medical research and to speed the translation of research findings into clinical practice. In fiscal year 2004, NIH is allocating approximately 0.05-0.06 percent of its budget to the Roadmap. Its three major themes are:

Within these themes, the NIH is pursuing 28 scientific initiatives. Dr. Zerhouni elaborated on several of them. He noted that two phenomena underpin the new pathways to discovery—the complexity of biological systems and the convergence between biological fields. To foster multidisciplinary collaborations, the NIH is investing in quantitative research, development of specific tools (e.g., molecular probes) for measuring effects on biological systems, production of molecular libraries that will be publicly available, and other related efforts. Ultimately, these bold, high-risk initiatives will enable researchers to use computational programs to search for biological interactions.

The NIH also is encouraging coordination of integrated, multidisciplinary research teams to test bold ideas and to solve problems in unexplored areas of research. One initiative under this theme is the NIH Director’s Pioneer Award, a 5-year grant for investigators who are exceptionally creative and diligent and who are pursuing bold research relevant to the NIH mission. All ICs are contributing funds to this award program.

Dr. Zerhouni noted that the obvious need to re-engineer the clinical research enterprise arises from a number of problems, which include the:

He noted that the problems are not insurmountable and that the NIH and PIOs can provide leadership to resolve them. Dr. Zerhouni emphasized that clinical research is ultimately driven by partnerships between researchers and patients, including patient advocacy groups. To tackle major health problems, the United States must develop a more unified and integrated system of health care with patients at the center.

Complete details and progress on the NIH Roadmap are presented on the NIH Web site: www.nih.gov


The participants congratulated Dr. Zerhouni on his efforts and thanked him for developing the NIH Roadmap.


The participants asked Dr. Zerhouni to consider forming a trans-NIH PIO. Dr. Zerhouni indicated that he would present this suggestion to the NIH Director’s Council of Public Representatives (COPR), which he has already asked to be more integrative of public input. He commented that the NIH faces the same organizational problem as the PIOs—“silos vs. synergy.”

NIH Information on the Impact of PIOs on Research

The participants asked whether the NIH has a single locus of information on the impact of PIOs on research. Dr. Zerhouni responded that the NIH has no single site, although several ICs have addressed this topic. For example, the National Institute of Diabetes and Digestive and Kidney Diseases compiles information on self-care for diabetes, and the NHLBI Office of Prevention, Education, and Control supports educational programs for patients with asthma, chronic obstructive pulmonary disease (COPD), and other conditions. The PIOs can access this information on the Web sites of the individual NIH components (see www.nih.gov.)

Communities of Research

Dr. Zerhouni emphasized that creation of “communities of research” that integrate patients, patient advocacy groups, and academic health centers is an essential aspect of re-engineering the clinical research enterprise. He cited the success of the NIH’s longstanding collaboration with the cystic fibrosis community in extending the life expectancy of patients with cystic fibrosis, as an example of the gains to be made from communities of research. Through such communities, evidence-based research can lead to identification of best practices for improving treatment, while the search for possible causes and a potential cure continues. Dr. Zerhouni noted that the NIH collaboration in cystic fibrosis is a proven model for other communities of research that PIOs may wish to emulate.

Collaboration between PIOs and the NIH

Responding to a question about how PIOs can collaborate with the NIH to help ensure the success of research programs, Dr. Zerhouni encouraged the PIOs to help:

Commenting on how the NIH could help match PIOs with promising researchers, Dr. Zerhouni encouraged the PIOs to peruse the CRISP database—a publicly available, searchable database of all federally supported biomedical research projects. CRISP stands for “Computer Retrieval of Information on Scientific Projects.” The database can be accessed through the NIH Web site or directly at CRISP

NIH Research on Rare Diseases

The participants thanked Dr. Zerhouni for NIH support of research on rare diseases, saying that it was like “being Cinderella with the glass slipper at the NIH ball.” Dr. Zerhouni noted that the NIH is very focused on rare diseases and that this research is a “driver” for the NIH initiative to develop molecular probes. He also noted that research on rare diseases is a unique feature of the NIH intramural research program, and he applauded the efforts of the NIH Office of Rare Diseases.

Commenting on the need to promote research on the relationship between lung and airway diseases and other diseases, Dr. Alving noted that the NHLBI is developing an initiative to foster collaboration among NIH components in research on lung diseases as they affect other organ systems.

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The NHLBI as a Catalyst for Public Involvement

Dr. William Martin, former President, American Thoracic Society (ATS), and two members of the ATS Public Advisory Roundtable (PAR) described the origin, activities, and current challenges for the ATS-PAR. Dr. Martin suggested that the ATS-PAR offers a model for increasing the influence and effectiveness of the PIOs within the medical research system. He noted that the PIOs are just beginning this venture and have the power to propel the system. The NHLBI serves as an important catalyst for this public involvement.

Origin of the ATS-PAR

Dr. Martin described the germination of his idea for a PAR, which began when he was a staff member of the U.S. Senate Labor and Human Resources Committee. At the time, the committee was responsible for many aspects of health care reform, including reauthorization of the NIH. Subsequently, Dr. Martin became a member of the NHLBAC and then President, ATS. These experiences convinced him of the power of patient advocacy groups on Capitol Hill and the necessity for the ATS to seize a moment of opportunity to involve PIOs in its efforts. The ATS is a membership organization representing approximately 12,000 physicians and scientists.

Dr. Martin emphasized that:

Under his leadership, the ATS board of directors approved the concept of a PAR in December 2000. The ATS-PAR convened an organizational gathering on January 31, 2001, in conjunction with the NHLBI’s second annual PIO meeting, and held its first meeting in March 2001 in conjunction with a meeting of the ATS board of directors. Approximately 35 PIOs related to respiratory diseases have expressed an interest in the ATS-PAR, and PIOs have embraced it with energy and enthusiasm.

Activities and Programs: Overview

Ms. Paula Yette Polite, President, Sarcoidosis Research Institute, served as the first chairperson of the ATS-PAR. She described its activities and programs.

In March 2001, the structure, mission, goals, and objectives of the ATS-PAR were defined at its first joint meeting with the ATS board of directors. Four PAR teams were established—advocacy, communication, education, and research. Their activities include the following:

Other ATS-PAR activities include an effort to address patient involvement in the ethical conduct of clinical trials, presentation of awards, outreach to other PIOs, and development of a strategic plan. Ms. Polite noted that ATS committees are represented on the ATS-PAR and that ATS-PAR representatives participate on major ATS committees. In 2003, the ATS-PAR received the ATS public service award and presented two awards, to Dr. Martin for public service and to the NHLBI for excellence.

Ms. Polite invited and encouraged all PIOs to:

Challenges and Future Directions

Mr. John Walsh, President and Chief Executive Officer, Alpha-1 Foundation, conveyed the attributes of the ATS-PAR and highlighted some future directions. He noted that the ATS-PAR logo is a bridge, reflecting its objective of helping to build a bridge among patient communities and, in relation to the NHLBI, to build a bridge between scientists and patients. The ATS-PAR is highly synergistic; it is a true partnership with the ATS and is committed to expanding its representation to the entire lung and airway community.

Mr. Walsh noted that the NHLBI has been a catalyst for PIOs to work together and in collaboration with the NHLBI. Two seed projects in which the ATS-PAR is involved, with the encouragement of the NHLBI, are the:

Mr. Walsh reported that 40 representatives from 22 PIOs attended this year’s ATS-PAR meeting, held on February 10 before the PIO meeting. The main topic was strategic initiatives for the future. Two key initiatives are:

Mr. Walsh urged all PIOs to “take collaboration to the next level and meet the needs of our communities.” He thanked the NHLBI for being the catalyst for collaboration.


Mr. Walsh asked the participants to suggest ideas for collaboration. They suggested the following.

Identify and Approach Other Professional and Scientific Organizations

Dr. Martin suggested that the ATS-PAR and the ATS could help PIOs develop strategies for approaching leading professional and umbrella organizations in the sciences. He also suggested that the ATS leadership could communicate with the leadership of other professional societies on behalf of the PIOs. He noted that two important aspects of developing a partnership relationship are trust and an alignment of interests, and he said that the PAR–ATS collaboration has added value to ATS.

Dr. Homer Boushey, Jr., President, ATS, elaborated on the value of PIOs to professional societies. Representing patients, the PIOs:

For PIOs, collaborations with professional societies offer:

”Be at the Table”

The participants emphasized that the PIOs must be “part of the process.” PIOs must bring the perspectives of patients to national and local discussions of issues concerning health care and medical systems (e.g., insurance, access to care, academic research, medical education).

Create Grass-roots Networks

The participants suggested that the PIOs could “piggyback” national models of collaboration (e.g., COPD-ALERT) onto local efforts. They noted that templates for collaboration need to be developed and suggested that the PIOs could approach the NHLBI and the NIH Office of Rare Diseases for support of “incubator,” capacity-building projects.

Stay Unified in Outreach and Advocacy

The participants highlighted the importance of having a unified message locally, regionally, and nationally. The hemophilia community, for example, was able to stimulate and obtain passage of federal legislation through a 5-year campaign unified at local, regional, and national levels. “One letter and one voice can make a difference.”

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Facilitated Discussions

Following the morning presentations, the attendees had an opportunity to participate in one of three facilitated discussions held in separate breakout rooms. The theme was collaborations—in disseminating public information, helping patients, and promoting relevant research. Approximately 25-30 individuals attended each session, which was facilitated by NHLBI staff and PIO representatives. The discussions were interactive and thought-provoking. The topics and comments are summarized below.

Collaborations in Disseminating Public Information

Dr. Robinson Fulwood, Public Health Program Development Manager, Office of Prevention, Education, and Control, NHLBI
Ms. Barbara Liu, Deputy Director, Office of Science and Technology, NHLBI
Ms. Virginia Ladd, President and Executive Director, American Autoimmune Related Diseases Association

The discussants addressed the reasons to collaborate (or not), how to work with other PIOs, and strategies for disseminating public information.

Reasons to Collaborate

Ms. Ladd provided a handout on this topic. By collaborating with other PIOs and organizations, a PIO can:

A PIO may choose not to collaborate if:

How to Work With Other PIOs

To work with others, a PIO will want to:

PIOs may choose partners that are not advocating for the same disease or disorder, but for related conditions (e.g., lymphedema and cancer). Competition, which is a barrier to effective collaboration, may arise when different organizations are focused on the same disease.

A helpful resource for learning how to form coalitions is the Allies Against Asthma's coalition connections Web site: Asthma Coalitions.

Strategies for Disseminating Public Information

When making plans to disseminate public information, PIOs need to identify all of the resources potentially available for helping with outreach. Four interrelated strategies are:

Celebrities and patients constitute good public spokespersons. PIOs can collaborate in having the same spokesperson. Celebrity spokespersons can give instant public credibility and visibility to a cause. Some celebrities may be reluctant to participate, may not convey the message exactly as intended, or may expect payment for their services, which could weaken their public credibility.

PIOs that are interested in finding a celebrity spokesperson could:

Patients who are spokespersons help to “put a face” on a disease and are very moving and credible when they share their experiences. A good public relations firm (many of them are inexpensive) can help a PIO leader or patient develop the skills needed to ba an effective spokesperson.

To engage the media (the press, local radio, and television stations) in its cause, a PIO can:

Corporate sponsors can help to defray costs and enable PIOs to reach a broader audience. (One PIO leader, for example, asked a company to donate popcorn for a booth at a health fair. While distributing the popcorn, the PIO asked recipients to complete a short survey.)

For PIOs to be effective, they must know the audience(s) they are trying to reach and identify methods most likely to be effective for this audience. PIOs should assess the needs of their constituencies before designing any information to be disseminated—not all communities have the same needs or consume information in the same way.

Some strategies for knowing and reaching your constituency are:

Collaborations in Helping Patients

Ms. Paula Blonski, Vice President, ARDS Foundation
Ms. Eleanor Schron, Nurse Scientist, Clinical Trials Scientific Research Group, NHLBI
Ms. Nancy Loving, Executive Director, WomenHeart: the National Coalition for Women with Heart Disease

The discussants focused on the following six ways that PIOs can collaborate to help their patients:

Working with the Media

Patients benefit from telling their stories, but most need some training before they can be effective spokespersons. PIOs can partner with public relations firms and offices that provide this training. Firms have been willing to donate their services as pro bono activities for nonprofit organizations. Public relations offices in community hospitals have provided media training for PIO members and, in exchange, the members appear in film clips featuring hospital activities and speak about health promotion events. Through such collaborations, PIOs can develop relationships with health reporters. PIOs should not hesitate to ask, or even beg, for help.

Serving as a Resource for Health Care Providers

Many health professionals are more willing to talk with medical colleagues than with patients whom they have never met. PIOs can establish doctor-to-doctor telephone lines for physicians to exchange opinions or receive advice from other physicians who are experts on the particular disease or condition. Serving as a resource for other health professionals can be one of the major responsibilities of a PIO's medical board members.

Facilitating Prayer and Support

Illness affects a patient’s emotional and spiritual health, as well as his or her physical health. PIOs can establish prayer networks and e-mail exchanges to help their members give support to each other. Many patients and families are comforted when other PIO members reach out to them or pray for them. However, PIOs should recognize that some patients and families are not comfortable being contacted by strangers or receiving prayers from people of a different faith.

Meeting Patients’ Diverse Needs

PIOs have used a variety of approaches to meet the diverse needs of patients. For example, some patients may not be fluent in English, some may be blind, and others may not be able to access the Internet. Some ideas are:

Maintaining a Viable and Successful Organization

Each PIO should focus on what it can do best, which may be:

It takes a strong leader to recognize that a PIO cannot do everything and must prioritize what it wants to accomplish. A PIO’s budget often drives its priorities.

To decide on its focus and priorities, a PIO may want to:

With a focus and priorities, PIO members will be eager to return to their communities and raise money for the PIO.

Identifying Available Resources

Sometimes it is not necessary to create a new PIO. Establishing a nonprofit organization is a complex and difficult undertaking. Patients and families might benefit by partnering with an existing entity or entities for the services they need.

One PIO representative recommended the Self-Help Group Sourcebook C Your Guide to Community and Online Support Groups(7th ed.), compiled and edited by Barbara J. White and Edward J. Madara, American Self-Help Group Clearinghouse, Saint Clare's Health Services, Denville, New Jersey. Associated with this sourcebook is a searchable database of support groups and other resources Selfhelp.

Collaborations in Promoting Relevant Research

Dr. Charles Peterson, Director, Division of Blood Diseases and Resources, NHLBI
Dr. William Martin, former President, American Thoracic Society
Dr. John Walsh, President and CEO, Alpha-1 Foundation

The facilitators drew on their experiences to emphasize the important roles that PIOs have in promoting relevant research. For example, PIOs can:

The discussants addressed ways to promote relevant research and patient registries.

Ways to Promote Relevant Research

The main barriers to conducting research that is relevant to the concerns of PIOs are physicians’ lack of awareness about PIOs’ concerns and the dearth of time and funds the physicians have to focus on research needs, which often pertain to rare diseases. PIOs can encourage relevant research by:

The discussants highlighted the need for a better understanding of the NIH application, review, and funding process and for regular interaction with the NIH. They suggested that the NIH (a) organize a 2-day seminar, for both PIOs and researchers, on “how the NIH works”; (b) create a Webcast presentation about the NIH; and (c) establish a trans-NIH public interest organization.

Patient Registries

The discussants noted the following points regarding patient registries:

Several resources of potential interest to PIOs are:

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Scientific Breakout Sessions

NHLBI staff presented four scientific talks in simultaneous breakout sessions. The participants could attend any of the sessions, which included brief question-and-answer periods.

Much Ado about Nearly Nothing: Nanotechnology in
Heart, Lung, Blood, and Sleep Research

Dr. Denis Buxton, Heart Research Program, Division of Heart and Vascular Diseases (DHVD), described Institute initiatives in the new and growing field of nanotechnology. The term nanotechnology refers to the engineering or creation of extremely small (nanoscale) devices—the “nearly nothing” in the title of Dr. Buxton’s presentation. Yes, there is “much ado” about this nearly nothing—at the NIH and elsewhere.

Through nanotechnology, scientists are producing many kinds of minute devices that can be used to perform different tasks and functions. These nanosized objects are extremely powerful, precisely because they are so small and can perform functions and tasks that cannot be done using larger objects. For example, certain changes in the DNA and proteins inside of cells can lead to disease. However, DNA and proteins exist on the nanoscale and are far too small to be manipulated in a controlled fashion using conventional tools. The nanodevices that scientists are creating today will be small enough to interact with DNA and proteins to prevent, diagnose, or treat disease. Scientists also are working on safe methods to introduce nanodevices into the body for use as nanomedicines.

In February 2003, the NHLBI convened a working group of experts in many fields to explore the promise of nanotechnology. The combined efforts of biologists, chemists, physicians, and biophysicists and of researchers in engineering, material science, and polymer science are needed to develop nanotechnology for medical applications.

The application of nanotechnology to heart, lung, blood, and sleep disorders and diseases is just beginning. Four areas in which nanomachines could have an immediate impact are:

In targeted therapeutics, scientists could use nanodevices to deliver drugs to an exact area of the body where they are needed. For example, they could couple a nanoparticle to a drug that kills blood vessels and to a targeting sequence that binds to new blood vessels in order to specifically kill new blood vessels contributing to the development of atherosclerosis. They could also couple antibiotics to nanoparticles designed to seek out bacterial biofilms in the lungs of patients with airway disease. By being able to target areas of the body, scientists will be able to (a) prevent a drug from entering other areas where it is not needed and could harm other tissues, thereby reducing a drug’s potential toxicity and side effects, and (b) achieve longer lasting effects by delivering drugs, some of which are not absorbed well by the body, over time.

In tissue engineering, scientists are already using nanodevices to help build new tissues to replace damaged ones. Many heart, lung, and blood diseases lead to organ or tissue damage. Using nanotechnology, scientists may be able to create new, healthy tissue to replace damaged tissue; make better artificial veins, arteries, and heart valves; develop a scaffold for growing patches of heart tissue to repair damage from heart attacks; and grow artificial lung tissue.

In molecular imaging, scientists strive to create nanodevices that can identify diseases in the body. Scientists hope to use nanoparticles to bind to blood clots and to help make clots more visible by ultrasound. They also hope to make nanodevices that will bind to viruses, bacteria, or other signs of disease—to see exactly where problems are occurring in the body.

In the areas of biosensors and diagnostics, scientists could use nanodevices as implantable sensors to detect problems inside the body and to improve diagnosis of disease. Scientists are pursuing the development of a nanodevice known as a nanocantilever to diagnose heart attacks more rapidly and specifically.

Researchers are working to make nanoparticles and nanodevices safe. Compared with larger objects, nanoparticles have different properties and their performance will be harder to predict. And scientists will have to carefully evaluate the biosafety of nanodevices before they can be approved for internal use.

To foster the development of nanotechnology, the NHLBI has prepared an initiative to fund nanotechnology centers and is formulating another initiative to support innovative research grants in this area. Nanotechnology is also a component of the NIH Roadmap; the NIH will hold a workshop in spring 2004 to plan for NIH Centers of Nanotechnology.


In response to questions, Dr. Buxton elaborated on the possibilities of nanotechnology. For example, nanotechnology might be used to (a) construct sensors that will allow doctors to detect hypoxia in patients with sleep disorders and (b) monitor cells transplanted by blood transfusion in patients with bone marrow diseases. Nanodevices will require a power source, but could remain in the body as long as the power can be maintained.

Patching Your Genes: Converting Gene Therapy’s
Promise to Practice

Dr. Sonia Skarlatos, Vascular Biology Research Program Director, DHVD, described the nature and potential of gene therapy for heart, lung, and blood diseases and disorders. The goal of gene therapy is to modify a person’s genotype (genetic makeup) to produce desired changes in the person’s phenotype (physical, biochemical, and physiological makeup). Each cell nucleus contains 23 pairs of chromosomes consisting of DNA. Similar to a file cabinet, a chromosome contains genes, or files. By “patching” genes, scientists could treat both hereditary and acquired diseases.

In general, gene therapy involves a gene, a vector, and a target. The scientist selects a gene, places it in a vector (delivery vehicle), and sends the vector to its target, the organ or tissue needing repair. Two types of gene therapy are possible:

An ideal vector would target the appropriate cell or organ, allow for regulation of gene expression, have no or minimal toxicity (too much expression could be toxic), not elicit an immune response, and allow for production of large quantities of the gene. Two types of vectors are possible:

The vectors used most commonly are adenovirus and AAV. To create a viral vector, the researcher must delete the harmful DNA (that portion that causes infection and viral replication) and insert the transgene that codes for the therapeutic protein. Because the viral vector is then unable to replicate, the researcher must use a “packaging” cell line. This cell line has the DNA that is missing from the vector, but is required for replication. By placing the vector into the cell line, the researcher enables the vector to replicate and generate large quantities of the gene.

Safety is a primary concern with gene therapy. Theoretically, the risks of gene therapy include:

Researchers have already conducted hundreds of gene therapy studies, and only one death has occurred in the United States, which was caused by an immune response to an adenovirus vector. Two cases of leukemia arose in Europe, which were caused by insertional mutagenesis of a retrovirus vector.

The first gene therapy trial occurred in 1988. The peak year for gene therapy trials was 1999 (91 trials). The number of trials decreased slightly after the death in the United States and the two leukemia cases in Europe. In 2002, there were 51 gene therapy trials and, in 2003, 57 trials.

All treatment protocols involving gene therapy must undergo a rigorous approval process. The U.S. Food and Drug Administration (FDA) must approve U.S. protocols. Studies supported by the NHLBI must be reviewed by the NIH Recombinant Advisory Council, the NHLBI, and a Data and Safety Monitoring Board. This review includes site visits before the study is approved and after it begins. The institution where the gene therapy study will be conducted also must approve the trial—through its Institutional Review Board and Institutional Biosafety Committee.

The FDA requires long-term follow-up of patients. Patients must be seen annually for the first 5 years after treatment and must complete questionnaires annually for years 6 through 15.

Most gene therapy trials have been for cancer. Researchers are or soon will be addressing several heart, lung, and blood diseases and disorders in gene therapy trials. Preceding the trials is a sequence of research—genomic research, cellular research, and studies in animal models. The trials also are sequenced—phase I, phase II, and phase III. The objectives are specific for each research stage. Research that fails to fulfill the objectives at one stage does not progress to the next stage.

Three examples of gene therapy studies supported by the NHLBI are:

To promote gene therapy research, the NHLBI is funding Programs of Excellence in Gene Therapy (PEGTs). The programs consist of national core centers that can produce vectors and offer training programs. The centers are intended to facilitate clinical trials of gene therapy.

As with new technologies in any field, gene therapy will evolve over time and experience setbacks. Many successes are likely as more resources and efforts are committed for the future.


In response to a question, Dr. Skarlatos observed that gene therapy might be useful to correct the venous malformation and vessel overgrowth seen in Klippel-Trenaunay syndrome. She also noted that the time from identifying gene deficiencies to initiating gene therapy protocols could be years.

Scientific Body Building: Tissue Engineering the
Cardiovascular System

Dr. Martha Lundberg, Clinical and Molecular Medicine Program, DHVD, summarized the research challenges, the role of the federal government, and NHLBI and NIH efforts in tissue engineering, or “scientific body building.” Tissue engineering has been defined as “the regeneration of biological tissue through the use of cells, with the aid of supporting structures and/or biomolecules.”

Tissue engineering is a fast-emerging field of research that promises to offer new treatments and cures. This promise is of particular interest to the many patients with end-stage disease requiring transplantation of organs and blood cells that are in short supply; patients who are not eligible for transplants; and patients who are critically ill and have no other options for treatment. For all them, tissue engineering offers the potential of new and effective alternative treatments.

The research challenges are many. First, researchers must clarify how cells interact with one another. With this understanding, they will able to make biomaterial scaffolds on which to support or inhibit cell growth. The scaffolds must be elastic, durable, and strong, and they must degrade at controllable rates and into biocompatible materials. Providing a blood supply to nourish new tissue will also be essential.

Getting tissue-engineered products to the clinic is another major challenge. The products must have useful shelf lives, and procedures must be in place to ensure quality control at all stages of development. Industry will be called upon for testing, production, and preservation of products. The FDA has established an Office of Combination Products to handle the review and regulation of drug–device combinations, which includes tissue-engineered products.

The federal government has an important role in fostering tissue-engineering research to solve public health problems. The government is:

Information on interagency activities related to tissue engineering is available at Tissue Engineering.

Two main activities at the NIH to promote research on tissue engineering are:

In addition, the NIH has issued several program announcements to encourage research on tissue engineering, including:

A BRP is a multidisciplinary research team that combines bioengineering expertise with basic and/or clinical investigators. It must use an integrative, systems approach to develop knowledge and/or methods to prevent, detect, diagnose, or treat disease or to understand health and behavior. The NHLBI has funded 37 BRPs. In one, researchers are developing vascular shunts for patients being treated for peripheral vascular disease or receiving hemodialysis. Another research team is developing artificial arteries that expand and contract like natural arteries.


In response to questions, Dr. Lundberg mentioned that tissue-engineered products could be compromised if a patient who is providing cells to be used in engineering tissue has a genetic problem. This limitation could potentially be overcome by using gene therapy.

The Cellular Jigsaw Puzzle: Putting It Together With
Genetics, Genomics, and Proteomics

Dr. Susan Old, Bioengineering and Genomic Applications Scientific Research Group Leader, DHVD, described the possibilities and approaches offered by genetics, genomics, and proteomics to complete the “jigsaw puzzle” of cell activity. The completed sequencing of the human genome, made possible by the NIH’s Human Genome Project, has created unprecedented opportunities for science. Today, researchers are moving forward to explore the expression and function of individual genes (genomics) and their protein products (proteomics).

This research has implications for greatly improved understanding of health and disease. All diseases have some genetic component. The genetic contribution can be significant in and of itself, as in cystic fibrosis—a single-gene disease—or complexly related to environmental factors, as in type II (adult-onset) diabetes mellitus or infectious diseases such as AIDS. By identifying the genes and their function(s), scientists may be able to improve diagnosis and devise targeted therapies (including gene therapy) for individuals with a disease. The possibility of “personalized medicine”—understanding each individual’s risk for disease, intervening to lessen the risk, and treating disease in a directed way when it arises—has enormous implications for medicine and health in the future.

Completion of the human genome sequence has shown us that all humans mostly share the same DNA. Yet, individuals can have dramatic genetic variation, as reflected in their phenotypes and, potentially, their health and disease. The spectrum of health and disease is dynamic and, at any one time, most individuals are in the middle of the spectrum. Through the process of gene discovery, scientists are beginning to explore the genetic variation of individuals along the spectrum.

Identifying the cause of single-gene diseases is relatively easy, compared with finding the cause(s) of complex disorders that involve multiple genes as well as environmental factors. Two approaches for “teasing out” genes and environmental factors are:

Microarray technology is a powerful tool for analyzing the dynamics of gene expression. Researchers across the United States can share microarray facilities supported by the NIH. Using this technology, they can:

NHLBI researchers are studying gene–environment interactions. An area of much investigation is pharmacogenetics—the individual’s response to drugs. A database from the NIH Pharmacogenetics Research Network, a nationwide collaborative research consortium, can be accessed at NIH Pharmacogenetics.

In addition, the NHLBI supports Programs for Genetic Applications (PGAs) in 11 centers across the United States. The PGA program fosters application of genetic and genomic research findings. Each center offers resources (e.g., biological products), information, research tools, and education for the research community.

Recently, the Institute established the NHLBI Proteomics Initiative to stimulate development of novel proteomic techniques and to facilitate interaction within multidisciplinary centers. Proteomics research is even more challenging than genetic or genomics research—the human genome contains approximately 30,000 genes, but an individual’s cell complement includes about 3 million proteins. Understanding the expression of these proteins and miscues in their expression is essential. Mass spectrometry and protein arrays are two tools researchers are using to compare proteins in normal and disease states.

A cell is a dynamic enterprise with many interactions within and outside the cell. Each pathway of action in the body is extremely complex and detailed, with molecular and cellular interactions at every level. Genetic, genomic, and proteomic studies to understand the interactions are necessarily dependent on bioinformatics and computational approaches and resources. Through the integration of “systems biology,” researchers can examine all elements, measure relationships, and perturb the system to understand and, eventually, predict reactions. By emphasizing new pathways of discovery, multidisciplinary research teams, and clinical applications, the NIH Roadmap is helping to chart this new course in medical research.

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Sleep and Its Disorders

The topic for the scientific presentation at the PIO meeting was sleep and its disorders. The NHLBI houses the National Center on Sleep Disorders Research (NCSDR). In March 2004, the NIH is holding a major meeting, Frontiers of Knowledge in Sleep and Sleep Disorders: Opportunities for Improving Health and Quality of Life, in Bethesda, Maryland. The meeting is sponsored by the NCSDR and the Trans-NIH Sleep Research Coordinating Committee. Several professional associations and PIOs are co-sponsors.

In his presentation, Dr. David White, Associate Professor of Medicine, Harvard Medical School, and Director, Sleep Disorders Program, Brigham and Women’s Hospital, addressed four topics:

He elaborated on these topics, giving examples from NIH-funded research.

Why Do We Sleep?

Dr. White noted that all species need sleep, but the reason why is not understood. Scientists have posited several theories over the years and, currently, are focusing on modulation in the brain’s neurochemistry. Studies of metabolic activity in the brain show that levels of adenosine increase during wakefulness and decrease during sleep. Because many of the studies have been done in cats, adenosine has been labeled the “cat-napping chemical.”

Physiological Determinants of Alertness and Performance

Researchers are learning about the physiological determinants of alertness and performance largely from studies of accidents (automobiles, trucks). The studies suggest four determinants:

Health Effects of Sleep Deprivation

Sleep deprivation is common in the United States and has many consequences beyond falling asleep at meetings or having accidents. Dr. White noted that more research is needed to understand the neurocognitive effects of sleep deprivation. Studies demonstrate that humans need 7-8 hours of sleep each night and cannot maintain health or function effectively if deprived of sleep over time.

Studies in young men sleeping 4 hours a night for 6 nights show impaired glucose tolerance (requiring a 50-percent increase in insulin), decreased leptin levels (indicating increased hunger), increased levels of cortisol (stress hormone) in the evening, and increased sympathetic nervous system activity (higher blood pressure, heart rate). The Nurses’ Health Study showed an 80 percent increase in incidence of myocardial infarction (MI) among nurses receiving only 5 hours of sleep, as well as an increased incidence of MI among those sleeping 9 or more hours. Mice and rats that are totally deprived of sleep consume higher amounts of energy, and their fur deteriorates.

Sleep Disorders

Dr. White focused on two types of sleep disorders—excessive daytime sleepiness and insomnia.

Excessive daytime sleepiness, or hypersomnolence, is a sleep disorder and, as such, is different from fatigue. Hypersomnolence is caused by an increased sleep drive (e.g., in narcolepsy), sleep disruption (e.g., from obstructive sleep apnea, restless legs syndrome [RLS]), inadequate sleep (self-imposed or as a result of shift work) and other conditions (e.g., medications, depression). It is associated with decreased quality of life, a sixfold increase in automobile accidents, mild pulmonary hypertension, systolic hypertension, and arrhythmia. Some evidence indicates that hypersomnolence also is associated with an increased incidence of congestive heart failure, myocardial infarction, and stroke.

Narcolepsy is a disorder of the components of REM (rapid eye-movement) sleep and has various manifestations, including hypersomnolence. Researchers have only recently identified a possible cause of narcolepsy, and their findings point to degradation of the cells in the hypothalamus—a neurodegenerative process. Current treatment is based on the use of stimulants, such as Ritalin, dexadrin, and modafinil, which reduce the need for sleep.

Obstructive sleep apnea is very common, perhaps as common as asthma, and is characterized by a recurring decrease of oxygen in the blood, which stimulates brain activity and respiration, causing the individual to wake up. The major defect causing this disorder is an inadequate (anatomically small) upper airway, which is predisposed to collapse during sleep. Studies show that the disorder contributes to increased pulmonary hypertension and increased systolic hypertension. Current treatments include nasal devices and dental appliances. The efficacy of surgery, a relatively new approach, is not consistent.

Insomnia is defined as being unable to sleep 3-4 nights per week. This sleep disorder is increasingly common in the United States, and the prevalence of chronic insomnia is estimated at 10-17 percent of the population. The causes are many; they include depression, anxiety, neurological and medical factors, conditioned responses, irregular sleep schedules, and circadian disorders (e.g., with shift work).

Dr. White elaborated on conditioned insomnia, which stems from an acute, stressful event and is maintained chronically overtime by negative associations and anxiety as a person seeks to fall asleep. Behavioral approaches approaches—such as maintaining good sleep hygiene (e.g., reducing intake of caffeine), cognitive therapy, relaxation training, sleep restriction, and stimulus control—and hypnotics (benzodiazepines, sedatives) are used to treat chronic insomnia. Behavioral are successful in many cases. The many and growing number of hypnotics differ in dosage, half-life, and duration of action (some 1-2 hours, others 4-18 hours). Dr. White noted that use of hypnotics for chronic insomnia is extensive in Europe, where they are prescribed for 1-5 years, but more limited in the United States, where they are generally prescribed for less than 6 months. Use of sedatives is increasing in the United States.

Dr. White summarized his remarks as follows: (a) many individuals are not getting enough sleep; (b) the NIH is funding much research on sleep and sleep disorders, (c) researchers are making progress, and (d) much more information is needed.


Dr. White said that the first signs or symptoms for consulting a physician about a possible sleep disorder are inability to sleep at night and excessive sleepiness during the day. In response to questions, he noted the following: (a) sleep apnea and other sleep disorders are often associated with lung diseases, such as asthma, emphysema, and COPD, and with heart disease, such as heart failure; (b) little is known about the short- or long-term effects of prednisone on sleep; (c) nothing is known about the neurobiology of idiopathic hypersomnia; (d) snoring may or may not be related to sleep apnea; and (e) ongoing studies of sleep deprivation among medical residents are expected to provide interesting data and to stimulate changes in practice.

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Participating in Research

Ms. Sheila Connolly, member of the Restless Legs Syndrome Foundation Advisory Council and the National Center on Sleep Disorders Research Advisory Board, shared her experiences of participating in clinical studies and discussed the process for volunteering and participating in a study. Ms. Connolly first became aware in 1989 that her “jumpy legs” were a defined medical disorder. A neighbor had read about RLS in literature from the National Organization of Rare Diseases (NORD).

Through initial contacts with NORD and with individuals suggested by NORD, Ms. Connolly began the grass-roots organization of the Restless Legs Syndrome Foundation. Through her physician, she identified a neurologist working in the field, who referred her to a researcher at Robert Wood Johnson Medical School and a potential benefactor. The researcher was conducting research on hereditofamilial RLS and became very interested in Ms. Connolly’s large, extended family, which included her five siblings, all of whom had RLS.

In 1990, Ms. Connolly began participating in a study as a volunteer. Although at first anxious and nervous, she came to realize that participation in a study can be:

Ms. Connolly emphasized that “the thought of not participating never occurred to me” because of the number of family members affected by RLS. Still, the study was more involved and lengthier than she realized. Identifying genes that cause and contribute to disease is a long-term research effort. Many hours are consumed in reconstructing family trees, contacting family members, obtaining informed consent, interviewing and obtaining blood samples, updating information in follow-up, and maintaining family members’ commitment.

An individual volunteer is asked to:

A volunteer will provide information and samples at the beginning of a study and then on a continuing or follow-up basis as needed. Ms. Connolly noted that her family’s participation in the initial research led to participation in a collaborative study conducted in Canada and a study conducted by the National Institute on Aging, NIH. On her death, her brain and spinal tissue will be harvested and stored for further research purposes.

In conclusion, Ms. Connolly captured her experience as follows:

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Sharing Best Practices/Lessons Learned

PIO representatives facilitated six concurrent discussions, each on a specific topic. Facilitators shared their experiences and provided handout materials, and participants were encouraged to circulate among the discussion tables as they wished. Approximately 6 to 15 individuals contributed to the informal and interactive discussions at each table. The six topics were:

The discussion at each table is summarized below.

Developing Materials for Patients and the Public

Ms. Dolores O’Leary, Director, Sarcoid Networking Association
Ms. Amy Verstappen, President, Adult Congenital Heart Association

Ms. O’Leary and Ms. Verstappen shared their experiences in developing print and Web-based materials for patients and the public. They provided, as handouts, examples of their print materials—pamphlets about the PIOs, a double-fold business card with business information on the front and disease information inside, a newsletter, small cards with inspirational messages and PIO information, and small writing pads. Other handouts included information on the responsible management of a PIO’s Web-site message board and/or listserv.

Message boards and listservs where patients can exchange and discuss health-related information are a wonderful resource and source of support for patients. They also can be a powerful teaching tool and, if monitored carefully, a way to counter misinformation. PIOs should become knowledgeable about the computer resources available in order to share this information with patients.

Not everyone has access to a computer or online service. To reach all patients and constituencies, PIOs need to develop and disseminate print materials, as well as Web-based information.

In discussion, the participants suggested the following tips for print and Web-based materials.

Tips for Developing Print Materials

Tips for Reducing the Cost of Print Materials

Tips for Responsibly Maintaining Online Message Boards and Listservs

Tips for Helping Patients Gain Access to Computers

Tips for Designing a Web Page

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Ms. Anne Garrett, Executive Director, Preeclampsia Foundation
Ms. Sue Byrnes, Executive Director, LAM Foundation.

Ms. Garrett and Ms. Byrnes facilitated separate discussions at adjacent tables. For handouts, they provided booklets, compact discs, and other materials used in fundraising.

Some tips for raising and using funds and other support are:

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Organizing a Scientific Advisory Board

Ms. Betsy Peterson, Founder, Children=s Heart Foundation
Ms. Judy Simpson, Founding President and Board Member Emeritus, Pulmonary Hypertension Association

Ms. Peterson and Ms. Simpson counseled the participants individually. A handout, entitled “Organizing a Scientific Advisory Board,” summarized the steps that the Children’s Heart Foundation took to form its Medical Advisory Board. The handout describes the mission of the Children’s Heart Foundation and elaborates on the board—its purpose, formation, duties and responsibilities, and diversity. A copy of the handout may be obtained from Ms. Peterson at 847-441-1709 or chfBetsy@aol.com.

Copies of the Pulmonary Hypertension Association’s journal, Advances in Pulmonary Hypertension, also were distributed. The journal is available on the association’s Web site: Pulmonary Hypertension Association.

Some tips for organizing a scientific advisory board are:

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Putting a Face on Disease

Ms. Wendy Chaite, Executive Director, Lymphatic Research Foundation
Mr. Robert Gelenter, Mended Hearts Inc.

Ms. Chaite and Mr. Gelenter noted that putting a “face” on a disease—to make it visible and identifiable to the public—can be difficult when the disease is very rare or when a disease has many faces (e.g., sarcoidosis). Diseases that cause an obvious physical deformity (e.g., lymphedema) are easier for the public to appreciate and to give support to.

Some tips for putting a face on disease are:

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Starting a Disease Registry and Mobilizing Patient Participation
in Research Studies

Ms. Shelly Bowen, President, Barth Syndrome Foundation, Inc.
Ms. Donna Appell, President and Founder, Hermansky-Pudlak Syndrome Network, Inc.

Ms. Bowen and Ms. Appell provided several handouts. Two pertained to disease registries, listing the benefits, potential pitfalls, and general guidelines for a disease registry and clinical database and describing the Genetic Alliance Biobank clinical data registry. Two other handouts gave suggestions for recruiting families for clinical trials and listed the benefits, potential pitfalls, and general guidelines for recruiting patients for research.

Ms. Bowen described the experience of the Barth Syndrome Foundation in establishing a disease registry. She suggested two examples of good registries—the Pediatric Cardiomyopathy Registry and the International Registry of Holoprosencephaly and Brain Development. Ms. Appell commented that she has a brief slide show to inform families about participating in research. Contact her at 516-922-3440 or Appell@worldnet.att.net.

In discussion, the participants suggested the following tips for starting a disease registry and mobilizing patients for research studies.

Starting a Disease Registry

Mobilizing Patient Participation in Research Studies

The participants addressed seven topics: IRBs, informed consent, privacy considerations, collection of data, recruitment of patients, barriers to participation, and building the public’s trust.

Institutional Review Boards

Informed Consent

Privacy Considerations

Collection of Data

Recruitment of Patients

Barriers to Participation

Potential barriers include:

Building the Public’s Trust

Public trust can be fostered by:

  • Strengthening the PIOs and their relationship with the NIH
  • Encouraging PIOs to reach out beyond their disease focus to other, related diseases and groups
  • Improving communication between physicians and patients (e.g., simplifying disease terminology for patients).

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    Starting and Sustaining Support Groups

    Dr. Eddie Glenn, Founder, Sarcoidosis of the Midlands of South Carolina
    Ms. Barbara Cady, Board Member, Take Off Pounds Sensibly (TOPS) Club

    Dr. Glenn and Ms. Cady shared their thoughts on starting and sustaining support groups. The discussants agreed that support groups are important—they give patients the opportunity to talk with others, find new ways to cope with their disease, and know that they are not alone. Support groups can extend the benefits for patients by including caregivers, families, and health care professionals in the group and by encouraging all members to share their experiences, knowledge, and feelings.

    Support groups may be organized by PIOs or be independent groups. They may be local entities or part of a national network, and they may be based on or maintained by telephone contact, Web-based communications, and face-to-face interactions. Each group is different, and each group will change over time as its members and goals change.

    Although the best interactions are face-to-face, online groups offer an attractive, alternative forum for support. Online interactions may be the main support for patients with rare diseases who are distributed throughout the United States and the world and for patients who are unable to travel easily. Through online groups, patients can access a wide network of medical resources and information on all aspects of their disease—symptoms, testing, treatment, and research—and can exchange information and experiences with others throughout the world. Patients should look for a friendly and helpful group, carefully weigh the accuracy of any medical information provided, and consider their own concerns about privacy.

    Some tips for starting and sustaining a support group are listed below.

    Starting a Support Group

    Sustaining a Support Group

  • Starting a group is not difficult, but sustaining a group is—yet it can be done.
  • Maintain the focus of the group—it is too easy to become only a social group.
  • Share leadership roles and maintain fluidity—have facilitators serve on a rotating basis.
  • Enlist volunteers—one person cannot do it all.
  • Hold group meetings in a location that is accessible and comfortable.
  • Schedule meetings at suitable times—not during holidays, vacation months (summer), or periods of inclement weather.
  • Stay in touch through e-mails and telephone calls during the months when the group does not meet. Study other support group models and draw on their strategies for success—for example, family counseling, 12-step programs.
  • Remember that the support group is a collection of individuals with different needs.
  • Try to have face-to-face “buddy days” once a month—it takes only two people to have a meeting.
  • Buddy up newer members with older members.
  • Keep the group fresh and energized—avoid becoming bogged down by patient complaints about their disease.
  • Alternate the content of meetings—share stories at one meeting, listen to an expert’s presentation at another.
  • Reinvent the group as needed—assess its accomplishments each year relative to its goals and changing membership.
  • Remain sensitive to the cultural and ethnic diversity of the group’s members.
  • Address patients’ needs locally—especially if the support group is part of a national network.
  • Hold retreats and reunions for group members—as possible within the physical and financial limitations of the members.
  • Host mini-regional conferences and meetings of related support groups.
  • Hold an annual conference of researchers and patients—this can be a wonderfully dynamic experience.
  • Reach out to and visit local hospitals, research laboratories, and drug manufacturers—to help researchers and health care professionals understand the problems patients face.
  • Consider structuring a “turn-key” approach for expanding local groups within a national network. TOPS has a “turn-key” kit available for sustaining a national network of local groups. Contact Ms. Cady at 304-363-3510 or BCady290@aol.com.

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    Closing Remarks

    Dr. Alving thanked the PIO representatives and the NHLBI staff for their contributions and participation.

    The meeting was adjourned at 4:30 p.m.

    Modified 7/12/04
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