The history of health advocacy in the United States dates back to at least 1893, when New York City nurses led by Lillian Wald1 advocated for and offered care to immigrant communities. These efforts would eventually become the Visiting Nurse Service of New York.2 Four decades later, the National Foundation for Infantile Paralysis (now known as the March of Dimes) spearheaded development of the polio vaccine through its advocacy and support of basic and clinical research.3,4 This successful model for health advocacy—covering a spectrum of activities that includes clinical research aimed at developing effective care practices, preventive interventions, and new therapeutics—has been adopted by many modern advocacy groups, commonly referred to as patient advocacy groups/voluntary health organizations (PAG/VHOs).5
Today, federal and state budget shortfalls, retrenchment of research and development activities among the medical products industry, and mounting difficulties in recruiting participants for clinical trials have made PAG/VHOs more relevant than ever. An analysis of their current roles and interactions with academic health centers (AHCs) is essential in planning future collaborations between these two types of organizations, both of which are critical to a healthy, sustainable clinical and translational research enterprise.
In this article, we characterize modern PAG/VHOs, describe their role in clinical and translational research, and examine attempts by the Clinical Research Forum (a nonprofit organization comprising AHCs, professional societies, and industry) to foster partnerships between AHCs and the growing, increasingly diverse field of PAG/VHOs.
What Are PAG/VHOs?
PAG/VHOs typically are not-for-profit organizations, often founded by families of patients to raise funds from the public. In the United States, this sector is large, enormously diverse, constantly evolving, and difficult to track.6 The advocacy organization Research!America estimates that philanthropic organizations and PAG/VHOs together contributed only 1% to 2% of the $140 billion spent on biomedical research in the United States in 2010, with the contribution of PAG/VHOs representing less than half of the total philanthropic contribution.7 But despite this comparatively modest investment, the impact of PAG/VHOs has been considerable. In particular, they offer breadth and diversity, dogged advocacy for enhanced support of clinical research, willingness to work on seemingly intractable problems, and, when required, readiness to take risks and make long-term investments.
Some PAG/VHOs are venerable and well established (e.g., American Cancer Society, March of Dimes); others, such as the Multiple Myeloma Research Foundation (MMRF),8 are relatively new. Some focus on one disease that may affect many people, such as diabetes or cancer; others target rare or “orphan” diseases, such as cystic fibrosis or progeria. Within this diversity, however, the following characteristics are hallmarks of effective PAG/VHOs:
- They have clear missions and governance structures and strong connections to the communities they serve;
- They provide well-researched, independent perspectives and are thus trusted sources of information;
- If they support research and training programs, those programs are targeted to the needs of their communities and are vetted by outstanding experts; and
- They have effective management teams that attract donors by keeping overhead costs low, staying focused on their goals, and directing most of their funds to supporting their programs.
Not all PAG/VHOs follow these practices, nor is it always easy to identify the PAG/VHOs that do not. When investigating a PAG/VHO, a good starting point is GuideStar,9 which is a clearinghouse for information on more than 1.8 million nonprofits. The Center for Media and Democracy warns that some groups claiming to represent patient interests are funded, and in some cases staffed, by companies selling treatments for those conditions.10 A recent study examining disclosure practices of 161 PAG/VHOs receiving grants from Eli Lilly and Company indicated that only 25% of them acknowledged those grants on their Web sites.11 If the findings of this study are generalizable, the PAG/VHO sector needs to be much more diligent in disclosing funding sources. Truly independent PAG/VHOs also minimize donor influences by adopting strong, independent governance structures that incorporate “firewall” policies. Such independent organizations exhibiting the hallmarks of effective PAG/VHOs can serve as excellent partners for AHCs.
New Models for Patient-Centered Organizations
Patient-centered organizations are emerging that incorporate some characteristics of PAG/VHOs, but with twists. For example, PatientsLikeMe12 adopts an interesting new for-profit model. Like many PAG/VHOs, PatientsLikeMe began with a family affected by illness. Three engineers (two of whom were brothers with a third brother affected by amyotrophic lateral sclerosis [ALS]) were inspired to create a data-sharing social network for patients with ALS. The company expanded its scope to patients with any condition in 2011. As of May 2013, their Web site had 180,198 members who share information about their conditions and treatments and who can exchange firsthand information with other patients about coping with and managing their conditions. Unlike most PAG/VHOs, PatientsLikeMe is a company, which sells aggregated, deidentified data that are self-reported by its members to partners that include pharmaceutical companies and medical device makers.
Why Are PAG/VHOs Important Collaborators for AHCs?
Because both PAG/VHOs and AHCs share a key priority—improving the health of the communities they serve through education and research—the two types of organization are natural partners. Adopting lessons learned from the success of the HIV-AIDS patient community’s advocacy for clinical and translational research in the late 1980s and 1990s13 and empowered by new social networking tools, the “voice” of PAG/VHOs has become both louder and more effective. Today, that voice is being used with increasing adaptability to influence research agendas and speed product development.
Different incentives drive different research sponsors of clinical and translational research. For-profit companies typically require prompt financial return on investment. In contrast, government prioritizes the greatest public good in allocating resources but is also strongly influenced by politics and the desire to avoid controversies. PAG/VHOs, however, are relatively free of the constraints that apply to government and for-profit sectors and are thus freer to invest in novel, high-risk investigations and support research that is politically sensitive or that has little potential for industry investment; they also are more free to make long-term investments.
The potential for high-value collaborations among these sectors is particularly relevant in the arena of U.S. clinical research, which is increasingly encumbered by high costs, slow progress, funding shortfalls, regulatory burdens, fragmented infrastructure, and shortages of qualified investigators and research volunteers.14 Overcoming these barriers will require collaboration among research sponsors, research organizations (and the investigators they fund), and regulatory entities in order to create an efficient clinical research system that safely speeds the development and application of technologies that improve health. PAG/VHOs need access to the knowledge and health care systems of AHCs, and AHCs need the increasingly powerful voice of patients to advocate for the process and regulatory streamlining essential for a robust, cost-effective clinical research enterprise.
Productive Interactions Between PAG/VHOs and AHCs
No single formula exists for productive interactions between AHCS and PAG/VHOs. Effective collaborations require mutual respect, good communication, shared governance, agreement on research priorities, and “meaningful involvement” in building the clinical research environment. However, these necessary attributes are often insufficient to establish effective partnerships if the incentives motivating persons working at PAG/VHOs and AHCs are misaligned. For example, a milestone-driven entrepreneurial PAG/VHO focused on finding cures for a given disease quickly might mandate that funded investigators participate in data-sharing research networks. In contrast, emphasis on prominent authorship in high-impact publications for career advancement at AHCs creates a disincentive for data sharing because of concerns about preempting publication. Similarly, tension can arise because PAG/VHOs often focus on a single condition and the needs of their patient communities, whereas AHCs are concerned with support for the entire biomedical research enterprise. Issues such as the compassionate use of unproven therapeutics, where a PAG/VHO’s commitment to helping individual patients may conflict with ongoing clinical research to prove the effectiveness of new agents, can strain relationships between AHCs and PAG/VHOs. Conflicts may also arise over ownership or control of intellectual property (IP) rights or revenues from PAG/VHO-supported research. Furthermore, multiple PAG/VHOs working on a single disease area may compete for finite amounts of funding, leading to a zero-sum outlook that discourages collaborations.15,16 However, despite the potential pitfalls of misaligned incentives and priorities, there have been many fruitful collaborations between these sectors, and their numbers continue to grow. Some examples are described below.
Providing stable support for a broad spectrum of research and training activities
Many of the largest, most broadly constituted PAG/VHOs have a history of supporting activities that build a field of research and help develop AHC faculty careers. For example, the American Heart Association (AHA)17 currently funds more than 2,000 researchers and scientists. We speculate that the AHA’s research support has been so expansive that most leading cardiology researchers at U.S. AHCs today have probably received AHA research grants at some point in their careers. In a similar manner, Autism Speaks has supported AHC investigators conducting basic and clinical research in a variety of fields including behavioral sciences, imaging, neurobiology, and epidemiology.18
Creating and strengthening a research field
The Huntington’s Disease Society of America (HDSA) was founded by Marjorie Guthrie, wife of folk musician and Huntington’s sufferer Woody Guthrie.19 For more than 50 years, the HDSA has worked to provide family services, education, and advocacy. It has also labored to create and support a networked HD research community from AHCs and other institutions—the HDSA Coalition for the Cure. In 1993, Coalition investigator Jim Gusella identified the first genetic marker for HD and the HD gene was located,20 ending an intensive 10-year search.21 With research progressing rapidly, the HDSA formed a pipeline for drug discovery in 2004 that begins in the laboratory and progresses to applied/transitional research before culminating at the patient bedside to test promising compounds.
Recruiting patients for clinical trials
The PAG/VHO community has become increasingly active in finding volunteers for clinical trials, and some groups are developing innovative models for recruiting participants. For example, the Dr. Susan Love Research Foundation partnered with the Avon Foundation for Women to establish the Army of Women, which recruits women via the Internet for breast cancer research, most of which is conducted at AHCs.22 Similarly, the for-profit organization PatientsLikeMe12 also uses Internet technologies to link its members to updated lists of trials from ClinicalTrials.gov.
Establishing networks that foster data sharing and interactions with industry
The MMRF8 and the Multiple Myeloma Research Consortium (MMRC)23 are linked organizations working to develop treatments for patients affected by multiple myeloma by catalyzing and supporting collaborative research between industry and academia. Their milestone-driven model uses standardized approaches to facilitate data sharing and collaboration among its network, which includes groups working at 13 AHCs. This network, which also incorporates industry partners, has helped MMRC launch more than 30 clinical trials of novel compounds and combination therapies.24
Providing centralized resources to facilitate research on extremely rare diseases
The Lymphangioleiomyomatosis (LAM) Foundation25 represents patients with a disease characterized by cystic lung changes that affects approximately one woman in a million. Founded by the mother of a young woman suffering from LAM, the foundation succeeded in raising funds for research into the biology of the disease. This in turn made clinical trials feasible26 because patients with LAM were no longer impossibly hard to find after being banded together by the foundation—yet another example of how a rare-disease PAG/VHO can become an essential partner in recruiting patients and providing support for research. In fact, this effort led to research that was identified as 1 of the top 10 clinical research advances by the Clinical Research Forum in 2012.27
Developing biomarkers and diagnostics
The Alzheimer’s Association (AA)28 helped establish the Alzheimer’s Disease Neuroimaging Initiative, a partnership involving many AHCs that was created to identify diagnostic biomarkers for assessing the safety and efficacy of potential therapies.29 A recent seminal observation, that positron emission tomography imaging using Pittsburgh Compound-B (which binds amyloid-beta peptide aggregates) is a useful in vivo diagnostic for Alzheimer disease,30 reflects the success enjoyed by AA and its partners with regard to this previously intractable issue. Another organization, Prize4Life, offers a $1 million prize to stimulate research into ALS.31 The prize was awarded in 2010 to Dr. Seward Rutkove from Beth Israel Deaconess Medical Center and Harvard Medical School for the development of electrical impedance myography as a biomarker for ALS.32
Concerns About PAG/VHO Interactions With AHCs
To discern possible problems that PAG/VHOs might encounter when working with AHCs, QE Philanthropic Advisors carried out individual telephone and in-person interviews with about a dozen representatives of PAG/VHOs, umbrella organizations, and endowed foundations. In addition, more formal responses were solicited using a Web-based survey distributed to PAG/VHO organizations belonging to the Health Research Alliance (www.Healthra.org; an alliance of over 50 nonprofit, nongovernment funders of health research that interact to optimize investments in health research and training) and the Genetic Alliance (www.geneticalliance.org; a network of over 1,000 disease-specific health advocacy organizations committed to transforming health through genetics and promoting an environment of openness). A very limited but diverse sampling of 37 organizations with budgets ranging from $100 million to $0.5 million responded to the Web survey. Despite the small sample, the results, which are summarized in detail elsewhere,33 were consistent and supported the information gleaned in the telephone and in-person interviews. Bureaucratic processes, negotiating IP rights, and institutional review board (IRB) delays were identified as the most problematic areas when establishing collaborations with AHCs. A few of the responding PAG/VHO staff also identified the burden of high indirect costs at AHCs as a major problem and noted that donors are increasingly unwilling to pay such costs. Further, even when donors are willing to pay indirect costs, variation across AHCs and/or uncertainty regarding how these costs are computed was noted as problematic.
How Can AHCs Enhance Interactions With PAG/VHOs?
Currently, there are extraordinary scientific opportunities for productive clinical and translational research collaborations between AHCs and PAG/VHOs. Indeed, given present constraints on federal spending, declining industry research and development budgets, and difficulties recruiting study participants, it is increasingly important that AHCs work effectively with the PAG/VHO sector. Each collaboration will have its unique features and challenges. Nonetheless, the following guidelines or actions should help reduce strife and ensure success for new collaborations:
- Agreement on the respective needs of each party, as well as a description of clear shared goal(s) and what “success” would look like;
- Establishment of appropriate governance structures and processes, which delineate responsibilities, enable open communication and build trust, manage conflicts of interest, support scientific rigor, and facilitate program evaluation and continual program improvement;
- Clarification of, and agreement on, critical policy issues such as how data and biospecimens will be obtained, stored, and shared; how indirect and direct costs will be funded and allocated among partners; and how decisions regarding IP, ownership of specimens, and authorship will be made; and
- Agreement on a timeline and an exit strategy if either partner is dissatisfied.
Unfortunately, bureaucratic processes at some AHCs are likely to make it difficult to easily complete these actions. We believe the following activities would help reduce delays in launching collaborations and enhance the interactions between the two sectors.
Improve communications and linkages
AHCs should establish formal communication links with the PAG/VHO sector, as well as processes that provide timely feedback to patients and PAG/VHOs on the status of trials for which they have been of assistance and/or been a research volunteer, such as engaging trial participants with webinars when trial results are ready to be disseminated. Groups such as ResearchMatch (an initiative of the Clinical and Translational Science Award [CTSA] program34 sponsored by the National Institutes of Health) and the Army of Women22 also allow investigators and potential subjects to connect and could be helpful. AHCs should use a variety of outreach tools, including social networking, to seek input from patients and PAG/VHOs representing patient communities regarding their needs, decisions affecting special population groups, research required to address patient needs, and experiences of study participants.
PAG/VHOs should also be considered as potential partners when AHCs design and implement processes to engage, support, educate, and (as necessary) prepare consumers, patients, and caregivers for their respective roles. This may include offering a yearly mini-medical school or AHC orientation, or using the educational resources of the CTSA network. Several CTSA programs—such as NetWellness in Ohio,35,36 the CTSA-led Sentinel Network initiative,37 and a variety of information technology applications currently in development—could help AHCs define their communities by identifying organizations, groups, and individuals and facilitating useful information exchange and collaboration.
Address bureaucratic stumbling blocks
We also suggest that AHCs consider conducting systems engineering process exercises that address the bureaucratic delays noted by many PAG/VHOs. Such exercises would examine an AHC’s clinical research enterprise, identify bottlenecks, and make improvements to streamline contracting, IP practices, adoption of electronic health records, and data sharing. These assessments and improvements could greatly expedite PAG/VHO interactions with AHC legal/IP departments. AHC processes should also better facilitate collaborations between multidisciplinary teams from different institutions including using centralized IRBs for multisite trials. Many CTSA programs play essential roles in such activities, and best practices should be disseminated widely. In addition, AHCs should work with PAG/VHOs to simplify both informed consent processes and documentation.
Leverage existing educational efforts and programs
AHCs can work with PAG/VHOs to improve recruitment of patients into clinical trials by using their existing networks and community programs, partnering in the creation of recruitment materials, and engaging them in broad-based campaigns that target both health care providers and patients.
Enhance investigator recruitment and retention
Finally, AHCs should work with PAG/VHOs to explore ways to recruit investigators for their respective disease areas. AHCs should also partner with PAG/VHOs to nurture and train future generations of clinical researchers and provide incentives for them to work in many of the multidisciplinary networks supported by PAG/VHOs.
The role of patient-driven organizations continues to evolve. Activities range from funding research and advocating for increased federal support for research to setting research agendas, catalyzing innovation, providing a bridge between AHCs and industry, functioning as virtual biotech companies, and leveraging social networking to foster the health of their communities. Although productive collaborations between AHCs and PAG/VHOs exist, barriers still persist. Efforts are needed to better align the incentives motivating academic clinical and translational investigators with the goals of PAG/VHOs. The CTSA program provides an important locus for more deliberate engagement with PAG/VHOs; in addition, AHC leaders should expand their efforts beyond the CTSA program to reengineer institution-wide processes to facilitate collaborations and align career incentives.
The authors would like to thank Kate Ahlport, executive director of the Health Research Alliance, and Sharon Terry, president and CEO of the Genetic Alliance, for their help designing and distributing the survey to their member organizations. The authors also thank Jonathan McCall of the Duke Clinical Research Institute for his assistance in editing and formatting this paper.
2. Fee E, Bu L. The origins of public health nursing: The Henry Street visiting nurse service. Am J Public Health. 2010;100:1206–1207
3. Oshinsky DM Polio: An American Story. 2005 New York, NY Oxford University Press
6. U.S. Department of Health and Human Services. . Directory of health organizations. http://Dirline.nlm.nih.gov
. Accessed May 10, 2013
11. Rothman SM, Raveis VH, Friedman A, Rothman DJ. Health advocacy organizations and the pharmaceutical industry: An analysis of disclosure practices. Am J Public Health. 2011;101:602–609
13. Engel J The Epidemic: A Global History of AIDS. 2006 New York, NY Smithsonian Books/Harper Collins Publishers:103–125
14. Califf RM. Clinical research sites—the underappreciated component of the clinical research system. JAMA. 2009;302:2025–2027
15. Brower V. The squeaky wheel gets the grease. Research funding is not necessarily allocated to those who need it most. EMBO Rep. 2005;6:1014–1017
20. . A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. The Huntington’s Disease Collaborative Research Group. Cell. 1993;72:971–983
21. Gusella JF, MacDonald ME, Ambrose CM, Duyao MP. Molecular genetics of Huntington’s disease. Arch Neurol. 1993;50:1157–1163
24. Giusti K. The Multiple Myeloma Research Foundation’s evolving focus on drug R&D. Nat Biotechnol. 2012;30:600–603
26. Taveira-DaSilva AM, Moss J. Progress in the treatment of lymphangioleiomyomatosis: From bench to bedside. Rev Port Pneumol. 2012;18:142–144
27. McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, et al.National Institutes of Health Rare Lung Diseases Consortium; MILES Trial Group. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011;364:1595–1606
29. Mueller SG, Weiner MW, Thal LJ, et al. The Alzheimer’s disease neuroimaging initiative. Neuroimaging Clin N Am. 2005;15:869–877, xi
30. Swaminathan S, Shen L, Risacher SL, et al.Alzheimer’s Disease Neuroimaging Initiative. Amyloid pathway-based candidate gene analysis of [(11)C]PiB-PET in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Brain Imaging Behav. 2012;6:1–15
34. Harris PA, Scott KW, Lebo L, Hassan N, Lightner C, Pulley J. ResearchMatch: A national registry to recruit volunteers for clinical research. Acad Med. 2012;87:66–73
35. Morris TA, Guard JR, Marine SA, et al. Approaching equity in consumer health information delivery: NetWellness. J Am Med Inform Assoc. 1997;4:6–13
36. Marine S, Embi PJ, McCuistion M, Haag D, Guard JR. NetWellness 1995–2005: Ten years of experience and growth as a non-profit consumer health information and Ask-an-Expert service. AMIA Annu Symp Proc. 2005:1043
37. Platt R, Wilson M, Chan KA, Benner JS, Marchibroda J, McClellan M. The new Sentinel Network—improving the evidence of medical-product safety. N Engl J Med. 2009;361:645–647