Rare Patient Advocacy Groups Reach Tipping Point of Influence


Applied Clinical Trials

Using venture philanthropy to get promising drug candidates past “the valley of death”-and supported by advanced scientific technology-rare disease patient organizations have moved beyond being just hopeful influencers, to now becoming powerful forces for change.

According to Malcolm Gladwell, the “tipping point” is “the moment of critical mass, the threshold, the boiling point” where “ideas…spread like viruses do.”Organizations originally created by patients and their caregivers have now reached a tipping point in their influence on government and industry. Always meeting new challenges, rare disease patient advocacy organizations use a myriad of tools to make their needs known and to ensure that promising research survives the well-known “valley of death.” 

Starting small

National advocacy organizations trace their roots back to public health education and social movements of the early 1900s. In 1904, the Boston Medical and Surgical Journal (predecessor to The New England Journal of Medicine) congratulated the five physicians who founded the National Association for the Study and Prevention of Tuberculosis (NASPT), stating: 

“There can be no question that concentrated and systematic study of the problem which tuberculosis presents will in the very near future lead to results of the utmost importance…the concentration of effort which this association stands for cannot fail to carry the matter much further than is possible by individual effort or by the efforts of small bodies of persons, however enthusiastic…”2

This statement-that a national group effort “cannot fail” to make a difference-is an understatement recognizing that the NASPT is now known as the American Lung Association.

In her history of the Orphan Drug Act, Mary Dunkle wrote that rare disease national organizations started as “‘kitchen-table’ groups formed by parents of patients or even patients themselves.”The story of the Cystic Fibrosis Foundation (CFF) is an example of an organization that grew out of “kitchen-table activism.” CFF started in 1955 with a small but motivated group of parents of children diagnosed with cystic fibrosis, all living in Pennsylvania.4

Making connections

Individuals with a rare disease are geographically dispersed to the extent that patients and their families might not ever know or meet another person dealing with their condition. One such condition is tuberous sclerosis. As Kari Rosbeck, president and CEO of the Tuberous Sclerosis Alliance (TS Alliance), explained:

“You know, in the old days, when our organization was founded (1974), we had a hard time connecting. The way our organization was founded is that one mom was able to get a story placed in Exceptional Parent Magazine. That’s how the four founding moms came together. Before them, people were living with this disease and had no real way to connect. Back in those days, it was phone calls and letters. Sometimes I think we take that for granted in our modern society, which is so fast paced that you can connect with somebody with a click of a button or a quick text on instant messaging.”5

A common problem

When these parents, caregivers, and patients did connect, they were galvanized by a common problem: A lack of available treatments. In the early 1970s, rare disease patient advocacy organizations began to find each other and collaborate, according to Dunkle. They sought to move the political machine into acknowledging the lack of treatments.Finally, in 1979, Marion Finkle, former head of the FDA's Office of New Drug Evaluation, submitted a report entitled “Significant Drugs of Limited Commercial Value,” urging the development of drugs for people with rare diseases.6



Activists like Marjorie Guthrie of the Committee to Combat Huntington’s Disease (later renamed the Huntington Disease Foundation7) and Abbey Meyers, a mother of a child with Tourette syndrome, urged members of their respective patient advocacy organizations to contact Rep. Henry Waxman of California and Sen. Nancy Kassebaum of Kansas, to encourage the development of treatments. Their work, alongside the advocacy of television celebrity Jack Klugman, helped move legislation to passage. Signed into law, the Orphan Drug Act in 1983 incentivized the pharmaceutical industry to develop treatments for patients with rare diseases by granting seven years of marketing exclusivity, 50% tax credit in cost of developing products for rare diseases, and federal funding through the FDA.3

Different types of advocacy

Although the Orphan Drug Act was a huge win, many point to the creation of ACT UP (AIDS Coalition to Unleash Power) as the beginning of the tipping point in patient advocacy. ACT UP members engaged in intense activism, necessitated by the urgency of the AIDS crisis. They called their approach the “inside-outside strategy.”Members blocked entrances (with their bodies like corpses) in civil disobedience to force legislators, FDA, and the pharmaceutical industry to meet with patients. Once inside, they offered intelligent, implementable, and viable proposals for research and action. 

Organizations like the Cystic Fibrosis Foundation (CFF) took a different approach to patient self-advocacy. One of its first strategies was to establish a care center network in 1961, followed with a patient registry in 1966 to collect information about the disease. Active fund-raising for basic academic medical research led to the discovery of the cystic fibrosis (CF) gene in 1989. However, progress stalled in creating treatments for the condition. To move the needle forward, the CFF tried a new approach, now called venture philanthropy, in which a foundation partners with pharmaceutical companies to develop medications for CF.4

Bridging “the valley of death”

The need for venture philanthropy is directly related to what Ronald Bartek calls “the valley of death.” Some larger pharmaceutical companies are moving away from the discovery, preclinical, and early clinical phases, considering them risky and expensive. By obtaining therapies after they have passed these early stages, drugmakers can move directly into conducting later-phase trials and advance the drug into the marketplace; unfortunately, this can also leave promising areas of research to perish.Rare diseases draw less attention because of the comparatively smaller populations that bear the impact. And, unlike CFF, not all rare disease patient advocacy organizations can subsidize a therapy from discovery through all the clinical trial phases to market.

The TS Alliance has moved to meet this challenge. To increase the visibility and awareness of tuberous sclerosis (TSC), the TS Alliance moved its headquarters from Southern California to Washington, DC. “We needed to work with Congress and get the attention of NIH to start doing research on this disease,” Rosbeck said.5

As Rosbeck explained, funding and supporting research were also part of the “founding mom’s” vision, demonstrated by the establishment of a medical board in 1975. “We have worked closely with physician advisors from the beginning,” she said. “The founding moms were able to connect with Dr. Manuel Gomez, who practiced at Mayo Clinic. He was the first person to actually publish a study of 160 cases of tuberous sclerosis.”5  

Moving the TS Alliance headquarters made a difference, but crossing the “valley” required consulting with other non-profits. Rosbeck said, “When I became CEO in 2007, I spent a lot of time talking to other non-profits who we wanted to emulate…We couldn’t do what they did, but we began to develop a plan, a way that worked for our organization, our community, our researchers.”5

One of the strengths of patient advocacy organizations is their relationship with their community of patients and caregivers. In a Harvard Business School case study of the Multiple Myeloma Research Foundation, Kathy Giusti, the founder, stated, “The hardest part of getting a drug approved is finding patients and getting them into a trial. We help create a groundswell of knowledgeable patients [who are] aware of what is going on in terms of research and clinical trials so that potentially good drugs do not languish for lack of patients in trials.”10

This is the case for the TS Alliance as well. In 2010, the group partnered with Inspire.com, an Arlington, VA-based healthcare social network that builds and manages online support groups for patients and caregivers. This partnership provided a dedicated support community online for patients with TSC and their caregivers.

“Our organization is and always has been grassroots up, meaning that everything we do comes from the community,” Rosbeck said. Through the continuous connection with patients and caregivers in online forums, the TS Alliance finds new topics that “bubble up” and is discovering previously unknown conditions that are associated with TSC. TSC-associated-neuropsychiatric-disorders (TAND) is one such example. Through continuous monitoring of their members’ communications, TAND has been identified, named, and a checklist of behaviors that indicate TAND has been developed. “We’re taking it the next step and developing consensus guidelines for treatment based on the checklist,” Rosbeck said.5

The TS Alliance started providing research grants in 1984. Rosbeck said, “In the early 2000s, our board of directors really started talking about how to better understand this disease, how do we better characterize the progression of the disease through a lifetime. We started a natural history database in 2006, both for ourselves, but also to interest the pharmaceutical industry in taking a look at tuberous sclerosis complex.” 



Medical records are collected in the natural history database. Since 2014, TSC has also established a biosample repository, collecting samples of blood, cheek swabs for DNA, or tissue samples for those who have undergone surgery.The importance of a natural history database cannot be overstated. Mapping out how the condition manifests over time from the patient’s perspective provides much needed endpoints in developing clinical trials and information critical to helping patients to diagnose.11

Like CFF, the TS Alliance established TSC comprehensive clinics in the U.S.; now there are over 60 across the country. In fact, one of the criteria at US News and World Report for judging the best Children’s Hospitals in the U.S. is having a TSC clinic.5

In 2011, the TS Alliance hired a new chief scientific officer, Steve Roberds, who came from the industry. With his expertise, the TS Alliance started to address some unmet needs of the pharmaceutical industry. One innovation was to start a preclinical consortium at the TS Alliance to encourage small or large biotechs to try their novel compounds in TSC.

“We have licensed mouse models in epilepsy and tumor growth that best characterize, and most mimic, the human condition and can provide a positive signal that’s rigorous and reproducible,” Rosbeck said. By supplying these mice, the TS Alliance reduced a barrier to research on TSC. “They can use the mice; we have the licenses so that they don’t have to go through that lengthy negotiation process,” she added. “They can join the consortium for a nominal fee and can run their screens confidentially so that they don’t have to set up their own research labs.”5

The TS Alliance also worked with the U.S. government to secure funding. “A grandfather of twins with TSC started our government relations program, so in 2001 we received our first appropriation from the Department of Defense-Directed Medical Research Program for fiscal year 2002,” Rosbeck said. Since then, there has been $83 million in appropriations for the TSC research program at the Department of Defense.5

The TS Alliance has taken a page from other patient organizations in gaining visibility with help from celebrities. “In 2004, a father of a child with TSC met [actress] Julianne Moore on the streets of New York,” Rosbeck said. Moore was moved by her interaction with the father and child. “Having a celebrity spokesperson who really advocated for us was a huge turning point,” Rosbeck added. “Julianne testified in Congress, went on every talk show you can imagine, did stories in People magazine.”5

Common strategies occurring

Patient advocacy groups are rapidly adopting strategies to attract interest in their rare conditions by providing researchers with access to a patient base or to tissue samples. 

First, by providing access to patients through their registries, patient advocacy organizations save trial sponsors time and money in recruitment. 

Second, access to tissues through advocacy groups’ tissue banks and biosample repositories can give researchers access to a variety of samples for identifying biomarkers for these diseases. 

Third, access to natural histories detailing patient-reported outcomes can be used to develop, refine, and validate clinical endpoints. Access to mice models, like those TS Alliance have obtained, also provide an easy way for pharma and biotechs to create and test compounds. Rosbeck stated, “TSC is a leading genetic cause of epilepsy. We are saying, ‘Come try it in our models, see if it works in TSC. We’re a rare epilepsy syndrome that has a lot of seizures and so if it can work in TSC as a model system, perhaps it can also be effective in the epilepsy community in general.’”5


In 1904, five physicians studying tuberculosis was considered “a concentration of effort.” Fifty years later, parents of children with cystic fibrosis in Pennsylvania got together to remove barriers to treatment. Now, rare disease patient advocacy organizations headquartered in Washington, DC, engage in venture philanthropy to get new drugs past “the valley of death.” They support advanced scientific technology, like the TS Alliance does with its genetic mice models. Millions of patients and caregivers congregate on social media every day. There are many worldwide organizations. It’s difficult to identify when patient and disease advocacy passed the tipping point from being just a hopeful influence into a powerful force for change-but there certainly is no going back. 


Kathleen D. Hoffman, PhD, MSPH, is a Senior Health Researcher and Writer with Inspire.

Acknowledgements: The author would like to thank Kari Luther Rosbeck, President and CEO of TS Alliance, for her time and insights. She would also like to thank Sara Ray, formerly of Inspire, for reviewing the manuscript.



  1. Gladwell, M. The tipping point: How little things can make a big difference. Boston: Little Brown and company; c.2000.
  2. The National Association for the Study and Prevention of Tuberculosis. The Boston Medical and Surgical Journal. [Internet]. 1904. [cited 2019 November 1] Available from: doi/full/10.1056/NEJM190412011512212.
  3.  Dunkle, M. 30-year retrospective: National Organization for Rare Disorders, the Orphan Drug Act, and the role of rare disease patient advocacy groups Orphan Drugs: Research and Reviews.  [Internet]. 2013 4 19-27. doi.org/10.2147/ODRR.S41070
  4. Our History, The Cystic Fibrosis Foundation. The Cystic Fibrosis Foundation; . [Internet]. c2019 [cited 2019 October 4]. Available from: https://www.cff.org/About-Us/About-the-Cystic-Fibrosis-Foundation/Our-History/
  5. Hoffman, K. (Inspire, Newton MA). Phone Conversation with Kari Rosbeck (CEO and President of the Tuberous Sclerosis Alliance, Washington, DC). January 15, 2019.
  6. Amand, G. How drugs for rare diseases became lifeline for companies. Wall Street Journal.  [Internet].  2005 [cited 2019 November 1] Available from: https://www.wsj.com/articles/SB113202332063297223
  7. HDSA History. (2019).Huntington’s Disease Society of America.. [Internet]. c2019 [cited 2019 October 8]. Available from: https://hdsa.org/about-hdsa/hdsa-history/
  8.  Aizeman, N. How to demand a medical breakthrough. Shots: Health News from NPR.. [Internet].  2019.[cited 2019 November 1] Available from: https://www.npr.org/sections/health-shots/2019/02/09/689924838/how-to-demand-a-medical-breakthrough-lessons-from-the-aids-fight
  9. Bartek, R. Publishers foundation-industry relationships - A new business model joint-venture philanthropy in therapy development. Current Topics in Medicinal Chemistry.. [Internet]. 14. 2014. Available from: https://pdfs.semanticscholar.org/02c5/4ccf511f945fa6adb90103333b68b5a9d860.pdf
  10. Hammermesh, R. Margolis, J. & Preble, M. Kathy Giusti and the Multiple Myeloma Research Foundation. Harvard Business School. . [Internet]. 2014. [cited 2019 November 1] Available from: https://www.themmrf.org/wp-content/uploads/HBS-CASE-STUDY.pdf
  11. Hoffman, K. Clinical trials and PROs: What patients with rare diseases say.  Patient Pulse Blog [blog on the Internet]. 2019 October [cited 2019 November 1] Avaliable from: https://corp.inspire.com/blog/clinical-trials-pros-social-media-rare-diseases/
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