Illustration by Shonagh Rae

Transforming Research Participation

In “From Bedside to Bench and Back” (Issues, Summer 2023), Tania Simoncelli highlights patients moving from being subjects of biomedical research to leading that research. Patients and their families no longer simply participate in research led by others and advocate for resources. Together they design and implement research agendas, taking the practice of science into their own hands. As Simoncelli details, initiatives such as the Chan Zuckerberg Initiative’s Rare as One Project—and the patient-led partnerships it funds—are challenging longstanding power dynamics in biomedical research.

Opportunities to center the public’s questions, priorities, and values throughout the research lifecycle are not limited to research on health outcomes. And certainly, the promise of participatory approaches is not new. Yet demand for these activities is pressing.

Today’s global challenges are urgent, local, and interconnected. They require all-hands-on-deck solutions in such diverse areas as climate resilience and ecosystem protection, pandemic prevention, and the ethical deployment of artificial intelligence. Benefits of engaging the public in these collective undertakings and of centering societal considerations in research are being recognized by those who hold power in US innovation systems, including by Congress in the CHIPS and Science Act.

Opportunities to center the public’s questions, priorities, and values throughout the research lifecycle are not limited to research on health outcomes.

On August 29, 2023, the President’s Council of Advisors on Science and Technology (PCAST) issued a letter on “Recommendations for Advancing Public Engagement with the Sciences.” PCAST finds, “We must, as a country, create an ecosystem in which scientists collaborate with the public, from the identification of initial questions, to the review and analysis of new findings, to their dissemination and translation into policies.”

To some observers outside the research enterprise, this charge is long overdue. To those already operating at the boundaries of science and communities, it is a welcome door-opener. And to entrenched interests concerned about movement away from a social contract supporting curiosity-driven fundamental research toward solutions-oriented research that focuses scientific processes on solutions and public good, PCAST may be shaking bedrock.

Increased federal demand can move scientific organizations toward participatory practices. For greatest impact, more on-the-ground capacity is needed, including training of practitioners who can connect communities with research tools and collaborators. Similarly essential is continued equity work within research institutions grappling with their history of exclusionary practices.

Boundary organizations that bridge the scientific enterprise with communities of shared interest or place are connecting the public with researchers and putting data, tools, and open science hardware into the hands of more people. The Association of Science and Technology Centers, which I led from 2018 through 2020, issued a community-science framework and suite of resources to build capacity among science-engagement practitioners. The American Geophysical Union’s Thriving Earth Exchange supports community science by helping communities find resources to address their pressing concerns. Public Lab is pursuing environmental justice through community science and open technology. The Expert and Citizen Assessment of Science and Technology (ECAST) Network developed a participatory technology assessment method to support democratic science policy decisionmaking.

I applaud these patient-led partnerships and community-science collaborations, and I look forward to the solutions they produce.

Former Senior Advisor for Management at the Office of Management and Budget

President Emerita of the Association of Science and Technology Centers

Former Chief of Staff of the Office of Science and Technology Policy

Tania Simoncelli paints a powerful picture of the increasingly central role of patients and patient communities in driving medical research. The many success stories she describes of the Chan Zuckerberg Initiative’s Rare as One project provide an assertive counternarrative to the rarely explicated but deeply held presumption that only health professionals with decades of training in science and medicine can and should drive the agenda in health research. These successes confirm that those who continue to treat patient engagement in research as a box-checking exercise do themselves and the patients they claim to serve a grave disservice.

However, these narratives do more than just celebrate accomplishments. They also highlight the limitations of our current systems of funding and prioritizing health research, which require herculean efforts from patients and families already facing their own personal medical challenges. Patient communities have clearly demonstrated that they can achieve the impossible, but they do so because our current systems for funding research provide limited alternatives. How would federal funding for health research need to change such that patients and families would not have to also become scientists, clinicians, drug developers, and fundraisers for their disease to receive attention from the scientific community?

Medical research—and rare disease research in particular—urgently needs substantial investment in shared infrastructure and tools to increase efficiency, reduce costs, and facilitate engagement of diverse patients and families with variable time and resources to contribute. These investments will not only increase efficiency; they will also increase equity insomuch as they reduce the likelihood that progress in a given disease will depend on the financial resources and social capital of a particular patient community. This concern is not just hypothetical; a 2020 study of research funding in the United States for sickle cell disease, which predominantly affects Black patients, compared with cystic fibrosis, which predominantly affects white patients, found an average of $7,690 in annual foundation spending per patient affected with cystic fibrosis compared with only $102 in sickle cell disease, with predicable differences in the numbers of studies conducted and therapies developed. The investments made by the Chan Zuckerberg Initiative have been critical in leveling the playing field, but developing an efficient, equitable, and sustainable approach to rare disease research in the United States will require a commitment on the part of federal policymakers and funders as well.

Medical research—and rare disease research in particular—urgently needs substantial investment in shared infrastructure and tools to increase efficiency, reduce costs, and facilitate engagement of diverse patients and families with variable time and resources to contribute.

To achieve this seismic shift, I see few stakeholders better situated to advise policymakers and funders than the patient communities themselves. While federal funders may support patient engagement in individual research efforts, there is also the need to move this engagement upstream, allowing patients a voice in setting research funding priorities. Of course, implementing increased patient engagement in federal research funding allocation will require a careful examination of whose voices ultimately represent the many, inherently diverse patient communities. Attention to questions of representation and generalizability within and across patient communities is an ongoing challenge in all patient engagement activities, and the responsibility for addressing this challenge lies with all of us—funders, researchers, industry partners, regulators, and patient communities alike. However, it would be a mistake to treat this challenge as impossible: patient communities will undoubtedly prove otherwise.

Senior Research Scholar

Center for Biomedical Ethics

Stanford University School of Medicine

Biomedical research has blind spots that can be reduced, as Tania Simoncelli writes, by “centering the largest stakeholders in medicine—the patients.” By focusing on rare diseases, the Chan Zuckerberg Initiative is partnering with the most daring rebels of the patient-led movement. These pioneers are breaking new paths forward in clinical research, health policy, and data rights management.

But it’s not only people living with rare diseases whose needs are not being met by the current approach to health care delivery and innovation. Equally exciting is the broader coalition of people who are trying to improve their lives by optimizing diet or sleep routines based on self-tracking or building their own mobility or disease-management tools. They, too, are driving research forward, often outside the view of mainstream leaders because the investigations are focused on personal health journeys.

For example, 8 in 10 adults in the United States track some aspect of their health, according to a survey by Rock Health and Stanford University’s Center for Digital Health. These personal scientists are solving their own health mysteries, managing chronic conditions, or finding ways to achieve their goals using clinical-grade digital tools that are now available. How might we create a biomedical research intake valve for those insights and findings?

Patients know their bodies better than anyone and, with training and support, are able to accurately report any changes to their care teams, who can then respond and nip issues in the bud. In a study conducted at Memorial Sloan Kettering Cancer Center, patients being treated with routine chemotherapy who tracked their own symptoms during treatment both lived longer and felt better. Why are we not helping everyone learn how to track their symptoms?

Hardware innovation is another front in the patient-led revolution.

People living with disability ingeniously adapt home health equipment to meet their needs. By improving their own mobility, making a home safer, and creatively solving everyday problems, they and their care partners save themselves and the health care system money. We should invest in ways to lift up and publicize the best ideas related to home care, just as we celebrate advances in laboratory research.

We should invest in ways to lift up and publicize the best ideas related to home care, just as we celebrate advances in laboratory research.

Insulin-requiring diabetes requires constant vigilance and, for some people, that work is aided by continuous glucose monitors and insulin pumps. But medical device companies lock down the data generated by people’s own bodies, ignoring the possibility that patients and caregivers could contribute to innovation to improve their own lives. Happily, the diabetes rebel alliance, whose motto is #WeAreNotWaiting, found a way to not only get access to the data, but also build a do-it-yourself open-source artificial pancreas system. This, by the way, is just one example of how the diabetes community has risen up to demand—or invent—better tools.

Finally, since any conversation about biomedical innovation is now not complete without a reference to artificial intelligence, I will point to evidence that patients, survivors, and caregivers are essential partners in reducing bias on that front as well. For example, when creating an algorithm to measure the severity of osteoarthritis in knee X-rays, a team of academic and tech industry researchers fed it both clinical and patient-reported data. The result was a more accurate estimate of pain, particularly among underserved populations, whose testimony had been ignored or dismissed by human clinicians.

The patient-led revolutionaries are at the gate. Let’s let them in.

Tania Simoncelli provides a thoughtful reminder of the reality faced by many families with someone who has a rare disease. The term “rare disease” is often misunderstood. Such diseases affect an estimated 1 in 10 Americans, which means each of us likely knows someone with one of the 7,000 rare diseases that have a diagnosis. As the former executive director of FasterCures, a center of the Milken Institute, and an executive in a rare disease biotech, I have met many of these families. They see scientific advances reported every day in the news. And yet they may be part of a patient community where there are no options. As Simoncelli points out, fewer than 5% of rare diseases have a treatment approved by the US Food and Drug Administration.

The author’s personal journey is a reminder that champions exist who are dedicated to finding models that can change the system. The Chan Zuckerberg Initiative that Simoncelli works for, which has donated $75 million through its Rare as One program, believes that its funded organizations can establish enough scientific evidence and research infrastructure—and leverage the power of their voices—to attract additional investment from government and the life sciences community. Successful organizations such as the Cystic Fibrosis Foundation have leveraged their research leadership to tap into the enormous capital, talent, and sense of urgency of the private sector to transform the lives of families through the development of treatments, and they have advocated for policies that support patient access. Rare as Oneorganizations are a beacon of light for families forging new paths on behalf of their communities.

The role of philanthropy is powerful, but it does not equate to the roles government and the private sector can play.

As Simoncelli also highlights, the role of philanthropy is powerful, but it does not equate to the roles government and the private sector can play. Since 1983, the Orphan Drug Act has been a major driver spurring the development of therapeutic advances in rare disease, and one study estimates that the FDA approved 599 orphan medications between 1983 and 2020. In August 2022, Congress passed the Inflation Reduction Act authorizing the Medicare program to begin negotiating the prices of drugs that have been on the market for several years. Congress believed that tackling drug prices was a key to ensuring patient affordability. However, critics have pointed to the law’s potential impact on innovation, citing specifically how it could disincentivize research into rare disease. The implementation of the law is ongoing, so it is too early to understand the consequences. But the patient community does not need to wait to advance new innovative models to address any disincentives that may surface.

Every Cure is one of these models that may help address the consequences that new Medicare drug negotiation may have on continuing investments in specific types of research programs. Its mission is to unlock the full potential of existing medicines to treat every disease and every patient possible. Every Cure is building an artificial intelligence-enabled, comprehensive, open-source database of drug-repurposing opportunities. The goal is to create an efficient infrastructure that enables research for rare diseases as well as more common conditions. By working in partnership with the patient community, clinical trials organizations, data scientists, and funders, Every Cure hopes to be a catalyst in advancing new treatment options for patients who currently lack options. Innovation can’t wait—because patients won’t.

Vice Chair of the Board

Every Cure

Tania Simoncelli illuminates a powerful transformation in medical research: enter patients and families to center stage. No longer passive recipients and participants, they are passionate drivers of innovation, teamwork, focus, and results. Science systematically and rigorously approaches truth through cycles of hypothesis and experimentation. Yet science is a human endeavor, and scientists differ in their knowledge, tribal affinities in cultural and scientific backgrounds, bias, creativity, open-mindedness, ambition, and many other critical factors, but often lack “skin in the cure game.”

Medicine prides itself as a science, but it is a social science, as humans are observed and observers. Less “soft” a science than sociology or psychology, medicine is far closer physics or chemistry in rigor and reproducibility. Patients were traditionally viewed as biased while physicians as objective. Double-blind studies revolutionized medicine by explicitly recognizing the bias of physician scientists. Biases run deep as humans are its reservoirs, vectors, and victims. Paradoxically, patients and families with skin in the game are exceptional collaborators who are immune to academic biases. They have revolutionized medical science.

Patients and families with skin in the game are exceptional collaborators who are immune to academic biases. They have revolutionized medical science.

Academics may myopically measure success by papers published in high-impact journals, prestigious grants, promotions, and honors. Idealistic and iconoclastic views of youth give way with success to perpetuating a new status quo that reinforces their theories and tribe; blinded by bias.

True scientists, masters of doubt about their own beliefs, and people with serious medical disorders and their families seek improved outcomes and cures. Teamwork magnifies medical science’s awesome power.

Dichotomies endlessly divide the road of discovery. What is the best path? Fund basic science, untethered from therapy, answering fundamental questions in biology? Or fund translational science, laser focused on new therapies? How often are biomarkers critical, distractions, or misinformation? What leads to more seminal advances—top-down, planned A-bomb building Manhattan projects, or serendipity, propelling Fleming’s discovery of penicillin? The answer depends on your smarts, team-building skills, and luck. Who can best decide how medical research funds should be allocated? Are those with seniority in politics, science, and medicine best? Should those affected have a say? Why can’t science shine its potent lens on the science of discovery instead of defaulting to “what is established” and “works based” but is not evidence-based?

A new paradigm has arrived. Families with skin in the game have a seat at the decision table. Their motivation is pure, and although no one knows the best path before embarking to discover, choices should be guided by the desire to improve health outcomes, not protect the status quo.

Professor of Neurology and Neuroscience

New York University Grossman School of Medicine

Students seeking a meaningful career in science policy that effects real-world change could do worse than look to the career of Tania Simoncelli. Her account in Issues of how the Chan Zuckerberg Initiative (CZI) is helping build the infrastructure that can speed the development and effectiveness of treatments for rare diseases is just her most recent contribution. It follows her instrumental role in bringing the lawsuit against the drug company Myriad Genetics that ultimately ended in a unanimous US Supreme Court decision invalidating patent claims on genes, as well as her productive stints at several institutions near the centers of power in biomedicine and government.

Rare diseases are rare only in isolation. In aggregate they are not so uncommon. But because they are individually rare, they face a difficult collective action problem. There are few advocates relative to cancer, heart disease, or Alzheimer’s disease, although each of those conditions also languished in neglect at points in their history before research institutions incorporated their conquest into their missions. But rare diseases can fall between the categorical institutes of the National Institutes of Health, or find research on them distributed among multiple institutes, no one of which has sufficient heft to be a champion.

The Chan Zuckerberg team that Simoncelli leads has taken a patient-driven approach. Mary Lasker and Florence Mahoney, who championed cancer and heart disease research by lobbying Congress, giving rise to the modern NIH, might well be proud of this legacy. Various other scientific and policy leaders at the time opposed Lasker and Mahoney’s approach, especially during the run-up to the National Cancer Act of 1971, favoring instead NIH’s scientist-driven research, responding to scientific opportunity. But patient-driven research is a closer proxy to social need. Whether health needs or scientific opportunity should guide research priorities has been the hardy perennial question facing biomedical research policy as it grew ten thousandfold in scale since the end of World War II.

Whether health needs or scientific opportunity should guide research priorities has been the hardy perennial question facing biomedical research policy as it grew ten thousandfold in scale since the end of World War II.

CZI and its Rare As One project are not starting from scratch. They are building on research and advocacy movements that have arisen for chordoma, amyotrophic lateral sclerosis, Castleman disease, and many other conditions. And they are drawing on the strategies of AIDS/HIV activists and breast cancer research advocates who directly influenced national research priorities by systematic attention to science, communication, and disciplined priority-setting from outside government.

Where the Howard Hughes Medical Institute and many other research funders have built on the broad base of NIH research by selecting particularly promising investigators or seizing on emerging scientific opportunities, which is indeed an effective cherry-picking strategy, the CZI is instead building capacity for many organizations to get up to speed on science, think through the challenges and resource needs required to address their particular condition, and develop a research strategy to address it. The scientific elite and grass-roots fertilization strategies are complements, but the resources devoted to the patient-driven side of the scale are far less well established, financed, and institutionalized. That makes the effort all the more intriguing.

The Chan Zuckerberg Initiative is at once helping address the collective action problem of small constituencies, many of which cannot easily harness all the knowledge and tools they need, and also building a network of expertise and experts who mutually reinforce one another. It is a potentially powerful new approach, and a promising frontier of philanthropy.

Professor, School for the Future of Innovation in Society and the Consortium for Science, Policy & Outcomes

Arizona State University

Cite this Article

“Transforming Research Participation.” Issues in Science and Technology 40, no. 1 (Fall 2023).

Vol. XL, No. 1, Fall 2023