Summary: Since the Internet’s earliest days, patients have used online resources to share experiences, learn about diseases and treatments, and become advocates. A newer phenomenon has seen a growing number of online communities evolve into centers of patient-driven research (PDR)—especially for orphan diseases. Thanks to Health 2.0 capabilities, various models of PDR are being developed, usually involving methods of data collection and aggregation that can eclipse RCTs as meaningful evidence. A radical shift from the classical research model, this may result in accelerated findings and dissemination at a fraction of the cost of classic medical research.

While research projects conducted in a medical environment require supervision by IRBs (institutional review boards), no such limitation currently exists in PDR. This results in both greater immediacy and potentially harmful forms of bias in these research models. Acceptance of PDR as valid clinical research requires validated methodologies and tools, democratization of data, ethical oversight, and immediacy. Without these critical drivers, such research will continue to be marginalized and its benefits available only to the activated minority.

Keywords: Participatory medicine, orphan diseases, patient-driven research, patient empowerment

Citation: Frydman GJ. Patient-driven research: rich opportunities and real risks. J Participat Med. 2009(Oct);1(1):e12.

Published: October 21, 2009.

Competing Interests: The author has no conflicts of interest to report with respect to this article.

Online Communities as Centers of Research

Since the Internet’s earliest days, patients have used online resources to share experiences, learn about diseases and treatments, and become advocates, all facilitated by the growth of disease-specific online communities. A number of these communities, used originally for information dissemination and support, have evolved into centers of patient-driven research (PDR)—especially for orphan diseases.

The Association of Online Cancer Resources (ACOR), an organization I co-founded with my wife 14 years ago, is just one of such information and support networks. Over 600,000 patients and caregivers have used one or more of its 163 public online communities. Starting years before the Institute of Medicine (IOM) published the seminal report Crossing the Quality Chasm,[1] they have contributed to a number of changes in models of care for patients suffering from rare and unusual diseases. These have been brought about by researching and sharing the latest scientific information and personal narratives of their conditions, by joining with others in public conversations, and, most remarkably, by organizing and developing new methodologies of data collection and aggregation—with the ultimate goal of guiding the research on their disease. Their efforts have also been instrumental in raising funds for scientific research and in policy making.

ACOR users, like so many other “e-patients,” have helped forge the participatory medicine model, where an important component of the patient contribution is to balance what evidence-based medicine or conventional medical wisdom recommends with what is possible, desirable, and most acceptable for the individual patient. As Kent Bottles, MD, president of The Institute for Clinical Systems Improvement, explains, “Many of them have understood that the art of care is to determine how all the various actors—researchers, medical professionals, drug and medical device companies, payers, afflicted persons in general, themselves specifically, and their caregivers—might best collaborate in order to optimize their care. In the world of participatory medicine, patients are no longer a target group and passive recipients of care, but crucial and active members of the care team, involved in the decision-making process at every step.” And, increasingly, they are showing that they can also generate specialized medical research, explain translational research to their peers,[2] and get actively involved in post-marketing surveillance.[3]

Participatory Medicine and PDR

For the general population, participatory medicine is a choice. And it is currently the choice of a mostly educated minority.[4] [5] [6] But for the population dealing with orphan diseases, active engagement in the care process, including PDR, can make the difference between life and death. For instance, from 1998 to 2000, hundreds of patients erroneously diagnosed with leiomyosarcoma joined the ACOR LMS group and were told by other group members to request their doctors to test them for the c-kit mutation. They were told that their doctors had almost certainly not heard about this new test and would object. Hundreds of them persisted, got tested, and those who were c-kit positive were diagnosed with gastrointestinal stromal tumor (GIST). That simple advice from a patient group transformed their life expectancy from less than 8 months to an unknown number of years. Many of them are still alive today.

To be clear, PDR, initiated by patient and caregiver groups, is not the same as public involvement in clinical research, nor is it equivalent to “community-based participatory research (CBPR),” which has political, societal, and intellectual roots in poor communities around the globe, and its own rich history of subject experts involving underserved communities in projects to improve health outcomes. In some ways, PDR can be construed as an evolution of CBPR, but it grew organically as a pragmatic solution to problems encountered by orphan-disease communities composed of highly educated individuals.[7] While CBPR is based on a “top-down” academic model, PDR is “bottom-up,” even when the projects involve academic teams. In PDR’s extreme form, the translational research enterprise is managed by patients or their loved ones and operates in frameworks different from what medical professionals and scientists are familiar with. It is a radical shift from the classic randomized controlled trials (RCTs) that currently inform most of the provider guidelines for diagnosing and treating conditions.

Orphan Diseases and PDR

Orphan disease communities share certain characteristics. They lack the number of patients needed for large-scale studies and, in a world of ever-growing new drug development costs, rarely attract research financing from the drug industry. There are only a limited number of clinical experts who study or have experience with their conditions. Thus, there are relatively few scientific breakthroughs and a sparse knowledge base in the literature. Not surprisingly, many contributions during the public comment period of the NIH Public Access Policy came from patients belonging to orphan disease online communities. For these stakeholders, open access to full-text articles can mean the difference between life and death. With few researchers and clinicians specializing in their diseases, many patient advocates become experts in disease-specific research. They mine published papers, make connections between their own diseases and information generated in related fields, closely follow any developments in the medical literature, and make important observations about and produce data sets on off-label drugs.

Further, patients suffering from orphan diseases often share a painful history of years of delayed diagnosis, problems interacting with the medical system, negative or nonproductive procedures, and a resulting overwhelming sense of loneliness, abandonment, and despair. Indeed, Jerome Groopman, MD, claims in his book How Doctors Think,[8] “The sickest patients are the least liked by doctors, and very sick people sense this disaffection.” There can be a profound sense of relief when patients discover an established online community of their peers and realize “they are not alone.” Thus, during the government hearings on open access in 2008, which ultimately resulted in a mandate that all articles resulting from NIH-funded research be fully accessible freely within 12 months of publication, advocates for patients with orphan diseases had a strong and unified voice, as exemplified by these two citizen testimonies:

I am dealing with my second cancer. At this time I believe it is important for me to be an informed patient, fully capable of participating in my treatment decisions. As such it is vital that I am current on published works concerning my disease. I also am on social security disability retirement as a result of the long term effects of radiation treatment for my first cancers. My income is $1,035 per month. I cannot afford to pay to read articles from medical journals. NIH funding for research is public monies therefore the report results should be available to the public at no charge.

I have a rare disorder. I use PubMed and other online resources to learn about my disorder. I am often frustrated by only being able to access the abstract. Accessing a single full article typically costs in excess of $30 (which is ridiculous). I’m glad to see the NIH making the publications that they sponsor available freely to the public.

The natural next step in the evolution of deeply engaged patients is awareness that their everyday experiences in living with their conditions can be a source of valuable information to understand and cope with the disease continuum. Long before Project HealthDesign—a national program of the Robert Wood Johnson Foundation created to stimulate innovation in personal health information technology—began to formally assess the value of “observations of daily life (ODLs),” patient groups were reaping the benefits of recorded and shared experiences until then unrecognized. In one dramatic example, in 2001 the Life Raft Group helped transform a nascent grassroots organization into a PDR powerhouse, performing groundbreaking research on the effects of Gleevec in GIST patients. For example, using a new scale for rating the severity of side effects from the patient’s point of view, rather than the clinical trial toxicity standards established by the National Cancer Institute, the group was able to demonstrate that certain Gleevec side effects had a much deeper impact on the quality of life than had been reported earlier.[9] As Dr. Daniel Vasella, CEO of Novartis, said in 2002, “The Life Raft Group has provided various people, patients, doctors, investigators with a unique kind of data bank that cannot be replicated anywhere else, not even in patient trials.”

New Models and Methodologies?

The communication, data-collecting, and aggregating possibilities offered by Internet-based communities, coupled with patients’ realization that the medical research enterprise has focused its efforts on studying common diseases, has helped to create significant numbers of citizen-scientists. There are examples of PDR going far beyond data collection, where new methodologies are developed in disparate silos, which could contribute to a new set of best practices for researching rare (and not-so-rare) conditions. Various groups have established tissue and specimen banks,[10] [11] created new cell lines for testing lead compounds,[12] established patient registries,[13] formed clinical trial networks,[14] and raised significant money for high-risk research that often cannot secure public funding.[15] [16]

Now, with the advent of Health 2.0 capabilities, various models of Internet-mediated research are being developed, almost always involving methods of data collection and aggregation that can eclipse RCTs as meaningful evidence. The MIT Media Lab, in association with a lymphangioleiomyomatosis (LAM) support group, recently created an open-source collective discovery platform called LAMsight. This provides users with tools to collect, explore, and discuss patient information, with the goal of influencing the direction and pace of clinical research,[17] Some ACOR communities are used to drive enrollment in clinical trials and collect data vital to researchers. PatientsLikeMe has managed to amass the largest patient database in the orphan disease ALS, opening up new opportunities for research and trials. CureTogether uses self-reporting to help people anonymously track and compare health data, to better understand their bodies and make more informed treatment decisions, and contribute data to research. There are a number of other emerging or existing models, sponsored by groups that include Health Commons[18] and LMSarcoma Direct Research Foundation (LMSdr), that approach research methodologies from different angles. What they all have in common, however, is the recognition that PDR and shared patient data can help identify drugs and effective treatments significantly faster and less expensively.

There are also movements that eventually move beyond the virtual realm, involving successful patient-led foundations and cooperatives, such as the parent- and grandparent-founded Organization for Autism Research, which funds research programs, holds conferences, and publishes guidelines. The Chordoma Foundation takes an active role in managing every aspect of the research process by formulating research priorities, recruiting researchers, initiating and funding cutting-edge projects, brokering collaborations, and breaking down barriers to progress. The Life Raft Group, besides providing regular up-to-date, high-level review of the latest developments in GIST treatment, has developed a large patient registry and tissue bank, and is now funding research with a novel approach that caps administrative overhead at 10%.

The developers of these models embrace a new paradigm of patient-owned data (see healthdatarights.org), as well as democratization of research and greater cooperation among funders, patients, clinicians, and researchers. It is clear to the stakeholders that this paradigm shift will result in accelerated findings at a fraction of the cost of classic medical research and in significantly improved acceptance and dissemination of these findings. Regardless of the business model they have chosen, these innovators are helping to develop technology-mediated frameworks in which patient research becomes data-driven on a larger and therefore more meaningful scale. This trend underlies one of the most promising aspects of participatory medicine. As Life Raft Group’s Norman Scherzer states[19]:

One of the great benefits of PDR is its speed. We can get lifesaving information out to the people who need it right away, much faster than professional researchers, who must go through many time-consuming steps. First you design your study. Then you arrange for funding. Then you must get everything approved—sometimes by several different committees. Then you recruit your subjects. So at last you can begin. Then you must wait for your results to trickle in. But that’s only the beginning.

Next you must analyze and interpret your data. You must write everything up. After all that, you’ll need to find a peer-reviewed journal to publish your work. And if you’re lucky enough to find one, you must go through even more long rounds of reviews, revisions, corrections, and proofing—as well as possible editorial or production delays. This can take several years. So professional research has a built-in lethal lag time—a period of delay between the time some people know about an important medical breakthrough and the time everybody knows.
As a result of this delay, many patients who could have been saved by the latest treatments die unnecessarily. In my experience, this lethal lag time is rarely less than two to three years. And it can sometimes be four to five years, or even more. Physicians are subject to this delay just like everyone else.

PDR Is Innovative. Is It Advancing Science?

Yet as often happens with Internet-mediated resources, the speed of innovation far outpaces the ability to generate validated evidence about the effectiveness of those innovations. Not everyone is convinced of the scientific validity of these new research models. The world of PDR is occurring in a parallel world, not bound by most of the regulations that have become the framework of RCTs. In the latter, every step must be IRB (institutional review board) approved and HIPAA compliant, while the former are usually not subject to these limitations. Although some work has been conducted[20] to help build a valid scientific framework for PDR, much remains to be done. This stems from the fact that orphan disease groups share a greater sense of urgency than doctors, researchers, and government officials. They are not afraid to be aggressive in their approach because their lives depend on it. They are not afraid to break rules concerning access, privacy, and other highly regulated areas. As often happens with pioneers, they also do not spend much time thinking of the real risks and quality challenges that are introduced by the new research methods. But these risks, many still unknown, clearly exist and must be properly studied and understood.[21] For example, the Life Raft Group receives significant funding from the pharmaceutical industry, creating potential conflicts of interest that may not be properly assessed by the organization. Charles Blanke, MD, Director of Gastrointestinal Oncology, Oregon Health and Science University, Oregon Cancer Institute said:

This is powerful and compelling work! I remain incredibly impressed by the data-coordinating abilities of the Life Raft personnel. I see the major purpose of this sort of data as hypothesis-generating. Unfortunately, it cannot be free of bias and thus cannot stand by itself, but it certainly can point investigators and the Company in the right direction and let us know what we need to be looking at more closely. Thus, its importance cannot be overstated.

There are other potential biases we can foresee, including population biases, as most of the PDR projects come from online communities with demographics very different from the general population. In some cases, the pressure to participate in PDR projects can put the results in jeopardy, since health professionals may consider the recruitment methods akin to coercion (personal communications). While research projects conducted in a medical environment requires that potential participants must sign an informed consent, no such limitation currently exists in PDR.

There is an urgency to this call-to-arms: acceptance of PDR as valid clinical research requires validated methodologies and tools, democratization of data, ethical oversight, and immediacy.  Without these critical drivers, such research will continue to be marginalized and its benefits available only to the activated minority. The Journal of Participatory Medicine stands ready to help address the urgency.


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Open Questions

  1. How can active involvement of patients in conducting and reporting clinical research help make important and life saving treatments and technologies more readily available to patients without the years of delay seen with today’s randomized clinical trial system?
  2. What are some ways that major research organizations such as the National Institutes of Health and the Robert Wood Johnson Foundation need to change to accommodate and facilitate more active involvement in medical research?
  3. How will we achieve broad participation of all patient groups in patient driven research, including uninsured patients and patients who aren’t connected to the Internet?

Copyright: © 2009 Gilles J. Frydman. Published here under license by The Journal of Participatory Medicine. Copyright for this article is retained by the author(s), with first publication rights granted to the Journal of Participatory Medicine. All journal content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. By virtue of their appearance in this open-access journal, articles are free to use, with proper attribution, in educational and other non-commercial settings.