For a long time, participation by people with severe illnesses or without specific treatment in medical research has been restricted to their presence in clinical trials or providing samples of biological material, such as blood and tissue, for analysis. This has changed in recent years. Lots of initiatives around the world are trying to promote more open and inclusive collaborations, in which the patients are recognized as having in depth knowledge of their own conditions and work with physicians and researchers in the search for effective therapies.
“The patients also have valid knowledge, acquired from their personal experiences with the illness, which enables them to identify questions to be asked and issues to be investigated and help to design effective solutions for their health issues,” highlights epidemiologist Isabela Bensenor, of the School of Medicine at the University of São Paulo (FM-USP), who coordinates collaborative research with people with atrial fibrillation, a type of arrhythmia in which the cardiac fibers contract randomly, preventing the blood from being pumped correctly by the heart.
The study investigates the needs and experiences of people with the disease attended in basic health centers in the Butantã neighborhood, in São Paulo, in order to refine their diagnosis and treatment, through the adaptation of known and new methods. “We promote meetings with the patients to discuss research questions based on their experiences and strategies for the detection of atrial fibrillation symptoms and reducing the risk of blood clots and vascular accidents,” says Bensenor. “Many stress the importance of teaching the population to recognize the disease by monitoring the pulse and that healthcare teams do the same in order to detect the problem early.”
The effort is related to a model known as citizen science, which seeks to involve individuals without scientific experience in the production of knowledge (see Pesquisa FAPESP issue nº 323). In the specific case of medical research, it is the result of a long maturation. One milestone, dates back to the 1980s when individuals with HIV/Aids in the USA engaged in research about their own illness, even experimenting drugs that had not yet been approved at their own expense and risk. As the disease spread out of control at the time and evolved quickly to death, the victims took a leading role in the search for some type of treatment and demanded that the urgency of their requests was incorporated into the strategies and the agenda formulated by the researchers.
Years before, activists with other types of health issues were already asserting their rights to participate in the regulation of clinical trials and of determining the level of risk that they were willing to take by participating in tests with experimental drugs. This led them to joining research ethics committees at hospitals and universities, and governmental advisory committees, aiding decision-making about the incorporation of medications, equipment, and protocols in health systems.
Universities and funding agencies have encouraged more effective participation of disease carriers in clinical studies, as is the case of the Clinical and Translational Research Center at Harvard University, in the USA, which has a support program with training, lines of funding for collaborative projects, and expert consulting to help bring scientists closer to groups of patients. In 2019, the National Institute for Health Research (NIHR), in the UK, launched a similar service for pharmaceutical, biotechnology, and medical technology companies. In turn, Cambridge Patient Led Research Hub, created in 2015, works to bring scientists and victims of rare diseases together.
Involvement in the production of clinical knowledge can go beyond the research itself. For some time, periodicals such as The BMJ have invited patients, their families, and caregivers to participate in the analysis of papers about the health issues that they face, in order to complement the scrutiny made by experts (see Pesquisa FAPESP issue nº 270). In 2016, the Patient-Centered Outcomes Research Institute, a US public organization that funds studies aimed at the needs of patients, launched a similar initiative, seeking to involve them in the analysis of the final reports of studies it supports—until now, at least 175 people with illnesses have contributed to the evaluation of more than 280 research reports. When commenting on a report about opioid prescription for pain treatment, one of them highlighted that it did not mention alternative therapies that could substitute the use of the substance, instead of just aiding pain control. The authors of the study redid the document, presenting a more balanced record, describing the pros and cons of long-term opioid treatment and possible alternatives.
Collaborations between patients and doctors could inspire new approaches or even improve the quality of the studies, says Bensenor, of FM-USP
The interest of institutions in this collaborative model is based on the understanding that the ill people, especially those with congenital or chronic diseases, can understand the reality of their conditions as well as or better than the doctors and researchers, and this experience can help generate faster and more effective results. “Such collaborations can also inspire new approaches or even improve the quality of the studies, allowing the scientists to improve their protocols and identify questions and problems to be resolved before the start of the research,” says physiotherapist Egmar Longo, of the Department of Physiotherapy at the Federal University of Paraíba (UFPB), who works with researchers from Utrecht University in the Netherlands on the creation of tools that encourage and enable partnerships between patients and scientists.
There are already cases of studies that started from investigations made by the patients themselves and were then incorporated by researchers. In 2002, in the USA, a patient-led movement called Clusterbusters used the internet to recruit individuals who suffer cluster headaches, a rare and serious neurological disease about which there is little research, characterized by excruciating headaches on one side of the head, accompanied by red, swollen, and watery eyes. The idea was that they would take part in self-experiments and develop protocols for the use of psilocybin, the active ingredient of hallucinogenic mushrooms, as a form of treatment.
The group’s activities attracted the attention of neurologist Emmanuelle Schindler, of Yale University, who began collaborating with the movement on a treatment protocol based on small doses of psilocybin—currently in clinical trials. The effort also paved the way for the US Food and Drug Administration (FDA) to approve, in 2019, the use of the monoclonal antibody Emgality in the prevention of crises triggered by the illness. Pharmacist Eli Lilly originally designed the drug for the treatment of migraines, but proposed a higher dose for pain caused by cluster headaches after interviewing members of Clusterbusters, some of whom took part in the clinical trial.
Another recent example occurred during the pandemic. On April 13, 2020, journalist Fiona Lowenstein published an article in the New York Times reporting her personal experience with prolonged symptoms of Covid-19. The text attracted thousands of people to the support group that she had created on the instant messaging program Slack to guide patients with the same issue, among them Brazilian Letícia Soares, who at the time was doing a postdoctoral fellowship about avian malaria at Western University, in Canada.
Soares had recently had Covid-19. She was not hospitalized, but was extremely debilitated, suffering from fatigue, and muscle and joint pains. These symptoms persisted after the acute phase of the illness and new ones appeared, such as memory loss and problems with concentration. “We noticed in our support group that lots of other people who had overcome the acute phase continued to have symptoms or developed other new ones that persisted,” she says. “Some patients from the group created by Lowenstein decided to register these cases, because it was clear that the harmful effects of the virus on the human body could be bigger and longer-lasting than it was thought.” The initiative gave rise to the Patient-Led Research Collaborative.
The group’s first study involved 3,700 individuals from 56 countries and identified symptoms initially neglected by the medical community, but which today are recognized as characteristics of post-Covid-19 syndrome, known as long Covid. “The report, published in the form of an article in July 2021, was one of the first to touch on this topic, at a time in which there was little discussion about this condition,” says Soares. “Various people found validation upon seeing their experience reflected in a study with other patients.” Some used the article to show doctors that their symptoms were frequent. Since then, the initiative has already published several other scientific articles in specialist magazines and has managed almost US$5 million in funding for new projects, all designed according to the priorities of its members.
Jônatas MoreiraThe initiative has transformed into a global network, in which scientists and patients with post-Covid-19 syndrome can connect to do new studies. One of them, carried out in Brazil by scientists from the Oswaldo Cruz Foundation (FIOCRUZ), in Rio de Janeiro, the Harvard University School of Public Health, in the USA, and the London School of Economics (LSE), in the UK, seeks to understand the health experiences and needs of people with long Covid. “Those who make up our team are involved from the beginning of the project, contributing to the definition of its objectives and data collection protocols,” Emma-Louise Aveling, a researcher from Harvard and one of the coordinators of the study, told Pesquisa FAPESP.
Cases like this show that communities of patients structured around data obtained from self-experimentation or from their experience with the illness can result in innovative research. In 2011, an observational study started by people with amyotrophic lateral sclerosis who used PatientsLikeMe, a platform on which users share data about their illnesses, symptoms, and possible treatment strategies, helped refute a work from 2008 that affirmed that lithium carbonate could slow the progression of the illness.
The advance of this category of research, however, has hit some ethical limits. Many critics argue that it does not follow the most rigorous standard of clinical investigation, aimed to guarantee the security of volunteers and reduce interference in the results: the double-blind, randomized, and placebo controlled clinical trials. As a consequence, besides not providing robust scientific proof, it could expose the participants to unexpected risks.
It is often the families of patients that dive into the scientific literature and gain a more advanced understanding of the illness. One of the best-known cases in Brazil is that of attorney Margarete Santos de Brito and her husband, designer Marcos Lins Langenbach. Still young, the couple’s daughter Sofia was diagnosed with Rett syndrome, a rare neurological disease that causes frequent convulsions. In 2013, after several frustrated treatment and surgery attempts, the couple discovered a case in the USA of a child with the same illness who was treated with cannabis extract.
They decided to try the same therapy and imported the product, illegally. It worked. The frequency of Sofia’s convulsions reduced by 60%. The family informed the neurologist that had been treating the girl about the new resource and also verified the improvement in her quality of life, besides not identifying any side effects. Margarete and Marcos began growing the plant at home and learned to extract the cannabis oil themselves. They joined together with other families to try and get the product legally. The effort gave rise to the Medical Cannabis Research and Patient Support Association (APEPI), which helps Brazilian patients with rare and neurological diseases to get access to cannabis oil.
APEPI today attends more than 5,000 people. It funds studies and collaborates with researchers from more than 10 institutions, including FIOCRUZ, the Research Institute of the Botanical Garden of Rio de Janeiro, and the University of Campinas (UNICAMP), in São Paulo, on work related to the use of medicinal cannabis. “One we did with UNICAMP indicated that cannabinoids could be effective in the treatment of neurological disorders. Others have presented good results involving the use of cannabinoids against nausea caused by chemotherapy, fibromyalgia, and sleep disturbances, as well as increasing appetite and reducing weight loss in HIV patients,” highlights pharmacist João Gabriel da Silva, responsible for the area of research at APEPI.
Despite the benefits, this collaborative model faces some difficulties in consolidating itself. It is not always easy and viable to include patients in research, especially because some issues require specific knowledge and training. “Many simply do not want to participate,” comments Egmar Longo, of UFPB.
At the same time, the participation of patients in clinical trials faces resistance on behalf of the medical and academic community. The argument is that they do not have scientific education or training in research to carry out complex studies. One of the factors that compromises the use of comments from patients that evaluate the content of papers, for example, is the quality of the revision itself. Few volunteers are capable of understanding and commenting on scientific and technical aspects of manuscripts or research proposals. For Aveling, from Harvard University, such objections reflect deeper issues, “associated with a skepticism about the value of patient experience and to the notion that medical knowledge is more important.”
But she recognizes that the dynamic may not be easy. “Gathering people with different experiences, perspectives, ways of thinking, and priorities in certain research contexts can create collaborative challenges,” she warns. “However,” she adds, “the idea is not to substitute medical or scientific knowledge, but to create a culture of collaboration that also accepts the views and observations of amateurs.” For this to work, according to Aveling, it is necessary for doctors and scientists to be open to dialogue and willing to share information and renegotiate the distribution of power in the decision-making in research.
Scientific articles
SUBBIAH, V. The next generation of evidence-based medicine. Nature Medicine. Vol. 29, pp. 49–58. Jan. 2023.
BENSENOR, I. M. et al. Patient and public involvement and engagement (PPIE): first steps in the process of the engagement in research projects in Brazil. Brazilian Journal of Medical and Biological Research. 2022.
MCCORKELL, Lisa et al. Patient-Led Research Collaborative: Embedding patients in the long Covid narrative. Pain Reports. Vol. 6, no. 1, pp. 1–5. 2021.
KEMPNER, J. & BAILEY, J. Collective self-experimentation in patient-led research: How online health communities foster Innovations. Social Science & Medicine. 2019.
LIP, Gregory Y. H. et al. The National Institute for Health Research (NIHR) global health research group on atrial fibrillation management. European Heart Journal. Vol. 40, no. 36, pp. 3005–7. 2019.
VAYENA, E. et al. Research led by participants: A new social contract for a new kind of research. Journal of Medical Ethics. Vol. 42, pp. 211–5. 2015.
WICKS, Paul et al. Accelerated clinical discovery using self-reported patient data collected online and a patient-matching algorithm. Nature Biotechnology. Vol. 29, no. 5, pp. 411–6. 2011.
