Why early participant involvement is now a top priority in genetic disease research –

In 2016, scientists behind a study called the Resilience Project analyzed the genetic data of more than 589,000 people and found 13 adults who carried genetic variants that were supposed to lead to serious — even fatal — childhood illnesses but who appeared to be otherwise healthy.

The DNA of these so-called “genetic superheroes” may contain clues about how to treat severe disease. By studying their natural resilience and using it to design new treatments, it could help many people.

However, the Resilience Project scientists used genomic data originally collected for other studies, and due to limitations in the informed consent policies of the original studies and lack of infrastructure to re-contact participants, none of the 13 individuals were contacted with follow-up questions or requests.

Whether these people really have a natural resistance to severe disease, and why that might be the case, remains a mystery.

At the time, Stephen Friend, one of the project’s founders, said: “There’s an important lesson here for genomics scientists around the world: The value of a project becomes exponentially greater when informed consent policies allow other scientists access to the original study participants. If we can get in touch with these three people… Ten, we may be closer to finding natural means of protection against diseases.

Fast forward to today, and although many large-scale genome studies still lack the infrastructure and consent policies to enable reconnection, this is beginning to change. High-profile programs such as NIHR BioResource and Our Future Health in the UK, all of us in the US, make reconnection and engagement an integral part of their design and operations.

Pharmaceutical and biotech companies are also adapting their approaches, launching patient-search and engagement programs that can begin years before clinical trials begin and allow them to conduct the “reconnect by genotype” studies that the Resilience Project would have liked to do.

Giving the participants something in return

The idea of ​​”genetic superheroes” and precision medicine is appealing to researchers, but the concept can be abstract and off-putting to participants. To make precision medicine a reality, reaching everyone who can help or benefit, we need to design research studies that closely resemble consumer experiences—and provide a clear value for participation that goes beyond altruism.

In our experience conducting more than 20 precision medicine studies, there are a few design principles that every research program—from biobanks to clinical trials—should take into account.

First, start co-development with the participants early in the process. This will help you answer basic questions about what your participants want, what their problems are, and how your research goals align (or don’t!) align with their priorities.

Second, build a concrete plan for communicating and “returning value” to participants in the short, medium and long term, and include this in your recruitment communications. Return of value can be monetary – including direct payments or donations to community organizations on behalf of participants – but relying on this is rarely effective. Non-monetary returns can include access to data, with insightful and personalized reports or summaries, access to sponsorships or specialized resources, or access to research summaries.

Third, design an experiment that minimizes the burden on the participants and maximizes the benefits for them while also achieving the scientific goals. In short, remove as many barriers to entry as possible.

What we learned is that participants come with clear expectations about the research experience, which are often not met. They expect the process to be straightforward and appropriate, and they want regular communication and feedback on the results. They also want opportunities to contribute details about their own experiences living with chronic and rare diseases, and the option to connect with experts, as well as others like them. After all, today’s participants are accustomed to a high level of online user experience, from food delivery to entertainment to shopping. Why should research be any different?

Sailing the right not to know

One of the controversial areas in genomics is the “patient’s right not to know”. Not everyone wants to contribute to a study and learn that they have an increased risk of developing a particular disease, so technology and processes must be designed so that participants are not shocked or surprised if they do not want to.

Often, researchers, ethics boards, and other stakeholders take the binary position that either all participants want to know, or information should not be returned to participants at all. In fact, even participants with a genetic risk for devastating diseases had legitimate reasons for wanting to control how they received information, such as giving them time to review insurance policies, talk to family members, or indeed not know at all, because of the psychological effect. By designing research with participants involved from the start, and with autonomy as a fundamental principle, we can escape the often-dominant binary and paternalistic perspectives.

And if participants choose to be aware of their risk of genetic disease, then communication should be carefully considered. Researchers in population genomics, biobanking, and clinical research programs meet this challenge, generating genomic data on millions of participants worldwide carrying risk factors for both common diseases and rare diseases. Large-scale genetic studies such as Our Future Health, All of Us, NIHR BioResource, Genomics England, FinnGen and DECODE have mass genetically tested millions of people, and have the consent and infrastructure to contact participants about their genetic results.

At the same time, the portion of clinical trials involving genetic markers is increasing. In the next decade, “genotype reconnection” to identify people at risk or with genetic diseases who are eligible for a new treatment or clinical trial will be a major force in shaping healthcare and research.

In the coming years, we will need to build a blueprint for the ethical framework, and the technological framework for running this process at the scale of millions of participants. In the US, Genomes2People – a research group led by Robert Green at Harvard Medical School – has published a number of studies on the impact of reconnection by genotype and genome sequencing in a healthcare screening setting.

Since then, an independent report by the PHG, commissioned by Genomics England, has provided us with a framework for genotype-return-of-value digital reconnection in the context of UK law. A pilot study by FinnGen, a consortium of Finnish biobanks with over 500,000 registered volunteers, found that re-contacting participants many years after signing up to engage in a digital platform had an uptake rate as low as 28%, and is therefore now encouraging participation from the ground up as a better way. to move on.

It’s a delicate balancing act: to dramatically accelerate the development of new medicines and to improve the experience of participating in groundbreaking research more than ever before. We have an amazing opportunity to rebuild health care to be more personalized and preventative, but the framework has to be right from the start. Collaboratively building technology and developing new methodologies for participant-centered design is the answer. Not only relying on participant boards and co-development, but also by subjecting features and functionality to rigorous external scrutiny by independent bodies, early in the development phase.

About the author

Patrick ShortDr. Patrick Short is CEO and Co-Founder of Sano Genetics, an emerging company that provides access to dynamic health and genetic data for precision medicine research that is transforming the experience of participating in research for participants.

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