There's a catch-22 in precision medicine research that some readers will be very familiar with. Healthcare providers and insurers won't offer genetic testing for patients diagnosed with diseases unless there's an approved therapy they could benefit from. Yet, without large-scale testing and the genomic data it yields, researchers can't identify relevant biomarkers and develop targeted treatments.
When a new precision medicine designed to treat a genetically-defined population does make it to the trial stage, researchers suddenly need to find enough patients with the specific rare genetic variant to take part in studies -- and quickly. But most patients won't know whether they're eligible or not because they've never had an opportunity to be tested.
Large-scale genetic databases and biobanks include individuals with the particular genetic subset of a disease -- but, frustratingly, due to the way many of these programs were historically set up, it can be impossible to recontact people and invite them to take part in further research.
In order to advance precision medicine, we need to focus on improving outreach to and the experience of patients.
A Rapidly Advancing Field
Advancements are being made in personalized medicine almost weekly, and not just for rare diseases like the recent approval of tofersen (Qalsody) for SOD1 amyotrophic lateral sclerosis (ALS) patients. There are clinical trials underway for genetic subtypes of common diseases too, such as APOE4 in Alzheimer's, PNPLA3 in non-alcoholic fatty liver disease, and LRRK2 and GBA in Parkinson's.
We've come a long way in a short time. In 2005, only 5% of medicines approved by the FDA had a biomarker and could be considered a personalized medicine. By 2018, this had grown to more than 40%.
Over the coming years, I expect this percentage will only grow. It makes sense: the one-size-fits-all treatments routinely administered to patients may be only 30% to 60% effective; although this varies by treatment. Meanwhile, medicines that use genetic biomarkers may be more likely to succeed.
Yet, there are huge challenges ahead. In the U.S., only a fraction of the population has done any sort of healthcare system-affiliated genetic test. To me, this seems to be a missed opportunity due to the continued growth in direct-to-consumer home DNA testing, which two in 10 Americans already say they have done.
This is not just because of the costs or the lack of incentive of an approved drug. In surveys looking at why patients aren't put forward for testing, healthcare professionals report concerns about how to talk to patients about the results and implications of tests. Healthcare systems are often ill-equipped to deal with the fallout from genetic testing -- which can result in psychological distress, lifestyle changes, insurance policy changes, and/or difficult decisions about whether or not to pursue treatments or surgeries.
Yet for researchers, mass genetic testing opens up a treasure trove of knowledge and accelerates drug discovery.
The Need for Representative Datasets
For this to be the case, however, large scale databases also need to be fully representative of the population, and there is a long-standing and entrenched issue of "Eurocentricity" within existing datasets. As of 2019, nearly 80% of participants in genetic studies were of European descent -- despite the fact that, globally, just 16% of people are of European descent.
Reaching people from representative ethnic backgrounds and socio-economic status must be a priority. But in communities where suspicion is high (for example, 55% of Black Americans say they distrust the healthcare system, while a quarter of Native Americans have reported discrimination at the doctor's or health clinic), building bridges will take time and a concerted effort.
We need to make better attempts to engage with participants in a meaningful way. Currently, getting involved in research can be time-consuming and inconvenient, and may mean taking time off work to travel to a medical center far away.
Once a sample has been collected, it's not uncommon for patients to never hear from researchers ever again, never to learn about the impact of their contribution.
I know this personally from research studies I've contributed to. The experience doesn't leave you feeling appreciated, or especially inclined to do it again.
This is a huge problem, and one (of many) reasons why it currently takes 10 to 15 years and more than $1 billion to develop new treatments: recruitment issues delay more than half of clinical trials, while 85% fail because they can't retain enough participants.
Improving the Patient Experience
We know that many patients do want to get involved in research, not only to improve the outlook for themselves and their families, but also to help others living with the same conditions. At the same time, a survey from my company showed that only 20% of patients have ever been alerted to relevant research opportunities.
We need better patient pipelines so that people with genetic variants of interest are identified early, informed about new research opportunities, updated on their progress and, equally as important, alerted if or when treatments are made available.
A better "user experience" will keep people engaged with research and minimize the duplication of recruitment efforts. A great experience means word of mouth sign ups. There's huge reach in participants' existing networks.
When it comes to engaging diverse participants, we can make sure we run our research programs and create content and information in different languages, and engage early and sensitively with trusted figures in communities we need to reach.
When it comes to large scale genomics studies, we're learning lessons from previous research. For example, All Of Us in the U.S. and Our Future Health in the U.K. are overcoming the limitations of previous biobanks by making patient recontact a key feature of their design and operations. The value to future research projects going forward cannot be understated.
There's no doubt the cost of genetic testing will continue to fall, removing one of the key hurdles from the perspective of health providers. But it's imperative that, in order to make the most of the wealth of opportunities that increased testing will offer, we start working to improve patient recruitment, engagement, and re-contacting infrastructure and processes now.
Patrick Short, PhD, is the CEO and co-founder of Sano Genetics, which helps precision medicine clinical operations teams accelerate trials by combining at-home genetic testing, participant recruitment, and long-term patient engagement, for faster enrollment and simplified operations.