Precision medicine research is based on large-scale genetic testing, but has long suffered from recruitment and retention headaches. The answer, says Patrick Short, CEO of Sano Genetics, is to start early and engage participants deeply.
I witnessed firsthand the power of genomics research on a national scale through my PhD where I analyzed genome sequence data from more than 8,000 families in the UK affected by neurodevelopmental disorders in initiatives such as the Deciphering Developmental Disorders study and the 100,000 Genomes project. These efforts have delivered diagnoses in thousands of patients with genetic diseases and discovered genetic factors that pave the way for precision medicine.
Now, large-scale precision medicine clinical trials and population genomics programs like Our Future Health expect to sequence the genome of millions of people in the coming years.
But precision medicine clinical trials suffer from a catch-22: Enrolling genetically defined patients in trials and demonstrating the efficacy of new therapies requires widespread genetic testing, but to make health care systems pay for testing, there must be clinical benefit.
In addition, precision medicine trials face challenges common to all clinical trials, such as poor enrollment and retention rates. An analysis of all discontinued trials in the Clinical Trials Database by GlobalData in 2018 found that the highest reason for trial termination — at 55 percent of total trials — was low enrollment. According to Forte research, about half of clinical trials are delayed due to recruitment issues, with some struggling to find one to start the trial, while 85 percent fail because they can’t keep enough participants.
Solving recruitment challenges
In precision medicine research, the main problems are lack of reach and lack of proactiveness. Data suggests that very few people have ever been asked to participate in research — even those living with diagnosed conditions.
A study by Sano Genetics of 900 study participants — 89 percent of whom were living with a range of chronic and rare conditions, the rest their parents or guardians — found that 80 percent had never been asked to participate in the study before applying.
That’s not to say that anyone asked to share their genetic data will seize the opportunity. There is a big problem of trust. Who is asking is just as important as what is requested. In the same survey, 64 percent of respondents said they would be “very likely” and 31 percent “somewhat likely” to sign up for a survey if a health care professional said they would qualify.
But there is also some reluctance among the medical community to refer patients for genetic testing. One study found that some clinicians were reluctant to order genetic testing for patients with Parkinson’s disease because they were uncomfortable explaining the meaning of test results to patients (19.6 percent) and because they were concerned about the implications of the patient’s genetic test results for their children and other family members (46.4 percent).
With dozens of precision medicine trials in specific forms of Parkinson’s and Alzheimer’s disease on the horizon, competition for the small number of patients to gain access to testing will be fierce.
What happens to participants after they receive test results is a huge responsibility that should not be left solely to clinicians. The recruitment of patients for trials should be supported by patient education. Genetic counselors and medical science liaisons are extremely helpful here, as they help participants understand the test results and how they can affect their families.
Of course, there are many avenues to recruiting beyond just clinicians. First, forging stronger relationships with patient organizations and advocacy groups, which are already reliable sources of up-to-date information from highly engaged audiences.
Benefits of Early Recruitment
Time is of the essence. And starting early with patient engagement, collaborative protocol development, and screening can also have a huge impact on costs.
Researchers from Tufts University, Janssen and Duke have modeled the financial impact of early patient involvement and found that the return on investment can exceed 500-fold. That is, a $100,000 early investment can be worth $50 million later by helping to avoid study design flaws that are easy to fix in the beginning, but incredibly time consuming and expensive to fix once studies get underway. and rolled out to tens or hundreds of research sites.
From a recruitment perspective, most studies do not take into account Muench’s third law: Researchers vastly overestimate the pool of available participants for their study. As a result, many studies start with the assumption that recruitment will not be a challenge, only to find that far fewer patients meet the criteria than expected – frustrating for patients and researchers alike.
The solution here again is to start early and identify patients through screening protocols and real-world evidence studies rather than relying on prevalence literature or other forms of desk research that may be flawed.
What will it bring to participants?
Trials are of course not always convenient for participants. When it comes to visits to clinics, there are upfront costs that need to be covered, as well as time away from work or home. But we have the tools at our disposal to make participation much easier.
For diagnosed patients who have not been tested, home genetic testing kits can be delivered to the patient’s home for free, and it takes less than 10 minutes to take the non-invasive saliva swab, package it and send it to be sequenced in a lab. Hybrid or fully decentralized pilot designs can further reduce the burden on eligible participants.
But we also need to seriously think about why a person would share their DNA data at all. From researching our participant base, we know that many people who suffer from pre-existing conditions are selflessly motivated to share their data to improve the outlook for other patients. Other willing participants include their friends and family who want to show their support and make a difference.
While some people give up their DNA for sequencing and forget it, most want to know the impact their contribution has on research. And this has long been a shortcoming of the vast majority of research studies.
Improving the attendee experience
I personally participated in research studies where I submitted samples for genetic testing and never heard from the researchers again.
And in clinical trials, participants are often asked to travel extensively and undergo a battery of tests, often with little flexibility around timing and frequency.
In both cases, participants often rightly ask, “What’s in it for me?” This results in a high dropout rate and a low repeat participation rate.
The participant experience needs to be improved. And this is where tech can play a leading role, making it easier for researchers to share updates with participants, as well as high-quality content about developments and breakthroughs in specific circumstances.
Secure user-facing platforms can also help participants gain full control over their own sensitive data and how it is used, and allow them to revoke their data at any time.
For older users, technology can be complemented by telephone helplines, targeted at demographic groups who may want to have a conversation about how their data is being used, give verbal consent, or receive explanations on how to use a test kit.
Clinical research teams know that recruitment and retention are major challenges, especially in precision medicine. The solution is not to throw more money at the problem, but rather to start – in many cases years before the trials start – with proactive efforts to involve patients and clinicians.
Patrick Short is CEO and co-founder of Sano Genetics, which supports pharmaceutical and biotech organizations to accelerate research and clinical trials through its digital platform.