Precision medicine research relies on genetic testing at scale, but has long suffered recruitment and retention headaches. The answer, says Patrick Short, CEO of Sano Genetics, is to start early and engage participants deeply.
I witnessed first-hand the power of national scale genomics research through my PhD work analyzing genome sequence data from more than 8,000 families across the U.K. affected by neurodevelopmental disorders in initiatives including the Deciphering Developmental Disorders study and the 100,000 Genomes project. These efforts have delivered diagnoses to thousands of patients with genetic diseases, and discovered genetic factors that will pave the way for precision medicines.
Now, large-scale precision medicine clinical trials and population genomics programs like Our Future Health are expecting to genome sequence millions of people in the coming years.
But clinical trials in precision medicine suffer from a catch-22: to enroll genetically defined patients into trials and demonstrate efficacy of new therapies, widespread genetic testing is needed, but for healthcare systems to pay for testing, there needs to be clinical benefit.
On top of this, precision medicine studies suffer from challenges common to all clinical trials like poor enrolment and retention rates. An analysis of all terminated trials within the Clinical Trials Database by GlobalData in 2018 found the single highest reason for trial termination – at 55 percent of total trials — was a low enrolment rate. Around half of clinical trials are delayed due to recruitment issues, and some struggle to find any to begin the trial at all, while 85 percent fail to continue as they cannot retain enough participants, according to Forte research.
Solving recruitment challenges
In precision medicine research, the main problems include lack of reach and lack of proactivity. Data suggests very few people have ever been asked to take part in research – even those living with diagnosed conditions.
A survey by Sano Genetics of 900 research participants – 89 percent of whom were living with an array of chronic and rare conditions, the rest their parents or guardians – found that, prior to signing up, 80 percent had never been asked to take part in research.
That’s not to say that everyone who is asked to share their genetic data will jump at the chance. There is a big issue of trust. Who is asking is just as important as what is being asked. In the same survey, 64 percent of respondents said they’d be “very likely” and 31 percent “somewhat likely” to volunteer for a study if a healthcare professional said they would be eligible.
But there is also some hesitancy among the medical profession to refer patients for genetic testing. One study revealed some clinicians were reluctant to order genetic testing for patients with Parkinson’s disease because they didn’t feel comfortable explaining the meaning of test results to patients (19.6 percent) and because they were worried 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 who do get access to testing will be fierce.
What happens to participants after receiving test results is a huge responsibility and one that shouldn’t be left to clinicians to deal with alone. Patient recruitment for trials must be supported by patient counseling. Genetic counselors and medical science liaisons are extraordinarily useful here, helping participants to make sense of test results and how they might impact their families.
Of course, there are many other avenues to recruitment than clinicians alone. For one, forging stronger relationships with patient organizations and advocacy groups, which are already trusted sources of up-to-date information by highly engaged audiences.
Benefits of early recruitment
Time is of the essence. And starting patient engagement, protocol co-development and screening early can also have an enormous impact on costs.
Researchers from Tufts University, Janssen and Duke modeled the financial impact of early patient engagement and found that the return on investment can exceed 500-fold. That is, a $100,000 investment early can be worth $50 million later by helping to avoid mistakes in study design that are easy to fix at the start, but incredibly time-consuming and expensive to fix once studies are underway and rolled out to tens or hundreds of research sites.
From a recruitment perspective, most studies fail to heed Muench’s Third Law: investigators greatly overestimate the pool of available participants for their study. As a result, many studies launch with the assumption that recruitment will not be a challenge, only to find out that far fewer patients meet the criteria than expected – frustrating for both patients and researchers.
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 can be flawed.
What’s in it for participants?
Of course, trials are not always convenient for participants. Where visits to clinics are involved, there are upfront expenses to cover, as well as time away from work or home. But we have the tools at our disposal to make participation far simpler.
For diagnosed patients who haven’t been tested, home genetic testing kits can be delivered to patients’ homes at no cost to them and it takes less than 10 minutes to do the non-invasive saliva swab, package it up and mail it off to be sequenced in a lab. Hybrid or fully decentralized trial designs can further reduce the burden for eligible participants.
But we also have to think seriously about why an individual would share their DNA data in the first place. From surveying our participant base, we know that many people suffering from pre-existing conditions are selflessly motivated to share their data to improve the outlook for other sufferers. Other willing participants are their friends and family who want to show their support and make a difference.
While some people will hand over their DNA for sequencing and forget about it, most want to know what impact their contribution is having on research. And this has long been a failing of the vast majority of research studies.
Improving the participant experience
I’ve personally taken part in research studies where I’ve 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 of these cases, participants often rightly ask: “What’s in it for me?” This results in high drop-out rates and low levels of repeat participation.
The participant experience has 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 conditions, too.
Secure user-facing platforms can also help participants take full control of their own sensitive data and how it’s used, and allow them to withdraw their data at any time.
For older users, tech can be supplemented with telephone helplines, catering to demographics who might want to have a conversation about how their data is used, give their consent verbally or be talked through how to use a testing kit.
Clinical trial 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 instead to start earlier – in many cases years before trials are planned to go live – with proactive efforts to engage patients and clinicians.
Patrick Short is CEO and co-founder of Sano Genetics which supports pharma and biotech organizations to accelerate research and clinical trials through its digital platform.