Genetic Testing in Clinical Trials: A New Level of Patient Centricity

At a panel hosted by WCG at the DIA Annual Meeting in June,

Applied Clinical Trials

’ Editorial Director Lisa Henderson moderated a session entitled “Clinical Trials in the Era of Precision Medicine.” The panel included Ken Getz, associate professor at the Tufts Center for the Study of Drug Development at the Tufts University School of Medicine; Jill Johnston, president, WCG’s site activation solutions; Karmen Trzupek, director of ophthalmology and rare disease programs at InformedDNA; and Travis Quigley, VP for Clinical Development at bluebird bio. During the session, these experts discussed many aspects of genetics and clinical trials, but in this article, based on a transcript of the event, we focus on the very different needs that patients in clinical trials have in regard to gene testing.

As Getz set the stage for the attendees, he recalled the excitement over the mapping of the human genome, completed in April 2003. “We thought overnight we would have treatments that would target a specific patient with a specific genetic profile. And we talked about the incredible importance of genetic information to actually target our therapies, but it’s taken a long time for that to influence our pipeline,” said Getz. “We’re really there at that time now.”

He noted that half of all drugs across all therapeutic areas are collecting biomarker and genetic data. In fact, in oncology, that number is closer to 80%. In addition, almost half of all pharmaceutical companies are earmarking biomarker and genetic data as the most critical areas to increase investment.

Getz said, “With the changes to these very highly-targeted therapies for rare and orphaned diseases, it’s introducing a host of challenges at the operating level. And it speaks to changes in the way we conduct our studies, in data that we collect, and how we interact with the patient community.”

Both Trzupek and Johnston noted an increase in the use of genetic testing in clinical trials, including for diagnostic purposes, prognostic purposes, or predictive purposes, such as potential response to a treatment, inclusion in a clinical trial, or to stratify patients into more personalized trials.

Johnston believes that increased patient involvement in all aspects of clinical trials, such as prescreening tests or protocol design, puts other considerations in focus for genetic tests. “We need to think not only about just simply adding a genetic test to a protocol, but also thinking how is the patient being prepped for that type of genetic testing, what will the outcomes be? How are they progressing through the study? What other information do they need? And, so, really thinking about it from a high level, but also a very detailed level-what’s going to happen with those particular patients?”

In developing bluebird’s genetic-based therapies, Quigley said, “These challenges can also be daunting when you start doing these tests in trials. Some of the providers don’t even want to know the results because they don’t have the resources to successfully manage their patients’ expectations and family expectations around what the results mean, and how it’s translatable to the reality of developing any diseases later on. From the sponsor side is the challenge of what information we actually share, or what do we truly think actionable for patients? And to have the investigators or providers communicate to patients, how do we build the resources to help them do that? But that’s a daunting task for a company who’s not up to date on those things.”

Said Trzupek, “A large part of [WCG and InformedDNA’s] partnership and collaboration is exactly around supporting patients and their families. When discussing genetic testing, there is complexity of the actual result. That’s something the genetic counselors at InformedDNA do every day and we spend a lot of time with the patients and providers doing that.”

What else should be considered for a patient-centric approach to gene testing?

Family members. In the area of genetic disease, there is a greater possibility that there is potential risk for the family of patients. Trzupek said, “The genetic counselors spend a lot of time with the patient, talking through all the downstream effects, both for their own healthcare and for potential risk to their family. Identifying that is a huge benefit to the patient, which increases engagement, but it’s also often a benefit on the other side because you end up identifying other individuals in the family who may also potentially qualify for a clinical trial or a therapy, and they’re often very grateful for that.”

Negative screen results. What do you do if a patient screens “no” for that gene or variant? Johnston said, “Those patients are suffering some sort of condition, and they’re looking for the next answer as well. You may not be providing deep genetic counseling for them, but they want education and information. And you don’t want to lose their engagement in the future.”

Trzupek provided an example of what education would look like in this “screen no” scenario. “A classic example would be BRCA1 and BRCA2 in breast cancer,” she said. “One of the most important components of genetic counseling for patients going through that testing is ensuring that women who screen no, who have a negative genetic test for that, don’t erroneously think that they’re no longer at risk for breast cancer. Across all diseases we see this, so we need to make sure the education is there.”

Incidental findings. In the course of genetic testing, indicators may show the patient has a propensity for another disorder. How should that be handled? Trzupek said that genetic counselors spend a lot of time thinking through the ethical challenges of that scenario. In clinical trials, she suggested that sponsors be made aware very early on of what they want from genetic testing. “We have to talk about this early as it is critical to the trial design,” said Trzupek. “How to be thoughtful about what test is being offered, how narrow or how broad is this test, and what are the potential implications? Do we have or need a plan to manage that?”

Quigley and Getz both shared that, at the end of the day, sponsors must be patient-centric in their approach in

genetic testing because of the ethical responsibility and disclosure for the patient community. Quigley closed with, “In starting to think about the right collaborations with providers or healthcare institutions, we have to understand how we’re going to handle all this data, and act on it moving forward, creating the right environment for patients to get the help they need to live healthy, stress-free, productive lives. It can also benefit the development of therapies for rare diseases. It takes a lot of people getting together, having conversations like this, and eventually taking that next step to create systems that can function to help everyone that’s involved.”

A modified design for disclosing genetic test results in Alzheimer’s research/see here