FDA has a message for sponsors that want to incorporate mHealth technology into their clinical trials: as long as the technology can be clinically meaningful, don’t let us get in your way.
FDA officials from CDER (Center for Drug Evaluation and Research) and CDRH (Center for Devices and Radiological Health) participated in a panel discussion on the use of mHealth technology in clinical trials at the DIA Annual Meeting, and the overwhelming message the officials wanted to share with the industry is that FDA is not the roadblock to using mHealth in clinical trials.
“There may be some regulatory confusion, and there may be some perceived regulatory barriers, which ultimately are regulatory barriers if they are perceived that way, but I think the existing regulations don’t necessarily prohibit these types of trials,” said Matthew Kirchoff, program management officer at the Office of Medical Policy, CDER, FDA said, speaking at the DIA Annual Meeting.
Ken Skodacek, policy analyst for the clinical trial program in the Office of Device Evaluation, CDRH, FDA, echoed his CDER colleague: “I want you to feel more comfortable about implementing mobile technology in clinical trials,” Skodacek said, because he believes the main obstacle to the use of mobile tech in clinical trials is industry apprehension.
Outlining FDA’s digital health policy principles, Skodacek noted that FDA uses a risk-based approach focused on a tech’s functionality and how it’s narrowly tailored for use.
“Perhaps most importantly, what is the clinical meaning of the measurement? Are you measuring something the patient would benefit from? What’s the size of the effect and the nature of the effect?” said Leonard Sacks, associate director of clinical methodology at the Office of Medical Policy in CDER.
John Marler, medical officer at CDER suggests, “while you are developing new methods, keep your sights on the final product of clinical research: a clinical trial report. The usefulness of the technology that we develop will depend on the credibility of that report and the expense of the trial it will take to produce it.”
Marler notes that when establishing a clinically meaningful effect, “accurate” doesn’t equal “objective,” and mHealth tech needs to be able to do both in clinical trials. Marler defines “accurate” as a representation of what happened in one instance with little measurement error and “objective” as the knowledge that the treatment assignment in a clinical trial does not influence the result of an outcome measurement.
In other words, FDA is asking mHealth measurements to be reliable, reproducible, sensitive and specific.
CDRH’s Skodacek told the DIA audience that FDA “wants to stay out of the way of rapidly evolving technologies that ultimately promote public health," and he pointed to several guidance documents that offer agency recommendations that help explain FDA’s current thinking on these topics. He was careful to remind the DIA audience, and the entire industry, that it’s important to look at multiple guidance documents, rather than one or two, to see the big picture of how FDA regulates digital health.
So how does a company proceed with using mHealth technology during a clinical trial? “The more important concern is not if or how FDA regulated the technology, but rather what plans you have to maximize the quality of the data being collected,” Skodacek said.
Beyond just the quality of the device itself, Skodacek told the DIA audience they must consider the quality and potential variability of the data being collected. Sponsors should be aware of whether the device is sensitive enough to measure clinically relevant changes and whether the data being gathered is reproducible. It’s also important to consider whether the use of the technology will introduce biases that could influence the trials’ results, for example human factors associated with the use of the technology.
All these questions raise uncertainties, and Skodacek suggests small feasibility studies can help evaluate and refine the use of the technology before using it in a larger trial.
Above all else, Skodacek recommends requesting formal feedback from FDA if you’re planning to conduct a trial that uses mobile technology. Think about the goal, the opportunities, and the obstacles you’re trying to overcome, and then provide a concise summary to tell your story to FDA about what you are trying to accomplish.
Skodacek ended on a cautionary note. “Although we encourage you to be creative, be careful. Don’t allow your interest in technology to become an all-consuming crusade.”
Skodacek points to the six-minute walk test. New technology could help improve the way we do the six-minute walk test, but not if the technology is only being used to measure the distance to the nearest millimeter when a patient walks a few hundred meters.
However FDA and industry resolve the mHealth’s role in clinical trials, it’s clear change is coming, and FDA knows it.
“My prediction is we will not recognize trials 10 years from now,” Sacks said.
We checked in with Kara Dennis, managing director of mHealth at Medidata, who attended the DIA panel discussion, and she summed it up best: “We were delighted by the perspective shared by the FDA representatives at DIA. They have consistently demonstrated openness to the inclusion of data produced by mHealth technology, including sensors, wearables and apps, and acknowledge the profound value it offers. We look forward to continuing our work with regulators and our partners to make sensor-captured data commonplace in clinical development."