FDA Outlines Best Ways to Collect Remote Data for Clinical Trials
The agency’s draft guidelines cover a wide range of complex issues, including patients’ ability to handle remote monitoring devices and correctly record data, how to validate their fitness for use, and how to evaluate patients’ risks while using these digital tools.
By John Halamka, M.D., president, Mayo Clinic Platform, and Paul Cerrato, senior research analyst and communications specialist, Mayo Clinic Platform
The new FDA guidelines, entitled Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, were designed to help clinical trial sponsors, investigators, institutional review boards, and other stakeholders as they navigate a paradigm shift in the way clinical trials are conducted. A growing number of pharmaceutical and academic researchers now realize that collecting massive amounts of clinical data through remote patient monitoring can be a cost-effective way to arrive at new insights and new products. The agency’s guidelines are an important step into this “brave new world.”
To make sense of the FDA guidelines, it helps to first spell out a few definitions. A digital health technology (DHT) is “a system that uses computing platforms, connectivity, software, and/or sensors for healthcare and related uses.” That includes devices used for general wellness and as medical devices. The term remote data acquisition refers to the “collection of data from locations that are distant from the investigator or trial personnel.” That can include glucose meters, smartphone-based ECG monitoring applications, and a host of other tools.
The FDA divided its draft guidelines into several broad categories, including:
- The description of the DHT and the rationale for choosing it
- Why the DHT is being selected for a specific clinical trial
- An explanation of the technology’s verification, validation, and usability
- The risks associated with the technology
- An evaluation of the clinical endpoints to be derived from using the collected data
- An evaluation of the statistical analysis
- Record protection and retention
Before a sponsor or clinical investigator thinks about using a remote patient monitoring device or software program, there are several factors to weigh: Do the patients who are being enrolled in the trial have the education, language skills, and technical aptitude to manage the technology and use in a way that will generate accurate metrics? Do they have the electric power to keep the devices running over the course of the experiment? Do the devices have enough storage capacity and is their internet connection robust enough to keep the data flowing over time? Although some of these requirements may seem too obvious, they can be easily overlooked in the rush to get marketable results.
Similarly, stakeholders must determine that the DHT meets certain performance specifications. “Verification can include testing according to consensus performance standards, when applicable … and/or an analysis to identify potential failure modes of a DHT and their causes and effects (e.g., failure modes and effects analysis). For some DHTs and investigations, it may be appropriate to identify the conditions (e.g., temperature range) under which the DHT functions reliably.” To ensure that the device is properly validated, FDA guidelines recommend certain steps be taken, depending on the particular device and the clinical investigation. They might include comparing the measurements coming from the DHT with a more traditional technology. Researchers may also have to take into account any physical factors that might disrupt measurement. “… participant activities that may be misinterpreted as the clinical event or characteristic of interest (e.g., a bumpy car ride misinterpreted as a tremor).”
The guidelines have a lot to say about the clinical endpoints being evaluated with the help of the data collected from the DHT. That’s especially important if the endpoint is novel. To begin with, investigators need to clearly define the endpoints, e.g., activity level, average heart rate, or sleep quality. The agency’s comments on novel endpoints are worth noting: “Novel endpoints based on data captured by DHTs may provide opportunities for additional insight into participant function or performance that was previously not easily measurable (e.g., tremors). While it is possible to measure some aspects of function or performance during a participant’s visit to the clinic at a point in time, the use of DHTs potentially provides for their measurement over a greater time period and in different settings. However, this may also lead to challenges in establishing an optimal and clinically relevant endpoint.”
On the issue of DHT risks, the guidelines focus on clinical risks and privacy-based risks. Even something as simple as a wristband can cut off blood supply or cause skin irritation. The agency expects you to keep track of these problems. Privacy related risks can take several forms. The remote device can be breached, or the general-purpose computing platform can be compromised. With these concerns in mind, the guidelines say: “Sponsors should ensure security safeguards are in place to secure data at rest and in-transit to prevent access by intervening or malicious parties.”
The “brave new world” of remote patient monitoring has the potential to revolutionize clinical trials and generate faster, more cost-effective results. But like all revolutions, it comes at a price. The FDA guidelines will help keep the risks small and the rewards large.