While many would like to see mHealth and wearable technologies incorporated in clinical trials, regulatory guidance has yet to be established for these innovations. However, some guidances do exist on the regulation and validation of mHealth use in consumer settings.
After recently chairing PanAgora’s Clinical Trials & IoT Forum, feedback from many who attended suggests that they had the opportunity to discuss, evaluate, and incorporate novel mHealth and wearable technologies in clinical trials. However, some of the biggest concerns in bringing such innovations into clinical trials include federal regulation on using such devices in clinical trial settings, and the needed levels of rigorous scientific and technology validations.
While regulatory agencies have not issued guidance documents on the use of mHealth and wearables in clinical trials, a few guidances exist on the regulation and validation of mHealth use in consumer health settings. In this article, we will go through some of these documents and demonstrate how to qualify mHealth and wearables for potential clinical trial use.
In August 2016, the International Medical Device Regulators Forum (IMDRF), a global consortium of regulatory agencies, released a proposed document on Software as a Medical Device (SaMD), and the FDA indicated that the final guidance on SaMD will represent the FDA’s thinking on the topic1.
What is an SaMD?
According to the guidance document, an SaMD is, “software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device.” For example, software on a smartphone that links to a Bluetooth-enabled blood glucose monitor intended for diabetes management would fall under the definition of an SaMD. Table 1 delineates SaMD category classes.
What is not an SaMD?
Any applications that are meant to retrieve information, organize data, optimize processes, or software that has already been used in closed-loop interventions, such as software that is already part of a physical medical device, is not considered an SaMD. The theme of the SaMD guidance seems to be geared towards software that informs, drives, diagnoses and treats illnesses.
If the software falls within the definition of an SaMD, the guidance document goes through a detailed validation process which includes scientific, clinical performance and analytical validity, as outlined in Table 2.
FDA Still Regulates Software that Does Not Fall Under SaMD
In February 2015, the FDA published a guidance document on Mobile Medical Applications (MMA) in order to regulate the large influx of health apps. In this guidance document, an MMA is defined as, “a mobile app that… is intended to be used as an accessory to a regulated medical device, or to transform a mobile platform into a regulated medical device.” The theme in this guidance document basically indicates that the FDA intends to regulate mobile medical manufacturers that create apps that are used with devices, and plan to market and distribute MMAs for commercial purposes. Table 3 delineates a few examples of what would fall under an MMA.
Application of mHealth, Wearables in Clinical Research
The aforementioned guidances have demonstrated how regulatory authorities plan to oversee mobile software applications that either are intended to inform, drive, diagnose and treat illnesses, or act as a component to a medical device in commercial settings. Understanding these concepts should help study teams conduct proper feasibility assessments on a variety of mHealth and wearable applications in clinical trials, however, it is important to first define the purpose of the application in order to (a) select the right technology/wearable, (b) conduct appropriate feasibility, and (c) develop proper vendor oversight programs.
Below is a set of questions that can stimulate thinking about incorporating mHealth/Wearable technology in clinical research:
1. Define the Objective: Is the purpose of the mHealth application/wearable to collect data used for regulatory submissions? Is it going to be used for patient engagement? Or simply to conduct patient reported outcomes?
2. Categorize the Tool: Is the tool and SaMD? An FDA regulated MMA? Or neither?
3. Ensure Tool Validation:
4. Develop Oversight Analytics: Like with any vendor in clinical research, it is important to measure service provider quality and conduct, hence, developing a customized set of Key Risk and Performance Indicators should demonstrate proper vendor oversight.
There is a lot of piloting going on, however, I haven’t yet seen full mHealth/Wearable adoption in clinical trials, and it is possible that the lack of innovation is stemming from (a) no clear regulatory guidance on incorporating wearables in clinical trials, and (b) the natural risk-averse culture in the biopharmaceutical industry, and (c) the simple fact that many in the industry don’t feel business pressure/urgency to innovate the R&D process.
It is important to note, however, that the business environment is changing at an alarming pace. To elaborate, the insurance industry recently rattled the biopharmaceutical industry, as CVS and Express Scripts made announcements to tackle high drug pricing (or in CVS’ words, ‘hyperinflationary drugs’3) by excluding a record number of medical products from coverage (34 and 154 medical products in 2012, and 2017, respectively (a 353% increase))4. This new trend in payer denial will likely continue to amplify, and pressure top line figures in the biopharmaceutical industry. While many biopharmaceutical companies may not necessarily feel an urgency to improve the efficiency of R&D at the moment, the environment will get to a point where the industry will eventually have no choice but to change. Those that invest and adopt mHealth and wearable technologies earlier will likely benefit in the long run.
To elaborate, the benefits of incorporating mHealth and wearables in clinical trials offers numerous benefits including reduced subject dropout, higher patient engagement, and lower variability in data leading to less subjects needed to achieve statistical outcomes and faster study completion timelines. Moreover, companies that successfully incorporate validated mHealth and wearable technologies in clinical trials are capable of generating data that they can use to offer more compelling real-world evidence that can be used in post-marketing settings as a competitive advantage, and for payers.