The biggest challenge facing clinical research today is the need to gather, analyze, and report data. To collect patient data more efficiently, the industry has turned to electronic patient-reported outcome (ePRO) tools. Early on, patients were provided with devices to use. But as more than three-quarters of Americans own smartphones1, more and more, researchers are exploring bring your own device (BYOD) strategies in which patients utilize their own devices to collect clinical trial data. While an increasing number of trials have successfully deployed this model with great results, some CROs and sponsors are still hesitant because of the absence of FDA guidance on the matter.
Convenience Is King, yet Uncertainty Remains
Many advantages make BYOD alluring for patients, sites, CROs, and sponsors. For patients, using their own device is convenient; there’s no learning curve to understand a new device, no need to keep track of an extra device, and no trips to pick up or return a provisioned device. Furthermore, few smartphone users are willing to part from their phones for very long, but the same can’t be said of provisioned device users. BYOD patients consistently show greater use of applications provided on their own devices versus provisioned devices. In an early case study conducted by Clinical Ink, patients leveraged the BYOD implementation twice as often and for twice as long2 (tables below), which benefits sites, CROs, and sponsors. BYOD significantly lowers — and might eliminate, in some trials — costs associated with data plans, shipping, lost or unreturned devices, and the overall logistics of inventory management. For a large trial, these savings could mean hundreds of thousands of dollars.
Despite these advantages, lack of experience fuels the industry’s reluctance to embrace BYOD. Researchers worry that some patients may:
- Break, lose, or upgrade their phone during the trial
- Delete the app
- Change the time
- Mute or turn off notifications
- Be incapable of, for whatever reason, downloading the application
- Be unwilling to use their own data plan or storage space for the clinical trial data collection
- Not have smartphones and be unable to participate, thus creating a bias in the results
These concerns can largely be addressed through software, or through a hybrid hardware model in which a percentage of provisioned devices are included as part of the de-risking strategy. An ePRO provider experienced with BYOD trials can evaluate the investigative sites’ demographics and estimate what percentage of the protocol’s patient population will need provisioned devices.
Importantly, patients who own devices are willing to use them. In a recent study of 155 patients with chronic pain, 94% said they definitely or probably would be willing to download a clinical trial app to their own device. Forty-five percent indicated that their own device would be the most convenient, 15% said they preferred a provisioned device, and 40% had no preference.[1]
Furthermore, while some researchers fear that choosing BYOD might preclude sponsors from providing standard ePRO vendor services (e.g., real-time summary reporting, diary detail, diary design, questionnaire licensing facilitation, patient engagement, diary reminders, and visit reminders), this is not always the case. Clinical Ink’s standard offerings, for example, do not change when implementing either a full BYOD or a hybrid solution.
Regulation, Questionnaire Copyrights, and Test Equivalency Must Be Accounted For
To date, multiple studies have submitted BYOD-captured primary endpoint data to the FDA. While there is currently no clear FDA guidance on BYOD, we do know that the FDA is willing to have conversations about BYOD on a study-by-study basis. Given the agency’s push to move away from paper-based trials, it seems likely that it would look favorably on a trial deploying BYOD for ePRO, particularly where the alternative would be paper-based.
Sponsors and CROs considering BYOD should evaluate a range of criteria. Two critical items are:
- Trial phase: Risk aversion will be greatest for higher-stakes, later-phase trials, but there are cases in which Phase 3 trials are well suited for BYOD/hybrid strategies.
- Nature of the endpoint: Risk aversion will rise as endpoint data ranges from exploratory to primary. However, even collection of the primary endpoint can offer scenarios well suited for BYOD/hybrid solutions.
Communicating with the FDA early in protocol review will enable agency feedback regarding a BYOD or hybrid strategy. Consider and review the questionnaires, study duration, patient population, and specific outcome measures within the trial. Implement only fit-for-purpose BYOD and hybrid hardware solutions. Depending on the requirements of your protocol and indication, an ePRO vendor may offer recommendations for your study.
Copyrighted Instruments: Consult With an Expert
There has been some pushback on approval when copyrighted instruments which have not previously been evaluated for use in a BYOD setting are included in the ePRO BYOD strategy. When copyright holders have reservations about patients using their own devices, it is critical that any BYOD approach be reviewed and approved by the copyright holders before ePRO development begins.
Discuss your specific situation with your ePRO partner. A vendor experienced in BYOD may have expertise working either with the specific copyright holder or they may have an existing relationship with a representative organization such as Mapi Research Trust, the nonprofit that manages electronic use requirements for many copyrighted questionnaires.
Measuring Equivalency: Less of a Concern Than Once Thought
Ensuring equivalency remains a significant concern for sponsors and CROs considering ePRO trials, particularly ones using a BYOD approach. Migrating a paper-based questionnaire into an electronic format requires proof of equivalency to ensure this change in format (e.g., change in screen size, display orientation, item placement, etc.) won’t affect patient responses.
However, hundreds of studies and several meta-analyses have shown high levels of agreement between paper and electronic modes. As more evidence becomes available about how screen size does not impact comprehension, content validity, and patient responses, adoption is growing among copyright holders, sponsors, and CROs. Assuming that the general principles of ePRO design good practices — such as those reported by Critical Path Institute’s ePro Consortium[2] — are followed, BYOD is an approach that should be considered.
Conclusion
BYOD may not be appropriate for every trial, but the strategy’s potential advantages make it worth considering, despite lack of clarity from the FDA. Sponsors or CROs considering a BYOD strategy should look for a qualified, BYOD-experienced vendor to help evaluate the risks and opportunities — particularly one that can help them work through regulatory and copyright concerns.
Beyond determining the appropriateness of a BYOD approach, the vendor should be able to assist and train sites. For sites unfamiliar with BYOD, a 24/7 helpdesk will assure them the support they need to install the app, train the patients, and handle smartphone upgrade, loss, or damage.
Your ePRO vendor should be able to proactively update core software and ensure alignment should patients upgrade their smartphones during the trial. The software should work on any Android or Apple iOS device and function seamlessly, even if patients need to switch between provisioned and personal devices.
Additionally, the software must enable consistency, which is especially important for equivalency. For example, Clinical Ink’s Lumenis platform offers the interactive tools required to ensure patient education and engagement. It also provides configurable standard questionnaire controls: The date/time spinner, yes/no, vertical VAS, multiple choice, numeric rating scales, audio notifications, and more are all configurable. These features enable consistency regardless of whether a patient-provided or provisioned device is used.
To gain experience, researchers might partner with their ePRO vendor and conduct a pilot and sensitivity analysis surrounding BYOD within their study. Particularly for studies supporting primary endpoints and using homegrown questionnaires, valuable information can be gained by incorporating some questions that ask patients about using their own devices. Further, exploratory, post-hoc statistical analysis could provide useful information on the classification of responders between the various modes used in the study, while also comparing adherence rates.
While BYOD isn’t right for all studies and the FDA has yet to fully weigh in, researchers and CROs that fail to consider BYOD are losing an opportunity to save time, reduce costs, and provide more convenience for the patients in their trials. Selectively deployed with guidance from an experienced ePRO vendor, BYOD or a hybrid BYOD model can deliver advantages that should not be missed.
------------------
1 Pew Research Center. Mobile Fact Sheet. https://www.pewinternet.org/fact-sheet/mobile/. Accessed April 29, 2019.
2 Pugliese L, Woodriff M, Crowley O, Lam V, Sohn J, Bradley S. Feasibility of the Bring Your Own Device Model in Clinical Research: Results from a Randomized Controlled Pilot Study of a Mobile Patient Engagement Tool. Cureus. 2016 Mar; 8(3): e535. doi: 10.7759/cureus.535.
3 Byrom B, Doll H, Muehlhausen W, et al. Measurement Equivalence of Patient-Reported Outcome Measure Response Scale Types Collected Using Bring Your Own Device Compared to Paper and a Provisioned Device: Results of a Randomized Equivalence Trial. Value in Health, 2018. https://www.valueinhealthjournal.com/article/S1098-3015(17)33615-X/pdf.
4 Critical Path Institute. Electronic Patient-Reported Outcome Consortium. https://c-path.org/programs/eproc/
epro-overview/best-practice-documents/. Accessed April 29, 2019.
