By David Babaian, JD LLM CIP RAC Associate Director at Advarra Consulting
Decentralization is one of many ways to modernize clinical trials.1 Yet, because of the varied approaches and possible components of a decentralized research program, it is difficult to define what decentralization actually means. This struggle to characterize the vision could be the reason behind slow implementation, despite the FDA’s stated interest in incorporating and expanding such methods into protocol design.
Decentralized clinical trials (DCT) are defined as studies executed through telemedicine and mobile/local healthcare providers, using processes and technologies differing from the traditional clinical trial model.2
Technology is the linchpin. Decentralization, of course, is a matter of perspective. When defining and shaping the trial’s impact, participant-centricity should be at the forefront. Patients can now participate in the clinical trial from their preferred location. Other aspects of decentralized methodologies benefit from centralization. This may include clinical trial oversight, whether through remote monitoring, fewer clinical investigators, or independent ethics review.
Nevertheless, the life sciences industry is making strides. Where many were reluctant in the face of perceived regulatory uncertainty in the past, the also afforded the FDA with the opportunity to meet the challenge and provide guidance to balance the field, rather than looking solely to industry leaders to forge ahead on an ad hoc basis. Here are a few examples.
Defining the role of local healthcare providers
The FDA clarifies the extent to which involved local healthcare providers (HCPs) might not be considered sub-investigators and need not be listed on the FDA Form 1572. The general standard of “direct and significant contribution to the data” remains, but procedures that do not differ from routine clinical practice do not qualify (as opposed to drug response assessments or procedures performed unique to the protocol and distinct from routine medical care).3 Instead, these HCPs should be documented in site records, such as the delegation log.4 Of course, the IRB-approved protocol should describe the particulars surrounding administration of the investigational drug.5
Ensuring effective, compliant trial documentation and IP distribution
The FDA emphasizes that investigators must ensure access to necessary documentation contained in the participant’s medical record, especially if the HCP administering the investigational product (IP) is not considered a sub-investigator. Consequently, the investigator must obtain consent from the participant to access trial-related data in the medical record (e.g., vitals and routine symptom evaluation associated with administering IP).6 The FDA also recommends the investigator communicate the intent to request these records from the HCP as soon as possible.7
The FDA confirms that IP may be shipped from a central distribution site directly to an HCP or — risk profile permitting — to a participant, provided such shipping occurs under investigator supervision using procedures to assure accountability and product quality (i.e., that IP storage conditions, as defined in the protocol, were maintained during shipping and that the IP packaging was intact upon receipt).8
Following the FDA’s lead
The FDA has sought to directly facilitate remote administration of clinical trials with access to the MyStudies application for electronic consent.9 Also, illustratively, the FDA has doubled down on making accessible, low risk digital health devices, specifically in the context of mental health.10
Clinical trials have come a long way over the course of the past year, but the progress must continue
As with those promulgated by many government offices,11 guidances, typically by their own limitation, are tethered to the duration of the pandemic. It is important to maintain the momentum, leveraging innovation and experience, to sustain adoption. Clarity — through consistency — in the regulatory landscape post-Covid-19 will go a long way in meeting industry expectation and solidifying gains. Whereas, a significant rollback could jeopardize the level of comfort with decentralized methodologies and best practices beginning to emerge—not to mention what, if any, significant and lingering impact the pandemic will have on participants’ general attitudes toward wider socialization and exposure, where convenient and safer alternatives have been introduced.
Decentralization will not cure all that ails clinical trials. Yes, these methodologies can lower the bar to participation in the long run and have the promise to reduce ethnic and other disparities in clinical trial participation. DCTs should have their most profound impact on participant retention, engagement, and satisfaction. Still, many of the same barriers to participation, such as clinical trial awareness, will exist and new challenges arise — whether they persist remains to be seen.
For more insights on decentralized clinical trials and what the future may hold, read the full article here.
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1Statement by FDA Commissioner Scott Gottlieb, M.D., on new strategies to modernize clinical trials to advance precision medicine, patient protections and more efficient product development, U.S. Food & Drug Admin., https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-new-strategies-modernize-clinical-trials-advance (last updated Mar. 14, 2019).
2 Clinical Trial Transformation Initiative, CTTI Recommendations: Decentralized Clinical Trials 2 (2018), available at https://www.ctti-clinicaltrials.org/sites/www.ctti-clinicaltrials.org/files/dct_recommendations_final.pdf.
3 U.S. Food & Drug Admin., Guidance for Industry, Investigators, and Institutional Review Boards: Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency 26 (2020), available at https://www.fda.gov/media/136238/download.
6Id. at 25.
9COVID MyStudies Application (App), U.S. Food & Drug Admin., https://www.fda.gov/drugs/science-and-research-drugs/covid-mystudies-application-app (last updated May 29, 2020).
10See U.S. Food & Drug Admin., Guidance for Industry and Food and Drug Administration Staff: Enforcement Policy for Digital Health Devices For Treating Psychiatric Disorders During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency (2020), available at https://www.fda.gov/media/136939/download.
11E.g., Telehealth: Delivering Care Safely During COVID-19, U.S. Dept. of Health & Human Services, https://www.hhs.gov/coronavirus/telehealth/index.html (last updated July 15, 2020).