Implementation of the Randomized Embedded Multifactorial Adaptive Platform for COVID-19 (REMAP-COVID) trial in a US health system-lessons learned and recommendations

UPMC REMAP-COVID Group, on behalf of the REMAP-CAP Investigators, David T Huang, Bryan J McVerry, Christopher Horvat, Peter W Adams, Scott Berry, Meredith Buxton, Gilles Clermont, William Garrard, Timothy D Girard, Ghady Haidar, Andrew J King, Kelsey Linstrum, Salim Malakouti, Florian B Mayr, Erin K McCreary, Stephanie K Montgomery, Christopher W Seymour, Alexandra Weissman, Derek C Angus, UPMC REMAP-COVID Group, on behalf of the REMAP-CAP Investigators, David T Huang, Bryan J McVerry, Christopher Horvat, Peter W Adams, Scott Berry, Meredith Buxton, Gilles Clermont, William Garrard, Timothy D Girard, Ghady Haidar, Andrew J King, Kelsey Linstrum, Salim Malakouti, Florian B Mayr, Erin K McCreary, Stephanie K Montgomery, Christopher W Seymour, Alexandra Weissman, Derek C Angus

Abstract

Background: The Randomized Embedded Multifactorial Adaptive Platform for COVID-19 (REMAP-COVID) trial is a global adaptive platform trial of hospitalized patients with COVID-19. We describe implementation at the first US site, the UPMC health system, and offer recommendations for implementation at other sites.

Methods: To implement REMAP-COVID, we focused on six major areas: engaging leadership, trial embedment, remote consent and enrollment, regulatory compliance, modification of traditional trial management procedures, and alignment with other COVID-19 studies.

Results: We recommend aligning institutional and trial goals and sharing a vision of REMAP-COVID implementation as groundwork for learning health system development. Embedment of trial procedures into routine care processes, existing institutional structures, and the electronic health record promotes efficiency and integration of clinical care and clinical research. Remote consent and enrollment can be facilitated by engaging bedside providers and leveraging institutional videoconferencing tools. Coordination with the central institutional review board will expedite the approval process. Protocol adherence, adverse event monitoring, and data collection and export can be facilitated by building electronic health record processes, though implementation can start using traditional clinical trial tools. Lastly, establishment of a centralized institutional process optimizes coordination of COVID-19 studies.

Conclusions: Implementation of the REMAP-COVID trial within a large US healthcare system is feasible and facilitated by multidisciplinary collaboration. This investment establishes important groundwork for future learning health system endeavors.

Trial registration: NCT02735707 . Registered on 13 April 2016.

Keywords: Adaptive trial; COVID-19; Clinical trial; Coronavirus; Platform trial; SARS-CoV-2.

Conflict of interest statement

MB is Chief Executive Officer of the Global Coalition for Adaptive Research, a 501(C) [3] nonprofit organization. SB reports being a part owner of Berry Consultants, LLC (a company that designs and implements platform and adaptive clinical trials for pharmaceutical companies, medical device companies, National Institutes of Health (NIH) cooperative groups, international consortia and non- profit organizations), and providing consulting for platform trials. DCA is the UPMC chief healthcare innovation officer.

Figures

Fig. 1
Fig. 1
UPMC REMAP-COVID Intake Form. This form is embedded into a patient’s electronic health record, solicits basic clinical information, and requests providers to ask the patient or legally authorized representative if s/he is interested in potential additional therapies for COVID-19. The intake form represents the singular route of entry into the REMAP-COVID trial at UPMC
Fig. 2
Fig. 2
Example of an embedded order alert. This order alert displays the randomization status of the patient and asks the treating clinician to approve the order for the randomized investigational treatment unless deemed to be not in the patient’s best interest
Fig. 3
Fig. 3
Remote consent and enrollment process. This process uses videoconference and document signing technologies to enable remote consent and enrollment
Fig. 4
Fig. 4
Current enrollment. As of Dec 14, 2020, there have been 319 patients enrolled among 2005 screened (16% enrollment) at 21 hospitals, after excluding those who were not candidates due to age 

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