Dataset Information

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

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.

SUBMITTER: UPMC REMAP-COVID Group, on behalf of the REMAP-CAP Investigators

PROVIDER: S-EPMC7841377 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled "a randomized embedded multifactorial adaptive platform." The design has five key features: 1) randomization, allowing robust causal inference; 2) embedding of study procedures into routine care processes, facilitating enrollment, trial efficiency, and generalizability; 3) a multifactorial statistical model comparing multiple interventions across multiple patient subgroups; 4) response-adaptive randomization with preferential assignment to those interventions that appear most favorable; and 5) a platform structured to permit continuous, potentially perpetual enrollment beyond the evaluation of the initial treatments. The trial randomizes patients to multiple interventions within four treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens. The trial generates estimates of superiority, inferiority, and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection. The trial will also compare ventilatory and oxygenation strategies, and has capacity to address additional questions rapidly during pandemic respiratory infections. As of January 2020, REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) was approved and enrolling patients in 52 intensive care units in 13 countries on 3 continents. In February, it transitioned into pandemic mode with several design adaptations for coronavirus disease 2019. Lessons learned from the design and conduct of this trial should aid in dissemination of similar platform initiatives in other disease areas.Clinical trial registered with www.clinicaltrials.gov (NCT02735707).

Project description:BackgroundThe Ankylosing Spondylitis Association of Switzerland (SVMB) aimed to implement physical activity recommendations (PAR) within their exercise groups (EGs). The PAR promote exercise in all fitness dimensions at the correct dose. To implement the PAR within EGs, they were translated into a new EG concept with five key activities: (a) training for supervising physiotherapists (PTs), (b) correctly dosed exercises in all fitness dimensions, (c) exercise counselling, (d) bi-annual fitness assessments, and (e) individual exercise training, in addition to EG. All these activities were realized in close coordination with SVMB management.ObjectivesTo analyse the implementation success by evaluating adherence/fidelity, feasibility, and satisfaction at the patient, PTs, and organisational level.MethodsThe five key activities of the new EG concept were developed, executed, and assessed after 6 months. The primary outcomes for implementation success were adherence of patients to the recommended exercise behaviour, self-reported by electronic diary; fidelity of PTs to the new concept, self-reported by diary; SVMB organisational changes. Secondary outcomes were feasibility and satisfaction with the new EG concept at all three levels. The tertiary outcome, to evaluate the effectiveness of PAR, was patient fitness, assessed through fitness assessments.Results30 patients with axSpA (ten women, mean age 58 ± 9 years) and four PTs (three women, mean age 46 ± 9 years) participated. The patients' self-reporting of adherence to the PAR was insufficient (43%), possibly due to technical problems with the electronic dairy. The PTs' fidelity to the new EG concept was satisfactory. On all levels, the new concept was generally perceived as feasible and useful for supporting personalised exercise.The frequency of exercise counselling and the fitness assessments was found by patients and PTs to be too high and rigid. Patients' cardiorespiratory fitness [ES 1.21 (95%CI 0.59, 1.89)] and core strength [ES 0.61 (95%CI 0.18, 1.06)] improved over the 6 months.ConclusionsThe pilot implementation of PAR showed acceptance and satisfaction to be sufficient, thus confirming the need for evidence-based EGs, provided by a patient organisation in order to support active PA behaviour. However, adaptations are necessary to increase its feasibility for nationwide implementation.Trial registrationSNCTP, SNCTP000002880. Registered 31 May 2018, https://www.kofam.ch/en/snctp-portal/search/0/study/42491 .

Project description:IntroductionAs the population ages, there is interest in strategies to promote resiliency, especially for frail patients at risk of its complications. The physiological stress of surgery in high-risk individuals has been proposed both as an important cause of accelerated age-related decline in health and as a model testing the effectiveness of strategies to improve resiliency to age-related health decline. We describe a randomised, embedded, multifactorial, adaptative platform (REMAP) trial to investigate multiple perioperative interventions, the first of which is metformin and selected for its anti-inflammatory and anti-ageing properties beyond its traditional blood glucose control features.Methods and analysisWithin a multihospital, single healthcare system, the Core Protocol for Strategies to Promote ResiliencY (SPRY) will be embedded within both the electronic health record (EHR) and the healthcare culture generating a continuously self-learning healthcare system. Embedding reduces the administrative burden of a traditional trial while accessing and rapidly analysing routine patient care EHR data. SPRY-Metformin is a placebo-controlled trial and is the first SPRY domain evaluating the effectiveness of three metformin dosages across three preoperative durations within a heterogeneous set of major surgical procedures. The primary outcome is 90-day hospital-free days. Bayesian posterior probabilities guide interim decision-making with predefined rules to determine stopping for futility or superior dosing selection. Using response adaptative randomisation, a maximum of 2500 patients allows 77%-92% power, detecting >15% primary outcome improvement. Secondary outcomes include mortality, readmission and postoperative complications. A subset of patients will be selected for substudies evaluating the microbiome, cognition, postoperative delirium and strength.Ethics and disseminationThe Core Protocol of SPRY REMAP and associated SPRY-Metformin Domain-Specific Appendix have been ethically approved by the Institutional Review Board and are publicly registered. Results will be publicly available to healthcare providers, patients and trial participants following achieving predetermined platform conclusions.Trial registration numberNCT03861767.