The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study

Kristof Vanmunster — Sat, 30 Sep 2023 19:32:49 +0000

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.

Adaptive platform trials: definition, design, conduct and reporting considerations

Kristof Vanmunster — Wed, 27 Sep 2023 19:41:18 +0000

Researchers, clinicians, policymakers and patients are increasingly
interested in questions about therapeutic interventions that are difficult or costly
to answer with traditional, free-standing, parallel-group randomized controlled
trials (RCTs). Examples include scenarios in which there is a desire to compare
multiple interventions, to generate separate effect estimates across subgroups of
patients with distinct but related conditions or clinical features, or to minimize
downtime between trials. In response, researchers have proposed new RCT designs
such as adaptive platform trials (APTs), which are able to study multiple
interventions in a disease or condition in a perpetual manner, with interventions
entering and leaving the platform on the basis of a predefined decision algorithm.
APTs offer innovations that could reshape clinical trials, and several APTs are now
funded in various disease areas. With the aim of facilitating the use of APTs, here
we review common features and issues that arise with such trials, and offer
recommendations to promote best practices in their design, conduct, oversight
and reporting.

Methodology – REMAP-CAP homepage

The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study

Adaptive platform trials: definition, design, conduct and reporting considerations