REMAP-CAP

Grand Rounds September 19, 2025: Hurdles for the Delivery of Clinical Trials: Insights From the REMAP-CAP Trial in Europe (Denise van Hout, MD, PhD)

Posted on by terren.green@duke.edu

Speaker

Denise van Hout, MD, PhD
Postdoctoral Researcher
Julius Center for Health Sciences and Primary Care
University Medical Center Utrecht, the Netherlands

Keywords

Adaptive platform trial, Regulatory efficiency, REMAP-CAP, Study design, Study startup.

Key Points

  • Randomised Embedded Multifactorial Adaptive Platform trial for Community-Acquired Pneumonia (REMAP-CAP) began in 2016 as a data driven analysis of ethical, administrative, and logistical and ethical (EARL) delays in clinical trials studying respiratory infections. The goal was embedded trials that are flexible, efficient, and agile to provide clinicians with high-quality evidence to make the best treatment decisions.
  • REMAP-CAP is a global multifactorial adaptive platform trial with a master protocol that can investigate multiple interventions in different treatment domains for a single disease.
  • Over 8000 patients in REMAP-CAP were randomized to 44 interventions in 16 different treatment domains between January 2019 and June 2023. Patients could be randomized to more than 1 domain resulting in 15656 randomizations. Enrollment increased during the COVID-19 pandemic.
  • Dr. van Hout believes that to improve clinical trials, we should treat the challenges as a scientific problem and solve them with the same rigor.
  • Regulatory requirements and informed consent regulations differed among sites causing confusion for the researchers about what documents should be submitted with the contract and protocol in each country. Drug labeling requirements in some countries also slowed protocol approval. EARL processes also slowed trial initiation and patient enrollment.
  • It was clear that overall enrollment in the UK outpaced the other 257 sites worldwide. The UK had a shorter period of time to a fully signed study contract and protocol approval compared with sites in other countries (5 days in the UK compared with 183 days in non-UK countries). This quicker time to signed contract was accomplished by either accepting the contract as-is or rejecting the contract – without negotiating small details. The UK was also 3 months faster than non-UK countries at enrolling the first patient after study approval (1 month vs 4 months, respectively) leading to more enrollment and more research questions answered.
  • In January of 2022 the EU centralized regulatory submission to a single portal (CTIS) to ease and speed the process of starting a new trial.

Discussion Themes

Adaptive platform trials were uncommon before the COVID-19 pandemic, but their value became clear during the pandemic. After the pandemic, REMAP-CAP focuses on different treatment domains for pneumonia. Maintaining the infrastructure for an adaptive platform trial is difficult if there is not a clear need such as there was during the COVID-19 pandemic.

Centralizing approval for trials under one government body could speed the approval process for studies. During times of high need, prioritizing one or two good trials over a lot of smaller trials can also help speed the process.

 

Learn more about REMAP-CAP at https://www.remapcap.eu/

Grand Rounds August 11, 2023: The REMAP-CAP Adaptive Platform Trial: Recent Insights and Future Directions (Patrick Lawler, MD, MPH)

Posted on by Damon Seils

Speaker

Patrick Lawler, MD, MPH
Cardiology and Critical Care Divisions
McGill University and University of Toronto

 

 

Keywords

REMAP-CAP; adaptive platform trials; critical care; pneumonia

Key Points

  • Clinical trials face challenges that were amplified during the COVID-19 public health emergency, including avoiding shortcomings of prior data, equipoise, heterogeneity of treatment effect, making trials happen quickly, the complexity of studying a single intervention in isolation, and the sustainability and efficiency of trial conduct.

  • REMAP-CAP is an adaptive platform trial simultaneously evaluation multiple treatments in domains using a master protocol. In adaptive trials, trial design features are modified during the trial to maximize statistical efficiency or achieve better patient outcomes. Examples include response-adaptive randomization, sample size reassessment, multi-arm designs, group sequential stopping, and others.

  • Most diseases have multiple component therapies, and several questions must be evaluated for each component, including whether there is heterogeneity of treatment effect. Clinical trials generally assume homogenous treatment effects; in reality there are heterogeneous treatment effects.

  • In therapeutic anticoagulation domain of REMAP-CAP, Bayesian techniques allowed for greater statistical efficiency in arriving at conclusions about effectiveness. A post hoc analysis evaluated strategies for further studying heterogeneity of treatment effect.

  • REMAP-CAP offered operational and statistical efficiencies, addressing challenges associated with the COVID-19 pandemic. The trial shortened the divide between clinical care and research and demonstrated a capacity for “parabiosis” with other trials in a multiple-platform trial. Adaptive designs increasingly empowered the trial to hunt for heterogeneity of treatment effect.

Discussion Themes

– When an adaptive design enables researchers to control for variations in usual baseline care for complex conditions, there are benefits for statistical efficiency and power and possibly an ability to isolate heterogeneity of treatment effect.

– There were advantages and disadvantages to the multi-platform approach. The approach definitely generated evidence more quickly. Prospective harmonization with other platform trials also brought operational efficiencies, including accelerated recruitment and enrollment.

– In applying this approach to studies of chronic conditions, different monitoring guidelines may be needed to evaluate more modest treatment effect. For example, futility criteria could be lowered. Two-stage designs could also be helpful, such as first evaluating safety outcomes before scaling up to a phase 3 study, or evaluating surrogate outcomes in a phase 2 component and then graduating the treatments that appear more likely have a greater benefit in phase 3, or other ways of mitigating the need for a large sample size.

– An adaptive platform can place additional burdens on the DSMB. REMAP-CAP has a single DSMB overseeing all domains, with its membership having both clinical expertise and experience adaptive trials, and the committee needing to review both primary outcome data and secondary endpoints and other information.

#pctGR, @Collaboratory1

August 9, 2023: REMAP-CAP Trial Returns to PCT Grand Rounds This Friday

Posted on by Damon Seils

Headshot of Dr. Patrick Lawler
Dr. Patrick Lawler

In this Friday’s PCT Grand Rounds, Patrick Lawler of the McGill University Health Centre will present “The REMAP-CAP Adaptive Platform Trial: Recent Insights and Future Directions.”

The Grand Rounds session will be held on Friday, August 11, 2023, at 1:00 pm eastern.

The REMAP-CAP trial (Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia) has a novel adaptive trial design to evaluate several treatment options simultaneously and efficiently. The design is able to adapt in the event of pandemics, and it increases the likelihood that patients will receive the treatment that is most likely to be effective for them.

REMAP-CAP was previously in the Rethinking Clinical Trials Grand Rounds spotlight on May 15, 2020, and April 2, 2021.

Lawler is a cardiologist and clinician-scientist at the McGill University Health Centre in Montreal and the Peter Munk Cardiac Centre at University Health Network in Toronto.

Join the online meeting.

April 2, 2021: Lessons from COVID-19: The First Year of the REMAP-CAP Global Adaptive Platform Trial (Derek Angus, MD, MPH)

Posted on by Gina Uhlenbrauck

Speaker

Derek C. Angus, MD, MPH
Chief Healthcare Innovation Officer, University of Pittsburgh Medical Center
Associate Vice Chancellor for Healthcare Innovation, University of Pittsburgh Schools of the Health Sciences
Distinguished Professor and Mitchell P. Fink Endowed Chair
Department of Critical Care Medicine
University of Pittsburgh and UPMC

Topic

Lessons from COVID-19: The First Year of the REMAP-CAP Global Adaptive Platform Trial

Keywords

COVID-19; REMAP-CAP; Adaptive platform trial; Learning health system; Response-adaptive randomization

Key Points

  • REMAP-CAP (Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia) uses a novel adaptive trial design to evaluate a number of treatment options simultaneously and efficiently. This design is able to adapt in the event of pandemics, and increases the likelihood that patients will receive the treatment that is most likely to be effective for them.
  • REMAP-CAP is an international trial with multiple coordinating centers and 300 sites in 19 countries.
  • The REMAP-CAP trial was initially drafted with a prespecified Pandemic Appendix to be activated in the event of an emergent pandemic. In 2020, this mode was activated as REMAP-COVID, which expanded enrollment to include all hospitalized patients with clinically diagnosed or microbiologically confirmed COVID-19.
  • While adaptive platform trials are likely here to stay, there is a need to build comfort with the modeling, inference, and interpretation; build appropriate infrastructure to keep up with the power of the engine; and invest in common data models.

Discussion Themes

It is possible to design adaptive platform trials with a smaller sample size, depending on the research question.

How did you convince study teams to join your effort rather than start their own?

In the future, small trials could be hosted within the REMAP-CAP adaptive platform.

Given the massive inertia in investment to develop adaptive infrastructures, what are your thoughts for funders across institutions and nations?

Read more about REMAP-CAP and how the REMAP-CAP platform was modified to respond to the COVID-19 pandemic.

Tags

#pctGR, @Collaboratory1