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. 2023 Sep 19;2(1):e000497.
doi: 10.1136/bmjmed-2023-000497. eCollection 2023.

Transparent reporting of adaptive clinical trials using concurrently randomised cohorts

Ian C Marschner  1 , Mark Jones  2 , James A Totterdell  2 , Robert K Mahar  3   4   5 , Thomas L Snelling  2   6 , Steven Y C Tong  7   8   9 ; Australasian Covid-19 Trial (ASCOT) study group
Collaborators, Affiliations

Transparent reporting of adaptive clinical trials using concurrently randomised cohorts

Ian C Marschner et al. BMJ Med. .

Abstract

Adaptive clinical trials have designs that evolve over time because of changes to treatments or changes to the chance that participants will receive these treatments. These changes might introduce confounding that biases crude comparisons of the treatment arms and makes the results from standard reporting methods difficult to interpret for adaptive trials. To deal with this shortcoming, a reporting framework for adaptive trials was developed based on concurrently randomised cohort reporting. A concurrently randomised cohort is a subgroup of participants who all had the same treatments available and the same chance of receiving these treatments. The reporting of pre-randomisation characteristics and post-randomisation outcomes for each concurrently randomised cohort in the study is recommended. This approach provides a transparent and unbiased display of the degree of baseline balance and the randomised treatment comparisons for adaptive trials. The key concepts, terminology, and recommendations underlying concurrently randomised cohort reporting are presented, and its routine use in adaptive trial reporting is advocated.

Keywords: clinical trial; research design; statistics.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Health and Medical Research Council, the Medical Research Future Fund of Australia, and the Snow Medical Foundation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1
Schematic representation of fixed designs within the overall adaptive design of Australasian Covid-19 Trial (ASCOT). In the overall adaptive design, 1556 participants were randomised to one of four anticoagulation treatments for covid-19, within one of three embedded fixed designs
Figure 2
Figure 2
Aggregated summaries of all treatment comparisons in Australasian Covid-19 Trial (ASCOT) based on randomised, indirect, and combined evidence. Treatments are low dose anticoagulation alone or in combination with aspirin, intermediate dose anticoagulation, and therapeutic dose anticoagulation. Relative risks >1 favour the first treatment
See this image and copyright information in PMC

References

    1. Pallmann P, Bedding AW, Choodari-Oskooei B, et al. . Adaptive designs in clinical trials: why use them, and how to run them. BMC Med 2018;16:29. 10.1186/s12916-018-1017-7 - DOI - PMC - PubMed
    1. Angus DC, Alexander BM, Berry S. Adaptive platform trials: definition, design, conduct and reporting considerations. Nat Rev Drug Discov 2019;18:797–807. 10.1038/s41573-019-0034-3 - DOI - PubMed
    1. Moher D, Hopewell S, Schulz KF, et al. . CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:c869. 10.1136/bmj.c869 - DOI - PMC - PubMed
    1. Dodd LE, Freidlin B, Korn EL. Platform trials–beware the non-comparable control group. N Engl J Med 2021;384:1572–3. 10.1056/NEJMc2102446 - DOI - PMC - PubMed
    1. Lipsky AM, Greenland S. Confounding due to changing background risk in adaptively randomized trials. Clin Trials 2011;8:390–7. 10.1177/1740774511406950 - DOI - PMC - PubMed

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