The required size of cluster randomized trials of nonpharmaceutical interventions in epidemic settings

  1. Justin K. Sheen
  2. Johannes Haushofer
  3. C. Jessica E. Metcalf
  4. Lee Kennedy‐Shaffer

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Abstract

To control the SARS‐CoV‐2 pandemic and future pathogen outbreaks requires an understanding of which nonpharmaceutical interventions are effective at reducing transmission. Observational studies, however, are subject to biases that could erroneously suggest an impact on transmission, even when there is no true effect. Cluster randomized trials permit valid hypothesis tests of the effect of interventions on community transmission. While such trials could be completed in a relatively short period of time, they might require large sample sizes to achieve adequate power. However, the sample sizes required for such tests in outbreak settings are largely undeveloped, leaving unanswered the question of whether these designs are practical. We develop approximate sample size formulae and simulation‐based sample size methods for cluster randomized trials in infectious disease outbreaks. We highlight key relationships between characteristics of transmission and the enrolled communities and the required sample sizes, describe settings where trials powered to detect a meaningful true effect size may be feasible, and provide recommendations for investigators in planning such trials. The approximate formulae and simulation banks may be used by investigators to quickly assess the feasibility of a trial, followed by more detailed methods to more precisely size the trial. For example, we show that community‐scale trials requiring 220 clusters with 100 tested individuals per cluster are powered to identify interventions that reduce transmission by 40% in one generation interval, using parameters identified for SARS‐CoV‐2 transmission. For more modest treatment effects, or when transmission is extremely overdispersed, however, much larger sample sizes are required.

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  1. Version published to 10.1002/sim.9365
  2. ScreenIT

    SciScore for 10.1101/2021.07.12.21260375: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We use the EoN python package to simulate the epidemic.35 Code used for simulations is provided at http://www.github.com/jsheen/NPI.
    python
    suggested: (IPython, RRID:SCR_001658)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2021.07.12.21260375v1 on medRxiv