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Methods

Criteria for considering studies for this review

Types of studies

We include RCTs including cluster-randomized and crossover trials.

Early-phase clinical trials, single-arm trials, non-randomized studies and modelling studies of interventions for COVID-19 are not included in the review.

We exclude studies about prognosis, systematic reviews and meta-analyses and diagnostic test accuracy studies.

No restriction on language

Protocol amendment:

As of March 1, 2022, the COVID-NMA stopped including preventive treatment trials. The analysis presented in this page includes preventive trials identified and included up to Feb 28, 2022.

Types of participants

For pharmacologic treatments we consider participants who have been exposed to patients with COVID-19 (confirmed and suspected cases):

  • People at high risk of COVID-19
  • People in close contacts of COVID-19 patients
  • Health care workers, medical staff
  • Healthy volunteers

    • For non-pharmacologic interventions: No specific population.

    Types of interventions

    We consider all types of prophylactic pharmacologic treatment provided to people exposed to COVID-19 patients aiming at reducing human-to-human transmission of COVID-19 in healthcare and in the community (such as Hydroxychloroquine, Ivermectine).

    In addition to, all non-pharmacologic interventions, such as use of masks, hand hygiene, physical distancing of at least 1 meter, avoidance of touching one’s face, respiratory etiquette, adequate ventilation in indoor settings, testing, contact tracing, quarantine and isolation...

    We exclude Traditional Chinese Medicine.

    Outcomes

    List of critical outcomes:

  • Incidence of symptomatic COVID-19 (confirmed with positive test for SARS-CoV-2 infection by RT-PCR or probable
  • Incidence of COVID-19 confirmed with positive test for SARS-CoV-2 infection by RT-PCR
  • Hospital admissions or death
  • All-cause mortality

    • In addition to the following safety outcomes for prevention of COVID-19:

  • Incidence of serious adverse events (SAEs)
  • Incidence of any adverse events List of critical outcomes:
  • ICU admissions or death
  • Incidence of symptomatic COVID-19 (confirmed with positive test for SARS-CoV-2 infection by RT-PCR or probable or suspected) or asymptomatic COVID-19 confirmed with positive test for SARS-CoV-2 infection by RT-PCR

    Assessment of risk of bias in the included studies

    Each study is assessed with the Cochrane 'Risk of Bias 2' (RoB 2) tool for randomized controlled trials.We record judgments and justification per domain for all collected outcomes. The Cochrane RoB 2 tool is structured into five domains: 1) risk of bias arising from the randomization process, 2) risk of bias due to deviations from intended interventions, 3) risk of bias due to missing outcome data, 4) risk of bias in the measurement of the outcome, 5) risk of bias in the selection of the reported result.

    The risk of bias judgement by domain corresponds to the highest risk of bias among outcomes by domain. The overall risk of bias corresponds to the overall highest risk of bias assessed among outcomes.

    Summary of findings and assessment of the certainty of the evidence

    We use the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness and publication bias) to assess the certainty of a body of evidence related to studies that contributed data to pairwise meta-analyses for prespecified outcomes.

    We present 'Summary of findings' tables to present estimated relative and absolute risks for critical outcomes only.

    For more information on our methods see our protocol here.