Methodological and reporting quality of non-inferiority randomised controlled trials comparing antiretroviral therapies: A systematic review


Background: It is unclear whether the reporting quality of antiretroviral non-inferiority randomised controlled trials (ARV NI-RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year.

Methods: We searched Medline, Embase, and Cochrane Central from inception to 14 November 2022. We included NI-RCTs comparing ≥2 antiretroviral regimens used for HIV treatment or prophylaxis. We used the Cochrane Risk of Bias 2.0 (RoB 2.0) tool to assess risk of bias. Screening and data extraction were performed blinded and in duplicate. Descriptive statistics were used to summarise data; statistical tests were two-sided, with significance defined as p<0.05. The systematic review was prospectively registered (PROSPERO CRD42022328586), and not funded.

Results: We included 160 articles reporting 171 trials. 101 of 160 (63.1%) did not justify the non-inferiority margin (NIM) used, and 28 (17.5%) did not provide sufficient information for sample size calculation. Eighty-nine of 160 (55.6%) reported both intention-to-treat (ITT) and per-protocol (PP) analyses, while 118 (73.8%) described missing data handling. Ten of 171 (5.9%) trials reported potentially misleading results. Pharmaceutical industry-funded trials were more likely to be double blinded (28.1% vs. 10.3%, p=0.029), and to describe missing data handling (78.5% vs. 59.0%, p=0.021). Overall risk of bias was low in 96 of 160 studies (60.0%).

Conclusion: ARV NI-RCTs should improve NIM justification, reporting of ITT and PP analyses, and missing data handling to increase CONSORT adherence.


Lo CKL, Komorowski AS, Hall CW, Sandstrom TS, Alamer AAM, Mourad O, Li XX, Al Ohaly R, Benoit MA, Duncan DB, Fuller CA, Shaw S, Suresh M, Smaill F, Kapoor AK, Smieja M, Mertz D, Bai AD




  • Population(s)
    • General HIV+ population
  • Prevention, Engagement and Care Cascade
    • Engagement and Care Cascade
  • Engagement and Care Cascade
    • Treatment


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