Article type
Abstract
Background: Although the speed of knowledge evolution is crucial in the context of a public health emergency, such as the COVID-19 pandemic, it is also essential that studies evaluating the effects of vaccines are well-planned, conducted and reported. Prioritizing methodological quality throughout these stages, including choosing relevant outcomes, is key to guarantee the reliability and applicability of the results of these studies.
Objectives: to analyse the general and primary outcome-related characteristics of clinical trial protocols on COVID-19 vaccines.
Methods: meta-research including all clinical comparative trial protocols on COVID-19 vaccines registered in ClinicalTrials.gov platform up to October 26, 2021.
Results: 282 trials were analysed. The median expected trial duration was 445 days (ranging from 38 to 1,423 days) and the median target sample size was 420 participants (quartile 1 = 130 and quartile 3 = 1,768). A retrospective registry (after the start date) was observed for 42.55% of the trials. Randomisation procedures were planned by 84.75% and full-blinding procedures by 34.75% of the 282 trials. Most trials were labelled as active or still recruiting and 14 trials (5%) were completed. None of the 14 trials labelled as completed on the date of our search had results available. Industry funding was reported by 198 trials (70.2%). Most studies declared more than one primary outcome, which was usually a safety or immunogenicity outcome and 59 studies (20.9%) had at least one primary efficacy outcome. The description of the primary efficacy outcomes was limited in most cases, referred as a non-specified ‘efficacy’ outcome (18.6%) or described as ‘COVID-19 cases’ (32.2%).
Conclusion: the primary outcomes of clinical trials on COVID-19 vaccines are poorly described and insufficient information about them is provided by the registers. The registry was retrospectively fulfilled for a considerable number of trials, which may lead to bias and research waste. Outcomes were generically described and unable to provide transparent information for replication in practice, further trials or meta-analyses.
Relevance to patients: to properly support health care, we need trials with trustworthy results, so the trials need to come from well-designed and -reported protocols addressing clinically relevant outcomes.
Objectives: to analyse the general and primary outcome-related characteristics of clinical trial protocols on COVID-19 vaccines.
Methods: meta-research including all clinical comparative trial protocols on COVID-19 vaccines registered in ClinicalTrials.gov platform up to October 26, 2021.
Results: 282 trials were analysed. The median expected trial duration was 445 days (ranging from 38 to 1,423 days) and the median target sample size was 420 participants (quartile 1 = 130 and quartile 3 = 1,768). A retrospective registry (after the start date) was observed for 42.55% of the trials. Randomisation procedures were planned by 84.75% and full-blinding procedures by 34.75% of the 282 trials. Most trials were labelled as active or still recruiting and 14 trials (5%) were completed. None of the 14 trials labelled as completed on the date of our search had results available. Industry funding was reported by 198 trials (70.2%). Most studies declared more than one primary outcome, which was usually a safety or immunogenicity outcome and 59 studies (20.9%) had at least one primary efficacy outcome. The description of the primary efficacy outcomes was limited in most cases, referred as a non-specified ‘efficacy’ outcome (18.6%) or described as ‘COVID-19 cases’ (32.2%).
Conclusion: the primary outcomes of clinical trials on COVID-19 vaccines are poorly described and insufficient information about them is provided by the registers. The registry was retrospectively fulfilled for a considerable number of trials, which may lead to bias and research waste. Outcomes were generically described and unable to provide transparent information for replication in practice, further trials or meta-analyses.
Relevance to patients: to properly support health care, we need trials with trustworthy results, so the trials need to come from well-designed and -reported protocols addressing clinically relevant outcomes.