Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

INTRODUCTION: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. METHODS AND ANALYSIS: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare. ETHICS AND DISSEMINATION: The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

Introduction: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INSPECT-SR project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare related interventions. Methods and analysis: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: 1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, 2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, 3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in 4) a consensus meeting to select checks to be included in a draft tool and to determine its format, 5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies, and will help patients by protecting them from the influence of false data on their healthcare.

Plausibility of Claimed Covid-19 Vaccine Efficacies by Age: A Simulation Study.

BACKGROUND: Multiple vaccines against Covid-19 have passed through phase-3 trials; however, concerns have been raised about alleged excessive similarity of efficacy across age groups for the Sputnik V vaccine. STUDY QUESTION: How likely are the observed efficacies for all age subgroups to fall within the range of by-age efficacies claimed for the AstraZeneca, Janssen, Moderna, Pfizer, and Sputnik V vaccines, assuming that there is no effect of age on efficacy? STUDY DESIGN: We performed a simulation study using R of 1000 and then 50,000 simulated trials for each vaccine, with random allocation to each arm but fixed enrollment numbers by age group. We used study-wide efficacy and infection rate for all age groups. We recorded the observed vaccine efficacies in each age group and summated how many simulations had all observed efficacies fall within the range of efficacies described in the relevant article. RESULTS: In the 1000-trial simulation for the AstraZeneca vaccine, in 23.8% of simulated trials, the observed efficacies of all age subgroups fell within the efficacy bounds for age subgroups in the published article. The J + J simulation showed 44.7%, Moderna 51.1%, Pfizer 30.5%, and 0.0% of the Sputnik simulated trials had all age subgroups fall within the limits of the efficacy estimates described by the published article. In 50,000 simulated trials of the Sputnik vaccine, 0.026% had all age subgroups fall within the limits of the efficacy estimates described by the published article, whereas 99.974% did not. CONCLUSIONS: The distribution of alleged vaccine efficacies of the Sputnik vaccine by age in the phase-III trial is very unlikely to occur in genuine experimental data, even if the number of patients recruited, vaccine efficacy, and overall infection rate are true and there is no underlying difference in vaccine efficacy by age.