Checklist for clinical applicability of subgroup analysis

Abstract

What is known and objective: Subgroup analysis plays an important role in clinical decision-making. Correct management of subgroup analysis is necessary to optimize effectiveness, safety and efficiency of treatments. No homogeneous criteria have been developed for interpretation of subgroup analysis. In this study, the researcher develops a checklist to evaluate the reliability and applicability of the results of subset analyses. Methods: With a review of previous literature, three main criteria were included in the checklist: statistical association, biological plausibility and consistency among studies. Statistical association considered interaction probability, prespecification of analysis, number of subgroups analysed, sample size and positive/negative result in global analysis. Each item was given an indicative score. Total score was related to a level of applicability for the results in clinical practice. Checklist validation included interinvestigator concordance and assessment about utility. Three drug examples were used to validate the tool.Results and discussion: Twenty-six evaluators showed adequate interinvestigator concordance (kappa 0.79, 1 and 0.83 for each drug example regarding applicability). Kappa values increased to 0.94, 1 and 1 after group discussion. Checklist utility score was greater than 4.7/5 in three drug examples. In pre-analysis, inter-researcher agreement on global applicability recommendation of subgroup results to practice was 92.3% (ramucirumab), 96% (nivolumab) and 100% (mepolizumab). In post-analysis, inter-researcher agreement on applicability recommendation of subgroup results was 100%, 94.45% and 100%, respectively. The checklist validation shows a high interindividual agreement of the results, both with respect to the evaluation of the applicability of subgroup analysis and concerning clinical decision-making. What is new and conclusion:We have developed the first validated tool for interpretation of subgroup analyses. The checklist contributes to the adoption of homogeneous criteria for subgroup analyses, thereby allowing discussion and evaluation of the effects of a health intervention. K E Y W O R D S checklist, clinical decision-making, data interpretation, drug evaluation, statistical, subgroup analysis, validation studies | 531 GIL-SIERRA Et AL. How to cite this article: Gil-Sierra MD, Fénix-Caballero S, Abdel kader-Martin L, et al. Checklist for clinical applicability of subgroup analysis. J Clin Pharm Ther. 2020;45:530-538.

Subgroup analysis in haematologic malignancies phase III clinical trials: A systematic review

“…As a result of important methodological problems bias, subgroup interpretation can lead to erroneous conclusions, producing wrongful clinical decision making. Several tools have been developed to assess the credibility of the effects of the subgroups reported in clinical trials 12–17 . In our study we used the 10 criteria to assess the credibility of subgroup claims by Sun et al 17 The credibility of subgroup claims in phase III haematology RCTs was low.…”

“…Concerns about the correct interpretation of subgroup analysis have increased recently. With the intention of reducing the problems related to subgroup analysis misinterpretation, several tools have been developed to assess the credibility of the effects of subgroups reported in RCTs 12–17 . The 10 criteria for assessing the credibility of a subgroup claim by Sun et al 17 is one of the most comprehensive tools for evaluating the credibility of subgroup analysis.…”

2SPD-032 Network meta-analysis of therapeutic alternatives in untreated metastatic squamous non-small cell lung cancer

“…1 The second methodology was a validated tool made up of preliminary questions to discard subgroup analyses without minimal relevance and a checklist. 2 This checklist provided recommendations of applicability for subgroup results. Results There were 31 results in the search and the following were excluded: 9 were not RCTs, 13 did not evaluate the effect of docetaxel, 4 had no subset analysis for VMD and 1 did not assess OS.…”

“…1 The second methodology was a two part validated tool: preliminary questions to discard subgroup analyses without minimal relevance, and a checklist. 2 The checklist assigned a recommendation for applicability of subset analysis in clinical practice. Results A total of 25 results were found in the search and the following were excluded: 10 were not RCTs, 9 studies had a different clinical context, 2 evaluated different drugs and 1 had no subset analysis.…”

2SPD-030 Positioning of doravirine in the pharmacotherapeutic guide of a third level hospital

“…1 The second methodology was a validated tool with preliminary questions to discard subset analysis without minimal relevance, and a checklist. 2 This checklist assigned a score related to a recommendation for applicability of subgroup analysis in clinical practice. Results 20 results were found after review; 16 studies were excluded because they were not RCTs and 1 study had no efficacy evaluation of remdesivir.…”