Division of Infectious Diseases, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Division of Medial Microbiology, McMaster University, Hamilton, Ontario, Canada.
Clin Infect Dis. 2021 Oct 5;73(7):e1696-e1705. doi: 10.1093/cid/ciaa1353.
Antibiotic noninferiority randomized controlled trials (RCTs) are used for approval of new antibiotics and making changes to antibiotic prescribing in clinical practice. We conducted a systematic review to assess the methodological and reporting quality of antibiotic noninferiority RCTs.
We searched MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and the Food and Drug Administration drug database from inception until November 22, 2019, for noninferiority RCTs comparing different systemic antibiotic therapies. Comparisons between antibiotic types, doses, administration routes, or durations were included. Methodological and reporting quality indicators were based on the Consolidated Standards of Reporting Trials reporting guidelines. Two independent reviewers extracted the data.
The systematic review included 227 studies. Of these, 135 (59.5%) studies were supported by pharmaceutical industry. Only 83 (36.6%) studies provided a justification for the noninferiority margin. Reporting of both intention-to-treat (ITT) and per-protocol (PP) analyses were done in 165 (72.7%) studies. The conclusion was misleading in 34 (15.0%) studies. The studies funded by pharmaceutical industry were less likely to be stopped early because of logistical reasons (3.0% vs 19.1%; odds ratio [OR] = 0.13; 95% confidence interval [CI], .04-.37) and to show inconclusive results (11.1% vs 42.9%; OR = 0.17; 95% CI, .08-.33). The quality of studies decreased over time with respect to blinding, early stopping, reporting of ITT with PP analysis, and having misleading conclusions.
There is room for improvement in the methodology and reporting of antibiotic noninferiority trials. Quality can be improved across the entire spectrum from investigators, funding agencies, as well as during the peer-review process.There is room for improvement in the methodology and reporting of antibiotic noninferiority trials including justification of noninferiority margin, reporting of intention-to-treat analysis with per-protocol analysis, and having conclusions that are concordant with study results.Clinical Trials Registration PROSPERO registration number CRD42020165040.
抗生素非劣效性随机对照试验（RCT）用于批准新抗生素，并在临床实践中改变抗生素的使用。我们进行了一项系统评价，以评估抗生素非劣效性 RCT 的方法学和报告质量。
我们从 MEDLINE、Embase、Cochrane 系统评价数据库和美国食品和药物管理局药物数据库中检索了从成立到 2019 年 11 月 22 日的比较不同全身抗生素治疗的非劣效性 RCT。包括抗生素类型、剂量、给药途径或持续时间的比较。方法学和报告质量指标基于临床试验报告统一标准。两名独立的评审员提取数据。
系统评价共纳入 227 项研究。其中，135 项（59.5%）研究得到了制药行业的支持。只有 83 项（36.6%）研究为非劣效性边界提供了依据。165 项（72.7%）研究同时报告了意向治疗（ITT）和符合方案（PP）分析。34 项（15.0%）研究的结论具有误导性。制药行业资助的研究因后勤原因提前停止的可能性较小（3.0%对 19.1%；比值比[OR] 0.13；95%置信区间[CI] 0.04-0.37），且结果不确定的可能性较小（11.1%对 42.9%；OR 0.17；95% CI 0.08-0.33）。随着时间的推移，研究的质量在盲法、提前停止、同时报告 ITT 和 PP 分析以及具有误导性的结论方面有所下降。
抗生素非劣效性试验的方法学和报告需要改进。质量可以从研究者、资助机构以及同行评审过程等各个方面得到提高。抗生素非劣效性试验的方法学和报告需要改进，包括非劣效性边界的合理性、同时报告 ITT 分析与 PP 分析以及与研究结果一致的结论。临床试验注册 PROSPERO 注册号 CRD42020165040。
