Exploring study dropout in drug trials for adults with PTSD: insights from a conventional and individual participant data meta-analysis

Background: Dropout rates and factors contributing to dropout in drug and placebo groups in pharmacotherapy trials for posttraumatic stress disorder (PTSD) are not well understood.
Objective: This study aimed to examine differences in all-cause study dropouts between drug and placebo groups, using conventional meta-analysis and an exploratory predictor analysis of individual participant data from three trials.
Method: We included randomized controlled trials (RCTs) of adults with PTSD, comparing drug monotherapy with placebo. Forty-three RCTs (n = 4829) were included in a conventional meta-analysis. Additionally, we conducted a small exploratory predictor analysis including participant-level data from three RCTs (n = 246).
Results: In the conventional meta-analysis, study dropout was marginally lower in the drug relative to the placebo group, but the difference was not significant, RR = 0.92, 95% CI [0.83, 1.02], p = .099. Drug class, dosing regimen, population, study duration, or gender were not related to dropout.
In the exploratory predictor analysis, study dropout did not differ significantly between drug and placebo groups (p = .617). In the drug group, gender was a significant predictor for dropout, with males having higher dropout rates (p = .046). When controlling for baseline PTSD symptom severity, gender was no longer a statistically significant predictor (p = .051). None of the other predictors in drug, placebo, and combined group analyses were significant in predicting drop-out.
Conclusions: This study demonstrated that study dropout rates in monotherapy pharmacotherapy RCTs for PTSD do not significantly differ between drug and placebo groups. These findings underscore the need for further research to identify the factors contributing to dropout in PTSD pharmacotherapy trials and to develop tailored treatment adherence strategies. Additionally, they highlight the importance of pooling participant-level data to facilitate more comprehensive and granular analyses in future research.

This study found no significant differences in dropout rates between drug and placebo groups in PTSD pharmacotherapy trials, with an overall high dropout rate of 28%, highlighting a major challenge in these trials.
Initial analyses indicated that males were at a higher risk of dropping out of drug treatment compared with females, though this effect was not significant after controlling for PTSD severity. This suggests a complex interaction between gender, PTSD severity, and dropout rates.
The study underscores the importance of standardized protocols for reporting reasons for discontinuation in clinical trials to identify precise predictors of dropout and improve the reliability and comparability of research findings.

This study found no significant differences in dropout rates between drug and placebo groups in PTSD pharmacotherapy trials, with an overall high dropout rate of 28%, highlighting a major challenge in these trials.
Initial analyses indicated that males were at a higher risk of dropping out of drug treatment compared with females, though this effect was not significant after controlling for PTSD severity. This suggests a complex interaction between gender, PTSD severity, and dropout rates.
The study underscores the importance of standardized protocols for reporting reasons for discontinuation in clinical trials to identify precise predictors of dropout and improve the reliability and comparability of research findings.

研究背景：目前对于创伤后应激障碍（Posttraumatic Stress Disorder, PTSD）药物治疗试验中，药物组与安慰剂组的脱落率及脱落相关影响因素尚不明确。
研究目的：本研究旨在通过传统元分析，结合三项试验的个体参与者数据探索性预测分析，对比药物组与安慰剂组的全因研究脱落率差异。
研究方法：本研究纳入对比药物单一疗法与安慰剂的成人创伤后应激障碍随机对照试验（Randomized Controlled Trial, RCTs）。其中43项随机对照试验（总样本量n=4829）被纳入传统元分析；此外，我们针对3项随机对照试验的个体参与者数据（总样本量n=246）开展了小型探索性预测分析。
研究结果：传统元分析结果显示，药物组的研究脱落率略低于安慰剂组，但该差异无统计学意义（相对危险度RR=0.92，95%置信区间CI[0.83, 1.02]，p=0.099）。药物类别、给药方案、研究人群、试验时长及性别均与脱落率无显著关联。
探索性预测分析结果显示，药物组与安慰剂组的研究脱落率无显著差异（p=0.617）。在药物组中，性别是脱落率的显著预测因素，男性脱落率更高（p=0.046）；但在控制基线创伤后应激障碍症状严重程度后，性别不再是具有统计学意义的预测因素（p=0.051）。药物组、安慰剂组及合并组分析中的其余预测因素均未对脱落率产生显著预测作用。
研究结论：本研究证实，创伤后应激障碍单一药物疗法随机对照试验中，药物组与安慰剂组的脱落率无显著差异。本研究结果提示，未来需开展进一步研究以明确创伤后应激障碍药物治疗试验中脱落的相关影响因素，并制定个体化的治疗依从性策略；同时，本研究也凸显了整合个体参与者数据的重要性，以便在未来研究中开展更全面、更精细的分析。

本研究发现，创伤后应激障碍药物治疗试验中，药物组与安慰剂组的脱落率无显著差异，整体脱落率高达28%，这凸显了此类试验面临的一项重大挑战。
初步分析结果显示，与女性相比，男性脱落药物治疗的风险更高，但在控制创伤后应激障碍症状严重程度后，该效应不再具有统计学意义。这提示性别、创伤后应激障碍症状严重程度与脱落率之间存在复杂的交互作用。
本研究强调，临床试验需建立标准化的脱落原因报告规范，以便精准识别脱落的预测因素，提升研究结果的可靠性与可比性。

本研究发现，创伤后应激障碍药物治疗试验中，药物组与安慰剂组的脱落率无显著差异，整体脱落率高达28%，这凸显了此类试验面临的一项重大挑战。
初步分析结果显示，与女性相比，男性脱落药物治疗的风险更高，但在控制创伤后应激障碍症状严重程度后，该效应不再具有统计学意义。这提示性别、创伤后应激障碍症状严重程度与脱落率之间存在复杂的交互作用。
本研究强调，临床试验需建立标准化的脱落原因报告规范，以便精准识别脱落的预测因素，提升研究结果的可靠性与可比性。