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性别、药物永久停药与临床试验中的研究保留率:来自 TIMI 试验的见解。

Sex, Permanent Drug Discontinuation, and Study Retention in Clinical Trials: Insights From the TIMI trials.

机构信息

Cardiology Division, Massachusetts General Hospital, Boston, MA (E.S.L.).

Harvard Medical School, Boston, MA (E.S.L., E.B., D.A.M., R.P.G., E.M.A., B.M.S., E.A.B., S.D.W., K.I., J.G., M.S.S., M.O.D., D.L.B., C.P.C.).

出版信息

Circulation. 2021 Feb 16;143(7):685-695. doi: 10.1161/CIRCULATIONAHA.120.052339. Epub 2021 Feb 15.

Abstract

BACKGROUND

Women are underrepresented across cardiovascular clinical trials. Whether women are more likely than men to prematurely discontinue study drug or withdraw consent once enrolled in a clinical trial is unknown.

METHODS

Eleven phase 3/4 TIMI (Thrombolysis in Myocardial Infarction) trials were included (135 879 men and 51 812 women [28%]). The association between sex and premature study drug discontinuation and withdrawal of consent were examined by multivariable logistic regression after adjusting for potential confounders in each individual trial and combining the individual point estimates in random effects models.

RESULTS

After adjusting for baseline differences, women had 22% higher odds of premature drug discontinuation (adjusted odds ratio [OR], 1.22 [95% CI, 1.16-1.28]; <0.001) compared with men. Qualitatively consistent results were observed for women versus men in the placebo arms (OR, 1.20 [95% CI, 1.13-1.27]) and active therapy arms (OR, 1.23 [95% CI, 1.17-1.30)]; there was some evidence for regional heterogeneity ( interaction <0.001). Of those who stopped study drug prematurely, a similar proportion of men and women in the active arm stopped because of an adverse event (36% for both; =0.60). Women were also more likely to withdraw consent compared with men (OR, 1.26 [95% CI, 1.17-1.36]; <0.001).

CONCLUSIONS

Women were more likely than men to prematurely discontinue study drug and withdraw consent across cardiovascular outcome trials. Premature study drug discontinuation was not explained by baseline differences by sex or a higher proportion of adverse events. Future trials should better capture reasons for drug discontinuation and withdrawal of consent to understand barriers to continued study drug use and clinical trial participation, particularly among women.

摘要

背景

女性在心血管临床试验中的代表性不足。女性是否比男性更有可能在开始服用研究药物后提前停药或退出临床试验,目前尚不清楚。

方法

纳入了 11 项 3/4 期 TIMI(心肌梗死溶栓)试验(135879 名男性和 51812 名女性[28%])。在每个单独的试验中调整潜在混杂因素后,通过多变量逻辑回归检查了性别与提前停药和退出同意之间的关联,并在随机效应模型中合并个体点估计值。

结果

在调整了基线差异后,女性提前停药的可能性比男性高 22%(调整后的优势比[OR],1.22[95%CI,1.16-1.28];<0.001)。在安慰剂组(OR,1.20[95%CI,1.13-1.27])和活性治疗组(OR,1.23[95%CI,1.17-1.30])中,女性与男性相比,结果基本一致;存在一定的区域异质性(交互作用<0.001)。在提前停止研究药物的患者中,活性药物组中提前停药的男性和女性比例相似,均因不良事件停药(分别为 36%;=0.60)。与男性相比,女性也更有可能退出同意(OR,1.26[95%CI,1.17-1.36];<0.001)。

结论

在心血管结局试验中,女性比男性更有可能提前停药和退出同意。提前停药不能用性别或更高比例的不良事件来解释。未来的试验应更好地记录停药和退出同意的原因,以了解继续使用研究药物和参与临床试验的障碍,尤其是在女性中。

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