以健康受试者为对象的药物临床试验筛选失败原因及风险因素探讨

Causes and Risk Factors for Screening Failure in Drug Clinical Trials Targeting Healthy Subjects

目的探讨以健康受试者为对象的药物临床试验筛选失败原因及风险因素。方法收集医院药物临床试验机构2018年1月至2021年12月开展的以健康受试者为对象的临床试验中筛选的受试者信息,描述筛选失败原因,通过单因素分析比较不同人口学特点和试验特点对筛选结果的影响,通过Logistics回归分析筛选失败的风险因素。结果共纳入899名健康受试者,筛选失败491名(54.62%);筛选失败514例次,筛选失败原因以实验室检查(28.02%)为首,其次为个人史(18.29%)、体格检查(16.54%)、辅助检查(16.34%)、撤回知情同意(10.89%)。单因素分析结果显示,年龄19~42岁受试者中年龄较大者筛选失败率更高(χ^(2)=11.549,P=0.003),男性筛选失败率高于女性(χ^(2)=15.467,P=0.000),采血点数量≤18个的试验筛选失败率高于采血点数量>18个的试验(χ^(2)=6.729,P=0.009)。Logistic回归分析结果表明,年龄增长[OR=1.036,95%CI(1.007,1.066),P=0.016],男性[OR=1.783,95%CI(1.332,2.388),P=0.000],较少的采血点数量[OR=0.925,95%CI(0.868,1.986),P=0.017]可能是筛选失败的风险因素。结论人口学和试验特点对筛选结果存在影响,建议优化招募环节、充分知情,以降低筛选失败率,提升以健康受试者为对象的药物临床试验质量。

Objective To investigate the causes and risk factors for screening failure in drug clinical trials targeting healthy subjects.Methods The information was collected and analyzed from the volunteers screened in the clinical trials targeting healthy subjects conducted by the Good Clinical Practice(GCP)Institution of the hospital from January 2018 to December 2021.The causes for screening failure were described and the effects of different demographic characteristics and trial characteristics on screening results were compared through the univariate factor analysis,and the risk factors of screening failure were screened through the Logistic regression analysis.Results A total of 899 healthy subjects were included,and 491 subjects(54.62%)failed to screen.Among the 514 failed screening cases,the main cause for screening failure was laboratory examination(28.02%),followed by individual history(18.29%),physical examination(16.54%),auxiliary examination(16.34%),and withdrawal of informed consent(10.89%).Univariate analysis results showed that the screening failure rate was higher in the elderly among subjects aged 19-42 years old(χ^(2)=11.549,P=0.003),the screening failure rate was higher in males than that in females(χ^(2)=15.467,P=0.000),and the screening failure rate of the test with fewer than or equal to 18 blood collection frequencies was higher than that of the test with more than 18 blood collection frequencies(χ^(2)=6.729,P=0.009).Logistic regression analysis results showed that age growth[OR=1.036,95%CI(1.007,1.066),P=0.016],males[OR=1.783,95%CI(1.332,2.388),P=0.000],and fewer blood sample collection frequencies[OR=0.925,95%CI(0.868,1.986),P=0.017]might be risk factors for screening failure.Conclusion Demography and trial characteristics have an impact on the screening results.It is suggested to optimize the recruitment process and strengthen informed communication to reduce the screening failure rate and improve the quality of drug clinical trials targeting healthy subjects.