Department of Biomedical Sciences, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA.
Department of Psychiatry and Behavioral Sciences, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA.
J Gen Intern Med. 2019 Jul;34(7):1236-1243. doi: 10.1007/s11606-019-04928-5. Epub 2019 Apr 29.
HIV/AIDS is associated with significant morbidity, mortality, and financial burden. For these reasons, robust clinical evidence is critical. We aim to investigate the fragility index, fragility quotient, and risk of bias of clinical trial endpoints in HIV medicine. The fragility index represents the minimum amount of trial endpoint "nonevents" changed to "events" in one trial arm required to nullify statistical significance. The fragility quotient contextualized the fragility index by dividing the index by the total trial sample size. We selected eligible trials from the Department of Health and Human Services guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents. We calculated the fragility index and fragility quotient for all included trials. The Cochrane "risk of bias" Tool 2.0 was used to evaluate the likelihood and sources of bias in the included trials. Thirty-nine RCTs were included for our analysis of fragility. Thirty-six were included for our analysis of the risk of bias. The median fragility index was 5. Three RCTs were at high risk of bias, all due to the selection of the endpoint or statistical test. Twenty had some concerns for risk of bias. The analyzed HIV medicine RCT endpoints were fragile, overall. This indicates that a median of 5 patients across all included studies would nullify the statistical significance of the endpoints. Furthermore, we found evidence that concerns for bias are present at a high rate.
艾滋病毒/艾滋病与重大发病率、死亡率和经济负担有关。出于这些原因，强有力的临床证据至关重要。我们旨在调查艾滋病毒医学临床试验终点的脆弱性指数、脆弱性商数和偏倚风险。脆弱性指数表示在一个试验臂中，需要改变多少个试验终点的“无事件”为“事件”，才能使统计意义无效。脆弱性商数通过将指数除以总试验样本量来对脆弱性指数进行背景化处理。我们从卫生与公众服务部关于在感染 HIV-1 的成人和青少年中使用抗逆转录病毒药物的指南中选择了合格的试验。我们计算了所有纳入试验的脆弱性指数和脆弱性商数。使用 Cochrane“偏倚风险”工具 2.0 评估纳入试验中偏倚的可能性和来源。我们对 39 项 RCT 进行了脆弱性分析。我们对 36 项 RCT 进行了偏倚风险分析。中位数脆弱性指数为 5。有 3 项 RCT 存在高偏倚风险，均归因于终点或统计检验的选择。有 20 项存在偏倚风险的担忧。分析的艾滋病毒医学 RCT 终点总体上是脆弱的。这表明，在所有纳入的研究中，中位数为 5 名患者将使终点的统计意义无效。此外，我们发现存在高偏倚风险的证据。
