ORISE Fellow, Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
Office of Biostatistics, Center for Drug Evaluation and Research, Silver Spring, MD, USA.
Value Health. 2021 Jun;24(6):822-829. doi: 10.1016/j.jval.2020.12.015. Epub 2021 Mar 18.
Unblinded trials are common in oncology, but patient knowledge of treatment assignment may bias response to questionnaires. We sought to ascertain the extent of possible bias arising from patient knowledge of treatment assignment.
This is a retrospective analysis of data from 2 randomized trials in multiple myeloma, 1 double-blind and 1 open label. We compared changes in patient reports of symptoms, function, and health status from prerandomization (screening) to baseline (pretreatment but postrandomization) across control and investigational arms in the 2 trials. Changes from prerandomization scores at ~2 and 6 months on treatment were evaluated only across control arms to avoid comparisons between 2 different experimental drugs. All scores were on 0- to 100-point scales. Inverse probability weighting, entropy balancing, and multiple imputation using propensity score splines were used to compare score changes across similar groups of patients.
Minimal changes from screening were seen at baseline in all arms. In the control arm, mean changes of <7 points were seen for all domains at 2 and 6 months. The effect of unblinding at 6 months in social function was a decline of less than 6 points (weighting: -3.09; 95% confidence interval -8.41 to 2.23; balancing: -4.55; 95% confidence interval -9.86 to 0.76; imputation: -5.34; 95% confidence interval -10.64 to -0.04).
In this analysis, we did not find evidence to suggest that there was a meaningful differential effect on how patients reported their symptoms, function or health status after knowing their treatment assignment.
肿瘤学中常采用开放性试验，但患者对治疗分组的了解可能会影响对问卷的应答。我们旨在确定患者对治疗分组了解所导致的偏倚程度。
这是对 2 项多发性骨髓瘤随机试验数据的回顾性分析，其中 1 项为双盲试验，1 项为开放性试验。我们比较了 2 项试验中对照臂和试验臂中患者在随机分组前（筛查）至基线（治疗前但随机分组后）时报告的症状、功能和健康状况的变化。仅在对照臂中评估治疗 2 个月和 6 个月时与随机分组前评分的变化，以避免比较 2 种不同的试验药物。所有评分均采用 0-100 分制。采用逆概率加权、熵平衡和倾向评分样条的多重插补法来比较相似患者组的评分变化。
在所有组中，基线时所有组的筛查后评分变化均较小。在对照臂中，在 2 个月和 6 个月时，所有领域的评分变化均小于 7 分。6 个月时社会功能的未盲效应为下降小于 6 分（加权：-3.09；95%置信区间-8.41 至 2.23；平衡：-4.55；95%置信区间-9.86 至 0.76；插补：-5.34；95%置信区间-10.64 至-0.04）。
在本分析中，我们没有发现证据表明，患者在了解治疗分组后报告其症状、功能或健康状况的方式存在有意义的差异效应。
