Background/Aim

In clinical trials, there is potential for bias from unblinded observers that may influence ascertainment of outcomes. This issue arose in the Strategies to Reduce Injuries and Develop Confidence in Elders trial, a cluster randomized trial to test a multicomponent intervention versus enhanced usual care (control) to prevent serious fall injuries, originally defined as a fall injury leading to medical attention. An unblinded nurse falls care manager administered the intervention, while the usual care arm did not involve contact with a falls care manager. Thus, there was an opportunity for falls care managers to refer participants reporting falls to seek medical attention. Since this type of observer bias could not occur in the usual care arm, there was potential for additional falls to be reported in the intervention arm, leading to dilution of the intervention effect and a reduction in study power. We describe the clinical basis for ascertainment bias, the statistical approach used to assess it, and its effect on study power.

Methods

The prespecified interim monitoring plan included a decision algorithm for assessing ascertainment bias and adapting (revising) the primary outcome definition, if necessary. The original definition categorized serious fall injuries requiring medical attention into Type 1 (fracture other than thoracic/lumbar vertebral, joint dislocation, cut requiring closure) and Type 2 (head injury, sprain or strain, bruising or swelling, other). The revised definition, proposed by the monitoring plan, excluded Type 2 injuries that did not necessarily require an overnight hospitalization since these would be most subject to bias. These injuries were categorized into those with (Type 2b) and without (Type 2c) medical attention. The remaining Type 2a injuries required medical attention and an overnight hospitalization. We used the ratio of 2b/(2b + 2c) in intervention versus control as a measure of ascertainment bias; ratios > 1 indicated the likelihood of falls care manager bias. We determined the effect of ascertainment bias on study power for the revised (Types 1 and 2a) versus original definition (Types 1, 2a, and 2b).

Results

The estimate of ascertainment bias was 1.14 (95% confidence interval: 0.98, 1.30), providing evidence of the likelihood of falls care manager bias. We estimated that this bias diluted the hazard ratio from the hypothesized 0.80 to 0.86 and reduced power to under 80% for the original primary outcome definition. In contrast, adapting the revised definition maintained study power at nearly 90%.

Conclusion

There was evidence of ascertainment bias in the Strategies to Reduce Injuries and Develop Confidence in Elders trial. The decision to adapt the primary outcome definition reduced the likelihood of this bias while preserving the intervention effect and study power.

中文翻译：

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减少老年人伤害和培养对老年人的信心的策略 (STRIDE) 试验中主要结果的确定偏倚的案例研究

背景/目标

在临床试验中，不设盲的观察者可能会产生偏差，这可能会影响结果的确定。这个问题出现在“减少老年人受伤和培养对老年人的信心的策略”试验中，这是一项整群随机试验，用于测试多组分干预与加强常规护理（控制）以防止严重跌倒伤害，最初定义为导致医疗救治的跌倒伤害。一名不设盲的护士跌倒护理经理实施了干预，而常规护理组不涉及与跌倒护理经理的接触。因此，跌倒护理经理有机会转介报告跌倒的参与者寻求医疗救助。由于这种类型的观察者偏差不会发生在常规护理组中，因此干预组可能会报告额外的跌倒，导致干预效果的稀释和研究功效的降低。我们描述了确定偏倚的临床基础、用于评估偏倚的统计方法及其对研究功效的影响。

方法

预先指定的中期监测计划包括一个决策算法，用于评估确定偏倚和在必要时调整（修订）主要结果定义。最初的定义将需要就医的严重跌倒伤分为第一类（胸/腰椎以外的骨折、关节脱位、需要缝合的割伤）和第二类（头部受伤、扭伤或拉伤、瘀伤或肿胀、其他）。监测计划提出的修订定义排除了不一定需要住院过夜的 2 型损伤，因为这些损伤最容易产生偏差。这些伤害分为接受（2b 类）和未接受（2c 类）医疗护理的伤害。其余的 2a 型伤害需要就医和住院过夜。我们使用干预与对照中的 2b/(2b + 2c) 比率作为确定偏差的量度；比率 > 1 表示跌倒护理经理偏差的可能性。我们确定了确定偏倚对修订版（类型 1 和 2a）与原始定义（类型 1、2a 和 2b）的研究功效的影响。

结果

确定偏差的估计值为 1.14（95% 置信区间：0.98，1.30），提供了跌倒护理经理偏差可能性的证据。我们估计，这种偏差将风险比从假设的 0.80 稀释到 0.86，并将原始主要结果定义的功效降低到 80% 以下。相比之下，采用修订后的定义将研究力保持在近 90%。

结论

有证据表明在“减少老年人伤害和培养对老年人的信心的策略”试验中存在确定性偏差。调整主要结果定义的决定降低了这种偏倚的可能性，同时保留了干预效果和研究能力。