Anthon Carl Thomas, Granholm Anders, Perner Anders, Laake Jon Henrik, Møller Morten Hylander
Department of Intensive Care 4131, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Centre for Research in Intensive Care (CRIC), Copenhagen, Denmark.
BMJ Open. 2017 Jul 11;7(7):e016187. doi: 10.1136/bmjopen-2017-016187.
Evidence exists that unblinded randomised clinical trials (RCTs) overestimate intervention effects compared with blinded RCTs. It has been suggested that this is less pronounced for objective (ie, not subject to interpretation) outcome measures, including mortality. This may not apply in the intensive care unit (ICU), as most deaths are preceded by decisions to withhold or withdraw treatments. Lack of blinding of physicians in RCTs of ICU interventions may potentially influence the decision towards a higher threshold for discontinuing treatment in patients who receive the investigational treatment and/or a lower threshold for discontinuing treatment in patients who receive the comparator (control). This may have important implications for patients, caregivers, researchers and society. Accordingly, we aim to assess whether lack of blinding affects mortality effect estimates in RCTs of ICU interventions.
We will conduct a systematic review with meta-analyses and assess the effect of blinding versus no blinding on mortality effect estimates in RCTs of interventions used in adult ICU patients.We will systematically search the Cochrane Library for systematic reviews reporting mortality effect estimates of any intervention used in adult ICU patients which includes at least one RCT with 'low risk of bias' in the bias domains 'blinding of participants and personnel' and/or 'blinding of outcome assessment' and one RCT with 'unclear' or 'high risk of bias' in the same bias domain(s). For each intervention, we will compare summary mortality effect estimates in blinded versus unblinded trials.
This research does not require ethical approval as we will use summary data from trials already approved by relevant ethical institutions. We will report the results in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and submit the final paper to an international peer-reviewed journal.
PROSPERO, registration number: CRD42017056212.
有证据表明，与盲法随机对照试验相比，非盲法随机对照试验（RCT）高估了干预效果。有人认为，对于包括死亡率在内的客观（即不受主观解释影响）结局指标，这种情况不太明显。这在重症监护病房（ICU）可能并不适用，因为大多数死亡之前都有关于停止或撤销治疗的决定。在ICU干预的RCT中，医生未设盲可能会潜在地影响对接受试验性治疗的患者做出更高的停止治疗阈值的决定，和/或对接受对照治疗的患者做出更低的停止治疗阈值的决定。这可能对患者、护理人员、研究人员和社会产生重要影响。因此，我们旨在评估未设盲是否会影响ICU干预RCT中的死亡率效应估计。
我们将进行一项系统评价并进行荟萃分析，评估设盲与未设盲对成人ICU患者使用的干预措施的RCT中死亡率效应估计的影响。我们将系统检索Cochrane图书馆，查找报告成人ICU患者使用的任何干预措施的死亡率效应估计的系统评价，其中包括至少一项在“参与者和人员的盲法”和/或“结局评估的盲法”偏倚领域具有“低偏倚风险”的RCT，以及至少一项在相同偏倚领域具有“不清楚”或“高偏倚风险”的RCT。对于每种干预措施，我们将比较设盲试验与未设盲试验中的汇总死亡率效应估计。
本研究不需要伦理批准，因为我们将使用已获相关伦理机构批准的试验的汇总数据。我们将根据系统评价和荟萃分析的首选报告项目（PRISMA）声明报告结果，并将最终论文提交给国际同行评审期刊。
PROSPERO，注册号：CRD42017056212。
