非盲法和盲法 N-of-1 试验与常规护理比较：一项旨在提高初级保健中他汀类药物使用率的随机对照试验。

Unblinded and Blinded N-of-1 Trials Versus Usual Care: A Randomized Controlled Trial to Increase Statin Uptake in Primary Care.

机构信息

Nuffield Department of Primary Care Health Sciences (K.T., J.B., P.A.), University of Oxford, Radcliffe Observatory Quarter, United Kingdom.

Department of Psychiatry, University of Oxford, Warneford Hospital, United Kingdom (K.T.).

出版信息

Circ Cardiovasc Qual Outcomes. 2022 Jun;15(6):e007793. doi: 10.1161/CIRCOUTCOMES.120.007793. Epub 2022 Jun 14.

DOI:10.1161/CIRCOUTCOMES.120.007793

PMID:35698974

Abstract

BACKGROUND

The aim was to assess whether an intervention incorporating a practicable open-label n-of-1 trial would lead to greater uptake of statin than usual care and comparable uptake to a closed-label gold-standard n-of-1 trial.

METHODS

We enrolled patients who had stopped or declined statins into a 3-arm trial (usual care, unblinded, and blinded n-of-1 intervention arms). Physicians advised participants randomized to usual care to take statin therapy to prevent cardiovascular disease. In both intervention arms, physicians delivered a theoretically informed informed intervention endorsing the value of experimenting with medication in n-of-1 trials to assess whether it caused side-effects. In these trials, participants alternated between 4 weeks of medication and no medication (unblinded arm) or randomly sorted active and placebo (blinded arm) and recorded symptoms and symptom attributions for 6 months. Thereafter, physicians discussed participants' symptom reports during active/inactive treatment periods and asked participants to resume statins if appropriate.

RESULTS

Seventy-three were randomized to the intervention arms and 20 to the control group. Fifty-six of 73 (77%) attempted the n-of-1 experiment; 28/36 (78%) in the unblinded arm; and 28/37 (76%) in the blinded arm. Forty-three of 56 (77%) completed the 6-month experiment and received feedback from the physician; 20/28 (71%) in the unblinded arm and 23/28 (82%) in the blinded arm. Thirty-three of 76 (45%) people restarted statins in the n-of-1 arms compared with 4/20 (20%) in the control arm, difference 24% (95% CI, 5%-43%; =0.041). There was no evidence this differed between blinded and unblinded arms, difference 2% (95% CI, -20% to 24%; =0.86). Adverse events occurred at a similar rate on and off statin.

CONCLUSIONS

In patients refusing or intolerant of statin, supporting experimentation with n-of-1 trials increases medication uptake compared with usual care. Alternating on-off medication in unblinded n-of-1 experiments appears as effective as a blinded experiment.

REGISTRATION

URL: https://doi.org/10.1186/ISRCTN11142694; Unique identifier: ISRCTN11142694.

摘要

背景

本研究旨在评估一种纳入可行的开放性自身对照 n-of-1 试验的干预措施是否会比常规护理更能增加他汀类药物的使用率，并与封闭性金标准 n-of-1 试验的使用率相当。

方法

我们招募了已停止或拒绝使用他汀类药物的患者，将其纳入一项 3 臂试验（常规护理、非盲和盲法 n-of-1 干预组）。医生建议随机分配至常规护理组的患者服用他汀类药物以预防心血管疾病。在两个干预组中，医生提供了一种基于理论的干预措施，支持在 n-of-1 试验中进行药物试验以评估其是否会引起副作用。在这些试验中，参与者交替服用 4 周药物和无药物治疗（非盲组）或随机分配活性药物和安慰剂（盲法组），并记录 6 个月的症状和症状归因。之后，医生根据参与者在用药/停药期间的症状报告进行讨论，并在适当的情况下要求患者恢复他汀类药物治疗。

结果

73 名患者被随机分配至干预组，20 名患者被分配至对照组。73 名患者中，56 名（77%）尝试了 n-of-1 试验；非盲组 28/36（78%）；盲法组 28/37（76%）。56 名患者中有 43 名（77%）完成了 6 个月的试验并收到了医生的反馈；非盲组 20/28（71%），盲法组 23/28（82%）。与对照组 4/20（20%）相比，n-of-1 组中有 33 名（45%）患者重新开始服用他汀类药物，差异为 24%（95%CI，5%-43%；=0.041）。盲法组和非盲法组之间没有证据表明存在差异，差异为 2%（95%CI，-20%至 24%；=0.86）。他汀类药物治疗期间和停药期间的不良事件发生率相似。