重复经颅磁刺激改善阿尔茨海默病认知功能：一项随机对照试验中期分析方案

Repeated Transcranial Magnetic Stimulation for Improving Cognition in Alzheimer Disease: Protocol for an Interim Analysis of a Randomized Controlled Trial.

作者信息

Moussavi Zahra, Koski Lisa, Fitzgerald Paul B, Millikin Colleen, Lithgow Brian, Jafari-Jozani Mohammad, Wang Xikui

机构信息

Biomedical Engineering Program, Faculty of Engineering, University of Manitoba, Winnipeg, MB, Canada.

Department of Psychiatry, University of Manitoba, Winnipeg, MB, Canada.

出版信息

JMIR Res Protoc. 2021 Aug 9;10(8):e31183. doi: 10.2196/31183.

DOI:10.2196/31183

PMID:34383681

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8386362/

Abstract

BACKGROUND

Many clinical trials investigating treatment efficacy require an interim analysis. Recently we have been running a large, multisite, randomized, placebo-controlled, double-blind clinical trial investigating the effect of repetitive transcranial magnetic stimulation (rTMS) treatment for improving or stabilizing the cognition of patients diagnosed with Alzheimer disease.

OBJECTIVE

The objectives of this paper are to report on recruitment, adherence, and adverse events (AEs) to date, and to describe in detail the protocol for interim analysis of the clinical trial data. The protocol will investigate whether the trial is likely to reach its objectives if continued to the planned maximum sample size.

METHODS

The specific requirements of the analytic protocol are to (1) ensure the double-blind nature of the data while doing the analysis, (2) estimate the predictive probabilities of success (PPoSs), (3) estimate the numbers needed to treat, (4) re-estimate the initial required sample size. The initial estimate of sample size was 208. The interim analysis will be based on 150 patients who will be enrolled in the study and finish at least 8 weeks of the study. Our protocol for interim analysis, at the very first stage, is to determine the response rate for each participant to the treatment (either sham or active), while ensuring the double-blind nature of the data. The blinded data will be analyzed by a statistician to investigate the treatment efficacy. We will use Bayesian PPoS to predict the success rate and determine whether the study should continue.

RESULTS

The enrollment has been slowed significantly due to the COVID-19 pandemic and lockdown. Nevertheless, so far 133 participants have been enrolled, while 22 of these have been withdrawn or dropped out for various reasons. In general, rTMS has been found tolerable with no serious AE. Only 2 patients dropped out of the study due to their intolerability to rTMS pulses.

CONCLUSIONS

Overall, the study with the same protocol is going as expected with no serious AE or any major protocol deviation.

TRIAL REGISTRATION

ClinicalTrials.gov NCT02908815; https://clinicaltrials.gov/ct2/show/NCT02908815.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31183.

摘要

背景

许多研究治疗效果的临床试验都需要进行中期分析。最近，我们正在开展一项大型、多中心、随机、安慰剂对照、双盲临床试验，以研究重复经颅磁刺激（rTMS）治疗对改善或稳定被诊断为阿尔茨海默病患者认知功能的效果。

目的

本文的目的是报告迄今为止的招募情况、依从性和不良事件（AE），并详细描述临床试验数据中期分析的方案。该方案将研究如果继续进行到计划的最大样本量，试验是否有可能实现其目标。

方法

分析方案的具体要求是：（1）在进行分析时确保数据的双盲性质；（2）估计成功的预测概率（PPoS）；（3）估计所需治疗人数；（4）重新估计初始所需样本量。样本量的初始估计为208例。中期分析将基于150名已纳入研究并完成至少8周研究的患者。我们的中期分析方案在第一阶段是确定每个参与者对治疗（假治疗或活性治疗）的反应率，同时确保数据的双盲性质。由统计学家对盲态数据进行分析以研究治疗效果。我们将使用贝叶斯PPoS来预测成功率并确定研究是否应继续进行。