非注册与注册随机对照试验中药物的危害效应：临床试验的回顾性队列研究。

Harm effects in non-registered versus registered randomized controlled trials of medications: a retrospective cohort study of clinical trials.

机构信息

Proof of Concept Center, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital, Second Military Medical University, Naval Medical University, Shanghai, China.

UQ Center for Clinical Research, The University of Queensland, Herston, Australia.

出版信息

BMC Med. 2024 Oct 11;22(1):450. doi: 10.1186/s12916-024-03621-7.

DOI:10.1186/s12916-024-03621-7

PMID:39394146

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11470660/

Abstract

BACKGROUND

Trial registration aims to address potential bias from selective or non-reporting of findings, and therefore has a vital role in promoting transparency and accountability of clinical research. In this study, we aim to investigate the influence of trial registration on estimated harm effects in randomized controlled trials of medication interventions.

METHODS

We searched PubMed for systematic reviews and meta-analyses of randomized trials on medication harms indexed between January 1, 2015, and January 1, 2020. To be included in the analyses, eligible meta-analyses should have at least five randomized trials with distinct registration statuses (i.e., prospectively registered, retrospectively registered, and non-registered) and 2 by 2 table data for adverse events for each trial. To control for potential confounding, trials in each meta-analysis were analyzed within confounder-harmonized groups (e.g., dosage) identified using the Directed Acyclic Graph method. The harm estimates arising from the trials with different registration statuses were compared within the confounder-harmonized groups using hierarchical linear regression. Results are shown as ratio of odds ratio (OR) and 95% confidence interval (CI).

RESULTS

The dataset consists of 629 meta-analyses of harms with 10,069 trials. Of these trials, 74.3% were registered, and 23.9% were not registered, and for those registered, 70.6% were prospectively registered, while 26.3% were retrospectively registered. In comparison to prospectively registered trials, both non-registered trials (ratio of OR = 0.82, 95%CI 0.68 to 0.98, P = 0.03) and retrospectively registered trials (ratio of OR = 0.75, 95%CI 0.66 to 0.86, P < 0.01) had lower OR for harms based on 69 and 126 confounders-harmonized groups. The OR of harms did not differ between retrospectively registered and non-registered trials (ratio of OR = 1.02, 95%CI 0.85 to 1.23, P = 0.83) based on 76 confounders-harmonized groups.

CONCLUSIONS

Medication-related harms may be understated in non-registered trials, and there was no obvious evidence that retrospective registration had a demonstrable benefit in reducing such selective or absent reporting. Prospective registration is highly recommended for future trials.

摘要

背景

试验注册旨在解决选择性或不报告研究结果所带来的潜在偏倚，因此在提高临床研究的透明度和问责制方面具有重要作用。本研究旨在调查试验注册对药物干预随机对照试验中估计的危害效应的影响。

方法

我们在 PubMed 中检索了 2015 年 1 月 1 日至 2020 年 1 月 1 日期间索引的药物危害的系统评价和荟萃分析。纳入分析的合格荟萃分析应至少包含五项具有不同注册状态（即前瞻性注册、回顾性注册和未注册）的随机试验，以及每个试验的不良事件的 2×2 表格数据。为了控制潜在混杂因素，使用有向无环图方法识别混杂-危害一致组内的每个荟萃分析中的试验。使用分层线性回归比较混杂-危害一致组内来自不同注册状态的试验的危害估计值。结果表示为比值比（OR）和 95%置信区间（CI）。

结果

数据集包括 629 项危害的荟萃分析和 10069 项试验。这些试验中，74.3%进行了注册，23.9%未注册，而在已注册的试验中，70.6%是前瞻性注册，26.3%是回顾性注册。与前瞻性注册试验相比，非注册试验（OR 比值=0.82，95%CI 0.68 至 0.98，P=0.03）和回顾性注册试验（OR 比值=0.75，95%CI 0.66 至 0.86，P<0.01）的危害比值较低，这基于 69 和 126 个混杂-危害一致组。回顾性注册试验和非注册试验的危害比值没有差异（OR 比值=1.02，95%CI 0.85 至 1.23，P=0.83），这基于 76 个混杂-危害一致组。