Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
Centre for Perinatal Neuroscience, Imperial College London, London, United Kingdom.
PLoS One. 2021 Mar 9;16(3):e0248263. doi: 10.1371/journal.pone.0248263. eCollection 2021.
Legal, ethical, and regulatory requirements of medical research uniformly call for informed consent. We aimed to characterize and compare consent rates for neonatal randomized controlled trials in low- and lower middle-income countries versus high-income countries, and to evaluate the influence of study characteristics on consent rates.
In this systematic review, we searched MEDLINE, EMBASE and Cochrane for randomized controlled trials of neonatal interventions in low- and lower middle-income countries or high-income countries published 01/01/2013 to 01/04/2018. Our primary outcome was consent rate, the proportion of eligible participants who consented amongst those approached, extracted from the article or email with the author. Using a generalised linear model for fractional dependent variables, we analysed the odds of consenting in low- and lower middle-income countries versus high-income countries across control types and interventions.
We screened 3523 articles, yielding 300 eligible randomized controlled trials with consent rates available for 135 low- and lower middle-income country trials and 65 high-income country trials. Median consent rates were higher for low- and lower middle-income countries (95.6%; interquartile range (IQR) 88.2-98.9) than high-income countries (82.7%; IQR 68.6-93.0; p<0.001). In adjusted regression analysis comparing low- and lower middle-income countries to high-income countries, the odds of consent for no placebo-drug/nutrition trials was 3.67 (95% Confidence Interval (CI) 1.87-7.19; p = 0.0002) and 6.40 (95%CI 3.32-12.34; p<0.0001) for placebo-drug/nutrition trials.
Neonatal randomized controlled trials in low- and lower middle-income countries report consistently higher consent rates compared to high-income country trials. Our study is limited by the overrepresentation of India among randomized controlled trials in low- and lower middle-income countries. This study raises serious concerns about the adequacy of protections for highly vulnerable populations recruited to clinical trials in low- and lower middle-income countries.
医学研究的法律、伦理和监管要求均要求获得知情同意。本研究旨在描述和比较低收入和中下收入国家与高收入国家新生儿随机对照试验的同意率，并评估研究特征对同意率的影响。
本系统评价检索了 MEDLINE、EMBASE 和 Cochrane 数据库中 2013 年 1 月 1 日至 2018 年 4 月 4 日发表的在低收入和中下收入国家或高收入国家开展的新生儿干预措施的随机对照试验。主要结局为同意率，即纳入研究的合格参与者中同意参加的比例，从文章或与作者的电子邮件中提取。使用分数依赖变量的广义线性模型，我们分析了在不同对照类型和干预措施下，低收入和中下收入国家与高收入国家同意参与的可能性。
我们筛选了 3523 篇文章，得到了 300 项符合条件的随机对照试验，其中 135 项来自低收入和中下收入国家，65 项来自高收入国家。低收入和中下收入国家的同意率中位数较高（95.6%；四分位距（IQR）88.2-98.9），高于高收入国家（82.7%；IQR 68.6-93.0；p<0.001）。在调整后的回归分析中，与高收入国家相比，无安慰剂-药物/营养试验的同意率为 3.67（95%置信区间（CI）1.87-7.19；p = 0.0002），安慰剂-药物/营养试验为 6.40（95%CI 3.32-12.34；p<0.0001）。
与高收入国家的试验相比，低收入和中下收入国家的新生儿随机对照试验报告的同意率始终较高。本研究的局限性在于，在低收入和中下收入国家的随机对照试验中，印度的代表性过高。这项研究严重关切在低收入和中下收入国家招募参加临床试验的高度脆弱人群的保护措施是否充分。
