Abstract
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.
Highlights
Legal, ethical and regulatory requirements of medical research uniformly call for informed consent [1,2,3]
Neonatal randomized controlled trials in low- and lower middle-income countries report consistently higher consent rates compared to high-income country trials
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
Summary
Ethical and regulatory requirements of medical research uniformly call for informed consent [1,2,3]. An unexpectedly high mortality rate was observed in one study arm of the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) in the United States, a trial comparing two different levels of oxygen targeting in premature babies This led to prolonged litigation as the risk of increased mortality was not explicitly mentioned in the consent form [7]. Concerns have been raised about pharmaceutical-sponsored paediatric clinical trials enrolling in India without adequate informed consent, leading to serious harm and death of participants [5, 6, 8]. These concerns prompted the government of India to tighten regulatory approval of research and to mandate audio-visual recording of the informed consent process [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
