Standard 2: Containing Risk of Bias

Abstract

* Abbreviations: CONSORT — : Consolidated Standards of Reporting Trials ITT — : intention to treat SPIRIT — : Standard Protocol Items: Recommendations for Interventional Trials StaR Child Health — : Standards for Research in Child Health There is a crisis of credibility facing the child health research community because of the paucity of reliable estimates of the effects of interventions in children. Associations between risk of bias assessments and treatment effect estimates have important implications, for the clinician, and the families face important challenges as decision-makers stemming from results that exaggerate treatment effectiveness or safety. Consequently, interventions that are not efficacious and potentially harmful may be prescribed, whereas interventions that truly are efficacious may be withheld.1–5 Positive trends in pediatric research have been observed since the first trial was published in 1948. Specifically, there has been a substantial increase in the number of trials published over time, the proportion of randomized to nonrandomized controlled trials, and the proportion of child to adult trials.6 Reporting of methods has also improved; however, methodological quality remains modest.6 Three studies have specifically examined risk of bias in pediatric trials by using the Cochrane Risk of Bias tool.7–9 The results are summarized in Table 1 by risk of bias domain. In 2 reviews, the overall risk of bias was unclear or high for the vast majority of trials.7,8 Both of these articles also revealed that trials at high or unclear risk of bias had exaggerated treatment effects compared with those at low risk of bias. Sequence generation and allocation concealment appear to be the domains that are consistently problematic. Importantly, several variables have been found to be associated with risk of bias including source of funding (industry-sponsored research revealing higher risk of bias), nature of the interventions (behavioral/educational interventions having higher risk of bias), and number of authors (higher risk of bias with fewer authors).9 View this table: TABLE 1 Summary of Reviews Documenting Risk of Bias by Domain Using Cochrane Collaboration Risk of … Address correspondence to Martin Offringa, MD, PhD, Senior Scientist and Program Head, Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. E-mail: martin.offringa{at}sickkids.ca