Standard 2: Containing Risk of Bias

Abstract

DILEMMAThere 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 decisionmakers 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][2][3][4][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][8][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 These analyses demonstrate that there is substantial room for improvement in the methodological and reporting quality of pediatric trials. The association between risk of bias assessments and treatment effect estimates has important implications for decision-making both in terms of false-positive and false-negative results. In practice, this may result in unrealistic expectations of treatment benefit and safety. Inadequate reporting can also have an impact on systematic reviews, which are being used increasingly as a basis for informed decisionmaking. Although systematic reviews aim to be comprehensive and include all relevant studies, the number of studies contributing to various analyses, be they qualitative or quantitative, is often considerably smaller due to inadequate reporting.Ensuring methodological rigor and complete reporting is essential for informed clinical decision-making. It is critical that issues of bias are recognized and addressed by every person who conducts trials, reviews trials, funds trials, or uses trials to guide practice. This standards article was motivated by 2 key factors: (1) emerging evidence demonstrating methodological flaws a...

Quantifying Bias in Randomized Controlled Trials in Child Health: A Meta-Epidemiological Study

“…Moreover, a recent standard, developed by the international organization StaR Child Health, for minimizing risk of bias in pediatric trials could be equally applied to any trial. [32] Consistent with Savovic et al’s findings, other features may be more salient in assessing possible bias such as choice of outcomes (subjective vs. objective).…”

Education in Health Research Methodology: Use of a Wiki for Knowledge Translation

“…In order to maximize credibility and familiarity, the wiki was established under the auspices of StaR Child Health, an international initiative dedicated to improving the quality of pediatric clinical research [38], and is available at www.starchildhealth-riskofbias.wikispaces.com. Specifically, the wiki was designed to contribute to the KT agenda of the StaR Child Health Risk of Bias Standard Development Group [39]. Content was structured to emphasize two main areas: risk of bias and the conduct of pediatric RCTs.…”

StaR Child Health: developing evidence-based guidance for the design, conduct and reporting of paediatric trials

“…Demonstrating a specific strategy on information and recruitment is a prerequisite for a successful trial and even more so for children. The standard uses clinical scenarios to discuss and provide guidance on (1) who should give consent for children, (2) what information is necessary to obtain consent, (3) ensuring equitable opportunity rather than exploitation, (4) discusses the issue of payment and compensation, (5) the potential conflict of a child's clinician also acting as the investigator and (6) issues on eligibility of patients invited to participate in a trial. Containing risk of bias :18 A high risk of bias in a trial can lead to an overestimate of treatment effects13 and reviews of paediatric trials have shown that many are at a high risk of bias 14. This StaR paper addresses how to reduce and limit bias, such as ensuring adequate (1) techniques and security of randomisation, (2) blinding, (3) follow-up and handling of missing outcome data and (4) outcome reporting.…”

“…Containing risk of bias :18 A high risk of bias in a trial can lead to an overestimate of treatment effects13 and reviews of paediatric trials have shown that many are at a high risk of bias 14. This StaR paper addresses how to reduce and limit bias, such as ensuring adequate (1) techniques and security of randomisation, (2) blinding, (3) follow-up and handling of missing outcome data and (4) outcome reporting.…”