Abstract
ObjectivesThe objective of this study was to examine how rescue medication is defined, reported, and accounted for in randomized controlled trials (RCTs) in eczema and asthma populations. Study Design and SettingThis is a systematic review of phase II/III RCTs evaluating monoclonal antibodies for treating chronic eczema or asthma. A search of EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials was conducted to identify eligible RCTs. ResultsSixty published RCTs were identified, of which 60 (100%) allowed use of rescue medication but only 28 (47%) reported its use. Twenty-seven (45%) articles summarized rescue use by arm, with an average of 25% (95% CI (17%, 36%)) greater use in the placebo arm. Nine (15%) trials undertook an analysis that adjusted the primary treatment effect estimate for rescue medication use, but 8 of these used a suboptimal approach using single imputation, including 4 which used “last observation carried forward” after setting postrescue data to missing. ConclusionRescue medication use in eczema and asthma trials evaluating monoclonal antibodies is often permitted, but not routinely reported. There is evidence of imbalance in rescue use between arms, but few articles attempted to estimate a rescue-adjusted treatment effect. In trials that did, the methods used were suboptimal which could introduce bias.
Highlights
Randomized controlled trials (RCTs) are the gold standard for determining efficacy and effectiveness of new drug therapies
Obtaining an unbiased treatment effect estimate adjusted for postrandomization variables, such as the use of rescue medication, requires statistical approaches that have been emerging over the last 10 years, and this review demonstrates that these approaches are currently not being used
The double screening was predominately based on abstracts and titles, but the second reviewer referred to the full texts of the articles where eligibility was not clear from the abstract or title alone
Summary
Randomized controlled trials (RCTs) are the gold standard for determining efficacy and effectiveness of new drug therapies. When participants experience an inadequate therapeutic effect or an exacerbation of symptoms, they may start nontrial treatment (which we throughout refer to as rescue medication) in addition to their randomized treatment in the trial [1]. Rescue medication presents a problem across the board; it is present in chronic conditions, such as asthma and eczema, and in areas such as mental health, cardiovascular health, and diabetes [2]. Access to rescue medication is often permitted for ethical reasons and to encourage recruitment and retention of participants. In trials an intention-to-treat (ITT) analysis will be performed, whereby all patients are analyzed as randomized regardless of any Conflict of interest: none.
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