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Introduction: Meta‐analysis traditionally uses aggregate data from published reports. Individual Participant Data (IPD) meta‐analysis, which obtains and synthesizes participant‐level data, is potentially more informative, but resource‐intensive. The impact on the findings of meta‐analyses using IPD in comparison with aggregate data has rarely been formally evaluated. Methods: We conducted a secondary analysis of a Cochrane systematic review of skincare interventions for preventing eczema and food allergy in infants to identify the impact of the analytical choice on the review's findings. We used aggregate data meta‐analysis only and contrasted the results against those of the originally published IPD meta‐analysis. All meta‐analysis used random effects inverse variance models. Certainty of evidence was evaluated using GRADE. Results: The pooled treatment effects for the Cochrane systematic review's co‐primary outcomes of eczema and food allergy were similar in IPD meta‐analysis (eczema RR 1.03, 95% CI 0.81, 1.31; I241%, 7 studies 3075 participants), and aggregate meta‐analysis (eczema RR 1.01 95% CI 0.77, 1.33; I253%, 7 studies, 3089 participants). In aggregate meta‐analysis, the statistical heterogeneity could not be explained but using IPD it was explained by one trial which used a different, bathing intervention. For IPD meta‐analysis, risk of bias was assessed as lower and more adverse event data were available compared with aggregate meta‐analysis. This resulted in higher certainty of evidence, especially for adverse events. IPD meta‐analysis enabled analysis of treatment interactions by age and hereditary eczema risk; and analysis of the effect of treatment adherence using pooled complier‐adjusted‐causal‐effect analysis, none of which was possible in aggregate meta‐analysis. Conclusions: For this systematic review, IPD did not significantly change primary outcome risk ratios compared with aggregate data meta‐analysis. However, certainty of evidence, safety outcomes, subgroup and adherence analyses were significantly different using IPD. This demonstrates benefits of adopting an IPD approach to meta‐analysis. [ABSTRACT FROM AUTHOR]

Background: Missing data are common in randomised controlled trials (RCTs) and can bias results if not handled appropriately. A statistically valid analysis under the primary missing-data assumptions should be conducted, followed by sensitivity analysis under alternative justified assumptions to assess the robustness of results. Controlled Multiple Imputation (MI) procedures, including delta-based and reference-based approaches, have been developed for analysis under missing-not-at-random assumptions. However, it is unclear how often these methods are used, how they are reported, and what their impact is on trial results. This review evaluates the current use and reporting of MI and controlled MI in RCTs.Methods: A targeted review of phase II-IV RCTs (non-cluster randomised) published in two leading general medical journals (The Lancet and New England Journal of Medicine) between January 2014 and December 2019 using MI. Data was extracted on imputation methods, analysis status, and reporting of results. Results of primary and sensitivity analyses for trials using controlled MI analyses were compared.Results: A total of 118 RCTs (9% of published RCTs) used some form of MI. MI under missing-at-random was used in 110 trials; this was for primary analysis in 43/118 (36%), and in sensitivity analysis for 70/118 (59%) (3 used in both). Sixteen studies performed controlled MI (1.3% of published RCTs), either with a delta-based (n = 9) or reference-based approach (n = 7). Controlled MI was mostly used in sensitivity analysis (n = 14/16). Two trials used controlled MI for primary analysis, including one reporting no sensitivity analysis whilst the other reported similar results without imputation. Of the 14 trials using controlled MI in sensitivity analysis, 12 yielded comparable results to the primary analysis whereas 2 demonstrated contradicting results. Only 5/110 (5%) trials using missing-at-random MI and 5/16 (31%) trials using controlled MI reported complete details on MI methods.Conclusions: Controlled MI enabled the impact of accessible contextually relevant missing data assumptions to be examined on trial results. The use of controlled MI is increasing but is still infrequent and poorly reported where used. There is a need for improved reporting on the implementation of MI analyses and choice of controlled MI parameters. [ABSTRACT FROM AUTHOR]

Objective: Eczema and food allergy start in infancy and have shared genetic risk factors that affect skin barrier. We aimed to evaluate whether skincare interventions can prevent eczema or food allergy. Design: A prospectively planned individual participant data meta‐analysis was carried out within a Cochrane systematic review to determine whether skincare interventions in term infants prevent eczema or food allergy. Data sources: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to July 2020. Eligibility criteria for selected studies: Included studies were randomized controlled trials of infants <1 year with healthy skin comparing a skin intervention with a control, for prevention of eczema and food allergy outcomes between 1 and 3 years. Results: Of the 33 identified trials, 17 trials (5823 participants) had relevant outcome data and 10 (5154 participants) contributed to IPD meta‐analysis. Three of seven trials contributing to primary eczema analysis were at low risk of bias, and the single trial contributing to primary food allergy analysis was at high risk of bias. Interventions were mainly emollients, applied for the first 3–12 months. Skincare interventions probably do not change risk of eczema by age 1–3 years (RR 1.03, 95% CI 0.81, 1.31; I2=41%; moderate certainty; 3075 participants, 7 trials). Sensitivity analysis found heterogeneity was explained by increased eczema in a trial of daily bathing as part of the intervention. It is unclear whether skincare interventions increase risk of food allergy by age 1–3 years (RR 2.53, 95% CI 0.99 to 6.47; very low certainty; 996 participants, 1 trial), but they probably increase risk of local skin infections (RR 1.34, 95% CI 1.02, 1.77; I2=0%; moderate certainty; 2728 participants, 6 trials). Conclusion: Regular emollients during infancy probably do not prevent eczema and probably increase local skin infections. [ABSTRACT FROM AUTHOR]