The validity and applicability of before-after studies compared to randomised controlled trials (RCTs) of fluconazole prophylaxis for very low birthweight (VLBW) infants is uncertain.
The aim was to examine whether the study design (before-after studies compared to RCTs) affected the estimate of effect size yielded in meta-analyses and to explore possible causes for any differences detected.
A systematic review and meta-analysis of before-after studies, which assessed the effect of fluconazole prophylaxis on the incidence of invasive fungal infection in VLBW infants, was undertaken. Data were compared with estimates generated from meta-analyses of RCTs. Funnel plots were examined for evidence of publication bias.
Meta-analysis of 11 before-after studies found a reduced risk of invasive fungal infection following introduction of fluconazole prophylaxis: RR 0.19 (95% CI 0.13 to 0.27). This estimate is significantly lower than the estimate generated from meta-analysis of RCTs: RR 0.48 (95% CI 0.31 to 0.73). Inspection of a funnel plot of before-after studies revealed that smaller studies with large effects sizes contributed an excess of data points.
Publication bias may be an important cause of effect size estimate inflation of before-after studies. Data from before-after studies of antifungal prophylaxis for VLBW infants should be interpreted and applied cautiously. Evidence to guide policy and practice for should instead be derived from well-designed RCTs.
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