The effect of fluconazole prophylaxis in very low birthweight infants is overestimated by before-after studies.


BACKGROUND 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. OBJECTIVES 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. METHODS 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. RESULTS 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. CONCLUSIONS 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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