Economic evaluations of treatments for systemic fungal infections: a systematic review of the literature.

We systematically reviewed published economic evaluations of systemic antifungal therapies and assessed their strengths and weaknesses. The study identified all economic evaluations published before May 2002 and critically appraised their methods using a published checklist. Over 1000 papers on antifungal treatments and costs were retrieved, 40 of which were economic evaluations. Fifteen of these were evaluations of systemic antifungal therapy. The majority of studies examined prophylaxis (11 out of 15), two examined empiric treatment and two examined the treatment of confirmed infections. Methods varied quite dramatically and the quality of the studies was, in general, very poor. Consequently, we were unable to find a coherent body of economic evidence for any particular patient group and/or indication. Three methodological issues were identified as requiring improvement in future economic evaluations of the prevention and treatment of systemic mucoses: cost estimates, outcome measures and evidence of effectiveness. Costs of both antifungal infection and treatment are important, and despite this, seven of the studies only collected cost information on drug acquisition costs. This is such a fundamental flaw that these studies should not be used to inform decision making on the use of antifungal medication. The estimation of costs in the other studies appeared appropriate, although limited reporting obscured other important issues, such as the appropriate use of per diem costs. Outcome measures were necessarily produced in all evaluations, yet only two studies produced cost-effectiveness ratios. This makes comparisons across studies very difficult. Also, small samples sizes meant that 'hard' outcome measures such as life-years saved could not be used, as deaths were rare within the studies. Both studies that produced incremental cost-effectiveness ratios were model-based studies. These allow simulations to be run on large cohorts of hypothetical patients, thus allowing differences in mortality between treatments to be evaluated. Evidence of effectiveness was limited, with many of the studies based on non-randomised clinical studies and consequently open to bias. Future clinical trials of the effectiveness of antifungal prophylaxis and treatment need to incorporate the collection of costs and economic outcome measures. Even quite simple analyses can be quite powerful, particularly when combined with modelling work to allow other data sources to be added.