Towards cost-effective utilisation of high-cost antifungal agents in Australian hospitals
thesisposted on 13.01.2017, 01:42 authored by Al-Badriyeh, Daoud
The expenditure on antifungal therapy has risen sharply throughout hospitals in Australia and many other countries over the last decade. This increase is due largely to the recent introduction of new and more expensive antifungal agents, and is consuming a growing portion of limited financial resources. The focus of this thesis was to assess various high-cost antifungals for their ability to produce the highest level of effectiveness at the lowest possible cost in the Australian hospital setting. Antifungal agents were addressed in the context of three treatment strategies: empirical, prophylactic and targeted. From the empirical standpoint, pharmacoeconomic comparisons among voriconazole, liposomal amphotericin B (LAmB) and caspofungin in febrile neutropenia were performed. Decision analytic models were constructed based on underlying probabilities and patterns derived directly from trial data and expert panels. Cost inputs were obtained from the latest Australian sources. Sensitivity and Monte Carlo uncertainty analyses were undertaken. Caspofungin was the most cost beneficial, with cost savings of AU$798 and AU$7,245 per patient over voriconazole and LAmB, respectively. LAmB had cost savings over voriconazole in the order of AU$1,422 per patient. Within the context of prophylaxis, an evaluation of the economics of posaconazole versus voriconazole as prophylaxis against invasive fungal infections in patients with acute myeloid leukaemia (AML) was undertaken. A decision analytic model was developed using data extracted from a six-year review of AML patients at an Australian tertiary hospital. Cost inputs were obtained from the latest Australian sources. Sensitivity and uncertainty analyses were undertaken. A total of 94 patients were evaluated. Posaconazole was associated with a net cost saving of AU$17,458 per patient over voriconazole. The posaconazole group was associated with less mortality and lower probability of discontinuation because of possible infections or intolerance, but with more proven infections. The targeted therapy investigated was the use of extemporaneous voriconazole eye drops for the treatment of fungal keratitis. A number of approaches were evaluated as means to optimise the utilisation of the eye drops. These were concerned with the long-term stability of the eye drops, the clinical success of the eye drops as monotherapy, and the usefulness of higher concentrations of the eye drops. One-percent and 2% voriconazole eye drops were shown to be stable for at least three months at 2-8 ºC. The 1% voriconazole eye drops demonstrated potential effectiveness as monotherapy in fungal keratitis, either as first-line or salvage therapy. In 13 human subjects, 2% voriconazole eye drops resulted in an ocular trough voriconazole concentration (1.67 +/- 0.97 µg/mL) similar to that reported with 1% voriconazole eye drops. It appears that the corneal penetration of topical voriconazole is concentration independent. In summary, the results from this thesis provide suggestions on how practices can mitigate the cost associated with high-cost antifungals in particular indications in Australian hospitals. The work suggests that greater cost-benefits can be achieved by improving on the current utilisation of caspofungin in the empirical therapy, and on the use of voriconazole eye drops, and by the wider application of posaconazole in prophylaxis.