Investigating an alternative regulatory and reimbursement framework for antimicrobials in Australia

Abstract

Background: The economic risks associated with antimicrobial development, including the emergence of resistance, have contributed to a substantial decline in new antimicrobials marketed by pharmaceutical companies. Antimicrobial resistance increases the risk of treatment failure, prolonged hospitalisation and increased mortality. Interventions to optimise and reduce the use of antimicrobials exerts downward pressure on antimicrobial sales, reducing the economic return for manufacturers. Disinvestment in antimicrobials by the pharmaceutical industry has also resulted in supply chain problems, resulting in frequent global shortages of commonly used antimicrobials. The lack of new antimicrobials in development is considered by the World Health Organization to be a public health crisis, requiring increased public and private investment in the research and discovery of new antimicrobials. Consequently, governments globally are seeking alternative registration pathways and innovative methods of reimbursement to support a sustainable pipeline of these essential medicines into the future. Aims: The purpose of this research was to explore the feasibility and sustainability of an alternative regulatory and funding model for antimicrobials in Australia, and contextualise that alternative framework within the broader global and national objective of antimicrobial stewardship. Specific aims of this thesis were to (1) determine the unmet need for registered antimicrobials in Australian clinical practice, firstly by quantifying the use of unregistered antimicrobials and secondly by identifying the clinical indications for which they are used; (2) explore the perspective of stakeholders regarding the feasibility of a de-linked reimbursement model in Australia and alternative methods of value assessment for regulatory and funding purposes; and (3) estimate the willingness of health care practitioners to pay for particular attributes of new antimicrobial drugs. Methods A sequential, mixed-methods approach was used for this research. A descriptive, pharmacoepidemiological study, triangulating three data sources, was undertaken to quantify the utilisation of unregistered antimicrobials in clinical practice. To determine the clinical indications where there is an unmet need, a retrospective review of applications submitted to the Therapeutic Goods Administration from two principal referral hospitals over a twoyear period was conducted. These studies, together with a review of the literature, informed a qualitative study involving semi-structured interviews of stakeholders. Finally, a discrete choice experiment was conducted, to investigate which attributes of a new antimicrobial are preferred by infectious disease specialists and pharmacists, and to determine their willingness-to-pay for narrow-spectrum agents. Results: Analysis of three different data sources indicated that the usage of antimicrobials not registered for use in Australia is increasing. A high proportion of unregistered antimicrobials dispensed from public hospitals are used in the outpatient setting. The most common clinical justification for utilising an unregistered antimicrobial was that the pathogen was resistant to registered antimicrobials or treatment with registered options had failed. Dominant themes from stakeholder interviews included: funding silos are a barrier to de-linking reimbursement from sales; the evidence required for public funding varies depending upon the setting; and funding status or cost is used as a stewardship tool. Policymakers were uncertain about how to incorporate future resistance into economic evaluations of new antimicrobials without a systematic method to capture costs avoided due to good stewardship. Results of the discrete choice experiment showed that price and spectrum of activity were the attributes with the main influence on the antimicrobial choice of health practitioners with expertise in antimicrobial stewardship. Patient co-payment, whether an antimicrobial was federally funded on the Pharmaceutical Benefits Scheme, and the route of antimicrobial administration also significantly impacts antimicrobial choice at the point of care. Conclusions: Overall these findings provide empirical evidence on the economic factors that impact on the appropriate use of antimicrobials in Australia. The price, the source of public or private funding and the cost to the patient all impact the selection of antimicrobials at the point of care. Federal funding of all antimicrobials, delinked from usage, could address unmet need, improve security of access and better facilitate efforts to ensure the effective stewardship of antimicrobials. From a policy perspective, this thesis highlights a number of challenges including the substantial legislative reform that would be required to support a centralised framework that de-links funding from sales and subsidises the cost of antimicrobials based on the appropriateness of use.