Changes in revenues associated with antimicrobial reimbursement reforms in Germany

The global threat of antimicrobial resistance (AMR) necessitates increased incentives for antimicrobial research and development (R&D). While push incentives like CARB-X and GARDP exist, pull incentives—post-market financial rewards—are gaining traction. Germany, a G7 nation, has implemented reimbursement reforms aimed at increasing antimicrobial revenues by exempting some new antimicrobials from health technology benefit assessments and reference pricing. This study assesses the effectiveness of this non-delinked approach compared to delinked pull incentives (like revenue guarantees or subscriptions) that decouple revenue from sales volume. The authors aim to determine if Germany's policy successfully incentivizes antibiotic R&D at the national level and whether it generates sufficient revenue comparable to a delinked pull incentive.

The paper reviews the global AMR crisis and the resulting stagnation in antimicrobial R&D. It highlights the insufficient number of new antimicrobials approved in recent decades and the financial difficulties faced by companies involved in their development, as shown by the accumulated deficits of small companies prior to their first FDA antibiotic approval. The authors discuss various proposed solutions to stimulate antimicrobial development, including push and pull incentives. Pull incentives are a focus, with a particular emphasis on delinked pull incentives that separate revenue from sales volume, thereby encouraging the responsible use of novel antimicrobials and mitigating the development of resistance. The paper mentions examples of pull incentives in other countries, such as the UK's subscription program and Sweden's minimum revenue guarantee, highlighting the different approaches taken. Finally, the study notes alternative proposals beyond financial incentives, such as open-source development and publicly funded initiatives.

The study used sales volume and revenue data from the IQVIA MIDAS database for antimicrobials introduced in Europe since 2010, specifically focusing on Germany from Q4 2016 to Q4 2022. The data, from a representative sample of German pharmacies and hospitals, provides estimates of total nationwide sales. The analysis focused on two antimicrobials, ceftazidime/avibactam and cefiderocol, which have both received “reserve” status in Germany and were selected for the UK antibiotic subscription program. An interrupted time series analysis was performed in SAS (version 9.4) using a macro by Caswell (2017) to determine if the granting of reserve status impacted price, revenue, and sales volume. The analysis considered seasonal autocorrelation and accounted for potential changes in trends and levels due to the policy change. Furthermore, calculations were made to determine the price increases needed to reach the "fair share" revenue targets based on Germany's GDP contribution towards global antimicrobial R&D, assuming no increase in sales volumes. Finally, revenue projections for each drug were created assuming consistent average monthly revenue over the patent lifecycle.

The analysis revealed that the granting of "reserve" status in Germany did not immediately and significantly impact sales volumes or revenue for ceftazidime/avibactam and cefiderocol. Interrupted time series analysis indicated no statistically significant change in trends or levels for revenue, price, and sales volume after the grant of reserve status. To achieve Germany's "fair share" revenue target (approximately €25 million annually), the study estimates that prices for these two drugs would need to increase by 320-330%, assuming sales volume remains constant. Projected revenues based on historical average monthly sales demonstrated that neither drug would reach the cumulative 10-year "fair share" revenue target before patent expiry. These findings suggest that the current German reimbursement reforms are insufficient to meet the financial requirements for incentivizing antimicrobial R&D at a level comparable to a delinked pull incentive.

The study's findings highlight the limitations of Germany's current reimbursement reforms as a sole mechanism for incentivizing antimicrobial R&D. The considerable price increases required to achieve "fair share" targets suggest that this approach may not be a viable long-term solution. The results align with a previous report indicating substantial price hikes are needed globally to create equivalent value to a pull incentive. The authors discuss alternative pathways for Germany to achieve "fair share" targets, including implementing a delinked revenue guarantee, amending its domestic reimbursement system, or supporting a broader EU-level delinked pull incentive. The lack of significant impact observed immediately following the granting of "reserve" status may indicate that longer-term data is needed to fully assess the effects of the reform. This further emphasizes the need to adopt other strategies to ensure adequate funding for antimicrobial R&D.

The study concludes that Germany's current reimbursement reforms have not yet delivered sufficient revenues to meet "fair share" targets for antimicrobial innovation. Substantial price increases or a substantial increase in sales volume are needed. The authors propose alternative strategies, such as delinked revenue guarantees or supporting EU-level incentives, to enhance the effectiveness of incentivizing antimicrobial R&D. Future research could focus on analyzing longer-term data to fully evaluate the reforms' impact and explore the effectiveness of different pull incentive models in different healthcare systems.

The study's reliance on data from a commercial database (IQVIA MIDAS) limits the scope of the analysis to a representative sample, potentially introducing sampling bias. The analysis focuses only on two drugs that have received "reserve" status, limiting generalizability to other antimicrobials. The analysis also assumes a constant sales volume, which may not hold true in the long term. Finally, the study's timeframe may not be sufficient to fully capture the long-term effects of the German reimbursement reforms.