The problem: investing in new antibiotics doesn’t pay off
One of the biggest challenges of our age is the looming threat of antimicrobial resistance (AMR). In the past few years, it has become a high-profile policy priority for governments and global institutions, thanks to many voices sounding the alarm on the implications of an antibiotics-free future. But despite the well-publicised threat, few new antibiotics are in the pipeline. The reason development has stalled has as much to do with economics as pharmacology; the pharmaceutical industry has no incentive to develop drugs that are expected to be used only rarely, assuming efforts in infection prevention and antimicrobial stewardship are successful. The purpose of DRIVE-AB was to create evidence for policymakers on new ways to stimulate drug and biotech companies to invest in new antibiotics in a way that’s consistent with efforts to responsibly limit their use.
Getting the terminology right, predicting resistance, estimating value
First off, the project partners agreed on some basic definitions. While we know that the overuse of antibiotic drugs is the reason for resistance, there’s not a whole lot of agreement on what “responsible” use looks like. DRIVE-AB project partners looked into the available literature and rated the varying definitions, ultimately settling on a description for responsible use that, they posit, should form the basis of any model that tackles the new-drugs-versus-sustainable-consumption solutions.
They then developed models created to predict the spread of antibiotic resistance, intended to help health systems and drug companies make decisions about where the money and effort needs to go. The project partners also described – and assigned value amounts to – the consequences for the different people affected by AMR; what is the cost to a patient, a hospital, society as a whole of untreatable infections? They did the same type of quantification in the reverse: what is it worth to society to have a new antibiotic that works?
The fire extinguisher analogy: buying protection from future fires
A key finding from DRIVE-AB is that antibiotics are very valuable to society as preparedness for future drug resistance. A useful analogy is fire suppression equipment: we invest in the equipment while hoping that the actual number of fires is zero. To apply the same thinking to antibiotics calls for dramatic changes in how societies pay for them. It would require delinking revenues to the company from the number of pills sold. Antibiotics should be reimbursed based on their value to society, not the volume of patients being treated today. Those that treat Gram-negative infections, for example, are considered more valuable because these bacteria are more dangerous.
The outcome: a rethink of antibiotics’ true value
They key takeaway is that new economic models should be based on this “true value” of the new drugs. DRIVE-AB quantitatively modelled the most promising incentive systems in terms of profitability and benefit to the public, covering everything from basic science to patient treatment. They did an in-depth analysis of dozens of ideas in the policy literature, and settled on four incentives that can be considered best suited to fill the antibacterial pipeline and keep them available. The project simulated the impact of market entry rewards, which are rewards or prizes for bringing new antibiotics to the market, and found that a global reward of USD 1 billion (approx. EUR 0.9 billion), based on certain assumptions, would result in a steady supply of more innovative antibiotics.
DRIVE-AB also recommended a long-term supply continuity model for important but rarely-used antibiotics. They recommend a country or group of countries would agree to annual payments to one or more manufacturers to ensure predictable supply, and a number of sustainable use obligations for developers.
Conflicting perspectives: seeing it from the other side
The project has had immense influence; anyone involved in AMR policy is never far removed from the highly networked DRIVE-AB community. The project only served to further expand and solidify this network. Its 16 public-sector partners and seven pharmaceutical companies operated as equal partners and spent three years meeting in various fora. While the motivations of the public and private partners didn’t always align, it was a great opportunity for each camp to see the issue of antimicrobial research from the other perspective. The partners were able to work together as equals to hypothesise a mutually beneficial investment environment that achieves a goal that is common to all sides. Such cross-over collaborations is one of the great potential advantages of participating a public-private funding vehicle like IMI.
Of the 12 policy recommendations, six are now being fully or partially implemented, say the project partners, including as part of the UK’s AMR review and an AMR report carried out by Boston Consultancy Group on behalf of the German federal government. The recommendations have also influenced the policies of the World Health Organisation, the Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections (EUJAMRAI), and the Global AMR R&D Hub.
Although not a delinked model, the US government has recently taken an initial step to change the reimbursement pattern for new antibiotics used in the hospital, and the United Kingdom recently announced a pilot project looking at a delinked model. Legislation that could create such a model is also being considered in the United States. We can expect to see more and more policymakers adopt, or take inspiration from, the work done through the DRIVE-AB project.