The United Kingdom is a step closer to implementing a first-of-its-kind, subscription-style model of paying for antibiotics.
The step comes in the form of draft guidance for how England's National Health Service (NHS) should estimate the full value of the two new antibiotics—cefiderocol and ceftazidime-avibactam—that have been selected to be part of the pilot project. The guidance will inform the discussions over how much the NHS should pay the drug manufacturers on a yearly basis under a subscription plan that aims to delink the value of the antibiotics from the number of units sold.
The guidance was developed by the UK's National Institute for Health and Care Excellence (NICE), which evaluated the benefit of the drugs to the health of the English population in terms of quality-adjusted life years (QALYs)—a measurement used to assess the economic value of a medical intervention.
"This draft guidance represents an important milestone in the UK project," Nick Crabb, of NICE's Science, Evidence and Analytics Directorate, said in a press release. "Its ultimate goal is to ensure NHS has access to effective new antimicrobials to call on when needed and patients aren't left without treatment options in the face of growing antimicrobial resistance."
Assessing the public health value of antibiotics
The idea behind the subscription-style model, launched by the UK government in 2019, is that the NHS—a publicly funded healthcare system that provides free care for English residents—will pay a fixed annual fee for patients to have access to cefiderocol and ceftazidime-avibactam, rather than reimbursing the drug makers based on the quantity of antibiotics sold. Although these two drugs are critical for patients with drug-resistant bacterial infections, they are used sparingly to avoid development of resistance, and the number of people who need them is relatively small.
The low sales and lack of return on investment for these and other new antibiotics have led many pharmaceutical companies and investors to abandon antibiotic development, resulting in a weak pipeline of new products, just as rising antimicrobial resistance (AMR) is threatening the effectiveness of current antibiotics. The hope is that guaranteeing companies a fixed annual fee that reflects the true public health value of the new antibiotics could help renew interest and spur more investment in antibiotic development to address the growing threat of AMR.
NHS and NICE selected cefiderocol (manufactured by Shionogi) and ceftazidime-avibactam (Pfizer) to be the first antibiotics purchased through the program in December 2020. Since then, NICE has been working on guidance for how to assess their value and cost-effectiveness.
While NICE's evaluation methods for most drugs focus on the benefits for those taking them, their evaluation for antibiotics takes more into consideration. It also accounts for their importance in limiting the spread of infections to other people, ensuring that chemotherapy, surgery, and other medical procedures can go ahead safely, and in providing a range of treatment options that can reduce the risk of resistance.
"It was a very comprehensive look at, and a much closer estimation of, the public health value [of these antibiotics]," David Hyun, MD, director of the Pew Charitable Trusts' Antibiotic Resistance Project, explained to CIDRAP News. "It was looking at the benefits at the public health level, rather than the individual patient level, which is where a lot of the past research has tried to demonstrate the economic benefits of treatment therapies."
For cefiderocol, which is licensed for treating patients with gram-negative bacterial infections who have limited treatment options, NICE estimated that payment should be based on a value of 970 QALYs per year. For ceftazidime-avibactam, recommended as an option for treating severe drug-resistant infections only when few alternatives are available, NICE estimated a value of 530 QALYs/year.
The next step is for NHS England to negotiate a 3-year contract for the drugs, with an option to extend the contract to 10 years, based on these estimates. The contracts will also require Shionogi and Pfizer to participate in the UK Antimicrobial Registry (UKAR), which will provide information on the relationship between patterns of antibiotic usage and emergence of resistance in the United Kingdom, as well as quantitative data on the clinical and safety outcomes of the antibiotics.
"UKAR will support the evaluation of the de-linkage scheme and provide a basis for considering extension of the scheme to other antimicrobials," David Jenkins, MBBS, president of the British Society for Antimicrobial Chemotherapy, which developed UKAR in partnership with Aberdeen University, said in a press release.
A 'moment to celebrate'
Hyun said the draft guidance is welcome news for those who have been pushing policymakers to adopt policies that address the challenging market conditions for antibiotics and incentivize antibiotic development. Pew is among many groups supporting the PASTEUR (Pioneering Antimicrobial Subscriptions to End Upsurging Resistance) Act, a bill that would a create a similar subscription-style payment model for antibiotics through Medicare.
"It's very encouraging news," he said. "A lot of places, including the United States, are looking at this pilot project with great interest to see how well it works out, and use it as a potential model to either replicate or adapt to their own countries."
Writing in the newsletter AMR.Solutions, John Rex, MD, chief medical officer of Advent Life Sciences, and CARB-X Executive Director Kevin Outterson, JD, said that while the monetary value of the contracts still needs to be worked out, the advancement of the pilot project is a "moment to celebrate."
"It's evident that the math shows that major new antibiotics have a real social value that can be estimated and should be rewarded," they wrote.
