UK to expand NHS Subscription Pilot! Consultation Period launches

Next steps and a call for your feedback: A 12-week public consultation period is launching on 10 July 2023 and is seeking input from experts across the board. If you would like to share your opinions, please do so via this link. Now is the time to engage. Make it so!

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[Alert: Increasingly wonkish text from this point!] Now that we’ve covered the basics of this big news, let’s do a dive into what this could look like in reality. Rewarding high-value antibiotics is a difficult and delicate process starting with defining what is high-value. We are all familiar with doing this in other settings — as one well-known example, think of the way NIH funds research via a peer-reviewed scoring system. No two organizations have the same standards or approval process and that is not a bad thing. The more trial and error in tandem with sharing information with our peers, the better … this is how the overall ecosystem is refined. 

So, how do we do this for new antibiotics? Well, it turns out that a lot of work has gone into this over the past 10 years. No one wants to sponsor a mediocre product! As that recent JAMRAI multi-country survey drove home, governments want to create a Pull incentive that will be focused on high-impact products. The desire to avoid paying for a lemon is really important in this debate: don’t miss Christine Ardal’s comments on this — you can get it in part from the newsletter but you can also jump to 11:18 in the video and hear it straight from her. 

Based on these themes, our goal should be to set high but attainable standards. If we clearly set these standards now, R&D teams can plan for them as projects evolve. And, we want the standards to be relatively similar on a global basis so that project teams can know that they are moving in a generally acceptable direction. On this point, the idea of “Shared Valuation Principles” was called out at the 4 June 2021 meeting of the G7 Health Ministers (see this 5 June 2021 newsletter and its YouTube video explainer for more).

To make this work, we need to do two things in parallel – measure the financial value to society (why is this worth paying for?) and develop scoring systems for measuring new products (what do we pay for?). To that end, you will find annotated reading lists for both themes below the signature block. The papers are given in chronological order … as you review them, you’ll readily see how elements have emerged that are now captured in the NHS scoring scheme.

In summary: The NHS Pilot’s initial scheme did more than just create a plan for the UK — it made the UK a world leader in developing an antibiotic subscription plan. It was a bold step and, after hearing the criticism from the original standards, we now are set to see further refinements to their scheme following the results of this consultation period. 

Thunderous round of applause for Team UK! What a year this has been thus far! Now, get to it and get involved with the UK’s public consultation.

All best wishes, John & Kevin

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Operating Partner, Advent Life Sciences. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: https://amr.solutions/blog/. All opinions are my own.

Kevin Outterson, JD, Professor of Law, Boston University & Executive Director, CARB-X (these views are personal and do not necessarily reflect the views of CARB-X or any of its funders) @koutterson

Financial Value Metrics (for more, see the Incentives page of AMR.Solutions website)

1. 2014: Analytical Framework for Examining the Value of Antibacterial Products from US Assistant Secretary for Planning and Evaluation
   • This was one of the first serious efforts to estimate the societal value of an antibiotic. The gap between the commercial value of a new drug for HABP/VABP and its value to society was staggering: -$4.5 million vs. $1.2 billion. Yes, that’s a negative sign in front of the $4.5m … not a typo.
2. 2014-16: Review on Antimicrobial Resistance led by Lord Jim O’Neill (aka the O’Neill Report)
   • Without action to create new antibiotics, cumulative global GDP losses as high as $100 trillion by 2050 along with as many deaths as cancer were estimated as possible. 
3. 2016: Drug-Resistant Infections: A Threat to Our Economic Future from The World Bank
   • Without action to create new antibiotics, the World Bank estimated that pandemic spread of AMR pathogens could lead to a global loss of annual GDP in the 1-4% range, an impact as large as the losses provoked by the 2008–2009 global financial crisis.
4. 2018: Framework for value assessment of new antimicrobials: implications of alternative funding arrangements for NICE Appraisal from the University of York
   • The STEDI principles for assessing value are identified (Spectrum, Transmission, Enablement, Diversity, and Insurance; see this newsletter, this newsletter, and this YouTube explainer for more on STEDI).
   • See also this webpage from the same group in which they provide the assessments that underpin the first two drugs in the pilot: Assessing the value of novel antimicrobials under new payment models
5. 2018: Stemming the Superbug Tide — Just A Few Dollars More by the OECD
   • This report concludes that “Every year between 2015 and 2050, up to USD 3.5 billion (adjusted for differences in prices across countries, expressed as purchasing power parities or PPPs) is expected to be spent on average between 2015-2050 on AMR-related complications across 33 OECD and EU28 countries, according to calculations from the OECD model.”
   • The underlying model is being updated by the recently formed Quadripartite Technical Group on the Economics of Antimicrobial Resistance (QTG-EA) as part of the run-up to UNGA 2024.
6. 2022: Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis by Murray et al.
   
   • This important paper looks at the human cost and concludes that “On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62–6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911–1·71) deaths attributable to bacterial AMR.”
7. 2022: An Ambitious USG Advanced Commitment for Subscription-Based Purchasing of Novel Antimicrobials and Its Expected Return on Investment and The World Needs New Antibiotics. A Proposed US Program to Develop Them Would Pay Off 28:1 from the Center for Global Development
   • As another variation on the human cost, this paper looks at the $ value in terms of DALYs (Disability-Adjusted Life Years) and concludes that $4.9T would be saved by spending $40B on new antibiotics (note that it is 4.9 Trillion vs. 40 Billion!)

Integrated Scoring Schemes

1. 2013: The US’s GAIN Act proposed the broad concept of Qualified Infectious Diseases Product (QIDP)
   • QIDP was based entirely on spectrum and this meant that almost everything qualified. We now recognize that this is too broad. Thus additional element are needed to define value. Read on…
2. 2016: Antibiotic reimbursement in a model delinked from sales: a benchmark-based worldwide approach
   • We (Outterson and Rex) defined a system in which spectrum, mechanistic novelty, and breadth of use (oral dosing, pediatric data) were proposed as ways to define value
3. WHO’s scoring scheme for products in development
   • Theuretzbacher et al. (2020) Critical analysis of antibacterial agents in clinical development
   • WHO (2021) Antibacterial agents in clinical and preclinical development: an overview and analysis
   • Butler et al. (2022): Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed
   • This was the big step forward! The scoring tool used here  both considered pathogen spectrum and proposed ways to value lack of cross-resistance, chemical novelty, target-based novelty, and mechanistic novelty … you’ll see that these appear in the NHS scoring scheme
4. 2023-2024: PASTEUR Act
   • Doesn’t define a scheme but clearly creates a path to one!