UK Antibiotic Subscription Pilot: Updates from a webinar

Dear All (and with thanks to Kevin Outterson for co-authoring),

We’ve written and talked before from various perspectives about the groundbreaking UK NHS England-, NHS Improvement-, and NICE-sponsored antibiotic subscription pilot project:

• 10 Feb 2021: Fabulous 5-minute video explainer on the economics of antibiotics by Andrew Jack of Financial Times
  • Superb discussions of Push/Pull, the role of the Netflix model, and more!
  • Cameos by Kevin (Outterson), Christine (Ardal), and Manica (Balasegaram)! Don’t miss it!
• 29 Mar 2020 newsletter: “UK Antibiotic Subscription Pilot Implies Pull Incentive Of Up To $4b Across The G20” 
• 3 Apr 2020 newsletter: “UK Antibiotic Subscription Pilot: Post-Webinar FAQ Document”
• 18 Dec 2020 newsletter: “UK Pilot Antibiotic Subscription Model: Two Candidate Antibiotics Chosen!”
• 22 Jan 2021 YouTube video (11 minutes): “The STEDI values of antibiotics and how this connects to the UK pilot”
  • For more on STEDI, see the references in Section 1 of the 14 Apr 2020 newsletter entitled “Pull Incentives For Antibiotics: How Much And Why? — A Literature Survey” 
• For global breadth…
  • See the 9 Dec 2020 newsletter entitled “Global Survey Of Novel Antibiotic Reimbursement Models / PASTEUR Act Introduced To US House.” This newsletter covers the US (PASTEUR) and the rest of the world (including the UK pilot)
  • The excellent paper by Gotham et al. on global reimbursement models is well worth a read
  • Similarly, an excellent global survey with a Canadian perspective was authored by Dutescu and Hillier
  • And finally, there was a call in the Swiss Parliament by Fiala Doris for “incentives … in which remuneration is independent of the amount purchased”!
• For a really deep dive, the 19 Sep 2020 newsletter entitled “In Praise Of Non-Inferiority” and its associated YouTube video take you through the background on why typical HTA metrics based on superiority outcomes in clinical trials are not a good idea for novel antibiotics!
  • And finally (shameless plug): I’ve just posted a 4-minute YouTube video on how Jane Austen’s Sense and Sensibility gives you insight into the almost magical effect of a good antibiotic on serious bacterial infections: embedded in this classic novel is a a great medical story that really highlights the importance of avoiding superiority designs when developing new antimicrobials!

—
Today’s news is that the project team gave a superb webinar update on 25 Jan 2021. The slides from the webinar are available on the project team’s home webpage; a video of the meeting is to follow. The key features of the program remain as previously discussed and can be briefly summarized as:

• The goal of the project is to test ways to reimburse for the full value of a new antibiotic
• To that end, two antibiotics will undergo a value assessment during 2021 by NICE based on both direct values (to the patient) and indirect values (to the system)
  • The inclusion of indirect values is the big step here based on the STEDI values discussed above
  • An example would be a Transmission value: treating patient #1 means that patient #2 never gets the infection: the Transmission value reimburses for the prevented infection.
• Contracts should be signed and delinked payments flowing by April 2022
• As demonstrated by this webinar, the project continues to share its insights globally
  • The hope is that we’ll see other countries create subscription programs that fit their unique health systems!

Some additional slide-by-slide notes are found just below our signature. We once again thank the UK team for their vision … it is fantastic to see this project coming to life! 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

1. Slide 6: The pilot seeks to reimburse for both direct value (to a treated patient) and indirect value (to the system)
   • “The principle of the model is that companies are paid for antimicrobials based on the estimated value
     of benefits to patients and the NHS which is consistent with good stewardship rather than payments
     based on volumes used.
   • “The value of the antimicrobials will be estimated by NICE through an adapted Health Technology Assessment with information from health economic modelling and expert opinion.
   • “The model will capture value not just from the direct health gain to patients treated, but also additional
     elements e.g. insurance value, diversity value, transmission value and enablement value.
   • “Value assessment will be used to inform commercial discussions, leading to payments to companies
     of an annual fixed fee in instalments.”
2. Slide 7: The pilot is designed to exercise the model: What data are needed to value a new antibiotic?
   • “The model is being tested through application to two antimicrobial products selected via competitive
     procurement exercise:
     • One existing antibiotic (has received marketing authorisation in past 2-3 years)
     • One antibiotic that is new to market (with expectation of a marketing authorisation by end 2020 and with plans to
       launch in UK)
   • “Future policy for the evaluation and purchasing of antimicrobials will be informed by the outcomes
     from this project.”
3. Slide 3 and Slide 12: Two products have been selected based on Spectrum (and how this addresses UK need), Novelty, Supply, etc.
   • Very recently licensed: Cefiderocol (Fetroja, Shionogi)
   • Already licensed: Ceftazidime with avibactam (Zavicefta, Pfizer)
   • Selection balanced the WHO priority list as well as unmet need in the UK
4. Slides 17-19: NICE will work during 2021 to model the value of these compounds
   • An enhanced version of the standard NICE technology appraisal will be used
   • Elements to be considered include Direct health effects to patients + indirect elements of value (e.g., Spectrum, Transmission, Enablement, Diversity and Insurance value; STEDI)
   • Modeling will be focused on high-value clinical scenarios
     • Specific examples were not given, but you could imagine the project examining values such as preventing ICU closure by stopping spread
   • The key metric is QALYs at a population level
5. The goal is for contracts to be signed and payments flowing by April 2022
6. There is an active outreach to share the project internationally
   • UK is the G7 President in 2021 — a great opportunity
   • The goal is to encourage development of shared principles such as
     • Quantitative and/or qualitative assessment of the value of new antimicrobials coming
       to market
     • Delinking reimbursement to companies from volume of sales
     • Robust stewardship of new and existing antimicrobials
     • Incentivising good manufacturing practice and robust supply