Adrian Towse's slides from a session will exploring how the benefits of antibiotics can best be captured in HTA, and how we should pay for them when their value may depend on restricting their use. Author(s) and affiliation(s): Adrian Towse, Office of Health Economics Conference/meeting: Health Technology Assessment International (HTAi) 2018 Location: Vancouver, Canada Date: 03/06/2018

1. Professor Adrian Towse
Director of the Office of Health Economics
HTAi Vancouver Meeting
3rd June 2018
The role of HTA in Incentivising new
Drugs and Vaccines to tackle AMR

2. Key messages
• We have a serious problem – lack of new drugs as AMR
builds
• A global consensus that “push” and “pull” incentives required
• “Push” initiatives underway – but “pull” initiatives needed
• The “missing” element is value assessment, i.e. using HTA to
assess value
• De-linkage accepted but not “market entry rewards”
• Need value assessment with partial de-linked contractual
arrangements
• Global co-ordination struggling to find a “big bang” solution.
The policy mix will need to vary by region

3. The antimicrobial drug pipeline is thin
• Few drug candidates in the pipeline
– Pew Charitable Trusts identified 48 antibiotics currently in phase I-III
testing (in contrast, in 2015, there were 836 drugs in the pipeline for
cancer)
– Very few drugs in development for most urgent AMR needs
• Low ROI for antimicrobials relative to public health benefits
– Clinical trial challenges
– Lack of rapid diagnostics
– Effective stewardship leads to low sales volumes
– Most health benefits accrue to patients who never need to be
treated and who can undergo other procedures because effective
antimicrobials exist
3
From “Securing New Drugs for Future Generations: The
Pipeline of Antibiotics”, The Review on Antimicrobial
Resistance. May 2015

4. Emerging global consensus to address AMR
• Chatham House, the Royal Institute of International Affairs, an
independent policy institute based in London, released a report
on business models for antimicrobial development in Oct. 2015
• The Review on Antimicrobial Resistance was commissioned by,
and reports to, the UK Prime Minister, released a final report on
May 19th, 2016
• The German Global Union for Antibiotics Research and
Development report (Feb. 2017) identified actions to improve
needed development
• DRIVE-AB, 16 public and 7 private partners from 12 countries,
released a final report (Jan. 2018)
• U.S. President’s Advisory Council on Combatting Antibiotic-
Resistant Bacteria (PAC-CARB) formed in 2015 and issued report
in 2017
• Convergence of principles:
̶ Provide push funding to
support R&D on
antimicrobials
̶ Implement pull incentives
that delink reimbursement
from sales volume
̶ Coordinate globally on
surveillance and
development efforts
4

5. “Push” alone cannot generate a return
Towse, A., Hoyle, C., Goodall, J., Hirsch, M., Mestre-Ferrandiz, J., Rex J. 2017. Time for a Change in How New
Antibiotics are Reimbursed: Development of an Insurance Framework for Funding New Antibiotics based on a
Policy of Risk Mitigation. Health Policy http://dx.doi.org/10.1016/j.healthpol.2017.07.011
“neither the current business model, nor the use
of public partnership funding of R&D together with
regulatory reform and a five-year patent extension
will increase the pipeline of new antibiotics”

6. Key messages
• We have a serious problem – lack of new drugs as AMR
builds
• A global consensus that “push” and “pull” incentives required
• “Push” initiatives underway – but “pull” initiatives needed
• The “missing” element is value assessment, i.e. using
HTA to assess value
• De-linkage accepted but not “market entry rewards”
• Need value assessment with partial de-linked contractual
arrangements
• Global co-ordination struggling to find a “big bang” solution.
The policy mix will need to vary by region

7. HTA challenges for antibiotics
• Concerns that current HTA/payer methods
may not capture the full range of benefits of
antibiotics, including value of tackling AMR
• Two key challenges:
1. Clinical trials typically designed to demonstrate
non-inferiority, whereas HTA bodies generally
require demonstration of clinical superiority
2. HTA bodies/payers generally do not have a
mechanism to assess the broader public health
benefits of antibiotics, including tackling rise in
AMR

8. However, promising indications of
acknowledgement of challenges at policy level
• France: agreement signed in December 2015 giving 5-year EU price
guarantee for antibiotics achieving ASMR IV (minor benefit). Other types
of treatments must achieve at least ASMR III
• Germany: legislation proposed in 2016 included to introduce new HTA
regulation to address AMR, but not in the final approved law
• UK, Sweden: government – industry dialogue on a new framework –
and government commissioned work on new approaches
• EEPRU (led by Univ of York) in the UK. Draft report submitted setting
out implications for NICE Appraisal;
• In Sweden, TLV, together with the Public Health Agency,
recommended December 2017 piloting a new payment model: a
fixed sum additional to the usual per item payment. Both institutions
exploring whether is good idea for Sweden to put in place some kind
of pull mechanism to incentivize the development of new antibiotics.
•

9. Elements of value relevant to antibiotics
Download from https://www.ohe.org/publications/additional-elements-value-health-technology-assessment-decisions Or
from https://www.aiminfection.org/article/bad-bugs-undervalued-drugs-time-to-change-the-way-we-value-antibiotics
Relevant benefits
included in
traditional HTA
Other types of benefit
of possible relevance
to antibiotics
Health gain Insurance value
Unmet need Diversity value
Cost offsets Diagnostic value
Productivity benefits Uniqueness or innovation
value
Enablement value
Spectrum value
• Need also to focus on the evidence requirements
for new elements of value

10. Relevant benefits included in traditional HTA
Health gain
• Both life extension and
quality of life gains
• Key criterion for positive
HTA recommendation
• Evidence typically
required by HTA bodies
often unachievable for
antibiotics (superiority
trials usually not feasible;
fast track regulatory
paths based on non-
inferiority and PK/PD
data)
Unmet need
• Includes both severity of
disease and current
availability of alternative
treatments
• Could include use of
priority pathogen lists

11. Other types of relevant benefit? (i)
Insurance value
• Value of having treatment
available in case of
catastrophic health event,
e.g. outbreak of MDR
infections which cannot be
contained by existing ‘last-
line’ antibiotics
• Analogous to availability of a
fire engine (Rex and
Outterson, 2016)
• Also need to add in the
“precautionary principle” –
maybe we have two fire
engines
• Use of modelling studies
Diversity value
• Selection pressure:
Antibiotic able to eradicate
susceptible species of
bacteria but not other
resistant pathogen so
resistant pathogens survive
and multiply and the
antibiotic becomes
ineffective
• Evidence that reducing
selection pressure by
withdrawing antibiotic for
period of time may lead to
restoration of
susceptibilities
• Use of modelling studies

12. Other types of relevant benefit? (ii)
Diagnostic value
• If infection is accurately
and speedily diagnosed
then appropriate
antibiotic therapy can be
started earlier
• Need evidence of test
accuracy
Uniqueness or
innovation value
• Potential value associated
with new or unique
mechanism of action (MOA)
• antibiotics with novel MOA
may avoid problems of
cross-resistance seen
amongst existing classes
• Discovery of new MOA
antibiotic makes it easier
for “follow on” products to
enter market
• Evidence of new or unique
mechanism of action

13. Other types of relevant benefit? (iii)
Enablement value
• Availability of effective
antibiotics underpins
many surgical procedures
and treatments for people
with compromised
immune systems
• Use of modelling studies
Spectrum value
• Narrow spectrum antibiotics
may be more valuable than
broad spectrum antibiotics
as could reduce spread of
AMR by preventing
‘collateral damage’ to the
microbiome
• Depends on the antibiotic

14. Innovation in payment mechanisms
• Entry Rewards anathema to payers
• Stewardship requires use of new antibiotics to be limited
to delay the build up of resistance
• Volumes will be low and unpredictable, so even with
high prices (recognising value fully), getting a return on
investment will be slow and risky
• Partial delinkage is needed between drug volumes / use
and revenue with some revenues coming via a separate
payment mechanism
• Could be an insurance policy, or a per-member-per-
month fee.

15. Key messages
• We have a serious problem – lack of new drugs as AMR
builds
• A global consensus that “push” and “pull” incentives required
• “Push” initiatives underway – but “pull” initiatives needed
• The “missing” element is value assessment, i.e. using HTA to
assess value
• De-linkage accepted but not “market entry rewards”
• Need value assessment with partial de-linked contractual
arrangements
• Global co-ordination struggling to find a “big bang” solution.
The policy mix will need to vary by region

16. References
• O’Neill J. Securing New Drugs for Future Generations: The Pipeline of
Antibiotics. Report of The Review on Microbial Resistance. May 2015
• Karlsberg Schaffer, S., West, P., Towse A., Henshall C., Mestre-
Ferrandiz J., Masterton R., and Fischer, A. Assessing the Value of New
Antibiotics: Additional Elements of Value for Health Technology
Assessment Decisions. Office of Health Economics Research Paper, May
2017. Download from https://www.ohe.org/publications/additional-
elements-value-health-technology-assessment-decisions Or from
https://www.aiminfection.org/article/bad-bugs-undervalued-drugs-
time-to-change-the-way-we-value-antibiotics
• Towse, A., Hoyle, C., Goodall, J., Hirsch, M., Mestre-Ferrandiz, J., Rex
J. 2017. Time for a Change in How New Antibiotics are Reimbursed:
Development of an Insurance Framework for Funding New Antibiotics
based on a Policy of Risk Mitigation. Health Policy
http://dx.doi.org/10.1016/j.healthpol.2017.07.011

17. Adrian Towse
The Office of Health Economics
The Office of Health Economics is a charity (registration number 1170829) and
a company limited by guarantee (registered number 09848965)
Southside, 7th Floor, 105 Victoria Street, London SW1E 6QT
Website: www.ohe.org Blog: http://news.ohe.org
Email: atowse@ohe.org
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