Slides from Adrian's presentation on value frameworks for antibiotics

1. Professor Adrian Towse
Director of the Office of Health Economics
Forum to Discuss the Assessment of the Value
of New Antibiotics
HTAi Rome June 2017
Towards a Value Framework for
Antibiotics

2. Structure of presentation
• Challenges of new drugs for AMR
• HTA challenges for antibiotics
• Why do we need additional elements of
value for antibiotics?
• What are the additional elements of
value for antibiotics
• Insights gained from the Value Forum
• Final Remarks

3. New OHE-AIM publication, May 2017
• This Briefing, from OHE and the
Academy of Infection Management,
discusses 10 elements of value which
can be split into two groups: four
relevant benefits typically included in
HTA, and six other types of benefits
not traditionally included. These were
discussed at a multi-country, multi-
disciplinary, multi-stakeholder Value
Forum.
• Free 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

4. Reasons for lack of new antibiotics
Scientific
• Challenges of antibiotic discovery
• Success rate for new antibiotic high throughput screening (HTS) four to five-fold
lower than that for targets in other therapy areas
Regulatory and Clinical
• Challenges of clinical trial design
• Superiority difficult to prove
• Available evidence at launch may not fully inform on the utility of the antibiotic
Economic
• Limited return on investment for novel antibiotics
• Traditional Price x Volume business model does not support antibiotic R&D
• Current HTA frameworks may not fully evaluate current and future benefit of
antibiotics to society

5. The dwindling antibiotic pipeline
Number of Antibacterial New
Drug Application Approvals
versus year intervals
Average number of new antibiotic
molecules per year

6. 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

7. 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 to
introduce new HTA regulation to address AMR
• UK, Sweden: government – industry dialogue
on a new framework

8. Why do we need additional elements of
value for antibiotics?
• AMR is a public health priority
• A diverse set of non-inferior antibiotics are
valuable to society
• Non-clinical and microbiology data are
important for demonstrating the value of
antibiotics
• Antibiotics have benefits that go beyond the
patient treated
• Antibiotics enable other types of treatment and
procedures

9. Additional Elements of Value Relevant to
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
• Includes both life
extension and quality of
life gains
• Generally accepted as
key criterion for positive
HTA recommendation
• Evidence typically
required by HTA bodies
often unachievable for
antibiotics (superiority
trials)
Unmet need
• Includes both severity of
disease and current
availability of alternative
treatments
• Could include use of
priority pathogen lists

11. Relevant benefits included in traditional HTA
Cost offsets
• Reduction in costs in
other areas that come
from use of new medicine
• Use of modelling studies
and/or evidence from
clinical trials
Productivity benefits
• Gains or losses related to
value of patient’s time,
receiving medical care or
out of work
• Use of modelling studies
and/or evidence from
clinical trials /
observational studies

12. Other types of benefit of possible relevance
to antibiotics
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

13. Other types of benefit of possible relevance
to antibiotics
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

14. Other types of benefit of possible relevance
to antibiotics
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

15. Insights gained from the Value Forum
• Some of the additional elements of value not typically considered in
traditional HTA are not unique to antibiotics
• Transmission value is important in assessing the value of a vaccine
• Surrogate end-points are used in a number of disease areas
• Measurement of some elements likely to require modelling studies,
evidence on decision-makers and/or the public’s attitudes towards risk
• Potential for use of multi-criteria decision analysis (MCDA), which uses
structured, explicit approaches to decisions involving multiple criteria
• New elements of value should be seen as additional elements within
current HTA frameworks rather than requiring a completely new
assessment framework for antibiotics.
• Need for collaboration and/or engagement with international and global
organisations such the OECD and EUnetHTA.

16. Final Remarks
• There is a need to refine and finalise the additional
elements of value within the framework.
• There is further work required to understand how
additional elements of value can be used to make HTA
decisions
• Further discussion is needed as to which elements of
value could usefully be assessed at the product level, and
so potentially by an HTA body, and which elements
require a broader public health perspective.
• There is a clear need for further education in order to
expand awareness among HTA bodies and health care
payers of the particular characteristics of antibiotics and
infectious diseases as a therapy area

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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