HTA and Regulatory Perspectives and Interactions:

bridging the gap

For Colleagues at the

2014 CADTH Symposium

April 7, 2014

Gatineau, Canada

Lawrence Liberti, MS, RPh, RAC

Executive Director

LLiberti@cirsci.org

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2025 - Landscape – A Viewpoint

• Complimentary evidence requirements from regulators and HTAs

• Tiered but convergent landscape between high, middle and low income countries

Convergent

•Trust: Acceptance of a Collaborative/work sharing environment –between agencies/regions

•Managing uncertainty: Innovative technologies for disease identification, treatment, management, adherence and vigilance monitoring

Collaborative

• Priorities: Patient and HCPs- facilitating access to “safe”, high quality and effective medicines globally

• Adoption of Risk-Based Facilitated Regulatory Pathways – development, approval, inspections, life cycle management, vigilance

Enabling

CIRS- Project 2020 3

Differences in

priorities seen

between functions

In this example only two

scenarios overlap between

Regulatory and

HEOR/Access

SC04 Evidentiary standards used by HTA agencies will be integrated into licensing body requirements with separate, but parallel reviews

SC19 Interaction between licensing bodies and HTA agencies will increase

HTA and Regulatory Alignment

Bruening L: Regulatory and HTA Alignment. Presented at CIRS Workshop Is there a commonality across the structured decision frameworks used by HTA and

regulatory agencies? which took place 1-2 October in Surrey UK.

How could the expectations of

diverse stakeholders, including

sponsors, regulators and HTA,

be aligned in an international

environment?

Through

• Joint Scientific Advice

• Common or aligned evidentiary requirements

• Consistency in review package evidence

Timing of HTA-related scientific advice at a global level N

um

be

r o

f c

on

su

lta

tio

ns

Timing of scientific advice by the type of advice

(Number of products, Number of companies)

Timing of development when advice was sought

7

1

2

1

2

2

1

0

2

4

6

8

10

12

Ph II (7,5) Ph III (4,3)

Formal advice from multiple HTA agenciespresented in the same meeting

Formal advice from a single HTA or payeragency

KOL Panel with primary purpose of payerinformation

Company sponsored payer advisory board

0 5 10 15 20

Extra patient visits requiredNeed for companion diagnostic

Societal benefitBudget impact / affordability issues

Cost effectiveness

Unmet needPlace in treatment pathway

Use of PRO measurePRO methodology

Patient enrichment (biomarkers)Sub-group analysis methodology

Patient selection

Use of adaptive trial designUse or applicability of patient crossover

External validity of trialTrial follow-up and longer-term outcomes

Analysis methodologyTrial durationStudy design

Benefit risk evaluationSafety evidence

Biomarkers used as a measure of efficacySpecification of non-inferiority margin

Health-related quality of lifeSpecification of superiority margin

Relative / Comparative efficacy evidenceUse of surrogate outcomes

Comparator choiceInclusion of a comparator arm in the trial

Secondary endpoint(s)HTA acceptable primary endpoint

The number of licensed products that incorporated HTA requirements into Phase 3 trials, by requirement type

Number of products

Efficacy

Safety

Trial design

PROs

Technical requirement

Patient selection

Cost

Value to healthcare system

Non-technical requirement

Non-price barriers to market

(CIRS HTA Industry Survey 2013)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Australia Canada England France Germany Italy Spain USA -Wellpoint

Phase III pivotal study,Phase IIIb pivotalstudy,Real-world evidence

Phase II study,Phase III pivotalstudy,Phase IV study,Real-worldevidencePhase II study,Phase III pivotalstudy,Real-world evidence

Phase III pivotal study,Phase IIIb pivotalstudy

Phase IIIb pivotal study

Phase III pivotal study

Phase II study,Phase IV study

Phase II study,Phase III pivotalstudy,Phase IIIb pivotal study

Phase II study,Phase III pivotal study

Phase II study

Pe

rce

nta

ge

of

Pro

du

cts

HTA review package by jurisdiction (an Overlap with Regulatory Dossiers?)

(CIRS HTA Industry Survey 2013)

Evidence used for recommendation by HTA agency

[Q17]

Total responses

5 agencies provided data overall Total reviews = 18 (CIRS HTA Agency Survey 2013)

“Input from Clinical Professionals” combines data from the

fields: “Written submissions from clinical professionals” and

“Personal statements from clinical experts presented at committee

meeting”

“Input from Patients” combines data from the fields:“Patient group

submitted information”, “Written submissions from patient experts”

and “Personal statements from patient experts presented at

committee meeting”

The association between European Medicines Agency approval and Health

Technology Assessment recommendations: HTA Assessment Outcomes (n=

86)

10

•The longer the approval time at EMA, the less beneficial

the HTA recommendation was*

•There were negative correlations between approval time

in

• HTA recommendations in England

• HTA recommendations in Netherlands

• total indicator of HTA recommendations

* All of the correlations had marginally significant tendencies

(Based on work conducted by Iga Lipska, Utrecht University 2014)

Regulatory and HTA interactions: considerations

• The independent regulatory and HTA systems are grounded

in science and focused on meeting stakeholder needs.

• Scientific advice: provides insights into what is expected,

practical, and achievable especially when provided jointly

• Opportunities to align regulatory and HTA requirements

►maximise process efficiency, consistency of outcomes.

• Sponsors: should address both regulatory and HTA data

requirements from the earliest stages of development

• Heterogeneous HTA processes are moving towards

alignment: integrating diverse needs (ie comparators, study

designs) will be challenging

• Convergent-Collaborative-Enabling: How can industry,

regulators and HTAs align to facilitate the evolution to these

goals?

HTA and Regulatory Perspectives and Interactions:

bridging the gap

For Colleagues at the

2014 CADTH Symposium

April 7, 2014

Gatineau, Canada

Lawrence Liberti, MS, RPh, RAC

Executive Director

LLiberti@cirsci.org

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