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Pharmaceutical Policy
Concurrent Session B3 — Oral Presentation
Monday, April 15, 2019
Special Thanks to: Jesmine Cai, Tina Wang, and Neil McAuslane
Lawrence Liberti
Executive Director
CIRS - Centre for Innovation in Regulatory Science
The Relationship of Conditional
Regulatory Approvals to HTA
Recommendations —
Outcome and Timing
Background
Over the last decade, there is increasing use of facilitated regulatory
pathway (FRP) by regulatory agencies to expedite the review of important
new treatments for serious illnesses or addressing unmet medical need
Facilitated Regulatory Pathways
Regulatory pathway designed to facilitate availability, review and/or approval of medicines where there is an unmet medical need by providing alternatives to standard regulatory review routes
ARE HTA RECOMMENDATIONS ALIGNED WITH FRPs TO ENABLE TIMELY
ACCESS TO MEANINGFUL NEW MEDICINES?
Study objective
Examples of Facilitated Regulatory Pathways
US FDA: ‐ Accelerated approval ‐ Breakthrough therapy designation ‐ Fast track ‐ Regenerative Medicine Advanced Therapy Designation (RMAT) ‐ Priority review designation ‐ Orphan designation ‐ Rare pediatric disease priority review voucher ‐ Real Time Oncology Review (RTOR)
EU EMA: ‐ PRIME ‐ Accelerated assessment ‐ Conditional marketing authorisation ‐ Orphan designation ‐ Advanced Therapy Medicinal Product Classification ‐ Exceptional Circumstances ‐ Adaptive pathways (via EMA HTA Parallel Scientific Advice)
Health Canada - Priority review
- Conditional (Notice of Compliance with conditions)
The purpose of the study was to investigate the relationship of
conditional approvals (including NOC-cs) to HTA
recommendations
in terms of the HTA outcomes and timing
Study method
Data source
CIRS HTAdock Database
An ongoing programme to monitor regulatory and HTA performance,;data collected for new
active substances (NASs) appraised by key HTA agencies, analysing synchronisation between
the regulatory decision and first HTA recommendation in timing and outcome.
Data collected on internationalised NASs)were evaluated in terms of:
• Type of regulatory review pathways (Standard vs. Conditional)
• HTA decisions/ recommendations
• Timing of regulatory submission to HTA decisions/recommendations
Regulatory approval from both of these agencies: (2012 to 2017)
EMA Health Canada
1st HTA recommendation by one of the following HTA agencies: (2015 to 2017)
CADTH HAS IQWIG SMC TLV
The 1st HTA recommendation was then classified into the following categories: • Positive • Positive with restrictions • Negative • Multiple
NASs were identified from the CIRS Regulatory Approval Times Database that had:
For this presentation, analyses focused on NASs appraised by key HTA agencies from 2015
to 2017 Datasets in this study
Study method-Trichotomous categorisation of HTA Decisions
Canada England Germany France Scotland Sweden
Positive
Positive with restrictions
Negative
List
List with clinical criteria
and/or conditions
Do not list at the submitted price
Do not list/ reimburse
Recommended
Managed Access Scheme
Indications differ from Market Authorisation
Not recommended
Major benefit
Important benefit
Moderate benefit
Minor benefit
Lesser benefit
Major added benefit
Considerable added benefit
Minor added benefit
Non-quantifiable added benefit
No added benefit proven
Less benefit
Accepted General subsidy
Accepted with restrictions Restricted
subsidy
Not recommended No subsidy
Where a green outline indicates that drug reimbursement is possible while a red outline indicates that drug reimbursement is not possible
Classification as described in CIRS R&D Briefing 69: Cai J, McAuslane N, Liberti L. 2018. R&D Briefing 69: Review of HTA outcomes and timelines in Australia, Canada and Europe 2014-2017. Centre for Innovation in Regulatory Science. London, UK
Conditional vs. standard approvals in Canada
11
6
49
11
4
0%
20%
40%
60%
80%
100%
Standard (64) Conditional (17)
Negative Restriction Positive
HTA recommendation - timelines
Time from HC submission to CADTH recommendation according to procedure
[CELLRANGE] [CELLRANGE]
[CELLRANGE] [CELLRANGE]
[CELLRANGE] [CELLRANGE]
-100
0
100
200
300
400
500
600
Standard Conditional Standard Conditional Standard Conditional
Tim
e (d
ays)
252 218
Median, Box : 25th and 75th percentiles,
Number of products submitted through Standard process: 40 Conditional process: 14
HC submission to HC approval
HC approval to CADTH submission
CADTH submission to CADTH recommendation
Comparison with Europe: 1st HTA Recommendations 2015-2017
11
6
7 1 5
29
3 13
3
5 1
49
11
20 6
23
3
17
20 2
25
1
4
29 5
46
9
20
8
22 4 18
3
1 2 2
0%
20%
40%
60%
80%
100%
Stan
dar
d (
64
)
Co
nd
itio
nal
(1
7)
Stan
dar
d (
56
)
Co
nd
itio
nal
(1
2)
Stan
dar
d (
75
)
Co
nd
itio
nal
(1
2)
Stan
dar
d (
68
)
Co
nd
itio
nal
(1
1)
Stan
dar
d (
57
)
Co
nd
itio
nal
(9
)
Stan
dar
d (
48
)
Co
nd
itio
nal
(5
)
Negative Restriction Positive Multiple
England France Germany Scotland Sweden Canada
Number of NASs with 1st HTA recommendation in 2015-2017
Liberti et al:
Frontiers
Pharmacol. 201
7;8:161
Comparison with US FDA
[PERCENTAGE]
Out of 12 FDA Standard Approval in this cohort, 100% were approved
as standard approval by HC
[PERCENTAGE]
48%
Out of 12 FDA Accelerated Approval in this cohort, 52% were approved as conditional
approval by HC
HC NOC-Cs HC Standard
This cohort contained 24 NASs that were approved by • Health Canada in 2015-2017 • FDA Accelerated process in 2015-2017
Summary (2015-2017)
• 21% (17/81) NASs were granted a NOC-C by Health
Canada
• For NOC-Cs the median time for HC approvals was
approximately one month faster than standard approvals.
• Median time to CADTH recommendation was only about 2
weeks longer than for standard, but NOC-Cs were more likely
to receive an initial negative recommendation.
• For Conditional Approvals, positive/positive with restriction
recommendations were more frequent in Europe than Canada
• This warrants a better understanding of the factors
underlying the initial negative recommendations, to better align
expedited access recommendations with NOC-Cs.
Recommendation 12
McAuslane et al: he Confluence of Accelerated
Regulatory and Health Technology Assessment
Access Pathways. CPT Nov 2018
Pharmaceutical Policy
Concurrent Session B3 — Oral Presentation
Monday, April 15, 2019
Special Thanks to: Jesmine Cai, Tina Wang, and Neil McAuslane
Lawrence Liberti
Executive Director
CIRS - Centre for Innovation in Regulatory Science
The Relationship of Conditional
Regulatory Approvals to HTA
Recommendations —
Outcome and Timing
