Collaboration between EMA and EUnetHTA Development of ... · EUnetHTA Joint Action 2010–2012 |...

EUnetHTA Joint Action 2010–2012 | www.eunethta.eu

REA of Pharmaceuticals

Collaboration between EMA and EUnetHTA

Development of consensus on HTA methodologies

Mira Pavlovic, MD

Deputy Head, HTA Division, HAS, France

EUnetHTA WP-5 co-lead, WP7 lead

Moscou, May 21, 2012

EUnetHTA | European network for Health Technology Assessment | www.eunethta.eu Joint Action 2010–20122

Development of consensus on HTA

methodologies

One of the aims of European Collaboration in the field of HTA

EUnetHTA JA1 (2009-12)

WP5: REA of pharmaceuticals

Pilot of joint REA assessment

Core HTA model for REA of pharmaceuticals

Methodology guidelines

WP7:

Planned and ongoing projects (POP) database

Additional evidence generation (EVIDENT database)


Development of consensus on HTA

methodologies

European collaboration (EUnetHTA)

EunetHTA JA2 (2012-15)

• WP7 : Increase the quality of evidence generation (all HT)

– Initial evidence:

• « Early Dialogue » between developers and HTA bodies

• « Disease-specific guidelines »

– Additional evidence : « Common core protocol »

• Harmonise methods of assessment (all HT)

– Methodology guidelines

– « Core HTA information »


9 guidelines:• Criteria for choice of most appropriate comparator(s)

• Methods of comparison: direct and indirect comparisons

• Endpoints used for REA of pharmaceuticals: – Clinical endpoints

– Surrogate endpoints

– Composite endpoints

– Health-related quality of life

– Safety

• Levels of evidence:– Internal validity

– External Validity (Applicability)

Primary objective: help HTA assessors in rapid REA of pharmaceuticals

16

WP5 Methodology guidelines

(EunetHTA JA1, REA of pharmaceuticals)


Process of developing methodological guidelines

5

Draft by individuals in partner HTA organisations

Review and comments by work package 5 members

Comments incorporated by original authors

Workshops on specific topics

Revisions by original authors and HAS

Consultation with Stakeholders and Public


WP5 Methodology guidelinesProcess of guidelines development

Guidelines WP5 and SAG

consultation

(3rd drafts)

EMA and Public

consultation

(4th drafts)

• Clinical EP

• Composite EP

• Surrogate EP

• Choice of comparator

• Direct and indirect

comparisons

March 7- April 13

• Comments received

• Revised versions

expected by May 7

May 14 – July 14

• HRQoL

• Safety

• Internal validity

• Applicablity

Just started:

April 18 – May 25

June 29 – Sept. 14


WP5 Methodology guidelinesProcess of guidelines development

• 1st internal review: 1274 comments received

• 2nd internal review (ongoing)– 15 – 170 comments per guideline

• Nature of comments received

– Structure,

– Scope,

– terminology,

– define most important concepts,

– Consistency between guidelines

– Give clear and useful recommendations for HTA assessors

– Content and recommendations challenged

Real input of guidelines on REA of pharmaceuticals reviewed by HTA doers themselves

Final documents: before the end of 2012

EUnetHTA | European network for Health Technology Assessment | www.eunethta.eu Joint Action 2010–20128 88

New EUnetHTA initiative on

Early dialogue

• Part of EUnetHTA JA2 WP7 (starts: October 2012)

• One of the EU priorities

• Preparatory Pilots conducted (HAS Coordinator)

• Supposed added benefit for patients

• All HEALTH TECHNOLOGIES

• Questions on clinical relative effectiveness, economical

and other aspects, relevant for the development plan

• Prospective in nature: development strategies, e.g.

planned phase III studies, cost-effectiveness studies

• Non binding and confidential

EUnetHTA | European network for Health Technology Assessment | www.eunethta.eu Joint Action 2010–20129 99


Early dialogue

Excellent possibility to test:

– HTA prospective thinking on evidence

requirements based on concrete example(s)

– Consolidated view/agreement (?) on the choice

of comparators and endpoints for REA

basis for the development of disease-specific

guidelines (WP7 JA2)

– Test EUnetHTA guidelines recommendations in

real examples of product development



Early dialogue: PILOTS

• Gain experience

• Prepare JA2 pilots

• Define how we want to work in future

• Timetable

– 1st pilot early dialogue meeting: end of May 2012

– 2nd pilot early dialogue meeting: end of June 2012

– Feedback from HTA and company: Sept. 2012, before start of JA2

– Procedure to be revised accordingly: Oct. 2012


EUnetHTA – EMA collaboration

• Methodology guidelines

– EMA comments on EUnetHTA guidelines

– EUnetHTA members can comment on EMA

guidelines

• EMA – HTA scientific advice

– EMA SA (drugs) + several HTA bodies

• EPARs improvement project


EMEA Scientific advice (SAWP)

The SAWP (CHMP working party): Multidisciplinary Expert Group, 28 members

Advice to companies on• all aspects of drug development: quality, non-

clinical, clinical

• non-product related issues = “broad advice”, (statistics, validation of a new scale)

• qualification of biomarkers

Prospective, optional, non-binding


EMA Scientific Advice Procedure

• 2 coordinators for each request

• 1 month to prepare the report

• Internal discussion at the SAWP at D30

• Discussion with the company if necessary at D60

• Draft joint report

• 2 peer-reviewers (1 from SAWP, 1 from CHMP)

• Presented, discussed and officially validated at the CHMP

• Sent to the company

• 400 advices per year



EMA – HTA parallel scientific advice

for drugs

• Pilot phase

• 6 advices organised by Tapestry network

• More and more advices requested directly by companies

• HTA agencies chosen by the company requesting advice

• HTA input within the EMA SA procedure at the time of the discussion meeting with the company (D60) only (minutes)




for drugs - content

EMA - targeted questions – product development plan

HTA – targeted questions – active comparisons, outcomes, added value,

design of pragmatic trials, COST-EFFECTIVENESS +++

Common questions

Final advice:• by each HTA body participating in the exercise ?

• compiled document ?

• Exchange of final advices? (EMA, HTA)




for drugs

• Possibility to test:

– Agreement on the choice of comparators and endpoints both for MA and REA

– EUnetHTA and EMA guidelines recommendations in real examples of product development

– Consistency with final decisions

• EMA: MA opinion

• HTA: reimbursement



EPARs improvement project

• The High Level Pharmaceutical Forum:

– the EMA to consider how the EPAR can further contribute to relative effectiveness assessments

• EMA - EUnetHTA (2010-2011) meetings:

– adapt assessment report template (in line with comments from MEDEV/EUnetHTA)

– assessment report templates revised by EMA and used for Opinions from November 2010.

– Develop questionnaire for monitoring of the implementation

– Perform parallel review and compare results

• Results presented and compared (Feb 22, 2012, Paris)



EPARs improvement project methodology

• Checklist (questionnaire) based on the action items agreed by EUnetHTA and EMA

• 36 questions targeting areas for improvement

• Two types of answers depending on the question:– Yes (1) / No (0) / Not Applicable (13 questions)

– Excellent (3) / Good (2) / Could be improved (1) / No (0) / Not Applicable (23 questions)

• Scope: Format / Scientific content / Support for SPC

• Compliance of the EPAR for each question



EPARs improvement project – parallel

review

Pumarix, Esbriet, Teysuno, Xeplion, Xiapex, Gilenya, Halaven, Jevtana, Pravafenix, Trobalt

EUnetHTA

• Each EPAR reviewed by two HTA organisations,

EMA

• First review (all EPARs): single reviewer

• Peer review: senior member of staff

Same questionnaire

Same assessment scales

Same evaluation tool


EPAR improvement project

EUnetHTA Observations

• Space for improvement in discussion of the key elements of the clinical study design.

– Patient population, Comparators, Duration of the study, Endpoints and/or composite endpoint use

• Shortcomings of efficacy data would benefit from more discussion in the assessment report.

• Additional analysis requested by the CHMP should be better identified and explained in the assessment report

• EUnetHTA (coordinated by HAS) to make a consolidated proposal for further improvements of the EPAR, highlight expectations


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