Download How to assess co-dependent technologies

How to assess co-dependent
technologies
Dr Mira Pavlovic-Ganascia
Deputy Director for HTA
Haute Autorité de Santé
France
How to assess
co-dependent technologies
• Key words:
– Harmonise, Synchronise, Co-ordinate
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Concepts
Development
MAA process
Assessment for reimbursement process
Safety reporting (out of scope)
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Co-dependent technologies
Harmonise, synchronise, co-ordinate
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Development:
– Harmonise:
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Concepts, definitions, terminology
Development requirements (regulatory, HTA) adequate for
the intended use
Synchronise the development of co-dependent
technologies
Synchronise and co-ordinate the process
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Industry
HTA bodies and payers
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Concepts, definitions, terminology
HTA
• Co-dependent technologies (PBAC, AU): health
technologies are co-dependent if their use needs to be
combined (either sequentially or simultaneously) to
achieve or enhance the intended clinical effect of either
technology
– Mostly drug + test
• Co-dependent products are products that depend on the
use of a diagnostic test to meet their labelled safety and
effectiveness claims (FDA)
• Hybrid HT combine the characteristics of different HT in
one entity
– Drug + medical device (e.g. insulin pumps)
– Procedure + drug + device
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Development requirements
depend on the type of HT
• In hybrid HT, the most important part of hybrid
HT drives development and assessment
– Chondroselect: drug part most important
• For co-dependent technologies, e.g. drug +
diagnostic test, both are equally important
– Development of IVDMD
– Development of a drug
– Co-development drug+IVDMD
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Development requirements
IVDMD
Scientific basis
Expression in diseased and non-diseased tissues
Consistent relationship between IVDMD and condition
Analytical performance = analytical validity
ability of a test to measure accurately marker of interest
early stage of development, before clinical trial
Diagnostic performance = clinical validity = diagnostic
accuracy
accuracy with which a test predicts the presence (absence)
of disease or a characteristic (able to adequately
select/stratify patients)
Specificity, sensitivity, NPV, PPV, Versus reference
test if available; phase I-II clinical trials, single arm 6
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Development requirements
IVDMD
Clinical utility = clinical usefulness
likelihood that the test will lead to improved outcome with a
given intervention by informing treatment decision
clinical utility needs to be demonstrated in population
that reflects clinical use
phase III pivotal test-drug clinical trial (RCT): test-drug
(cost)-effectiveness and safety vs adequate comparator
if available
RELEVANT FOR INTENDED USE
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Development requirements
Intended use
• Predictive use: pre-treatment patient characteristic that
determines if a patient is a good candidate for treatment with a
specific product
– Related to a particular therapeutic intervention
• Identify patients who are most likely to benefit from a product
• Exclude patients at increased risk for product-related serious
adverse reactions
• Monitor response to treatment
– Drug effects compared in marker+ vs marker- patients (?)
• Prognostic use
– No intrinsic relation to specific intervention
• Indicates natural history of a disease
– Disease outcomes compared in marker+ and marker- patients
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Development requirements for predictive use
Unselected or enriched population?
• Predictive claims for IVDMD rely upon understanding the
effects of the drug in both marker+ and marker- patients
(FDA, EMA)
• Enrolment of enriched population only (marker+)
acceptable (EMA) (enriched design):
– If true predictive marker
– if cut-off point established
• Inclusion of marker- population will depend of the
knowledge available ; justification necessary to include
marker- patients if a benefit is not expected in this group
• Case by case decisions
– scientific advice/early dialogue useful
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Drug+test
Regulatory setting
• Drug MAA: EMA
• Test: NB
– Conformity assessment procedure
• Test: EMA
– Diagnostic performance, cut-off values (in the
context of clinical evidence)
– Clinical utility
• Consultation procedure between EMA and
NB: planned
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Drug+test
HTA setting
France:
• Haute Autorité de Santé (HAS)
• Unique HTA body for the assessment of
all health technologies (drugs, MD,
IVDMD, procedures)
• Different committees
– Drugs: CT
– MD and IVDMD: CNEDIMTS
– Procedures: CNEDIMTS, CEEPS
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Drug+test
HTA setting (France)
HAS submission file request for drug and IVDMD available online (http://www.hassante.f r/portail/jcms/c1046750/depot-de-dossier-de-transparence)
IVDMD: data to submit on
• Intended use
• CE marking dossier
• Reference test?
• Data on IVDMD from MAA file
• Analytical validation data
• Diagnostic performance data
• Impact on the test on efficacy and safety of a drug (interaction test drug, target population, effect size, NNT)
• Conditions of testing
• Other possible use?
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Drug+test
HTA setting (France)
• IVDMD and drug assessment done in parallel, not in
combination
• Positive reimbursement decision is not automatically
extended to a diagnostic test
• Two HT follow different routes:
– Different HAS Committees: Transparency committee (drugs) and
CNEDIMTS (IVDMD)
– Different Sponsors (pharm company for drugs, another company
for IVDMD, or healthcare professionals for in-house IVDMD)
– Different timelines of assessment (longer for IVDMD, up to 1
year)
– Different decision bodies (CEPS for drugs, UNCAM for IVDMD)
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Drug+test
HTA setting (France)
• IVDMD reimbursement delayed as compared to a codeveloped drug
– In-house tests, temporarily financed by different types
of organisms, especially by INCA for cancer-related
IVDMD, may bridge the gap
• Final decision (UNCAM) based on HTA guidance given
by HAS:
– reimbursement of CE-marketed test
– both CE-marketed and in-house test
• No coordination between CEPS (drugs) and UNCAM
(IVDMD)
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Possible solutions
Synchronise and co-ordinate the process
• Before submission, (industry)
– Different sponsors for drug and test
• Different views
• Different timelines
– Same sponsor, different departments
• Different indications requested for MD and for drug
• After submission, (HTA bodies)
– Independent committees
– Different timelines
– Different final decision bodies?
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Synchronise and co-ordinate the process
Before submission (industry)
• Parallel EMA-HTA scientific advice
• Early dialogues (EUnetHTA JA2, WP7)
– between the industry and HTA bodies
– to optimise co-development
• Early contacts with regulatory and HTA
bodies for procedural matters
– EMA and NB
– HTA and payers
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Synchronise and co-ordinate the process
After submission (France)
HTA bodies and payers
• Coordinate work of different committees
• Coordinate decision bodies
• Use innovation path (CED – art. 165.1.1)
when possible
• Plan, communicate…
• Speed up…
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References
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Co-dependent and hybrid technologies. MSAC, PBAC,
[email protected]
In vitro companion diagnostic devices. FDA draft guidance, July 14,
2011
EMA/CHMP/641298/2008
EMA/CHMP/PGxWP/128435/2006
EMA/CPMP/EWP/1119/98/Rev.1
AHRQ Methods guide for medical tests reviews
AHRQ Methods research report. Addressing Challenges in Genetic
Test Evaluation
European Commission Proposal for a REGULATION OF THE
EUROPEAN PARLIAMENT AND OF THE COUNCIL on in vitro
diagnostic medical devices. COM(2012) 541 final
Annexe au dossier type: actes associés à l’utilisation d’un
médicament http://www.has-sante.fr/portail/jcms/c1046750/depotde-dossier-de-transparence
R Simon. Per Med 2010;7(1):33-47
P Landais et al. Thérapie 2009;64(3):195-201
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