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Global Value Dossiers; Meeting the Needs of PayersThursday July 18th, 2013
Introductions
Tim Clark
Vice President Scientific AffairsICON Clinical Research
James EatonLead Market Access Researcher
Leticia BarcenaSenior Systematic Reviewer
What we will discuss
Agenda
• What is a Global Value Dossier?• Considerations to be met in scoping out a dossier• Dossier development and meeting the needs of payers• Designing a systematic review for a GVD• Summary and key points
What is a Global Value Dossier?
• A Global Value Dossier GVD is a comprehensive information source which presents a summary of the clinical, economic, and humanistic value and supporting evidence (studies) for a new product in a disease area as well as background information on that disease (i.e., burden of illness, epidemiology, etc.)
• Evidence based, a well designed GVD is central to reimbursement applications and global HTA submissions
• GVDs can also inform future clinical studies, publication strategies, and other evidence generation activities
• The development and distributions of a GVD allows an integrated and consistent approach to reimbursement across multiple jurisdictions
• When maintained centrally a GVD can quickly and easily be updated with new information
Many types of dossier
• Value Dossier– Tells a story, first step in developing evidence for submissions.
Based on TPP it summarises the therapeutic area and addresses the unmet need, and how the product meets the unmet need.
• Regulatory Dossier (EMA)– Predominantly clinical in nature but should be used in preparing
reimbursement dossiers, as the HTA agency will use the regulatory documents in their deliberations.
• Reimbursement/Submission Dossier– As GVD but driven predominantly by the needs of the HTA agency,
will include fully reported systematic reviews, evidence synthesis and economic models.
– Each country’s healthcare system is different – these details should be addressed in GVD
– The key clinical messages and evidence should align across all dossiers
What to consider when developing a GVD?
• What materials are already available?– Evidence reviews– Systematic reviews– Regulatory submissions– Market research material
• Who is your client?– Have affiliates participated in the RfP process– What markets are you targeting?– What research has been conducted to determine the requirements
of the dossier?
• What format does the GVD need to be in?– Word documents/PDFs - Implications for version control– Electronic versions– Centrally or locally held dossiers
What to consider when developing a dossier?
• Timelines?– Begin GVD development as early as possible– Final dossiers should should be released with updated systematic
reviews no earlier than 6 months before submissions
• How often should dossiers be updated?– As often as is required, publications for the product, ongoing and
finished studies should be updated as soon as feasible after release.
– Systematic reviews should be kept current – this will in part be determined by outstanding reimbursement submissions and ongoing trials of the product in question
A clear understanding of the disease landscape establishes the basis for dossier development
Defining and Quantifying the Value Construct
Background
Establishing the Background and Disease Burden
• What is the current disease burden? • Epidemiology, incidence, prevalence,
humanistic and economic burden• How might be or are patients segmented?• What is the natural history of the
disease?
Gap analysis ‐ evidence synthesis
Characterizing natural history
Burden of illness
Treatment Guidelines/Pathways
Items to consider for the disease background and burden
• Burden of Illness often differs between countries – how do you capture and present this data– Incidence and prevalence – where evidence is limited engage with
local affiliates– Economic burden– Present data by jurisdiction or provide country summaries?– Evidence presented here will be used in various elements of the
dossier
• Treatment pathways/guidelines differ between countries – how do you capture local guidelines– Treatment options vary - important consideration for the scope of
any review of comparators– May need to consider previous HTA assessments of the indication
in your review of pathways– Involving affiliates at an early stage can ensure the relevant
guidance is captured
Defining and quantifying products value is critical to the dossier
Product Profile
Defining and Quantifying the Unmet Need
• Where is the opportunity for a new product?
• Summarize the product profile and clinical evidence for Product X.
• What are the logical linkages in our value construct? What are the strengths and weaknesses?
• What is the role of patient reported outcomes in this treatment?
• How does the current and planned evidence resonate with payers?
• How do we optimize the Target Product Profile?
Summarise the Opportunity for a new product
Is there a Demonstrable Impact on Disease Burden
Identify the Unmet Need
How does Product X address that need
Gap Analysis and Evidence Generation
Items to consider for the product profile
• GVD can contain varying levels of information on the product, but what is really required?– Consider providing only information from clinical studies in
the main text of the dossier– Ensure that the clinical evidence for the product in the GVD
and the regulatory dossier are aligned, regardless of which is produced first
– Provide SmPCs and product literature as appendices to the main document (allows for rapid alterations)
– If you use CSRs to populate the clinical sections, as soon as those studies are published update them and reference the publication
Effectively comparing and contrasting the evidence for Product X
Comparator review
• What evidence exists for current comparators within this therapeutic area?
• What are the efficacy and safety associated with these?
• Quantify the unmet need• How does Product X compare? • Is there a need for evidence synthesis?
Generating and Communicating Clinical
evidence
Evidence Synthesis (meta‐analysis)
Systematic Review of Clinical Studies
Systematic Review of CE studies
Utilites
Systematic Review of CE studies for Product of Interest, Costs and Utilites
Comparative Efficacy of Product X
Comparative efficacy – meeting the needs of payers
• Comparators differ by jurisdiction
• Scope of HTA’s can also include comparators not well defined at a national level
• Requirements for developing systematic reviews also differ by jurisdicition
• How do you ensure that the systematic review encompasses the needs of multiple jurisdictions– One overarching systematic review or multiple focused
systematic reviews – implications for budget and timelines
Steps in a systematic review
1. Defining an appropriate research question
2. Eligibility criteria
3. Identifying relevant studies
4. Study selection
5. Extracting data
6. Critical appraisal of included studies
7. Data synthesis
8. Report writing
Defining the review clinical question
• Define clinical question according to:- Patients- Intervention- Comparative therapy (this may between countries)- Endpoints- Study types
• Development of eligibility criteria
Inclusion/exclusion criteria
Identifying relevant studies
• Search for published literature
– MEDLINE– EMBASE– Cochrane library (CENTRAL)
Germany: Requirement of search to be conducted individually in each database and using a search strategy adapted for the database in question (use of appropriate controlled vocabulary terms):
• MeSH terms in Medline and Cochrane library
• EMTREE terms in EMBASE
The search strategy should be set up in blocks, separated according to indication, intervention and study types.
Documentation of search strategy
Search strategies should be documented including:
- The search strategy with number of hits- Database - Service provider- Date the search was conducted
Germany, UK, Canada require justification of any general restrictions such as language or year restrictions
Constructing search strategies to meet the needs of individual countries
The choice of comparators to be included in the systematic review may differ in each country, e.g. some drugs may be licensed in one country but not in others.
When constructing the search strategies terms for all relevant comparators are included so that the search will meet the requirements for all countries.
From this search a set of individual searches including the comparators relevant to each country can be run to identify studies that are relevant for one particular country
Identifying relevant studies
• Search for unpublished studies- Provided by manufacturer- Conference abstract search
• Search for on-going studies
Germany requires search:
- International Clinical Trials Registry Platform Search Portal (ICTRP- search portal of the WHO)
- Clinicaltrials.gov- Clinicalstudyresults.org (not longer available)
Selection of studies
Number of reviewers involved in the selection processSelection by two independent reviewers
Reasons for exclusionTwo phases in the selection process:
• Abstract screening phase
• Full paper review phase
Reasons for exclusion at the abstract screening phase are required for Australia (hard copies of printouts indicating excluded citations with reasons for each exclusion)
Documentation of study selection
A flow diagram detailing the study selection process should be included.
PRISMA flow diagram
PRISMA flow diagram
Critical appraisal of included studies
Cochrane risk of bias tool
• Random sequence generation
• Allocation concealment
• Blinding of participants and personnel
• Blinding of outcome assessment
• Incomplete outcome data
• Selective reporting
• Other bias
Comparative efficacy and quantitative synthesis–meeting the needs of payers
Comparative efficacy and quantitative synthesis–meeting the needs of payers
• Requirements for indirect comparisons and meta-analysis vary by jurisdiction – Decide on your base-case analysis for the dossier– Ensure that data extraction for the systematic review is
conducted to allow re-analysis and addition of endpoints/comparators
• Consult with local affiliates– What are their expectations for evidence synthesis
• Understand your potential comparators in advance and plan accordingly
Effectively Communicating the Economic Argument for the Product
Economic review and budget impact
• What evidence exists for current cost‐effectiveness estimates, cost and utilities?
• Cost effectiveness of Product X from one jurisdiction.
• Full report of methods, justification for model, results often reported as required for the primary country of interest (e.g. NICE) and discussion.
• Budget Impact what are the implications for HealthCare budgets. Again often in primary jurisdiction of interest.
Constructing the Economic Argument
Other requirements (often provided by company)
Core Global Model for Primary Jurisdiction
Budget Impact Model
Appendices: Methods, References, Additional studies as required
Executive Summary
Reporting cost-effectiveness evaluations and budget impact models in GVDs – meeting the needs of payers
• Decide on the basecase jurisdiction for the CE model and BIM to be included in the dossier– Choose a jurisdiction that has relevance to you – UK often used as
similar requirements in Canada, Australia, Korea among others
• Develop the model to allow for ready adaption to other jurisdictions, consider other requirements and understand whether they can readily be incorporated
• Keep reporting to a minimum in the dossier – capture the full model report in an appendix or stand-alone document– Present only the most relevant results and sensitivity analysis– Provide instructions/user guide on adapting the model as an
appendix and list which parameters can be used to adapt the model
Choosing the appropriate format
• Generally ‘horses for courses’ approach; benefits and risks to all formats
• Word documents/PDF’s distributed to affiliates– Easy to edit– ‘cut and paste’ into submission templates– Can be readily adapted/updated by local affiliates– Issues with version control and providing updates
• eDossier formats– Less easy to edit and ‘cut and paste’– Improved version control and updates can be managed centrally– Often require licence agreements and ‘hosting’ by third party
• Prepare effectively for the development of your GVD• Understand what material you already have and will produce before the GVD is
complete• Include relevant stakeholders (affiliates) early in the process preferably
before the GVD is started• Ensure that your requirements are clearly laid out and communicated in
the RfP• A GVD can never fully encompass the needs of every jurisdiction but
ensure that the information and tools to adapt and personalize the GVD are readily available to the end user
In Summary
ICON Signature Series
• ICON Signature Series is our thought leadership program that offers expert insights into value-driven strategies for clinical development.
• The program features ICON and external experts in all aspects of clinical development and post-approval product value strategies.
• For a list of featured topics and upcoming events go to: http://www.iconplc.com/icon-views/
