benchmarking the impact of hta on new medicines...
TRANSCRIPT
Introduction Health Technology Assessment (HTA) is increasingly used to evaluate new medicines in order to inform coverage decision making for efficient allocation of healthcare resources. Beyond the traditional regulatory requirements of quality, efficacy and safety, HTA considers the effectiveness, appropriateness and cost of medicinal products and technologies. Pharmaceutical companies are under pressure to adjust their drug development and submission strategy to accommodate both regulatory and HTA requirements for commercial success.
In addition, the variability in HTA organisations and methodologies that are utilised in HTA appraisal and coverage decision-making processes in different countries results in a complex and challenging environment and it is therefore important for companies to incorporate a clear understanding of HTA requirements into early strategic planning to mitigate risk.
As a result of this, CIRS (Centre for Innovation in Regulatory Science) initiated an annual benchmarking project to meet the needs of participant companies for comparative data and information in order to understand and quantify the impact of HTA on clinical development programmes, reimbursement timing and outcomes in different jurisdictions.
This poster summarises the methodology of this long-term benchmarking project, and the preliminary results from 2011-2013 studies.
Center For Innovation in Regulatory Science Mission To maintain a leadership role in identifying and applying scientific principles for the purpose of advancing regulatory and HTA policies and processes in developing and facilitating access to medicinal products Contact [email protected] [email protected]
Benchmarking the impact of HTA on new medicines development and coverage decision making
Methodology • Define the performance metrics The study questionnaire was developed in collaboration with nine multinational pharmaceutical companies to benchmark the HTA process by following individual products. Appropriate performance metrics were agreed upon by all participants to enable meaningful comparison between companies. The questionnaire comprised 19 questions, which related to eight main topics: three topics on the global development of new products and five topics on the roll-out phase in different jurisdictions; Figure 1 illustrates the schematic outline of the questionnaire. Based on the 19 questions, 62 key metrics were collected for each product, which were a combination of both quantitative metrics (for example, milestones) and qualitative indicators (for example, scientific advice activities ).
• Confirm the study scope and criteria The data collection focused on current products entering into pivotal trials to enable the most up-to-date snapshot of HTA-related activity in clinical development, as well as on licensed products to enable comparison between market access outcomes across jurisdictions. The data was captured separately with the long-term aim of being able to track products through phase III development and across roll-out to multiple jurisdictions over the coming years. The jurisdictional data collection focused on both national level and regional level recommendations for each product. The key jurisdictions included in the study were determined by the study participants: Australia, Canada (national, British Columbia, Ontario), England, France, Germany, Italy (national, Lombardia, Emilia Romagna), Spain (national, Madrid, Catalan) and the USA (CMS Medicare, Wellpoint, United).
• Establish a data collection protocol To ensure the accuracy, timeliness and security of data collection, an online data collection tool was designed to facilitate the provision of high-quality and comparable data across pharmaceutical companies.
Results Data on 19 products that entered phase III and 30 products achieving first worldwide regulatory approval from 2009-2012 were collected and analyzed.
•For the phase III projects, 63% received HTA scientific advice, of which 61% occurred during phase II. Company-sponsored advisory boards were the most frequent source of advice as well as the most influential on the development programme. (Figure 2) The main reason HTA-related scientific advice was not implemented was due to the prioritisation of regulatory requirements.
•The majority of the phase III projects (69%) included an active comparator in the development plan; the main choice of comparators was “the gold standard comparator for the indication” (Figure 3). In addition to inclusion of active comparators, HTA-related requirements were implemented in development programmes. The inclusion of requirements was extremely heterogeneous, with the main requirements being patient-reported outcomes (84%), HTA-acceptable endpoints (74%), and cost-effectiveness analysis (74%).
•Additional comparators for local HTA submission were requested by all jurisdictions except the USA (Figure 4), the main reasons for requesting additional comparators were “local standard of care” and “least costly therapy”. England and France showed the highest percentage of products being reimbursed as per the regulatory label (50% and 55% respectively).
•For licensed products, the median time from regulatory submission to reimbursement decision varied from 639 days (Australia) to 846 days (Italy). For most jurisdictions, there was a gap between the regulatory approval and HTA submission.
Conclusion Current benchmarking study results show that companies are actively taking scientific advice and incorporating HTA requirements into their development process, although they are still challenged by divergence in HTA processes and requirements across jurisdictions.
By continuing to develop this project into 2015 and beyond, the benchmarking database will become more robust and as it matures, could be used as a tool to help companies to achieve greater understanding of the diversity in HTA systems, to make the process more predictable and in particular, to identify and learn from outlier products and HTA reviews.
Tina Wang • Neil McAuslane • Lawrence Liberti Centre for Innovation in Regulatory Science, London, UK
Purpose of the study To give participating companies insight into how HTA requirements are impacting drug development and payer decision making in the context of new medicines being brought to market Objectives Define performance targets to help focus on ongoing performance improvement; Identify activities and designs through early incorporation into development programmes that best address the HTA needs; Provide a clear understanding of the HTA systems in various jurisdictions; Improve the timeliness, transparency, and process predictability of HTA review.
Figure 1: Schematic outline of project structure
Figure 2: Type and impact of HTA-related scientific advice given during development
Figure 3: Five key reasons for the choice of active comparators included in the development
Figure 4: Types of additional HTA-related information required by each jurisdiction
Figure 5: Median time to roll-out at key jurisdictions
Bibliography •Hughes B. Payers growing influence on R&D decision making. Nature Reviews Drug Discovery. 2008; 7(11):876-878. •Liberti L, Pichler, F, Walker SR. Preparing for Regulatory Review and Reimbursement Decisions: A Case for Cooperation between Regulatory Authorities, Sponsors and Health Technology Assessment Agencies. Pharm Med. 2009;23:263-267. •Pichler F, Wang T. Benchmarking time and process in HTA and decision making. Poster presentation, Rio de Janeiro, Brazil: Health Technology Assessment International Annual Conference, June 2011.
Top five HTA-related information required for local submission
Contextualise the evidence to local
population
Locally relevant economic analysis Sub-group analysis Customized
formatted dossierFormal indirect
comparisons
Australia
Canada
England
France
Germany
Spain
Italy
US United
US Wellpoint
Additional information required
No information required
A new comparator recently listed in the formulary
Based on published guidelines from HTA agency
The best characterised comparator for that indication
Based on official guidance from regulatory agency
The gold standard comparator for that indication
50%
25%
17%
4%
4%
Percentage of products
Company sponsored payer advisory board
KOL panel with primary purpose of payer information
Formal advice from a single HTA or payer agency
Formal advice from multiple HTA agencies presented in the same meeting
Formal joint advice from HTA and Regulatory presented in the same meeting
Company sponsored payer advisory board
Formal advice from multiple HTA agencies presented in the same meeting
Formal advice from a single HTA or payer agency
KOL panel with primary purpose of payer information
Formal joint advice from HTA and Regulatory presented in the same meeting
Most sought advice
Least sought advice
Freq
uenc
y of
adv
ice
Impa
ct o
f adv
ice
Most influential advice
Least influential advice
10% consultations led to major programme change, 70% consultations led to
minor programme changes
Advice led to minor programme changes
50% consultations led to minor programme changes
40% consultations led to minor programme changes
No advice under this route was captured in the study
HTA submission to coverage decision (national level)Regulatory authority review timeGap between first world wide submission and submission to local regulatory authority
Median time (days)
0 100 200 300 400 500 600 700 800 900
Australia
England
France
Canada (national)
Italy (national)
Germany
USAUnited
Wellpoint
Key
topi
csDrug development
HTA-related scientific advice
Inclusion of active comparators
Inclusion of HTA-related requirement
Jurisdiction roll-outReview and reimbursement milestones
Local submission strategy
Review characteristics
HTA appraisal/Coverage outcome
Reason for success /Outstanding issues
Access to formulary
Applicationfor market
authorisationHTA Appraisal Reimbursement
Decision MakingPreclinical
developmentClinical
development
Incorporate HTA considerations in
development to improve jurisdictional outcomes
Improve understanding of HTA requirements to
strengthen R&D planning and effectiveness
Exa
mpl
e of
key
ques
tions
• Was HTA-related scientific advice sought and complied with?
• When and from whom did company seek advice?• What was the rationale for the company’s choice of
active comparator?• What was the timing of the inclusion of HTA
requirements?• Did the inclusion of HTA requirements impact the
review process, including outcome?
• Was local scientific advice sought and complied with?• What were the local evidentiary requirements? • What were the company’s expectations of outcomes prior to submission?• How does time to market access differ between jurisdictions?• Were multiple submissions required, and if so, at what stage?• What was the outcome of the coverage decision per region?• Which requirements were deemed insufficient by the HTA/payer agency?• Were there any key issues raised during the HTA or coverage decision-making process?
10 questions (28 metrics) 9 questions (34 metrics)