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By Erika Turkstra and Ola Lubojemska
Behind every successful launch there is much groundwork to ensure that the evidence package supporting a new medicine or medical device meets the requirements of key stakeholders, including regulators, payers, clinicians and patients.
One of the tools that can be successfully utilized by manufacturers in their pursuit of a successful launch is early scientific advice (ESA). ESA is engagement with regulators and/or payers that can be initiated by manufacturers to create an evidence package that meets the requirements of key regulatory and payer stakeholders. It provides biopharmaceutical companies with the opportunity to ask questions about:
Some market access considerations do not always align with the regulatory perspectives including population covered, comparators, real-life benefits and outcomes. Additionally, health technology assessment (HTA) agencies and payers in the different markets have different evaluation criteria, depending on the market archetype (i.e., comparative clinical effectiveness markets, budget impact markets, and cost-effectiveness markets) and methodologies to assess either clinical or economic value to the healthcare system. The HTA evaluation will also impact the price of the new treatment in each market. As a result, an evidence package that is suitable for reimbursement in the UK, may not be sufficient to support reimbursement in Germany. To mitigate some of these uncertainties, several HTA agencies offer ESA as a fee-for-service consultation to biopharmaceutical companies wishing to engage with payers early during drug development process.
The UK (National Institute for Health and Care Excellence (NICE) Scientific Advice service) and Canada (Canadian Agency for Drugs & Technologies in Health (CADTH) Scientific Advice Program) are two cost-effectiveness markets that have well-established examples of ESA. Both within CADTH and NICE, the ESA service is independent of the evaluation process. It offers advice on the trial protocol and evidence-generation activities to support the clinical and economic value. Most important ESA provides opportunities for global drug development teams to better understand reimbursement hurdles and guidance on what is considered to be complete and relevant evidence for a future reimbursement evaluation of their products by payers.
The process and timeframe of the engagement for both agencies are similar, taking approximately 18 weeks from the moment the briefing book (a document prepared by the biopharmaceutical company, providing background information and specifying questions for which advice is sought and determining the full scope of the engagement) is submitted (Figure 1). With the development of the briefing booklet itself taking up to 12 weeks (depending on the organization and complexity of the project), the manufacturers should plan for the process to take approximately 30 weeks from start to finish.
Figure 1: Overview of Scientific Advice process provided by NICE (England) and CADTH (Canada)
Note: For more complex projects or where clarification steps are required, the timeframe may extend beyond 18-week period by a few weeks
Solid line: Key activities
Dashed line: Optional activities
Building on the synergies between the two programs, in early 2019, CADTH and NICE announced their collaboration resulting in the Parallel Scientific Advice Program. The initiative provides the participating biopharmaceutical companies with consolidated, comprehensive and practical advice from two HTA agencies in a single, streamlined process. By engaging, manufacturers not only can identify the similarities in the advice provided by participating agencies but also, perhaps more importantly, in the words of CADTH, “clarify areas of divergence in order to confirm a single approach that meets the needs of each agency,” resulting in relevant evidence generation for both the Canadian and English markets. The outcome of the engagement is a single advice report providing joint summary highlighting the areas of alignment between CADTH and NICE, as well as two separate reports with advice from each of the partaking agencies.
Overall, the timeframe of the engagement, from the moment of the final briefing book submission to the moment of final Advice Report release, is only approximately two weeks longer than a single engagement with either NICE or CADTH (20 vs. 18 weeks, with slightly longer timelines for larger/more complicated projects). Additionally, compared with two separate engagements, the process is likely to be a more efficient and less time-consuming for the applicant, with only one submission dossier and one joint scientific advice meeting with NICE, CADTH and experts engaged by each agency (Figure 2)
Figure 2: NICE and CADTH Parallel Scientific Advice – Overview of the Process
The purpose of obtaining ESA is to reduce uncertainty in the comparative clinical and economic value of the new treatment for payers. It thereby increases the likelihood of timely market access, patient population covered by the marketing authorization with a price that meets healthcare budget expectations. But with time commitments and fees associated with the engagement (£47-68k and $65-100k per NICE and CADTH ESA, respectively), is ESA worth it?
Parexel conducted a study to understand if ESA might have improved reimbursement outcomes in England and Canada. ESA is confidential and no records of ESA taking place are publicly available. Therefore, Parexel analyzed negative appraisals from England (NICE) and Canada (CADTH) and based on the negative feedback, attempted to determine whether an ESA might have improved the final assessment outcome. Whenever a negative outcome was driven by inappropriate study design or comparator, it was assumed that ESA could have been beneficial. In other cases (i.e., where negative feedback focused on clinical value, cost-effectiveness or budget impact) the impact of ESA was considered low as the information was confounded by study outcomes rather than just data quality (this was part of a bigger study presented by Parexel at ISPOR Europe 2022 in Vienna).
Of the 19 appraisals which resulted in a negative reimbursement decisions (9 in England and 10 in Canada), nearly half (48%) could have potentially benefited from ESA (Table 1), based on our assessment of reasons for negative reimbursement decision (Figure 3). ESA could have helped with the trial design and the choice of a comparator(s) that would be more reflective of clinical practice, which might reduce uncertainty in clinical and economic value. Of the analyzed reports, trial design and comparator were cited (among others) as reasons for the negative appraisals in 58% and 26% of submissions, respectively. To what extent this would have influenced the reimbursement outcomes is hard to say; however, the time and effort spent on ESA may be worthwhile if the revenue from a successful launch is at stake. Especially, if the market access was denied or restricted on grounds of a wrong comparator or insufficient data package at the time of submission, factors that could potentially be avoided with the foresight provided by ESA and the right tactics employed at the right time.
Table 1: Appraisals that could have benefited from ESA in England and Canada
Note: Negative technology appraisals published between 1st January 2021 to 31st May 2022 were manually screened and assessed
Figure 3: Drivers of the negative HTA outcome shown as proportion of decisions
Note: More than one reason could be provided per appraisal
Parexel offers unique strength in market access. We can help you navigate the landscape of numerous payer engagement opportunities to ensure that your engagement results in constructive and actionable advice obtained in a time- and resource-efficient manner. Our staff are subject matter experts who have a broad experience of engaging with various agencies on early scientific advice and/or are former HTA agency employees who can provide first-hand payer perspectives.. We have been supporting manufacturers with ESA engagements since 2010 and submitted 3 out of 7 ESA during the pilot ESA program run by EUnetHTA. With over a decade of experience in driving ESA engagements, we have covered a variety of disease areas including neurology (multiple sclerosis), cardiovascular diseases, hem oncology, and autoimmune diseases (atopic dermatitis, rheumatoid arthritis). With extensive global access strategy experience, we are in the best position to assist you asking the right questions, interpreting the answers, and determining what evidence-generation activities are essential vs. “nice-to-have”. By supporting you in devising the optimal HTA strategy, we can reduce the uncertainty in the decision-making and, ultimately, help you to deliver the right treatments to the patients who need them across the world. We cover everything from global pricing and market access (P&MA) strategy to local market access planning and HTA submission through HTA and early payer engagement, evidence optimization, and value communication. By extension, we can help you maximize your chances of a successful launch.
Further reference material can be found at:
New Medicines, Novel Insights: Achieving patient-guided drug development
Oct 30, 2023
Why Rare Disease Therapeutics Need Early Market Access Planning
Jan 4, 2023
Three strategies for articulating a coherent product value story
Dec 18, 2021
Pragmatic Trials: Targeting evidence generation to inform market access and meet payers’ needs
Feb 8, 2022
How biotechs can strengthen their value story with advanced analytics
Feb 15, 2022
Overview of China's Market Approval Policy Med Insurance Payment System
Apr 7, 2022
China's Market Approval Policy and Medical Insurance Payment System for Rare Disease
Jul 21, 2022
Preparing for a new era in European Market Access
Jul 22, 2022
U.S. price reforms 2022: How can drug manufacturers best prepare for the Inflation Reduction Act?
Aug 17, 2022
Innovative modeling method could speed patient access to critical IO therapies
Jan 4, 2023
Expedite payer coverage with surrogate endpoints
Sep 6, 2023
Are you using real-world evidence?
Feb 1, 2023