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13/9/24

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Early Evidence Generation: A Strategic Roadmap to Successful Market Access

Authors

Evangelos Papastergios

In Part 1 of this series, we explored why successful market access requires more than just regulatory approval, emphasising the need for a thorough evidence strategy that captures the value of a new technology for all relevant stakeholders.

An evidence strategy should link the aspirational value proposition to unmet medical needs, identify evidence gaps, and plan research activities to address these evidence gaps from the earliest stages of clinical development.To minimise uncertainty and set the stage for successful market access, an early evidence strategy should focus on four key areas (Table 1).

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Burden of illness & unmet needs

At the outset, manufacturers should leverage the literature to grasp the clinical, economic and humanistic burden of the disease. Epidemiological studies can be used to estimate the size of the patient population and how it might change over time. Concurrently, a careful examination of demographic and clinical patient characteristics can reveal subgroups with the highest unmet need and potential to benefit from the new technology.

Economic and patient-reported outcome (PRO) data allows manufacturers to quantify the impact of the disease on healthcare systems and patients’ quality of life. This data also forms the foundation of future cost-effectiveness models. Therefore, early reviews of the economic and PRO literature are critical for identifying evidence gaps and planning real-world evidence (RWE) generation.

Drug developers should next thoroughly map the patient journey, treatment options and determinants of treatment choice through a pragmatic review of international and local clinical guidelines. The resulting insights facilitate optimal positioning of the new technology within treatment pathways and reveal its closest comparators.

Collectively, these activities identify the clinical context, patient profiles and outcomes where the new product can offer the greatest incremental value. A data-driven vision then serves as the cornerstone of evidence generation by guiding the design of clinical trials, indirect treatment comparisons (ITCs) and economic models.

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Market access environment

Understanding the market access environment begins with mapping payers, health technology assessment (HTA) processes and evidentiary requirements in geographies of interest. This is best achieved through a targeted review of HTA guidance on clinical and supporting evidence requirements. Potential areas of focus include stakeholders’ acceptance and preferred methodologies for ITCs, RWE and specific outcomes. Special evaluation procedures and criteria relating to the sponsor's indication and drug type should also be considered.

The second important phase of HTA-related research includes a pragmatic review of past appraisals of related competitor products.This exercise documents assessors’ criticisms of previously submitted evidence and how challenges were resolved in practice.

Lastly, sponsors can gain tailored feedback by directly engaging with HTA agencies through early advice services. These formal discussions may encompass the therapeutic landscape, proposed clinical development program, economic analyses and supporting evidence plans. Early advice is offered not only by single HTA agencies, such as NICE,² G-BA³ and CADTH,⁴ but increasingly also through joint consultations with various HTA and regulatory agencies, including EMA/EUnetHTA 21,^{5, 6} MHRA/NICE⁷ and NICE/CADTH.⁸ Single HTA advice is better suited to exploring country-specific considerations, while parallel advice can identify divergent evidentiary requirements and promote alignment.

As the value of early advice depends on the quality of questions posed, it is important to precisely define uncertainties, select the right advisory service and prepare a comprehensive briefing book to guide discussions. Timing is also key as the consultation should happen once there is sufficient alignment on the clinical development plan and outstanding questions, but also enough time to incorporate the feedback into the design of pivotal trials, evidence synthesis and economic models. Despite these logistical challenges, however, early advice represents a great investment toward circumventing reimbursement hurdles.

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Competitive landscape

Early literature reviews and ITCs serve multiple strategic functions in evidence generation. Firstly, they are valuable tools for exploring the treatment landscape. By reviewing relevant completed and ongoing trials of relevant interventions, they can reveal how a technology might compare to current and future alternatives. This informs evidence generation planning,value messaging and positioning. Secondly, early literature reviews assess the heterogeneity between relevant comparator trials (e.g. in patient characteristics and endpoints) and the feasibility of an ITC. Early awareness of evidence gaps can guide trial design and RWE generation in a way that enables indirect comparisons to the future standard of care during HTA. Lastly,the results of ITCs can serve as valuable inputs to early health economic models.

Ultimately, reimbursement decisions hinge on comparative evidence demonstrating the efficacy, safety and cost-effectiveness of a technology versus alternatives. The preferred type of evidence consists of head-to-head randomised controlled trials (RCTs) versus the comparator(s) of interest. In their absence, however, HTA agencies often accept rigorous ITCs, such as network meta-analyses (NMAs), informed by systematic literature reviews(SLRs). SLRs comprehensively identify, appraise and synthesise all available evidence on alternative interventions for an indication. NMAs can then estimate relative treatment effects between competing interventions by statistically synthesising the findings of both direct (i.e. interventions compared in ahead-to-head trial) and indirect comparisons (i.e. interventions separately compared to a common comparator).

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Economic value

Health economic modelling can demonstrate the cost-effectiveness of a new therapy against alternatives. Late-stage models that inform HTA submissions and pricing discussions are typically constructed based on completed Phase 3 and subsequent studies. However, economic models can also be created earlier in the drug development process, using clinical data from Phase 1, 2 or (interim) Phase 3 trials and economic data from the literature. Early models offer several strategic benefits.

Firstly, early economic models provide an early readout of potential cost-effectiveness and market potential, helping to determine a technology’s economically justifiable price and commercial viability. These insights are critical for go/no-go decisions and effective resource allocation.Conversely, a given drug price and incremental cost-effectiveness ratio can serve as model inputs to determine the target efficacy that would facilitate successful reimbursement.

Secondly, early models highlight the main value drivers and expose related data gaps. As a model’s predictions are only as accurate as its inputs, cost-effectiveness modelling should be paired with a rigorous evidence synthesis program distilling the most up-to-date information. Based on these insights, manufacturers can ensure that key economic measures are incorporated into pivotal trials and real-world studies.

Lastly, designing economic models early allows manufacturers to stress-test their modelling methods and assumptions with opinion leaders, payers and assessors. Through continuous refinement, the early model can be developed into a robust final economic model that successfully supports HTA submissions and satisfies stakeholders.

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Final thoughts: adapting to the evolving landscape

At its core, an evidence generation strategy involves the systematic identification of evidence gaps and the development of a research program to address them in time for launch of a new technology. Crucially, the evolving disease, market and policy landscape means that evidence generation should bean iterative process. Literature reviews, NMAs and economic models should be living documents, updated regularly as relevant new information about the technology becomes available. This process requires significant resources,coordination and cross-functional expertise but represents an investment that removes blind spots and ensures that research efforts are focused where they will have the greatest impact.

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Early evidence generation and Symmetron

Symmetron is committed to improving patient outcomes by empowering our clients with robust evidence to successfully launch their groundbreaking therapies. We recognise the importance of a holistic approach to evidence generation and take pride in our interdisciplinary expertise and ongoing cross-functional collaboration. This approach allows us to anticipate and overcome diverse market access challenges, guaranteeing that your product’s value is substantiated by the data and methodologies that are most compelling to decision-makers.

To find out more about how we can help you develop your early evidence strategy, please contact us.

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