Stakeholder dialogue in Europe’s adaptive pathways pilot

The European Medicines Agency (EMA) has worked for several years to speed patient access to new medicines. Evidence suggests that medicines using the resulting accelerated access initiatives experience variable reimbursement outcomes due to uncertainties in the clinical or economic evidence base. In other words, what is satisfactory from a regulatory perspective might not be from a reimbursement perspective.

One such EMA initiative is the adaptive pathways (AP) concept, which was launched in 2014 as a pilot to improve access to medicines in therapeutic areas addressing high unmet need. Now, it is worth exploring what we’ve learned and to look ahead to
the future of accelerated access initiatives.

The principles underpinning the AP concept

The AP approach is designed for products in therapeutic areas of high unmet need and for which it may be difficult to generate clinical data via the regular route. To be eligible, products must also meet criteria associated with three key principles:

1. The use of an iterative development plan whereby evidence can be collected in a stepwise fashion and approval can be sought in a restricted patient population
2. The use of real-world evidence (RWE) as a complement to clinical trial data to support reimbursement decisions after Conditional Marketing Authorisation (CMA) is granted
3. The involvement of multiple stakeholders in discussing the product development programme and risk management so that the company can plan how to meet their demands.

The principles in practice

Of the 62 applications the EMA received for the AP pilot, seven were included in the process. So, what have we learned from the experience?

Principle 1

Discussions of the drug development plan emphasised assessing the feasibility of the proposed methodology for delivering the required data. Specifically, groups discussed the robustness of data sources; whether

the endpoints suggested were clear-cut, actionable and methodologically reliable; and whether the proposed methodology would allow for reliable treatment comparisons
to quantify therapeutic efficacy.

Principle 2

Applicants suggested that RWE be applied in a number of ways, which include using:

• Disease registries to identify the natural history of the disease, the current standard of care, resource utilisation and adherence to treatment
• Single-arm studies in rare diseases for comparison to outcomes inferred from disease registries
• Efficacy and safety data from early compassionate use programmes to supplement clinical trials
  in small populations
• Effectiveness and long-term outcomes from post-authorisation drug registries
• Drug registries linked to risk-sharing schemes for reimbursement.

Principle 3

The pilot provided a ‘safe harbour’ for informal dialogue between key stakeholders in which companies could explore different scenarios and options in a confidential forum. In the scientific advice sessions, involvement was limited to regulators and HTA bodies and, in some instances, clinicians and patients.

Payers participated in only one case in which they provided high-level comments on a risk-sharing plan. Indeed, the payer community has highlighted a number of weaknesses with the AP concept, including a concern over immature or incomplete data.

The future for accelerated access in Europe

Multi-stakeholder engagement is central to the AP concept, and it is likely that for products with a particularly high unmet need, a dialogue across a larger group of stakeholders will be required in the future. Asset owners will need to be fully prepared for such meetings with a well- developed value proposition; relevant, targeted questions; and a credible and realistic RWE plan.

The payer community is expected to have a more prominent role in advice procedures, particularly with respect to post-authorisation monitoring and RWE collection. Companies may also be granted more timeline flexibility in gathering advice from multiple stakeholders. Finally, the concept of ‘high unmet need’ will need to be further defined.

In conclusion, it is clear that early and enhanced dialogue with wide stakeholder groups is crucial to being able to respond to an unmet medical need with sufficient evidence to ensure accelerated access.

Matthew Bending is the head of HTA, Strategy & Communication, Commercialisation & Outcomes at ICON plc, with responsibility for a global team based in the US and Europe. He is a leader in Integrated Scientific Advice, combining HTA, regulatory and patient perspectives, and supporting companies to eliminate the silo effect.

For more information visit www.ICONplc.com/commercialisation