Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Adaptive Pathways - Challenges of a global development program for early patient access in the context of the current Health Care System and Health Technology Assessment Landscape in Europe, USA and Japan

Hannah Hähl (Abschlußjahr: 2018)

Summary
Language: English
This theses discusses the concept and the surrounding regulatory framework of Adaptive Pathways, which aims to enable early patient access of promising drugs, that are able to address a high unmet medical need. Although this concept was mainly shaped in the European area, Adaptive Pathways can be applied in even more regions such as the U.S. and Japan. Therefore this thesis also outlines the regulatory framework in these regions and describes the different Health Technology Assessment (HTA) and payer systems in Europe, Japan and the US in order to identify possible approaches to pricing and reimbursement because patient access ultimately depends on the HTA body’s or payer’s decision to reimburse new technologies.
The thesis further shows that, despite certain regional strains, every region faces similar challenges and barriers due to the present HTA and payer landscape. The restructured development program of Adaptive Pathways is associated with an evidence shift from the pre- to the post-approval phase, which leads to the major payer concern, that Adaptive Pathways will enable approval of high priced drugs with an uncertain benefit-risk profile. Those products are not considered to be cost-effective in their eyes, which often results in reimbursement denials and prevent patients from receiving urgently needed treatments. In order to avoid these situations, sponsors must establish a suitable development program, which is able to demonstrate value to regulators and, even more important to payers and HTA bodies. This exercise is often challenging because payer and HTA bodies needs significantly differ from regulatory requirements. Payer and HTAb focus on comparative benefits, real world effectiveness and economic value. Regulators instead, are mainly interested in a drug’s safety and efficacy. Moreover, because large parts of evidence will only be obtained after approval, initial uncertainties on a drug’s value will never be completely eliminated. Therefore, it is absolutely necessary, that all involved stakeholders engage very early in the development. Moreover, sponsor and payers need to share the risks, that are associated with the initial limited evidence base. This can be achieved with the employment of so-called Risk Sharing Agreements or Managed Entry Agreements. However, these agreements are very complex and only a limited number of payers has sufficient experience in order to enter in these agreements. Additional region-specific barriers make the employment of such agreements even more difficult. Moreover, they often require additional data collection, preferably presented as Real World Data in order to demonstrate an adequate level of evidence to payers and HTA bodies. The thesis shows, that this is also one of the bottlenecks of Adaptive Pathways, because none of the regions, which are discussed in this thesis can provide a sufficiently developed infrastructure which allows for appropriate Real World Data collection.
In order to still enter these pathways, the thesis outlines possible ways forward on a  product-specific level and gives recommendations in order to establish the required framework, that may enable a successful implementation of Adaptive Pathways.
Continuous collaboration with patients and their caregivers along the entire development pathway is key for an adaptive pathway approach. Moreover, an increased level of transparency is of major importance in order to enhance the level of trust between relevant stakeholders. This is required to effectively manage the current challenges and develop appropriate risk sharing agreements and Real World Data strategies. However, it is even more important to establish a well-functioning Real World Data infrastructure, because this will most likely determine the success of the adaptive pathway approach in a particular country. Because this won’t be achieved by the efforts of regional regulatory authorities or individual stakeholders of a particular healthcare system, the establishment of a sound Real World Data infrastructure should be in the interest of a broader stakeholder group including policymakers, who should focus on this need and also ensure that this will be addressed in the near future.  
Pages: 81