Masterstudiengang "Drug Regulatory Affairs"
Master-Thesis
Impact of Health Technology Assessment (reimbursement) on considerations for international regulatory strategies ***
Dr. Maren Ulrike Koban (Abschlußjahr: 2010)
In an environment of increasing healthcare costs, policy makers and payers try to protect healthcare budgets mainly by cost containment measures regarding prices of medicinal products whilst considering their (legal) responsibility to provide access to innovative medicines. For active substances that have run out of patent, a healthy generic competition serves to regulate prices. Costs of innovative medicines particularly in areas of high need such as oncology or orphan diseases are, however, raising and consequently increase the relative budget spent. Therefore, during the development of an innovative medicinal product, not only quality, safety and efficacy need to be considered but also pricing and reimbursement requirements. Pricing and reimbursement is, also in the EU, a national responsibility as it is influenced by national processes and value judgements that are partially determined by national factors. Conditions are either negotiated prior to market or after market entry.
The costs of innovative medicines are mainly driven by increasing development costs partially due to higher regulatory requirements but also marketing spent. Premium prices are paid increasingly only for substantiated added therapeutic value, a major but not the only determinant of which are clinical and patient-relevant benefits compared to standard therapeutic intervention. Added therapeutic benefit can arise from increased efficacy/effectiveness, lesser side effects, improved applicability, convenience or quality of life. It is the task of health technology assessment (HTA) organisations to review data related to added therapeutic benefit in order to inform policy decision makers and payers in their considerations of pricing and reimbursement. Relative efficacy data to determine at least initially the added therapeutic benefit/relative effectiveness of an innovative medicinal product could be obtained from phase III registration studies. However, the design of these studies needs to accommodate requirements of both, regulatory competent authorities and HTA organisations regarding endpoint selection, comparators, study duration (longer follow-up) and population as well as statistical approaches and hence impacts the overall regulatory strategy. Regulatory competent authorities and HTA bodies should attempt to harmonise key requirements to avoid duplication of the clinical development programme and engage in an early and continuous dialogue with the company to guide them in their regulatory and HTA strategy.
This master thesis provides a brief overview of regulatory approval procedures, pricing and reimbursement systems and HTA approaches that need to be taken into consideration when discussing regulatory and HTA-relevant strategy within a development project team of an international company. The focus of this work is on European systems and developments relating to innovative medicinal products whilst occasionally looking towards relevant ex-EU countries. The potential impact of HTA requirements on the design of regulatory phase III studies to yield useable (relative) efficacy and effectiveness data is analysed. Furthermore, interaction and information exchange interfaces between regulatory competent authorities (CAs) health technology assessment (HTA) organisations and companies are discussed. Attention has been given to specific issues related to the effectiveness assessment of orphan drugs and new delivery modes.
In conclusion, policy decision makers, payers and companies are increasingly aware of the need of (relative) efficacy/effectiveness data and a harmonised approach to their assessment to support national pricing and reimbursement decisions. To avoid duplication of development programmes, phase III clinical studies need to be designed to meet the joint requirements of HTA and regulatory review. Early and continuous dialogue between regulatory competent authorities, HTA organisations and pharmaceutical companies is required to shape the clinical strategy suiting both purposes.