Analysis of policies regarding market access of oncology drugs.

Changing demographics, earlier detection and treatment of cancer and a growing number of therapeutic options and combination therapies lead to an increasing trend in expenditures on cancer medicines. Regulations for market access of cancer medicines, including marketing authorization, price setting and reimbursement, should ensure that effective and safe medicines are affordable for society, accessible for individual patients and profitable for pharmaceutical companies in order to foster research and development towards medicines that address the needs for the patients.  

Marketing authorization for cancer medicines is provided at European level on the condition that the quality, safety and efficacy of the medicine is demonstrated. Decisions on price setting and reimbursement have to be made at the level of individual European member states. However, at the time the decision need to be made, the evidence about clinical benefits is often still limited Furthermore, different stakeholders each have a different view on what composes the benefit of a cancer medicine.

The aim of this project is to study procedures that are applied within the process for market access of cancer medicines. Based on the results, recommendations to improve transparency, efficacy and sustainability of market access of oncology medicines are made.

Part 1 investigates instruments applied for market access of cancer medicines. In the first chapter, a review of price setting and reimbursement mechanisms in European countries indicates that cancer medicines are often exempted from cost-saving measures such as penalties for budget overspending, lump-sum payments in the hospital and thresholds for cost-effectiveness. Furthermore, cancer medicines are often subjected to managed entry agreements. Managed entry agreements address uncertainties about the clinical and financial impact of a medicine by defining measures for further evidence collection or financial compensations by the pharmaceutical company. Chapter 2 investigates orphan designations for rare cancers. Orphan designations can be applied in an early stage of medicine development and lead to scientific, regulatory and commercial incentives for the development of medicines that intent to treat rare diseases. A large share of products with orphan designations intent to treat rare cancers. Chapter 2 also shows that orphan designations for medicines that intent to treat rare cancers are granted based on more advanced stages of development compared to orphan designations for medicines that intent to treat other indications. Furthermore, orphan designations for rare cancers have to proof more often that they provide added clinical benefit compared to alternative treatments. This suggests that there is a lot of competition in the field of cancer medicines, even when the indication is rare.

Chapter 3 describes an in-depth analysis of reimbursement criteria applied by the Commission of Reimbursement of Medicines (CRM) for cancer medicines in Belgium. The CRM evaluates reimbursement applications and provides an advice on reimbursement to the Minister of Social Affairs. The results show a higher likelihood to obtain a positive advice for reimbursement if the medicine proof a significant difference for a primary end-point in a randomized controlled trial (RCT) and if alternative treatments are present. The presence of alternative treatments allows the health insurer to compare the new medicine with alternative and require benefits in terms of health or money. These results suggest that competition enables reimbursement of cancer medicines in Belgium.

The aim of chapter 4 is to compare the application of managed entry agreements for cancer medicines between different European countries. The results show that the application of managed entry agreements is heterogeneous across different countries. Financial-based agreements represent the majority of the agreements. The experience with performance-based agreements in limited to Italy and the Netherlands.

Part 2 focusses on the perspectives of the pharmaceutical industry on market access of cancer medicines. Chapter 5 present industry perspectives on the challenges related to market access of innovative medicines in general and cancer medicines in particular. Industry representatives call for a broad value definition and a system that allows a dynamic value approach that leads to reward for valuable medicines based on the assessment and appraisal of cancer medicines at both national and European level. Financial targets both at the side of the industry as well as the payers are identified as hurdles for value-based pricing.

In Part 3, societal preferences on market access of cancer medicines is addressed. Chapter 6 includes a discrete choice experiment (DCE) in the Belgian population. The following attributes were included in the choice experiment: number of patients treated by the medicine, life expectancy of the patient who can be treated by the medicine, effect of the medicine on life expectancy, quality of life of the patient who can be treated by the medicines, effect of the medicine on quality of life, cost for society related to the medicine. The results of this study indicate that the value of one unit gain in quality of life is dependent on the initial quality of life of the patients. The value of one unit gain in quality of life is higher than the value of one year gain in life expectancy, when the initial quality of life of the patient is low.

Based on the results of these individual studies, seven recommendations to promote transparency, efficiency and sustainability of market access are made.

The first recommendation calls for increased attention to added benefit of cancer medicines at European level. The procedure for marketing authorization does not take into account benefit compared to existing treatments, or benefits that are broader than clinical effects in terms of survival. Increased attention for added benefit can foster the set-up of clinical trials that are powered to show added benefits. Furthermore, the consideration of added benefit at European level can provide a basis for added benefit assessment in the individual member states during price setting and reimbursement.

The second recommendation promotes a multi-criteria decision approach where criteria for assessment and appraisal of cancer medicines are made transparent. A multi-criteria decision approach can clearly define the conditions that apply to exempt cancer medicines from particular measures, for example cost-effectiveness.

The third recommendation is based on the results of societal preferences provided in chapter 6.  Market access needs to be provided to those products that deliver the highest utility to society and therefore, quality of life should be acknowledged in clinical benefit assessment. In order to make this work, objective and valid tools to measure quality of life are required.

In the fourth recommendation, it is discussed how health-economic frameworks take into account a higher value for gain in quality of life than for gain in life expectancy.

As revealed in chapter 5, value of cancer medicines should be rewarded in terms of price in order to enable investments of the pharmaceutical industry in future innovation. A cancer medicine can, however, often be deployed in several different indications. Given the fact that the benefit of an individual cancer medicine is heavily influenced by the stage of disease, it is unlikely that a single medicine can deliver the same benefits across different indications. In order to take the value of a medicine into account, price should be set in function of the indication. Therefore, managed entry agreements should be applied in an indication specific manner to foster value-based pricing (recommendation 5). Additionally, the sixth recommendation urges to avoid mechanisms that work against value consideration such as external reference price setting.

The seventh and last recommendation emphasizes the opportunities to apply performance-based agreements to reach price setting and reimbursement in function of the value of cancer medicines.