CSL Behring
The Role of Patient Reported Outcomes to Support Reimbursement and Market Access in Major European Countries and the US
Lothar Tremmel
The effect of new therapies on health-related quality of life (HRQoL) has become an important consideration in establishing reimbursement and market access in many countries. A patient reported outcome is any report of the status of a patient’s health condition that comes directly from the patient without interpretation of the patient’s response by a clinician or anyone else.1 The objective of this brief report is to describe the ways in which PROs are used to support reimbursement and market access in major European markets as well as the US.
Countries that rely on cost-effectiveness modeling to evaluate reimbursement, such as the UK, use generic PROs that do not apply to a specific disease. The EQ-5D-5L is the tool preferred by NICE, the UK reimbursement agency, to determine the decrement in HRQoL associated with different health states included in cost-effectiveness models.2 The time that patients stay in different health states differ for different therapies. The different therapies used in the treatment of a condition are then compared in terms of their mean costs as well as the mean decrements in HRQoL associated with each therapy through the cost per quality of life year gained. Therapies with higher costs may still be cost-effective relative to other therapies if they lead to better outcomes and less time in health states associated with greater decrements in HRQoL.
In Germany, reimbursement is evaluated based on the therapy’s impact on mortality, morbidity, HRQoL and the adverse effects associated with the new treatment.3For the assessment of HRQoL, Germany prefers the SF-36 which is a different generic PRO but PROs developed for a specific disease are accepted provided they are well validated. GBA, the Germany reimbursement agency, has also established its own criteria to assess a clinically meaningful difference between the effect of the new therapy on HRQoL relative to standard of care.
France recommends inclusion of a short generic questionnaire such as the EQ-5D-5L to support economic evaluations as well as well-validated disease specific PROs.4Unlike the UK and Germany, France prefers PROs that are included as primary or secondary endpoints to adjust for multiplicity. Although the effect of PROs on the benefit rating cannot usually be isolated,the absence of HRQoL data may negatively impact reimbursement decisions involving chronic conditions with a high HRQoL impact as well as end of life treatments. HRQoL assessments indirectly affect pricing through the benefit rating assigned.
According to a recent review of HTA submissions in decentralized markets including Italy, Spain and the US, PROs have been influential in certain reimbursement submissions particularly for Oncology but there are no formal processes established for consideration of PROs in reimbursement decisions. In the US, this is now slowly changing because the Institute for Clinical and Economic Review (ICER) has been conducting economic evaluations based on cost-effectiveness modeling to influence the reimbursement of new therapies by various payers in the US.
Early clarity on the target markets and on the purpose for which the PROs will be used is essential.
In addition to influencing pricing and reimbursement directly as described above, PROs may also be useful in differentiating new therapies from existing treatments to gain market share. This is particularly useful when there is a highly competitive landscape where there are many therapies available to healthcare providers and patients for the treatment of a specific condition. Publication of PRO results from clinical trials to evaluate HRQoL is critical. New standards have been established for conducting comparisons of competing therapies based on HRQoL and utility measures in Europe.6In certain situations, for chronic conditions where the impact on HRQoL is substantial, the ability to promote a new therapy’s impact on HRQoL relative to its competitors may be highly desirable.
When determining which PROs to include in clinical trials, the needs of these various stakeholders must be considered. The purpose of including disease specific PROs is to determine the effect of the new therapy on HRQoL in relation to the comparator included in the clinical trial as well as the durability of the effect with the experimental treatment over time. By contrast, the primary reason to include the EQ-5D-5L in clinical studies is to determine the decrement in HRQoLfor certain clinical events or health states likely to be included in the cost-effectiveness analysis.If the decrements in HRQoL are well-documented in the published literature,it may not be necessary to include the EQ-5D-5L in the clinical program in certain situations. If the purpose of including the PROs is to include the HRQoL results in a regulatory label in order to actively promote the results in relation to its competitors, then the PROs generally need to be included in Phase III studies as primary or secondary endpoints with adjustment for multiplicity. This is also an important consideration for reimbursement decisions in France. The standards for PROs established by each targeted regulatory agency must be met. The standards differ for different regulatory agencies just as they do for different reimbursement agencies.Early clarity on the target markets, and on the purpose for which the PROs will be used is essential.
