Analysing criteria for price and reimbursement of orphan drugs in Spain.

OBJECTIVE: There are differences between countries regarding data requirements for orphan drug evaluation and it  is also unknown which criteria might determine the price and reimbursement decision. This study aimed to identify the key  criteria for price and reimbursement of orphan drugs in Spain, approved by the European Commission, between January 2012 and June 2018. METHOD: A descriptive analysis of the orphan drugs and its characteristics was performed. Outcomes criteria assessed  were: therapeutic area, existence of alternative treatment, rarity of the disease, clinical trial outcomes and therapeutic  positioning report assessment. Hypotheses for each variable regarding Spanish pricing and reimbursement were made  and tested with two regression analyses. RESULTS: Out of 78 orphan drugs approved by the European Commission, 82.1% asked pricing and reimbursement in  Spain. From this, 43.8% had pricing and reimbursement approved and 20.3% rejected. Mean time from Spanish  marketing authorisation approval to pricing and reimbursement approval was 12.1 ± 5.1 months. Having a positive  therapeutic positioning report and no therapeutic alternatives would be associated with a positive pricing and  reimbursement in Spain. CONCLUSIONS: It remains challenging to establish which are the driving criteria for pricing and reimbursement approval  of orphan drugs in Spain. Further research should be done including other variables that might influence the pricing and  reimbursement final decision in Spain.

Objetivo: Los requisitos para la evaluación de los medicamentos huérfanos difieren entre los países  miembros de la Unión Europea y tampoco se sabe qué criterios influyen en la decisión final sobre  precio y financiación. Este estudio ha tenido como objetivo identificar los criterios clave para establecer el precio y la financiación de los medicamentos huérfanos en España, una vez  aprobados por la Comisión Europea, entre enero de 2012 hasta junio de 2018.Método: Se realizó un análisis descriptivo de los medicamentos huérfanos y sus características. Los  criterios evaluados fueron: área terapéutica, existencia de tratamientos alternativos, rareza de la  enfermedad, tipo de resultados de los ensayos clínicos e informe de posicionamiento terapéutico. Para  cada variable se estableció una hipótesis con respecto a la aprobación de precio y  financiación y se analizaron con dos análisis de regresión.Resultados: De las 78 aprobaciones de medicamentos huérfanos realizadas por la Comisión Europea,  el 82,1% solicitaron precio y financiación en España. De estas, el 43,8% fueron aprobadas  y el 20,3% fueron rechazadas. El tiempo medio desde la aprobación de la autorización de comercialización en España hasta la aprobación del precio y la financiación fue de 12,1 ± 5,1  meses. Un informe de posicionamiento positivo y la falta de alternativas terapéuticas se asociaría con  una aprobación de precio y financiación.Conclusiones: Sigue siendo un reto establecer cuáles son los criterios clave para la aprobación de los  medicamentos huérfanos en España. Los próximos estudios deberían incluir un mayor número de  variables que puedan influir en el precio y la decisión de financiación.

Development of ACRODAT®, a new software medical device to assess disease activity in patients with acromegaly.

PURPOSE: Despite availability of multimodal treatment options for acromegaly, achievement of long-term disease control is suboptimal in a significant number of patients. Furthermore, disease control as defined by biochemical normalization may not always show concordance with disease-related symptoms or patient's perceived quality of life. We developed and validated a tool to measure disease activity in acromegaly to support decision-making in clinical practice. METHODS: An international expert panel (n = 10) convened to define the most critical indicators of disease activity. Patient scenarios were constructed based on these chosen parameters. Subsequently, a panel of 21 renowned endocrinologists at pituitary centers (Europe and Canada) categorized each scenario as stable, mild, or significant disease activity in an online validation study. RESULTS: From expert opinion, five parameters emerged as the best overall indicators to evaluate disease activity: insulin-like growth factor I (IGF-I) level, tumor status, presence of comorbidities (cardiovascular disease, diabetes, sleep apnea), symptoms, and health-related quality of life. In the validation study, IGF-I and tumor status became the predominant parameters selected for classification of patients with moderate or severe disease activity. If IGF-I level was ≤1.2x upper limit of normal and tumor size not significantly increased, the remaining three parameters contributed to the decision in a compensatory manner. CONCLUSION: The validation study underlined IGF-I and tumor status for routine clinical decision-making, whereas patient-oriented outcome measures received less medical attention. An Acromegaly Disease Activity Tool (ACRODAT) is in development that might assist clinicians towards a more holistic approach to patient management in acromegaly.

Appraising the holistic value of Lenvatinib for radio-iodine refractory differentiated thyroid cancer: A multi-country study applying pragmatic MCDA.

BACKGROUND: The objective of the study was to reveal through pragmatic MCDA (EVIDEM) the contribution of a broad range of criteria to the value of the orphan drug lenvatinib for radioiodine refractory differentiated thyroid cancer (RR-DTC) in country-specific contexts. METHODS: The study was designed to enable comprehensive appraisal (12 quantitative, 7 qualitative criteria) in the current disease context (watchful waiting, sorafenib) of France, Italy and Spain. Data on the value of lenvatinib was collected from diverse stakeholders during country-specific panels and included: criteria weights (individual and social values); performance scores (judgments on evidence-collected through MCDA systematic review); qualitative impacts of contextual criteria; and verbal and written insights structured by criteria. The value contribution of each criterion was calculated and uncertainty explored. RESULTS: Comparative effectiveness, Quality of evidence (Spain and Italy) and Disease severity (France) received the greatest weights. Four criteria contributed most to the value of lenvatinib, reflecting its superior Comparative effectiveness (16-22% of value), the severity of RR-DTC (16-22%), significant unmet needs (14-21%) and robust evidence (14-20%). Contributions varied by comparator, country and individuals, highlighting the importance of context and consultation. Results were reproducible at the group level. Impacts of contextual criteria varied across countries reflecting different health systems and cultural backgrounds. The MCDA process promoted sharing stakeholders' knowledge on lenvatinib and insights on context. CONCLUSIONS: The value of lenvatinib was consistently positive across diverse therapeutic contexts. MCDA identified the aspects contributing most to value, revealed rich contextual insights, and helped participants express and explicitly tackle ethical trade-offs inherent to balanced appraisal and decisionmaking.

Integrated health outcomes research strategies in drug or medical device development, pre- and postmarketing: time for change.

The implementation of health outcomes research as a healthcare decision-making tool has expanded rapidly in the last decade. Drugs and medical devices are increasingly being required to demonstrate not only their efficacy and safety characteristics, but also their performance in at least three core dimensions of health outcomes research: clinical effectiveness, patient-reported outcomes and economic outcomes. However, the current integration of health outcomes research lacks coordination and communication and as a result, money and time is being spent on the generation of health outcomes research data which can be both insufficient and fail to satisfy the information demands of all the relevant stakeholders. In response to this, a new paradigm is evolving which involves the implementation of health outcomes research strategies that encompass the development, pre- and postmarketing stages of a drug or medical device.