11th November 2014 Making models more accessible to decision makers Michael Barry, PhD National Centre for Pharmacoeconomics, Dublin 11th November 2014 The NCPE conducts the health technology assessment (HTA) of pharmaceutical products for the Health Service Executive Recommendations on 192 medicines for 208 indications 3rd November 2014 1 11th November 2014 The HTA process The process begins with the price Rapid review to application by the determine whether a manufacturer full HTA is required Full HTA with a 90 day time frame NCPE submission to the HSE – CPU. This report will be considered by the New Drugs Group Committee 11th November 2014 Economic evaluations conducted in the Irish healthcare setting are usually in the form of CEA or CUA. Cost-effectiveness analysis (CEA) e.g. COST/LYG Cost-utility analysis (CUA) e.g. COST/QALY 2 11th November 2014 Cost-effectiveness threshold The line passing through the origin represents our ‘acceptable’ cost- effectiveness ratio. That is our maximum (or threshold) willingness-to-pay for a unit of effect ( life year or QALY). Cost (€) Q4 Q1 Effect (QALY) Q3 Q2 The QALY threshold to be used in the HTA process is € 45,000/QALY 11th November 2014 Number of products reviewed by the NCPE 2006 - 2014 3 11th November 2014 We will read through the HTA submission ……carefully ! 11th November 2014 Products reviewed in 2014 • HTA not required = 24 (44%) • Reimbursement recommended = 5 (9%) • Full HTA required = 12 (22%) • Reimbursement not recommended = 13 (24%) 5 at the submitted price & 7 oncology products 1st November 2014 4 11th November 2014 Medications associated with a ‘negative’ HTA in 2014 • Vismodegib (Erivedge®) – metastatic basal cell carcinoma (mBCC) • Abiraterone acetate (Zytiga®) – metastatic castration resistant prostate cancer (mCRPC) • Enzalutamide (Xtandi®) – metastatic castration resistant prostate cancer (mCRPC) • Brentuximab vedotin (Adcetris®) – relapsed/refractory CD30 positive Hodgkin’s Lymphoma • Teriflunomide (Aubagio®) – relapsing/remitting Multiple Sclerosis (MS) • Buprenorphine/naloxone (Suboxone®) - opiate addiction • Mannitol Dry Powder (Bronchitol®) – Cystic Fibrosis • Regorafenib (Stivarga®) – metastatic colorectal cancer (mCRC) • Trastuzumab emtansine (Kadcyla®) – HER2 positive, unresectable locally advanced or metastatic BC • Lixisenatide (Lyxumia®) – type 2 diabetes mellitus • Canagliflozin (Invokana®) – type 2 diabetes mellitus • Nab-paclitaxel (Abraxane®) – metastatic pancreatic cancer • Delta-9-tetrahydrocannabinol/cannabidiol (Sativex®) – spasticity in patients with multiple sclerosis 11th November 2014 The Review Team will require access to the economic model The submitted model should be clear and “You will receive a complex economic transparent model …………. you wont have a clue etc … how to use it” 5 11th November 2014 Modelling issues with negative HTAs • Incomplete modelling of the relevant clinical scenario (abiraterone) • Validity of the chosen health states (Sativex®) • Uncertainty around the natural history of disease progression (teriflunomide, Sativex®) • Time horizon (nab-paclitaxel, suboxone, regorafenib) • The choice of survival model used to extrapolate progression free survival (PFS) and overall survival (OS) beyond the trial period (brentuximab vedotin, regorafenib, trastuzumab emtansine, nab- paclitaxel) 11th November 2014 Parametric modelling methods impact the ICER The choice of parametric model can influence survival estimates and cost-effectiveness e.g. abiraterone in the treatment of mCRPC after failure of ADT in whom chemotherapy is not yet clinically indicated: Parametric model ICER Log-logistic € 159,055/QALY Weibull € 174,188/QALY 6 11th November 2014 Survival Analysis requirements for HTA submissions In general, a systematic approach to survival analysis has not been taken and justification for the methods chosen has not always been provided. In order to ensure a more systematic approach the NCPE requires; • Parametric models should be used to extrapolate survival data (unless the empirical data is complete). • A range of parametric models should be presented within the submissions. • Parametric model fit should be assessed systematically. Visual inspection alone should not be relied upon. McCullagh L, Barry M Value in Health 2013;16(7):A398 11th November 2014 Modelling issues with negative HTA • Lack of comparative efficacy data for treatment arms (vismodegib, brentuximab vedotin) • Data synthesis, indirect treatment comparisons (enzalutamide, lixisenatide, canagliflozin) • Pricing issues (canagliflozin, regorafenib) • Utility values used in the modelling (nab-paclitaxel, Sativex®, trastuzumab emtansine, regorafenib, suboxone, enzalutamide, abiraterone, vismodegib) 7 11th November 2014 Guidance to aid key stakeholders 11th November 2014 “I don’t mind if NICE or the NCPE criticise my model as long as I get reimbursement” 8 11th November 2014 The NCPE conducts the health technology assessment (HTA) of pharmaceutical products for the Health Service Executive Dr Roisín Adams Dr Emer Fogarty Dr Laura McCullagh Dr Cara Usher Dr Aisling O’Leary Dr Lesley Tilson Niamh Geraghty Prof Susi Schmitz Prof Cathal Walsh Brian Reddy Dr Jennifer Kieran Dr Susan Spillane Dr Kathleen Bennett 11th November 2014 Thank you 9 .