EVIDENCE BASED HAEMOPHILIA CARE – CURRENT STATUS AND WHERE TO GO? Alfonso Iorio Health Information Research Unit & Hamilton-Niagara Hemophilia Program McMaster University

In compliance with COI policy, EAHAD requires the following disclosures to the session audience: ShareholderNo relevant conflicts of interest to declare Grant / Research SupportBayer, Baxalta, Biogen, Novo Nordisk, Pfizer ConsultantBayer, Baxalta, Novo Nordisk EmployeeNo relevant conflicts of interest to declare Paid InstructorNo relevant conflicts of interest to declare Speaker bureauNo relevant conflicts of interest to declare HonorariaNo relevant conflicts of interest to declare All funding administered via McMaster University – no personal compensation received

Overview What is evidence based care (EBC) ? What are the key components of EBC? Is the EBC framework a value for hemophilia? Can the EBC framework be applied to haemophilia? Can EBC guidelines be issued in hemophilia? Is the hemophilia community going toward EBC?

Overview What is evidence based care (EBC) ? What are the key components of EBC? Is the EBC framework a value for hemophilia? Can the EBC framework be applied to haemophilia? Can EBC guidelines be issued in hemophilia? Is the hemophilia community going toward EBC?

Overview What is evidence based care (EBC) ? What are the key components of EBC? Is the EBC framework a value for hemophilia? Can the EBC framework be applied to haemophilia? Can EBC guidelines be issued in hemophilia? Is the hemophilia community going toward EBC?

The “concept” of comparison DimensionCountryControlMildModSevere EQ5D-5LA (some prophy) B (no prophy) Chronic painA (some prophy) 28%53%68%78% B (no prophy) 30%56%70%86% Investigators – Unpublished data * % patient reporting

The “concept” of comparison DimensionCountryControlMildModSevere EQ5D-5LA (some prophy) B (no prophy) Chronic pain*A (some prophy) 28%53%68%78% B (no prophy) 30%56%70%86% Investigators – Unpublished data * % patient reporting

The “concept” of comparison DimensionCountryControlMildModSevere EQ5D-5LA (some prophy) B (no prophy) Chronic painA (some prophy) 28%53%68%78% B (no prophy) 30%56%70%86% +56% Investigators – Unpublished data * % patient reporting

Components of a comparison Comparator – Historical – Inactive – Active Study design – Randomized – Observational Comparator – Registration – HTA/reimbursement – Adoption in care Study design – Registration – HTA/pricing – Adoption in care

The concept of comparable sample

Multivariable analysis Propensity score Stratification RCT

S P MV Wedge shape design Interrupted time series

Overview What is evidence based care (EBC) ? What are the key components of EBC? Is the EBC framework a value for hemophilia? Can the EBC framework be applied to haemophilia? Can EBC guidelines be issued in hemophilia? Is the hemophilia community going toward EBC?

Why would the hemophilia community embrace EBC? Evolving scenario - challenges – Hemophilia has been a prototype has been the betrayal of the dream of a cure for a male’s disease in the roaring ‘60es of the infinite power of progress – Many more rare diseases with more expensive treatment learning to advocate for their treatment in absence of alternatives – Different economical models landing on the stage

Why would the hemophilia community embrace EBC? Evolving scenario - opportunities – Hemophilia Strong and widespread network of HTC, NMO, patients Rare, but sizeable disease – many less patients studied that one could Long tradition of collaboration among all relevant stakeholders

Cost effective, but also would cost an additional $65 billion over the next 5 years – Chatwal J et al. Ann Intern Med. 2015;162: Mc Carthy M. New drug for hepatitis C contributes to 13% rise in spending on prescription drugs in US. BMJ. 2015;350:h2055. By JOSEPH WALKER April 8, :37 p.m. ET

Overview What is evidence based care (EBC) ? What are the key components of EBC? Is the EBC framework a value for hemophilia? Can the EBC framework be applied to haemophilia? Can EBC guidelines be issued in hemophilia? Is the hemophilia community going toward EBC?

Cochrane Collaboration data CFIRBCDCBD Trials (CENTRAL) SR (Cochrane) Completed Ongoing7164 CF = Cystic Fibrosis IRBCD = inherited red blood cell disorders CBD = Congenital bleeding disorders

List of Cochrane Reviews and trials

RCTs on secondary prophylaxis Morfini Aronstam Kavakli Powell valentino Manco-Johnson Publication year Malanghu valentino + 467

HTA in hemophilia Swedish Council on Health Technology Assessment. Treatment of Hemophilia A and B and von Willebrand Disease (2011). – 0Hemophilia%20A%20and%20B.pdf 0Hemophilia%20A%20and%20B.pdf – Accessed February 2, IQWIG Rapid Report – with-haemophilia.pdf with-haemophilia.pdf – Accessed February 2, 2016.

SBU report IQWIG Rapid Report 27 studies / 8 reviews Firm conclusions cannot be drawn for – Different regiments for acute bleed and surgery – Optimum time to start, dose, dose interval, discontinuation – [Need for registries] 16 studies DomainA+AC Mortality EQ5D ✔ Chronic pain ✔ Acute pain Joint function Severe bleeds ✔✔ Life threatening bleeds Inhibitor HR-QoL

Overview What is evidence based care (EBC) ? What are the key components of EBC? Is the EBC framework a value for hemophilia? Can the EBC framework be applied to haemophilia? Can EBC guidelines be issued in hemophilia? Is the hemophilia community going toward EBC?

WFH guidelines Srivastava, A, Brewer, A, Mauser-Bunschoten, E.P., Key, N.S., Kitchen, S., Llinas, A., Ludlam, C., Mahlangu, J.N., Mulder, K., Poon, M.C. & Street, A. – Haemophilia 2013, 19, e1–e Examination of Guidelines [ from the IQWIG Rapid Report ] – There are 13 treatment guidelines. Only three are evidence based. But most of the guidelines are in line with the results of the report. – The WFH treatment guidelines from 2012 were considered as “not evidence based”

Guidelines in rare diseases Developing methodology for the creation of clinical practice guidelines for rare diseases: A report from RARE-Best Practices. – Pai, M., Iorio, A., Meerpohl, J., Taruscio, D., Laricchiuta, P., Mincarone, P., Morciano, C., Leo, C.G., Sabina, S., Akl, E., Treweek, S., Djulbegovic, B. & Schunemann, H. – Rare Diseases, 2015, 3, e

Overview What is evidence based care (EBC) ? What are the key components of EBC? Is the EBC framework a value for hemophilia? Can the EBC framework be applied to haemophilia? Can EBC guidelines be issued in hemophilia? Is the hemophilia community going toward EBC?

Take home message ItemAdoptedFeasibleValuePotential Robust study design Comparative effectiveness Rigorous EBP guidelines

Take home message ItemAdoptedFeasibleValuePotential Robust study design Sometimes ModerateHigh Comparative effectiveness Rigorous EBP guidelines

Take home message ItemAdoptedFeasibleValuePotential Robust study design Sometimes ModerateHigh Comparative effectiveness RarelyYesHigh Rigorous EBP guidelines

Take home message ItemAdoptedFeasibleValuePotential Robust study design Sometimes ModerateHigh Comparative effectiveness RarelyYesHigh Rigorous EBP guidelines RarelyYESHigh

Take home message ItemExamples Robust study design Registry based CCT Comparative effectiveness PROBE Rigorous EBP guidelines GRADE / RARE BestPractice

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