HTA-challenges in the Medical Device Industry

1. HTA-challenges in the Medical Device Industry HTA-course, Danish Society for Biopharmaceutical Statistics, May 26 2014 Jeppe Sørensen, International Health Economist

2. Agenda • Introduction to Coloplast • HTA challenges for medical devices – same or different? • Product characteristics • Licensing requirements • Country specific approaches to HTAs and medical devices – examples and implications for evidence • How does Coloplast respond to the challenges? Value based argumentation • “Traditional” cost-effectiveness analysis • Disease specific PROMs • Discreet choice experiments

3. 1. INTRODUCTION Coloplast’s business areas, typical users and products Ostomy Care Continence Care Urology Care Wound & Skin Care People in need of bladderor bowel management People who have had their intestine redirected to an opening in the abdominal wall People with dysfunctional urinary and reproductive systems People with difficult-to-healwounds SenSura® Mio Launchedin 2011 SpeediCath® Compact Set Launched in 2012 New Biatain® Silicone Launched in 2013 Altis® Single Incision sling Launched in 2012

4. 1. INTRODUCTION #1global position 35-40% global market share Business areas 2012/13Ostomy Care 42%of Coloplast revenue 7%organic growth rate 4.8 billion DKKannual revenue Innovative solutions

5. 1. INTRODUCTION #1globalposition 40-45% global marketshare Business areas 2012/13Continence Care 35% of Coloplast revenue 7%organic growth rate 4.1 billion DKKannual revenue • Award winning Products

6. 2. MEDICAL DEVICES – SAME OR DIFFERENT? Product characteristics of medical devices influence conditions for establishing evidence Reasons why devices are different in relation to RCTs • Difficult/impossible to do blinded studies with devices • No “steady state” period: Frequent product modifications and • Device-Operator Interactions: Efficacy depends on how it is used and RCT risks demonstrating experience rather than differences Source: Drummond, M., Griffin, A. and Tarricone, R. (2009), Economic Evaluation for Devices and Drugs—Same or Different?. Value in Health, 12: 402–404

7. 2. MEDICAL DEVICES – SAME OR DIFFERENT? Different licensing requirements compared to drugs mean different conditions for producing evidence Pharma • 10-15 years development and clinical trials aiming at a strong regulatory file for FDA/EMA approval Medical devices • Often a CE-mark is the only licensing requirement for disposable medical devices • 2-3 years from idea to market • Fewer and smaller trials

8. 2. MEDICAL DEVICES – SAME OR DIFFERENT? Example: Evidence on hydrophilic coated vs. uncoated catheters and occurrence of UTIs Independently, both studies indicate a 21 % UTI reduction Institutional data is the best measure for a difference in UTI rates, however it overestimates the real life UTI rates. Low patient number Patients UTI rates in community is the most relevant measure for real life picture of the UTI rate.

9. 3. APPROACHES TO HTA Very different funding systems and HTA-requirements – two examples

10. 3. APPROACHES TO HTA Example: France – reimbursement system & characteristics CommunityReimbursement system Key characteristics HAS: The French National Authority for Health evaluatesreimbursement in 2 steps (outsidecategory) • Nationalcategorieswithfixedprices: • OC: 17 sub-categories • IC: 3 sub-categories(CD: 8 sub-categories) • WC: sub-categoriesbasedonsize • Application time in category: < 1 week • (only need safety registration in Afssaps) • Clinical data not required • No international reference pricing • Review every 5th year (longer in reality) • Brand specificreimbursementpossible • Application time: 6 – 12+ months • Clinical data required • International reference pricing • Review every 5th year (incl reference price) • Co-payment: none for chroniccare(OC/ CC) • 35% non Chronics (but 90% insured) 1st step: Medical evaluation 2nd step: Economic evaluation ECONOMICAL EVALUATION Committee2 (CEPS) TECHNICAL & MEDICAL EVALUATION Committee 1 (CEPP/ CNEDiMTS) • MEDICAL SERVICE : YES/ NO • MEDICAL SERVICE IMPROVEMENT (MSI): • 5 grades • REIMBURSEMENT PRICE -> LPPR • Major improvement → high price • Important improvement → premium price • Moderateimprovement → price level ? • Minorimprovement → parity/ low price • No improvement → No reimbursement / low price Decision-makers = physicians  Spotlight clinical data Cost-minimisation politic for Healthcare  Spotlight budget impact and EU prices/ reimbursement

11. 3. APPROACHES TO HTA The Coloplast payer landscape – differs across markets ? Reimbursement/ Value based Reimbursement/ Fixed categories Procurement/ Tenders 100 %Co-payment Pricing / feature based Performance/value based Page 11

12. 4. VALUE BASED ARGUMENTATION Example on how health economics is used for value argumentation in relation to intermittent catheterization Published article show that by using a hydrophilic coated catheter, a UTI reduction of 21 % can be obtained Urologist and rehab specialist panel Health economic analysis Findings Hydrophilic coated catheters are 4% more expensivethan uncoated catheters HCIC increase QALY by 5%, increase additional life years by4%and decrease the risk of UTI by16 %with a lifetime perspective Consolidated possible adverse events

13. Chronic Urinary Retention – HCIC vs. uncoated No/minor renal impairment Major renal impairment Chronic kidney failure No UTI UTI responding to initial treatment No UTI UTI responding to initial treatment No UTI UTI responding to initial treatment UTI not responding to initial treatment UTI not responding to initial treatment UTI not responding to initial treatment No UTI No presence of treatment-requiring urinary tract infections No/minor renal impairment No or minor renal impairment requiring dietary changes only UTI responding to initial treatment • Presence of treatment-requiring urinary tract infections that responds well to initial treatment - including 7% multiple drug resistance. • Monthly risk at IC: 32,6% (Cindolo 2004, Cardenas 2009 + 2011, De Ridder 2005, Giannantoni 2001, Duffy 1995 & King 1992) • Risk reductions HCIC vs. uncoated: 10% (meta analysis) 21% (Cardenas 2011 – controlled part), 53% (Cardenas 2009) Major renal impairment • Careful monitoring is needed. • Monthly risk : 0,020% (1/4 of upper tract abnormalities, Weld 2000) UTI not responding to initial treatment Chronic kidney failure • Dialysis or renal replacement therapy needed. • Monthly risk : 0,0035% (UK renal registry, Lawrenson 2001) • Including cases leading to epididymitis, pyelonephritis and urosepsis. • Monthly risk: 0,320% (Chai 1995, Perrouin-Verbe 1995, Weld 2000) • Risk reduction HCIC vs. uncoated: 10% (Expert assumption) Background adverse events Bladder stones 0.117% (Perrouin-Verbe 1995, Chai 1995) Kidney stones 0.117% (assumed the same as bladder stones) Urethral damage 0.189% (Perrouin-Verbe 1995, Chai 1995 and Weld 2000)

14. 4. VALUE BASED ARGUMENTATION Fulloverview of the CEM CUR Model No/minorrenalimpairment Major renalimpairment Chronickidneyfailure No UTI UTI responding to initial treatment UTI not responding to initial treatment Data input Modelling Output Urinary Tract Infections Results Adverse Events Cost Data

15. 4. VALUE BASED ARGUMENTATION Output Data input Modelling Output Mean cost Mean QALY Mean LYG UTIs ICER Cost-effectiveness ratio depends on local costing data Adverse Events

16. 4. VALUE BASED ARGUMENTATION Limitations in conventional CUAs in relation to effects of medical devices – defining and measuring QOL

17. 4. VALUE BASED ARGUMENTATION Example: SpeediCath Compact and quality of life Intermittent Self-Catherisation Questionnaire (ISC-Q) QoL HRQoL • Validated instrument accepted for publication (Pinder 2013) • Total score 0-100 based on 24 questions in 4 domains: • Ease of use, convenience, discreteness and psychosocial wellbeing SF-36 EQ-5D Disease QoL Qualiveen C-IQoL Compact trial results on quality of life (ISC-Q) Compact: 17 point improvement out of 100 Randomised controlled trial of 118 neurogenic users from 5 countries using Compact 6 weeks vs. non-Compact for 6 weeks (Chartier-Kastler 2013). ISC-Q But what is better quality of life worth ? Page 17

18. 4. VALUE BASED ARGUMENTATION One way is to base willingness to pay on a discreet choice experiment

19. 4. VALUE BASED ARGUMENTATION Example of WTP results for specific catheter attributes • WTP puts a value on the benefit of certain features to the users • Can be used to link an improvement in quality of life to monetary units • In Coloplast WTP is used to describe user-perceived value of various aspects (i.e. coating, risk of infection, convenience etc.) • A regular cost-minimisation analysis only counts costs – WTP counts the value for the users

20. 4. VALUE BASED ARGUMENTATION Existence of evidence within the field of stoma care is very limited Details: Subjects in trials: <6,000 in total – 2 trials accounts for ~5,000 25 trials registered – 15 by Coloplast 15 RCTs registered – 13 by Coloplast 0 blinded trials registered – Not possible to blind stoma appliance trials International perspective on evidence gap Use of Willingness-to-pay study Use of less valid study designs The DialogueStudy • >3,000 subjects included • Improved Quality of Life • Improved leakage level • Improved skin condition Combining willingness-to-pay study with cost-minimisation analysis (niklas.hedberg@tlv.se) Half of all patient ever studied in stoma care

21. Any questions or comments ?

22. Jeppe Sørensen International Health Economist, Coloplastdkjsor@coloplast.com