1. Negoziazione e rimborsabilità: strumenti per la sostenibilità? Francesco Perrone Director Clinical Trials Unit National cancer Institute of Naples Italy

2. Preamble I’m a medical oncologist External advisor for AIFA from 2005 to 2012 … I’m not delegated by AIFA The things I’m going to say represent my personal views

3. AIFA Was born in 2004 General directors – Nello Martini (2004-2008) I thanks him for some slides… – Guido Rasi (2008-2011), current EMA director – Luca Pani (from 2011)

4. The Italian scenario, few years ago The context – An advisory group focused on cancer drugs was created by Dr. Martini in 2005 – The only available infrastructure was the “price commission” – Many new drugs were in the “waiting list” and their cost was very high… The needs – To make drugs available shortly and without discrimination – To build a link between benefit size and reimbursment – To look for “easy to establish” and “not expensive” solutions

5. The proposal was to build an impressive machinary …

6. The Italian Registry… In 2005 the IT partner was CINECA – the major Italian computer center, a non-profit consortium including 70 Universities, 5 research bodies and the Ministry of Instruction, University and Research In 2012, the technological partner changed – ACCENTURE a multinational management consulting services private company, the world's largest consulting firm as measured by revenues and a Fortune Global 500 company In 2015, the technological partner changed again… – ALMAVIVA an Italian company based in Rome, 13,000 employees in Italy and 32,000 abroad, the 6th private Italian Group in terms of employees worldwide and the 3rd based on business management

7. The Italian Registry… The first version of the Italian Registry (working well) was closed on Dec 31, 2012 And I will show you some data downloaded on Dec 30, the “day before”…

9. 1.507 units treating cancer 35 “new” drugs 215.464 patients

10. The aims of the registry To introduce new drugs being sure that their use was appropriate (tutorial function) To provide an informatic platform to build a bridge between clinical practice and reimbursement strategy To provide the scientific community (and the patients) with solid evidences on drug consumption in clinical practice

11. The aims of the registry To introduce new drugs being sure that their use was appropriate (tutorial function) To provide an informatic platform to build a bridge between clinical practice and reimbursement strategy To provide the scientific community (and the patients) with solid evidences on drug consumption in clinical practice

12. 227.792- 216.897= ----------- 10.895 (5%)patients who were avoided an inappropriate treatment

14. The aims of the registry To introduce new drugs being sure that their use was appropriate (tutorial function) To provide an informatic platform to build a bridge between clinical practice and reimbursement strategy To provide the scientific community (and the patients) with solid evidences on drug consumption in clinical practice

15. The bridge In clinical practice we are able to measure success/failure Reimbursement strategies that link payment to the success (lack of failure) of the treatment can be put in place … – Payment by result (based on individual outcome) – Risk sharing (based on individual outcome) – Cost sharing (based on trial results and checked in real world)

16. Nello Martini MEAs : Payment by results - Cost Sharing Risk sharing – Success Fee (1)Cost sharing = payback of 50% treatment for all patients at the follow up (2)Payment by results = payback of 100 % treatment for all patients non responders (3)Risk sharing = payback of 50% treatment for all patients non responders (4)Success Fee = PbR reversed RegistriesMEAs 34PbR- Payment by Results 19CS - Cost Sharing 2RS- Risk Sharing 1SF – Success Fee 40 drugs x 56 indicazioni

19. Not only cancer Registries have been expanded in Italy to other disciplines – Orphan drugs – Antidiabetics – Antirheumatics – Cardiovascular – Psoriasis End of 2014, 76 drugs for 58 indications 505.000 patients

23. The trajectory of imatinib price

24. Price/volume means… Time (eg years) Volume Price

25. The aims of the registry To introduce new drugs being sure that their use was appropriate (tutorial function) To provide an informatic platform to build a bridge between clinical practice and reimbursement strategy To provide the scientific community (and the patients) with solid evidences on drug consumption in clinical practice

26. This was (and still is) a failure

27. Today No publication in scientific journals with data from the cancer registries Few official reports I believe there were (are) interesting data and many questions might be addressd Unofficially, I prepared one slide with data from the baseline form of the first generation registry …

29. Age of patients Drug/indicationRegistryRegistration trial NmedianN Avastin/CRC27.343642792 (  3)60 Avastin/NSCLC1.7716187843%≥65 Avastin/breast4.7865672256 Tarceva/NSCLC25.5676773161.4 Mabthera/lymphoma23.97667671 (  2)59 Erbitux/CRC14.7736659961 Alimta/NSCLC_1°_line10.32664172561 Alimta/NSCLC_2°_line3.8516557158 Nexavar/HCC10.0467060265 Nexavar/kidney3.6396690358 Sutent/kidney9.5786675060.5

30. Thanks to the registry… This is the strongest evidence and one of the few empirical demonstrations that the population receiving cancer drugs after registration is almost always older than that enrolled in registrative trials There are many implications… – Generalizability of registrative trials – Need for elderly-specific studies Safety Comorbidities Poly-pharmacotherapy Possible (but mostly unknown) drug-drug interactions

31. Actually AIFA has established a program of analysis and publication of registry data in scientific peer- reviewed journals They have started from non-cancer drug The model envisages cooperation with scientific societies or major stakeholders in the field

32. Conclusion… I believe… The AIFA experience with MEAS – began very early – (in my view) was “useful” Successful for tutorial and access aims MEAS are “one tool” but not enough with skyrocketing drug price Strategies linking initial price to true drug value (eg cost-efficacy) need to be implemented at the EU level to make easier the challenge in single EU contries

33. Thank you for your attention f.perrone@istitutotumori.na.it