Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

The importance of post-marketing registries for payers and regulators to manage drug pricing and conditional reimbursement

700 views

Published on

Entela Xoxi, PharmD, PhD, MSc.

Pharma Pricing & Market Access Congress 2017 22 February 2017 London

Published in: Retail
  • Have You Seen Linda Allen's new Candida System yet? It's called "Yeast Infection No More" I've read the whole thing (all 150 pages) and there's some great information in there about how to naturally and permanently eliminate your yeast infection without drugs, creams or any kind of gimmicks. I highly recommend it - it's very honest and straightforward without all the hype and b.s. you see all over the net these days. Here's the website where you can get more information: ■■■ https://tinyurl.com/y3flbeje
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • This program is a must read for anyone suffering from Candida or ones like me who has ever taken antibiotics and is now experiencing any of the many problems that go along with intestinal flora imbalance. I must also add that several people in my church have been following this book and are doing great! ■■■ http://scamcb.com/index7/pdf
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • Hey guys! Who wants to chat with me? More photos with me here 👉 http://www.bit.ly/katekoxx
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here

The importance of post-marketing registries for payers and regulators to manage drug pricing and conditional reimbursement

  1. 1. THE IMPORTANCE OF POST-MARKETING REGISTRIES FOR PAYERS AND REGULATORS TO MANAGE DRUG PRICING AND CONDITIONAL REIMBURSEMENT Entela Xoxi PharmD, PhD, M.Sc. Former Co-ordinator of AIFA’s Registries (until 2016) Former member European Commission Expert Group STAMP Former Observer at AdaptSmart, EUnetHTA member
  2. 2. The outlines of this talk ① European regulatory process ② Interaction between Regulatory & HTA bodies ③ Registries & Pricing Reimbursement process
  3. 3. ① European regulatory process ② Interaction between Regulatory & HTA bodies ③ Registries & Pricing Reimbursement process
  4. 4. Positive Opinion: may often have ‘follow up measures’ Post-authorisation Efficacy or Safety Studies (PAES or PASS): ‘Any study relating to an authorised medicinal product conducted with the aim of identifying, characterising or quantifying a safety hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of risk management measures’ Full MA (Classic & Accelerate Assessment) Conditional MA (CMA) The CMA is granted in order to meet unmet medical needs of patients and in the interests of public health, before all data are available. When the missing data are provided, it should be possible to replace it with a Full MA. In contrast, it will normally never be possible to assemble a full dossier in respect of a MA under EC Exceptional circumstances MA This MA may be granted in exceptional circumstances for safety reason. The medicinal product is authorised only for objective, verifiable reasons and must be based according to Annex I to Directive 2001/83/EC. Continuation of the authorisation shall be linked to the annual reassessment of these conditions. CHMP opinions & Market Authorisation
  5. 5. Launched by EMA to enhance support for the development of medicines that target an unmet medical need. This voluntary scheme is based on enhanced interaction and early dialogue with developers of promising medicines, to optimize development plans and speed up evaluation so these medicines can reach patients earlier. PRIME scheme Recommendations on eligibility to PRIME scheme Cumulative overview of recommendations on PRIME eligibility requests adopted by 26 January 2017 By therapeutic area * This indicates eligibility requests received but not started by EMA as they were deemed outside the scope of the scheme or with a format and content inadequate to support their review. These are not included in the breakdown by type of applicant or by therapeutic area. By type of applicant
  6. 6. Adaptive Pathway (2 scenarios) based on 3 principles ①  Iterative development, which either means: §  approval in stages, beginning with a restricted patient population then expanding to wider patient populations §  confirming the B-R balance of a product, following a conditional approval based on early data (using surrogate endpoints) considered predictive of important clinical outcomes ②  Gathering evidence through real-life use to supplement CTs data ③  Early involvement of patients and HTA bodies in discussions on a medicine’s development. - Widening of indication Scenario (1) - Prospectively planned reduced Of Uncertainty (CMA) Scenario (2)
  7. 7. ① European regulatory process ② Interaction between Regulatory & HTA bodies ③ Registries & Pricing Reimbursement process
  8. 8. 23 September 2015 EMA/334645/2015 Senior Medical Officer What can EMA contribute to HTA-JA3? The European Medicines Agency (EMA) will become a collaborating partner in the Health Technology Assessment-Joint Action 3 (HTA-JA3), sponsored by the EC. HTA-JA3 will run from 2016-2019. At the recent (8th May 2015) EMA-EUnetHTA meeting, EMA was asked by the Commission (Jerome Boehm) to outline EMA’s estimated contributions - both scientific synergies and resources/logistics - to the HTA- JA3. 1. Maximise scientific synergies between HTA and regulation 1.1. Shaping the early drug development plan (early scientific advice) Since 2010 EMA has put in place a pilot project of Parallel Scientific Advice in partnership with HTA bodies that allows developers to receive simultaneous feedback from both regulators and national HTA bodies on their development plans for new medicines. The following HTA bodies have participated so far: AEMPS (Spanish Medicines Agency), AIFA (Italian Medicines Agency), CAHIAQ (Catalan Agency for Health Information, Assessment and Quality), GBA (German Federal Joint Committee), HAS (French National Authority for Health), HVB (Association of Austrian Social Insurance Institutions), IQWiG (Institute for Quality and Efficiency in Healthcare, Germany), INAMI (National Institute for Sickness and Invalidity Insurance, Belgium), NICE (British National Institute for Health and Clinical Excellence), NOMA (Norwegian Medicines Agency), TLV (Swedish Dental and Pharmaceutical Benefits Agency), ZIN (Dutch National Health Care Institute, formerly CVZ), and AOTMiT (Polish Agency for Health Technology Assessment and Tariff System). A wide spectrum of indications has been covered, such as diabetes, heart failure, lung cancer, breast cancer, pancreas cancer, melanoma, mesothelioma, glioblasoma, asthma, rheumatoid arthritis, multi- resistant bacterial infections, viral and fungal infections, food allergies, diabetic gastroparesis, Alzheimer’s disease, depression, osteoporosis, ophthalmology conditions such as retinitis pigmentosa What can EMA contribute to HTA-JA3? framework of the EUnetHTA Joint Actions (JA) 1 and 2, and EMA was invited to participate as observer in the multi-HTAs early dialogues of EUnetHTA JA2. Since September 2013, under the coordination by HAS, 14 HTAs have initiated the SEED (Shaping European Early Dialogues for health technologies) project, financed by the EU Commission, to perform 10 additional multi-HTAs early dialogues (7 on medicinal products and 3 on medical devices) and explore possible scenarios for conducting early dialogues in the future. EMA is associated to the SEED project and took part in 4 of these dialogues as EMA SEED parallel advice procedures. These 4 procedures were hosted by EMA. It is anticipated that the number of procedures and the number of EU-HTA bodies contributing to the early scientific advice procedure will grow in the near future, i.e. during the period of the HTA-JA3. EMA is willing and able to continue to support this activity. See paragraphs 2.1. and 2.2. 1.2. Shaping on-market evidence generation (late scientific advice, registries) In 2015 EMA is reinforcing its Scientific Advice Working Party with experts in on-market evidence generation from the Pharmacovigilance Risk Assessment Committee (PRAC). In addition, a new Scientific Advice Procedure (which may include Parallel Scientific Advice with HTA bodies) will be introduced that concludes with advice being adopted by the PRAC. This forms the foundation for pharmaceutical companies to obtain expert advice on the development of their products beyond the initial marketing authorisation application including evidence generation using observational methods and including patient outcomes of interest to HTA bodies. In this way EMA can offer to coordinate Parallel Scientific Advice which delivers expert advice throughout the product lifecycle. EMA is actively supporting efforts to build capacity to generate on-market evidence, including of efficacy and safety of medicines and health outcomes. Capacity building efforts will include HTA bodies where appropriate and this includes: • supporting the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) and developing guidance on methods for studies that can support medicines regulation and HTA, • developing and piloting tools to improve the feasibility and quality of patient registries (including governance models, core protocols and data fields), including registries that can support both regulatory and HTA questions, • a pilot of supporting companies to generate evidence by building on existing registries (and HTA involvement through Parallel Scientific Advice is envisaged), EMA & HTA bodies interactions
  9. 9. JA3 EUnetHTA Work Package 5 - Life cycle approach to improve Evidence Generation Strand A: Early dialogues (initial evidence generation) Strand B: Post-Launch Evidence Generation & Registries •  Standards for registers in HTA tool - Candidate registers and participating HTA agencies identified. •  Report on current processes for using register data in HTA assessments in European HTA agencies. •  Start of pilots •  Identify options for a mechanism for independently accrediting or assuring registers using the Quality Standards for Registers in HTA, including updating the standards in line with methodological developments. •  Tool for Registers in HTA prepared. •  Post Launch Evidence Generation, start of last pilots Options for a business model for ongoing delivery of a mechanism for independently accrediting or assuring registers using the Quality •  Standards for Registers in HTA, including updating the standards in line with methodological developments. •  Post-launch evidence generation tool produced
  10. 10. §  Patients §  Patient organisations §  Regulatory authority §  P & R body, Insurance bodies §  HTA body §  Physicians §  Pharmacists §  Pharma companies §  Regions §  Health managers §  CRO §  Ethical Committees Stakeholders: rules & responsabilities Region Local Health Unit Pharmacy Pharma Industry Region Local Health Unit/ Hospital Public Corporation Hospital Pharmacy Pharma Industry Region Local Health Unit/ Hospital Public Corporation Hospital Department Section Hospital-PhysicianHospitalPharmacyTerritoryPharmacy
  11. 11. Patients are not equally responsive to beneficial effects, and not equally susceptible to AEs. Bridging the efficacy-effectiveness gap: a regulator's perspective on addressing variability of drug response. Nat Rev Drug Discov. 2011 Jul 1;10(7):495-506. Eichler HG, et al. Bridging the efficacy – effectiveness gap Regulatory decisions are based on population-level information, with an understanding that the B-R will not necessarily be positive for all treated patients.
  12. 12. 4 DatasourcesDatasources Patient derived data (via smart phone or web based technologies) Electronic health records Primary care data, hospital records Registries Existing disease Registries / new product registries Prescription databases Drug utilisation Patient and caregiver surveys Which Data? The Future Social media data Claims data RWE is already in routine use in the EU Particularly true for marketed products - safety monitoring and drug utilisation.
  13. 13. Registries as part of Real World Data REGISTRIES are one of the many sources of RWD: •  electronic medical records, observational studies, •  administrative data, •  claims databases, •  health surveys, •  patient reported outcomes (PROs) RWD is defined as an umbrella term regarding the effects of health interventions that are not collected in the context of conventional RCTs. RWE is defined as the evidence derived from the analysis and/or synthesis of RWD (GetReal Consortium. IMI-GetReal Glossary. IMI-GetReal; 2015) Adaptive pathways workshop, 2016/12/13 http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/ events/2016/09/event_detail_001324.jsp&mid=WC0b01ac058004d5c3
  14. 14. 1.  RWD collection and use for reimbursement activities, such as relative effectiveness assessment, risk-sharing agreements and pharmaco-economics analysis is the most noted actual context. 2.  RWD collection and use for regulatory activities. RWS can be designed to collect information on long-term safety and effectiveness as part of phase IV, PASS and pharmacovigilance commitments. RWS can also demonstrate compliance of prescribing patterns in populations approved in marketing authorizations or adherence to national guidance. In some cases, they can also inform a need for treatment pathways, or license extension to a new indication or treatment population. 3.  Collection and use of RWD during drug development. RWD is used, amongst other things, to help drug developers study the natural history of disease, define patient populations for CTs, standardize outcome measurements, define sub-populations for treatment, understand treatment patterns both pre- and at product launch, and, as previously- stated, long-term safety and effectiveness outcomes. 4.  Use of RWD in drug utilisation studies to investigate, for example, drug dosing in clinical practice, patient compliance, SoC & treatment flows in different clinical contexts.
  15. 15. 24 Patient Registries Strengths • Systematic assessment of investigator designed measurements of relevant clinical parameters • Natural history of disease • Disease burden • Standard of care • Patient stratification • RCTs • Open label studies possible • Capture off label use • Captures information on high risk groups and rare diseases • Patient reported outcomes Limitations • Substantial set up and running costs (sustainability) • Time consuming to initiate • Medications commonly missing • ADRS not routinely recorded • Co-morbidities missing • Data ownership/governance challenges • Data Quality - absence of clear benefit for clinical practice limits HCP commitment • If no comparator will limit utility Adaptive pathways workshop, 2016/12/13 http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/events/ 2016/09/event_detail_001324.jsp&mid=WC0b01ac058004d5c3
  16. 16. q  Fragmentation q  Lack of interoperability q  Increased cross border collaborations are required to leverage existing data and knowledge. 26 ….fragmentation, ……lack of interoperability, ……..increased cross border collaborations are required to leverage existing data and knowledge RWE is already in routine use in Europe, particularly true in the post authorisation stage Europe is rich in datasets but there are multiple challenges in their exploitation. Integration of multiple databases may be needed to increase power in order to study rare exposures or outcomes or diverse populations.
  17. 17. Redefined eHealth European Interoperability Framework (2015) Legal and regulatory Policy Research process Information Applications IT Infrastructure Legal and regulatory Policy Care process Information Applications IT Infrastructure Compatible legislation and regulations Collaboration agreements Alignment of care processes and workflows Data model, terminologies, formatting Integration in healthcare applications Communication and network protocols Organization A Organization BChange Change Change Change Change Change The Belgian “start up” project on patient registries EMA Patient Registries Workshop, 2016.10.28 - London [Healthcare data – Interoperability] = Pain
  18. 18. BIG DATA (4V’s) means different things to different people and there isn’t, and probably never will be, a commonly agreed upon definition out there. But the phenomenon is real and it is producing benefits in so many different areas, so it makes sense for all of us to have a working understanding of the concept. BIG DATA is that everything we do is increasingly leaving a digital trace (or data), which we (and others) can use and analyze. Big Data therefore refers to that data being collected and our ability to make use of it.
  19. 19. ① European regulatory process ② Interaction between Regulatory & HTA bodies ③ Registries & Pricing Reimbursement process
  20. 20. Early dialogue/ scientific advice European & National approval Conditional Reimbursement (MEAs) Re- assessment The Italian approach Clinical drug- development Market Entry Monitoring Registries Further policy actions
  21. 21. The Italian post-marketing registries Entela Xoxi, Carlo Tomino, Luca de Nigro, Luca Pani Italian Medicines Agency, Roma, Italy The post-marketing registries, established by the Italian Medicines Agency in 2005, represent the example of a national application of an automated workflow handling the personalized drug distribution in hospital pharmacies and local public pharmaceutical services, with the intent of both improving the efficacy/ efficiency of analysis and regulatory activities themselves, as well as closely monitoring the clinical activity. In fact, within the correct clinical practice the prescriber shall take into account the parameters, such as therapeutic drug indication, actual benefit the patient should gain in comparison to the trials, potential and actual risk of adverse reactions, drugs interactions, and cost of the therapy. On the track of the cancer registry’s experience, the Italian Medicines Agency has extended the scope to the following areas: ophthalmology, rheumatology, dermatology, orphan drugs, cardiology, diabetology, respiratory, and neurological diseases. It involves more than 60 drugs (most of them with risk sharing schemes on a population of over 400 000 patients) and is available from http://monitoraggio-farmaci.agenziafarmaco.it. Keywords: AIFA, MEAs, NHS, DB, CIRR The Registries of Italian Medicines Agency The aim of drugs monitoring is the computerized national management1 of the whole process concern- ing the request of dispensation and analysis of consumption data of an innovative drug. The computerized drugs prescription requires a change of mentality and a restructuring of the whole process; for these reasons, it’s still struggling to be used extensively. The Italian Medicines Agency (AIFA) has developed a treatment registration form and can monitor and control in real time the correct use of the drug. The first regulatory experience was the cancer drugs register.2 Based on this experience, AIFA has extended the scope to the following areas: ophthal- mology, rheumatology, dermatology, orphan drugs, cardiology, diabetology, respiratory, and neurologi- cal diseases. It involves more than 60 drugs (most of them with managed entry agreements (MEAs) on a population of over 400 000 patients (Table 1) and is available from http://monitoraggio-farmaci. agenziafarmaco.it. Through this network, AIFA will implement the monitoring process and the exchange of data between dose of the drug regarding a patient whose diagnosis corresponds to parameters of the authorized ther- apeutic indication (Fig. 1). The electronic form application, valid for a single administration, is automatically sent by email to the hospital pharmacy, which proceeds to close the form by formally and practically dispensing the requested drug. The system is accessible from any computer connected to the internet through the use of a username and password. It is also targeted to non-computer experts and does not require specific training. The procedures for entering and managing the data are standardized; however, the flows depend on the specificity of the drug and its therapeutic indication. For each prompt, the system offers additional compile a number of forms relating to the follow-up. In addition, and not least, is very important also to analyse the use of the innovative therapies directly with the pharmaceutical companies, according to the principle of risk sharing or pay by result: the awareness and evaluation of results of clinical practice and the purpose of defining the right cost to be incurred by the national health system. et al., 2012 The boat will leave from the Marine Etablissement Amsterdam. After the dinner there will be transfer to the hotels and the Central Station by bus. Wednesday 2 March (9:00 – 12:45) Conference venue: Marine Etablissement Amsterdam (MEA) Kattenburgerstraat 7, 1018 JA Amsterdam 08:30-09:00h Welcome and coffee 09:00-09:15h Opening and review of Tuesday Kees de Joncheere, moderator of the conference, Director, Department of Essential Medicines and Health Products World Health Organization (WHO) Geneva, Switzerland 09:15-09:45h Introduction objective 3: What are necessary conditions to come to an acceptable outcome of the pathway for the payer (“managed entry schemes and exit”) Entela Xoxi, Co-ordinator AIFA Registries, Italian Medicines Agency (AIFA) PROGRAMME ‘Innovation for the benefit of the patient: early interaction between market authorization, health technology assessment and payer in order to optimize patient access to innovative medicines’ Amsterdam, 29 February - 2 March 2016 Monday 29 February (19:00 – 21:00) Welcome drink and buffet. Venue: Kitchen & Bar Van Rijn, Address: Rembrandtplein 17, 1017 CT Amsterdam. 1 PROGRAMME ‘Innovation for the benefit of the patient: early interaction between market authorization, health technology assessment and payer in order to optimize patient access to innovative medicines’ Amsterdam, 29 February - 2 March 2016 Monday 29 February (19:00 – 21:00) Welcome drink and buffet. Venue: Kitchen & Bar Van Rijn, Address: Rembrandtplein 17, 1017 CT Amsterdam. Tuesday 1 March (9:00 – 22:00) Conference venue: Marine Etablissement Amsterdam (MEA) Address: Kattenburgerstraat 7, 1018 JA Amsterdam 08:30-09:00h Registration and coffee Make sure you arrive timely as entrance procedures may take some time 09:00-09:10h Opening Opening words by Edith Schippers, Dutch Minister of Health, Welfare and Sport 09:10-09:30h Introduction Introduction by Kees de Joncheere, moderator of the conference, Director Department of Essential Medicines and Health Products World Health Organization (WHO) Geneva, Switzerland 09:30-10:30h Presentation on Adaptive Pathways – Regulatory and HTA perspectives Tomas Salmonson, Chair of Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency, EMA and Senior Scientific Advisor at the Medical Products Agency (MPA), Sweden. Nick Crabb, Programme Director - Scientific Affairs, Centre for Health Technology Evaluation, National Institute for
  22. 22. Telematic tools @National AND @patient level designed to: ①  Verify label use (Appropriateness) collecting post-marketing data on clinical practice use (broad collection of baseline characteristics and follow ups) ②  Capture DATA available to the HTA bodies and stakeholders for B/R Assessment ③  Apply a risk-sharing approach or Managed Entry Agreements (*) ④  Govern the public drug expenditure (**) AIFA Registries within National Pricing & Reimbursement system (*) LD 2015 (**) ITS, 135/2012 Italian Law Patient Demographic information Eligibility & Clinical Data Drug Prescription Drug Dispensing Follow Up End of Treatment
  23. 23. DAAs registries http://www.agenziafarmaco.gov.it/it/content/registri-farmaci-sottoposti-monitoraggio 2017/02/13 update Criterion 1 - Patients with cirrhosis in Child class A or B and/or HCC with complete response to therapy resettive surgical or loco regional not candidates for liver transplantation in which the liver disease significantly affects prognosis Criterion 2 - Recurrent hepatitis HCV RNA-positive liver transplant patients in clinically stable and with optimal levels of immunosuppression Criterion 3 - Chronic hepatitis with severe HCV-related extrahepatic manifestations (cryoglobulinemic syndrome with organ damage, B-cell lymphoproliferative syndromes) Criterion 4 - Chronic hepatitis with fibrosis METAVIR F3 (or corresponding Ishak) Criterion 5 - In the list for liver transplantation with cirrhosis MELD <25 and/or HCC within the Milan criteria with the possibility of waiting in a list of at least 2 months Criterion 6 - Chronic hepatitis after solid organ transplantation (not liver) or marrow fibrosis METAVIR ≥2 (or corresponding Ishack) Criterion 7 - Chronic hepatitis with fibrosis METAVIR F0-F2 (or corresponding Ishak) Trend cumulativo dei trattamenti avviati 67,638 patients treated Trattamenti avviati per criterio Criterio N. Trattamenti 1 43.145 4 18.229 3 3.145 2 1.903 7 618 6 306 5 292 Criterion Treated patients
  24. 24. Dealing with Uncertainty
  25. 25. Managing budget impact Non Outcome based (single or combined) • Cost sharing • Capping • Price volume Managing uncertainty relating to clinical benefit & cost effectiveness Outcome based • Payment by result • Risk sharing • Success fee Managing utilization to optimize Appropriateness • Safety monitoring • Prescription plans • AIFA Notes Combination MEAs and P&R process SCHEME AGREEMENTS chè sono nati i Registri data di pubblicazione on ro dei Farmaci Oncologici OM), con la registrazione oro di un gruppo multidi- he ha ideato il progetto e rmaci oncologici: il grup- ell’AIFA (Sperimentazione Informazione sui Farmaci o di Consultazione sulla he riuniva rappresentanti ncologia Medica (AIOM), ologia (SIE), della Società gica (SIOG), della Società era (SIFO), degli Assesso- lla Commissione Tecnico frutto di competenze di- olatorie - scientifiche - as- rantire la complessità del assa critica estesa in gra- dozione delle procedure a necessità di individuare novazione e sostenibilità onsapevolezza che i nuovi sti di trattamento indotti per anno) e per le impli- rocesso assistenziale (de- terapeutica H-T), doveva- me terreno di verifica dei feribilità e di sostenibilità esentavano due principali esso FDA (Food and Drug opean Medicines Agency), e nei diversi paesi con un n termini di efficacia e di ia naturale della malattia; sposta clinica, per cui si molti pazienti per avere uale limitata di casi, ren- to rischio-beneficio. si contrapponevano due eva che non esistevano le so e mercato e chi affer- ncrementale doveva esse- gici. Per uscire da tale situazione dicotomica l’AIFA ha rite- nuto necessario, invece, individuare soluzioni e strategie basate su due principi semplici e condivisi: - un nuovo farmaco oncologico (o un’estensione delle indicazioni) va rimborsato solo se efficace nel singo- lo paziente, in quanto i sistemi sanitari di welfare non possono farsi carico dei fallimenti (failures) a fronte di costi così elevati; - introdurre procedure cliniche ben definite (scheda di arruolamento - scheda di follow-up - scheda di fine trattamento) per individuare i pazienti responders e attribuire alle aziende farmaceutiche i costi di tratta- mento mediante una procedura di pay-back. Pertanto l’adozione dei Registri e delle procedure di share scheme non hanno costituito un atteggiamento riduttivo o di razionamento ma il vero trade-off tra inno- vazione e sostenibilità economica. Veniva pertanto fissato il principio di riconoscere alle aziende farmaceutiche l’accesso ai nuovi farmaci in on- cologia ma altrettanto legittimo era il principio dell’AIFA di rimborsare il nuovo farmaco in quanto efficace, non essendo possibile sostenere un onere economico ele- vatissimo, facendosi carico dei fallimenti terapeutici nei pazienti che, nonostante il nuovo farmaco, manifestava- no una progressione della malattia. 2.3.2 Metodologia Nella Figura 15 viene sinteticamente riassunta la metodo- logia e la procedura di attivazione del Registro di monito- raggio e dell’adozione della procedura di share scheme. Risulta evidente che il Registro attraverso la scheda di ar- ruolamento assicura l’appropriatezza, facendo in modo che la prescrizione si riferisca esattamente all’indicazione auto- Figura 15 Metodologia e procedura del Registro di Monitoraggio mPFS of KM: tempo di follow-up calcolato sulla mediana della PFS della curva di Kaplan-Meier nel gruppo di controllo New anticancer drugs Follow-up mPFS of KM control group Evaluation of res onse Entire drug treat ent in charge of Drug treat ent in charge of Co an Responders Non responders Pa ent b results A ro riateness Italian LD 2015:Analysis after 2 Ys of monitoring. If the benefits obtained are lower than those expected, AIFA must initiate a process of re- negotiation with MAH, in order to reduce NHS costs
  26. 26. 44 Legend: BI: Limit budget impact, CE: Address uncertainties regarding the cost-effectiveness, Use: Monitor use in clinical practice, Access+CE: Improve patient access and cost-effectiveness. BE: Belgium, CY: Cyprus, CZ: Czech Republic, EN: England, IT: Italy, LT: Lithuania, MT: Malta, NL: Netherlands, PT: Portugal, SE: Sweden As shown in Figure 6.4 the objectives countries are trying to achieve in different disease areas seem to be distributed across different disease areas proportionally to the number of agreement in each objective group and the number of agreement per ATC-group. The only objective which appears to be disproportionately represented among oncological and immune- modulating treatments is cost-effectiveness. This is not surprising as these types of drugs 0 50 100 150 200 250 IT PT NL LT CZ SE EN BE CY BI+CE+Use CE+Use BI+Use BI+CE Use CE BI Managed entry agreements for pharmaceuticals: the European experience Alessandra Ferrario and Panos Kanavos
  27. 27. 30/03/201612/11/201523/07/2015 http://www.aifa.gov.it/it/content/sovaldiharvoni-attività-di-rimborso-alle-regioni-attuazione-del-meccanismo-prezzovolume http://www.aifa.gov.it/it/content/sovaldi-harvoni-attività-di-rimborso-alle-regioni-attuazione-del-meccanismo-prezzo-volume http://www.agenziafarmaco.gov.it/it/content/sovaldiharvoni-attivit%C3%A0-di-rimborso-alle-regioni-attuazione-del-meccanismo-prezzovolume-0 http://www.aifa.gov.it/it/content/farmaci-anti-hcv-raggiunti-scaglioni-stabiliti-da-accordi-prezzovolume-che-consentono-rimbor Regional allocations of P/V Agreement by Gilead (≈ 835MM) 27/12/2016
  28. 28. NO EU Regulation & Legal framework
  29. 29. Indication MEA should match the clinical indication and should mitigate uncertainties associated with it Proper Contract MEA should use appropriate parameters and should be consensually accepted by stakeholders Organization Budget holder should have dedicated person or unit in charge of contract design and monitoring Databases Budget holder should have the necessary infrastructure for data collection and validation MEAs can only be successful if: Adopted by David Dankò SEFH Managed Entry Agreements workshop 2016/11/03
  30. 30. • Long-term and comparative effectiveness • Place in therapy • Long-term safety profile Clinical • Future costs • Cost-effectiveness • Measures of QoL Economic • Number of eligibles • Market share • Treatment duration Utilisation • Overall impact on healthcare budgetFinancial Even if cost- effectiveness analysis did provide a reliable way forward, there is still a budgetary problem to be considered. Bach, N Engl J Med 2015 Value-based pricing under Uncertainty Xoxi E, Agenda item 4 - Real world evidence data collection Italian Experience on Registries, Commission expert group on "Safe and Timely Access to Medicines for Patients" (STAMP) Brussels, 10 March 2016 https://ec.europa.eu/health/sites/health/files/files/committee/stamp 2016-03_stamp4/4_real_world_evidence_aifa_presentation.pdf
  31. 31. Specific MEA for each therapeutic indication (Bach, Jama 2014)‘when costs are essentially the same but benefit differs widely, Value si not the same’ à crude metric value cost/Y of life gained Multiple drug-indications: Discrimination Price DrugX (List Price €1,000) Indication1 PbR T = 4 months Indication2 PbR T = 6 months Ceiling cap € 20mln Indication3 CS (20% discount 3 cycles Same list price, value-based cost Xoxi E, Agenda item 4 - Real world evidence data collection Italian Experience on Registries, Commission expert group on "Safe and Timely Access to Medicines for Patients" (STAMP) Brussels, 10 March 2016 https://ec.europa.eu/health/sites/health/files/files/committee/stamp 2016-03_stamp4/4_real_world_evidence_aifa_presentation.pdf
  32. 32. ①  All stakeholders – regulators, HTAbs, payers, healthcare professionals and patients – live with some uncertainty, and regulatory decisions routinely take account of the Uncertainty in the evaluation of the benefits and risks of medicines (*) ②  RWE as a complement to RCTs; in particular in the post-authorisation phase where RCTs might become less feasible and might not be an appropriate method to address the question of interest (*) ③  From a national payer perspective, registries should accelerate access of drugs to sub clusters of patients §  Prevent exclusion of drugs with potential efficacy §  Early exclusion of drugs with safety issues ④  Generate RWD. Integration of multiple databases may be needed to increase power in order to study rare exposures or outcomes or diverse populations (*) ⑤  Contain NHS expenditure optimizing allocation of resources and the sustainability of the system Conclusions (*) Adaptive pathways workshop briefing book Readers’ guidance http://www.ema.europa.eu/docs/en_GB/document_library/Other/2016/11/WC500216553.pdf
  33. 33. Thank you for the attention Entela Xoxi PharmD, PhD, MSci entelaxoxi@gmail.com www.linkedin.com/in/entela-xoxi @exoxi

×