NI2: PATIENT ACCESS SCHEMES IN UK ARE DRIVEN BY HEALTH TECHNOLOGY ASSESMENT Toumi M1, Jarosławski S2 1-Université Claude Bernard, Lyon I 2-Creativ-Ceutical, Paris Achieving market access for new products has become critical for pharmaceutical companies’ revenues 2 Understadning motivations is a prior requirement for establishing Market Access Agreements • • • • • • • • • The industry To optimize international reference pricing To capture product’s value (ensure profitability) To reduce the cost of an additional clinical trial To achieve access for patients and further explore drug’s potential To achieve competitive advantage (over cheaper or equally priced comparator drugs) To capture value of non-clinical or real-life benefits of the drug To obtain comparative real-life effectiveness data versus a comparator To mitigate a failure to achieve reimbursement or HTA recommendation and achieve global coverage (for policy reasons) To improve company’s image • • • • • • • • • The health care payer To provide patients with access while staying within budget To control expenditure To improve ICER of expensive products (and stay within a fixed threshold) To prioritize certain interventions to patients who most need it To align with a national/regional policy that prioritizes certain health outcomes Under pressure from patient associations, government or media To prevent media coverage of negative reimbursement decision To expand the list of innovative accessible interventions in the country (favourable publicity) To reduce uncertainty about real-life effectiveness or non-clinical drug benefits (e.g. compliance) METHODS • We reviewed official and grey literature on the websites of UK’s HTA Agency – NICE, the Department of Health (DoH), the industry and in the Internet. • We searched for documents containing words: scheme, risk-sharing, agreement, PAS, “patient access scheme”. • We selected PASs approved in England between 2006 - 2009 4 SEARCH RESULTS • We identified documents reffering to 10 PAS, • Using a reading grid, we extracted key information regarding NICE’s critics of the manufactirer’s submission and the desing of PAS 5 Reading grid layout Target population (elderly/ young; large/small) Chronic condition? Primary reason for NICE decision („Consideration of evidence”) Restrictions for use (second line, subgroup...) Role of other stakeholders (i.e. patients, associations) Role of price negotiations (another indications for the same product) Type of data considered by NICE for decision making (clinical trial, vs comparator, vs placebo…) Clinical primary endpoints taken into consideration by NICE Safety / tolerability superior or inferior to comparator Desired type of comparators provided by the company? Meta analysis /mixed treatment comparison / indirect comparison NICE’s comments on clinical evidence Cost effectiveness / ICER Subpopulations ICERs provided by the company Payer accepted unmet clinical claim/lack of other options Type of MAA Details of MAA design 6 Results • Cost-effectiveness of a medicine was the primary reason of PAS implementation • PAS could be grouped accodring do NICE critics regarding the cost-effectiveness (ICER) 7 Results 1: Cost-Effectiveness not acknowledged Medicine ERLOTINIB RITUXIMAB NICE comments MAA type Inferior efficacy and higher cost vs Cost genericized comparator. However, Containment few alternatives to comparator exists for patients No gain in Overall Survival. Gain in Cost Progression-Free Survival require Containment preference-based utilities which were not provided and this created high uncertainity aroung ICER value 8 MAA details This scheme has an automatic discount as credit note supplied against orders of erlotinib and or other Roche medicines by agreement and should have been credited automatically by Roche. Interim solution of the manufacturer: Free drug (for the full licensed course of treatment) for the first 300 patients to sign up Results 2: Uncertainity around long-term effect of a medicine Medicine NICE comments LENALIDOMIDE Uncertainty in the results of the indirect comparison. Trial duration inadequate RANIBIZUMAB MAA type Cost cap: free to NHS after a specified period No evidence that treatment Cost cap: free to effect can be extrapolated NHS after a beyond 2 years period of specified period RCT 9 MAA details The drug cost of lenalidomide (excluding any related costs) for people who remain on treatment for more than 26 cycles (each of 28 days; normally a period of 2 years) will be met by the manufacturer. The cost of ranibizumab beyond 14 injections (=2years=RCT duration) in the treated eye is met by the manufacturer Results 3A: Base case ICER challenged Medicine SUNITINIB CETUXIMAB NICE comments None. Sunitinib is a clinically effective first-line treatment for advanced and/or metastatic RCC for patients Statistically significant improvements in progression-free survival and response rates were associated with cetuximab PEMETREXED Generic gemcitabine become available and pemetrexed/cisplatin was no longer cost-effective. Committee concluded that pemetrexed/cisplatin was more clinically effective than gemcitabine/cisplatin MAA type Commercial agreement: free package (per patient basis) MAA details First cycle to a patient is free to NHS Commercial agreement: Rebate (per patient basis) The manufacturer rebates 16% of the amount of cetuximab used on a per patient basis. Commercial agreement: Rebate (per patient basis) Discounted price for drug after certain preagreed level of expenditure at full price has been reached. 10 Results 3B: Base case ICER challenged Medicine BORTEZOMIB NICE comments Clear evidence that bortezomib monotherapy is more clinically effective than HDD monotherapy for the treatment of relapsed multiple myeloma. However, not cost-effective. MAA type Outcome-based on per patient basis 11 MAA details Treatment is discontinued and its cost rebated in people whose disease had responded less than partially. Treatment continued only in those whose disease had responded at least partially. This lowered ICER to £20,700 per QALY gained. Results 3B: Base case ICER challenged Medicine CERTOLIZUMAB USTEKINUMAB NICE comments Cost saving with PAS in place, as compared to other biologicals NICE concluded that the estimates of the cost effectiveness of ustekinumab compared with supportive care were acceptable. MAA type Mix of outcomebased and Commercial agreement Mix of outcomebased and Commercial agreement 12 MAA details Supplied for free for the first 12 weeks and then only responders will continue the treatment. Flat price per patient, once a given dosage is reached. The manufacturer provide the higher dose needed for people who weigh more than 100 kg at the same total cost as the lower dose for people who weigh 100 kg or less. PAS is a tool used by NICE to lower the ICER of medicines Adalimumab Cost per QALY ICER Certolizumab Scenario 1 Scenario 2 add-on vs. generic vs. adalimumab Without PAS £41,000 £102,000 £46,192 £13,000 WITH PAS £29,600 £27,100 -£582 -£451 ICERs calculated by NICE and published in relevant appraisals 13 Topology and rationale of PAS in UK: HTA is the main driver Cost-Effectiveness not acknowledged NICE appraisal ERLOTINIB Cost Containment Uncertainty around long term effect RITUXIMAB Free TT after a defined period Cost-Effectiveness acknowledged LENALIDOMIDE RANIBIZUMAB SUNITINIB Cost containment ( ICER) CETUXIMAB PEMETREXED Basse-case ICER challenged Outcome based ( ICER) BORTEZOMIB Mixed of Cost containement Outcome based CERTOLIZUMAB USTEKINUMAB Could a UK PAS Make a Non-effective Drug Effective? NICE said YES • “The evidence available to support *the clinical effectiveness+ of dasatinib and nilotinib was very poor” • (...) “It would be heartening to hear that manufacturers are prepared to share some of the very high cost of these drugs with the NHS” Peter Littlejohns, clinical and public health director at NICE. • (...) Now if that isn't a call for a cost-share (or should we say 'patient-access scheme’), then I don't know what is” IN VIVO Blog Commentary PAS has become an additional instrument for cost containment 15 Conclusions • Formalized Health Technology Assessment is both a prerequisite and reason for implementing Patient Access Schemes in the UK. • If the comparative (cost-) effectiveness of a drug is acknowledged, the agreement is based of costcontainment. • If it is questioned, the PAS may have a form of a risk-sharing scheme and may be linking the payment to health outcomes (performance-based scheme). 16 Are PAS an appropriate answer for a true problem? 17 Actual questions: How to fairly price medicine? How to integrate affordability • Assume a Common perspective based on established rules • Only one rule « Value Based Pricing » – Better medicine deserve a better price – Does not say if the second best should lower the price or the first best increase the price • HTA is though to be the way to identify better medicine • ICER is though to address the affordability issue 18 Why doing HTA! • “Some fear that evidence based medicine will be hijacked by purchasers and managers to cut the costs of health care. This would not only be a misuse of evidence based medicine, but suggests a fundamental misunderstanding of its financial consequences. Doctors practicing evidence based medicine will identify and apply the most efficacious interventions to maximize the quality and quantity of life for individual patients; this may raise rather than lower the cost of their care.” • (Sackett et al, BMJ, 1996) 19 Affordability is the actual issue • ICER does not address affordability but efficiency which are different concepts • HTA does not address affordability but define the best therapeutic options for patient management • Neither HTA nor ICER address the public health priorities 20 Questioning the value based pricing has become inescapable Not only a matter of money, But money matters! It is just a nightmare for society... In the meantime we will all continue to do MAA 21 Thank you! University Claude Bernard Lyon 1 UFR d’Odontologie 11, rue Guillaume Paradin 69372 LYON Cedex 08 [email protected] Mobile: +33 6 8666 3550 Web: www.emaud.org 22