Patient Access Scheme Research Articles

Methodology for the management of outsourced outpatient services within the NHS pharmacy service

ObjectivesThe successful management of outsourced services is a skill which is increasingly required in the UK National Health Service (NHS). However, it is not something that is widely taught and...

The Clinical and Cost Effectiveness of Ustekinumab for the Treatment of Psoriatic Arthritis: A Critique of the Evidence.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ustekinumab (Janssen) to submit evidence for the clinical and cost effectiveness of ustekinumab for the treatment of active psoriatic arthritis (PsA) as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics Technology Appraisal Group at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the ERG review of the manufacturer's evidence submission, and summarises the NICE Appraisal Committee's final guidance (TA340) issued in June 2015. The manufacturer presented evidence on ustekinumab for two patient populations: (1) a tumour necrosis factor-α (TNFα)-inhibitor-naïve population who had not previously received any TNFα inhibitors (biologics); and (2) a TNFα-inhibitor-exposed population who had previously received at least one TNFα inhibitor. The clinical evidence for ustekinumab was derived from two randomised controlled trials (PSUMMIT 1 and 2), in which a total of 927 patients who had not responded to previous disease-modifying antirheumatic drug therapies received ustekinumab 45 mg, ustekinumab 90 mg, or placebo. These data suggested that ustekinumab is more effective than placebo over 16-24 weeks in terms of both joint and skin response. In the absence of head-to-head comparisons between different biologics (ustekinumab, golimumab, etanercept, adalimumab and infliximab), the manufacturer conducted a network meta-analysis to estimate the relative efficacy of treatments for the TNFα-inhibitor-naïve population. Results of this analysis were marked as academic in confidence and are therefore not reported. For the TNFα-inhibitor-exposed population, the clinical analysis was limited to ustekinumab versus conventional management only, and was based on a subgroup of 180 patients from the PSUMMIT 2 trial. The ERG raised concerns relating to the lack of data on the long-term efficacy of ustekinumab, the limited data available for the exposed population, and the lack of consideration of the sequential use of treatments. Based on the manufacturer's original model, the ERG found ustekinumab to be dominated by golimumab in the anti-TNF-inhibitor-naïve population, and had an incremental cost-effectiveness ratio (ICER) of £29,843/quality-adjusted life-years versus conventional management in the exposed population. The ERG's analyses highlighted the fact that there is significant uncertainty around the model results. In addition, the ERG's exploratory cost-effectiveness analysis, which incorporated the sequential use of TNFα inhibitors, suggested that ustekinumab would not be cost effective if it were used as second-line treatment. The initial NICE recommendations asserted that ustekinumab was not recommended for treating active PsA. However, the manufacturer submitted a post-consultation model that included a Patient Access Scheme (PAS), halving the unit cost of ustekinumab 90 mg to £2147 (the same as a 45 mg dose). The NICE final recommendations were that, dependent on the inclusion of the PAS, ustekinumab is recommended as an option, along or in combination with methotrexate, for treating active PsA in adults only when treatment with TNFα inhibitors is contraindicated but would otherwise be considered, or the person has previously had treatment with one or more TNFα inhibitors, which has failed.

Vedolizumab for the Treatment of Adults with Moderate-to-Severe Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The Evidence Review Group (ERG) produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from GEMINI 1, a Phase 3, multicentre, randomised, double-blinded, placebo-controlled study of the induction and maintenance of clinical response and remission by vedolizumab (MLN0002) in patients with moderate-to-severe active UC with an inadequate response to, loss of response to or intolerance of conventional therapy or anti-tumour necrosis factor (TNF)-α. The clinical evidence showed that vedolizumab performed significantly better than placebo in both the induction and maintenance phases. In the post hoc subgroup analyses in patients with or without prior anti-TNF-α therapy, vedolizumab performed better then placebo (p value not reported). In addition, a greater improvement in health-related quality of life was observed in patients treated with vedolizumab, and the frequency and types of adverse events were similar in the vedolizumab and placebo groups, but the evidence was limited to short-term follow-up. There were a number of limitations and uncertainties in the clinical evidence base, which warrants caution in its interpretation--in particular, the post hoc subgroup analyses and high dropout rates in the maintenance phase of GEMINI 1. The company also presented a network meta-analysis of vedolizumab versus other biologic therapies indicated for moderate-to-severe UC. However, the ERG considered that the results presented may have underestimated the uncertainty in treatment effects, since fixed-effects models were used, despite clear evidence of heterogeneity among the trials included in the network. Results from the company's economic evaluation (which included price reductions to reflect the proposed patient access scheme for vedolizumab) suggested that vedolizumab is the most effective option compared with surgery and conventional therapy in the following three populations: (1) a mixed intention-to-treat population, including patients who have previously received anti-TNF-α therapy and those who are anti-TNF-α naïve; (2) patients who are anti-TNF-α naïve only; and (3) patients who have previously failed anti-TNF-α therapy only. The ERG concluded that the results of the company's economic evaluation could not be considered robust, because of errors in model implementation, omission of relevant comparators, deviations from the NICE reference case and questionable model assumptions. The ERG amended the company's model and demonstrated that vedolizumab is expected to be dominated by surgery in all three populations.

Lenalidomide for the Treatment of Low- or Intermediate-1-Risk Myelodysplastic Syndromes Associated with Deletion 5q Cytogenetic Abnormality: An Evidence Review of the NICE Submission from Celgene.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic abnormality, as part of the Institute’s single technology appraisal (STA) process. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company’s submission, the ERG review, and the NICE’s subsequent decisions. The ERG reviewed the evidence for clinical and cost effectiveness of the technology, as submitted by the manufacturer to the NICE. The ERG searched for relevant additional evidence and validated the manufacturer’s decision analytic model to examine the robustness of the cost-effectiveness results. Clinical effectiveness was obtained from a three-arm, European, randomized, phase III trial among red blood cell (RBC) transfusion-dependent patients with low-/intermediate-1-risk del5q31 MDS. The primary endpoint was RBC independence for ≥26 weeks, and was reached by a higher proportion of patients in the lenalidomide 10 and 5 mg groups compared with placebo (56.1 and 42.6 vs 5.9 %, respectively; both p < 0.001). The option of dose adjustments after 16 weeks due to dose-limiting toxicities or lack of response made long-term effectiveness estimates unreliable, e.g. overall survival (OS). The de novo model of the manufacturer included a Markov state-transition cost-utility model implemented in Microsoft Excel. The base-case incremental cost-effectiveness ratio (ICER) of the manufacturer was £56,965. The ERG assessment indicated that the modeling structure represented the course of the disease; however, a few errors were identified and some of the input parameters were challenged. In response to the appraisal documentation, the company revised the economic model, which increased the ICER to £68,125 per quality-adjusted life-year. The NICE Appraisal Committee (AC) did not recommend lenalidomide as a cost-effective treatment. Subsequently, the manufacturer submitted a Patient Access Scheme (PAS) that provided lenalidomide free of charge for patients who remained on treatment after 26 cycles. This PAS improved the ICER to £25,300, although the AC considered the proportion of patients who received treatment beyond 26 cycles, and hence the ICER, to be uncertain. Nevertheless, the AC accepted a commitment from the manufacturer to publish, once available, data on the proportion of patients eligible for the PAS, and believed this provided reassurance that lenalidomide was a cost-effective treatment for low- or intermediate-1-risk MDS patients.

Cost-utility of fingolimod compared with dimethyl fumarate in highly active relapsing-remitting multiple sclerosis (RRMS) in England

Objective:The cost-effectiveness of new oral disease-modifying therapies (DMTs) has not been modeled in highly active (HA) relapsing-remitting multiple sclerosis (RRMS) requiring escalation therapy. This study sought to model the cost-effectiveness of fingolimod compared to dimethyl fumarate (DMF), for which relevant HA RRMS sub-group data were available, from the perspective of the National Health Service (NHS) in England.Methods:A cohort Markov model based on Expanded Disability Status Scale scores, similar to previous model designs, was constructed. Published post hoc clinical data in the HA RRMS sub-groups were taken from the pivotal trials for fingolimod and DMF vs placebo. Utility data for each health state and for relapses were used in line with previous similar models. Published costs were inflated to NHS cost year 2013–2014 and UK list prices used for both drugs. Possible Patient Access Scheme (PAS) discount scenarios were investigated.Results:In the base case, using list prices for each DMT, the average probabilistic incremental cost-effectiveness ratio (ICER) for fingolimod vs DMF was found to be £14,076, with a 73% chance of fingolimod being cost-effective at a willingness-to-pay threshold of £30,000. Scenario and sensitivity analyses showed that uncertainty in disability progression efficacy was a key model driver. The model was robust to other changes and the majority of PAS permutations do not contradict the base case finding of cost-effectiveness of fingolimod.Conclusions:In conclusion, fingolimod remains cost-effective in HA RRMS following the introduction of DMF to the UK market, and this paper supports the evidence that has led fingolimod to be the only oral DMT reimbursed for HA RRMS in England. This model supports the restriction imposed by National Institute for Health and Care Excellence (NICE) on DMF in HA RRMS and highlights the importance of considering different sub-groups of multiple sclerosis when performing health economic analyses.

PSY81 - How much is nice really prepared to pay for Orphan and end-of-life Drugs?

New health technologies are required to demonstrate clinical and cost-effectiveness before recommendation by the National Institute for Health and Care Excellence (NICE) for reimbursement in England; however, higher cost-effectiveness thresholds may be considered for orphan and end-of-life (EOL) therapies. To help inform future submissions, the incremental cost-effectiveness ratios (ICERs) of – and rationale behind – accepted NICE submissions for orphan and EOL therapies were assessed. All NICE single technology appraisals from January 2009 to December 2014 were included in the analysis. The decision, rationale, and manufacturer’s ICER (including patient access scheme where applicable) for each submission were extracted. Appraisals were then assessed for meeting NICE EOL or European orphan drug criteria. Multiple technology appraisals, resubmissions, vaccination programmes, requests for advice, and submissions where an ICER could not be determined were excluded. Of 111 relevant NICE submissions, 12 met orphan drug criteria, 16 met EOL criteria and 4 met both. For orphan drugs, 8/12 (67%) were accepted, with a mean ICER of £33,725 for accepted submissions (range: £24,544 - 56,693). For EOL drugs, 12/16 (75%) were accepted, with a mean ICER of £40,906 for accepted submissions (range: £14,795-£62,829). This compared with an overall acceptance rate for non-orphan/EOL NICE submissions of 71/87 (82%), with a mean ICER of £15,303 for accepted submissions (range: £1,537-£35,208). Rationale for acceptance of orphan and EOL drug submissions included unmet therapeutic need, lack of alternative treatment options, and innovation. Based on the evidence, NICE’s decision threshold was significantly higher for orphan/EOL drugs than for others (p<0.001). However, the overall acceptance rate was lower, and restrictions to patient sub-populations as well as patient access schemes were often applied. Nevertheless, the incorporation of elements such as unmet need into the decision-making process makes high ICERs appropriate where there is strong evidence of demonstrable clinical benefit.

Dabrafenib for Treating Unresectable, Advanced or Metastatic BRAF V600 Mutation-Positive Melanoma: An Evidence Review Group Perspective.

The National Institute for Health and Care Excellence (NICE) invited GlaxoSmithKline, the manufacturer of dabrafenib, to submit evidence for the clinical and cost effectiveness of dabrafenib for the treatment of unresectable, advanced or metastatic BRAF V600 mutation-positive melanoma in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the company and provides a summary of the Appraisal Committee's (AC) final decision in October 2014. The clinical evidence for dabrafenib was derived from an ongoing phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BREAK-3) involving 230 patients randomized 2:1 to receive either dabrafenib or dacarbazine. A significant improvement in median progression-free survival (PFS) but not overall survival (OS) was reported in the dabrafenib arm compared with dacarbazine. Vemurafenib is considered a more appropriate comparator than is dacarbazine. The clinical evidence for vemurafenib was derived from a completed phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BRIM-3) involving 675 patients randomized 1:1 to receive either vemurafenib or dacarbazine. A significant improvement in median PFS and OS was reported in the vemurafenib arm compared with dacarbazine. As there is no direct evidence comparing dabrafenib versus vemurafenib, the company presented an indirect treatment comparison (ITC) that demonstrated no statistical differences between dabrafenib and vemurafenib for PFS or OS. The ERG expressed concerns with the ITC, mainly in relation to the validity of the assumptions underpinning the methodology; the ERG concluded this resulted in findings that are unlikely to be robust or reliable. Dabrafenib and vemurafenib are both available to patients treated by the National Health Service (NHS) in England via a Patient Access Scheme (PAS) in which the costs of the drugs are discounted. Using these discounted costs, the incremental cost-effectiveness ratios (ICERs) generated by the company were £60,980 per quality-adjusted life-year (QALY) for dabrafenib versus dacarbazine and £11,046 per QALY gained for dabrafenib versus vemurafenib. The ERG considered the economic model structure developed by the company to derive the ICERs to be overly complex and based on unsubstantiated assumptions, most importantly in relation to the projection of OS. Applying the latest OS data from BREAK-3 to a less complex model structure increased the estimated ICER for dabrafenib compared with dacarbazine from £60,980 to £112,727 per QALY gained. Since the results from the ITC were considered by the ERG to be neither reliable nor robust, the ERG also considered a cost-effectiveness comparison to be inappropriate due to a lack of meaningful or reliable data. In spite of limitations in the data, the AC took the view that dabrafenib and vemurafenib were "likely" of similar clinical effectiveness. Since the overall costs of these two drugs were similar, the AC recommended the use of dabrafenib in patients with unresectable, advanced or metastatic BRAF V600 mutation-positive melanoma.

Patient access schemes in Asia-pacific markets: current experience and future potential.

ObjectivesPatient access (or risk-sharing) schemes are alternative market access agreements between healthcare payers and medical product manufacturers for conditional coverage of promising health technologies. This study aims to identify and characterize patient access schemes to date in the Asia-Pacific region.MethodsWe reviewed the literature on patient access schemes over the last two decades using publicly available databases, Internet, and grey literature searches. We extracted key features of each scheme identified, including the drug, clinical indication, stakeholders involved, and details of the scheme. We categorized schemes according to a previously published taxonomy of scheme types and by country.ResultsWe identified 3 schemes in South Korea, 5 in New Zealand, and 98 in Australia. Most (97.2%; n = 103) schemes focused on pharmaceuticals, few on medical technologies. More than half of the schemes related to treatments for cancer and inflammatory diseases such as rheumatoid arthritis. The majority (77.4%; n =82) involved pricing arrangements. Evidence generation schemes were rarely used. About half (41.8%; n = 41) of schemes in Australia were hybrid by nature, consisting of pricing arrangements with a conditional treatment continuation component.ConclusionsAustralia has the most experience with patient access schemes and its experience may provide useful insights for other Asia-Pacific countries. The main targets are pharmaceuticals likely to have high budget impact (due to high per-patient costs and/or large volumes of use), and pharmaceuticals that may be adopted more widely than indicated. With the proliferation of high-cost medicines, the use of schemes may increase to address rising cost pressures, consumer demands, and uncertainties, while attempting to provide patient access to innovative care within finite budgets. Future research is warranted to evaluate the performance of patient access schemes.

Medicines and universal health coverage: challenges and opportunities.

Medicines and universal health coverage: challenges and opportunities.

Market-access agreements for anti-cancer drugs.

Newly marketed pharmaceuticals command increasingly high prices, particularly in oncology where single treatment cycles can be very costly, even though data at market approval are usually inadequate to describe thoroughly their effectiveness and cost-effectiveness. Both manufacturers and payers have shown interest in solutions to achieve rapid access for patients – known as ‘market-access agreements’. Although the literature offers a variety of definitions, these agreements can be roughly grouped under two main types: financial-based and performance-based. Financial-based schemes focus on the budget impact of a new drug and usually consist of price/dose discounts. Performancebased schemes involve collecting clinical evidence once a new drug has been marketed in a healthcare system and lead to payment only for patients responding to therapy, an objective which is methodologically and practically challenging while not without political appeal. The underlying strategy is to help reduce the likelihood of payers adopting technologies that turn out not to be cost-effective, while at the same time helping manufacturers increase market access time and take profit. Market-access agreements can also be considered an opportunistic way for manufacturers to keep official prices high such as maintaining a common European price, while granting health authorities confidential rebates, thus preventing parallel trade and undermining effective external reference pricing. The English and Italian health services have been the first countries to introduce market-access agreements on specific drugs. These contracts are now called Managed Entry Agreements (MEA) in Italy and Patient Access Schemes (PAS) in England and Wales. We focus on the area of oncology, where many new drugs are costly and fall under these arrangements. Italy

Pharmaceutical Market Access in Emerging Markets Through Innovative Patient Access Schemes.

Pharmaceutical Market Access in Emerging Markets Through Innovative Patient Access Schemes.

Correlation Between End-of-Life Status of A Treatment And Likelihood of A Patient Access Scheme in The Setting of A Nice Review in The UK.

Correlation Between End-of-Life Status of A Treatment And Likelihood of A Patient Access Scheme in The Setting of A Nice Review in The UK.

Optimizing the Position and Use of Omalizumab for Severe Persistent Allergic Asthma Using Cost-Effectiveness Analysis

BackgroundThere has been some controversy on whether the costs of omalizumab outweigh its benefits for severe persistent allergic asthma. ObjectivesThis study aimed to resolve the uncertainties and limitations of previous analyses and establish the cost-effectiveness of omalizumab under the list price and Patient Access Scheme (PAS) discounted price for the UK National Health Service. MethodsA decision-analytic model was developed to evaluate the long-term cost-effectiveness of omalizumab under the perspective of the National Health Service. Outcomes were expressed as quality-adjusted life-years (QALYs). Patient subgroups were defined post hoc on the basis of data collected in clinical trials: previous hospitalization, on maintenance oral corticosteroids, and three or more previous exacerbations. ResultsThe incremental cost-effectiveness ratio varied from £30,109 to £57,557 per QALY gained depending on the population considered using the PAS price; incremental cost-effectiveness ratios were over a third higher using the list price. Omalizumab is likely to be cost-effective at the threshold of £30,000 per QALY gained in the severe subgroups if the improvement in health-related quality of life from omalizumab is mapped from an asthma-specific measure to the EuroQol five-dimensional questionnaire (vs. the EuroQol five-dimensional questionnaire directly collected from patients) or asthma mortality refers to death after hospitalization from asthma (vs. asthma-mortality risk in the community). ConclusionsAlthough the cost-effectiveness of omalizumab is more favorable under the PAS price, it represents good value for money only in severe subgroups and under optimistic assumptions regarding asthma mortality and improvement in health-related quality of life. For these reasons, omalizumab should be carefully targeted to ensure value for money.

Eribulin for the treatment of advanced or metastatic breast cancer: a NICE single technology appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of eribulin (Eisai Ltd) to submit evidence for the clinical and cost effectiveness of eribulin as treatment for patients with locally advanced or metastatic breast cancer (LABC/MBC) pre-treated with at least two chemotherapy regimens. This article summarizes the review of evidence by the Evidence Review Group (ERG) and provides a summary of the NICE Appraisal Committee's (AC's) decision. The clinical evidence was derived from a multi-centred, open-label, randomized, phase III study comparing eribulin with treatment of physician's choice (TPC) in 762 patients with LABC/MBC. Clinical effectiveness results were submitted for two populations: the overall intention-to-treat (ITT) population and a subset (n = 488) that included only patients from North America, Western Europe and Australia (Region 1). For the primary endpoint of overall survival (OS), a primary analysis (after 55 % of patients had died) and an updated analysis (after 77 % of patients had died) were conducted. In the ITT population, treatment with eribulin was associated with a significant improvement in median OS compared with TPC in both primary [difference in median OS 2.5 months; hazard ratio (HR) 0.81, 95 % confidence interval (CI) 0.66-0.99] and updated analyses (2.7 months; HR 0.81, 95 % CI 0.67-0.96). A statistically significant improvement in progression-free survival (PFS) was reported for eribulin compared with TPC when assessed by the investigator (difference in median PFS 1.48 months; HR 0.76, 95 % CI 0.64-0.90), but not when assessed by the ERG (1.44 months; HR 0.87, 95 % CI 0.71-1.05). Gains in OS were greater for Region 1 patients than for the ITT population (3.1 vs. 2.7 months). Health-related quality of life (HRQoL) data suggested a benefit for eribulin responders, but was based on phase II studies. In the eribulin arm, serious adverse events included febrile neutropenia (4.2 %) and neutropenia (1.8 %), with peripheral neuropathy being the most common reason for treatment discontinuation. The manufacturer's economic evaluation using Patient Access Scheme costs reported a base-case incremental cost-effectiveness ratio (ICER) for eribulin versus TPC (Region 1) of £46,050 per quality-adjusted life year gained (corrected to £45,106 when an erroneous data entry was removed). The ERG's revised ICERs were £61,804 for Region 1 and £76,110 for the overall population. The AC concluded that the evidence had not demonstrated sufficient benefit in OS, cost effectiveness or HRQoL and that eribulin was not recommended for use in this patient group.

A Comparative Analysis of Two Contrasting European Approaches for Rewarding the Value Added by Drugs for Cancer: England Versus France

Within Europe, contrasting approaches have emerged for rewarding the value added by new drugs. In Ireland, The Netherlands, Sweden and the UK, the price of, and access to, a new drug has to be justified by the health gain it delivers compared with current therapy, typically expressed in quality-adjusted life-years (QALYs) gained. By contrast, in France and Germany, the assessment of added benefit is expressed on an ordinal scale, based on an assessment of the clinical outcomes as compared with existing care. This assessment then influences price negotiations. The objective of this paper is to assess the pros and cons of each approach, both in terms of the assessments they produce and the efficiency and practical feasibility of the process. We reviewed the technology appraisals performed by the National Institute for Health and Care Excellence (NICE) relating to 49 anticancer drug decisions in the UK from September 2003 to January 2012. Estimates of the QALYs gained and incremental cost per QALY gained were then compared with the assessments of the Amélioration du Service Médical Rendu (ASMR) made by the Haute Autorité de Santé (HAS) in France for the same drugs in the same clinical indications. We also undertook a qualitative assessment of the two approaches, considering the resources required, timeliness, transparency, stakeholder engagement, and political acceptability. In the UK, the estimates of QALYs gained ranged from 0.003 to 1.46 and estimates of incremental cost per QALY from £3,320 to £458,000. The estimate of cost per QALY gained was a good predictor of the level of restriction imposed on the use of the drug concerned. Patient access schemes, which normally imply price reductions, were proposed in 45 % of cases. In France, the distribution of ASMRs was I, 12 %; II, 18 %; III, 24 %; IV, 18 %; V, 22 %; and uncategorized/non-reimbursed, 4 %. Since ASMRs of IV and above signify minor or no improvement over existing therapy, these ratings imply that, in around 40 % of cases, the drugs concerned would face price controls. Overall, the assessments of value added in the two jurisdictions were very similar. A superior ASMR rating was associated with higher QALYs gained. However, a superior ASMR was not associated with a lower incremental cost per QALY. There are substantial differences in respect of the other attributes considered, but these mainly reflect the result of institutional choices in the jurisdictions concerned and it is not possible to conclude that one approach is universally superior to the other. The two approaches produce very similar assessments of added value, but have different attributes in terms of cost, timeliness, transparency and political acceptability. How these considerations impact market access and prices is difficult to assess, because of the lack of transparency concerning prices in both countries and the fact that market access also depends on a broader range of factors. There is some evidence of convergence in the approaches, with the movement in France towards producing cost-effectiveness estimates and the movement in the UK towards negotiated prices.

A cost–utility analysis of degarelix in the treatment of advanced hormone-dependent prostate cancer in the United Kingdom

Objective:To determine the cost-effectiveness of the treatment of advanced hormone-dependent prostate cancer with degarelix compared to luteinizing hormone-releasing hormone (LHRH) agonists in the UK using the latest available evidence and the model submitted to AWMSG.Methods:A cost-effectiveness model was developed from the perspective of the UK National Health Service evaluating monthly injection of degarelix against 3-monthly leuprorelin therapy plus anti-androgen flare cover for the first-line treatment of patients with advanced (locally advanced or metastatic) hormone-dependent prostate cancer. A Markov process model was constructed using the patient population characteristics and efficacy information from the CS21 Phase III clinical trial and associated extension study (CS21A). The intention-to-treat (ITT) population and a high-risk sub-group with a PSA level >20 ng/mL were modeled.Results:In the base-case analysis using the patient access scheme (PAS) price, degarelix was dominant compared to leuprorelin with cost savings of £3633 in the ITT population and £4310 in the PSA > 20 ng/mL sub-group. The chance of being cost-effective was 95% in the ITT population and 96% in the PSA > 20 ng/mL sub-group at a threshold of £20,000 per quality-adjusted life-year (QALY). In addition, degarelix remained dominant when PSA progression was assumed equal and only the benefits of preventing testosterone flare were taken into account. Treatment with degarelix also remained dominant in both populations when the list price was used. The additional investment required to treat patients with degarelix could be offset in 19 months for the ITT population and 13 months for the PSA > 20 ng/mL population. The model was most sensitive to the hazard ratio assumed for PSA progression between degarelix and leuprorelin and the quality-of-life (utility) of patients receiving palliative care.Conclusion:Degarelix is likely to be cost-effective compared to leuprorelin plus anti-androgen flare cover in the first-line treatment of advanced hormone-dependent prostate cancer.

Health economic evaluation in England

The 2010 National Health Service Constitution for England specified rights and responsibilities, including health economic evaluation for the National Institute for Health and Care Excellence (NICE) and the Joint Committee on Vaccinations and Immunisations. The National Screening Committee and the Health Protection Agency also provide advice to the Government based on health economic evaluation. Each agency largely follows the methods specified by NICE. To distinguish the methods from neoclassical economics they have been termed "extra-welfarist". Key differences include measurement and valuation of both benefits (QALYs) and costs (healthcare related). Policy on discounting has also changed over time and by agency. The debate over having NICE's methods align more closely with neoclassical economics has been prominent in the ongoing development of "value based pricing". The political unacceptability of some decisions has led to special funding for technologies not recommended by NICE. These include the 2002 Multiple Sclerosis Risk Sharing Scheme and the 2010 Cancer Drugs Fund as well as special arrangements for technologies linked to the end of life and for innovation. Since 2009 Patient Access Schemes have made price reductions possible which sometimes enables drugs to meet NICE's cost-effectiveness thresholds. As a result, the National Health Service in England has denied few technologies on grounds of cost-effectiveness.

The Cost Effectiveness of Dry Powder Antibiotics for the Treatment of Pseudomonas aeruginosa in Patients with Cystic Fibrosis

Cystic fibrosis (CF) affects over 9,000 people in the UK and limits life expectancy. CF patients are susceptible to lung infections, most commonly Pseudomonasaeruginosa. Once infection is established, patients require lifetime treatment using nebulised antibiotics. Newer dry powder formulations of antibiotics may reduce treatment burden and improve compliance. Our objective was to evaluate the cost effectiveness of (i) colistimethate sodium dry powder for inhalation (DPI) and (ii) tobramycin DPI versus nebulised tobramycin for the treatment of chronic P.aeruginosa lung infection in patients with CF from the perspective of the National Health Service (NHS) and Personal Social Services (PSS). We developed a state transition model based on transitions between three strata of lung function measured in terms of forced expiratory volume in 1 second (FEV1) % predicted. Additional health states representing post-lung transplantation and dead are also modelled. The model structure was informed by systematic reviews of evidence concerning the plausibility of potential relationships between intermediate endpoints and final outcomes. The model assumes that treatment impacts on FEV1 trajectory, which manifest as changes in health-related quality of life. No survival benefit is assumed due to the absence of robust quantifiable evidence. Model parameters were informed by patient-level and aggregate data from two randomised controlled trials together with the best available evidence from the literature. Resource use and costs associated with drug acquisition, the management of exacerbations and reduced nebuliser maintenance were drawn from reference sources and expert opinion. Costs were valued at 2011/2012 prices. Costs and health outcomes were discounted at a rate of 3.5%. Simple and probabilistic sensitivity analyses were undertaken, including additional analyses of Patient Access Scheme (PAS) price discounts offered by the manufacturers of both DPI products. Colistimethate sodium DPI is expected to produce fewer quality-adjusted life-years (QALYs) than nebulised tobramycin. Based on its list price, colistimethate sodium DPI is expected to be dominated by nebulised tobramycin. When the PAS is incorporated, the incremental cost-effectiveness ratio (ICER) for colistimethate sodium DPI versus nebulised tobramycin is expected to be approximately £288,600 saved per QALY lost. Based on its current list price, the ICER for tobramycin DPI versus nebulised tobramycin is expected to be approximately £124,000 per QALY gained. When the proposed PAS is included, tobramycin DPI is expected to dominate nebulised tobramycin. Under their list prices, neither DPI product is likely to represent good value for money for the NHS given current cost-effectiveness thresholds. The PAS discounts have a significant impact upon the economic attractiveness of both DPI products compared against nebulised tobramycin. The clinical effectiveness and cost effectiveness of the DPIs against other nebulised antibiotics, such as aztreonam and inhaled colistimethate sodium, remains unclear.

PHP9 - The Impact of Indication Extensions on Pharmaceutical Prices

To assess the impact of an indication extension on pharmaceutical prices in 9 markets: Australia, Brazil, France, Germany, Italy, Japan, Spain, Turkey, and the UK. Websites of the EMA and national regulatory agencies were surveyed to indentify medicines granted an indication extension between 2007 and 2013. Eight case studies (bevacizumab, trastuzumab, sunitinib, ivabradine, telmisartan, aripiprazole, paliperidone, and omalizumab) were selected based on market share and availability across the geographies of interest. The list prices, at ex-manufacturer levels, of these eight drugs and those of the medicines belonging to their therapeutic class (at ATC level 3) were collected for the period 2007-13. Price movements for these eight medicines were compared to the price evolution within their therapeutic class over the period. Based on the selected case studies, there is ambivalent synchrony between indication extensions and pharmaceutical list price movements in the countries analysed. The data show that list prices tend to remain stable following an indication extension. When list prices changed subsequent to an indication extension, the movements could not directly be linked to the indication extension, as external factors such as a class trend or a wider pricing and reimbursement process (e.g. blanket price cuts) could also play a role. There is inconclusive evidence that indication extensions lead to list price changes in the countries analysed. Moreover, the impact of commercial agreements and discounts should be taken into account as secondary indications may be subject to separate pricing arrangements (e.g., patient access schemes). As such, the selection of the indication for the first marketing-authorisation filing (such as a high medical need, niche indication, commanding a premium price) is pivotal for the commercial success of a medicine, as its launch price seems unlikely to be reviewed following subsequent approvals in broader patient populations.

PCN186 - Three Years of the Gefitinib UK Single Patient Access (SPA) Scheme: Duration of Treatment for Patients with EGFR Mutation Positive NSCLC in NHS Clinical Practice

PCN186 - Three Years of the Gefitinib UK Single Patient Access (SPA) Scheme: Duration of Treatment for Patients with EGFR Mutation Positive NSCLC in NHS Clinical Practice