Patient Access Scheme Research Articles

Onasemnogene Abeparvovec for Treating Pre-symptomatic Spinal Muscular Atrophy: An External Assessment Group Perspective of the Partial Review of NICE Highly Specialised Technology Evaluation 15.

As part of the National Institute for Health and Care Excellence (NICE) highly specialised technology (HST) evaluation programme, Novartis submitted evidence to support the use of onasemnogene abeparvovec as a treatment option for patients with pre-symptomatic 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the survival of motor neuron (SMN) 1 gene and up to three copies of the SMN2 gene. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the External Assessment Group (EAG). This article summarises the EAG's review of the evidence submitted by the company and provides an overview of the NICE Evaluation Committee's final decision, published in April 2023. The primary source of evidence for this evaluation was the SPR1NT trial, a single-arm trial including 29 babies. The EAG and committee considered that the SPR1NT trial results suggested that onasemnogene abeparvovec is effective in treating pre-symptomatic SMA; however, long-term efficacy data were unavailable and efficacy in babies aged over 6 weeks remained uncertain. Cost-effectiveness analyses conducted by the company and the EAG (using a discounted price for onasemnogene abeparvovec) explored various assumptions; all analyses generated incremental cost-effectiveness ratios (ICERs) that were less than £100,000 per quality-adjusted life-year (QALY) gained. The committee recommended onasemnogene abeparvovec as an option for treating pre-symptomatic 5q SMA with a bi-allelic mutation in the SMN1 gene and up to three copies of the SMN2 gene in babies aged ≤12 months only if the company provides it according to the commercial arrangement (i.e. simple discount patient access scheme).

Improving Patient Access Scheme in Malaysia: lessons from Italy

PurposeMedicine prices are increasing globally, including in Malaysia where previous studies show prices higher than international averages. Patient Access Scheme (PAS) is a mechanism adopted by Malaysia in 2018 to facilitate access to expensive medicines, similarly used by Italy since 2005. This study aims to compare the implementation of PAS in Malaysia and Italy.Design/methodology/approachThis review systematically searched for peer-reviewed articles in PubMed, Scopus and ScienceDirect on how Italy implemented PAS system from 2012 to 2022 using the related keywords. The systematic review is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.FindingsThe search identified 363 articles. A total of eight studies were included. Most of the studies found that PAS is able to control the expenditure on expensive drugs. PAS has also had several challenges, such as high administrative burden, high upfront cost and the need for good data infrastructure.Originality/valueThis study’s unique focus on Italy’s adoption of managed entry agreements (MEA) can provide valuable insights for Malaysia’s pricing mechanisms and access to expensive drugs. Notably, this research addresses a gap in the literature regarding the practical implications of MEA implementation in developing countries. The findings have the potential to improve access to essential medicines for Malaysian citizens while offering a fresh perspective on MEA utilization in emerging markets.

HPR148 The Impact of Patient Access Schemes on the Access of Innovative Oncology Medicines in Asia-Pacific Region: A Targeted Review

HPR148 The Impact of Patient Access Schemes on the Access of Innovative Oncology Medicines in Asia-Pacific Region: A Targeted Review

PD48 Does Unmet Need Influence The Scottish Medicines Consortium Health Technology Assessment Decisions For Rare Disease Conditions?

IntroductionThe Scottish Medicines Consortium (SMC) defines end-of-life medicines as drugs used for treating conditions that usually lead to death within three years using currently available treatments. Orphan medicines are drugs used for the treatment of very rare conditions and ultra-orphan drugs are used for the treatment of extremely rare conditions. The objective of this study is to determine the influence of unmet need on SMC health technology assessment (HTA) decisions for rare disease conditions.MethodsThe reimbursement data between 2004 and 2021 from SMC for rare disease conditions were included. These data were categorized based on the presence of an unmet need, that is, drugs considered under the orphan or ultra-orphan process, or those that fulfilled SMC end-of-life criteria. A chi square test was conducted to determine an association between the presence of an unmet need and the HTA decision. HTAs without a decision were excluded.ResultsA total of 91 HTAs were included in the analysis of which, 57.1 percent (n = 52) were recommended, and 42.9 percent (n = 39) were not recommended. Out of the recommended reviews, 32.7 percent (n = 17) addressed an unmet need and 67.3 percent (n = 35) did not. Recommended drugs had positive clinical evidence and high cost-effectiveness or the submission of a patient access scheme while negative decisions were associated with lower or uncertain cost-effectiveness. The chi square test result showed no association between the presence of an unmet need and the HTA decision (p = 0.315).ConclusionsUnmet need does not influence the SMC HTA decisions for rare disease conditions. Economic elements were the driving factors in the decision-making process.

Using 5 consecutive years of NICE guidance to describe the characteristics and influencing factors on the economic evaluation of orphan oncology drugs.

ObjectiveOrphan oncology drugs used in this article were defined by the type of disease treated by drugs, as drugs used to treat rare diseases with a prevalence of ≤ 500 per million people per year. In this article, our concern was to explore focus on the economic evaluation of the National Institute for Health and Care Excellence (NICE), when orphan oncology drugs were appraised for reimbursement, and provide advice and suggestions to decision-makers.MethodsA retrospective study was used in this study. Thirty guidance were gathered as our subject by NICE from 2016 to 2020, excluded drugs were not identified as orphan by European Medicines Agency (EMA) and orphan drugs were not used for cancer, and orphan oncology drugs were terminated at the time of data collection at NICE. Qualitative analysis, descriptive statistics, and Fisher's exact test were conducted.ResultsOf all guidance, the partitioned survival model was used most to appraise orphan oncology drugs, and every drug had a kind of commercial arrangement such as patient access scheme (PAS), managed access arrangements (MAAs), and commercial access agreement (CAAs). End of life is an important indicator that had been defined by NICE in the methods of technology appraisal in 2013, and drugs that met the criterion would be given a higher threshold of ICER. In addition, we found that potential health benefits were increasingly concerned such as drug delivery.ConclusionIn the setting of uncertain clinical and cost efficacy, orphan oncology drugs are comprehensively evaluated in multiple additional dimensions, which include life-extending benefits, and innovation. NICE uses a combination of special considerations for incomplete data, appropriate economic models, and appropriate health technology assessment (HTA) methods during the assessment process, besides, orphan oncology drugs with insufficiency evidence were recommended Cancer Drugs fund (CDF) to afford for patients, which would obtain more availability and accessibility, based on which, high-quality drugs for treating rare cancers can fall within the scope of affordable healthcare provided by the English medical insurance fund.

HTA59 The Impact of the Patient Access Schemes on Appraisals for the Innovative Medicines in Scotland 2011-2020

The patient access scheme (PAS) has been implemented as a formal part of the pricing and reimbursement environment in the United Kingdom (UK) since 2009, which aims to improve cost-effectiveness and enable patients to gain access to high-cost drugs and treatments. This study was to investigate the impact of the patient access scheme on the appraisals for the innovative medicines in Scottish Medicines Consortium (SMC) between 2011 and 2020.

Stakeholders’ Views on Patient Access Schemes in Malaysia

ObjectivesThe healthcare system aspires to ensure improved access to treatment while working within the existing financial constraints and increasing demands. Patient access schemes (PASs) are initiated to improve access. This study seeks the stakeholders’ views on the PAS in the public healthcare sector in Malaysia. MethodsThis is an exploratory qualitative study using a web-based online survey and semistructured interviews. The participants were recruited by purposive sampling, where the Ministry of Health of Malaysia staff, pharmaceutical organization personnel, and patient advocacy organization personnel with experience in PAS were invited to participate. A total of 42 consenting participants answered the survey, whereas the face-to-face interview had 8 participants. Interviews were thematically analyzed using the qualitative data analysis software NVivo V.12. The Medical Research and Ethics Committee, Ministry of Health of Malaysia, approved the study. ResultsOnly finance-based PAS was reportedly implemented, and it covered drugs for antineoplastic or immunomodulating therapy, alimentary tract and metabolism, sensory organs, and systemic hormonal preparations. A total of 3 major themes were identified. High upfront cost and high budget impact are a major concern leading to the need for PAS. Identifying the treatment needs was a major concern as well. The readiness of the health system to implement PAS will determine whether the PAS can be successfully implemented. Challenges similar to other jurisdictions were observed in Malaysia, concerns on data availability, the responsibility of the stakeholders, and the need for a legal framework. ConclusionMost stakeholders responded positively that the PAS would grow. Trust among stakeholders and a structured access plan would enhance the implementation and ensure its success.

POSA279 The Impact of the COVID-19 Pandemic on the MHRA’s Early Access to Medicines Scheme

To descriptively analyse public assessment reports (PAR) published by the MHRA through their early access to medicines scheme (EAMS) to establish any trends in product characteristics granted a positive scientific opinion (SO), the impact of an SO on subsequent technology assessment (TA) by the National Institute for Health and Care Excellence (NICE), and the impact of the COVID-19 pandemic on the EAMS process. All available PARs and NICE TA documents were obtained from their respective websites, and data relating to drug, indication, justifications for positive SO, and NICE recommendation details extracted. Of the 41 available PARs published between July 2015 and June 2021, oncology and genetic disorders were the most assessed indications with 24 (58.5%), and 9 (22%) related PARs respectively. The most frequent drug class were monoclonal antibodies, featuring in n=19 (46%) PARs. Of those granted an SO, n=28 underwent a NICE TA resulting in n=26 approvals, of which n=4 were recommended for use only within the cancer drugs fund. Of the recommended therapies, 20 (77%) had a commercial agreement such as a simple discount patient access scheme, in place. During the COVID-19 pandemic (April 2020-April 2021), 11 drugs were granted a positive SO versus 5 drugs in the previous 12 months. Monoclonal antibodies were the most common drug class in both time periods, with 3 (27%) and 2 (40%) granted an SO between April 2019-2020, and April 2020-2021 respectively. High rates of NICE TA approval (>90%) were observed in products granted an positive SO through EAMS however, most were subject to a commercial agreement, suggesting that engaging with the EAMS scheme doesn’t lead to preferential pricing. The COVID-19 pandemic appears to have had no impact on the EAMS scheme, with an increase noted in the number of positive SOs granted during the pandemic versus the previous year.

PP452 Impact Of Patient Access Schemes On Health Technology Assessment Agency Guidance For Rare Diseases In England and Scotland

IntroductionPatient access schemes (PAS) are agreements that may enable patients to access drugs or other treatments that may not be cost effective under normal circumstances. The aim of this study was to determine whether the use of PAS by the National Institute for Health and Care Excellence (NICE) and Scottish Medicines Consortium (SMC) for recommended drugs can lead to greater access to medications for rare diseases.MethodsReimbursement data for rare diseases between 2004 and 2021 from health technology assessment (HTA) agencies, namely the SMC (Scotland) and NICE (England), were included. The reviews with positive HTA decisions were considered, while those with negative decisions were excluded. Several observations were made from these data and reported.ResultsAmong the total positive reviews (n = 81), 43 included PAS. The inclusion of PAS in manufacturer submissions was more frequent for NICE than for the SMC (79% and 40% percent, respectively). Most of the drugs with PAS were included in the HTA guidance from both agencies. The positive NICE reviews contingent on PAS consisted of 20 drugs. For the same set of drugs, the SMC recommended 14 with PAS and one without PAS; five drugs were not assessed. Adalimumab was recommended by NICE with a PAS (base-case incremental cost-effectiveness ratio of GBP12,336 [EUR14,256]; GBP13,676 [EUR15,804]) and by the SMC without a PAS (base-case incremental cost-effectiveness ratio of GBP22,519 [EUR26,023]). Hence, without a PAS, the drug was costlier per quality-adjusted life-year for the National Health Service (NHS) Scotland.ConclusionsPAS submissions for rare diseases are more frequent for NICE than for the SMC. With the PAS discounts, the overall cost of the drugs is reduced, resulting in cost effectiveness. The SMC approved some drugs for which NICE required a PAS to improve the economic argument. Hence, the use of PAS for these drugs could lead to potential cost-savings to the NHS Scotland.

Healthcare Costs for Metastatic Castration-Resistant Prostate Cancer Patients Treated with Abiraterone or Enzalutamide

ObjectiveThe aim was to assess the real-world healthcare resource use and direct medical costs for metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide, in whom chemotherapy is not yet indicated (pre-chemotherapy) or who had previously received docetaxel-based chemotherapy (post-chemotherapy), before commencing these medicines.MethodsA retrospective cost analysis of mCRPC patients who commenced abiraterone or enzalutamide between 2012 and 2015 was conducted. Routinely collected datasets from the largest health board in Scotland and the UK, Greater Glasgow and Clyde, were linked. They contained information on patient demographics, diagnosis, outpatient consultations, hospital admissions, treatments (abiraterone and enzalutamide), and supportive medicines. Unit costs were obtained from the Scottish Health Service Costs, Personal Social Services Research Unit, and British National Formulary. Generalised linear model-based regression was used to estimate total mean direct costs, and two-part models were used to estimate separate cost components. All models were adjusted for propensity score and key variables. Sensitivity analysis was conducted to explore the impact of hypothetical patient access scheme discounts.ResultsEstimated total mean direct medical costs of treating mCRPC patients were similar, albeit with wide and overlapping confidence intervals. Across both treatments, patients who received abiraterone or enzalutamide in a pre-chemotherapy setting incurred the highest total mean direct medical costs. However, post-chemotherapy patients were associated with higher outpatient clinic visits, inpatient hospital admissions, and supportive medicines. Regarding relative contribution to the total mean direct medical cost, the treatment costs were the main contributor, followed by inpatient admissions, outpatient clinic visits, and supportive medicines.ConclusionThe total mean direct medical costs were similar for abiraterone and enzalutamide patients. The costs were not driven by the choice of treatment regimen, but treatment setting (pre-chemotherapy or post-chemotherapy indications) and related healthcare resource utilisation. Future studies should focus on economic evaluations, such as cost-effectiveness analyses, using real-world data.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-021-00307-1.

PCN66 A Systematic Literature Review of the Economic Evaluations of Different Treatments in Patients with Chronic Myeloid Leukemia

Management of chronic myeloid leukemia (CML) is associated with extensive economic burden. With improvements in economic level and clinical research, findings and conclusions with regards to this crucial issue are evolving. The objective of this systematic literature review (SLR) was to conduct a comprehensive assessment of economic evaluations in CML. Literature search of English language publications from 2010-2020 was conducted in Embase®, MEDLINE®,NHS EED and relevant conference proceedings to identify economic evaluations of CML that fulfilled pre-defined inclusion criteria. Relevant health technology assessment reports (HTAs) were also included. Data on model specifications, patient characteristics, cost and main outcomes were extracted from included studies. The SLR retrieved 1492 records; 44 fulfilled eligibility criteria. Majority of studies evaluated first-line treatment with tyrosine kinase inhibitors (TKIs). Treatments evaluated included imatinib, nilotinib, ponatinib and bosutinib. Most studies used a Markov model and time horizon varied from ≤5 years to life-time. Most studies and HTAs reported cycle length of 1 month. As first-line therapy, imatinib was cost-effective versus nilotinib and dasatinib in six studies; nilotinib was cost-effective versus imatinib and dasatinib in five studies. As second-line therapy, nilotinib and dasatinib were cost-effective versus high-dose imatinib. Bosutinib and dasatinib were cost-effective under patient access schemes. As third-line treatment, ponatinib yielded discounted quality adjusted life years (QALYs) and improved outcomes versus second-generation TKIs. Imatinib is cost-effective in newly-diagnosed patients with CML as first-line therapy, while nilotinib and dasatinib are cost-effective as second-line agent in patients who are resistant/intolerant to imatinib. Limited evidence exists regarding the economic evaluations in the third-line setting. More studies assessing the long-term efficacy and cost-effectiveness of novel treatments in CML are necessary.

PRO11 Analysis of NICE Assessments for Orphan Treatments and the Role of Managed Access Agreements (MAAs)

There are challenges in the development of orphan treatments, such as small patient numbers limiting clinical trial recruitment and uncertainties related to trial outcomes. This can lead to challenges in the health technology assessment (HTA) of orphan treatments. Treatments may receive recommendation with an MAA for further data collection to address uncertainties while enabling patient access. Pricing agreements such as a patient access scheme (PAS) or commercial access agreement (CAA) may also be required. We reviewed NICE assessments of orphan treatments and the role of MAAs. The EMA website was searched to identify orphan treatments approved between January 2010 and December 2020. The NICE website was searched for assessments of these treatments. Decision outcomes and key drivers were evaluated. Between 1st January 2010 and 17th December 2020, the EMA approved 137 orphan treatments. As of 4th January 2021, 65 had undergone complete NICE HTA with 92% recommended. A greater proportion of orphan treatments for oncology indications (80%) had a completed NICE assessment compared with non-oncology indications (31%). HTAs were in progress for 18 treatments (14 non-oncology) and 42 treatments were not assessed (40 non-oncology). Only 10% of recommended treatments did not have a PAS/CAA. MAAs were required for 19% of recommended non-oncology treatments and 33% of oncology treatments were recommended through the Cancer Drugs Fund (CDF) with an MAA. Uncertainties resulting in the requirement for an MAA included the lack of long-term and/or comparative data, and uncertainties in the size of the clinical benefit and cost-effectiveness estimates. Although NICE recommended most orphan treatments assessed, an MAA (including CDF) was required for 27% of treatments as further data collection was required. Furthermore, a CAA/PAS was important for 90% of recommended treatments. Understanding of the data uncertainties identified by HTA bodies may inform the market access strategy for orphan treatments in development.

Real-world experience with caplacizumab in the management of acute TTP

The cornerstone of life-saving therapy in immune-mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti–von Willebrand factor nanobody trialed in 2 multicenter randomized controlled trials (RCTs) leading to European Union and US Food and Drug Administration approval, has been available in the United Kingdom (UK) through a patient access scheme. Data were collected retrospectively from 2018 to 2020 for 85 patients (4 children) receiving caplacizumab from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial end points and historical outcomes in the precaplacizumab era. Eighty-four of 85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalization (3 days), duration of PEX (7 days), and hospital stay (12 days) were comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalization were favorable compared with historical outcomes (P < .05). Thrombotic thrombocytopenic purpura (TTP) recurred in 5 of 85 patients; all had persistent ADAMTS13 activity < 5 IU/dL. Of 31 adverse events in 26 patients, 17 of 31 (55%) were bleeding episodes, and 5 of 31 (16%) were thrombotic events (2 unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4 of 5 deaths, caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients, including pediatric patients, receiving caplacizumab outside of clinical trials. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.

Abstract PS10-25: Tolerability and efficacy of palbociclib in combination with an aromatase inhibitor (AI) in older women (≥75 years) with ER +ve, HER2-ve metastatic breast cancer. A large ‘real world’ UK multi-centre study

Abstract IntroductionThe management of metastatic oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer has evolved with the introduction of CDK4/6 inhibitors improving disease outcomes when added to an AI in the first line setting. The FDA evaluated toxicity of all CDK4/6 inhibitors in women ≥75 years (n=198), and found increased toxicity and dose modifications [1], however, toxicity profiles differ between the CDK4/6 inhibitors. Palbociclib has been shown to be well tolerated in patients ≥75 years (n=83) [2] and ≥ 70 years (n=92) [3], however, more real-world data is essential to inform prescribing practices in larger datasets.MethodsWe undertook a national multi-centre retrospective study with 15 cancer centres participating. All patients aged ≥75 years with ER+/HER2- advanced breast cancer who had received at least 1 cycle of Palbociclib + AI as part of a patient access scheme or NICE approved by 1st December 2019 were included. Data collected included baseline characteristics, comorbidities, disease characteristics, toxicities with palbociclib, dose modifications, dose delays, discontinuation and response to treatment.ResultsData from 123 patients aged ≥75 years are included in this analysis from 3 UK cancer centres. Median age was 79 years (range 75 - 90). 98% had an ECOG performance status of 0-2. Co-morbidities were scored using Charlston comorbidity index (CCI - higher score signifies more co-morbidities). 102 patients had a CCI of ≤10 and 18 had a CCI &amp;gt;10. The starting dose of palbociclib was 125mg in 115 patients, but 8 (6.5%) patients started at a lower dose, a third of whom had a CCI of &amp;gt;10. The average number of concurrent medications was 4 (range 0-12). Visceral metastases were present in 52% of patients, and 33 patients (26.8%) had bone only metastases. The median number of cycles received was 10 (range 1 -36). 60 (48.8%) patients required one dose reduction, 18 patients required a 2nd dose reduction and 2 patients required a 3rd dose reduction. The most common cause for dose reductions was neutropenia G3-4 (n=31) and fatigue G1-3 (n=12). 75 patients (61%) required a dose delay and 9% of patients discontinued treatment due to toxicity. The rate of all grade neutropenia was 88.6% with only 1 patient (0.8%) developing febrile neutropenia. Other all grade common toxicities were fatigue (62.6%), anaemia (61.8%) and thrombocytopaenia (57.7%). 12 (9.7%) patients required hospital admission due to side effects of treatment. At the time of data analysis, 111 patients had had a radiological response assessment and the best response was stable disease in 57.7%, partial response in 32.4% and complete response in 0.9% (1 patient) with a clinical benefit rate (CR+PR+SD ≥24 weeks) of 83.8%. 10 patients (9%) had disease progression. The median progression free survival is immature, but at the time of this analysis was 13 months (range 1-36 months).ConclusionOur real world data contributes to the existing smaller published datasets in the over 75s to reassure clinicians that palbociclib is an effective and manageable treatment choice in older women. Compared to published data in older patients [2, 3], febrile neutropenia rates from palbociclib were lower. Despite a higher dose reduction and delay rate than published data [3], the clinical benefit rate was not adversely affected and the early PFS signal is reassuring. Citation Format: Salma El Badri, Daniel Hills, Alicja Synowiec, Catherine Harper-Wynne, Maung Moe, Caroline Wilson. Tolerability and efficacy of palbociclib in combination with an aromatase inhibitor (AI) in older women (≥75 years) with ER +ve, HER2-ve metastatic breast cancer. A large ‘real world’ UK multi-centre study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-25.

Cost Effectiveness of Nivolumab in Patients with Advanced, Previously Treated Squamous and Non-squamous Non-small-cell Lung Cancer in England.

ObjectiveThe aim of this study was to investigate the cost effectiveness of nivolumab versus docetaxel in previously treated, advanced non–small-cell lung cancer (NSCLC) in England and assess how conditional reimbursement within the Cancer Drugs Fund (CDF) can be used to ensure timely patient access to effective treatments.MethodsCost-effectiveness models developed for the National Institute for Health and Care Excellence (NICE) TA483 (squamous) and TA484 (non-squamous) technology appraisals were supplemented with updated overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation data collected as part of the CDF data collection agreement. Both models were developed by using a partitioned-survival approach based on PFS and OS predictions from CheckMate 017 and CheckMate 057 to estimate the projected proportion of patients in each health state (progression free, progression, death) throughout the model’s time horizon. The primary outcomes were estimated costs, quality-adjusted life-years (QALYs), and the resulting incremental cost-effectiveness ratio (ICER) expressed as cost/QALY gained.ResultsBase-case ICERs for treating patients with nivolumab versus docetaxel were £35,657/QALY and £38,703/QALY for squamous and non-squamous NSCLC patients, respectively, which are substantially lower than those obtained from what were deemed to be the most appropriate analyses for decision making in the original submissions when run with the same patient access scheme discount: £68,576/QALY and £73,189/QALY gained for squamous and non-squamous NSCLC, respectively.ConclusionsNivolumab versus docetaxel is cost effective for treating locally advanced/metastatic NSCLC after prior chemotherapy in adults, regardless of tumour histology or programmed death-ligand 1 expression status.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-020-00245-4.

PNS141 Deal or No Deal: Twenty Years of Pricing and Access Agreements in Products Assessed by NICE

Since their introduction, access arrangements such as patient access schemes (PAS) have become increasingly common in the UK. The objective of this analysis is to describe trends in uptake of commercial arrangements over time and to compare arrangements that have been implemented for National Institute for Health and Care Excellence (NICE) recommended medicines. A complete list of appraisals undertaken by NICE up to 30 June 2020 was extracted and analysed against published details of commercial arrangements. Products receiving negative recommendations were excluded from analysis. Decisions from multiple technology appraisals assessing >1 product or indication were counted as discrete outcomes. The proportion of appraisals utilising a commercial arrangement was calculated each year using the number of positive recommendations as the denominator. A total of 956 decisions were reviewed, of which 739 (77%) were positive. The proportion of approved products with any commercial arrangement generally increased from 2007 to 2020, with a peak of 91% (50 of 55 recommended products) in 2018. Over the last 5 years, approximately two thirds of positive recommendations were supported by a commercial arrangement of some form. The most common type of arrangement was the simple PAS, accounting for an average of 61% of all commercial arrangements from 2007 onwards. We identified a shift away from use of the complex PAS, towards more frequent use of commercial access agreements (CAA, with or without associated PAS) over the last 5 years (from 14% to 36%). There has been an increasing trend towards confidential agreements (such as simple PAS and CAA) since 2007. In part this is likely to reflect the challenges of achieving UK access in a wider context of global markets and price referencing. With the increasing prevalence of high cost therapies, this is a trend that is set to continue.

PMS19 Validation of a Cost-Effectiveness MODEL in Rheumatoid Arthritis

Rheumatoid arthritis (RA) has multiple previous health technology assessment (HTA) appraisals for advanced therapies. Cost-effectiveness models (CEMs) in RA are complex, especially with the increasing use of patient-level simulation, therefore, replicating them is an important step prior to HTA submission. Validation can ensure that models provide consistent representation of the disease and intervention, and a solid basis for decision-making. The objective of this study was to validate our patient-level CEM against a published model that was developed by academic experts in previous NICE appraisals. A patient-level, discrete-event simulation model was developed to evaluate the cost-effectiveness of new treatments for moderate-to-severe RA, following an approach developed by Stevenson et al.1 which estimated cost and health benefits using long-term, non-linear health-assessment questionnaire disability index trajectories. Our model was validated against a cost-effectiveness analysis of sequences of biologics (abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, tocilizumab) for RA patients in England published by Stevenson et al. in 2017.2 It was possible to replicate the analysis of Stevenson et al.2 2017 in most respects. Stevenson et al.2 reported lifetime incremental QALY gains of 1.5-2.0 and incremental costs of £60,000-£100,000 for the seven drugs. Our model predicted incremental QALYs of 1.54-1.71 and incremental costs of £69,000-£102,000. Estimated ICERs were £48,800-£52,300 and £44,700-£66,700 for Stevenson et al.2 and our model, respectively. The upper ICERs from our model were considered overestimates due to using list prices where patient access scheme prices were confidential. The results of the model validation demonstrate that it is possible to successfully replicate a complex, patient-level model. This illustrates the importance of validation when developing models for HTA to ensure consistency with previous assessments and provide a reliable basis for decision-making. REFERENCES 1. Stevenson M et al. Health Technology Assessment. 2016;20(35):1-610. 2. Stevenson M et al. J Rheumatol. 2017;44(7):973-80.

PCN69 The IMPACT of Patient Access Schemes for Innovative Cancer Therapies in FOUR Asian Countries: A MIXED-Method Review

PCN69 The IMPACT of Patient Access Schemes for Innovative Cancer Therapies in FOUR Asian Countries: A MIXED-Method Review

Selective internal radiation therapies for unresectable early-, intermediate- or advanced-stage hepatocellular carcinoma: systematic review, network meta-analysis and economic evaluation.

Hepatocellular carcinoma is the most common type of primary liver cancer. Treatment choice is dependent on underlying liver dysfunction and cancer stage. Treatment options include conventional transarterial therapies for patients with intermediate-stage disease and systemic therapy [e.g. sorafenib (Nexavar®; Bayer plc, Leverkusen, Germany)] for patients with advanced-stage disease. Selective internal radiation therapies deliver radiation to liver tumours via microspheres that are injected into the hepatic artery. There are three selective internal radiation therapies: TheraSphere™ [BTG Ltd, London, UK (now Boston Scientific, Marlborough, MA, USA)], SIR-Spheres® (Sirtex Medical Ltd, Woburn, MA, USA) and QuiremSpheres® (Quirem Medical BV, Deventer, the Netherlands). To assess the clinical effectiveness and cost-effectiveness of selective internal radiation therapies for treating patients with unresectable early-, intermediate- or advanced-stage hepatocellular carcinoma. A search was undertaken to identify clinical effectiveness literature relating to selective internal radiation therapies and relevant comparators for the treatment of hepatocellular carcinoma. Studies were critically appraised and summarised. The network of evidence was mapped to estimate the relative effectiveness of the different selective internal radiation therapies and comparator treatments. An economic analysis evaluated the cost-effectiveness. Twenty studies were included in the clinical effectiveness review. Two large randomised controlled trials rated as having a low risk of bias [SARAH: Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca AD, Pageaux GP, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled Phase 3 trial. Lancet Oncol 2017;18:1624-36; and SIRveNIB: Chow PKH, Gandhi M, Tan SB, Khin MW, Khasbazar A, Ong J, et al. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol 2018;36:1913-21] found no significant difference in overall survival or progression-free survival between SIR-Spheres and sorafenib (systemic therapy) in an advanced population, despite greater tumour response in the SIR-Spheres arm of both trials. There were some concerns regarding generalisability of the SARAH and SIRveNIB trials to UK practice. All other studies of SIR-Spheres, TheraSphere or QuiremSpheres were either rated as being at a high risk of bias or caused some concerns regarding bias. A network meta-analysis was conducted in adults with unresectable hepatocellular carcinoma who had Child-Pugh class A liver cirrhosis and were ineligible for conventional transarterial therapies. The analysis included the SARAH and SIRveNIB trials as well as a trial comparing lenvatinib (Kisplyx®; Eisai Ltd, Tokyo, Japan) (systemic therapy) with sorafenib. There were no meaningful differences in overall survival between any of the treatments. The base-case economic analysis suggested that TheraSphere may be cost-saving relative to both SIR-Spheres and QuiremSpheres. However, incremental cost differences between TheraSphere and SIR-Spheres were small. In a fully incremental analysis, which included confidential Patient Access Scheme discounts, lenvatinib was the most cost-effective treatment and dominated all selective internal radiation therapies. In pairwise comparisons of sorafenib with each selective internal radiation therapy, sorafenib also dominated all selective internal radiation therapies. The existing evidence cannot provide decision-makers with clear guidance on the comparative effectiveness of treatments in early- and intermediate-stage hepatocellular carcinoma or on the efficacy of TheraSphere or QuiremSpheres. In the advanced-stage hepatocellular carcinoma population, two large randomised trials have shown that SIR-Spheres have similar clinical effectiveness to sorafenib. None of the selective internal radiation therapies was cost-effective, being more costly and less effective than lenvatinib, both at list price and with Patient Access Scheme discounts. Future studies may wish to include early- and intermediate-stage hepatocellular carcinoma patients and the low tumour burden/albumin-bilirubin 1 subgroup of advanced-stage patients. Future high-quality studies evaluating alternative selective internal radiation therapies would be beneficial. This study is registered as PROSPERO CRD42019128383. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 48. See the NIHR Journals Library website for further project information.

HT3 SYSTEMATIC ASSESSMENT OF HTA DECISIONS FOR PERSONALIZED MEDICINES FOR AN ORPHAN DISEASE: ACUTE MYELOID LEUKEMIA (AML)

AML is a rare, aggressive cancer with few available personalized treatments. These high-cost drugs are in the focus of HTA bodies and reimbursement decisions globally. The present research examines HTA assessments for AML drugs. 7 HTA bodies were screened: US (ICER), England (NICE), Scotland (SMC), France (HAS), Canada (pCODR), Australia (PBAC) and Germany (G-BA) for the assessment of 4 drugs (Midostaurin, Gemtuzumab-ozogamicin, Daunorubicin/Cytarabine and Enasidenib) for AML treatment, approved in the last 5 years (since 2015). ICER assessed no drugs for AML. Midostaurin: All HTA bodies made a positive assessment for newly diagnosed FLT3+ AML. NICE and SMC with a restriction for the use [Patient Access Scheme (PAS) / Commercial agreement]. G-BA and HAS assessed the additional benefit with different gradings (Considerable and ASMR IV respectively). In Germany a price reduction of 26% was agreed after G-BA assessment. Daunorubicin/Cytarabine: NICE, SMC, G-BA and HAS made a positive assessment for newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes. In Germany, a price reduction of 18% was agreed after G-BA assessment. Gemtuzumab-ozogamicin: NICE, SMC, G-BA and HAS made a positive assessment for untreated de novo CD33+ (AML) except acute promyelocytic leukemia. NICE and SMC with a restriction for the use (PAS / Commercial agreement). G-BA assessed the added benefit as Not Quantifiable, with a price reduction of 36% after G-BA assessment. HAS rated ASMR V. Enasidenib: pCODR did not recommend reimbursement for relapsed/refractory AML (IDH2 mutation). HTA assessment depicted varying outcomes and decisions due to differences in the applicable underlying laws, and patient population across drugs assessed. Major factors driving decisions were, superior efficacy and acceptable safety for HAS and G-BA; clinical benefit and cost-effectiveness for pCODR, PBAC, NICE and SMC; and end of life criteria across HTAs. Cost-effectiveness for NICE, SMC was by PAS under a commercial agreement with manufacturers.