J. Mark. Access Health Policy, Volume 7, Issue 1 (January 2019) – 30 articles

Background: Non-medical switching (NMS) is defined as switching to a clinically similar but chemically distinct medication for reasons apart from lack of effectiveness, tolerability or adherence. Objective: To update a prior systematic review evaluating the impact of NMS on outcomes. Data sources: An updated search through 10/1/2018 in Medline and Web of Science was performed. Study selection: We included studies evaluating ≥25 patients and measuring the impact of NMS of drugs on ≥1 endpoint. Data extraction: The direction of association between NMS and endpoints was classified as negative, positive or neutral. Data synthesis: Thirty-eight studies contributed 154 endpoints. The direction of association was negative (n = 48; 31.2%) or neutral (n = 91; 59.1%) more often than it was positive (n = 15; 9.7%). Stratified by endpoint type, NMS was associated with a negative impact on clinical, economic, healthcare utilization and medication-taking behavior in 26.9%,41.7%,30.3% and 75.0% of cases; with a positive effect seen in 3.0% (resource utilization) to 14.0% (clinical) of endpoints. Of the 92 endpoints from studies performed by the entity dictating the NMS, 88.0%were neutral or positive; whereas, only 40.3%of endpoints from studies conducted separately from the interested entity were neutral or positive. Conclusions: NMS was commonly associated with negative or neutral endpoints and was seldom associated with positive ones. Full article

Background and objective: We previously built a weighted Depressive Health State Index (DHSI) based on 29 parameters routinely collected in an automated healthcare database (AHDB). We now propose a linear DHSI (L-DHSI) which is easier to use and to replicate across AHDBs. Methods: A historical cohort of patients with ≥1 episode of depression was identified in the Clinical Practice Research Datalink (CPRD). The DHSI was calculated for each treated episode of depression. Validation was performed by using validated definitions of remission (proxy and Patient Health Questionnaire 9 or PHQ-9) and comparing the L-DHSI between subgroups. Reliability was assessed using Cronbach’s alpha. Results: Between 1 January 2006 and 31 December 2012, 309,279 episodes of depression were identified in the CPRD. Remission was observed in 5% of the patients with lowest L-DHSI scores and in 78% of the patients with highest L-DHSI scores. Although less sensitive than the weighted DHSI, the L-DHSI was reliable and relatively easy of use. The L-DHSI was highly correlated to the weighted DHSI (Spearman coefficient 0.790, p < 0.001). Conclusion: The L-DHSI represents a good balance between reliability, usability, and reproducibility. In addition, the linearity of this index allows for an easier interpretation than the original weighted DHSI. Full article

Objectives: We aimed to conduct a modelling study to estimate and predict the economic burden of AD to support the healthcare management of AD in China. Methods: The economic burden of AD was estimated with an evaluation of the prevalence of AD patients and a simulation of annual resource use and cost per AD patient in China using a published model. Percentage of AD patients being treated was assumed to be 5% from 2010 to 2050, with three scenarios testing the value of this parameter of 10%, 20% and 40% throughout 2020 to 2050. Results: The costs of AD were estimated to be from around 91 billion RMB in 2010 to 332 billion in 2050. Most of the current burden was related to private caregivers paid by families. With the percentage of patients being treated changing from 5% to 40%, costs were estimated to double. This was related to more hospitalisations and more use of care facilities, while the burden for families would decrease. Conclusion: A high economic burden related to AD is predicted. The burden would be driven mainly by indirect costs related to the social support of the patients. Investment in improving awareness and care of AD patients is needed and worth it. Full article

Background: Pain management in emergency departments is a complex objective. The absence of a care pathway or a high level of activity complicates diagnostic or analgesic therapeutic strategies. Medical innovation can impact both individual practices and the functioning of an emergency department. Objective: We then wanted to understand how medico-economic studies on pain were carried out in an emergency department. Study design: We reviewed the literature of the last 20 years (between 1998 and 2018). Setting: Of 846 titles screened, a total of 268 abstracts qualified for further screening, and 578 titles were excluded. A total of 14 studies qualified for inclusion in the review. Studies on medicoeconomics in an emergency department are very diverse. None of the methods used are identical; the studies differ in their very nature (prospective, retrospective, cost-effectiveness, etc.) and the determination of emergency room costs differs according to the part of the world studied. In addition, organizational impact is rarely measured, although it is an essential dimension for choosing or not a medical innovation. Full article

Background and Objectives: Utility elicitation studies for schizophrenia generate different utility values for the same health states. We reviewed utility values used in schizophrenia pharmacoeconomic evaluations and evaluated the impact of their selection on the incremental cost-effectiveness ratio (ICER). Methods: A systematic search was performed in Medline and Embase. Health state definitions, associated utility values, elicitation studies, and value selection processes were extracted. Sets of utility values for all schizophrenia health states were used in a cost-effectiveness model to evaluate the ICER. Results: Thirty-five cost-utility analyses (CUAs) referring to 11 utility elicitation studies were included. The most frequent health states were ‘stable’ (28 CUAs, 7 utility elicitation studies, 10 values, value range 0.650–0.919), ‘relapse requiring hospitalisation’ (18, 5, 7, 0.270–0.604), ‘relapse not requiring hospitalisation’ (18, 5, 10, 0.460–0.762), and ‘relapse only’ (10, 5, 6, 0.498–0.700). Seventeen sets of utility values were identified with difference in utility values between relapse and stable ranging from −0.358 to −0.050, resulting in ICERs ranging from −56.2% to +222.6% from average. Conclusion: The use of utility values for schizophrenia health states differs among CUAs and impacts on the ICER. More rigorous and transparent use of utility values and sensitivity analysis with different sets of utility values are suggested for future CUAs. Full article

Incentives for the development of Orphan Medicinal Products (OMP) development have been introduced in both the European Union and the US, yet there has been a relatively little investigation of the success of these policies. An in-depth analysis of the EU market has not been performed, neither in terms of access nor, especially, in terms of the industrial consequences. In order to provide potential measures of success of the OMP program in Europe, we have assessed the levels of OMP designation/approval by EMA and the financial performance of the manufacturing companies during the 5-year period between 2011 and 2015. Of the 1706 products that were granted an OMP designation by EMA during this period, only 138 products (8,1%) reached the market. These products were generally developed by small to medium enterprises (SMEs). In comparison to more mature companies with broader portfolios, these OMP-SMEs are more vulnerable to economic failure due to proportionally higher R&D investment costs, higher sales costs and more limited access to cash at preferential rates. The cost development and their lack of cash availability pout them at financial stake. While this legislation has been effective in creating access to OMP designation, patients are very highly unlikely to benefit from these developments, often because of non-clinical issues: the marketplace is still immature, and companies are still financially vulnerable. Financial and nonfinancial incentives will be critical to allow OMP products to reach the market, so that a fully functioning and competitive market can be established. Full article

Background: The Trump administration’s ‘American Patients First’ blueprint proposes to reduce drug prices in the USA by increasing drug prices abroad, ex USA. The possibility of the Trump administration to raise drug prices ex USA through legal action via the WTO and bilateral negotiations with foreign trade partners was reviewed. Methods: A literature review was conducted through PUBMED, EMBASE, Media and grey literature to consolidate publications of the Trump administrations’ policies and strategies towards foreign countries and drug prices. Results: The Trump administration has withdrawn from and halted major multilateral agreements including the TPP, Paris Agreement, TTIP, UNESCO, NAFTA (now USMCA), and NATO. The Trump administration has been successful in bilateral negotiations for pharmaceuticals’ pricing, as seen with Japan, South Korea, Germany, and Mexico and Canada. Conclusion: The objective of raising prices abroad is attainable. Action through the WTO is unlikely, due to its nondiscriminatory principle. Bilateral trade negotiation have proven more promising. In this bilateral framework, financial security and military protection are strong assets for the USA to levy higher drug prices abroad. Although raising drug prices ex USA is possible, further questions as to whether this will directly translate into lower drug prices for American patients are raised. Full article

Introduction: The appraisal of medicines is often a complex and iterative process. We compared the health technology assessment (HTA) process in England and France taking as a case study the example of ixazomib for multiple myeloma. Methods: We undertook an analysis of eight relevant published documents identifed from the websites of the French and English HTA bodies (HAS and NICE, respectively). We analyse patients’ availability of ixazomib resulting in the different stages of the appraisal process. Results: We identified differences in the assessment, one of these being the use of an appraisal scope in England allowing the differentiation of populations and comparators according to previously approved treatments. Ixazomib became available earlier in France as part of an early access programme, but the availability was soon discontinued for newly eligible patients following an HAS determination that Ixazomib yielded no additional benefit. This opinion resulted in long pricing discussions. In England, despite the absence of an early access programme and following a process that included cost-effectiveness evaluation combined with pricing discussions, the medicine was fairly rapidly recommended for use. Conclusions: Differences in the HTA process may result in appreciable differences in time from marketing authorisation to health service adoption of newly licensed drugs. Full article

Background: Outcomes-based reimbursement (OBR) can reduce decision uncertainty and accelerate patient access to cell and gene therapies, however, OBR is rarely applied in practice in England. Oncology is the therapy area with the most cell and gene therapies in late-stage development, and the Systemic Anti-Cancer Therapy (SACT) dataset and The European Society for Blood and Marrow Transplantation (EBMT) registry are two data collection infrastructures that could potentially act as conduits for implementing OBR in cancer in England. Objective: To perform a gap analysis to identify the key requirements for upgrading the SACT and EBMT databases for the purposes of enabling OBR, and a top-level estimation of how much this upgrade may cost, using either a manual (staff-heavy) workaround or part automation (technology-heavy) approach. Methodology: The analysis of current data capture and gaps is informed by secondary research, while the assumptions and data used to derive the top-level cost estimates were informed by consensus-based primary research with experts in healthcare information technology (IT) systems integration and platform development, as well as experts of SACT and EBMT. Findings: In its current form, the SACT dataset in isolation is largely unfit for enabling OBR in oncology, whether through clinical, economic or humanistic outcomes. The EBMT registry has a greater potential; however, this relates to key clinical outcomes only, not economic or humanistic outcomes. Part automation requires a higher upfront investment than the manual workaround (~£1.8 million vs. ~£400k); however, lower annual costs (~£200 vs. ~£260k–£850k) mean that part automation becomes a more cost-effective approach over time. Conclusions: An appropriately automated and scalable data collection infrastructure should be implemented, with the ability to integrate clinical, economic and humanistic outcomes with healthcare cost data and payment systems, to enable OBR not only in cancer but also in other therapy areas. Full article

Objective: To update the health economic evaluation of pirfenidone in the treatment of idiopathic pulmonary fibrosis (IPF) compared to all available alternatives strategies (Best supportive care—BSC and nintedanib), based on a cost-utility model previously validated by the CEESP’s (French Committee for Economic Evaluation) in 2014. Methods: A standard Markov cohort model, adapted to French methodology guidelines, was used to simulate the therapeutic management and the course of IPF patients (including potential adverse events) using the collective perspective. Cost-effectiveness was evaluated regarding life years (LY); quality-adjusted life-years (QALY); average cumulative costs; the incremental cost-effectiveness ratio (ICER) expressed in cost per QALY gained. Data were retrieved from trials, meta-analysis, literature, health insurance and hospitalisation databases, and national tariffs. Results: Over 15 years, total costs accumulated in the pirfenidone strategy were estimated at €99,477 per patient, €104,610 in nintedanib, and €14,177 in Best Supportive Care (BSC). The total number of QALYs accumulated equalled 5.20 (6.91 LYs), 4.52 (5.98 LYs), and 3.79 (4.98 LYs), respectively. Pirfenidone was estimated to be dominant over nintedanib with incremental costs of −€5,133 and 0.67 more QALYs accumulated. Incremental cost versus BSC was €85,300 and 1,404 QALY gained. The cost-effectiveness ratio was estimated at 60,738€/QALY when compared to BSC. Conclusion: Pirfenidone is likely to be a cost–effective strategy compared to BSC and seems more efficient and less costly compared to nintedanib for the treatment of patients with IPF in France. Full article

The importance of understanding the impact of disease and treatment on children’s Health-Related Quality of Life (HRQoL) has given rise to an increasing use of child self-report and observer or proxy instruments. In this article, we review the status quo and challenges of HRQoL measurement specific to children under five. A number of HRQoL questionnaires exist for use with children and/or proxies, and both guidelines and reviews have been published on paediatric HRQoL. However, none address the challenges of measurement for children under five, for whom proxy measures should be used. In reality, there is significant heterogeneity in the cut-off age for self-report questionnaires. Recommendations are that proxies should be used for observable concepts, but not for concepts that require interpretation. Some research has been undertaken on dimensions/concepts in paediatric HRQoL questionnaires. However, no HRQoL models have been developed specifically for children, and heterogeneity in questionnaire dimensions underlines that there is no clear grasp of what HRQoL means in paediatric populations. There is a need to carry out research in order to develop theoretical models of HRQoL that are specific to children at different developmental stages, in order to evaluate and support new and existing measures for paediatric HRQoL and their use in clinical practice as well as clinical trials. Full article

Background: Actinic keratosis (AK) is characterized by the occurrence of thick and scaly skin areas caused by damage from ultraviolet radiation. The management of AK aims to reduce lesions and prevent their recurrence by regular monitoring. French guidelines, last updated in 2009, reflect European guidelines for the management of face and scalp AK. However, they do not address all current, available options. Objective: To assess the management of face and scalp AK in French clinical practice. Methods: A two-part online questionnaire comprising a survey among French dermatologists and an analysis of patient medical records was performed to describe AK patients treated with topical therapy, patients’ profiles, and characteristics of the affected lesion areas. Results: Decisions for topical treatments for face and scalp AK made by dermatologists were mainly driven by the lesion size. According to the last 10 patients they have seen, dermatologists were prescribing physical therapy in 53% of the cases, a combination of topical and physical therapy in 27% and topical only in 20%. Patient records revealed the average surface area targeted for treatment was 139 ± 113 cm². Conclusions: Discrepancies between the guidelines on the treatment of face and scalp AK and clinical practice exist. Further research may help to standardize the treatment. Full article

Background: Spinal muscular atrophy type 1 (SMA1) is a devastating genetic disease for which gene-replacement therapy may bring substantial survival and quality of life benefits. Objective: This study investigated the cost-effectiveness of onasemnogene abeparvovec (AVXS-101) gene-replacement therapy for SMA1. Study design: A Markov model was used to estimate the incremental cost-effectiveness ratio (ICER), expressed as cost/quality-adjusted life year ($/QALY), of AVXS-101 versus nusinersen over a lifetime. Survival, healthcare costs and QALYs were estimated using natural history data for SMA patients who achieved motor milestones (sitting/walking). Health utility weights were obtained from the CHERISH trial. Setting: USA; commercial payer perspective. Participants: SMA1 infants. Interventions: AVXS-101 was compared to nusinersen. Main outcome measure: The primary outcome was the ICER. Results: Expected survival (undiscounted) over a lifetime predicted by the model was 37.20 life years for AVXS-101 and 9.68 for nusinersen (discounted QALYs, 15.65 and 5.29, respectively). Using a potential AVXS-101 price range ($2.5-5.0M/treatment), the average lifetime cost/patient was $4.2–6.6M for AVXS-101 and $6.3M for nusinersen. The ICER range was (-$203,072) to $31,379 per QALY gained for AVXS-101 versus nusinersen, indicating that AVXS-101 was cost-effective with prices of ≤$5M. Conclusion: Single-dose AVXS-101 was cost-effective compared to chronic nusinersen for SMA1 patients. Full article

Background: The umbrella term ATMPs (Advanced Therapy Medicinal Products) comprises cell therapies, gene therapeutics and tissue engineered products. After implementation of the Regulation 1394/2007, only a couple of products have obtained a centralized European marketing authorisation. Objectives: The aim of the presented study is to give an overview on ATMPs available within the European Union either via centralized marketing authorisation or via national Hospital exemption. Additionally, a forecast on innovative ATMPs in the process of EMA approval as well as in phase III and IV clinical trial is provided. Methods: Systematic literature search including ‘grey literature’ and database reviews as well as manual search following pre-defined search terms. Results: 8 ATMPs are currently available via centralized marketing authorisation. 6 new product launches are expected before 2020. At least 32 additional ATMPs are available in individual European Union member states via Hospital exemption. Another 31 potential ATMP candidates could be identified in industry-driven phase III research projects. Conclusion: Advanced therapeutic medicinal therapies are still in their early days, but constantly evolving. By 2020, innovative therapies targeting retinal dystrophy, ß-thalassemia, scleroderma, sickle-cell anaemia, adrenoleukodystrophy and leukaemia shall be available on the market. Full article

Background: The relative efficacy and safety can vary among drugs over time. Sumatriptan, a first choice drug for acute migraine, can illustrate this phenomenon. Objective: To assess the evolution of the relative efficacy and tolerability of oral sumatriptan against placebo between its approval in 1991 and 2006. Methods: A systematic literature review of randomized controlled trials (RCTs) of adults suffering from acute migraine episodes was performed using Medline. Meta-analyses estimated odds ratios of the occurrence of pain-free at 2 hours and of any adverse event. Results: Out of the 67 RCTs identi.fied, pain-free at 2 hours and adverse events were reported in 25 and 28 studies, respectively. For pain-free, the relative effect of sumatriptan increases considerably over time, despite an increase in the absolute placebo effect. The odds ratio (95% CI) equaled 3.13 (1.67–5.86) around approval (1991–1994) and increased up to 4.14 (3.67–4.67) on the following decade. No specific variation was observed in the relative tolerability effect of sumatriptan over placebo over time. Conclusions: The relative effect of sumatriptan evolved substantially over time. This phenomenon may impact the results of network meta-analysis and indirect comparisons performed to evaluate the potential of a new drug, compared to widely prescribed older drugs. Full article

Background and objectives: Governments in Asia Pacific (APAC) are increasingly using pharmaceutical pricing strategies to contain rising healthcare costs. The objective of this narrative review is to discuss formal pricing strategies for reimbursed prescription medication in APAC, supported by relevant examples of implementation differences across countries. In the discussion section, we examine key advantages and disadvantages of each strategy. Methods: A narrative review of the peer-reviewed and grey literature was undertaken to retrieve information, including strategy definitions, practising countries, country-specific implementation considerations, and merits and demerits of each strategy. Results: Seven strategies (Internal Reference Pricing, External Reference Pricing, Special Pricing Agreements, Pharmacoeconomic Evaluation, Cost plus pricing, Price Maintenance Premium, and Tendering and negotiations) were identified as most commonly practised in APAC through the review process. Most countries use multiple strategies that differ in how they are implemented. Conclusion: APAC countries use multiple strategies simultaneously with varying implementation methods, including different formulae and sub-types of medication that a strategy applies to, whether the strategy is a mandate or guideline, and the extent of negotiations and transparency. Strategies are instituted partly with the aim of cost containment, and may also promote price stability, innovation, and increased access in the short and longer term. Abbreviations: APAC—Asia Pacific; WHO—World Health Organisation; IRP—Internal Reference Pricing; ERP—External Reference Pricing; SPA—Special Pricing Agreement; MES—Managed Entry Scheme; PVA—Price-Volume Agreement; RSA—Risk Sharing Agreement; NHIS—National Health Insurance System; PE—Pharmacoeconomic Evaluation; CEA—Cost-Effectiveness Analysis; QALY—Quality-adjusted Life Year; BIA—Budget Impact Analysis; PMP—Price Maintenance Premium; R&D—Research & Development. Full article

Objective: Doctor-shopping has significant consequences for patients and payers and can indicate misuse of drugs, polypharmacy, less continuity of care, and increased medical expenses. This study reviewed the literature describing doctor-shoppers in the adult population. Methods: A systematic literature review was performed in PubMed and supplemented by a Google search of grey literature. Overall, 2885 records were identified; 43 papers served as a source of definition of a doctor-shopper, disease, treatment, patient characteristics, patient special needs, country. Results: Definitions of doctor-shopping were heterogeneous. Overall, 40% of studies examined the use of opioids, antidepressants, or psychoactive drugs, while the others focused on chronic or frequent diseases. Most studies were conducted in countries with easy access to healthcare resources (USA, France, Taiwan, Hong Kong). The prevalence of doctor-shopping ranged from 0.5% among opioid users in the USA to 25% of patients registered at general practices in Japan. Comorbidities, active substance abuse, greater distance from healthcare facility, younger age, longer disease and poor patient satisfaction increased doctor-shopping. Conclusions: Knowing the characteristics of doctor-shoppers may help identify such patients and reduce the associated waste of medical resources, but concerns about the misuse of drugs or healthcare resources should not prevent proper disease management. Full article

The debate on drug prices has reached new heights with the controversy around the role of prices in promoting innovation. Critics claim that prices of innovative drugs are excessive and argue that lowering prices will not harm the flourishing innovation. On the opposite end, the pharmaceutical industry insists that restrictive pricing policies will have a detrimental impact on their ability to generate innovation. Amid these two divergent positions, this manuscript presents a conceptual framework to better understand the role played by drug prices to influence the ability of pharmaceutical firms to raise money in capital markets and hence finance pharmaceutical innovation. We argue that deviations from established value-based pricing principles, by either firms or payers, will distort access by firms to capital and lead to an undesirable level of innovation in the long term. We hope that this framework helps policy-makers anticipate the impact of their proposals, and ultimately guide policies towards setting optimal drug prices as a means to maximise social welfare. Full article

Background: Drug prices in the United States are the highest in the world, restricting access to the domestic lower income population. President Trump campaigned heavily on promises to reduce drug prices. Methods: A literature review was conducted through PUBMED, EMBASE, Media and grey literature to consolidate and analyze publications addressing President Trump’s promises from the campaign trail as well as the shortcomings and achievements of the Trump administration. Results: Major promises ranged from repealing and replacing Obamacare, expanding coverage, allowing cross-state insurance purchasing, and reducing drug prices. Main accomplishments of the Trump administration have been two executive orders (13765 and 13813), the proposition of the American Health Care Act, and the passing of the Tax Cuts and Jobs Act of 2017. The American Patients First blueprint further revealed the administration’s strategies for lowering drug prices. The administration has also engaged in unconventional strategies, such as via bilateral leverage directly with trade partners. Conclusion: The Trump administration has not yet been able to fulfill the major campaign promises, primarily the ones requiring legislative and/or administrative action. If enough legislative action is accomplished to implement the Trump administration’s promises, the effects on the pharmaceutical industry could be direct, yet minimal, unless Medicare can directly negotiate with manufacturers. Full article

Background & Objective: Poor people, in general, get poor quality of health services. The situation is very much worsening for the poor who live in the remote areas in the coastal belt of Bangladesh as health care facilities and services are often less complete, farther away, and therefore most costly to reach than in urban hospitals and physician. Ensure of better health service for the poor, it is essential to examine the effectiveness of Universal Health Coverage (UHC). This study sets its objectives to evaluate the health service for the poor in the coastal area of Bangladesh and develop an approach of management strategy. Methods: This study followed a two-stage cluster sampling technique and carried out a household survey through the open-ended questionnaire. In addition, the study applied the logistic regression model to generate empirically supported assessments. Results: Result from the disparity rate ratio (DRR) revealed that there is a big health care disparity of different income groups like poor and rich. Furthermore, results from the model demonstrated that Medicaid, Medicare, Social Health Insurance, Telemedicine and Capitation under the provision Universal Health Coverage (UHC) are statistically significant compared to reduce the health care disparity. Conclusion: UHC becomes a critical issue for improved and quality health care system for all the groups especially, the poor in coastal Bangladesh. This study showed that Medicaid, Medicare and Social Health Insurance and Capitation perform well to provide better health care facilities for all. Full article

Introduction: Numerous real-world studies have compared non-vitamin K antagonist oral anticoagulants (NOACs) with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF). A meta-analysis was performed to synthesize the available evidence. Methods: Systematic searches were performed through 12/2016 to identify non-randomized NVAF studies comparing NOACs with VKAs, and reporting effectiveness, safety, or persistence. Results: Of 562 citations identified, 49, 79, and 18 compared rivaroxaban, dabigatran, and apixaban, respectively, with VKAs and were included. Compared with VKAs, rivaroxaban was associated with a reduced risk of ischemic stroke (IS) (hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.75–0.93), intracranial haemorrhage (ICH) (HR = 0.69, 95% CI = 0.52–0.90), and non-persistence (HR = 0.62, 95% CI = 0.60–0.65). Dabigatran was associated with a significantly lower risk of IS (HR = 0.80, 95% CI = 0.65–0.98) and ICH (HR = 0.45, 95% CI = 0.36–0.58), but not for non-persistence (HR = 0.91, 95% CI = 0.53–1.55), compared with VKAs. Apixaban was associated with a lower risk of ICH than VKAs (HR = 0.41, 95% CI = 0.28–0.60), but was not different to VKAs in terms of IS (HR = 1.01, 95% CI = 0.87–1.17) or non-persistence (HR = 1.08, 95% CI = 0.81–1.45). Conclusion: NOACs appear to be at least as effective and safe as VKAs for stroke prevention in patients with NVAF. Full article

Background: Cell and gene therapies are associated with uncertainty around their value claims at launch due to limitations of supporting clinical data; furthermore, their high costs present affordability issues for payers. Outcomes-based reimbursement can reduce payer decision uncertainty and improve patient access, however, requires data collection infrastructure and practice to be operational. Objective: To identify indications most likely to see launch of cell or gene therapies in the UK over the next five years, and to perform a qualitative assessment of how conducive the existing data collection infrastructure and clinical practice is in facilitating adoption of outcomes-based reimbursement in the corresponding indications. Methodology: Through secondary research, we identified target indications for cell or gene therapies at a mature clinical development stage (Phase III) with EU and/or US trial sites, and assessed availability of relevant data collection infrastructures in the UK. Secondary research findings were validated through primary research (expert interviews). Key parameters considered for the suitability of existing data collection infrastructure in supporting outcomes-based reimbursement include time horizon of data collection, whether data entry is mandatory and whether infrastructure is product or therapy area-specific. Findings: We identified 58 cell or gene therapies, spanning 47 indications, 20 of which are in oncology. Oncology seems well placed for outcomes data collection (through the mandatory Systemic Anti-Cancer Treatment database), however data entry compliance can be an issue (due to resource limitations), and upgrading will be needed for the purpose of outcomes-based reimbursement. Among non-oncology indications ~two-thirds have data collection infrastructures in place, but only three come close to the requirements for outcomes-based reimbursement. Conclusions: Existing data collection infrastructure in indications with potential cell or gene therapies launches in the next five years in the UK is overall not sufficient to facilitate outcomes-based reimbursement. Full article

Background: Little is known about the costs associated with vitamin K antagonist (VKA) treatment in patients with non-valvular atrial fibrillation (NVAF) in France. Objectives: To evaluate monthly per-patient costs attributable to VKA treatment in NVAF patients from a French societal perspective. Study design: Retrospective data were obtained from 7 international normalised ratio (INR) monitoring centres in France. Patients older than 18 years of age with NVAF treated with VKA were recruited. Additional patient-level data assessing resource use corresponding with VKA treatment were collected via self-completed questionnaires. Unit costs applicable to 2015 were multiplied by resource use and summed to generate VKA treatment costs. Results: 363 patients were included; 53% were men. The majority of patients received fluindione (72%). The number of INR tests per patient per month was 1.69 (95% CI, 1.59–1.80). The monthly patient cost was €39.72 (€36.23–43.21) from the French societal perspective. Direct medical costs comprised 76% of overall costs, with drug costs representing 7.4% (€2.4); direct non-medical and indirect costs comprised 10% and 14% respectively. Conclusions: Costs associated with VKA treatment in NVAF cannot be estimated only with drug costs. When direct and indirect attributable costs associated with VKA treatment are considered, the VKA treatment costs are more substantial. Full article

Background: Corticosteroids may be temporarily effective for ulcerative colitis (UC), but long-term use increases the risk of adverse drug reactions. Objective: The goal of the study was to examine steroid use in remission induction therapy after diagnosis of UC. Study Design: A retrospective observational study using the Japan Medical Data Center (JMDC) Claims Database from January 2008 to December 2014. Setting: Clinics, university hospitals, and national/public hospitals. Intervention: Initiation of steroids after diagnosis of UC. Main outcome measures: Start time and annual rate of steroid use, and use during the first 6 months of remission induction therapy. Results: The subjects were 399 patients were newly diagnosed with UC in the study period. The rate of steroid use after diagnosis was 58.4% in 2009, and showed a significant decreasing trend yearly after 2010 (p ≤ 0.0001). Regarding the start time, 52.2% of patients began steroids within 60 days after diagnosis of UC. At 6 months after initiation, 23.7% continued to use steroids and 73.9% of these patients used high-dose steroids. Conclusion: In treatment of UC after diagnosis, many patients continue to use steroids for >6 months after initiation. Reduced use of steroids based on clinical practice guidelines for UC should be promoted. Full article

Reimbursement decisions on new oncology drugs are now often made while uncertainty remains about a drug's risk–benefit profile. One consequence of this is a delay in patient access to valuable new medicines. We share our perspectives on strategies to mitigate sources of uncertainty in the health technology assessment process. These include flexible approaches for evaluating the additional benefit, such as better use of surrogate endpoints and health-related quality of life data, and renewed research efforts to define the optimal target population and generate real-world evidence post-authorisation. Full article

Background and objective: A Depressive Health State Index (DHSI) based on 29 parameters routinely collected in an automated healthcare database (AHDB) was developed to evaluate the health state of depressive patients, and its evolution. The study objective was to describe and validate this DHSI. Methods: A historical cohort of patients with at least one episode of depression was identified in the Clinical Practice Research Datalink (CPRD). The DHSI was calculated for each episode of depression. Validation was performed by comparing the DHSI between subgroups and using validated definitions of remission (proxy and PHQ-9). Robustness was studied by assessing the impact of modifying parameters of the DHSI. Results: 309,279 episodes of depression were identified in the CPRD between 1 January 2006 and 31 December 2012. Remission was observed in 8% of the patients showing the lower DHSI scores and in 88% of the patients showing the higher DHSI scores. The DHSI was robust to a modification of the most frequent variables and to the removal of rare parameters. Conclusion: The DHSI is specific to depression severity (with remission rates in accordance with the expected variations of the DHSI) and robust. It represents a promising tool for the analysis of AHDBs. Full article

The economic evaluation which supports Health Technology Assessment (HTA) should inform policy makers of the value to society conferred by a given allocation of resources. However, neither the theory nor practise of economic evaluation satisfactorily reflect social values. Both are primarily concerned with efficiency, commonly conceptualised as the maximisation of utility or quality adjusted life years (QALYs). The focus is upon the service and the benefits obtained from it. This has resulted in an evaluation methodology which discriminates against groups and treatments which the population would like to prioritise. This includes high cost treatments for patients with rare diseases. In contrast with prevailing methods, there is increasing evidence that the public would prefer a fairness-focused framework in which the service was removed from centre stage and replaced by the patient. However methods for achieving fairness are ad hoc and under-developed. The article initially reviews the theory of economic evaluation and argues that its focus upon individual utility and efficiency as defined by the theory omits potentially important social values. Some empirical evidence relating to population values is presented and four studies by the first author are reviewed. These indicate that when people adopt the social perspective of a citizen they have a preference for sharing the health budget in a way which does not exclude patients who require services that are not cost effective, such as orphan medicinal products (OMP’s) and treatments for patients with ultra-rare diseases (URD’s). Full article

Non-profit drug research and development (R&D) has the potential to deliver innovative treatments at affordable prices. Using the case study methodology, we discuss some ethical and economic issues, including the possible impact of non-profit companies on innovation efforts from for-profit firms. Like other non-profits, Genethon is willing to adopt an ethical attitude toward their donors by pricing their products affordably. It remains to be seen if the approach to internalize the marketing authorization, manufacturing and distribution activities prove to be efficient and sustainable. Also, the firm faces an ethical dilemma because lower prices of innovative drugs can dry the for-profit R&D in the area and prevent patient access to future innovations. Full article