A systematic review on the appropriate discounting rates for the economic evaluation of gene therapies: whether a specific approach is justified to tackle the challenges?

OBJECTIVES: Discounting the cost and effect for health intervention is a controversial topic over the last two decades. In particular, the cost-effectiveness of gene therapies is especially sensitive to the discount rate because of the substantial delay between the upfront cost incurred and long-lasing clinical benefits received. This study aims to investigate the influence of employing alternative discount rates on the incremental cost-effectiveness ratio (ICER) of gene therapies. METHODS: A systematic review was conducted to include health economic evaluations of gene therapies that were published until April 2023. RESULTS: Sensitivity or scenario analysis indicated that discount rate represented one of the most influential factors for the ICERs of gene therapies. Discount rate for cost and benefit was positively correlated with the cost-effectiveness of gene therapies, that is, a lower discount rate significantly improves the ICERs. The alternative discount rate employed in some cases could be powerful to alter the conclusion on whether gene therapies are cost-effective and acceptable for reimbursement. CONCLUSIONS: Although discount rate will have substantial influence on the ICERs of gene therapies, there lacks solid evidence to justify a different discounting rule for gene therapies. However, it is proposed that the discount rate in the reference case should be updated to reflect the real-time preference, which in turn will affect the ICERs and reimbursement of gene therapies more profoundly than conventional therapies.

Implicit factors influencing the HTA deliberative processes in 5 European countries: results from a mixed-methods research.

Background: Health technology assessment (HTA) bodies across Europe rely on explicit factors for decision making. However, additional undefined factors play a role. This mixed-methods research aimed to identify the implicit factors involved in HTA deliberative processes in five European countries, and to analyze their impact on decision making. Methods: Between February and May 2021, semi-structured interviews (n = 20) were conducted with HTA experts of three different profiles (chair, advisor, and committee member) from France, Germany, Italy, Spain, and the United Kingdom. The degree of influence of a set of implicit factors and attributes that play a role in the HTA deliberative process, as previously identified in a systematic literature review, was scored by the experts. Experts were also asked to make recommendations on ways of improving the deliberative process. A qualitative analysis and descriptive statistics of quantitative variables are reported. Results: Most (18/20) experts concurred that implicit factors play a role in the HTA deliberative process. Recommendations for improving the process fell into three categories: transparency, methodology improvement, and stakeholder involvement. The results suggest a need for 1) increased external involvement HTA and 2) development of a methodology to mitigate the influence of implicit factors in the deliberative process. This could be achieved by updating the current frameworks to acknowledge these implicit factors and by developing methods to address them.

Supporting health education policies: translation, cross-cultural adaptation and validation of a health literacy instrument, in French.

Background: Oral health is a fundamental human right and is inseparable and indivisible from overall health and well-being. Oral Health Literacy (OHL) has been proved to be fundamental to promoting oral health and reducing oral health inequalities. To our knowledge, no OHL instrument to evaluate OHL level is currently validated in French language despite the fact it is the fifth most widely spoken languages on the planet. The Oral health literacy Instrument (OHLI) appears to be the most interesting OHL instrument to adapt into French because it is already available in English, Spanish, Russian, Malaysian, and it contains both reading comprehension and numeracy sections. Its psychometric properties have been rated as adequate. Objective: The aim of this study was to translate and adapt cross-culturally the OHLI into French, to evaluate its psychometric properties and to compare its results to oral health knowledge. Method: This study followed and applied well-established processes of translation, cross-cultural adaptation and validation, based on the recommendations of the World Health Organization guidelines and on the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) study design checklist for patient-reported outcomes. Two psychometric assessments were planned, the comparison of OHLI-F scores according to education level and frequency of dental visits, and the test-retest reliability of the OHLI-F. Results: A total of 284 participants answered the OHLI-F. The OHLI-F scores were significantly different between participants with different levels of education and frequency of dental visits (p < 0.001). Participants with an education level lower than the baccalaureate, and those who never visit the dentist or only in case of pain, had significantly lower OHLI-F scores. Internal consistency was excellent (Cronbach's alpha = 0.881-0.914). Test-retest reliability was very high (intraclass correlation = 0.985 to 0.996). Conclusion: The OHLI-F has demonstrated adequate psychometric properties and can therefore be used to measure oral health literacy in French-speaking populations.

Mental Health Mobile Apps in the French App Store: Assessment Study of Functionality and Quality.

BACKGROUND: Approximately 800 million people, representing 11% of the world's population, are affected by mental health problems. The COVID-19 pandemic exacerbated problems and triggered a decline in well-being, with drastic increase in the incidence of conditions such as anxiety, depression, and stress. Approximately 20,000 mental health apps are listed in mobile app stores. However, no significant evaluation of mental health apps in French, spoken by approximately 300 million people, has been identified in the literature yet. OBJECTIVE: This study aims to review the mental health mobile apps currently available on the French Apple App Store and Google Play Store and to evaluate their quality using Mobile App Rating Scale-French (MARS-F). METHODS: Screening of mental health apps was conducted from June 10, 2022, to June 17, 2022, on the French Apple App Store and Google Play Store. A shortlist of 12 apps was identified using the criteria of selection and assessed using MARS-F by 9 mental health professionals. Intraclass correlation was used to evaluate interrater agreement. Mean (SD) scores and their distributions for each section and item were calculated. RESULTS: The highest scores for MARS-F quality were obtained by Soutien psy avec Mon Sherpa (mean 3.85, SD 0.48), Evoluno (mean 3.54, SD 0.72), and Teale (mean 3.53, SD 0.87). Mean engagement scores (section A) ranged from 2.33 (SD 0.69) for Reflexe reussite to 3.80 (SD 0.61) for Soutien psy avec Mon Sherpa. Mean aesthetics scores (section C) ranged from 2.52 (SD 0.62) for Mental Booster to 3.89 (SD 0.69) for Soutien psy avec Mon Sherpa. Mean information scores (section D) ranged from 2.00 (SD 0.75) for Mental Booster to 3.46 (SD 0.77) for Soutien psy avec Mon Sherpa. Mean Mobile App Rating Scale subjective quality (section E) score varied from 1.22 (SD 0.26) for VOS - journal de l'humeur to 2.69 (SD 0.84) for Soutien psy avec Mon Sherpa. Mean app specificity (section F) score varied from 1.56 (SD 0.97) for Mental Booster to 3.31 (SD 1.22) for Evoluno. For all the mental health apps studied, except Soutien psy avec Mon Sherpa (11/12, 92%), the subjective quality score was always lower than the app specificity score, which was always lower than the MARS-F quality score, and that was lower than the rating score from the iPhone Operating System or Android app stores. CONCLUSIONS: Mental health professionals assessed that, despite the lack of scientific evidence, the mental health mobile apps available on the French Apple App Store and Google Play Store were of good quality. However, they are reluctant to use them in their professional practice. Additional investigations are needed to assess their compliance with recommendations and their long-term impact on users.

Multiple criteria decision analysis for therapeutic innovations in a hemophilia care center: A pilot study of the organizational impact of innovation in hemophilia care management.

BACKGROUND: Several innovative drugs liable to lead to changes in healthcare organization are or soon will be available for the management of hemophilia. Analyzing their implementation can shed further light on healthcare decision-making, to anticipate changes and risk of breakdown in the patient's care pathway. METHODS: Multiple criteria decision analysis (MCDA), based on ISPOR recommendations, was used to assess the organizational impact of innovation in hemophilia care management. The MCDA process designed for this specific context involved ten French experts in hemophilia care management (physicians, nurses, pharmacist, physiotherapist and psychologist) in the hemophilia care center of Chambéry, in the Rhône-Alpes Region of France. This pilot study involved seven steps: (i) defining the decision problem; (ii) selecting and structuring criteria; (iii) assessing the relative weight of each criterion with software-assisted simulation based on pairwise comparisons of different organizational change scenarios; (iv) measuring the performance of the selected innovations; (v) scoring alternatives; (vi) calculating aggregate scores; (vii) discussion. The endpoint was to determine the expected overall organizational impact on a 0-100 scale. RESULTS: Seven organizational criteria were selected. "Acceptability for patient/caregiver/association" was the most heavily weighted. Factor VIII by subcutaneous route obtained the highest aggregate score: i.e., low impact on care organization (88.8 out of 100). The innovation with strongest organizational impact was gene therapy (27.3 out of 100). CONCLUSION: This approach provided a useful support for discussion, integrating organizational aspects in the treatment decision-making process, at healthcare team level. The study needs repeating in a few years' time and in other hemophilia centers.

Systematic literature review on the implicit factors influencing the HTA deliberative process in Europe.

Objectives: Deliberative processes in Health Technologies Assessment (HTA) result in recommendations that determine the reimbursement of medicines, diagnostics or devices. These processes are governed by explicit criteria, but are also influenced by implicit factors. The objective of this work was to identify the implicit factors influencing HTA deliberative processes in five European countries (France, Germany, Italy, Spain and the UK). Methods: A systematic review of literature published between 2009 and 2019 was conducted. The search was performed in Pubmed, The Cochrane Database of Systematic Reviews, Google Scholar and Center for Reviews and Dissemination. The ISPOR database was searched manually. Results: Out of 100 eligible publications, eight articles were selected for data extraction and analysis. The implicit factors in the HTA deliberative process most frequently mentioned in the identified literature are value judgments, biases, preferences and subjectivity. Five out of the eight articles highlight the need to further improve the transparency of the process, and three provide recommendations on how to address the influence of implicit factors on the HTA deliberative process through a framework. Conclusion: Even in countries with a long HTA history, evidence on implicit factors is scarce. Some methods have been recommended for addressing these factors. Further research is required to characterize the implicit factors in the HTA deliberative process at a country level and explore potential ways to mitigate the influence of these factors on the HTA deliberative process.

Oral-Hygiene-Related Mobile Apps in the French App Stores: Assessment of Functionality and Quality.

Mobile health apps can contribute to increased quality of individual oral hygiene behaviors. This study provides an overview and an evaluation of quality of oral-hygiene-related mobile apps currently available in Google Play Store and the French Apple App. A shortlist of nine apps was assessed by 10 oral health professionals using the Mobile App Rating Scale. Intraclass correlation was used to evaluate interrater agreement. Best quality scores were obtained by Oral-B (3.4 ± 0.97), Colgate Connect (3.20 ± 0.63), and Preventeeth (3.10 ± 1.1) and worst ones by Mimizaur se brosse les dents (1.80 ± 0.79) and Kolibree (2.30 ± 0.82). The subjective quality scores ranged from 2.62 ± 0.61 (Oral-B) to 1.5 ± 0.61 (MSD). Specificity of the content ranged from 3.46 ± 0.84 (Preventeeth) to 1.78 ± 0.47 (Mimizaur se brosse les dents). Thus, even if oral health professionals positively evaluated the quality of oral-hygiene-related mobile apps, they are less assertive concerning their impact on the user's knowledge, attitudes, and intentions to change, as well as the likelihood of actual change in the oral hygiene behavior. Further investigations are needed to assess whether information from these apps is consistent with oral hygiene recommendations and to determine the long-term impacts of these apps.

Nutrition-Related Mobile Apps in the French App Stores: Assessment of Functionality and Quality.

BACKGROUND: The global burden of disease attributes 20% of deaths to poor nutrition. Although hundreds of nutrition-related mobile apps have been created, and these have been downloaded by millions of users, the effectiveness of these technologies on the adoption of healthy eating has had mixed. OBJECTIVE: The aim of this study was to review which nutrition-related mobile apps are currently available on the French market and assess their quality. METHODS: We screened apps on the Google Play Store and the French Apple App Store, from March 10 to 17, 2021, to identify those related to nutritional health. A shortlist of 15 apps was identified, and each was assessed using the French version of the Mobile App Rating Scale: 8 dietitians and nutritionists assessed 7 apps, and the remaining apps were randomly allocated to ensure 4 assessments per app. Intraclass correlation was used to evaluate interrater agreement. Means and standard deviations of scores for each section and each item were calculated. RESULTS: The top scores for overall quality were obtained by Yazio - Régime et Calories (mean 3.84, SD 0.32), FeelEat (mean 3.71, SD 0.47), and Bonne App (mean 3.65, SD 0.09). Engagement scores ranged from a mean of 1.95 (SD 0.5) for iEatBetter: Journal alimentaire to a mean of 3.85 (SD 0.44) for FeelEat. Functionality scores ranged from a mean of 2.25 (SD 0.54) for Naor to a mean of 4.25 (SD 0.46) for Yazio. Aesthetics scores ranged from a mean of 2.17 (SD 0.34) for Naor to a mean of 3.88 (SD 0.47) for Yazio. Information scores ranged from a mean of 2.38 (SD 0.60) for iEatBetter to a mean of 3.73 (SD 0.29) for Yazio. Subjective quality scores ranged from a mean of 1.13 (SD 0.25) for iEatBetter to a mean of 2.28 (SD 0.88) for Compteur de calories FatSecret. Specificity scores ranged from a mean of 1.38 (SD 0.64) for iEatBetter to a mean of 3.50 (SD 0.91) for FeelEat. The app-specific score was always lower than the subjective quality score, which was always lower than the quality score, which was lower than the rating from the iOS or Android app stores. CONCLUSIONS: Although prevention and information messages in apps regarding nutritional habits are not scientifically verified before marketing, we found that app quality was good. Subjective quality and specificity were associated with lower ratings. Further investigations are needed to assess whether information from these apps is consistent with recommendations and to determine the long-term impacts of these apps on users.

Reinforcing Collaboration and Harmonization to Unlock the Potentials of Advanced Therapy Medical Products: Future Efforts Are Awaited From Manufacturers and Decision-Makers.

Some advanced therapy medicinal products (ATMPs) hold great promises for life-threatening diseases with high unmet needs. However, ATMPs are also associated with significant challenges in market access, which necessitates the joint efforts between all relevant stakeholders to navigate. In this review, we will elaborate on the importance of collaborations and harmonization across different stakeholders, to expedite the market access of promising ATMPs. Manufacturers of ATMPs should proactively establish collaborations with other stakeholders throughout the whole lifecycle of ATMPs, from early research to post-market activities. This covered engagements with (1) external developers (i.e., not-for-profit organizations and commercial players) to obtain complementary knowledge, technology, or infrastructures, (2) patient groups and healthcare providers to highlight their roles as active contributors, and (3) decision-makers, such as regulators, health technology assessment (HTA) agencies, and payers, to communicate the uncertainties in evidence package, where parallel consultation will be a powerful strategy. Harmonization between decision-makers is desired at (1) regulatory level, in terms of strengthening the international standardization of regulatory framework to minimize discrepancies in evidence requirements for market authorization, and (2) HTA level, in terms of enhancing alignments between regional and national HTA agencies to narrow inequity in patient access, and cross-border HTA cooperation to improve the quality and efficiency of HTA process. In conclusion, manufacturers and decision-makers shared the common goals to safeguard timely patient access to ATMPs. Collaboration and harmonization will be increasingly leveraged to enable the value delivery of ATMPs to all stakeholders.

Ocrelizumab not recommended in France for patients with primary progressive multiple sclerosis while recommended in England: a review comparing the assessment by HAS and NICE.

INTRODUCTION: Ocrelizumab is the first approved drug for primary progressive multiple sclerosis. Following appraisal by health technology assessment (HTA) bodies, this medicine has not been widely covered across European countries. We have compared the HTA process in England and France. AREA COVERED: We undertook an analysis of relevant documents that were published by the two HTA bodies. We analyzed patients' availability of Ocrelizumab at the different stages of the process. EXPERT OPINION: We identified differences in the assessment, one being the use of a different population of the pivotal trial, which has resulted in the consideration of distinct clinical effectiveness estimates. Ocrelizumab became available earlier in France as part of an early access program. However, rapid access was discontinued for newly eligible patients following an opinion concluding that Ocrelizumab yielded no additional benefit over placebo. This opinion was not compatible with the criteria allowing reimbursement in France.In England, there was no early access program and following an appraisal that included cost-effectiveness evaluation combined with pricing agreements, medicine was finally recommended. In conclusion, differences in the HTA process may result in appreciable differences in timing and outcome from marketing authorization to the adoption of newly licensed drugs.

Use of Patient Preference Information in Benefit-Risk Assessment, Health Technology Assessment, and Pricing and Reimbursement Decisions: A Systematic Literature Review of Attempts and Initiatives.

Objectives: Inclusion of patient preference (PP) data in decision making has been largely discussed in recent years. Healthcare decision makers-regulatory and health technology assessment (HTA)-are more and more conscious of the need for a patient-centered approach to decide on optimal allocation of scarce money, time, and technological resources. This literature review aims to examine the use of and recommendations for the integration of PP in decision making. Methods: A literature search was conducted through PubMed/Medline in May 2019 to identify publications on PP studies used to inform benefit-risk assessments (BRAs) and HTAs and patient-centered projects and guidelines related to the inclusion of PPs in health policy decision making. After title and abstract screening and full-text review, selected publications were analyzed to retrieve data related to the collection, use, and/or submission of PPs informing BRA or HTA as well as attempts and initiatives in recommendations for PPs integration in decision-making processes. Results: Forty-nine articles were included: 24 attempts and pilot project discussions and 25 PP elicitation studies. Quantitative approaches, particularly discrete choice experiments, were the most used (24 quantitative elicitation studies and 1 qualitative study). The objective of assessing PPs was to prioritize outcome-specific information, to value important treatment characteristics, to provide patient-focused benefit-risk trade-offs, and to appraise the patients' willingness to pay for new technologies. Moreover, attempts and pilot projects to integrate PPs in BRAs and HTAs were identified at the European level and across countries, but no clear recommendations have been issued yet. No less than seven public and/or private initiatives have been undertaken by governmental agencies and independent organizations to set guidance targeting improvement of patients' involvement in decision making. Conclusion: Despite the initiatives undertaken, the pace of progress remains slow. The use of PPs remains poorly implemented, and evidence of proper use of these data in decision making is lacking. Guidelines and recommendations formalizing the purpose of collecting PPs, what methodology should be adopted and how, and who should be responsible for generating these data throughout the decision-making processes are needed to improve and empower integration of PPs in BRA and HTA.

Organizational aspect in healthcare decision-making: a literature review.

BACKGROUND: Organizational aspect is rarely considered in healthcare. However, it is gradually seen as one of the key aspects of the decision-making process as well as clinical and economic dimensions. Our primary objective was to identify criteria already used to assess the organizational impact of medical innovations. Our secondary objective was to structure them into an inventory to support decision-makers to select the relevant criteria for their complex decision-making issues. MATERIALS AND METHODS: A search using the Medline database was conducted in June 2019. The records published between January, 1990 and December, 2018 were identified. The publications cited by the authors of the included articles and the websites of health technology assessment agencies, units or learned societies identified during the search were also consulted. The identified criteria were structured in an inventory. RESULTS: We selected 107 records of a wide range of evidence mostly published after the 2000s. We identified 636 criteria that we classified into five categories: people, task, structure, technology, and surroundings. CONCLUSION: Criteria selection is a crucial step in any multi-criteria decision analysis (MCDA). This work is the first step in the development of a validated MCDA method to assess the organizational impact of medical innovations.

Will the US$5 million onasemnogene abeparvosec treatment for spinal muscular atrophy represent 'value for money' for the NHS? A rapid inquiry into suggestions that it may be cost-effective.

OBJECTIVES: Nusinersen (Spinraza®, Biogen) and onasemnogene abeparvosec (Zolgensma®, Novartis) are novel gene-based therapies for the orphan disease Spinal Muscular Atrophy. Onasemnogene abeparvosec has been allocated an acquisition cost of up to US$5 million per patient. We undertook a rapid inquiry to evaluate if onasemnogene abeparvosec is likely to be cost-effective for the UK NHS. METHODS: We used publicly available cost-effectiveness data and recommended methodology to perform cost-utility evaluation of onasemnogene abeparvosec versus best supportive care and nusinersen. RESULTS: Our evaluations highlight wide variations in cost and benefit estimates of nusinersen and indicate that onasemnogene abeparvosec is unlikely to represent value for money according to current standards of reimbursement. Results are discussed in the context of reimbursement decisions for orphan diseases. CONCLUSION: Commonly implemented commercial confidentiality practices combined with uncertain data obscure scrutiny and justification of past and present reimbursement decisions for orphan drugs. Future cutting edge expensive therapies will be numerous, they will entail very substantial economic strains. We conclude that there is an urgent and increasing need for the development of improved procedures that can lead to equitable, consistent, and transparent decision-making.

Multiple criteria decision analysis approach to consider therapeutic innovations in the emergency department: The methoxyflurane organizational impact in acute trauma pain.

BACKGROUND: Acute trauma pain is poorly managed in the emergency department (ED). The reasons are partly organizational: ED crowding and rare trauma care pathways contribute to oligoanalgesia. Anticipating the organizational impact of an innovative care procedure might facilitate the decision-making process and help to optimize pain management. METHODS: We used a multiple criteria decision analysis (MCDA) approach to consider the organizational impact of methoxyflurane (self-administered) in the ED, introduced alone or supported by a trauma care pathway. A MCDA experiment was designed for this specific context, 8 experts in emergency trauma care pathways (leading physicians and pharmacists working in French urban tertiary hospitals) were recruited. The study involved four steps: (i) Selection of organizational criteria for evaluating the innovation's impact; (ii) assessment of the relative weight of each criterion; (iii) choice of appropriate scenarios for exploring the organizational impact of MEOX under various contexts; and (iv) software-assisted simulation based on pairwise comparisons of the scenarios. The final outcome measure was the expected overall organizational impact of methoxyflurane on a 0-to-100 scale (score >50: positive impact). RESULTS: Nine organizational criteria were selected. "Mean length of stay in the ED" was the most weighted. Methoxyflurane alone obtained 59 as a total score, with a putative positive impact for eight criteria, and a neutral effect on one. When a trauma care pathway was introduced concomitantly, the impact of methoxyflurane was greater overall (score: 75) and for each individual criterion. CONCLUSIONS: Our model highlighted the putative positive organizational impact of methoxyflurane in the ED-particularly when supported by a trauma care pathway-and the relevance of expert consensus in this particular pharmacoeconomic context. The MCDA approach could be extended to other research fields and healthcare challenges in emergency medicine.

Medico-economic study of pain in an emergency department: a targeted literature review.

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 medico-economics 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.

Comparison of health technology assessment for new medicines in France and England: an example based on ixazomib for patients with relapsed or refractory multiple myeloma.

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.

Why "American Patients First" is likely to raise drug prices outside of the United States.

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.

Medication adherence in pediatric transplantation and assessment methods: a systematic review.

Background: Medication adherence is a major concern in public health. It is fully established that immunosuppressive therapy (IT) and concomitant medications affect transplant outcomes in the pediatric population, showing interest in adherence to this therapy. The aim of the present review was to report on medication adherence in pediatric population post-transplantation. This will enable us to know the situation in this particular population. Methods: A literature search was performed using the MEDLINE database. Studies that were published from January 1999 to January 2016 in English language and which investigated medication adherence in pediatric transplantation were included. The type of organ and the methods used to assess medication adherence were studied. Results: A total of 281 records were identified, from which 34 studies were selected: 38% (n=13) on kidney transplantation, 32% (n=11) on liver transplantation, and 23% (n=10) on the transplantation of other organs. Medication adherence was found to be lower than 80% in two-thirds of the studies (64%), and varied from 22% to 97%. This wide range was explained in part by the important heterogeneity of assessment methods among studies. The methods used were objective, non-objective, or combined both types. Most studies did not fully describe the data collected: the time since transplantation, the period over which adherence was assessed, the population, the medications, and the threshold discriminating adherence and non-adherence. Conclusion: The present study found poor medication adherence in the pediatric population post-transplantation. There was a wide range of medication adherence, explained largely by the heterogeneity of assessment methods. Future studies must consider the characteristics of each methodology, but also the threshold defining adherence should be chosen on the basis of clinical outcomes, and describe all data collected to gain precision. To improve adherence in this population, it is essential to identify factors influencing medication (IT and concomitant medications) adherence.

Cost-effectiveness of tumor-treating fields added to maintenance temozolomide in patients with glioblastoma: an updated evaluation using a partitioned survival model.

PURPOSE: A first cost-effectiveness analysis has raised a strong concern regarding the cost of tumor treatment fields (TTF) added to maintenance temozolomide for patients with glioblastoma. This evaluation was based on effectiveness outcomes from an interim analysis of the pivotal trial, moreover it used a "standard" Markov model. Our objective was to update the cost-effectiveness evaluation using the more flexible potential of the "partitioned survival" model design and using the latest effectiveness data. METHODS: We developed the model with three mutually exclusive health states: stable disease, progressive disease, and dead. Good fit parametric models were developed for overall survival and progression free survival and these generated clinically plausible extrapolations beyond the observed data. We adopted the perspective of the French national health insurance and used a 20-year time horizon. Results were expressed as cost/life-years (LY) gained (LYG). RESULTS: The base case model generated incremental benefit of 0.604 LY at a cost of €453,848 which, after 4% annual discounting of benefits and costs, yielded an incremental cost effectiveness ratio (ICER) of €510,273/LYG. Using sensitivity analyses and bootstrapping methods results were found to be relatively robust and were only sensitive to TTF device costs and the modelling of overall survival. To achieve an ICER below €100,000/LYG would require a reduction in TTF device cost of approximately 85%. CONCLUSIONS: Using a different type of model and updated survival outcomes, our results show TTF remains an intervention that is not cost-effective, which greatly restrains its diffusion to potentially eligible patients.