Development of Seasonal Influenza Vaccination Recommendations: Relevance and Influence of the Evidence on the Decision-Making Process in France and the Netherlands.

BACKGROUND: Target groups for seasonal influenza vaccination are defined at the country level and are based on several factors. However, little is known about the national decision-making procedures. OBJECTIVE: The purpose of this study was to compare the evidence used for the development of recommendations and its impact on the choice of target groups in France and the Netherlands. METHODS: A preliminary documentary analysis identified institutions to include in the assessment: governmental authorities, research institutions, associations, and manufacturers. At least one expert from each group was invited to our study. Thirty-three semi-structured interviews were conducted in 2013 (16 France, 17 the Netherlands). We used NVivo10® to perform a thematic content analysis. RESULTS: Clinical/epidemiological studies were the evidence most used in both countries. Economic models were increasingly being used; these had greater influence on the decision making in the Netherlands than in France, probably because of the presence of a modeler. Generally, the quality of the evidence used was poor, although no systematic use of standard protocol for its assessment was observed. A general protocol was sometimes used in France; however, the personal judgment of the experts was crucial for the assessment in both countries. CONCLUSIONS: There were differences in the target groups, for example, pregnant women, recommended only in France. France and the Netherlands use similar evidence for developing vaccination recommendations, although different decisions are sometimes made regarding target groups. This could be associated with the lack of systematic standard appraisals, increasing the influence of the experts' judgment on decision making. The development of standards for the appraisal of evidence is recommended.

COST-EFFECTIVENESS OF TREATMENTS FOR MILD-TO-MODERATE OBSTRUCTIVE SLEEP APNEA IN FRANCE.

OBJECTIVES: Untreated obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with excessive daytime sleepiness, increased risk of cardiovascular (CV) disease, and road traffic accidents (RTAs), which impact survival and health-related quality of life. This study, funded by the French National Authority for Health (HAS), aimed to assess the cost-effectiveness of different treatments (i.e., continuous positive airway pressure [CPAP], dental devices, lifestyle advice, and no treatment) in patients with mild-to-moderate OSAHS in France. METHODS: A Markov model was developed to simulate the progression of two cohorts, stratified by CV risk, over a lifetime horizon. Daytime sleepiness and RTAs were taken into account for all patients while CV events were only considered for patients with high CV risk. RESULTS: For patients with low CV risk, incremental cost-effectiveness ratio (ICER) of dental devices versus no treatment varied between 32,976 EUR (moderate OSAHS) and 45,579 EUR (mild OSAHS) per quality-adjusted life-year (QALY), and CPAP versus dental devices, above 256,000 EUR/QALY. For patients with high CV risk, CPAP was associated with a gain of 0.62 QALY compared with no treatment, resulting in an ICER of 10,128 EUR/QALY. CONCLUSION: The analysis suggests that it is efficient to treat all OSAHS patients with high CV risk with CPAP and that dental devices are more efficient than CPAP for mild-to-moderate OSAHS with low CV risk. However, out-of-pocket costs are currently much higher for dental devices than for CPAP (i.e., 3,326 EUR versus 2,430 EUR) as orthodontic treatment is mainly non-refundable in France.

Economic burden of seasonal influenza B in France during winter 2010-2011.

BACKGROUND: In France, 2-15% of the population is affected annually by influenza, which causes significant socioeconomic disruption. Nevertheless, despite its importance for policy makers, few published studies have evaluated the impact of influenza B. Therefore, we assessed the costs associated with influenza B during 2010-2011 in France. METHODS: Cases of lab-confirmed influenza B were analyzed as part of the Influenza B in General Practice Study. Cost calculations were based on micro-costing methods according to the French Health Insurance (FHI) perspective (in Euros, 2011). Costs were compared between age groups using the Kruskal-Wallis test, and when significant, by multiple comparisons based on rank. Moreover, uncertainties were assessed using one-way sensitivity and probabilistic analyses. Overall economic burden was estimated by multiplying cost per patient, flu attack rate, and the French population. RESULTS: A total of 201 patients were included in the study. We found that the mean cost associated with Influenza B was 72€ (SD: 205) per patient: 70€ (SD: 262) for younger children, 50€ (SD: 195) for older children, 126€ (SD: 180) for adults, and 42€ (SD: 18) for elderly. Thus, we observed significantly different costs between the distinct age groups (p<0.0001). Finally, the economic burden of influenza B for the FHI was estimated to be 145 million Euros (95% CI: 88-201). CONCLUSIONS: Our findings highlight the important impact of influenza B and encourage further investigation on policy regarding vaccination strategies in France.

Glossary of healthcare pathways: a methodological approach involving a transdisciplinary team in public health.

Introduction: The healthcare pathway is at the heart of public health organization concerns, but communication between the various players can be an obstacle. This work, produced by a French transdisciplinary team, offers a methodological approach based on formalized consensus to elaborate a glossary of healthcare pathways. A two-steps procedure was elaborated, including a double rounded Delphi method to formalize expert consensus, and two groups of experts: a workgroup and a review group. Methods: The workgroup provided a list of words or expressions that, in their opinion, described, evaluated or compared the healthcare pathways for patients, caregivers or regulators. The review group checked this list and added or deleted words or expressions. Then, definitions were added by the workgroup based into account three dimensions: official, academic and from the field. The review group validated the definitions and provided complementary proposals if needed. Results: After pooling the list of words proposed by each of the six members of the working group, 417 words/expressions were ranked. After the two rounds of evaluation, 294 words/expressions were rated "appropriate" and were analyzed by the review group. This group, after two rounds of evaluation, agreed on 263 words/expressions that were transmitted to the working group who defined them. These definitions were rated by the review group. The first round of evaluation established 195 definitions as being appropriated whereas 68 definitions were amended by the review group. Conclusion: This glossary supports transdisciplinary communication, reduces the extent of variations in practice and optimizes decision-making. International debate on all aspects might be strengthened by an improved understanding of the concept of health pathway.

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.

Chemotherapeutic errors in hospitalised cancer patients: attributable damage and extra costs.

BACKGROUND: In spite of increasing efforts to enhance patient safety, medication errors in hospitalised patients are still relatively common, but with potentially severe consequences. This study aimed to assess antineoplastic medication errors in both affected patients and intercepted cases in terms of frequency, severity for patients, and costs. METHODS: A 1-year prospective study was conducted in order to identify the medication errors that occurred during chemotherapy treatment of cancer patients at a French university hospital. The severity and potential consequences of intercepted errors were independently assessed by two physicians. A cost analysis was performed using a simulation of potential hospital stays, with estimations based on the costs of diagnosis-related groups. RESULTS: Among the 6, 607 antineoplastic prescriptions, 341 (5.2%) contained at least one error, corresponding to a total of 449 medication errors. However, most errors (n = 436) were intercepted before medication was administered to the patients. Prescription errors represented 91% of errors, followed by pharmaceutical (8%) and administration errors (1%). According to an independent estimation, 13.4% of avoided errors would have resulted in temporary injury and 2.6% in permanent damage, while 2.6% would have compromised the vital prognosis of the patient, with four to eight deaths thus being avoided. Overall, 13 medication errors reached the patient without causing damage, although two patients required enhanced monitoring. If the intercepted errors had not been discovered, they would have resulted in 216 additional days of hospitalisation and cost an estimated annual total of 92,907€, comprising 69,248€ (74%) in hospital stays and 23,658€ (26%) in additional drugs. CONCLUSION: Our findings point to the very small number of chemotherapy errors that actually reach patients, although problems in the chemotherapy ordering process are frequent, with the potential for being dangerous and costly.

[Cost-effectiveness analysis of active TDM in elderly patients treated with aminoglycosides]. / Étude coût-efficacité de l'adaptation bayésienne des posologies des aminosides en gériatrie.

OBJECTIVE: Aminoglycoside antibiotics use has been limited by the risk of toxicity and their pharmacokinetic variability, thus requiring therapeutic drug monitoring (TDM). As elderly patients are particularly at risk of accumulation, active therapeutic drug monitoring (ATM) can be performed using a Bayesian method. The objective was to analyse the clinical and economic impact of ATM in elderly patients. METHODS: A two-year retrospective study was performed to compare two geriatric hospitals, one using ATM (SG1) and the other using non-guided TDM (SG2). Efficacy was evaluated by internal reference to target concentration. Direct medical costs were research. Cost-effectiveness results expressed as ratios. RESULTS: In SG1 56 patients received aminoglycosides and 47 patients in SG2. The cost per patient was 114 € for ATM and 165 € for non-guided TDM. The sensitivity analysis confirmed these results. CONCLUSION: ATM for aminoglycoside is better on three criteria: efficacy, toxicity and cost.

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.

Systematic Literature Review of Economic Evaluations of Biological Treatment Sequences for Patients with Moderate to Severe Rheumatoid Arthritis Previously Treated with Disease-Modifying Anti-rheumatic Drugs.

OBJECTIVE: This systematic literature review (SLR) had two objectives: to analyse published economic evaluations of biological disease-modifying anti-rheumatic drugs (bDMARDs) for patients with moderate to severe rheumatoid arthritis (RA) previously treated with DMARDs and to assess the quality of those that included sequences of treatments. METHODS: We performed an SLR on PubMed, Central, Cochrane, and French databases from January 2000 to December 2018. The search focused on cost-effectiveness/utility/benefit analyses. We extracted data on treatment sequences, outcomes (e.g. quality-adjusted life year) and choices of economic evaluation methods (e.g. model type, type of analysis, and method of utility estimation). We analysed the improvement of methods by comparing two sub-periods (2000-2009 and 2010-2018). The quality of reporting and the quality of the methods were assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and a set of eight key aspects for a reference case for economic evaluation of bDMARDs based on the Outcome Measures in Rheumatology (OMERACT) and Drummond checklists. Data extraction and study assessment were performed independently by two health economists. RESULTS: From the 824 records identified in the initial search, 51 publications were selected. Of these, 31 included sequences. Individual models such as discrete-event simulations were used in over two-fifths (22/51, 43%) of the selected studies. Few studies (7/51, 14%) used utility scores based on generic instruments (e.g. EQ-5D). Estimation of hospitalization costs was described in only approximately one-third of studies (19/51). Loss of quality of life (QoL) related to adverse events such as tuberculosis and pneumonia was included in one-tenth (5/51, 10%) of the studies. It was difficult to compare the results of the economic evaluations (i.e. incremental cost-effectiveness ratios) due to the high heterogeneity of studies in terms of disease stage, data sources, inputs, and methods of health outcome assessment used. For identified studies including sequences, the CHEERS assessment of reporting quality showed insufficient reporting of uncertainty analyses and utility weights in more than a third of the studies (11/31, 35%; 9/25, 36%). An in-depth assessment of the quality of the studies revealed that only seven, mostly conducted during the sub-period 2010-2018, addressed the majority of methodological quality assessment issues such as the simulation of patient sequence pathways, the use of systematic reviews and meta-analyses of comparative effectiveness, the choice of treatment sequence, and rules for switching. CONCLUSION: Our SLR identified a lack of high-quality evaluations assessing bDMARD sequences, although some improvements were made in the reporting and modelling of patients' pathways in studies published after 2010. In order to improve economic evaluations of RA, clear health technology assessment guidance on RA health-related QoL instruments must be provided, and data including long-term disease progression must be made available.

A micro-costing evaluation of lobectomy by thoracotomy versus thoracoscopy.

BACKGROUND: Two surgical strategies called video-assisted thoracoscopy surgery (VATS) and thoracotomy are used for lobectomy following lung cancer diagnosis. The aim of this study was to assess the total cost of each technique (thoracotomy and VATS) during hospitalization in France. METHODS: A micro-costing methodology from the hospital perspective was implemented to assess the hospitalization costs, using direct observations, interviews, and data collection based on medical records in four hospitals. The average real cost of each technique was compared. RESULTS: From the hospital perspective, VATS was more expensive than thoracotomy but the difference was not significant (€6,941.30 vs. €5,950.11). CONCLUSIONS: According to this micro-costing study, thoracotomy seems to be the less expensive technique for the hospital. Our data will be included in a cost-utility analysis to assess the medico-economic impact of the VATS strategy.

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.

Influenza vaccination policy-making processes in France and The Netherlands: Framework and determinants.

OBJECTIVES: Target groups for seasonal influenza vaccination are nationally defined based on several factors. However, few studies have explored the policy-making processes at the country-level. We investigated key differences in the policy-making process for the development of vaccination recommendations between France (FR) and The Netherlands (NL). This paper presents preliminary results on the evidence used in the decision-making process and focuses on the interactions between the experts and stakeholders. METHODS: A documentary analysis identified the stakeholders of this process as governmental authorities, research institutions, associations, and manufacturers. This qualitative study included at least one expert from each stakeholder group. Thirty-three semi-structured interviews were performed in 2013 (16 FR, 17 NL). We used NVivo10® to perform a thematic content analysis on the data. RESULTS: National Immunization Technical Advisory Groups (NITAGs) were the key stakeholders in the development of recommendations. There was no systematic standard evaluation of evidence during the decision-making process in both countries. Likewise, voting was not systematic, although it did occur more often in FR. A declaration of interests was obligatory in both countries. Experts with no conflicts of interest were rare because many depend on private funding for their research on influenza vaccination. CONCLUSIONS: The transparency of the NITAGs' procedures for the development of recommendations should be improved. We believe improvements might be achieved by the systematic standard evaluation of evidence, consistent voting, clear declarations of interest, and increased public funding for vaccination research.

Role of clinical, patient-reported outcome and medico-economic studies in the public hospital drug formulary decision-making process: results of a European survey.

CONTEXT: Over the past 20 years, drug information has grown rapidly, but little is known of its actual use in hospital decision-making. OBJECTIVE: To describe the role of clinical studies (CS), patient-reported outcome studies (PROS) and medico-economic studies (MES) in public hospital drug formulary decision-making. METHODS: A postal survey was conducted in 400 randomly selected public hospitals stratified by country (France, Germany, The Netherlands and the United Kingdom) and profession (doctor or pharmacist). RESULTS: The participation rate was 78% (143 doctors and 169 pharmacists), and the response rate 44%. Responders were generally interested in CS (86%), PROS (71%) and MES (71%). They reported high but unmet expectations concerning information available on PROS and MES, the methodology of these studies and interpretation of the results. CONCLUSIONS: To increase the impact of PROS and MES, we suggest training decision-makers in the study methodology and provide them with support of health and economic experts.

A literature review to identify factors that determine policies for influenza vaccination.

OBJECTIVES: To conduct a literature review of influenza vaccination policy, describing roles and interactions between stakeholders and the factors influencing policy-making. METHODS: Major databases were searched using keywords related to influenza vaccination, decision-making and health policy. Titles and abstracts were screened according to defined criteria using independent reviewers. Selected articles were analysed and compared against a checklist. RESULTS: 342 papers were identified, but only 111 included. A wide range of countries was represented in articles published in 1994-2012. We identified numerous stakeholders at the national and international level and found a variety of interactions between them. Using these data, we suggest a scheme for the most important stakeholders and their interactions. Determinants of policy-making were mainly related to the vaccine/disease, political-economic context, and stakeholders communication. The most relevant evidence was clinical/epidemiological studies. After the 2009 pandemic: the importance of mathematical modelling and ethical issues was greater; and the need for better communication between stakeholders was emphasised. CONCLUSIONS: The relevance of evidence and factors influencing policy-making varied between countries, according to complex interactions between the stakeholders involved at different levels of decision-making process. These interactions remain unclear, especially at national level, where the most important influenza policy decisions are made. To better define and understand the exact interactions and use of evidence, we recommend undertaking future qualitative studies at national level using small number of countries.

A qualitative approach to the use of economic data in the selection of medicines for hospital formularies: a French survey.

OBJECTIVE: Qualitative interviews were conducted with pharmacists in hospitals and clinics in the Rhône-Alpes region of France to determine the role of economic data when selecting medicines for formularies, to identify barriers to the use of this information and to study to what degree a healthcare establishment's financing system influences the use of this data. METHOD: A stratified sample of healthcare establishments with over 100 short-stay beds were included: (1) thirteen public and semi-private hospitals financed through annual global budgets and (2) six private clinics financed on a fee-for-service basis. Interviews were carried out between October 1999 and January 2000, and coded independently by two researchers. MAIN OUTCOME MEASURE: A multiple correspondence analysis was performed to compare the two groups of healthcare establishments. RESULTS: The influence of economic data in the decision-making process is limited, for other factors appear to have greater weight: (1) efficacy and safety of medicines (2) relations between decision-makers and the pharmaceutical industry and (3) patient quality of life. Economic data used was mainly related to medication prices and quantities consumed. This data was used in a large number of decisions and seemed to have more importance in hospitals than in clinics. Information related to resources that could be saved by the inclusion of a new medicine on formularies was seldom used and apparently considered less important in hospitals than in clinics. Pharmacoeconomic evaluations were very rarely used. Six barriers to the use of economic data were raised by the pharmacists, including: lack of time, which limits the collection and analysis of such information; insufficient health economics training, an obstacle to decision-makers' analytical capacity; and closed budgets within hospitals. CONCLUSION: Economic data concerning 'medication budgets' appears to have a greater impact in public and semi-private hospitals than in private clinics. Obstacles linked to the decision-making context itself were particularly highlighted, and it can be concluded that in order to increase the use of economic data, it is first necessary to create an environment that is more favourable to its application.