Do Behavioral Characteristics Influence the Breast Cancer Diagnosis Delay? Evidence From French Retrospective Data.

OBJECTIVES: This study aimed to analyze the behavioral determinants of breast cancer (BC) diagnosis delays in France. To do so, we investigated whether time discounting, risk tolerance, and personality traits influenced the BC diagnosis delay of patients. METHODS: We used original retrospective data collected on 2 large online patient networks from 402 women diagnosed of BC. The BC diagnosis delay was measured by the difference between the date of diagnosis and the date of first symptoms. Time discounting and risk tolerance are measured with both self-reported questions and hypothetical lotteries. Personality traits are measured with the 10-item Big Five indicator. Ordinary least square and probit models were used to analyze whether these behavioral characteristics influenced the BC diagnosis delay. RESULTS: Results showed that risk tolerance and time discounting were not significantly associated with the BC diagnosis delay. However, we found a longer diagnosis delay for women with a neuroticism personality trait (standardized coefficients ranged from 0.104 [P-value = .036] to 0.090 [P-value = .065]). CONCLUSIONS: Overall, our findings underline the need for an increased consideration of cancer screening public health policy for women with mental vulnerabilities since such vulnerabilities were found to be highly correlated with a neuroticism personality trait.

Impact of tariff refinement on the choice between scheduled C-section and normal delivery: Evidence from France.

Studying quasi-experimental data from French hospitals from 2010 to 2013, we test the effects of a substantial diagnosis-related group (DRG) tariff refinement that occurred in 2012, designed to reduce financial risks of French maternity wards. To estimate the resulting DRG incentives with regard to the choice between scheduled C-sections and other modes of child delivery, we predict, based on pre-admission patient characteristics, the probability of each possible child delivery outcome and calculate expected differences in associated tariffs. Using patient-level administrative data, we find that introducing additional severity levels and clinical factors into the reimbursement algorithm had no significant effect on the probability of a scheduled C-section being performed. The results are robust to multiple formulations of DRG financial incentives. Our paper is the first study that focuses on the consequences of a DRG refinement in obstetrics and develops a probabilistic approach suitable for measuring the expected effects of DRG fee incentives in the presence of multiple tariff groups.

Generating comparative evidence on new drugs and devices before approval.

Fewer than half of new drugs have data on their comparative benefits and harms against existing treatment options at the time of regulatory approval in Europe and the USA. Even when active-comparator trials exist, they might not produce meaningful data to inform decisions in clinical practice and health policy. The uncertainty associated with the paucity of well designed active-comparator trials has been compounded by legal and regulatory changes in Europe and the USA that have created a complex mix of expedited programmes aimed at facilitating faster access to new drugs. Comparative evidence generation is even sparser for medical devices. Some have argued that the current process for regulatory approval needs to generate more evidence that is useful for patients, clinicians, and payers in health-care systems. We propose a set of five key principles relevant to the European Medicines Agency, European medical device regulatory agencies, US Food and Drug Administration, as well as payers, that we believe will provide the necessary incentives for pharmaceutical and device companies to generate comparative data on drugs and devices and assure timely availability of evidence that is useful for decision making. First, labelling should routinely inform patients and clinicians whether comparative data exist on new products. Second, regulators should be more selective in their use of programmes that facilitate drug and device approvals on the basis of incomplete benefit and harm data. Third, regulators should encourage the conduct of randomised trials with active comparators. Fourth, regulators should use prospectively designed network meta-analyses based on existing and future randomised trials. Last, payers should use their policy levers and negotiating power to incentivise the generation of comparative evidence on new and existing drugs and devices, for example, by explicitly considering proven added benefit in pricing and payment decisions.

Evaluating the Impact of Intensive Case Management for Severe Vocational Injuries on Work Incapacity and Costs.

Purpose This study investigates the impact of an intensive case management program on sick leave days, permanent work incapacity levels and treatment costs for severe vocational injuries set up by the French National Insurance Fund in five health insurance districts. Methods The method employed relies on a four-step matching procedure combining Coarsened Exact Matching and Propensity Score Matching, based on an original administrative dataset. Average Treatment effects on the Treated were estimated using a parametric model with a large set of covariates. Results After one-year follow-up, workers in the treatment group had higher sickness absence rates, with 22 extra days, and the program led to 2.7 (95% CI 2.3-3.1) times more diagnoses of permanent work incapacity in the treatment group. With an estimated yearly operational cost of 2,722 € per treated worker, the average total extra treatment cost was 4,569 € for treated workers, which corresponds to a cost increase of 29.2% for the insurance fund. Conclusions The higher costs found for the treatment group are mainly due to longer sick leave duration for the moderate severity group, implying higher cash transfers in the form of one-off indemnities. Even though workers in the treated group have more diagnoses of permanent work incapacity, the difference of severity between groups is small. Our results on longer sick leave duration are partly to be explained by interactions between the case managers and the occupational physicians that encouraged patients to stay longer off-work for better recovery, despite the higher costs that this represented for the insurance fund and the well-documented adverse side effects of longer periods off-work.

COST-EFFECTIVENESS OF INTERVENTIONS BASED ON PHYSICAL ACTIVITY IN THE TREATMENT OF CHRONIC CONDITIONS: A SYSTEMATIC LITERATURE REVIEW.

OBJECTIVES: The aim of this study is to review evidence on the cost-effectiveness of exercise-based interventions in the treatment of chronic conditions a decade after the publication of Roine et al. in 2009 (Roine E, Roine RP, Räsänen P, et al. Int J Technol Assess Health Care. 2009;25:427-454). METHODS: We carried out a review of published articles in PUBMED and JSTOR between January 1, 2008, and December 31, 2016. Full economic evaluations of exercise programs targeting patients with a chronic condition were eligible for inclusion. Data on program, design, and economic characteristics were extracted using a predefined extraction form. The quality of the economic evaluations was appraised using the adjusted Consensus Health Economic Criteria List. RESULTS: A total of 426 articles were identified and thirty-seven studies were selected. Eleven studies dealt with musculoskeletal and rheumatologic disorders, ten with cardiovascular diseases, six with neurological disorders, three with mental illnesses, three with cancers, and four with diabetes, respiratory diseases, or pelvic organ prolapse. In total, 60 percent of exercise programs were dominant or cost-effective. For musculoskeletal and rheumatologic disorders, 72 percent of programs were dominant or cost-effective while this was the case for 57 percent of programs for cardiovascular diseases using a nonsurgical comparator. CONCLUSIONS: There is clear evidence in favor of exercise-based programs for the treatment of musculoskeletal and rheumatologic disorders and, to a lesser extent, for the treatment of cardiovascular diseases. More research is needed to evaluate the cost-effectiveness of physical activity in the treatment of neurological disorders, mental illnesses, cancers, respiratory diseases, and diabetes/obesity.

Medico-economic evaluation of health products in the context of the Social Security Financing Act for 2012.

The participants in round table 6 of the Giens Workshops 2012 drafted recommendations based on the collective interpretation of important elements of the decree concerning the medico-economic evaluation of health products published a few days earlier (02 October 2012). The medico-economic evaluation (MEE), becomes an additional determinant for fixing the prices of health products by the Health products economic committee (Comité économique des produits de santé, CEPS) via the hierarchisation of treatment strategies, and thus modifies the market access conditions. Limiting the analysis to medicinal products and medical devices for which a major, important or moderate improvement in the medical service rendered (ASMR) or of the expected service (ASA) has been requested and presenting a significant budget impact on the Social Security expenses, excludes health products with ASMR or ASA with a lower level requested which often create complex price fixing problems and often have a major budget impact. This latter concept remains to be defined in detail. The MEE envisaged for the first registration must include the need to confirm or refute the initial hypotheses especially concerning the actual position in the therapeutic strategy at the time of renewal of the registration. For the first registration, the conventional reference to European prices guaranteeing a minimum price to innovative medicinal products, the medico-economic models submitted by the industry to the French Drug Authority (Haute autorité de santé, HAS) must be used to guide the compilation of new data to be requested at the time of the registration renewal and to negotiate the level of the discounts in the framework of a price-volume agreement, if applicable. The MEE will allow comparing the result of the analysis to the model hypothesis at the time of the renewal of the registration, which may contribute to the renegotiation (either up or down) of the price of health goods. The costs related to obtaining new data must be controlled. In order for the MEE to allow confirming the relationship between the price requested and the benefit expected, the group privileges the definition of reference values with an indicative and non-normative value, likely to evolve with time rather than a threshold. Concerning the evaluation procedure: the time to market access must not be lengthened; while the possibility of regular meetings between the industry and the HAS is recommended to avoid methodological divergences. A transitory period should allow the implementation of the entire evaluation procedure which must also take into account the specificities of health products registered before the 3 October 2013.

A systematic review of the cost-effectiveness of interventions to increase cervical cancer screening among underserved women in Europe.

BACKGROUND: This study aimed to conduct a systematic review of the cost-effectiveness studies of interventions to increase cervical cancer screening uptake rates in underserved women in Europe. METHODS: A search of Embase, Medline, Global Health, PsychINFO, and NHS Economic Evaluation Database was conducted for studies published between January 2000 and September 2022. Studies were eligible if they analysed the cost-effectiveness of any interventions to improve participation in cervical cancer screening among underserved women of any age eligible to participate in cervical cancer screening in European countries, in any language. Study characteristics and cost-effectiveness results were summarised. Study quality was assessed using the Drummond Checklist, and methodological choices were further compared. RESULTS: The searches yielded 962 unique studies, with 17 of these (from twelve European countries) meeting the eligibility criteria for data extraction. All studies focused on underscreened women as an overarching group, with no identified studies focusing on specific subgroups of underserved women. Generally, self-HPV testing and reminder interventions were shown to be cost-effective to increase the uptake rates. There was also research showing that addressing access issues and adopting different screening modalities could be economically attractive in some settings, but the current evidence is insufficient due to the limited number of studies. CONCLUSION: This systematic review has revealed a gap in the literature on the cost-effectiveness of interventions to improve uptake rates of cervical cancer screening through tailored provision for specific groups of underserved women.

Multicentre, randomised, economic evaluation of a web-based interactive education platform, simple or enhanced, for patients with end-stage renal disease: the PIC-R trial protocol.

INTRODUCTION: End-stage renal disease (ESRD) affects 84 000 persons in France and costs an estimated €4.2 billion. Education about their disease empowers patients and allows improved management of their disease and better health outcomes. This study aims to explore whether the addition of an interactive web-based platform to patient education is effective and cost-effective and additionally whether complementing the platform with social functions and features improves its performance. METHODS AND ANALYSIS: Patients with severe, ESRD or post-transplant will be randomised 1:1:1 to either standard therapeutic education; or education using a specific application; or the enhanced interactive app with social features. The total follow-up duration is 18 months. Primary endpoint is the cost utility of using app-based therapeutic intervention; secondary endpoints are: compliance with treatment guidelines, app use (professionals and patients), patients' satisfaction, budget impact analysis. ETHICS AND DISSEMINATION: The findings will inform the deployment and reimbursement of the application. The study has ethical approval by the Ile de France ethics committee. Dissemination of the results will be presented at conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03090828.

Inequities in cancer drug development in terms of unmet medical need.

This study measures inequality and inequity in the distribution of clinical trials on cancer drug development between 1996 and 2016, comparing the number of clinical trials with cancer need, proxied by prevalence, incidence, or survival rates for both rare and non-rare cancers. We leverage a unique global database of clinical trials activity and costs between 1996 and 2016, constructed for 227 different cancer types to measure for rare and non-rare cancers: i) inequalities and inequity of clinical trial activity, considering all trials as well as split by R&D stage; ii) inequalities and inequity in R&D investment proxied by trial enrollment and duration; iii) evolution of inequity over time. Inequalities are measured with concentration curves and indices and inequities measured with the health inequity index. We find four important results. First, we show pro-low need inequity across cancer types for both rare and non-rare cancers, for all need proxies. Second, we show inequity differs across R&D stages and between rare and non-rare cancers. The distribution of clinical trials for non-rare cancers disproportionately favors low-need non-rare cancers from earlier to later stages of R&D, whilst for rare cancers this only occurs in Phase 2 trials. Third, inequity analyses in R&D investment show that only trial enrollment for rare cancers and trial duration for non-rare cancers are disproportionately concentrated among low-need cancers. Finally, while pro-low need inequity has persisted between 1996 and 2016 for non-rare cancers, it has faded for rare cancers post-EU orphan drugs' legislation.

Cost-effectiveness of strategies to control the spread of carbapenemase-producing Enterobacterales in hospitals: a modelling study.

BACKGROUND: Spread of resistant bacteria causes severe morbidity and mortality. Stringent control measures can be expensive and disrupt hospital organization. In the present study, we assessed the effectiveness and cost-effectiveness of control strategies to prevent the spread of Carbapenemase-producing Enterobacterales (CPE) in a general hospital ward (GW). METHODS: A dynamic, stochastic model simulated the transmission of CPE by the hands of healthcare workers (HCWs) and the environment in a hypothetical 25-bed GW. Input parameters were based on published data; we assumed the prevalence at admission of 0.1%. 12 strategies were compared to the baseline (no control) and combined different prevention and control interventions: targeted or universal screening at admission (TS or US), contact precautions (CP), isolation in a single room, dedicated nursing staff (DNS) for carriers and weekly screening of contact patients (WSC). Time horizon was one year. Outcomes were the number of CPE acquisitions, costs, and incremental cost-effectiveness ratios (ICER). A hospital perspective was adopted to estimate costs, which included laboratory costs, single room, contact precautions, staff time, i.e. infection control nurse and/or dedicated nursing staff, and lost bed-days due to prolonged hospital stay of identified carriers. The model was calibrated on actual datasets. Sensitivity analyses were performed. RESULTS: The baseline scenario resulted in 0.93 CPE acquisitions/1000 admissions and costs 32,050 €/1000 admissions. All control strategies increased costs and improved the outcome. The efficiency frontier was represented by: (1) TS with DNS at a 17,407 €/avoided CPE case, (2) TS + DNS + WSC at a 30,700 €/avoided CPE case and (3) US + DNS + WSC at 181,472 €/avoided CPE case. Other strategies were dominated. Sensitivity analyses showed that TS + CP might be cost-effective if CPE carriers are identified upon admission or if the cases have a short hospital stay. However, CP were effective only when high level of compliance with hand hygiene was obtained. CONCLUSIONS: Targeted screening at admission combined with DNS for identified CPE carriers with or without weekly screening were the most cost-effective options to limit the spread of CPE. These results support current recommendations from several high-income countries.

Combined incentive actions, focusing on primary care professionals, to improve cervical cancer screening in women living in socioeconomically disadvantaged geographical areas: a study protocol of a hybrid cluster randomised effectiveness and implementation trial- RESISTE.

INTRODUCTION: Cervical cancer (CC) causes thousands of deaths each year. Nearly 100% of cases are caused by oncogenic strains of human papillomavirus (HPV). In most industrialised countries, CC screening (CCS) is based on the detection of HPV infections. For many reasons including lower adherence to CCS, underserved women are more likely to develop CC, and die from it. We aim to demonstrate that the use of incentives could improve screening rates among this population. METHODS AND ANALYSIS: Our cluster randomised, controlled trial will include 10 000 women aged 30-65 years eligible for CCS, living in deprived areas in four French departments, two mainlands and two overseas, and who did not perform physician-based HPV testing within the framework of the nationally organised screening programme. HPV self-sampling kit (HPVss) will be mailed to them. Two interventions are combined in a factorial analysis design ending in four arms: the possibility to receive or not a financial incentive of €20 and to send back the self-sampling by mail or to give it to a health professional, family doctor, gynaecologist, midwife or pharmacist. The main outcome is the proportion of women returning the HPVss, or doing a physician-based HPV or pap-smear test the year after receiving the HPVss. 12-month follow-up data will be collected through the French National Health Insurance database. We expect to increase the return rate of HPV self-samples by at least 10% (from 20% to 30%) compared with the postal return without economic incentive. ETHICS AND DISSEMINATION: Ethics approval was first obtained on 2 April 2020, then on July 29 2022. The ethics committee classified the study as interventional with low risk, thus no formal consent is required for inclusion. The use of health insurance data was approved by the Commission Nationale Informatique et Libertés on 14 September 2021 (ref No 920276). An independent data security and monitoring committee was established. The main trial results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04312178.

Hospital payment schemes and high-priced drugs: Evidence from the French Add-on List.

Under prospective payment schemes, hospitals may be disincentivised to use high-priced drugs. In this context, supplementary payment schemes have been implemented to fund hospitals beyond hospital tariffs for the use of such technologies. In France, since 2004, an add-on list scheme ensures that listed high-priced drugs are reimbursed by the state, thereby imposing no cost on hospitals while drugs are on the list. Yet little is known about the impact of drug delisting, i.e., when drugs are removed from the add-on list, on hospital utilisation. In this paper, we investigate the effects of delisting for 12 cancer drugs on the volumes prescribed, the generic shares and the purchase prices negotiated by hospitals. Using French hospital-level data over the period 2008-2016, we construct volumes, generic shares and purchase prices at the molecule level to account for potential substitutions across therapeutically equivalent drugs. Hospital fixed effects allow for time-invariant unobserved hospital heterogeneity linked to e.g., prescription preferences or hospitals' bargaining power. Our results indicate that prescription volumes, generic shares and price levels are not systematically affected by delisting, nor do we find evidence of response heterogeneity by hospital type. Overall, our findings mitigate concerns that the financial incentives associated with add-on lists may lead to hospitals over-prescribing high-priced drugs.

Competition between Public and Private Maternity Care Providers in France: Evidence on Market Segmentation.

The purpose of this paper is to investigate the potential for segmentation in hospital markets, using the French case where private for-profit providers play an important role having nearly 25% of market shares, and where prices are regulated, leading to quality competition. Using a stylized economic model of hospital competition, we investigate the potential for displacement between vertically differentiated public and private providers, focusing on maternity units where user choice is central. Building over the model, we test the following three hypotheses. First, the number of public maternity units is likely to be much larger in less populated departments than in more populated ones. Second, as the number of public maternity units decreases, the profitability constraint should allow more private players into the market. Third, private units are closer substitutes to other private units than to public units. Building an exhaustive and nationwide data set on the activity of maternity services linked to detailed data at a hospital level, we use an event study framework, which exploits two sources of variation: (1) The variation over time in the number of maternity units and (2) the variation in users' choices. We find support for our hypotheses, indicating that segmentation is at work in these markets with asymmetrical effects between public and private sectors that need to be accounted for when deciding on public market entry or exit.

Comparative effectiveness research and evidence-based health policy: experience from four countries.

CONTEXT: The discussion about improving the efficiency, quality, and long-term sustainability of the U.S. health care system is increasingly focusing on the need to provide better evidence for decision making through comparative effectiveness research (CER). In recent years, several other countries have established agencies to evaluate health technologies and broader management strategies to inform health care policy decisions. This article reviews experiences from Britain, France, Australia, and Germany. METHODS: This article draws on the experience of senior technical and administrative staff in setting up and running the CER entities studied. Besides reviewing the agencies' websites, legal framework documents, and informal interviews with key stakeholders, this analysis was informed by a workshop bringing together U.S. and international experts. FINDINGS: This article builds a matrix of features identified from the international models studied that offer insights into near-term decisions about the location, design, and function of a U.S.-based CER entity. While each country has developed a CER capacity unique to its health system, elements such as the inclusiveness of relevant stakeholders, transparency in operation, independence of the central government and other interests, and adaptability to a changing environment are prerequisites for these entities' successful operation. CONCLUSIONS: While the CER entities evolved separately and have different responsibilities, they have adopted a set of core structural, technical, and procedural principles, including mechanisms for engaging with stakeholders, governance and oversight arrangements, and explicit methodologies for analyzing evidence, to ensure a high-quality product that is relevant to their system.

National Authority for Health: France.

The French National Authority for Health (Haute Autorité de Santé, or HAS) was established to assist France's public institutions in optimizing the basket of reimbursable goods and services and to help health care professionals continuously improve their clinical practice by defining best-care standards and identifying relevant tools and methods. HAS carries out single technology assessment (STA) and multiple technology assessment (MTA), assessing both the intrinsic benefit of the new technology and its effectiveness compared with that of existing technologies. A new treatment may not be covered unless it provides either improved benefit or lower cost, and STA is mandatory before a new drug, device, or medical procedure can be added to the benefit list for sickness funds. While HAS recommendations are advisory, the decision-making bodies (the Ministry of Health or the union of sickness funds) accept its findings in most cases.

Innovative Curative Treatment of Beta Thalassemia: Cost-Efficacy Analysis of Gene Therapy Versus Allogenic Hematopoietic Stem-Cell Transplantation.

Seventy-five percent of patients with beta thalassemia (ß-thalassemia) do not have human leukocyte antigen-matched siblings and until recently had no access to a curative treatment. Gene therapy is a promising treatment that can be proposed to these patients. This study estimates its cost and efficacy. In a monocentric retrospective study and cost-efficacy analysis, this study compared the two-year outcomes and costs of patients with ß-thalassemia treated by gene therapy and hematopoietic stem-cell transplantation (HSCT). Grade III and grade IV complications, hospitalizations, and length of stay were extracted from the hospital discharge data. Costs were estimated from hospital accounting information and national cost studies. A total of seven patients with ß-thalassemia treated between 2009 and 2016 were included, of whom four received gene therapy. Patients treated by gene therapy were older and had fewer complications and hospital admissions. Infectious complications were three times more frequent for patients treated with HSCT than for gene therapy. Average costs were €608,086 for patients treated by gene therapy and €215,571 for HSCT. The total cost of the vector was 48% of the total cost of gene therapy. Gene therapy as a curative alternative for patients lacking human leukocyte antigen-matched donors was costlier but resulted in fewer complications than HSCT.

HTA agencies facing model biases: the case of type 2 diabetes.

When evaluating new drugs or treatments eligible for reimbursement, health technology assessment (HTA) agencies are repeatedly faced with cost-effectiveness analyses that evidence lack of adequate data and modeling biases. The case of type 2 diabetes illustrates this difficulty. In spite of its high disease burden, type 2 diabetes is poorly documented through existing cost-effectiveness analyses. We support this statement by an exhaustive literature review that enables us to precisely pinpoint the limitations of models used for the assessment of newly marketed (and expensive) drugs. We find that models are mostly restricted to surrogate endpoints and based on non-inferiority clinical trial data; they also show biases in the choice of comparators and inclusion criteria. Such limitations undermine the scope and applicability of HTA practice guidelines based on cost-effectiveness evidence. Nevertheless, cost-effectiveness models remain an opportunity to better inform decision makers and to reduce the uncertainty surrounding their decisions. HTA agencies are best placed to provide incentives for companies to improve the quality of the cost-effectiveness studies submitted for pricing and reimbursement decisions. One such incentive is to include stages of discussion between the company and the health authority during the evaluation process.