Coverage rate of opportunistic and organised breast cancer screening in France: Department-level estimation.

OBJECTIVE: In France, the national breast cancer screening programme (NBCSP), targeting women aged 50-74 years was rolled out nationwide in 2004. It aims at reducing breast cancer mortality. In addition to the NBCSP, the use of opportunistic screening is permitted in France. The objective of this study is to estimate both opportunistic use and overall coverage rates of breast cancer screening, among women 40-84 years of age, in France. METHODS: The French medico-administrative health data system (SNDS) was used to identify women performing an opportunistic or organised mammography screening in France in 2016-2017. RESULTS: The two-yearly opportunistic mammography screening is 18 % among women aged 40-84; it is 11 % among women aged 50-74, i.e., the target age range for organised screening, 36 % among women aged 40-49 and 13 % among women aged 75-84. The overall two-yearly screening coverage is 48 % for all women aged 40-84; it is 60 % among women aged 50-74, 36 % among women 40-49 and 16 % for those aged 75-84. Geographical variations in screening are lessened when the two screening strategies are considered, as they balance each other. CONCLUSION: Although coverage in the NBCSP is around 50 % in France, more than one third of the women make use of opportunistic screening within and outside the target age range. Organized screening appears to improve equity of access to mammography screening service. The lack of data on opportunistic screening practices hinders the evaluation of French screening practices as a whole.

Updated evidence-based recommendations for cervical cancer screening in France.

INTRODUCTION: A national organized cytology-based cervical cancer screening program was launched in 2018 and rollout is ongoing. Concomitantly, the High Authority for Health (HAS) recently assessed new evidence on primary HPV testing to update screening recommendations. METHODS: The HAS commissioned systematic reviews and meta-analyses to evaluate the effectiveness of primary HPV screening; accuracy of HPV testing on self-samples; effectiveness of self-sampling to reach underscreened women; and triage strategies to manage HPV-positive women. Recommendations developed by the HAS were reviewed by a multidisciplinary group. RESULTS: Compared with cytology screening, HPV screening is more sensitive to detect precancers but less specific. In women aged ≥30, if the test is negative, HPV screening greatly reduces the risk of developing precancer and cancer for at least 5 years. HPV testing, using validated PCR-based assays, is as sensitive and slightly less specific on self-samples than on clinician-taken samples. Self-sampling is more effective to reach underscreened women than sending invitations to have a specimen taken by a clinician. Two-time triage strategies ensure a sufficiently high risk if triage-positive to justify referral and low risk if triage-negative allowing release to routine screening. CONCLUSIONS: The HAS recommends three-yearly cytology screening for women aged 25-29 and HPV screening for those aged 30-65 with an extension of the screening interval to 5 years if the HPV test is negative. Self-sampling should be offered to underscreened women aged ≥30. HPV-positive women should be triaged with cytology. Those with abnormal cytology should be referred for colposcopy and those with normal cytology re-tested for HPV 12 months later. Recommendations for implementation of HPV-based screening in the organized program are provided.

Breast cancer screening programme participation and socioeconomic deprivation in France.

The objective was to quantify the relationship between deprivation and national breast cancer screening programme (NBCSP) participation at an ecological level in mainland France. Data from 4,805,390 women-living in 36,209 municipalities within 95 departments-participating in the 2013-2014 NBCSP were analysed using the French Deprivation Index (FDep). FDep population quintiles by municipality were computed to describe NBCSP participation according to deprivation. To better examine the relationship between continuous value of deprivation index and participation rates at the municipality level, we built a generalized linear mixed model. Geographical variations in participation rates were marked. The national standardized participation rate was higher in the intermediate quintiles (55%), 45% for the least deprived one and 52% for the most deprived one. Using our model, we also obtained an inverted U-curve for the relationship between NBCSP participation and municipality deprivation: participation was lower for both the least and most deprived municipalities. This relationship was also observed for each of the two subpopulations-urban municipalities and rural ones-considered separately. Introducing the FDep in the model reduced slightly the unexplained variations in participation rates between departments and between municipalities (with a proportional change in variance of 14% and 12% respectively). We highlight major disparities in departmental participation rates and FDep/participation profiles. However, deprivation appears to have only little influence on geographical variation in participation rates. There is a need to further understand the factors affecting geographical variation in participation rates, in particular the use of opportunistic screening.

Population-based organized cervical cancer screening pilot program in France.

In France, cervical cancer screening is recommended every 3 years for women aged 25-65 years. With the exception of a few local organized programs, screening is mainly opportunistic. In view of setting up a nationwide population-based organized screening program, a pilot intervention was implemented in nine geographic areas using a common protocol. Women aged 25-65 years who had not undergone a cytological screening in the past 3 years were invited for screening during 2010-2012 and reminded up to 1 year after the initial invitation. Cytological results and follow-up data were collected up to the end of 2014 for all women screened irrespective of whether spontaneously or following invitation. Aggregate data were centralized nationally. Among the 2.4 million women from the total target population aged 25-65 years, 1.3 million were invited for screening. The overall screening coverage during 2010-2012 was 62.3%, with wide variations across geographic areas, ranging from 41.6 to 72.5%. Initial invitations and reminders enabled nearly 280 000 women to be screened, corresponding to an estimated increase in coverage of 12% points. Overall, 4.2% of the women screened had an abnormal smear. A total of 5180 high-grade cervical precancers and 323 invasive cervical cancers were reported, corresponding to detection rates of, respectively, 623 and 39 per 100 000 women screened 3-yearly. This study indicates that such organized screening may markedly improve the uptake of cervical cancer screening. On the basis of this pilot program, nationwide organized cervical cancer screening is currently being rolled out in France.

Health-state utility estimates for health technology assessment: a review of the manufacturers' submissions to the French National Authority for Health.

BACKGROUND: Our aim was to review the selection and methods used for deriving health state utility (HSU) estimates included in the cost-utility analyses (CUA) submitted by manufacturers to the National Authority for Health (HAS) during the first 2 years after the introduction of the economic evaluation for price setting in France. METHODS: We reviewed all manufacturers' submissions that included a CUA and were assessed by HAS by the end of October 2015 (N = 34). We reviewed the identification, selection, and methods used to estimate HSU and compared them with those recommended by HAS. RESULTS: A literature review to identify HSU was reported in only 13 (38%) submissions. The instruments for describing HSU were a preference-based generic instrument in 20 (59%) submissions; vignettes in five (15%); a condition-specific instrument in three (9%); and a combination of instruments in six (18%). The valuation perspective was the general population in 26 (76%) submissions; in only nine (26%) submissions, the valuation set was derived from the French general population. CONCLUSIONS: We identified numerous concerns in the selection, valuation and use of HSU, as well as a frequent lack of clarity in the methods used. Most submissions (79%) included HSU that did not meet HAS recommendations.

Exploring Uncertainty in Economic Evaluations of Drugs and Medical Devices: Lessons from the First Review of Manufacturers' Submissions to the French National Authority for Health.

OBJECTIVES: The objective of this paper was to evaluate how uncertainty has been accounted for in the cost-effectiveness analyses (CEAs) submitted by manufacturers to the French National Authority for Health (HAS) and to identify recurring concerns in these submissions. METHODS: We used a cross-sectional design to evaluate manufacturers' submissions from the beginning of the evaluation process in October 2013 to the end of May 2015 (n = 28). The sources of uncertainty attached to these CEAs were categorized and assessed. Relevant data were extracted independently by two assessors. RESULTS: Adherence to the HAS reference case was generally considered to be acceptable. Methodological uncertainty and parameter uncertainty were the sources of uncertainty that were most frequently explored by manufacturers. The quality of reporting of deterministic sensitivity analysis and probabilistic sensitivity analysis varied substantially across submissions, with a frequent lack of justification of the plausible range of parameter point estimates in 12 submissions (43 %). Structural uncertainty was explored much less frequently. Concerns related to omission of either important clinical events or relevant health states or extrapolation of the effects of the technology beyond the time horizon of the clinical trials were identified in 16 submissions (57 %). CONCLUSIONS: This study presented a characterization of the treatment of uncertainty for the first 28 manufacturers' submissions to the HAS. This work identified important concerns regarding the exploration of sources of uncertainty. The findings may help manufacturers to improve the quality of their submissions and may provide useful insights for extending guidelines on uncertainty analysis in CEAs submitted to the HAS.

Is There a European View on Health Economic Evaluations? Results from a Synopsis of Methodological Guidelines Used in the EUnetHTA Partner Countries.

OBJECTIVES: The objectives of this study were to review current methodological guidelines for economic evaluations of all types of technologies in the 33 countries with organizations involved in the European Network for Health Technology Assessment (EUnetHTA), and to provide a general framework for economic evaluation at a European level. METHODS: Methodological guidelines for health economic evaluations used by EUnetHTA partners were collected through a survey. Information from each guideline was extracted using a pre-tested extraction template. On the basis of the extracted information, a summary describing the methods used by the EUnetHTA countries was written for each methodological item. General recommendations were formulated for methodological issues where the guidelines of the EUnetHTA partners were in agreement or where the usefulness of economic evaluations may be increased by presenting the results in a specific way. RESULTS: At least one contact person from all 33 EUnetHTA countries (100 %) responded to the survey. In total, the review included 51 guidelines, representing 25 countries (eight countries had no methodological guideline for health economic evaluations). On the basis of the results of the extracted information from all 51 guidelines, EUnetHTA issued ten main recommendations for health economic evaluations. CONCLUSIONS: The presented review of methodological guidelines for health economic evaluations and the consequent recommendations will hopefully improve the comparability, transferability and overall usefulness of economic evaluations performed within EUnetHTA. Nevertheless, there are still methodological issues that need to be investigated further.

HIV testing practices as reported by HIV-infected patients in four European countries.

HIV testing constitutes an important strategy to control the HIV epidemic, which therefore merits an observation of HIV testing practices to help improve testing effectiveness. In 2008, a cross-sectional survey among recently diagnosed (≤ 3 years) HIV-infected patients was conducted in Belgium, Estonia, Finland and Portugal. Participants were questioned about reasons for HIV testing, testing place and testing conditions. Univariate and multivariate analyses were performed. Out of 1460 eligible participants, 629 (43%) were included. Forty-one per cent were diagnosed late and 55% had never undergone a previous HIV test with perceived low risk being the primary reason for not having been tested earlier. Heterogeneity in HIV testing practices was observed across countries. Overall, tests were most frequently conducted in primary care (38%) and specialised clinics (21%), primarily on the initiative of the health care provider (65%). Sixty-one per cent were tested with informed consent, 31% received pretest counselling, 78% received post-test counselling, 71% were involved in partner notification and 92% were in care three months after diagnosis. The results showed that HIV testing is done in a variety of settings suggesting that multiple pathways to HIV testing are provided. HIV testing practice is being normalised, with less focus on pretest counselling, yet with emphasis on post-test follow-up. Major barriers to testing are centred on the denial of risk. Efforts are needed to concurrently promote public awareness about HIV risk and benefits of HIV testing and train clinicians to be more proactive in offering HIV testing.

Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France.

BACKGROUND: Five diseases are currently screened on dried blood spots in France through the national newborn screening programme. Tandem mass spectrometry (MS/MS) is a technology that is increasingly used to screen newborns for an increasing number of hereditary metabolic diseases. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is among these diseases. We sought to evaluate the cost-effectiveness of introducing MCADD screening in France. METHODS: We developed a decision model to evaluate, from a societal perspective and a lifetime horizon, the cost-effectiveness of expanding the French newborn screening programme to include MCADD. Published and, where available, routine data sources were used. Both costs and health consequences were discounted at an annual rate of 4%. The model was applied to a French birth cohort. One-way sensitivity analyses and worst-case scenario simulation were performed. RESULTS: We estimate that MCADD newborn screening in France would prevent each year five deaths and the occurrence of neurological sequelae in two children under 5 years, resulting in a gain of 128 life years or 138 quality-adjusted life years (QALY). The incremental cost per year is estimated at €2.5 million, down to €1 million if this expansion is combined with a replacement of the technology currently used for phenylketonuria screening by MS/MS. The resulting incremental cost-effectiveness ratio (ICER) is estimated at €7 580/QALY. Sensitivity analyses indicate that while the results are robust to variations in the parameters, the model is most sensitive to the cost of neurological sequelae, MCADD prevalence, screening effectiveness and screening test cost. The worst-case scenario suggests an ICER of €72 000/QALY gained. CONCLUSIONS: Although France has not defined any threshold for judging whether the implementation of a health intervention is an efficient allocation of public resources, we conclude that the expansion of the French newborn screening programme to MCADD would appear to be cost-effective. The results of this analysis have been used to produce recommendations for the introduction of universal newborn screening for MCADD in France.

Chlamydia control activities in Europe: cross-sectional survey.

BACKGROUND: Chlamydia is the most commonly reported bacterial sexually transmitted infection in Europe. The objective of the Screening for Chlamydia in Europe (SCREen) project was to describe current and planned chlamydia control activities in Europe. METHODS: The authors sent a questionnaire asking about different aspects of chlamydia epidemiology and control to public health and clinical experts in each country in 2007. The principles of sexually transmitted infection control were used to develop a typology comprising five categories of chlamydia control activities. Each country was assigned to a category, based on responses to the questionnaire. RESULTS: Experts in 29 of 33 (88%) invited countries responded. Thirteen of 29 countries (45%) had no current chlamydia control activities. Six countries in this group stated that there were plans to introduce chlamydia screening programmes. There were five countries (17%) with case management guidelines only. Three countries (10%) also recommended case finding amongst partners of diagnosed chlamydia cases or people with another sexually transmitted infection. Six countries (21%) further specified groups of asymptomatic people eligible for opportunistic chlamydia testing. Two countries (7%) reported a chlamydia screening programme. There was no consistent association between the per capita gross domestic product of a country and the intensity of chlamydia control activities (P = 0.816). CONCLUSION: A newly developed classification system allowed the breadth of ongoing national chlamydia control activities to be described and categorized. Chlamydia control strategies should ensure that clinical guidelines to optimize chlamydia diagnosis and case management have been implemented before considering the appropriateness of screening programmes.

HIV testing in Europe: mapping policies.

OBJECTIVES: In the absence of treatment and in the context of discrimination, HIV testing was embedded within exceptional procedures. With increasing treatment effectiveness, early HIV diagnosis became important, calling for the normalization of testing. National HIV testing policies were mapped to explore the characteristics and variations across European countries. METHODS: Key informants within the health authorities of all EU/EEA countries were questioned on HIV testing policies, which were assessed within a conceptual framework and the level of exceptionalism and normalization was scored based on defined attributes. RESULTS: Twenty-four out of 31 countries participated in the survey. Policies tended to support confidential voluntary testing, informed consent, and counselling. In the majority of countries, specific groups were targeted for provider-initiated testing. Taking together all attributes of HIV testing, 14 countries obtained a high score for exceptionalism, while only 3 achieved a high score on normalization. Italy, Lithuania and Romania had primarily exceptional procedures; Norway leant more towards normalization; Netherlands, the United Kingdom, and Denmark scored high in both. CONCLUSIONS: In most EU/EEA countries, policies are integrating HIV testing in health care settings, through voluntary and targeted testing strategies. Current HIV testing policies exhibited a high level of exceptionalism with varying degrees of normalization. Further research should compare HIV testing policies with practices.

The epidemiology of HIV and AIDS reports in migrants in the 27 European Union countries, Norway and Iceland: 1999-2006.

BACKGROUND: To describe the epidemiology of HIV and AIDS by geographical origin in the EU, 1999-2006. METHODS: AIDS and HIV cases from the EU 27, Norway and Iceland reported to European Centre for Epidemiological Monitoring of AIDS were analysed. RESULTS: Of 75,021 AIDS reports over 1999-2006, 35% were migrants. Of 2988 heterosexual AIDS reports in 2006, 50% were migrants, largely from Sub-Saharan Africa (SSA), 20% of 1404 AIDS cases in men who have sex with men (MSM) were migrants from Latin-America and Western Europe. Of 57 mother-to-child transmission (MTCT) AIDS cases, 23% were from SSA. AIDS cases decreased from 1999 to 2006 in natives (42%), Western Europeans (40%) and North Africa and Middle East (34%), but increased in people from SSA (by 89%), Eastern Europe (by 200%) and Latin-America (50%). Of 17,646 HIV infections in men and 9066 in females in 2006, 49 and 76% were migrants, largely from SSA. Of 169 MTCT infections, 41% were from SSA. CONCLUSION: Migrants, largely from SSA, represent a considerable proportion of AIDS and HIV reports in EU, especially among heterosexual and MTCT infections. Their contribution is higher among female reports. A substantial percentage of diagnoses in MSM are migrants, largely from Western Europe and Latin-America.

How to best define target populations of medicines in view of their coverage by the national health insurance scheme?

The target population of a medicine may include different populations that may partially overlap including the population that has been evaluated in the clinical trials, the population for which the medicine provides an actual benefit (SMR), that for which the drug provides an improvement of the actual benefit (ASMR), etc. The definition of the target population in both qualitative and quantitative terms has key public health and economic implications. Recommendations are made to shed light on the definitions, to clarify the requests of the public decision makers and to improve the methods and the sources allowing the quantification of target populations.

Barriers to HIV testing in Europe: a systematic review.

BACKGROUND: In the European Union (EU) and neighbouring countries, HIV/AIDS, of all infectious diseases, has one of the highest morbidity and mortality rates. An estimated 30% of people living with HIV are unaware of their infection, and may therefore not benefit from timely treatment or may transmit HIV to others, unknowingly. Evidence shows that opportunities are being missed to diagnose HIV infections in EU Member States, particularly in regular health care settings. There is a need to better understand the barriers to HIV testing and counselling with the aim to contribute to the decrease of the number of undiagnosed people. METHODS: A systematic review of literature on HIV testing barriers in Europe was conducted, applying a free text strategy with a set of search terms. RESULTS: A total of 24 studies published in international peer-reviewed journals and meeting the review's eligibility criteria were identified. Fourteen studies report on barriers at the level of the patient; six on barriers at health care provider level and seven on institutional barriers referring to the policy level. The barriers described are centralized around low-risk perception; fear and worries; accessibility of health services, reluctance to address HIV and to offer the test; and scarcity of financial and well trained human resources. CONCLUSIONS: Some barriers to HIV testing and counselling have been illustrated in the literature. Nevertheless, there is lack of structured information on barriers considering (i) legal, administrative and financial factors, (ii) attitudes and practices of health care providers and (iii) perception of patients. Such data is critical to improve effectiveness of HIV testing and counselling.

Trends in HIV prevalence in blood donations in Europe, 1990-2004.

INTRODUCTION: The comparison of HIV prevalence among blood donations in European countries provides an indication of the relative safety of the blood supply in different countries and over time. METHODS: Data between 1990 and 2004 on annual numbers of blood donations and HIV prevalence in blood donations were collected from national correspondents in the 52 countries of the World Health Organization European Region. Data are presented for three geographic areas: West, Centre and East. RESULTS: Since 1990, the number of blood donations has declined by 43% in the East and by 26% in the Centre, while remaining relatively stable in the West. In 2004, the number of blood donations was more than twice as high in the West in comparison with the East and the Centre. Over the same period, HIV prevalence among blood donations increased dramatically in the East, remained stable in the Centre and declined in the West. Since 2001, HIV prevalence levels of more than 10 per 100 000 donations were reported from six countries in the East (with a high of 128/100 000 in Ukraine), whereas in the rest of Europe the reported national HIV prevalence levels were lower than 10/100 000 donations. The prevalence of HIV was much lower among donations from repeat donors than from first-time donors. CONCLUSION: In some eastern European countries public health interventions, such as deferring individuals at risk of HIV infection from donating blood and constituting a pool of regular donors, are urgently needed to assure the safety of the blood supply.

Cost-effectiveness of HIV post-exposure prophylaxis in France.

OBJECTIVE: To assess the cost-effectiveness of HIV post-exposure prophylaxis (PEP) in France. METHODS: We used a decision tree to evaluate, from a society's perspective, the cost of PEP per quality-adjusted life-year (QALY) saved. We used 1999-2003 PEP surveillance data and literature-derived data on per event transmission probabilities, PEP efficacy and quality of life with HIV. HIV prevalence and lifetime cost of HIV/AIDS management in the HAART era were derived from French studies. We assumed that mean life expectancy in full health was 65 years among uninfected individuals and that the mean survival time after HIV infection was 22.5 years. The costs of PEP drugs and follow-up were derived from the French public sector. A 3% annual rate was used to discount future costs and effects. RESULTS: During 1999-2003, PEP was prescribed to 8958 individuals (heterosexual sex: 47.6%; homosexual sex: 28.4%; occupational exposure: 23.4%; drug injection: 0.6%); of those, 2143 were exposed to a known HIV-infected source. PEP was estimated to prevent 7.7 infections and saved 64.5 QALY at a net cost of euro 5.7 million, resulting in an overall cost-effectiveness ratio of euro 88,692 per QALY saved. PEP was cost saving for 4.4% of cases and cost effective (< euro 50,000 per QALY) in a further 11.3% of cases. In contrast, 72 and 52% of prescriptions had a cost-effectiveness ratio exceeding euro 200,000 and euro 2 millions, respectively, per QALY saved. CONCLUSION: Overall, the French PEP programme is only moderately cost effective. PEP guidelines should be revised to target high-risk exposures better.