Acceptability of interventional materials: public participation in public health interventional research / Acceptabilité d'une intervention : exemple de participation des publics en recherche interventionnelle en santé publique

Introduction: The uptake rate of colorectal cancer screening remains insufficient in France and decreases as the level of deprivation increases. Participants' health literacy appears to be an important determinant of screening uptake. Aim of the study: The aim of this study, nested in our multicenter-randomized controlled trial, was to present the development and acceptability of interventional material (training and a pictorial brochure) for general practitioners and healthcare users in disadvantaged geographical areas using a participatory involvement approach. Methods: The development of the brochure and the training was carried out in three stages, two for the development, usability, and acceptability testing and a third for its evaluation with the target audience. We used a qualitative approach based on focus groups and cognitive interviews. The qualitative analysis was based on Morville's "Honeycomb" conceptual model and the COREQ checklist. Results: The development and test of the acceptability of the material enabled us to adjust the content of the training by proposing examples that were more rooted in professional reality, and to produce a brochure that was easy to read, understand, acceptable and adapted to the intervention's targeted audience. Conclusions: This experience illustrates in a concrete way the feasibility of public participation and its value in the context of interventional research, and more generally in the creation of interventional material.

Introduction: Le taux de participation au dépistage du cancer colorectal reste insuffisant en France et diminue à mesure que le niveau de précarité augmente. La littératie en santé est un déterminant important du recours au dépistage. But de l'étude: Cette étude, nichée dans notre essai randomisé multicentrique, a pour but de présenter la procédure d'élaboration (procédé itératif de test d'utilisabilité et d'acceptabilité) et de vérification de l'acceptabilité de l'intervention (formation et brochure imagée) ciblant les médecins généralistes et usagers du soin dans des zones géographiques défavorisées, selon une approche participative. Méthodes: Le développement de la brochure et de la formation a été réalisé en trois étapes : deux pour l'élaboration et tests itératifs d'utilisabilité et acceptabilité et une troisième pour vérifier l'acceptabilité auprès des publics cibles. Nous avons utilisé une approche qualitative par focus group et entretiens individuels cognitifs dont l'analyse repose sur le « nid d'abeille ¼ de Morville et la grille COREQ. Résultats: Le développement itératif et la vérification de l'acceptabilité du matériel nous ont permis, d'une part, de réaliser des ajustements quant au contenu de la formation, en proposant des exemples plus ancrés dans la réalité professionnelle et, d'autre part, de produire une brochure imagée facile à lire et à comprendre, acceptable et adaptée au public ciblé par l'intervention. Conclusions: Cette expérience illustre, de manière concrète, la faisabilité de cette modalité de participation des publics concernés et son intérêt dans le cadre de la recherche interventionnelle et, plus généralement, dans le matériel interventionnel.

Impact of a health literacy intervention combining general practitioner training and a consumer facing intervention to improve colorectal cancer screening in underserved areas: protocol for a multicentric cluster randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer burden worldwide. In France, it is the second most common cause of cancer death after lung cancer. Systematic uptake of CRC screening can improve survival rates. However, people with limited health literacy (HL) and lower socioeconomic position rarely participate. Our aim is to assess the impact of an intervention combining HL and CRC screening training for general practitioners (GPs) with a pictorial brochure and video targeting eligible patients, to increase CRC screening and other secondary outcomes, after 1 year, in several underserved geographic areas in France. METHODS: We will use a two-arm multicentric randomized controlled cluster trial with 32 GPs primarily serving underserved populations across four regions in France with 1024 patients recruited. GPs practicing in underserved areas (identified using the European Deprivation Index) will be block-randomized to: 1) a combined intervention (HL and CRC training + brochure and video for eligible patients), or 2) usual care. Patients will be included if they are between 50 and 74 years old, eligible for CRC screening, and present to recruited GPs. The primary outcome is CRC screening uptake after 1 year. Secondary outcomes include increasing knowledge and patient activation. After trial recruitment, we will conduct semi-structured interviews with up to 24 GPs (up to 8 in each region) and up to 48 patients (6 to 12 per region) based on data saturation. We will explore strategies that promote the intervention's sustained use and rapid implementation using Normalization Process Theory. We will follow a community-based participatory research approach throughout the trial. For the analyses, we will adopt a regression framework for all quantitative data. We will also use exploratory mediation analyses. We will analyze all qualitative data using a framework analysis guided by Normalization Process Theory. DISCUSSION: Limited HL and its impact on the general population is a growing public health and policy challenge worldwide. It has received limited attention in France. A combined HL intervention could reduce disparities in CRC screening, increase screening rates among the most vulnerable populations, and increase knowledge and activation (beneficial in the context of repeated screening). TRIAL REGISTRATION: Registry: ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: 2020-A01687-32 . Date of registration: 17th November 2020.

[Regional differences in hospitalisations for complications of chronic hepatitis C in 2012]. / Disparités régionales des hospitalisations pour complication de l'hépatite chronique C en 2012.

Objective: Only limited recent information is available concerning the regional incidence and prevalence of chronic hepatitis C (CHC), but this information is critical for optimal definition of public health policies for the management of hepatitis C. The objective of this study was to evaluate the feasibility of mapping potential regional differences in the prevalence of CHC and its complications using data from a health administrative database. Methods: The 2012 PMSI MCO hospital database contains information on diagnosis and healthcare resource use, essentially related to all hospitalisations in France. Hospital stays related to CHC were identified on the basis of ICD-10 disease codes. Hospital stays were classified according to stage of liver disease: non-cirrhotic liver disease, compensated cirrhosis, decompensated cirrhosis or hepatocellular carcinoma (HCC). All study variables were documented for each French administrative region in 2012. Results: In 2012, 12,040 patients were hospitalised in France for a reason related to CHC, corresponding to a standardised age- and gender- adjusted prevalence rate of 19.3/100,000 persons. The highest prevalences of CHC and HCC were observed in the Ile de France, Alsace and Provence-Alpes-Côte-d'Azur regions. Conclusions: This study demonstrates the feasibility of using the PMSI database to identify regional differences in the prevalence of CHC. This information may be useful for planning regional healthcare resource provision for CHC.

Chronic hepatitis C: Burden of disease and cost associated with hospitalisations in France in 2012 (The HEPC-LONE study).

BACKGROUND AND OBJECTIVE: This retrospective hospital database analysis aimed to determine the burden and cost of hospitalisations related to chronic hepatitis C (CHC) infections in France in 2012. METHODS: All hospital stays with CHC (ICD-10 code B18.2) coded as the principal, related or significantly associated diagnosis were extracted from the French National Hospital database 2012 (PMSI). Hospitalisations not directly related to CHC were excluded. Patients were assigned to a liver disease stage, namely non-cirrhotic liver disease, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma or post-liver transplantation. Costing was performed using French national tariffs and expressed in 2013 Euros. We documented 22,056 hospital stays involving 12,040 patients who were considered to be directly related to CHC. Of these stays, 11,779 (53.4%) were documented in patients with severe complications (decompensated cirrhosis, hepatocellular carcinoma or liver transplantation). RESULTS AND CONCLUSIONS: The mean number and duration of hospital stays increased with disease severity. Overall, 1181 patients (9.8%) died during hospitalisation. The total cost of hospital stays for CHC was estimated to be € 61 million, of which 26.4% were attributable to hepatocellular carcinoma, 32.5% to post-liver transplantation and 21.0% to decompensated cirrhosis. Compared with a previous analysis in 2009, the number of patients hospitalised fell by 22%, although the patients hospitalised were overall more severely ill. The total cost of hospitalisation decreased by 8%, with a notably marked reduction in the number of biopsies performed (32%). This study illustrates the persistently high burden of CHC infections in France.

What is the impact of disease prevalence upon health technology assessment?

As national budgets for health care will remain under stress for the foreseeable future, health technology assessment (HTA) aimed at offering guidance to policy-making will have an increasing role to play in optimizing resources. The emergence of new treatment paradigms and health technologies, and the prevalence studies which determine when a disease is a current or future burden for patients and the community are in the roots of the HTA process. Analysing studies on screening test strategies and health care policy, this paper revisits two key concepts in epidemiology, prevalence and incidence, in order to show their major impact upon HTA. Utilization of the predictive values of screening tests that include prevalence in their calculations, and analysing all options for screening strategies are necessary in HTA. Cost-effectiveness analyses and statistical models should include potential externalities, especially the impact of prevention and treatment on infectious disease prevalence. Beyond estimates of cost-effectiveness ratios, decision makers also need to know by how much their annual health care budget is likely to increase or decrease in the years following the emergence of new technologies: hence the importance of incidence- or prevalence-based economic evaluations. As new paradigms are occurring, especially in the field of oncology, with treatments targeted to 'small' groups of patients identified through genetic testing, prevalence data are strongly needed. Precise estimates of disease prevalence, in general populations as well as in risk or targeted groups, will therefore be necessary to improve HTA process.

How did chronic hepatitis C impact costs related to hospital health care in France in 2009?

AIMS: To evaluate the health care burden of chronic hepatitis C (CHC) in French hospitals. METHODS: All hospital stays with CHC ICD-10 code were extracted from the 2009 French hospital discharge database and classified in five groups: non-complicated CHC, liver cirrhosis (CIR), hepatocarcinoma (HCC), liver transplantation (LT) and unclassified. Hospital costs were calculated according to the French official prices and expressed in 2010 euro. The economic analysis was carried out from the Social Security point of view. RESULTS: Twenty-seven thousand two hundred and fifty-eight of the 68,683 hospital stays with CHC ICD-10 code corresponding to 15,482 patients were considered as directly related to HCV: 52% for non-complicated CHC, 33% for CIR, 11% for HCC, 2% for LT and 2% unclassified. The total cost of hospital stays for CHC and its complications was estimated at 65,956,938 €. Almost half (47%) of total costs were attributable to CIR while HCC and LT contributed to 18% and 19%, respectively. CONCLUSION: This first analysis of the French hospital discharge database focused on CHC brings new and essential information. It shows that 84% of HCV-related hospital costs are attributable to advanced liver diseases. Together with more efficient therapies, enhancing screening and access to treatment policies could substantially relieve the hospital burden of CHC.

High dose daily interferon-alpha induction and secondary adjunction of ribavirin in treatment-naive patients with chronic hepatitis C. A multicentric, randomised, controlled trial.

OBJECTIVES: To evaluate in naive patients with chronic hepatitis C 1- the efficacy and safety of one month interferon alpha (IFN-alpha) induction regimen; 2- the potential virological benefit of a secondary adjunction of ribavirin among HCV RNA negative patients after 20 weeks of IFN therapy, with or without an initial 4-week IFN induction. MATERIAL AND METHODS: 151 naive HCV-RNA positive patients presenting with biopsy- proven chronic hepatitis C and elevated ALT were randomised in a 2: 1 ratio in two arms: IFN-alpha 3 MU thrice a week (tiw) for 24 weeks (non-induced patients); IFN-alpha 6 MU daily for two weeks, then 3 MU daily for two weeks then 3 MU tiw for 20 weeks (induced patients). At week 24, HCV-RNA negative patients were randomised to receive in addition or not ribavirin 1-1.2 g daily for 24 additional weeks. Induction efficacy was assessed on the early viral response (EVR) defined as undetectable HCV RNA at week 4 then week 20. Ribavirin efficacy was assessed on the proportion of maintained complete response until the end of follow-up, 24 weeks after discontinuation of treatment. Data were analysed on an intent-to-treat basis. RESULTS: Efficacy of IFN-alpha induction: 104 patients were randomised to the non-induction group, 47 to the induction group. Gender, age, genotype distribution and HCV viral load at baseline did not differ significantly between the two groups. There was one treatment discontinuation because of adverse events in induced patients versus four in non-induced patients (P > 0.05). The 4 week EVR was significantly greater in induced patients in patients with HCV genotype 1, 4 or 5 (47% vs 12%, P=0.0002) only. There was no impact of induction in patients with HCV genotype 2 or 3. Efficacy of ribavirin: at week 24, 28 and 26 HCV-RNA negative patients were randomised to addition of ribavirin or not, respectively. Patients randomised to secondary additive ribavirin were more often HCV-RNA negative at the end of follow-up than patients treated with IFN-alpha alone: 18/28 (64%) vs 10/26 (39%); P=0.06. Among patients randomised to bitherapy, the relapse rate was significantly lower in patients with genotype 2 or 3 (0/12 vs 6/13, P=0.01) and not in those with genotype 1, 4 or 5 (5/11 vs 3/6, P=0.99). CONCLUSION: A 4 week IFN-alpha induction significantly increases the EVR rate in patients with HCV genotype 1, 4 or 5. Late secondary adjunction of ribavirin to IFN-alpha for 6 months in HCV-RNA negative patients after 6 months of IFN-alpha significantly decreases the relapse rate in patients with HCV genotype 2 or 3, but not in patients with genotypes 1, 4 or 5.

Independent prospective multicenter validation of biochemical markers (fibrotest-actitest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis C: the fibropaca study.

OBJECTIVES: Fibrotest (FT) and Actitest (AT) are biochemical markers of fibrosis and activity for use as a non-invasive alternative to liver biopsy in patients with chronic hepatitis C virus (HCV). The aim of this study was to perform an external validation of FT and AT and to study the discordances between FT/AT and liver biopsy in patients with chronic hepatitis C. METHODS: A total of 519 consecutive patients with chronic HCV were prospectively included in five centers, with liver biopsy and biochemical markers taken at the same day. Fifteen patients were excluded because their biopsies could not be interpreted. Diagnostic accuracies were assessed by receiver operating characteristic (ROC) curve analysis. RESULTS: Median biopsy size was 15 mm (range: 2-58), with 9 portal tracts (1-37) and 1 fragment (1-12). 46% (230/504) were classified F2-F4 in fibrosis and 39% A2-A3 in activity. FT area under ROC curve for diagnosis of activity (A2-A3), significant fibrosis (F2-F4), and severe fibrosis (F3-F4) were 0.73 [0.69-0.77], 0.79 [0.75-0.82], and 0.80 [0.76-0.83], respectively. Among the 92 patients (18%) with 2 fibrosis stages of discordance between FT and biopsy, the discordance was attributable to FT in 5% of cases, to biopsy in 4%, and undetermined in 9%. CONCLUSIONS: This prospective independent and multicenter study confirms the diagnostic value of FT and AT found in the princeps study and suggests that FT and AT can be an alternative to biopsy in most patients with chronic HCV.

Prevention could be less cost-effective than cure: the case of hepatitis C screening policies in France.

OBJECTIVES: To access the cost-effectiveness of French recommendations for hepatitis C virus (HCV) screening and the extent to which earlier identification of carriers may or not improve the cost-effectiveness of therapeutic strategies. METHODS: Cost-effectiveness analysis were performed using decision-tree analysis and a Markov model. Four alternative strategies were compared: no screening and no treatment; initiation of HCV treatment after the diagnosis of cirrhosis; and two alternative strategies refer to the current French policies of HCV testing, i.e., two enzyme immunoblot assay (EIA) tests in series, or a polymerase chain reaction (PCR) analysis after the first positive EIA test. Costs were computed from the viewpoint of the health care system. The analysis has been applied to populations particularly at risk of infection, as well as the general population. RESULTS: The "wait and treat cirrhosis" strategy was more cost-effective in the general population and in transfusion recipients. The incremental cost-effectiveness ratio of this strategy compared with baseline strategy was 3,476 of euros and Euro15,300 in respective cohorts. Considering the HCV screening strategy, the additional cost would be of Euro4,933 and Euro240,250 per additional year of life saved, respectively. In the intravenous drug user (IDU) population, the "two ElA" screening strategy was the more cost-effective alternative, with an additional cost of Euro3,825 per additional year of life saved. CONCLUSIONS: HCV screening would be discarded for transfusion recipients but should be encouraged for IDUs and also for the general population, in which the additional cost of screening is an order of magnitude more acceptable.