Robert Launois

Construction and validation of a quality of life questionnaire in chronic lower limb venous insufficiency (CIVIQ).

Quality of life may be considerably reduced in patients who are suffering from chronic lower limb venous insufficiency, although existing generic quality of life instruments (NHP, SF-36 or SIP) cannot completely identify their specific complaints. The Chronic Venous Insufficiency Questionnaire (CIVIQ) has been developed by iterative process. First, a pilot group of 20 patients was used to identify a number of important features of quality of life affected by venous insufficiency, other than physical symptoms of discomfort. A second study involving 2,001 subjects was used to reduce the number of items. Subjects were asked to score both the severity of their problems and the importance they attributed to each problem on a 5-point Likert scale. The importance items found in patients with venous insufficiency were subjected to factorial analyses (PCA, PAF). The final version is a 20-item self-administered questionnaire which explores four dimensions: psychological, physical and social functioning and pain. Internal consistency of the questionnaire was validated for each dimension (Cronbachs alpha > 0.820 for three out of four factors). Reproducibility was confirmed in a 60 patient test-retest study. Pearsons correlation coefficients for both the four dimension subscales and for the global score at 2-week intervals were greater than 0.940. Finally, the questionnaire was tested in a randomized clinical trial of 934 patients in order to assess responsiveness and the convergent validity of the instrument, together with the patients own quality of life. This study demonstrated that convergence was valid: Pearsons correlation coefficients between clinical score differences and quality of life score differences were small (from 0.199–0.564) but were statistically different from 0 (p<0.001). Standardized response mean (SRM) and effect size (ES) were calculated to assess sensitivity to change. SRM and ES both demonstrated considerble responsiveness to change (>0.80). Reliability, face, content, construct validity and responsiveness were also determined for this specific quality of life questionnaire relating to venous insufficiency. Results suggest that this questionnaire may be used with confidence to assess quality of life in clinical trials on chronic venous insufficiency.

A cost-utility analysis of second-line chemotherapy in metastatic breast cancer. Docetaxel versus paclitaxel versus vinorelbine.

SummaryThe aim of this study was to determine the incremental effectiveness, the incremental health-related quality of life (differences in quality-adjusted progression-free survival between treatments), the incremental cost and the incremental cost-effectiveness and cost-utility ratios, for docetaxel, paclitaxel and vinorelbine, when these drugs were used as second-line treatment in patients with metastatic breast cancer.In the absence of comparative direct evidence of the relative efficacy of docetaxel, paclitaxel and vinorelbine in this setting, a model was designed to determine the effects of the 3 interventions on health outcome and cost. A Markov process model, based on 53 disease states, was thus constructed to evaluate the socioeconomics of the 3 treatment regimens.The model allows assessments from the start of second-line chemotherapy until death. Costs were evaluated from the combined view of the healthcare system and the patient. Direct nonmedical and indirect costs were excluded. Consumption per episode of care was estimated by retrospective analysis of 153 medical reports from 5 different hospitals. Hospital costs were allocated values from the national accounting costs by diagnosis-related group (DRG). The content of the health states was based on the multiattribute health states classification system (MASH). Preference values were assigned by application of a standard reference lottery using 20 oncological nurses as proxies for the patients. The health-related quality-of-life score was used as a quality adjustment weighting factor to calculate quality-adjusted progression-free survival associated with the 3 different regimens.Docetaxel reduces the time spent in progression, decreases the number of complications due to progressive disease and thereby provides better quality of life. It provides a benefit of 57 disease- and discomfort-free days compared with vinorelbine and 22 days compared with paclitaxel.Docetaxel may be thought of as self-financing as a result of savings in hospital admissions, providing net savings of 6800 French francs (FF; 1993 values) compared with expenditure associated with vinorelbine treatment and FF700 compared with the equivalent figures for paclitaxel.

Budget impact model of rituximab after failure of one or more TNFα inhibitor therapies in the treatment of rheumatoid arthritis

OBJECTIVES To estimate the budget impact implied by the introduction of rituximab after failure of one or more anti-TNFalpha therapies in the perspective of the French health care system. METHODS A Markov model reproduced the course, over 4years, of patients treated either by infliximab, etanercept, adalimumab or RTX, after failure of one or more anti-TNFalpha therapies, in a multicentric study. A sensitivity analysis was developed to account for patients in 3rd and subsequent lines of treatment who are expected to consume more healthcare resources. RESULTS When RTX is not used, total annual medical cost is euro16,555 per patient, euro13,206 of which are dedicated to drug acquisition. When RTX is the only treatment in use, these costs decrease respectively to euro11,444 and euro7469. Total savings per patient and per year is euro5000. Over 4 years, total savings for the targeted population reach euro118M. In the sensitivity analysis, the difference between H2 and H2-coeff 2 (20%) reaches euro5,400,000 in total direct costs during the first year of simulation. This difference decreases along the period, to reach euro2,400,000 the fourth year of simulation, and is due to the fact that rituximab acquisition costs are independent from the treatment line. CONCLUSION If TNFalpha inhibitors were the only treatment available, the annual global cost of treatment would be euro16,555 per patient versus euro11,444 for patients treated exclusively with rituximab. RTX is expected to produce important savings (-31%) if used after failure of one or more TNFalpha therapies. This is mainly due to its lower drug acquisition cost. These savings could increase with the development of rituximab in earlier stages of treatment.

Cost-effectiveness of activated protein C in real-life clinical practice.

BackgroundRecombinant human activated protein C (rhAPC) has been reported to be cost-effective in severely ill septic patients in studies using data from a pivotal randomized trial. We evaluated the cost-effectiveness of rhAPC in patients with severe sepsis and multiple organ failure in real-life intensive care practice.MethodsWe conducted a prospective observational study involving adult patients recruited before and after licensure of rhAPC in France. Inclusion criteria were applied according to the label approved in Europe. The expected recruitment bias was controlled by building a sample of patients matched for propensity score. Complete hospitalization costs were quantified using a regression equation involving intensive care units variables. rhAPC acquisition costs were added, assuming that all costs associated with rhAPC were already included in the equation. Cost comparisons were conducted using the nonparametric bootstrap method. Cost-effectiveness quadrants and acceptability curves were used to assess uncertainty of the cost-effectiveness ratio.ResultsIn the initial cohort (n = 1096), post-license patients were younger, had less co-morbid conditions and had failure of more organs than did pre-license patients (for all: P < 0.0001). In the matched sample (n = 840) the mean age was 62.4 ± 14.9 years, Simplified Acute Physiology Score II was 56.7 ± 18.5, and the number of organ failures was 3.20 ± 0.83. When rhAPC was used, 28-day mortality tended to be reduced (34.1% post-license versus 37.4% pre-license, P = 0.34), bleeding events were more frequent (21.7% versus 13.6%, P = 0.002) and hospital costs were higher (€47,870 versus €36,717, P < 0.05). The incremental cost-effectiveness ratios gained were as follows: €20,278 per life-year gained and €33,797 per quality-adjusted life-year gained. There was a 74.5% probability that rhAPC would be cost-effective if there were willingness to pay €50,000 per life-year gained. The probability was 64.3% if there were willingness to pay €50,000 per quality-adjusted life-year gained.ConclusionThis study, conducted in matched patient populations, demonstrated that in real-life clinical practice the probability that rhAPC will be cost-effective if one is willing to pay €50,000 per life-year gained is 74.5%.

Construction and international validation of CIVIQ-14 (a short form of CIVIQ-20), a new questionnaire with a stable factorial structure

BackgroundThe factorial instability of the CIVIQ-20 social dimension in different populations has necessitated the development of a new stable questionnaire to interpret results from international studies.ObjectiveConstruction of a stable and psychometrically validated questionnaire from CIVIQ-20.Methods and major findingsA prospective, international study was used to construct a stable CIVIQ scale and to validate its psychometric properties. An iterative process was implemented to eliminate the more unstable items (six), and the social and physical dimensions were combined. The resulting instrument comprised 14 items, split into three dimensions (pain, physical, and psychological), and was named CIVIQ-14. The stability of the CIVIQ-14 factorial structure was confirmed in Polish, Czech, Spanish, and French populations using principal component analysis and multitrait/multimethod analysis. Psychometric assessment demonstrated that CIVIQ-14 was reliable (intra-class coefficient >0.8; weighted kappa >0.8), valid (correlation coefficients between dimension scores and clinical severity scores between 0.3 and 0.6), and sensitive (effect sizes >0.6 for psychological dimension; >0.8 for the other dimensions).ConclusionCIVIQ-14 is a reliable, valid, and sensitive instrument applicable to international studies of patients with chronic venous disease.

Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis with multiple organ failure

OBJECTIVES The aim of this study was to estimate the expected cost and clinical benefits associated with the use of drotrecogin alfa (activated) (Xigris; Eli Lilly and Company; Indianapolis, IN) in the French hospital setting. METHODS The recombinant human activated PROtein C Worldwide Evaluation in Severe Sepsis (PROWESS) study results (1271 patients with multiple organ failure) were adjusted to 9,948 hospital stays from a database of Parisian area intensive-care units (ICUs)-the CubRea (Intensive Care Database User Group) database. The analysis features a decision tree with a probabilistic sensitivity analysis. RESULTS The cost per life year gained (LYG) of drotrecogin treatment for severe sepsis with multiple organ failure (European indication) was estimated to be dollars 11,812. At the hospital level, the drug is expected to induce an additional cost of dollars 7545 per treated patient. The incremental cost-effectiveness ratio ranges from dollars 7873 per LYG for patients receiving three organ supports during ICU stay to dollars 17,704 per LYG for patients receiving less than two organ supports. CONCLUSIONS Drotrecogin alfa (activated) is cost-effective in the treatment of severe sepsis with multiple organ failure when added to best standard care. The cost-effectiveness of the drug increases with baseline disease severity, but it remains cost-effective for all patients when used in compliance with the European approved indication.

Chemonucleolysis versus Surgical Discectomy for Sciatica Secondary to Lumbar Disc Herniation

SummaryThe objective of this study was to evaluate and compare the cost and effects on quality of life [using quality-adjusted life years (QALYs)] of 2 treatments for sciatica secondary to lumbar disc herniation: chemonucleolysis and surgical discectomy.The design involved a combination of decision analysis and Rosser index. with assessment of probabilities from long term clinical series. Utility was based on patients’ subjective assessment using a simplified self-administered Health Measurement Questionnaire (HMQ). 146 patients from 7 hospitals were enrolled, 2 to 3 months after chemonucleolysis or surgery. The end-points used were cost and QALYs for each intervention, every year for years 1 to 7.At the time of analysis (1990), the total cost of surgical discectomy was FF15 400. compared with FF8000 for chemonucleolysis.After 1 year, and including the costs of reoperation for failure and relapse and long term medical costs for the non-reoperated unsatisfactory results. discectomy costs were almost 40% higher than those of chemonucleolysis. Ratios remain unchanged after 7 years. QALY results reveal an additional benefit of 52 days of good health associated with chemonucleolysis.

Systematic review and bivariate/HSROC random-effect meta-analysis of immunochemical and guaiac-based fecal occult blood tests for colorectal cancer screening.

Background Current literature evidences higher accuracy of immunological (iFOBT) vis-à-vis guaiac-based (gFOBT) fecal occult blood tests for colorectal cancer (CRC) screening. Few well-designed head-to-head comparisons exist. Aim This meta-analysis assesses the performances of two iFOBTs compared with an established gFOBT using colonoscopy as the gold standard. Methods We mobilized a bivariate and a hierarchical summary receiver operating characteristic (HSROC) model. Positive likelihood ratio (LR+) and negative likelihood ratio (LR−) and diagnostic odds ratios were back-calculated. We constructed bivariate credibility ellipses in the HSROC space and calculated areas under the curve to obtain a global measure of test performance. Estimates are presented at 95% credibility levels. Results We included and analyzed 21 studies. OC-Sensor was the best test for CRC screening, with high sensitivity (0.87; 95% credibility interval: 0.73–0.95) and specificity (0.93; 95% credibility interval: 0.84–0.96), optimal LR+ (12.01) and LR− (0.14), and a high diagnostic odds ratio (88.05). Bivariate credibility ellipses showed OC-Sensor’s dominance over Hemoccult (sensitivity: 0.47; 95% credibility interval: 0.37–0.58; specificity: 0.93; 95% credibility interval: 0.91–0.95). Conclusion Our findings support the use of OC-Sensor for CRC detection. The diagnostic estimates obtained may be extended to derive model parameters for economic decision models and to offer insight for future clinical and public health decision making. Our findings could influence the future of FOBTs within the CRC screening arsenal.

Cost-effectiveness analysis of rifaximin-α administration for the reduction of episodes of overt hepatic encephalopathy in recurrence compared with standard treatment in France.

Background: Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that occurs most often in a context of acute or chronic liver disease. Despite the seriousness of the pathology, only a few treatments have been developed for improving its management. Rifaximin-α is the first treatment that has been clinically developed for overt HE (OHE) episodes. Recent results of clinical studies demonstrated its significant improvement in the health-related quality of life. The objective of the current study was to estimate the long-term cost-effectiveness of rifaximin-α used in combination with lactulose compared with lactulose monotherapy in cirrhotic patients, who have experienced at least two prior OHE events. Methods: A Markov model was used to estimate rifaximin-α cost-effectiveness, evaluating it from the perspective of all contributors as recommended by French health technology assessment guidelines. Costs were based on current French treatment practices. The transition between health states was based on the reanalysis of the rifaximin-α pivotal clinical trials RFHE3001 and RFHE3002. The main outcome of the model was cost per quality adjusted life year (QALY). Results: The results indicate that rifaximin-α is a cost-effective treatment option with an incremental cost per QALY gained of €19,187 and €18,517 over two different time horizons (2 and 5 years). The robustness of the model was studied using probabilistic sensitivity analysis. Conclusion: For the societal willingness to pay threshold of €27,000 per QALY gained, rifaximin-α in combination with lactulose is a cost-effective and affordable treatment for patients who have experienced at least two prior overt HE episodes.

Assessment of the Cost Effectiveness of Travoprost versus Latanoprost as Single Agents for Treatment of Glaucoma in France

Background and objective:Control of intraocular pressure (IOP) is a major factor in avoiding visual impairment related to glaucoma. Both the cost and the effectiveness of therapy should be considered when initiating this lifelong treatment. The aim of this study was to assess the cost effectiveness of travoprost versus latanoprost as single agents for the treatment of glaucoma in France.Methods:Two surveys, one documenting efficacy and the other costs, were used to provide data for a Markov model. The model reproduced the 5-year course of patients receiving a prostaglandin analogue, travoprost or latanoprost, as monotherapy. The effectiveness criterion was fitted with a Weibull distribution from a national study. Transition probabilities and costs per treatment line were extracted from two French observational databases. Bootstrap techniques were implemented to drive the probabilistic sensitivity analyses. The study compared both treatments given once daily as monotherapy to ambulatory patients with primary open-angle glaucoma or ocular hypertension. The main outcome measure was mean time to treatment change (MTTC). Possible treatment changes were the addition of adjunctive medication, treatment substitution, laser therapy or surgery. After laser therapy or surgery, patients could continue with no treatment or proceed to prostaglandin analogue as monotherapy or treatment substitution. IOP was stratified at treatment onset as ≤20, 21–23 and ≥24 mmHg, respectively. All costs were expressed in 2005 euros.Results:MTTC was 44.3 months for travoprost and 37.8 for latanoprost. Additional 5-year costs for travoprost were €51, resulting in an incremental cost-effectiveness ratio without treatment change of €95 per year. Of patients treated with latanoprost, 1.9% underwent laser therapy or surgery, compared with 1.2% of patients treated with travoprost. The results differed with baseline IOP values, such that 55.6%, 53.9% and 50.4% of patients with pretreatment IOP values of ≤20, 21–23 and ≥24 mmHg, respectively, continued to receive travoprost treatment at 5 years, compared with 32.3%, 26.1% and 26.1% of patients, respectively, receiving latanoprost. Thus, incremental cost-effectiveness ratios (ICERs) without treatment change were €140, €45 and €123 per year, respectively.Conclusion:Travoprost demonstrated a longer effectiveness profile than latanoprost and minimized early treatment changes. The smaller proportion of patients needing a new treatment, laser therapy or surgery virtually compensated for the higher travoprost acquisition cost. Overall, travoprost is cost effective compared with latanoprost, and is most cost effective in patients with pretreatment IOPs between 21 and 23 mmHg.