Bruno Bregman

A health economic analysis of screening and optimal treatment of nephropathy in patients with type 2 diabetes and hypertension in the USA

BACKGROUND Nephropathy is an indicator of end-organ damage and is a strong predictor of an increased risk of cardiovascular disease and death in patients with diabetes. Screening can lead to early identification and treatment, both of which incur costs. However, identification and treatment may slow or prevent progression to a more expensive stage of the disease and thus may save money. We assessed the health economic impact of screening for nephropathy (microalbuminuria and overt nephropathy) followed by optimal renoprotective-based antihypertensive therapy in a US setting. METHODS A Markov model simulated the lifetime impact of screening with semi-quantitative urine dipsticks in a primary care setting of hypertensive patients with type 2 diabetes and subsequent treatment with irbesartan 300 mg in patients identified as having nephropathy. Progression from no nephropathy to end-stage renal disease (ESRD) was simulated. Probabilities, utilities, medication and ESRD treatment costs came from published sources. Clinical outcomes and direct medical costs were projected. Second order Monte Carlo simulation was used to account for uncertainty in multiple parameters. Annual discount rates of 3% were used where appropriate. RESULTS Screening, followed by optimized treatment, led to a 44% reduction in the cumulative incidence of ESRD and improvements in non-discounted life expectancy of 0.25 +/- 0.22 years/patient (mean +/- SD). Quality-adjusted life expectancy was improved by 0.18 +/- 0.15 quality-adjusted life years (QALYs)/patient and direct costs increased by

Management of chronic myeloid leukaemia in clinical practice in France: results of the French subset of patients from the UNIC study

244 +/- 3499/patient. The incremental cost-effectiveness ratio was

Treatment patterns and outcomes in patients with advanced melanoma in France

20 011 per QALY gained for screening and optimized treatment versus no screening. There was a 77% probability that screening and optimized therapy would be considered cost effective with a willingness to pay a threshold of

The importance of baseline viral load when assessing relative efficacy in treatment-naïve HBeAg-positive chronic hepatitis B: a systematic review and network meta-analysis

50 000. CONCLUSION In patients with type 2 diabetes and hypertension, screening for nephropathy and treatment with a renoprotective-based antihypertensive agent was projected to improve patient outcomes and represent excellent value in a US setting.

Hospitalisation costs of metastatic melanoma in France; the MELISSA study (MELanoma In hoSpital coSts Assessment)

Abstract Objective: To assess real-life treatment practices with imatinib for chronic-phase chronic myeloid leukaemia (CP-CML) in France. Research design and methods: In the observational ‘Unmet Needs in CML’ (UNIC) study of CML management in Europe, case report forms were completed retrospectively for eligible patients (≥18 years of age, currently treated for CML) during enrolment (September 2006–March 2007). Results from the subset of patients from France are presented. Main outcome measures: Primary objectives were to estimate from the collected data the proportions of patients ever treated with imatinib and those experiencing imatinib resistance and/or intolerance as determined by physicians’ diagnoses of resistance/intolerance leading to a change in imatinib use. Collected data were analysed descriptively. Secondary descriptive measures included imatinib dose modifications and methods for treatment response monitoring. Results: Of the 654 French CP-CML patients, 95.9% had received imatinib. Of these, 15% were judged by physicians as imatinib-resistant and 31% as imatinib-intolerant (not mutually exclusive) during treatment, 44% required dose modification and 23% discontinued imatinib. In the 12 months preceding the last observation, 65% had a cytogenetic features analysis and 93% had a polymerase chain reaction (PCR) assessment of molecular response. Importantly, and contrasting with European recommendations, 46% of imatinib-resistant patients had never been assessed for BCR-ABL mutations. Limitations: The observational study design limits data collection and interpretation. The findings are specific to the French healthcare system and may not apply to other countries. Conclusion: This observational study of CP-CML management in France confirmed that most patients are treated with imatinib, a treatment widely recognised as efficacious. The study highlights opportunities for optimising CML management, as a proportion of patients may require alternative treatment strategies due to imatinib resistance/intolerance. Response monitoring rates differ from recommendations, representing another opportunity for improving care for CP-CML patients through early identification of patients failing current therapy.

An Assessment of The Hospitalization Costs of Melanoma in France in the Advanced/Metastatic Setting: the Melissa Study (Melanoma in Hospital Costs Assessment)

Abstract Background: Melanoma is associated with high mortality and poor response to standard chemotherapy. In order to benchmark benefits of recently introduced treatments, outcome with standard chemotherapy in everyday practice should be documented. Objectives: To document treatment pathways in patients with advanced melanoma, to compare clinical outcomes between treatment lines, and to measure associated healthcare resource utilisation in terms of hospital visits and adverse event management. Methods: An observational, longitudinal survey of patients with unresectable stage III/IV melanoma in France evaluated 278 patients with ≥2 months follow-up. Data were collected retrospectively for 2–3 years following the index consultation. Treatment history was documented and outcomes determined for each treatment line. Complete and partial response rates were compared between treatment lines. Overall and progression-free survival were determined by Kaplan–Meier analysis. Health resource utilisation was documented hospitalisations, hospice stays, emergency room visits, outpatient visits and adverse event management. Results: In total, 271 patients (97.5%) received first-line therapy, 161 (57.9%) second-line therapy and 85 (30.6%) third-line therapy. The most frequent first-line therapy strategies were systemic treatment alone (46.5%) or in combination with surgery (22.9%). The most frequently used chemotherapy was dacarbazine monotherapy (62.3% of chemotherapy). Median duration of first-line systemic therapy was 11.9 (IQR: 6.6–24.0) weeks. First-line therapy was discontinued in 190 patients (68.3%), principally due to disease progression (150 patients). Median overall survival was 17.1 (95% CI: 14.6–20.1) months since diagnosis, 9.5 (95% CI: 6.7–12.8) months since initiation of first-line therapy and 5.3 (95% CI: 3.7–7.2) months since initiation of second-line therapy. Median progression-free survival time was 2.8 (95% CI: 2.5–3.3) months. Ninety-six patients (40.2%) received medication to manage adverse events and 131 patients (47.1%) required hospitalisation (mean: 3.1 hospitalisations; mean duration: 27 days). Study limitations: The retrospective data collection precludes ascertainment of medical information and completion of missing data. Conclusions: Existing therapies provide limited survival benefit to patients with unresectable stage III/IV melanoma. New more effective treatment options are needed.

PDB33 COST-CONSEQUENCE ANALYSIS OF SCREENING AND OPTIMIZED TREATMENT OF NEPHROPATHY IN HYPERTENSIVE PATIENTS WITH TYPE-2 DIABETES INA FRENCH SETTING

BackgroundTo date no network meta-analysis (NMA) has accounted for baseline variations in viral load when assessing the relative efficacy of interventions for chronic hepatitis B (CHB). We undertook baseline-adjusted and unadjusted analyses using the same data to explore the impact of baseline viral load (BVL) on CHB treatment response.MethodsWe searched Embase, Medline, Medline in Process and the Cochrane CENTRAL databases for randomised clinical trials (RCTs) of monotherapy interventions at licensed doses for use in CHB. Search strategies comprised CHB disease and drug terms (a combination of controlled vocabulary and free text terms) and also a bespoke RCT filter.The NMA was undertaken in WinBUGs using fixed and random effects methods, using data obtained from a systematic review. Individual patient data (IPD) from an entecavir clinical trial were used to quantify the impact of different baseline characteristics (in particular undetectable viral load (UVL) at 1 year) on relative treatment effect. Study level mean baseline values from all identified studies were used. Results were generated for UVL and presented as relative risks (RRs) and 95% credible intervals (CrIs) using entecavir as reference treatment.ResultsOverall, for all eight relevant interventions we identified 3,000 abstracts. Following full text review a total of 35 (including the contents of six clinical study reports) met the inclusion critera; 19 were in hepatitis B e antigen (HBeAg)-positive patients and 14 of the 19 contained outcome information of relevance to the NMA.Entecavir and tenofovir studies had heterogeneous patient populations in terms of BVL (mean values 9.29 and 8.65 log10 copies/ml respectively). After adjusting UVL for BVL using an informative prior based on the IPD analysis, the difference between entecavir and tenofovir was not statistically significant (RR 1.27, 95% CrI 0.96 to 1.47 - fixed effects). A similar conclusion was found in all sensitivity analyses. Adjusted tenofovir results were more consistent with observed clinical trial response rates.ConclusionsThis study demonstrates the importance of adjusting for BVL when assessing the relative efficacy of CHB interventions in achieving UVL. This has implications for both clinical and economic decision making.

Kinetic of chronic myeloid leukaemia (CML) prevalence in Northern France since the introduction of imatinib

BackgroundManagement of metastatic melanoma is changing rapidly following the introduction of innovative effective therapies, with consequences for the allocation of healthcare resources. The objective of this study was to assess hospitalisation costs of metastatic melanoma in France from 2011 to 2013 from the perspective of the government payer.MethodsThe population studied corresponded to all adults with metastatic melanoma hospitalised in France between 1st January 2011 and 31st December 2013 who required chemotherapy, immunotherapy or radiotherapy due to tumour progression and unresectable Stage III or Stage IV melanoma. Metastatic melanoma was identified by ICD-10 codes documented in the hospital patient discharge records. For each patient, hospital stays were stratified into a pre- or post- progression health state using proxy variables for the RECIST criteria. All healthcare expenditure documented in the French national hospital claims system database and incurred between the index hospitalisation (or change of progression state) and the end of follow-up were analysed. For the principal analysis, valuation of healthcare resource consumption was performed using official national hospitalisation tariffs. Any expensive therapy administered during the stay was documented from a linked database of expensive drugs (FICHCOMP).ResultsSeventy-eight thousand seven hundred fifty hospital stays by 10,337 patients with metastatic melanoma were identified over the three-year study period. Annual per capita costs of hospitalisation were € 5046 in the pre-progression stage and € 19,006 in the post-progression stage. Hospitalisations attributed to adverse drug reactions to chemotherapy or immunotherapy were observed in 27% of patients. Annual per capita costs of these hospitalisations related to adverse drug reactions were € 3762 in the pre-progression stage and € 5523 in the post-progression stage.ConclusionsHospitalisation costs related to metastatic melanoma rise substantially as the disease progresses. Treatment strategies which slow down disease progression would be expected to reduce costs of hospitalisation for metastatic melanoma, although they may also entail significant acquisition costs. This will entail organisational changes of resource allocation for the treatment of metastatic melanoma in hospitals.

A Retrospective 20-Year Survey of the Incidence of Chronic Myeloid Leukemia in the Northern France Region.

1 Heva, Lyon, France 2 Medical Oncology, Skin Cancers, Centre Léon Bérard, Lyon, France 3 Medical Information Department, Groupe OC Santé, Montpellier, France 4 Bristol-Myers Squibb, Health Economics & Public Health, Rueil-Malmaison, France AN ASSESSMENT OF THE HOSPITALIZATION COSTS OF MELANOMA IN FRANCE IN THE ADVANCED/METASTATIC SETTING: THE MELISSA STUDY (MELANOMA IN HOSPITAL COSTS ASSESSMENT) PCN 99

Changes in the quality of life of advanced melanoma patients after 12 weeks of treatment with ipilimumab compared to gp100 in a phase III clinical trial.

PDB33 COST-CONSEQUENCE ANALYSIS OF SCREENING AND OPTIMIZED TREATMENT OF NEPHROPATHY IN HYPERTENSIVE PATIENTS WITH TYPE-2 DIABETES IN A FRENCH SETTING Palmer AJ,Valentine WJ, Roze S, Chen R, Gabriel S, Bregman B, Mehin N, Parving HH CORE Center for Outcomes Research, Binningen, Switzerland; Bristol-Myers Squibb, Princeton, NJ, USA; Sanofi-Aventis, Bagneux, France; Bristol-Myers Squibb, Rueil-Malmaison, France; Steno Diabetes Center, Gentofte, Denmark OBJECTIVES: Type-2 diabetes patients with hypertension have a high risk of developing nephropathy, with increased risks of morbidity/mortality. Screening for, and treatment of nephropathy, is currently suboptimal in France. We assessed the long-term impact of screening for nephropathy followed by optimal antihypertensive therapy in those in which nephropathy is detected in France. METHODS: A Markov model projected lifetime impacts of screening, identification, and appropriate treatment of nephropathy using semi-quantitative urine dipsticks in a primary care setting, followed by treatment with irbesartan 300 mg added to conventional antihypertensives in a typical cohort of hypertensive Type-2 diabetes patients. The model simulated progression from no renal disease to end-stage renal disease (ESRD). Probabilities and costs came from published sources. Cumulative incidence of ESRD, years free of ESRD, life expectancy (LE) and direct costs were projected. Second-order Monte Carlo simulation was used to account for uncertainty in multiple parameters. RESULTS: In a cohort of 1000 patients, screening for nephropathy followed by optimal treatment reduced cumulative incidence of ESRD from (mean ± SD) 11.0 ± 1.7% to 6.5 ± 1.1%, increased number of ESRD-free years by 524 ± 80 years, increased undiscounted LE by 361 ± 60 years, and reduced costs (discounted 3% annually) by €3,340,200 ± 799,800. Sensitivity analysis showed that screening was most beneficial in younger patients. CONCLUSIONS: In hypertensive type-2 diabetes patients, screening for albuminuria followed by optimal antihypertensive treatment that includes irbesartan 300 mg, is projected to lead to substantial reductions in the incidence of ESRD, improvements in ESRD-free survival and life expectancy, and overall cost savings.