Jörg Ruof

Economic evaluation of orlistat in overweight and obese patients with type 2 diabetes mellitus.

AbstractObjective: To estimate the economic value of pharmacological treatment of type 2 diabetes mellitus in overweight and obese patients using orlistat in addition to standard diabetes therapy (i.e., a sulphonlyurea, metformin or insulin) and weight management strategies as compared with standard diabetes therapy and weight management strategies alone in a US-based healthcare setting. The perspective of the study was from the viewpoint of a US healthcare provider. Design and setting: Markov state transition model simulating diabetes-related complications and mortality for a period of 11 years. Patients were modelled to continue orlistat therapy for a 52-week period, assuming a 3-year period of weight regain where after 3 years bodyweight would match that of the placebo group. The impact of orlistat on glycosylated haemoglobin (HbA1c) values was evaluated directly using data from four randomised, placebo-controlled, 1-year trials of orlistat in overweight or obese adults with type 2 diabetes who also received standard diabetes pharmacotherapy and intensive lifestyle modification. Incidence rates of micro- and macrovascular complications associated with type 2 diabetes and the estimated relative reduction in incidence rates associated with a decrease in mean updated HbA1C values were derived from the United Kingdom Prospective Diabetes Study (UKPDS) estimates for a reference population of male patients, 52 years of age.US cost estimates were derived from published sources and presented in 2001 US dollars. Discounting of 3% was applied. Probabilistic sensitivity analysis was applied to evaluate the robustness of the results of the persistence of the effect of orlistat after treatment. Main outcome measures: Average costs and event-free life-years gained during the 11-year period expressed as the incremental costs divided by the incremental gain in life expectancy. Results: Treatment with orlistat, 120mg three times daily, increased event-free life expectancy by 0.13 years over an 11-year period. Average treatment costs were estimated to be

Patient relevant endpoints in oncology: current issues in the context of early benefit assessment in Germany

US19 987 in the orlistat group compared with

Questioning Patient Subgroups for Benefit Assessment: Challenging the German Gemeinsamer Bundesausschuss Approach

US18 865 in the group that received diabetes medication and weight management alone. This translated into a cost-effectiveness ratio of

Cost-Efficacy Comparison among Three Antiretroviral Regimens in HIV- 1 Infected, Treatment-Experienced Patients

US8327 per event-free life-year gained. Conclusion: Adding orlistat as a pharmacological treatment to conventional diabetes and weight management approaches seems to be a cost-effective treatment option for overweight and obese patients with type 2 diabetes.

G-Ba Does not Adjust Evidence Requirements in Early Benefit Assessment in Cases of Pre-Defined, Efficacy-Based Cross-Over Decisions in Oncology Trials

The German AMNOG healthcare reform includes a mandatory early-benefit-assessment (EBA) at launch. As per German social code, EBA is based on registration trials and includes evaluation of the patient-relevant effect of the new medicines compared to an appropriate comparator as defined by the Federal Joint Committee (G-BA). Current EBA decisions released have unveiled issues regarding the acceptance of some patient-relevant endpoints as G-BA and IQWiG are grading the endpoints, focusing on overall survival as the preferred endpoint in oncology.A taskforce of experienced German outcomes research, medical, health-technology assessment and biostatistics researchers in industry was appointed. After agreement on core assumptions, a draft position was prepared. Input on iterative versions was solicited from a panel of reviewers from industry and external stakeholders.Distinctive features of registration trials in oncology need to be considered when these studies form basis for EBA, especially in cancer-indications with long post-progression survival; and with several consecutive therapeutic options available post-progression. Ethical committees, caregivers and patients often demand cross-over-designs diluting the treatment-effect on overall survival. Regulatory authorities require evaluation of morbidity-related study endpoints including survival of patients without their disease getting worse (i.e., progression-free survival). Also, progression requires treatment-changes, another strong indicator for its relevance to patients.Based on specific guidelines and clinical trial programs that were developed to be consistent with regulatory guidance, endpoints in oncology are thoroughly evaluated in terms of their patient-relevance. This extensive knowledge and experience should be fully acknowledged during EBA when assessing the patient-relevant benefit of innovative medicines in oncology.JEL codesD61; H51; I18.

Early benefit assessment (EBA) in Germany: analysing decisions 18 months after introducing the new AMNOG legislation

Questioning Patient Subgroups for Benefit Assessment: Challenging the German Gemeinsamer Bundesausschuss Approach Jorg Ruof, MD, MPH, MBA*, Charalabos-Markos Dintsios, PhD, MPH, Friedrich Wilhelm Schwartz, MD Roche Pharma AG, Grenzach-Wyhlen, Germany; Hannover Medical School, Hannover, Germany; German Association of Researchbased Pharmaceutical Companies (vfa), Berlin, Germany; Department of Public Health, Heinrich Heine University, Dusseldorf, Germany

Analysis of endpoints used in marketing authorisations versus value assessments of oncology medicines in Germany.

AbstractBackground and objective: In the face of increasing antiretroviral (ARV) treatment options and costs, payers are progressively challenged with prioritising resources. The cost effectiveness of the ARV agent enfuvirtide has been shown to be comparable to that of other available HIV treatment strategies, based on Markov modeling. However, an evaluation of enfuvirtide treatment costs that considers the impact of virological and immunological responses to therapy may provide a more clinically meaningful perspective for primary HIV healthcare providers. The aim of this study was to assess the cost per unit change in efficacy (HIV RNA decreases and CD4 count increases) of three different ARV regimens for triple class-experienced HIV-1 infected patients using actual drug costs and data from randomised, controlled clinical trials. Study design: The analysis included three steps. First, re-analysis of 48-week clinical trial data (T-20 vs Optimized Regimen Only [TORO]) to allow for a more direct comparison of enfuvirtide versus other commonly used ARV agents. All patients included in the re-analysis received a common optimised background (COB) regimen of three drugs: two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and a ritonavir-boosted protease inhibitor (PI), lopinavir. HIV RNA levels and CD4 count changes were determined for three patient groups according to the treatment received —group 1: COB + enfuvirtide; group 2: COB + PI; group 3: COB + NRTI + PI. The second step of the analysis involved calculating the annualised regimen costs (

Inconsistent approaches of the G-BA regarding acceptance of primary study endpoints as being relevant to patients - an analysis of three disease areas: oncological, metabolic, and infectious diseases

US wholesaler acquisition cost) for each patient group. In the third step, cost-efficacy ratios were calculated and compared between groups: (a) the annualised regimen cost (

Comparison of post-authorisation measures from regulatory authorities with additional evidence requirements from the HTA body in Germany – are additional data requirements by the Federal Joint Committee justified?

US)/change in viral load from baseline, and (b) the annualised regimen cost (

Early Benefit Assessments in Oncology in Germany: How Can a Clinically Relevant Endpoint Not Be Relevant to Patients?

US)/change in CD4+ cell count from baseline. Results: One hundred and fifty-seven patients were included in this previously unplanned secondary analysis (group 1: 79 patients; group 2: 42 patients; group 3: 36 patients). HIV RNA and CD4 count changes from baseline to week 48 were −1.80, −0.89 and −0.61 log 10 copies/mL (p < 0.001 for enfuvirtide vs each non-enfuvirtide group) and +102, +57 and +52 cells/mm3 (p < 0.05 for enfuvirtide versus each non-enfuvirtide subgroup) for groups 1, 2 and 3, respectively. The annualised costs of the combination therapies were