Health insurance coverage for all citizens is often considered a requisite for reducing disparities in health care accessibility. In Germany, health insurees are covered either by statutory health insurance (SHI) or private health insurance (PHI). Due to a 20%–35% higher reimbursement of physicians for patients with PHI, it is often claimed that patients with SHI are faced with longer waiting times when it comes to obtaining outpatient appointments. There is little empirical evidence regarding outpatient waiting times for patients with different health insurance status in Germany.

Objectives: Progression-free survival (PFS) has not been validated as a surrogate endpoint for overall survival (OS) for anthracycline (A) and taxane-based (T) chemotherapy in advanced breast cancer (ABC). Using trial-level, meta-analytic approaches, we evaluated PFS as a surrogate endpoint. Methods: A literature review identified randomized, controlled A and T trials for ABC. Progression-based endpoints were classified by prospective definitions. Treatment effects were derived as hazard ratios for PFS (HR_PFS) and OS (HR_OS). Kappa statistic assessed overall agreement. A fixed-effects regression model was used to predict HR_OS from observed HR_PFS. Cross-validation was performed. Sensitivity and subgroup analyses were performed for PFS definition, year of last patient recruitment, line of treatment, and constant rate assumption. Results: Sixteen A and fifteen T trials met inclusion criteria, producing seventeen A (n = 4,323) and seventeen T (n = 5,893) trial-arm pairs. Agreement (kappa statistic) between the direction of HR_OS and HR_PFS was 0.71 for A (p = .0029) and 0.75 for T (p = .0028). While HR_PFS was a statistically significant predictor of HR_OS for both A (p = .0019) and T (p = .012), the explained variances were 0.49 (A) and 0.35 (T). In cross-validation, 97 percent of the 95 percent prediction intervals crossed the equivalence line, and the direction of predicted HR_OS agreed with observed HR_OS in 82 percent (A) and 76 percent (T). Results were robust in sensitivity and subgroup analyses. Conclusions: This meta-analysis suggests that the trial-level treatment effect on PFS is significantly associated with the trial-level treatment effect on OS. However, prediction of OS based on PFS is surrounded with uncertainty.

Objective.: We performed a meta-analysis on adverse events seen with bevacizumab to combine the existing evidence about its safety in patients with advanced cancer. Methods.: A systematic literature search was conducted to identify published, randomized controlled trials of bevacizumab in cancer patients with data on adverse events available. The primary endpoint was “severe adverse event,” a composite of grade 3 and 4 adverse events. Secondary endpoints for the exploratory analysis were individual adverse events. We used random-effects meta-analysis to combine data. Results.: Thirteen eligible publications were identified and eight trials reported the primary endpoint. Compared with the control group, the bevacizumab group had a slightly higher risk for any severe adverse event (pooled relative risk, 1.10; 95% confidence interval [95% CI], 1.01–1.19). The pooled risk difference was 7% (95% CI, 1%–13%), with a number needed to harm of 14 treated patients. Exploratory analyses showed a statistically significant higher risk for eight of the 15 evaluated secondary endpoints: bevacizumab was associated with a fourfold higher risk for hypertension, epistaxis, and gastrointestinal hemorrhage/perforation; a threefold higher risk for any bleeding events; and a lower, but elevated risk for proteinuria, leukopenia, diarrhea, and asthenia. No statistically significant differences were found for any thrombotic event (arterial or venous), hemoptysis, cardiac event, thrombocytopenia, neutropenia, impaired wound healing, or death related to an adverse event. Conclusion.: Treatment with bevacizumab was associated with a slightly higher risk for any severe (grade 3 or 4) adverse event in patients with cancer. The result may impact individual benefit–risk assessments and policy guidelines.

Lynch syndrome (LS) screening among patients with newly diagnosed colorectal cancer can decrease mortality in their affected first-degree relatives. In Germany, it is not yet clinical practice and the cost-effectiveness of different testing strategies is unknown. We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the German Statutory Health Insurance system. A total of 22 testing strategies considering family-history assessment, analysis of tumor samples (i.e., immunohistochemistry (IHC), microsatellite instability, and BRAF mutation testing) and genetic sequencing were analyzed. Life-years gained in relatives by closed-meshed colonoscopy and aspirin prophylaxis were estimated by Markov models. Uncertainty was assessed deterministically and probabilistically. On average, detected mutation carriers gained 0.52 life-years (undiscounted: 1.34) by increased prevention. Most strategies were dominated, with three exceptions: family assessment by the Bethesda criteria followed by IHC and BRAF testing and genetic sequencing; IHC and BRAF testing and genetic sequencing; and direct sequencing of all index patients. Their incremental cost-effectiveness was €77,268, €253,258, and €4,188,036 per life-year gained, respectively. The results were less favorable than those of previous models. Chemoprevention appears to provide comparably low additional benefit and improves cost-effectiveness only slightly. Genet Med 17 10, 765–773.

Transition from hospital to home is a critical period for older persons with acute myocardial infarction (AMI). Home-based secondary prevention programs led by nurses have been proposed to facilitate the patients’ adjustment to AMI after discharge. The objective of this study was to evaluate the effects of a nurse-based case management for elderly patients discharged after an AMI from a tertiary care hospital. In a single-centre randomized two-armed parallel group trial of patients aged 65 years and older hospitalized with an AMI between September 2008 and May 2010 in the Hospital of Augsburg, Germany, patients were randomly assigned to a case management or a control group receiving usual care. The case-management intervention consisted of a nurse-based follow-up for one year including home visits and telephone calls. Key elements of the intervention were to detect problems or risks and to give advice regarding a wide range of aspects of disease management (e.g. nutrition, medication). Primary study endpoint was time to first unplanned readmission or death. Block randomization per telephone call to a biostatistical center, where the randomization list was kept, was performed. Persons who assessed one-year outcomes and validated readmission data were blinded. Statistical analysis was based on the intention-to-treat approach and included Cox Proportional Hazards models. Three hundred forty patients were allocated to receive case-management (n=168) or usual care (n=172). The analysis is based on 329 patients (intervention group: n=161; control group: n=168). Of these, 62% were men, mean age was 75.4 years, and 47.1% had at least either diabetes or chronic heart failure as a major comorbidity. The mean follow-up time for the intervention group was 273.6 days, and for the control group it was 320.6 days. During one year, in the intervention group there were 57 first unplanned readmissions and 5 deaths, while the control group had 75 first unplanned readmissions and 3 deaths. With respect to the endpoint there was no significant effect of the case management program after one year (Hazard Ratio 1.01, 95% confidence interval 0.72-1.41). This was also the case among subgroups according to sex, diabetes, living alone, and comorbidities. A nurse-based management among elderly patients with AMI had no significant influence on the rate of first unplanned readmissions or death during a one-year follow-up. A possible long-term influence should be investigated by further studies. ISRCTN02893746