Heregulin (HRG) assessment for clinical trial eligibility testing in a molecular registry (PRAEGNANT) in Germany.

BACKGROUND: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry. METHODS: Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor-positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria. RESULTS: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive. CONCLUSION: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials. TRIAL REGISTRATION: Clinicaltrials, NCT02338167 , Registered 14 January 2015 - retrospectively registered.

Gynaecological endoscopic surgical education and assessment. A diploma programme in gynaecological endoscopic surgery.

In recent years, training and education in endoscopic surgery has been critically reviewed. Clinicians, both surgeons as gynaecologist who perform endoscopic surgery without proper training of the specific psychomotor skills, are at higher risk to increased patient morbidity and mortality. Although the apprentice-tutor model has long been a successful approach for training of surgeons, recently, clinicians have recognised that endoscopic surgery requires an important training phase outside the operating theatre. The Gynaecological Endoscopic Surgical Education and Assessment programme (GESEA) recognises the necessity of this structured approach and implements two separated stages in its learning strategy. In the first stage, a skill certificate on theoretical knowledge and specific practical psychomotor skills is acquired through a high-stake exam; in the second stage, a clinical programme is completed to achieve surgical competence and receive the corresponding diploma. Three diplomas can be awarded: (a) the Bachelor in Endoscopy, (b) the Minimally Invasive Gynaecological Surgeon (MIGS) and (c) the Master level. The Master level is sub-divided into two separate diplomas: the Master in Laparoscopic Pelvic Surgery and the Master in Hysteroscopy. The complexity of modern surgery has increased the demands and challenges to surgical education and the quality control. This programme is based on the best available scientific evidence, and it counteracts the problem of the traditional surgical apprentice-tutor model. It is seen as a major step toward standardisation of endoscopic surgical training in general.

Gynaecological Endoscopic Surgical Education and Assessment. A diploma programme in gynaecological endoscopic surgery.

In recent years, training and education in endoscopic surgery has been critically reviewed. Clinicians, both surgeons as gynaecologist who perform endoscopic surgery without proper training of the specific psychomotor skills are at higher risk to increased patient morbidity and mortality. Although the apprentice-tutor model has long been a successful approach for training of surgeons, recently, clinicians have recognised that endoscopic surgery requires an important training phase outside the operating theatre. The Gynaecological Endoscopic Surgical Education and Assessment programme (GESEA), recognises the necessity of this structured approach and implements two separated stages in its learning strategy. In the first stage, a skill certificate on theoretical knowledge and specific practical psychomotor skills is acquired through a high stake exam; in the second stage, a clinical programme is completed to achieve surgical competence and receive the corresponding diploma. Three diplomas can be awarded: (a) the Bachelor in Endoscopy; (b) the Minimally Invasive Gynaecological Surgeon (MIGS); and (c) the Master level. The Master level is sub-divided into two separate diplomas: the Master in Laparoscopic Pelvic Surgery and the Master in Hysteroscopy. The complexity of modern surgery has increased the demands and challenges to surgical education and the quality control. This programme is based on the best available scientific evidence and it counteracts the problem of the traditional surgical apprentice tutor model. It is seen as a major step toward standardization of endoscopic surgical training in general.

Breast cancer surgery and financial reimbursement in Germany.

The reimbursement for breast cancer-specific operative interventions in Germany is regulated by the diagnosis-related group (DRG) system. The essential elements of the German DRG system, which was developed as a per-case lump-sum payment system, are presented, including the participating institutions. The actual treatment situation in breast cancer surgery is now aptly reflected in the introduction of the OPS (operation and treatment procedure classification) 2012. This is oriented on the classification model of Hoffmann and Wallwiener, with its complexity-based differentiation that reflects the basic idea of different resource usage. Despite the actual potential of the appropriately differentiated encryption of surgical procedures, which illustrates their differences in resource costs and consumption, appropriate reimbursement has still not been achieved. Hopefully, in the future the calculation of the DRGs in the field of breast cancer surgery will be based on data feedback from the hospitals and treatment institutions, and will be more suited to the main purpose of the DRG system, i.e. that reimbursement reflects resource expenditure. A necessary basic tool for differentiated, complexity-oriented encryption has been achieved with the OPS 2012, which mirrors our classification model for oncological, oncoplastic and reconstructive breast surgery.

Results of the Zometa cost-utility model for the german healthcare system based on the results of the ABCSG-12 study.

BACKGROUND: The ABCSG-12 trial investigated the efficacy of gonadotropin-releasing hormone (GnRH)analogs in combination with tamoxifen or anastrozole + or - zoledronic acid (4 mg, q6m for 3 years) in 1,803 premenopausal women with hormone receptor-positive (HR+) breast cancer. After 48 months of follow-up, there was a 36% improvement in the disease-free survival (DFS) (recurrence-free survival 35%) using zoledronic acid. Based on these data, the costutility of zoledronic acid was calculated for the German healthcare system. MATERIALS AND METHODS: Costs of surveillance, adverse effects, recurrence, contralateral breast cancer, metastasis, and end-of-life care were determined based on the Einheitlicher Bewertungsmabetastab (EBM 2009) and the diagnosis-related groups (DRG) system. Utilities were surveyed with a questionnaire (n = 95). Estimation of the cost-utility was made by calculating the incremental costeffectiveness ratio (ICER) per quality-adjusted life year (QALY), using a Markov model. RESULTS: Including zoledronic acid as adjuvant therapy for 3 years resulted in total costs of euro 2,262. The use of zoledronic acid is dominant when clinical efficacy and quality of life are taken into consideration (- euro 45.83/QALY) (95% confidence interval (CI) - euro 1,838 to E 2,375; 0.02-0.41 QALY). The sensitivity analyses present with a probability of 90% that the cost per QALY gained are