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Background: Precision oncology programs using next-generation sequencing to detect predictive biomarkers are extending therapeutic options for patients with metastatic breast cancer (mBC). Regularly, based on the recommendations of the interdisciplinary molecular tumor board (iMTB), an inclusion in a clinical trial is not possible. In this case, the German health insurance system allows for the application of reimbursement for an off-label drug use. Here, we describe the current challenges and our experience with reimbursement of molecular therapies in mBC. Methods: A total of 100 applications for reimbursement of off-label therapies recommended by an iMTB were filed for patients with mBC, of which 89 were evaluable for this analysis. The approval rate was correlated with the molecular level of evidence of the respective therapy according to the National Center for Tumor Diseases (NCT) and European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) classification as well as with pretreatment therapy lines. Findings: Overall, 53.9% (48/89) of reimbursement applications were approved. Applications for therapies based on level of evidence m1 (NCT classification), tier I and II (ESCAT classification) had a significantly and clinically relevant increased chance of reimbursement, while a greater number of previous treatment lines had no significantly increased chance of approval, though a trend of approval toward higher treatment lines was detectable. Interpretation: Currently, the German jurisdiction seems to aggravate the clinical implementation of clinically urgently needed molecular therapies.
RESUMO
OBJECTIVE: This study examines the recommendations of international guidelines on the use of antepartum and intrapartum cardiotocography. MATERIAL AND METHODS: The guidelines of Germany, Canada, UK, USA, Sri Lanka, Australia as well as FIGO have been compared. The recommendations on the use of cardiotocography were separately evaluated for antepartum and intrapartum use. RESULTS: Antepartum: In risk-free pregnancies the use of cardiotocography is not recommended in all countries. On the other hand the use of cardiotocography is indicated in the presence of a defined maternal and fetal risk factors. While the NICE guidelines recommend cardiotocography in the case of maternal hypertension, as well as preeclampsia, the German guidelines as well as SOGC list considerably more risk factors. Intrapartually, the recommendations vary greatly from country to country. While German guidelines suggest the use of cardiotocography from late 1st stage of labor, the other countries strongly recommend the auscultation of the fetal heart rate of non-risk pregnancies. This is due to the current study situation, which does not show any advantage of cardiotocography as opposed to intermittent auscultation. Furthermore studies have indicated that the use of cardiotocography caused an increase in iatrogenic induced cesarean sections. In high risk pregnancies the use of cardiotocography is strongly recommended in the compared countries, however there are major differences in the definition of high risk pregnancy and therefore the indication for cardiotocographic monitoring. CONCLUSION: Intermittent auscultation is a more cost-effective alternative compared to cardiotocography. However, in the case of legal litigation intermittent auscultation is harder to reconstruct the well-being of the newborn during birth. On the other hand cardiotocography might result in a higher cesarean section rate, but can be more helpful to prove fetal well-being during birth for a legal litigation process. Despite the lack of evidence only German guidelines recommend cardiotocographic monitoring from the late 1st stage of labor for risk-free pregnancies.
