Economic evaluation of prescribing conventional and newer oral anticoagulants in older adults.

INTRODUCTION: Anticoagulants refer to a variety of agents that inhibit one or more steps in the coagulation cascade. Generally, clinical conditions that require the prescribing of an oral anticoagulant increase in frequency with age. However, a major challenge of anticoagulation use among older patients is that this group of patients also experience the highest bleeding risk. To date, economic evaluation of prescribing of anticoagulants that includes the novel or newer oral anticoagulants (NOACs) in older adults has not been conducted and is warranted. Areas covered: A review of articles that evaluated the cost of prescribing conventional (e.g. vitamin K antagonists) and NOACs (e.g. direct thrombin inhibitors and direct factor Xa inhibitors) in older adults. Expert commentary: While the use of NOACs significantly increases the cost of the initial treatment for thromboembolic disorders, they are still considered cost-effective relative to warfarin since they offer reduced risk of intracranial haemorrhagic events. The optimum anticoagulation with warfarin can be achieved by providing specialised care; clinics managed by pharmacists have been shown to be cost-effective relative to usual care. There are suggestions that genotyping the CYP2C9 and VKORC1 genes is useful for determining a more appropriate initial dose and thereby increasing the effectiveness and safety of warfarin

Exploring the Impact of Treatment Switching on Overall Survival from the PROfound Study in Homologous Recombination Repair (HRR)-Mutated Metastatic Castration-Resistant Prostate Cancer (mCRPC).

BACKGROUND: In oncology trials, treatment switching from the comparator to the experimental regimen is often allowed but may lead to underestimating overall survival (OS) of an experimental therapy. OBJECTIVE: This study evaluates the impact of treatment switching from control to olaparib on OS using the final survival data from the PROfound study and compares validated adjustment methods to estimate the magnitude of OS benefit with olaparib. PATIENTS AND METHODS: The primary population from PROfound (Cohort A) was included, alongside two populations approved for treatment with olaparib by the European Medicines Agency and US Food and Drug Administration: BRCAm and Cohort A+B (excluding the PPP2R2A gene). Five methods were explored to adjust for switching: excluding or censoring patients in the control arm who receive subsequent olaparib, Rank Preserving Structural Failure Time Model (RPSFTM), Inverse Probability of Censoring Weights, and Two-Stage Estimation. RESULTS: The RPSFTM was considered the most appropriate approach for PROfound as the results were robust to sensitivity analysis testing of the common treatment effect assumption. For Cohort A, the final OS hazard ratio reduced from 0.69 (95% CI 0.5-0.97) to between 0.42 (0.18-0.90) and 0.52 (0.31-1.00) for olaparib versus control, depending on the RPSFTM selected. Median OS reduced from 14.7 months to between 11.73 and 12.63 months for control. CONCLUSIONS: The magnitude of the statistically significant (P < 0.05) survival benefit of olaparib versus control observed in Cohort A of PROfound is likely to be underestimated if adjustment for treatment switching from control to olaparib is not conducted. The RPSFTM was considered the most plausible method, although further development and validation of robust methods to estimate the magnitude of impact of treatment switching is needed