This pragmatic approach is said to reflect the overall effectiveness of a treatment policy if it were selleck Tipifarnib introduced on a wider scale. However, this is only the case where switching treatments is a feasible option. If the treatment is not currently available then treatment switching may not be an option in practice. It is often of interest to estimate the effectiveness of the experimental treatment alone, in the absence of switch ing. This appropriate policy effectiveness is especially important when assessing the cost effectiveness of a treatment, something which is increasingly used as an input to drug reimbursement decisions. Appropriate policy effectiveness is often quantified using a per protocol approach which measures how well a patient fares dependent on the treatment they actually receive, regardless of which treatment arm they were randomised to.

Patients who switch from their ran domised treatment are therefore Inhibitors,Modulators,Libraries excluded from the ana lysis or censored at the time of their switch. This approach can lead to severe selection bias if those excluded differ in prognosis from those retained in the analysis, which is likely in this setting as patients often switch treatments because their condition has deterio rated. The National Institute for Health and Clinical Excel lence has considered several drugs where cross over has been a feature of the key clinical trials. In the appraisal of trastuzumab for the treatment of metastatic breast cancer, 75% of patients randomised to control treatment in the key trial eventually switched to the experimental arm.

Inhibitors,Modulators,Libraries These patients were excluded com pletely from the analysis and a median survival gain of 17. 9 months was found. However, if all Inhibitors,Modulators,Libraries control patients had been Inhibitors,Modulators,Libraries included, this median survival gain was greatly reduced to just 7 months. The true median survival gain from the treatment is likely to be somewhere between these two values. Crossover was also a feature of trials used in the recent Inhibitors,Modulators,Libraries appraisal of renal cell carcinoma therapies where the impact of alternative approaches on estimates of cost effectiveness was highlighted. For sunitinib, an analysis of overall survival which excluded all patients who received any subsequent therapy led to an Incre mental Cost Effectiveness Cost Ratio of ��59, 819 compared to standard care, based on a hazard ratio of 0. 65.

However if these patients were not excluded from selleck chemical the analysis, the overall hazard ratio is increased to 0. 82, increasing the ICER to ��118,005. In reality, the ICER is likely to lie somewhere in between these two estimates. Various methods have been proposed to evaluate the appropriate policy effectiveness of a treatment taking into account deviations from the randomised treatment group. These range from relatively simple methods, such as per protocol analysis, to methods that account for switching using either a proportional hazards or accelerated failure time model.