The model takes the form switch treatments, or to Group AB or BA if they switched from their allocated treatment to the other treatment. The hazard rates in each group are assumed proportional. A Cox model is then fitted with a time varying covariate for switching time. Full details of the method can be found in the paper itself. The method makes selleck compound a number of assumptions which may not be appropriate in all situations. Inhibitors,Modulators,Libraries The assumption that the underlying hazard rates of switchers and non switchers allocated to each treatment can be expressed as multiplicative factors may not be appropriate and is not testable. Also, it is assumed that switching onto a new treatment will cause an instantaneous improve ment, which may be important, but would be difficult to test in reality.

The method also makes the assumption that the treatment effect for patients switching on to a treatment will be the same as for those initially allocated to receive it. This assumption is unlikely to be true Inhibitors,Modulators,Libraries in a real trial setting for a number of reasons, the most important of which may be that patients switching onto a treatment will typically be at a more advanced stage of their disease than those in the treatment arm were at the start of the trial. This assumption could be tested for a real dataset by comparing the survival times of patients from their switch with the survival times of treatment arm patients, although analysis of this type would itself be subject to bias. Problems with this method have been raised by White. Patients are grouped as described above according to future events, i. e.

a treatment switch which has not where l0 is the baseline hazard function and Xi takes a value of zero while a patient Inhibitors,Modulators,Libraries is receiving the control and 1 while they are receiving the experimental treatment. However, like the PP methods presented above, this method can break the randomisation balance and is therefore subject to selection bias if switching is related to prognosis. Adjusted hazard ratio methods The two methods described here make adjustments to the hazard ratio in order to take into account patients switching from one treatment arm to the other. Adjusted Inhibitors,Modulators,Libraries Cox model Law and Kaldor propose a method of adjusting the standard Cox model to take into account patients who depart from their randomised treatment. The method can be used in situations where patients switch both from control to experimental Inhibitors,Modulators,Libraries treatment and or in the opposite direction.

The method works on the principle that patients can be divided into four groups depending on their switch ing pattern. So given an RCT comparing two treatments, patients are classified as being in Group AA or BB http://www.selleckchem.com/products/Temsirolimus.html if they were allocated to A or B and did not yet occurred. So for example, subjects in group AB are said to have a certain hazard function before they switch. However, in reality they have a hazard of zero up to the point at which they switch treatment, as they cannot die before this point or they would be in group AA.