Garnet Anderson Katie Arnold SWOG Statistical Center Fred Hutchinson Cancer Research Center October 24, 2014

Consent to Randomization Surgery Best Medical Care Surgery Best Medical Care Yes No

 Outcome: Number of “good” days (D) Counted from day of randomization or enrollment through day 91  Design factor: Consent to be randomized (C)  Treatment: Surgery vs Best Medical Care (S)  Adjustment factors (X) Cancer site: colorectal vs ovarian vs other Patient and disease characteristics Provider characteristics

Good Days (D) = function of :  0 +  1 *X Baseline, adjustment factors +  2 *C Difference between randomized and non-randomized cohorts +  1 * S Effect of surgery +  2 * S*C Difference in effect of surgery between randomized and non-randomized cohorts

 Intent-to-treat (ITT) and pseudo ITT based on treatment choice at consent  After controlling for all known confounders, determine if surgery effect is similar across cohorts (Is  2 = 0?) If so, estimated effect of surgery is  1 based on all data If not,   1 is the estimated surgery effect based on RCT alone   2 is an estimate of the bias in the non-randomized study

Consent to Randomization Surgery Best Medical Care Surgery Best Medical Care Yes No     

 Need patients randomized at each site  Monitoring treatment choices in the non- randomized component  Collection of confounder variables for the multivariate analysis  Need all patients managed and monitored identically after initial treatment choice