Endpoint Selection
Endpoint Selection
Running CompARE
For each composite component, the user is prompted for the anticipation of:
 The probability of having the event in the reference group
 The relevant effect (HR) to detect
 The correlation between endpoints
CompARE computes the Assympotic Relative Efficiency^{1} (ARE), so that if the ARE is higher than 1, the use of the composite endpoint (CE) consiting of the union of both endpoints is recommended as the primary endpoint of the trial. If the ARE is lower than 1, the use of the Relevant endpoint is preferred over the CE as the primary endpoint of the trial.
Input Items
 P_{01}: Probability of event for the Endpoint 1 in control group
 P_{02}: Probability of event for the Endpoint 2 in control group
 HR_{1}: Hazard Ratio on the Endpoint 1
 HR_{2}: Hazard Ratio on the Endpoint 2
 ρ: Spearman correlation between endpoints (assumed equal in both groups)
Output Items
 Plot: Graphical representation of the ARE value according to different values of the Spearman correlation (Xaxis) and different values of HR_{2} (lines). A point representing the selected ρ in the left panel is drawn over each line. If the whole line is above the value 1, then the use of the Composite endpoint is recommended regardless of the correlation value. On the other hand, if the whole line is below the value 1, then the use of the Composite endpoint is not recommended in any case.
 Table: ARE value according to different correlations (ρ) and different values of HR_{2}. The other parameters are fixed:

 β_{1} and β_{2} are the selected shape parameters from the weibull distribution for the 2 endpoints: 0.5, 1 or 2 depending if the hazards are decreasing, constant or increasing over time, respectively
 P_{01} and P_{02} are the selected probabilities of having the event in the control group
 HR_{1} is the selected Hazard Ratio for the Endpoint 1
Example
Zodiac Trial compared the efficacy of the Vandetanib plus docetaxel versus docetaxel as secondline treatment in patients with advanced nonsmallcell lung cancer. The main endpoint is the Progression Free Survival (PFS) composed by Overall Survival (OS, Endpoint 1) and the Objective Tumor Progression (OTP, Endpoint 2). The probabilities of observing each component in the control group were P_{01}=0.59 and P_{02}=0.74, respectively. The reported causespecific HRs for each component were HR_{1}=0.91 for the OS and HR_{2}=0.77 for the OTP. The correlation between endpoints is not reported, but it is known than the HR for the Composite endpoint (PFS) is 0.79. Under this situation, if we assume constant hazards (Risk over time) for both endpoints, the use of PFS as composite endpoint is preferred. In fact, in any combination of hazards (increasing, decreasing or constant), the design with the PFS as the primary endpoint is mors efficient than the use of the Endpoint 1.
References
 Gomez G, Lagakos SW. Statistical considerations when using a composite endpoint for comparing treatment. 2013. Statistics in Medicine. 32(5):71938. doi: 10.1002/sim.5547.