Table 1.
Attributes of estimands and graphical display of statistical methods
| Objective | Attributes | Graphical display | |||
|---|---|---|---|---|---|
| Population | Variables (endpoints) | Strategies for dealing with death | Effect measures | ||
| Time-to-deterioration (TTD) analysis (method for evaluating composite variables) | |||||
| • Evaluate time to deterioration (death or deterioration) | • All participants | • Time to first event (death or deterioration) |
• Composite endpoint • Death and deterioration are equally treated |
• Event probability at a specified time • Hazard ratio • Median (or mean) time to event |
• Describe the proportion of deterioration by survival curves |
| Prioritized composite outcome approach (method for evaluating composite variables) | |||||
| • Evaluate “win” by multiple aspects (multiple endpoints) | • All participants |
• Composite endpoint by death and deterioration • “Win” defined by generalized pairwise comparisons |
• Composite endpoint • Requires eliciting expert opinion on ordering death and QOL |
• Win ratio [27] • Net benefit [15] |
• Describe the combination of two step charts of cumulative probability of death and that of QOL deterioration |
| Semi-competing risk analysis (method for evaluating composite variables) | |||||
| • Evaluate the cumulative probability of QOL deterioration having occurred in the presence of death | • All participants | • Time to deterioration | • Competing risks |
• Sub-distributional hazard ratio • Cause specific hazard ratio |
• Describe the cumulative probability of QOL deterioration (cumulative incidence function) |
| Linear mixed model for repeated measures (MMRM) (method for evaluating QOL itself) | |||||
| • Evaluate the magnitude of worsening QOL | • All participants |
• QOL at the time of primary interest • QOL at every visit |
• Assuming missing at random for death • Implicitly impute data beyond death |
• Mean difference in QOL at the time of primary interest • Difference in slopes of QOL trajectories over time |
• Describe a trajectory of mean QOL over time using a line chart with a measure of uncertainty |
| Principal stratification for survivor average causal effect (SACE) (method for evaluating QOL itself) | |||||
| • Evaluate the magnitude of worsening QOL | • Participants who would not die regardless of which treatment they received (“always survivors”) |
• QOL at the time of primary interest • QOL at every visit |
• Death in the target population does not occur • The target population is not directly identifiable |
• Mean difference in QOL at the time of primary interest • Difference in slopes of QOL trajectories over time |
• Describe a trajectory of QOL over time by line chart with a measure of uncertainty |
QOL quality of life