Four main statistical approaches to validate a surrogate end point
| Concepts . | Approach . | Paradigm . | Data . | Treatment effect . | Question addressed . |
|---|---|---|---|---|---|
| Proportion of treatment effect | Single-trial | Causal effect | IPD | Observed | What is the proportion of treatment effect on OS, that is, explained by the surrogate? |
| Trial-level coefficient of determination | Multiple trial | Causal association | IPD | Observed | Based on past trials, how will treatment effect measured by surrogate predict the treatment effect on OS in a future trial? |
| Principal stratification | Single trial, or multiple trial | Causal association | IPD | Potential (using counterfactuals) | Granted the status of the surrogate, can the treatment assignment predict OS? |
| Mediation analysis | Single trial | Causal effect | IPD | Potential (using counterfactuals) | How is the treatment effect on OS mediated by the surrogate end point? |
| Concepts . | Approach . | Paradigm . | Data . | Treatment effect . | Question addressed . |
|---|---|---|---|---|---|
| Proportion of treatment effect | Single-trial | Causal effect | IPD | Observed | What is the proportion of treatment effect on OS, that is, explained by the surrogate? |
| Trial-level coefficient of determination | Multiple trial | Causal association | IPD | Observed | Based on past trials, how will treatment effect measured by surrogate predict the treatment effect on OS in a future trial? |
| Principal stratification | Single trial, or multiple trial | Causal association | IPD | Potential (using counterfactuals) | Granted the status of the surrogate, can the treatment assignment predict OS? |
| Mediation analysis | Single trial | Causal effect | IPD | Potential (using counterfactuals) | How is the treatment effect on OS mediated by the surrogate end point? |