Table 2.
Strengths and Weaknesses of Five Proposed Endpoints in Chronic GVHD Therapy Trials
| Proposed Endpoint | Definition | Statistical Considerations | Strengths | Weaknesses |
|---|---|---|---|---|
| GVHD Response | Complete plus partial response based on clinician-reported measures | • Comparison of proportions with treatment response at a specific time point | • Direct measure of success • Lengthy follow-up not needed • Easily applied |
• Scales not fully qualified |
| Failure free survival | Survival for a defined period without new systemic treatment, death or recurrent malignancy | • Time-to-event, or • Comparison of proportions with failure-free survival at a specific time point |
• Benchmarks available for 1st and 2nd-line treatment • Correlates with overall improvement reported by providers and patients • Correlates with ability to discontinue systemic treatment |
• Indirect measure of failure • Improvement is not measured (i.e., GVHD manifestations may persist) • New treatment decisions are subject to bias and inconsistency • Not accepted for regulatory approvals |
| Survival without progressive impairment | Survival without an enduring chronic GVHD-related effect that threatens or compromises physical well-being or function in ways that cannot be easily reversed | • Time-to-event, or • Comparison of proportions surviving without progressive impairment at a specific time point |
• Failure directly measured • Correlates with overall improvement reported by providers and patients |
• Improvement is not measured (i.e., GVHD manifestations may persist) • Impairment is not yet fully defined • Some impairment measures might not be entirely specific for chronic GVHD • Impairment can be caused by adverse events |
| Patient-reported outcomes | Self-reported patient information on symptoms and multi-dimensional quality of life | • Comparison of proportions with clinically meaningful improvement at a specific time point • Comparison of distributions between study arms |
• Captures the patient perspective • Lengthy follow-up not needed • Easily applied |
• Subject to respondent biases • Missing data difficult to control • Claims limited to PROs |
| Composite scale | Selected measures from provider and patient | • Comparison of proportions with clinically meaningful improvement at a specific time point • Comparison of distributions between study arms |
• Aggregates data from multiple perspectives | • Scale not developed or qualified |