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Reverse Time-to-Death as Time-Scale in Time-to-Event Analysis for Studies of Advanced Illness and Palliative Care.
Yin Bun Cheung1,2,3, Xiangmei Ma2, Isha Chaudhry1,4
1Programme in Health Services & Systems Research, Duke-NUS Medical School, National University of Singapore, Singapore, Singapore.
Statistics in Medicine
|January 23, 2025
Summary
Reverse time-to-death (rTTD) analysis mitigates confounding in advanced illness studies. This novel time-scale improves the accuracy of time-to-event analyses, especially when dealing with time-varying confounders near end-of-life.
Area of Science:
- Biostatistics
- Epidemiology
- Gerontology
Background:
- Adverse events increase as patients with advanced illness approach end-of-life.
- Exposures near end-of-life, like palliative care, can be confounded by proximity to death.
Purpose of the Study:
- To introduce and evaluate reverse time-to-death (rTTD) as a time-scale for time-to-event analysis.
- To mitigate time-varying confounding in studies of advanced illness.
Main Methods:
- Proposed the reverse time-to-death (rTTD) concept and applied it to time-to-event analysis using partial likelihood.
- Utilized data on palliative care uptake and emergency department visits in advanced cancer patients in Singapore.
- Compared rTTD with the conventional time-on-study (TOS) time-scale.
Main Results:
- rTTD analysis demonstrated that palliative care patients had higher emergency department visit rates due to being closer to end-of-life.
- rTTD analysis mitigated confounding, showing minimal change in hazard ratio estimates when covariates were omitted, unlike TOS analysis.
- Simulations confirmed rTTD had smaller relative bias and root mean square error than TOS-based analysis.
Conclusions:
- Reverse time-to-death (rTTD) offers a robust method for controlling time-varying confounding in advanced illness research.
- This approach is effective even with unmeasured confounders, enhancing the reliability of time-to-event analyses.
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