EVALUATING THE ROBUSTNESS OF TIME-TO-EVENT ANALYSES IN DE-IDENTIFIED REAL-WORLD DATASET USING A PROXY DATE OF DEATH ALGORITHM: A VALIDATION STUDY IN PATIENTS WITH MULTIPLE MYELOMA
Author(s)
Elisabet Viayna, PhD1, Rahul Rajkumar, MD2, Dan Wheedleton, MPP3, Jiani Zhou, PhD, MSPH4, Jonathan Lilley, BS5, Marley Boyd, MS3, Elisabeth Calderón-Gómez, PharmD, PhD1, Jeffrey Brown, PhD3.
1Grifols S.A., Sant Cugat del Valles, Spain, 2Boston Strategic Partners, Inc, Boston, MA, USA, 3TriNetX, LLC, Cambridge, MA, USA, 4Associate Director, Global HEOR&RWE, Grifols SSNA, Durham, NC, USA, 5Boston Strategic Partners, Boston, MA, USA.
1Grifols S.A., Sant Cugat del Valles, Spain, 2Boston Strategic Partners, Inc, Boston, MA, USA, 3TriNetX, LLC, Cambridge, MA, USA, 4Associate Director, Global HEOR&RWE, Grifols SSNA, Durham, NC, USA, 5Boston Strategic Partners, Boston, MA, USA.
OBJECTIVES: Accurate date of death (DoD) ascertainment is critical for time-to-event analyses in real-world studies; however, many databases provide death data in partially de-identified formats (e.g., month/year). This study evaluated the performance of a pragmatic proxy DoD algorithm against full DoD records by comparing severe infection-free survival (IFS) and overall survival (OS) estimates.
METHODS: This retrospective study utilized TriNetX Dataworks-USA to identify adults with multiple myeloma initiating B-cell maturation antigen bispecific antibodies (BsAbs) between Jun-2021 and Jun-2025. Patients initiating immunoglobulin-replacement therapy (IgRT) within 60 days after index BsAbs initiation without severe infection evidence were considered exposed to primary IgRT prophylaxis; remaining patients were classified as unexposed. To mitigate immortal-time bias, IgRT was modeled as a time-dependent exposure. IFS (severe infection or death) and OS were assessed using the Simon-Makuch method with Mantel-Byar comparison, and hazard ratios (HR) were estimated using Cox proportional hazards models. When only month-year of death was available, a proxy DoD was assigned as either the last encounter discharge date within the month of death, or the last day of the month. Proxy-derived survival estimates were compared against analyses using full DoD records.
RESULTS: There was 100% concordance between mortality status and death month-year. The mean difference between actual and proxy DoD was −10 days (median −7; IQR −1-to-0; range −30-to-19). Inference was consistent across approaches. Both Mantel-Byar comparisons remained statistically significant for IFS (0.015 vs. 0.024) and OS (0.0086 vs. 0.0098). Cox models yielded near-identical estimates: HR 0.72 vs. 0.73 for IFS (both p=0.02) and 0.48 vs. 0.46 for OS (both p=0.01).
CONCLUSIONS: In this study of adult patients with multiple myeloma, the proxy DoD algorithm using month-year of death produced survival results practically identical to those derived from full DoD records, confirming the robustness of mortality-related analyses limited to month-year granularity.
METHODS: This retrospective study utilized TriNetX Dataworks-USA to identify adults with multiple myeloma initiating B-cell maturation antigen bispecific antibodies (BsAbs) between Jun-2021 and Jun-2025. Patients initiating immunoglobulin-replacement therapy (IgRT) within 60 days after index BsAbs initiation without severe infection evidence were considered exposed to primary IgRT prophylaxis; remaining patients were classified as unexposed. To mitigate immortal-time bias, IgRT was modeled as a time-dependent exposure. IFS (severe infection or death) and OS were assessed using the Simon-Makuch method with Mantel-Byar comparison, and hazard ratios (HR) were estimated using Cox proportional hazards models. When only month-year of death was available, a proxy DoD was assigned as either the last encounter discharge date within the month of death, or the last day of the month. Proxy-derived survival estimates were compared against analyses using full DoD records.
RESULTS: There was 100% concordance between mortality status and death month-year. The mean difference between actual and proxy DoD was −10 days (median −7; IQR −1-to-0; range −30-to-19). Inference was consistent across approaches. Both Mantel-Byar comparisons remained statistically significant for IFS (0.015 vs. 0.024) and OS (0.0086 vs. 0.0098). Cox models yielded near-identical estimates: HR 0.72 vs. 0.73 for IFS (both p=0.02) and 0.48 vs. 0.46 for OS (both p=0.01).
CONCLUSIONS: In this study of adult patients with multiple myeloma, the proxy DoD algorithm using month-year of death produced survival results practically identical to those derived from full DoD records, confirming the robustness of mortality-related analyses limited to month-year granularity.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
RWD19
Topic
Clinical Outcomes, Real World Data & Information Systems, Study Approaches
Topic Subcategory
Data Protection, Integrity, & Quality Assurance, Reproducibility & Replicability
Disease
Oncology