Negative-Control Calibration and E-Value Bounding of Cancer-Survivor Mortality Contrasts: A Design-Aware Competing-Risks Analysis
4 affiliations
- 1Department of Mathematics, University of Architecture, Civil Engineering and Geodesy (UACEG), 1 Hristo Smirnenski Blvd., 1164 Sofia, Bulgaria
- 2Department of Applied Computer Science and Mathematical Modelling, Faculty of Mathematics and Computer Science, University of Warmia and Mazury in Olsztyn, Słoneczna 54, 10-710 Olsztyn, Poland
- 3Department of Mathematical Modelling and Numerical Methods, Faculty of Applied Mathematics and Informatics, Technical University of Sofia, 8 “Kliment Ohridski” Blvd., 1000 Sofia, Bulgaria
- 4Faculty of Mathematics and Informatics, Sofia University “St. Kliment Ohridski”, 5 James Bourchier Blvd., 1164 Sofia, Bulgaria
Abstract
Objective: Cardiovascular death among cancer survivors is widely studied in population surveys, yet the survivor-versus-non-survivor contrast those studies rest on is rarely tested for confounding, and a survey cohort of prevalent survivors is left-truncated by design. The objective of this article is to test that contrast itself. Methods: The methods we used built a nationally representative survivor cohort from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 (3826 survivors among 52,398 examined adults) linked to the National Death Index, with 288 deaths from diseases of the heart and 497 cancer deaths, and paired survey-weighted Fine–Gray competing-risks models with designed probes of what these data cannot support. Results: Our results are that accidental death, a negative-control outcome, was raised among survivors (hazard ratio 1.78, 95% CI: 0.89–3.54) and equally among participants whose only malignancy was a skin cancer (2.01, 0.87–4.66). For cardiovascular death, that negative-control exposure reproduced the survivor contrast (0.87, 0.65–1.18 against 0.84, 0.71–1.00), leaving a calibrated contrast of 0.96 (0.70–1.32). Refitting on the time-since-diagnosis scale with delayed entry left the comorbidity index’s association with cardiovascular death unchanged (1.41, 1.22–1.64 against 1.40, 1.24–1.59). Net survival against internally modeled expected mortality, 0.897 (0.869–0.924) at 10 years, agreed with the recorded cancer-death incidence of 0.115 (0.102–0.127). Conclusions: The conclusions drawn are that what such a survey establishes about survivor mortality is narrower than it appears.
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BibTeX
@article{naskinova2026negativecontrol,
title = {{Negative-Control Calibration and E-Value Bounding of Cancer-Survivor Mortality Contrasts: A Design-Aware Competing-Risks Analysis}},
author = {Irina Naskinova and Mikhail Kolev and Meglena Lazarova and Hristo Kalinov and Velin Klisurov},
journal = {Cancers},
year = {2026},
month = nov,
doi = {10.3390/cancers18213544},
url = {https://www.mdpi.com/2072-6694/18/21/3544},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Negative-Control Calibration and E-Value Bounding of Cancer-Survivor Mortality Contrasts: A Design-Aware Competing-Risks Analysis
AU - Irina Naskinova
AU - Mikhail Kolev
AU - Meglena Lazarova
AU - Hristo Kalinov
AU - Velin Klisurov
PY - 2026
DA - 2026/11/04
JO - Cancers
DO - 10.3390/cancers18213544
UR - https://www.mdpi.com/2072-6694/18/21/3544
AB - Objective: Cardiovascular death among cancer survivors is widely studied in population surveys, yet the survivor-versus-non-survivor contrast those studies rest on is rarely tested for confounding, and a survey cohort of prevalent survivors is left-truncated by design. The objective of this article is to test that contrast itself. Methods: The methods we used built a nationally representative survivor cohort from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 (3826 survivors among 52,398 examined adults) linked to the National Death Index, with 288 deaths from diseases of the heart and 497 cancer deaths, and paired survey-weighted Fine–Gray competing-risks models with designed probes of what these data cannot support. Results: Our results are that accidental death, a negative-control outcome, was raised among survivors (hazard ratio 1.78, 95% CI: 0.89–3.54) and equally among participants whose only malignancy was a skin cancer (2.01, 0.87–4.66). For cardiovascular death, that negative-control exposure reproduced the survivor contrast (0.87, 0.65–1.18 against 0.84, 0.71–1.00), leaving a calibrated contrast of 0.96 (0.70–1.32). Refitting on the time-since-diagnosis scale with delayed entry left the comorbidity index’s association with cardiovascular death unchanged (1.41, 1.22–1.64 against 1.40, 1.24–1.59). Net survival against internally modeled expected mortality, 0.897 (0.869–0.924) at 10 years, agreed with the recorded cancer-death incidence of 0.115 (0.102–0.127). Conclusions: The conclusions drawn are that what such a survey establishes about survivor mortality is narrower than it appears.
SN - 2072-6694
ER -