ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2022
The Timing, the Treatment, the Question: Comparison of Epidemiologic Approaches to Minimize Immortal Time Bias in Real-World Data Using a Surgical Oncology Example.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Identifying, handling and impact of immortal time bias on addressing treatment effects in observational studies using routinely collected data.BMC medical research methodology · 2025Pooled it
- Mycophenolate and azathioprine in fibrotic interstitial lung disease.American journal of respiratory and critical care medicine · 2026Observational
- Dipeptidyl Peptidase-4 Inhibitor Use and Risk of Pemphigus Vulgaris and Foliaceus: A Retrospective Cohort Study Using Databases of the Korea National Health Insurance Claims and the National Health Screening Examination.The Journal of dermatology · 2026Article
- Variation in Surgical Management of Stage IV Breast Cancer: Local/Institutional and Regional Geographic Considerations.Annals of surgical oncology · 2026Article
- ASO Author Reflections on "Variation in Surgical Management of Stage IV Breast Cancer: Local/Institutional and Regional Geographic Considerations."Annals of surgical oncology · 2026Article
- Clarifying risk and treatment trajectories in ductal prostate cancer.World journal of urology · 2026Article
- Primary care physician documentation in oncology electronic health records: prognostic marker or immortal-time bias?ESMO real world data and digital oncology · 2026Article
- Oral glucocorticoid treatment for checkpoint inhibitor-associated inflammatory arthritis does not affect cancer progression-free survival: a RADIOS Registry study.Annals of the rheumatic diseases · 2026Observational
- A Cautionary Note for Plasmode Simulation Studies in the Setting of Causal Inference.Statistics in medicine · 2026Article
- Article
- Timing of Antidiabetic Medication Initiation and Risk of Cardiovascular Events and Mortality.JAMA network open · 2026Article
- Candidemia in Türkiye demonstrates nationwide predominance of non-albicans Candida and Candida auris detection.Scientific reports · 2026Article
- Effect of Primary Breast Surgery on Prognosis in Breast Cancer Patients Presenting with Isolated Bone Metastases.Cancers · 2026Article
- Methodological Challenges of Emulating a Target Trial to Assess Effectiveness of Timing of PCSK9 Inhibitor Treatment Initiation Post Myocardial Infarction.Pharmacoepidemiology and drug safety · 2026Article
- Tumor microenvironment-oriented HNGCIscore identifies immunotherapy-sensitive subgroups in ICI retreatment of HER2-negative advanced gastric cancer.Frontiers in oncology · 2026Article
- When to Start, How to Classify, and Whom to Include: A Methodological Assessment and Illustrative Example of the Clone-Censor-Weight Approach for Evaluating Intervention Timing in Observational Studies.Clinical epidemiology · 2026Article
- Associations between Immune-related Adverse Events and Prognosis in Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy.Internal medicine (Tokyo, Japan) · 2026Review
- Effect of fresh-frozen plasma transfusion on intraventricular hemorrhage risk in preterm infants with prolonged APTT: a target trial emulation with causal forest analysis.Frontiers in neuroscience · 2026Article
- The Impact of Immortal Time Bias on Survival Estimates of Patients with Heart Failure with Improved Ejection Fraction.CJC open · 2025Article
- Comments Regarding: "Survival Outcomes of Cytoreductive Surgery with HIPEC in Gastric Adenocarcinoma: A National Cancer Database Study".Annals of surgical oncology · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
backgroundStudies evaluating the effects of cancer treatments are prone to immortal time bias that, if unaddressed, can lead to treatments appearing more beneficial than they are.
methodsTo demonstrate the impact of immortal time bias, we compared results across several analytic approaches (dichotomous exposure, dichotomous exposure excluding immortal time, time-varying exposure, landmark analysis, clone-censor-weight method), using surgical resection among women with metastatic breast cancer as an example. All adult women diagnosed with incident metastatic breast cancer from 2013-2016 in the National Cancer Database were included. To quantify immortal time bias, we also conducted a simulation study where the "true" relationship between surgical resection and mortality was known.
results24,329 women (median age 61, IQR 51-71) were included, and 24% underwent surgical resection. The largest association between resection and mortality was observed when using a dichotomized exposure [HR, 0.54; 95% confidence interval (CI), 0.51-0.57], followed by dichotomous with exclusion of immortal time (HR, 0.62; 95% CI, 0.59-0.65). Results from the time-varying exposure, landmark, and clone-censor-weight method analyses were closer to the null (HR, 0.67-0.84). Results from the plasmode simulation found that the time-varying exposure, landmark, and clone-censor-weight method models all produced unbiased HRs (bias -0.003 to 0.016). Both standard dichotomous exposure (HR, 0.84; bias, -0.177) and dichotomous with exclusion of immortal time (HR, 0.93; bias, -0.074) produced meaningfully biased estimates.
conclusionsResearchers should use time-varying exposures with a treatment assessment window or the clone-censor-weight method when immortal time is present. IMPACT: Using methods that appropriately account for immortal time will improve evidence and decision-making from research using real-world data.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.