ArticleEuropean journal of epidemiology2017
Immortal time bias in pharmacoepidemiological studies on cancer patient survival: empirical illustration for beta-blocker use in four cancers with different prognosis.
Article in European journal of epidemiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Genetically proxied therapeutic inhibition of antihypertensive drug targets and risk of pancreatic cancer: a mendelian randomization analysis.BMC cancer · 2025Pooled it
- Impact of beta blockers on cancer neuroimmunology: a systematic review and meta-analysis of survival outcomes and immune modulation.Frontiers in immunology · 2025Pooled it
- Primary care physician documentation in oncology electronic health records: prognostic marker or immortal-time bias?ESMO real world data and digital oncology · 2026Article
- Antitumour Effects of β-Blockers: A Narrative Review of the Literature.Current issues in molecular biology · 2026Review
- Review
- Pharmacological interventions targeting β-adrenoceptors in colorectal cancer: an evolving paradigm.Inflammopharmacology · 2025Review
- The Impact of Beta Blockers on Survival in Cancer Patients: A Systematic Review and Meta-Analysis.Cancers · 2025Review
- Immortal time bias in survival outcomes when comparing treatment with chemotherapy versus immunochemotherapy for non-small cell lung cancer.Translational lung cancer research · 2025Article
- The influence of immortal time bias in observational studies examining associations of antifibrotic therapy with survival in idiopathic pulmonary fibrosis: A simulation study.Frontiers in medicine · 2023Article
- Beta-blocker exposure and survival outcomes in patients with advanced pancreatic ductal adenocarcinoma: a retrospective cohort study (BETAPANC).Frontiers in pharmacology · 2023Article
- Timing of adjuvant chemotherapy initiation and mortality among colon cancer patients at a safety-net health system.BMC cancer · 2022Article
- Risk of Cancer in Association with Ranitidine and Nizatidine vs Other H2 Blockers: Analysis of the Japan Medical Data Center Claims Database 2005-2018.Drug safety · 2021Article
- Beta-blockers have no impact on survival in pancreatic ductal adenocarcinoma prior to cancer diagnosis.Scientific reports · 2021Article
- Effects of Antihypertensive Drugs Use on Risk and Prognosis of Colorectal Cancer: A Meta-Analysis of 37 Observational Studies.Frontiers in pharmacology · 2021Article
- Does sympathetic nervous system modulate tumor progression? A narrative review of the literature.Journal of drug assessment · 2020Review
- Tumour innervation and neurosignalling in prostate cancer.Nature reviews. Urology · 2020Review
- Observational
- Use of Antihypertensive Medications and Survival Rates for Breast, Colorectal, Lung, or Stomach Cancer.American journal of epidemiology · 2019Article
- Article
- Cardiovascular Disease and Cancer: Is There Increasing Overlap?Current oncology reports · 2019Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immortal time bias (ITB) is still seen frequently in medical literature. However, not much is known about this bias in the field of cancer (pharmaco-)epidemiology. In context of a hypothetical beneficial beta-blocker use among cancer patients, we aimed to demonstrate the magnitude of ITB among 9876 prostate, colorectal, lung and pancreatic cancer patients diagnosed between 1998 and 2011, which were selected from a database linkage of the Netherlands Cancer Registry and the PHARMO Database Network. Hazard ratios (HR) and 95% confidence intervals from three ITB scenarios, defining exposure at a defined point after diagnosis (model 1), at any point after diagnosis (model 2) and as multiple exposures after diagnosis (model 3), were calculated to investigate the association between beta-blockers and cancer prognosis using Cox proportional hazards regression. Results were compared to unbiased estimates derived from the Mantel-Byar model. Ignoring ITB led to substantial smaller HRs for beta-blocker use proposing a significant protective association in all cancer types [e.g. HR 0.18 (0.07-0.43) for pancreatic cancer in model 1], whereas estimates derived from the Mantel-Byar model were mainly suggesting no association [e.g. HR 1.10 (0.84-1.44)]. The magnitude of bias was consistently larger among cancer types with worse prognosis [overall median HR differences between all scenarios in model 1 and Mantel-Byar model of 0.56 (prostate), 0.72 (colorectal), 0.77 (lung) and 0.85 (pancreas)]. In conclusion, ITB led to spurious beneficial associations of beta-blocker use among cancer patients. The magnitude of ITB depends on the duration of excluded immortal time and the prognosis of each cancer.
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