ArticleInternational journal of epidemiology2020
Reflection on modern methods: trial emulation in the presence of immortal-time bias. Assessing the benefit of major surgery for elderly lung cancer patients using observational data.
Article in International journal of epidemiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 3 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
128 citing papers in PubMed, 3 syntheses or guidelines pooled it, 173 citations in OpenAlex.
- 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
- Use of sensitivity analyses to assess uncontrolled confounding from unmeasured variables in observational, active comparator pharmacoepidemiologic studies: a systematic review.American journal of epidemiology · 2025Pooled it
- Conducting observational analyses with the target trial emulation approach: a methodological systematic review.BMJ open · 2024Pooled it
- Morning versus afternoon administration of immune checkpoint inhibitors in metastatic non-small-cell lung cancer.Journal for immunotherapy of cancer · 2026Trial
- Effectiveness of treatment initiation for secondary fracture prevention in the older population: Japanese Bone-fracture Osteoporosis in Late-stage population Database study (J-BOLD) - emulation of a randomized target trial.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Trial
- Nirmatrelvir/ritonavir use in pregnant women with SARS-CoV-2 Omicron infection: a target trial emulation.Nature medicine · 2024Trial
- Comparative Effectiveness Analysis of Lumpectomy and Mastectomy for Elderly Female Breast Cancer Patients: A Deep Learning-based Big Data Analysis.The Yale journal of biology and medicine · 2023Trial
- Nirmatrelvir and risk of hospital admission or death in adults with covid-19: emulation of a randomized target trial using electronic health records.BMJ (Clinical research ed.) · 2023Trial
- Target Trial Emulation and Bias Through Missing Eligibility Data: An Application to a Study of Palivizumab for the Prevention of Hospitalization Due to Infant Respiratory Illness.American journal of epidemiology · 2023Trial
- Early versus deferred intravenous calcium in patients with sepsis and ionized hypocalcemia: a target-trial emulation.Journal of intensive care · 2026Article
- Aligning time zero and treatment assignment in target trial emulation of left ventricular unloading.Critical care (London, England) · 2026Article
- Target trial emulation studies in oncology: a comprehensive analysis.The oncologist · 2026Article
- Ultra-early versus early adjunctive vasopressin initiation after norepinephrine escalation in septic shock: a target trial emulation.Intensive care medicine · 2026Article
- Causal Effects of Early Discontinuation of Proton Pump Inhibitors on Kidney Failure.Kidney international reports · 2026Article
- Upfront or deferred radiotherapy combined with chemoimmunotherapy for inoperable oesophageal squamous cell carcinoma: a target trial emulation in China.EClinicalMedicine · 2026Article
- Early Mitral Valve Surgery and Survival in Asymptomatic Severe Primary Mitral Regurgitation.JAMA network open · 2026Article
- COVID-19 vaccination around immune checkpoint inhibitor start and survival in a nationwide cohort of patients with cancer.Nature medicine · 2026Article
- Association of antifungal treatment duration with 90-day mortality in critically ill adults with candidemia: a multicenter target trial emulation in France.EClinicalMedicine · 2026Article
- Study protocol for a target trial emulation: CHoosing the right diAlysis Modality in clinical PractIce: hemOdiafiltratioN or hemodialysis (CHAMPION).BMC nephrology · 2026Article
- Early versus delayed or no empagliflozin initiation after hospitalization for heart failure in the United States: a target trial emulation.ESC heart failure · 2026Article
68 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Acquiring real-world evidence is crucial to support health policy, but observational studies are prone to serious biases. An approach was recently proposed to overcome confounding and immortal-time biases within the emulated trial framework. This tutorial provides a step-by-step description of the design and analysis of emulated trials, as well as R and Stata code, to facilitate its use in practice. The steps consist in: (i) specifying the target trial and inclusion criteria; (ii) cloning patients; (iii) defining censoring and survival times; (iv) estimating the weights to account for informative censoring introduced by design; and (v) analysing these data. These steps are illustrated with observational data to assess the benefit of surgery among 70-89-year-old patients diagnosed with early-stage lung cancer. Because of the severe unbalance of the patient characteristics between treatment arms (surgery yes/no), a naïve Kaplan-Meier survival analysis of the initial cohort severely overestimated the benefit of surgery on 1-year survival (22% difference), as did a survival analysis of the cloned dataset when informative censoring was ignored (17% difference). By contrast, the estimated weights adequately removed the covariate imbalance. The weighted analysis still showed evidence of a benefit, though smaller (11% difference), of surgery among older lung cancer patients on 1-year survival. Complementing the CERBOT tool, this tutorial explains how to proceed to conduct emulated trials using observational data in the presence of immortal-time bias. The strength of this approach is its transparency and its principles that are easily understandable by non-specialists.
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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.