How to estimate the effect of treatment duration on survival outcomes using observational data

Hernán, Miguel A.

doi:10.1136/bmj.k182

Cited by 119 publications

(129 citation statements)

References 17 publications

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“…In addition, because eligible individuals could not be uniquely assigned to a strategy at baseline when emulating target trials with a grace period, we duplicated ("cloned") eligible individuals and assigned 1 clone to each treatment strategy (eFigure 3 in the Supplement). 30 We then censored clones if they had no data compatible with their assigned treatment strategy by the end of the grace period. 6,30 Details on all possible censoring schemes are given in eAppendix 2 in the Supplement.…”

Section: Resultsmentioning

confidence: 99%

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Estimates of Overall Survival in Patients With Cancer Receiving Different Treatment Regimens

et al. 2020

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IMPORTANCEThe Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database may provide insights into the comparative effectiveness of oncological treatments for elderly individuals who are underrepresented in clinical trials. OBJECTIVE To evaluate the suitability of SEER-Medicare data for assessing the effectiveness of adding a drug to an existing treatment regimen on the overall survival of elderly patients with cancer. DESIGN, SETTING, AND PARTICIPANTS This comparative effectiveness study analyzed SEER-Medicare data from 9549 individuals who received a new diagnosis of stage II colorectal cancer (2008-2012) and 940 patients who received a new diagnosis of advanced pancreatic adenocarcinoma (2007-2012), with follow-up to December 31, 2013 (SEER-Medicare data released in 2015). Two (hypothetical) target trials were designed and emulated based on 2 existing randomized clinical trials: (1) adjuvant fluorouracil after curative surgery for individuals with stage II colorectal cancer and (2) erlotinib added to gemcitabine for individuals with advanced pancreatic adenocarcinoma. Data were analyzed January 2018 to March 2019. EXPOSURES The following treatment strategies were compared: (1) fluorouracil initiation vs no initiation within 3 months of tumor resection and (2) erlotinib initiation vs no initiation within 12 weeks of gemcitabine initiation. MAIN OUTCOMES AND MEASURES All-cause mortality within 60 months of baseline for the fluorouracil trial and within 72 weeks for the erlotinib trial. RESULTS Compared with 3293 individuals in the existing fluorouracil trial, 9549 eligible individuals included in the present analyses were more likely to have colon cancer (8565 [90%] vs 2291 [71%]) and were older (median [interquartile range], 79 [73-84] vs 63 [56-68] years). The 5-year risk difference for initiation vs noninitiation of fluorouracil after surgery was −3.8% (95% CI, −14.8% to 12.6%), and the mortality hazard ratio (HR) was 0.95 (95% CI, 0.85-1.04). Compared with 569 individuals in the existing erlotinib trial, 940 eligible patients included in the present analysis were older (median [range], 74 [66-93] vs 64 [36-92] years) and more likely to be male (547 [58%] vs 298[52%]). The 1-year risk difference for initiation vs noninitiation of erlotinib was 4.7% (95% CI, −9.4% to 18.0%), and the corresponding mortality HR was 1.04 (95% CI, 0.86-1.42). In naive analyses, the mortality HR estimate was 1.14 (95% CI, 0.95-1.36) for the fluorouracil emulation and 0.68 (95% CI, 0.54-0.87) for the erlotinib emulation.

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Section: Resultsmentioning

confidence: 99%

“…30 We then censored clones if they had no data compatible with their assigned treatment strategy by the end of the grace period. 6,30 Details on all possible censoring schemes are given in eAppendix 2 in the Supplement.…”

Section: Resultsmentioning

confidence: 99%

Estimates of Overall Survival in Patients With Cancer Receiving Different Treatment Regimens

et al. 2020

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“…An observational study design, as shown in this study, from a large clinical databases can be more representative to real patient population, may better reflect real-world practice, relatively inexpensive, the ethical issues appear less complex (no patients are randomized). In addition, the studies are in progress to use the big data and/or large observational study for causal analyses, besides correlation analyses [31][32][33] .…”

Section: Discussionmentioning

confidence: 99%

Perioperative use of renin-angiotensin system inhibitors and outcomes in patients undergoing cardiac surgery

Ding¹,

Zhang²,

Liu³

et al. 2018

Preprint

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This study examined association between use of perioperative renin-angiotensin system inhibitors (RASi) and outcomes in patients undergoing coronary artery bypass graft (CABG) and/or valve surgery. Of all the patients, 8,112 patients met inclusion criteria and were divided into four groups: with or without preoperative (PreRASi) or postoperative RASi (PostRASi) respectively. With the use of propensity scores matching and sensitivity analyses to reduce treatment selection bias, this cohort study showed that PreRASi was associated with a significant reduction in postoperative 30-day mortality compared with without one (3.41% vs. 5.02%, OR 0.69, 95% CI 0.54 – 0.90, P=0.01); PostRASi was associated with reduced long-term mortality rate compared with without one (3.66% vs. 4.86%, RR 0.75, 95% CI 0.57 – 0.93 at 1 year; 17.12% vs. 19.91%, RR 0.86, 95% CI 0.75 – 0.97 at 6 year; P= 0.0250 respectively). The results suggest that perioperative use of RASi has a significant benefit for the postoperative and long-term survival among patients undergoing cardiac surgery.

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“…In recent years, many excellent methods to control these biases have been developed, such as propensity score analysis, inverse probability weighting, marginal structural modeling, bootstrapping, instrumental variable, etc. [5][6][7][8]. Given the low cost and easy accessibility of DBs and the necessity of bias control, observational studies are considered an excellent tool for new researchers.…”

Section: Modern Epidemiology and Clinical Researchmentioning

confidence: 99%

“…For analyses of these longitudinal data with time-varying confounders, Robins reported a g formula to measure the healthy worker survivor effect [7]. Although this formula is complicated, Hernan recently reported a simple three-step approach to estimate the effect of treatment duration on survival outcomes using observational data [8]. The first step is duplicating people to assign them to treatment duration strategies at time zero, eliminating immortal time bias [33][34][35].…”

Section: Flow Of a Propensity Score Analysismentioning

confidence: 99%

Introduction to clinical research based on modern epidemiology

Hoshino

2020

Clin Exp Nephrol

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Over the past 20 years, recent advances in science technologies have dramatically changed the styles of clinical research. Currently, it has become more popular to use recent modern epidemiological techniques, such as propensity score, instrumental variable, competing risks, marginal structural modeling, mixed effects modeling, bootstrapping, and missing data analyses, than before. These advanced techniques, also known as modern epidemiology, may be strong tools for performing good clinical research, especially in large-scale observational studies, along with relevant research questions, good databases, and the passion of researchers. However, to use these methods effectively, we need to understand the basic assumptions behind them. Here, I will briefly introduce the concepts of these techniques and their implementation. In addition, I would like to emphasize that various types of clinical studies, not only large database studies but also small studies on rare and intractable diseases, are equally important because clinicians always do their best to take care of many kinds of patients who suffer from various kidney diseases and this is our most important mission.

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How to estimate the effect of treatment duration on survival outcomes using observational data

Cited by 119 publications

References 17 publications

Estimates of Overall Survival in Patients With Cancer Receiving Different Treatment Regimens

Estimates of Overall Survival in Patients With Cancer Receiving Different Treatment Regimens

Perioperative use of renin-angiotensin system inhibitors and outcomes in patients undergoing cardiac surgery

Introduction to clinical research based on modern epidemiology

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