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Comparison of a Target Trial Emulation Framework vs Cox Regression to Estimate the Association of Corticosteroids With COVID-19 Mortality.
Hoffman, Katherine L; Schenck, Edward J; Satlin, Michael J; Whalen, William; Pan, Di; Williams, Nicholas; Díaz, Iván.
  • Hoffman KL; Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medicine, New York, New York.
  • Schenck EJ; Division of Pulmonary and Critical Care, Department of Medicine, Weill Cornell Medicine, New York, New York.
  • Satlin MJ; Division of Infectious Disease, Department of Medicine, Weill Cornell Medicine, New York, New York.
  • Whalen W; Division of Pulmonary and Critical Care, Department of Medicine, Weill Cornell Medicine, New York, New York.
  • Pan D; Division of Pulmonary and Critical Care, Department of Medicine, Weill Cornell Medicine, New York, New York.
  • Williams N; Mailman School of Public Health, Department of Epidemiology, Columbia University, New York, New York.
  • Díaz I; Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medicine, New York, New York.
JAMA Netw Open ; 5(10): e2234425, 2022 10 03.
Article in English | MEDLINE | ID: covidwho-2047378
ABSTRACT
Importance Communication and adoption of modern study design and analytical techniques is of high importance for the improvement of clinical research from observational data.

Objective:

To compare a modern method for statistical inference, including a target trial emulation framework and doubly robust estimation, with approaches common in the clinical literature, such as Cox proportional hazards models. Design, Setting, and

Participants:

This retrospective cohort study used longitudinal electronic health record data for outcomes at 28-days from time of hospitalization within a multicenter New York, New York, hospital system. Participants included adult patients hospitalized between March 1 and May 15, 2020, with COVID-19 and not receiving corticosteroids for chronic use. Data were analyzed from October 2021 to March 2022. Exposures Corticosteroid exposure was defined as more than 0.5 mg/kg methylprednisolone equivalent in a 24-hour period. For target trial emulation, exposures were corticosteroids for 6 days if and when a patient met criteria for severe hypoxia vs no corticosteroids. For approaches common in clinical literature, treatment definitions used for variables in Cox regression models varied by study design (no time frame, 1 day, and 5 days from time of severe hypoxia). Main Outcomes and

Measures:

The main outcome was 28-day mortality from time of hospitalization. The association of corticosteroids with mortality for patients with moderate to severe COVID-19 was assessed using the World Health Organization (WHO) meta-analysis of corticosteroid randomized clinical trials as a benchmark.

Results:

A total of 3298 patients (median [IQR] age, 65 [53-77] years; 1970 [60%] men) were assessed, including 423 patients who received corticosteroids at any point during hospitalization and 699 patients who died within 28 days of hospitalization. Target trial emulation analysis found corticosteroids were associated with a reduced 28-day mortality rate, from 32.2%; (95% CI, 30.9%-33.5%) to 25.7% (95% CI, 24.5%-26.9%). This estimate is qualitatively identical to the WHO meta-analysis odds ratio of 0.66 (95% CI, 0.53-0.82). Hazard ratios using methods comparable with current corticosteroid research range in size and direction, from 0.50 (95% CI, 0.41-0.62) to 1.08 (95% CI, 0.80-1.47). Conclusions and Relevance These findings suggest that clinical research based on observational data can be used to estimate findings similar to those from randomized clinical trials; however, the correctness of these estimates requires designing the study and analyzing the data based on principles that are different from the current standard in clinical research.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Drug Treatment Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Qualitative research / Randomized controlled trials / Reviews Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: JAMA Netw Open Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Drug Treatment Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Qualitative research / Randomized controlled trials / Reviews Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: JAMA Netw Open Year: 2022 Document Type: Article