Dataset Information

Gastrointestinal prophylaxis for COVID-19: an illustration of severe bias arising from inappropriate comparators in observational studies.

ABSTRACT:

Objectives

We aimed to use setting-appropriate comparisons to estimate the effects of different gastrointestinal (GI) prophylaxis pharmacotherapies for patients hospitalized with COVID-19 and setting-inappropriate comparisons to illustrate how improper design choices could result in biased results.

Study design and setting

We identified 3,804 hospitalized patients aged ≥ 18 years with COVID-19 from March to November 2020. We compared the effects of different gastroprotective agents on clinical improvement of COVID-19, as measured by a published severity scale. We used propensity score-based fine-stratification for confounding adjustment. Based on guidelines, we prespecified comparisons between agents with clinical equipoise and inappropriate comparisons of users vs. nonusers of GI prophylaxis in the intensive care unit (ICU).

Results

No benefit was detected when comparing oral famotidine to omeprazole in patients treated in the general ward or ICUs. We also found no associations when comparing intravenous famotidine to intravenous pantoprazole. For inappropriate comparisons of users vs. nonusers in the ICU, the probability of improvement was reduced by 32%-45% in famotidine users and 21%-48% in omeprazole or pantoprazole users.

Conclusion

We found no evidence that GI prophylaxis improved outcomes for patients hospitalized with COVID-19 in setting-appropriate comparisons. An improper comparator choice can lead to spurious associations in critically ill patients.

SUBMITTER: Lin KJ

PROVIDER: S-EPMC9296251 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Gastrointestinal prophylaxis for COVID-19: an illustration of severe bias arising from inappropriate comparators in observational studies.

Lin Kueiyu Joshua KJ Feldman William B WB Wang Shirley V SV Pramod Umarje Siddhi S D'Andrea Elvira E Tesfaye Helen H Zabotka Luke E LE Liu Jun J Desai Rishi J RJ

Journal of clinical epidemiology 20220720

<h4>Objectives</h4>We aimed to use setting-appropriate comparisons to estimate the effects of different gastrointestinal (GI) prophylaxis pharmacotherapies for patients hospitalized with COVID-19 and setting-inappropriate comparisons to illustrate how improper design choices could result in biased results.<h4>Study design and setting</h4>We identified 3,804 hospitalized patients aged ≥ 18 years with COVID-19 from March to November 2020. We compared the effects of different gastroprotective agent ...[more]

PMID: 35868493

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Project description:BackgroundA large proportion of proton pump inhibitor (PPI) prescriptions, including those for stress ulcer prophylaxis (SUP), are inappropriate. Our study purpose was to systematically review the effectiveness of de-implementation strategies aimed at reducing inappropriate PPI use for SUP in hospitalized, non-intensive care unit (non-ICU) patients.MethodsWe searched MEDLINE and Embase databases (from inception to January 2020). Two authors independently screened references, performed data extraction, and critical appraisal. Randomized trials and comparative observational studies were eligible for inclusion. Criteria developed by the Cochrane Effective Practice and Organisation of Care (EPOC) group were used for critical appraisal. Besides the primary outcome (inappropriate PPI prescription or use), secondary outcomes included (adverse) pharmaceutical effects and healthcare use.ResultsWe included ten studies in this review. Most de-implementation strategies contained an educational component (meetings and/or materials), combined with either clinical guideline implementation (n = 5), audit feedback (n = 3), organizational culture (n = 4), or reminders (n = 1). One study evaluating the de-implementation strategy effectiveness showed a significant reduction (RR 0.14; 95% CI 0.03-0.55) of new inappropriate PPI prescriptions. Out of five studies evaluating the effectiveness of de-implementing inappropriate PPI use, four found a significant reduction (RR 0.21; 95% CI 0.18-0.26 to RR 0.76; 95% CI 0.68-0.86). No significant differences in the occurrence of pharmaceutical effects (n = 1) and in length of stay (n = 3) were observed. Adverse pharmaceutical effects were reported in two studies and five studies reported on PPI or total drug costs. No pooled effect estimates were calculated because of large statistical heterogeneity between studies.DiscussionAll identified studies reported mainly educational interventions in combination with one or multiple other intervention strategies and all interventions were targeted at providers. Most studies found a small to moderate reduction of (inappropriate) PPI prescriptions or use.

Project description:Background and objectiveObservational studies may provide valuable evidence on real-world causal effects of drug effectiveness in patients with coronavirus disease 2019 (COVID-19). As patients are usually observed from hospital admission to discharge and drug initiation starts during hospitalization, advanced statistical methods are needed to account for time-dependent drug exposure, confounding and competing events. Our objective is to evaluate the observational studies on the three common methodological pitfalls in time-to-event analyses: immortal time bias, confounding bias and competing risk bias.MethodsWe performed a systematic literature search on 23 October 2020, in the PubMed database to identify observational cohort studies that evaluated drug effectiveness in hospitalized patients with COVID-19. We included articles published in four journals: British Medical Journal, New England Journal of Medicine, Journal of the American Medical Association and The Lancet as well as their sub-journals.ResultsOverall, out of 255 articles screened, 11 observational cohort studies on treatment effectiveness with drug exposure-outcome associations were evaluated. All studies were susceptible to one or more types of bias in the primary study analysis. Eight studies had a time-dependent treatment. However, the hazard ratios were not adjusted for immortal time in the primary analysis. Even though confounders presented at baseline have been addressed in nine studies, time-varying confounding caused by time-varying treatment exposure and clinical variables was less recognized. Only one out of 11 studies addressed competing event bias by extending follow-up beyond patient discharge.ConclusionsIn the observational cohort studies on drug effectiveness for treatment of COVID-19 published in four high-impact journals, the methodological biases were concerningly common. Appropriate statistical tools are essential to avoid misleading conclusions and to obtain a better understanding of potential treatment effects.

Dataset Information

Gastrointestinal prophylaxis for COVID-19: an illustration of severe bias arising from inappropriate comparators in observational studies.

Objectives

Study design and setting

Results

Conclusion

Publications

Gastrointestinal prophylaxis for COVID-19: an illustration of severe bias arising from inappropriate comparators in observational studies.

Similar Datasets

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