A proposed framework to guide evidence synthesis practice for meta-analysis with zero-events studies

Xu, Chang; Furuya‐Kanamori, Luis; Zorzela, Liliane; Lin, Lifeng; Vohra, Sunita

doi:10.1016/j.jclinepi.2021.02.012

Cited by 66 publications

(52 citation statements)

References 36 publications

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“…For example, when the total event count in one of the arms or both arms is zero in the meta-analysis, one-stage methods are no longer feasible. A recent framework for meta-analysis with zero-events studies proposed by our group could be considered to help systematic review authors appropriately make use of zero-events in meta-analysis [ 21 ]. Based on the total event count within the meta-analysis and zero-events type of individual studies, we can classify meta-analyses with zero-events studies into six subtypes (see Additional file: Fig.S 3 for details).…”

Section: Discussionmentioning

confidence: 99%

“…For each subtype of meta-analysis, the applicability of available methods could be well distinguished. They are listed under the diagram of the framework (Additional file: Fig.S 4 ), and systematic review authors can easily identify one or more appropriate methods for their meta-analysis [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“… First, standard meta-analysis methods, say, the inverse-variance method with continuity correction, are not recommended as the primary choice for meta-analysis with zero-events studies [ 5 , 6 , 29 ]. Second, in case that the total event count of each arm of a meta-analysis is at least 10, the one-stage methods, e.g., the mixed Poisson regression models, the beta-binomial model, the generalized linear mixed models, and the generalized estimating equations, could be considered as the primary option [ 5 , 6 , 11 , 16 , 18 , 19 , 21 , 43 ]. Third, when the total event count of a meta-analysis is < 10 or one-stage methods cannot achieve convergence, two-stage methods such as Peto’s OR, Mantel-Haenszel OR, and Mantel-Haenszel RD could be considered, while Peto’s OR and Mantel-Haenszel OR can only be considered when there are no studies with no events in both arms [ 6 , 26 , 38 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…Second, in case that the total event count of each arm of a meta-analysis is at least 10, the one-stage methods, e.g., the mixed Poisson regression models, the beta-binomial model, the generalized linear mixed models, and the generalized estimating equations, could be considered as the primary option [ 5 , 6 , 11 , 16 , 18 , 19 , 21 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…The contradictory views regarding studies with zero events in both arms complicate decisions for systematic review authors and policymakers, who ultimately determine healthcare practice [ 20 , 21 ]. The preference on dealing with such studies may influence future systematic review authors.…”

Section: Introductionmentioning

confidence: 99%

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Utilization of the evidence from studies with no events in meta-analyses of adverse events: an empirical investigation

Zhou

Zorzela

et al. 2021

BMC Med

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Backgrounds Zero-events studies frequently occur in systematic reviews of adverse events, which consist of an important source of evidence. We aimed to examine how evidence of zero-events studies was utilized in the meta-analyses of systematic reviews of adverse events. Methods We conducted a survey of systematic reviews published in two periods: January 1, 2015, to January 1, 2020, and January 1, 2008, to April 25, 2011. Databases were searched for systematic reviews that conducted at least one meta-analysis of any healthcare intervention and used adverse events as the exclusive outcome. An adverse event was defined as any untoward medical occurrence in a patient or subject in healthcare practice. We summarized the frequency of occurrence of zero-events studies in eligible systematic reviews and how these studies were dealt with in the meta-analyses of these systematic reviews. Results We included 640 eligible systematic reviews. There were 406 (63.45%) systematic reviews involving zero-events studies in their meta-analyses, among which 389 (95.11%) involved single-arm-zero-events studies and 223 (54.93%) involved double-arm-zero-events studies. The majority (98.71%) of these systematic reviews incorporated single-arm-zero-events studies into the meta-analyses. On the other hand, the majority (76.23%) of them excluded double-arm-zero-events studies from the meta-analyses, of which the majority (87.06%) did not discuss the potential impact of excluding such studies. Systematic reviews published at present (2015-2020) tended to incorporate zero-events studies in meta-analyses than those published in the past (2008-2011), but the difference was not significant (proportion difference=−0.09, 95% CI −0.21 to 0.03, p = 0.12). Conclusion Systematic review authors routinely treated studies with zero-events in both arms as “non-informative” carriers and excluded them from their reviews. Whether studies with no events are “informative” or not largely depends on the methods and assumptions applied, thus sensitivity analyses using different methods should be considered in future meta-analyses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Utilization of the evidence from studies with no events in meta-analyses of adverse events: an empirical investigation

Zhou

Zorzela

et al. 2021

BMC Med

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Prolonged vs Intermittent Infusions of β-Lactam Antibiotics

Pang,

Sun

2024

JAMA

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Correction Rates and Clinical Outcomes in Hospitalized Adults With Severe Hyponatremia

Ayus,

Moritz,

Fuentes

et al. 2024

JAMA Intern Med

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ImportanceHyponatremia treatment guidelines recommend limiting the correction of severe hyponatremia during the first 24 hours to prevent osmotic demyelination syndrome (ODS). Recent evidence suggests that slower rates of correction are associated with increased mortality.ObjectiveTo evaluate the association of sodium correction rates with mortality among hospitalized adults with severe hyponatremia.Data SourcesWe searched MEDLINE, Embase, the Cochrane Library, LILACS, Web of Science, CINAHL, and international congress proceedings for studies published between January 2013 and October 2023.Study SelectionComparative studies assessing rapid (≥8-10 mEq/L per 24 hours) vs slow (&lt;8 or 6-10 mEq/L per 24 hours) and very slow (&lt;4-6 mEq/L per 24 hours) correction of severe hyponatremia (serum sodium &lt;120 mEq/L or &lt;125 mEq/L plus severe symptoms) in hospitalized patients.Data Extraction and SynthesisPairs of reviewers (N.A.F., J.R.M., J.M.A., A.C.) independently reviewed studies, extracted data, and assessed each included study’s risk of bias using ROBINS-I. Cochrane methods, PRISMA reporting guidelines, and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to rate the certainty of evidence were followed. Data were pooled using a random-effects model.Main Outcomes and MeasuresPrimary outcomes were in-hospital and 30-day mortality, and secondary outcomes were hospital length of stay (LOS) and ODS.ResultsSixteen cohort studies involving a total of 11 811 patients with severe hyponatremia were included (mean [SD] age, 68.22 [6.88] years; 56.7% female across 15 studies reporting sex). Moderate-certainty evidence showed that rapid correction was associated with 32 (odds ratio, 0.67; 95% CI, 0.55-0.82) and 221 (odds ratio, 0.29; 95% CI, 0.11-0.79) fewer in-hospital deaths per 1000 treated patients compared with slow and very slow correction, respectively. Low-certainty evidence suggested that rapid correction was associated with 61 (risk ratio, 0.55; 95% CI, 0.45-0.67) and 134 (risk ratio, 0.35; 95% CI, 0.28-0.44) fewer deaths per 1000 treated patients at 30 days and with a reduction in LOS of 1.20 (95% CI, 0.51-1.89) and 3.09 (95% CI, 1.21-4.94) days, compared with slow and very slow correction, respectively. Rapid correction was not associated with a statistically significant increased risk of ODS.Conclusions and RelevanceIn this systematic review and meta-analysis, slow correction and very slow correction of severe hyponatremia were associated with an increased risk of mortality and hospital LOS compared to rapid correction.

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A proposed framework to guide evidence synthesis practice for meta-analysis with zero-events studies

Cited by 66 publications

References 36 publications

Utilization of the evidence from studies with no events in meta-analyses of adverse events: an empirical investigation

Utilization of the evidence from studies with no events in meta-analyses of adverse events: an empirical investigation

Prolonged vs Intermittent Infusions of β-Lactam Antibiotics

Correction Rates and Clinical Outcomes in Hospitalized Adults With Severe Hyponatremia

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