Evidence map›Paper›PMID 24499406›Full record

Trial reportTrials2013

The effect of covariate adjustment for baseline severity in acute stroke clinical trials with responder analysis outcomes.

Kyra M Garofolo, Sharon D Yeatts, Viswanathan Ramakrishnan, Edward C Jauch, Karen C Johnston, Valerie L Durkalski

Registry-linked trialAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Trials, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01369069 (Stroke Hyperglycemia Insulin Network Effort), which is not on this map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT01369069 phase3completednot on this map

Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial

TypeinterventionalSponsorUniversity of VirginiaRan2012 to 2018Enrolled1,151ConditionsAcute Ischemic Stroke, Diabetes, HyperglycemiaArmsIV insulin to maintain target glucose concentration of 80-130 mg/dL, Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Assessing type I error and power of multistate Markov models for panel data-A simulation study.Communications in statistics: Simulation and computation · 2017
    Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Kyra M Garofolo
Sharon D Yeatts
Viswanathan Ramakrishnan
Edward C Jauch
Karen C Johnston
Valerie L DurkalskiDepartment of Public Health Sciences, Medical University of South Carolina, 135 Cannon Street, Charleston, SC 29425, USA. durkalsv@musc.edu.

Funding

The Stroke Hyperglycemia Insulin Network Effort (SHINE) TrialU01NS069498 · NINDS · UNIVERSITY OF VIRGINIA · PI BRUNO, ASKIEL, HALL, CHRISTIANA · 2011 to 2017
$27.7M
Neurological Emergencies Treatment Trials Network Statistical and Data ManagementU01NS059041 · NINDS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DURKALSKI, VALERIE L, PALESCH, YUKO Y · 2006 to 2015
$9.1M
NINDS NIH HHS 1U01-NS069498NINDS NIH HHS U01-NS059041NINDS NIH HHS U01 NS069498
6 · The paper itself

Abstract

backgroundTraditionally in acute stroke clinical trials, the primary clinical outcome employed is a dichotomized modified Rankin Scale (mRS). New statistical methods, such as responder analysis, are being used in stroke studies to address the concern that baseline prognostic variables, such as stroke severity, impact the likelihood of a successful outcome. Responder analysis allows the definition of success to vary according to baseline prognostic variables, producing a more clinically relevant insight into the actual effect of investigational treatments. It is unclear whether or not statistical analyses should adjust for prognostic variables when responder analysis is used, as the outcome already takes these prognostic variables into account. This research aims to investigate the effect of covariate adjustment in the responder analysis framework in order to determine the appropriate analytic method.

methodsUsing a current stroke clinical trial and its pilot studies to guide simulation parameters, 1,000 clinical trials were simulated at varying sample sizes under several treatment effects to assess power and type I error. Covariate-adjusted and unadjusted logistic regressions were used to estimate the treatment effect under each scenario. In the case of covariate-adjusted logistic regression, the trichotomized National Institute of Health Stroke Scale (NIHSS) was used in adjustment.

resultsUnder various treatment effect settings, the operating characteristics of the unadjusted and adjusted analyses do not substantially differ. Power and type I error are preserved for both the unadjusted and adjusted analyses.

conclusionsOur results suggest that, under the given treatment effect scenarios, the decision whether or not to adjust for baseline severity when using a responder analysis outcome should be guided by the needs of the study, as type I error rates and power do not appear to vary largely between the methods. These findings are applicable to stroke trials which use the mRS for the primary outcome, but also provide a broader insight into the analysis of binary outcomes that are defined based on baseline prognostic variables.

trial registrationThis research is part of the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial, Identification Number NCT01369069.

Indexed as

HumansLogistic ModelsSeverity of Illness IndexStroke

Identifiers

PMID24499406
PMCPMC3821551

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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.