Dataset Information

A new randomization procedure based on multiple covariates and applicable to parallel studies with simultaneous enrollment of all subjects prior to intervention.

ABSTRACT:

Background

Parallel intervention studies involving volunteers usually require a procedure to allocate the subjects to study-arms. Statistical models to evaluate the different outcomes of the study-arms will include study-arm as a factor along with any covariate that might affect the results. To ensure that the effects of the covariates are confounded to the least possible extent with the effects of the arms, stratified randomization can be applied. However, there is at present no clear-cut procedure when there are multiple covariates.

Methods

For parallel study designs with simultaneous enrollment of all subjects prior to intervention, we propose a D-optimal blocking procedure to allocate subjects with known values of the covariates to the study arms. We prove that the procedure minimizes the variances of the baseline differences between the arms corrected for the covariates. The procedure uses standard statistical software.

Results

We demonstrate the potential of the method by an application to a human parallel nutritional intervention trial with three arms and 162 healthy volunteers. The covariates were gender, age, body mass index, an initial composite health score, and a categorical indicator called first-visit group, defining groups of volunteers who visit the clinical centre on the same day (17 groups). Volunteers were allocated equally to the study-arms by the D-optimal blocking procedure. The D-efficiency of the model connecting an outcome with the study-arms and correcting for the covariates equals 99.2%. We simulated 10,000 random allocations of subjects to arms either unstratified or stratified by first-visit group. Intervals covering the middle 95% of the D-efficiencies for these allocations were [82.0, 92.0] and [93.2, 98.4], respectively.

Conclusions

Allocation of volunteers to study-arms with a D-optimal blocking procedure with the values of the covariates as inputs substantially improves the efficiency of the statistical model that connects the response with the study arms and corrects for the covariates.

Trial registration

Dutch Trial Register NL7054 ( NTR7259 ). Registered May 15, 2018.

SUBMITTER: Schoen ED

PROVIDER: S-EPMC7469365 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

A new randomization procedure based on multiple covariates and applicable to parallel studies with simultaneous enrollment of all subjects prior to intervention.

Schoen Eric D ED Wopereis Suzan S

BMC medical research methodology 20200903 1

<h4>Background</h4>Parallel intervention studies involving volunteers usually require a procedure to allocate the subjects to study-arms. Statistical models to evaluate the different outcomes of the study-arms will include study-arm as a factor along with any covariate that might affect the results. To ensure that the effects of the covariates are confounded to the least possible extent with the effects of the arms, stratified randomization can be applied. However, there is at present no clear-c ...[more]

PMID: 32883212

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Project description:Multicenter clinical trials attempt to select sites that can move rapidly to randomization and enroll sufficient numbers of patients. However, there are few assessments of the success of site selection.In the CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials), we assess factors associated with the time between site selection and authorization to randomize, the time between authorization to randomize and the first randomization, and the average number of randomizations per site per month. Potential factors included characteristics of the site, specialty of the principal investigator, and site type.For 147 sites, the median time between site selection to authorization to randomize was 9.9 months (interquartile range, 7.7, 12.4), and factors associated with early site activation were not identified. The median time between authorization to randomize and a randomization was 4.6 months (interquartile range, 2.6, 10.5). Sites with authorization to randomize in only the carotid endarterectomy study were slower to randomize, and other factors examined were not significantly associated with time-to-randomization. The recruitment rate was 0.26 (95% confidence interval, 0.23-0.28) patients per site per month. By univariate analysis, factors associated with faster recruitment were authorization to randomize in both trials, principal investigator specialties of interventional radiology and cardiology, pre-trial reported performance >50 carotid angioplasty and stenting procedures per year, status in the top half of recruitment in the CREST trial, and classification as a private health facility. Participation in StrokeNet was associated with slower recruitment as compared with the non-StrokeNet sites.Overall, selection of sites with high enrollment rates will likely require customization to align the sites selected to the factor under study in the trial.URL: http://www.clinicaltrials.gov. Unique identifier: NCT02089217.

Dataset Information

A new randomization procedure based on multiple covariates and applicable to parallel studies with simultaneous enrollment of all subjects prior to intervention.

Background

Methods

Results

Conclusions

Trial registration

Publications

A new randomization procedure based on multiple covariates and applicable to parallel studies with simultaneous enrollment of all subjects prior to intervention.

Similar Datasets

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