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dc.contributor.authorDiakite, Ibrahimen_US
dc.contributor.authorMooring, Eric Q.en_US
dc.contributor.authorVelásquez, Gustavo E.en_US
dc.contributor.authorMurray, Megan B.en_US
dc.date.accessioned2016-10-11T20:28:59Z
dc.date.issued2016en_US
dc.identifier.citationDiakite, Ibrahim, Eric Q. Mooring, Gustavo E. Velásquez, and Megan B. Murray. 2016. “Novel Ordered Stepped-Wedge Cluster Trial Designs for Detecting Ebola Vaccine Efficacy Using a Spatially Structured Mathematical Model.” PLoS Neglected Tropical Diseases 10 (8): e0004866. doi:10.1371/journal.pntd.0004866. http://dx.doi.org/10.1371/journal.pntd.0004866.en
dc.identifier.issn1935-2727en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29002727
dc.description.abstractBackground: During the 2014 Ebola virus disease (EVD) outbreak, policy-makers were confronted with difficult decisions on how best to test the efficacy of EVD vaccines. On one hand, many were reluctant to withhold a vaccine that might prevent a fatal disease from study participants randomized to a control arm. On the other, regulatory bodies called for rigorous placebo-controlled trials to permit direct measurement of vaccine efficacy prior to approval of the products. A stepped-wedge cluster study (SWCT) was proposed as an alternative to a more traditional randomized controlled vaccine trial to address these concerns. Here, we propose novel “ordered stepped-wedge cluster trial” (OSWCT) designs to further mitigate tradeoffs between ethical concerns, logistics, and statistical rigor. Methodology/Principal Findings We constructed a spatially structured mathematical model of the EVD outbreak in Sierra Leone. We used the output of this model to simulate and compare a series of stepped-wedge cluster vaccine studies. Our model reproduced the observed order of first case occurrence within districts of Sierra Leone. Depending on the infection risk within the trial population and the trial start dates, the statistical power to detect a vaccine efficacy of 90% varied from 14% to 32% for standard SWCT, and from 67% to 91% for OSWCTs for an alpha error of 5%. The model’s projection of first case occurrence was robust to changes in disease natural history parameters. Conclusions/Significance: Ordering clusters in a step-wedge trial based on the cluster’s underlying risk of infection as predicted by a spatial model can increase the statistical power of a SWCT. In the event of another hemorrhagic fever outbreak, implementation of our proposed OSWCT designs could improve statistical power when a step-wedge study is desirable based on either ethical concerns or logistical constraints.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pntd.0004866en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979980/pdf/en
dash.licenseLAAen_US
dc.subjectMedicine and Health Sciencesen
dc.subjectClinical Medicineen
dc.subjectClinical Trialsen
dc.subjectCluster Trialsen
dc.subjectPharmacologyen
dc.subjectDrug Research and Developmenten
dc.subjectBiology and Life Sciencesen
dc.subjectImmunologyen
dc.subjectVaccination and Immunizationen
dc.subjectVaccinesen
dc.subjectPublic and Occupational Healthen
dc.subjectPreventive Medicineen
dc.subjectTropical Diseasesen
dc.subjectNeglected Tropical Diseasesen
dc.subjectViral Hemorrhagic Feversen
dc.subjectEbola Hemorrhagic Feveren
dc.subjectInfectious Diseasesen
dc.subjectViral Diseasesen
dc.subjectInfectious Disease Controlen
dc.subjectPeople and placesen
dc.subjectGeographical locationsen
dc.subjectAfricaen
dc.subjectSierra Leoneen
dc.subjectPeople and Placesen
dc.subjectGeographical Locationsen
dc.subjectLiberiaen
dc.subjectDemographyen
dc.subjectDeath Ratesen
dc.subjectPopulation Biologyen
dc.subjectPopulation Metricsen
dc.titleNovel Ordered Stepped-Wedge Cluster Trial Designs for Detecting Ebola Vaccine Efficacy Using a Spatially Structured Mathematical Modelen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Neglected Tropical Diseasesen
dash.depositing.authorDiakite, Ibrahimen_US
dc.date.available2016-10-11T20:28:59Z
dc.identifier.doi10.1371/journal.pntd.0004866*
dash.contributor.affiliatedDiakite, Ibrahim
dash.contributor.affiliatedMooring, Eric
dash.contributor.affiliatedMurray, Megan


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