title: Assessing different measures of population-level vaccine protection using a case-control study.
abstract: BACKGROUND
  Case-control studies have not been examined for their utility in assessing population-level vaccine protection in individually randomized trials.
  
  
  METHODS
  We used the data of a randomized, placebo-controlled trial of a cholera vaccine to compare the results of case-control analyses with those of cohort analyses. Cases of cholera were selected from the trial population followed for three years following dosing. For each case, we selected 4 age-matched controls who had not developed cholera. For each case and control, GIS was used to calculate vaccine coverage of individuals in a surrounding "virtual" cluster. Specific selection strategies were used to evaluate the vaccine protective effects.
  
  
  RESULTS
  66,900 out of 108,389 individuals received two doses of the assigned regimen. For direct protection among subjects in low vaccine coverage clusters, we observed 78% (95% CI: 47-91%) protection in a cohort analysis and 84% (95% CI: 60-94%) in case-control analysis after adjusting for confounding factors. Using our GIS-based approach, estimated indirect protection was 52% (95% CI: 10-74%) in cohort and 76% (95% CI: 47-89%) in case control analysis. Estimates of total and overall effectiveness were similar for cohort and case-control analyses.
  
  
  CONCLUSIONS
  The findings show that case-control analyses of individually randomized vaccine trials may be used to evaluate direct as well as population-level vaccine protection.
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea; Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. Electronic address: mali25@jhu.edu.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Young Ae
authors.initials: YA
authors.lastname: You
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Kanungo
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Byomkesh
authors.initials: B
authors.lastname: Manna
authors.affiliation: Menzies School of Health Research, Casuarina, NT, Australia.
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Deen
authors.affiliation: University of the Philippines Manila, National Institutes of Health, Philippines.
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Lopez
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wierzba
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Sujit K
authors.initials: SK
authors.lastname: Bhattacharya
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Dipika
authors.initials: D
authors.lastname: Sur
authors.affiliation: icddr,b, Dhaka, Bangladesh; UCLA Fielding School of Public Health, Los Angeles, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Clemens
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002771:Cholera / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016896:Treatment Outcome; D014894:Weights and Measures; D055815:Young Adult
chemical_list: D022121:Cholera Vaccines; D010919:Placebos
keywords: Case–control study; Cohort study; Herd effect; Randomized controlled trial; Vaccine effectiveness