title: Use of Patients With Diarrhea Who Test Negative for Rotavirus as Controls to Estimate Rotavirus Vaccine Effectiveness Through Case-Control Studies.
abstract: BACKGROUND
  Case-control studies are often performed to estimate postlicensure vaccine effectiveness (VE), but the enrollment of controls can be challenging, time-consuming, and costly. We evaluated whether children enrolled in the same hospital-based diarrheal surveillance used to identify rotavirus cases but who test negative for rotavirus (test-negative controls) can be considered a suitable alternative to nondiarrheal hospital or community-based control groups (traditional controls).
  
  
  METHODS
  We compared calculated VE estimates as a function of varying values of true VE, attack rates of rotavirus and nonrotavirus diarrhea in the population, and sensitivity and specificity of the rotavirus enzyme immunoasssay. We also searched the literature to identify rotavirus VE studies that used traditional and test-negative control groups and compared VE estimates obtained using the different control groups.
  
  
  RESULTS
  Assuming a 1% attack rate for severe rotavirus diarrhea, a 3% attack rate for severe nonrotavirus diarrhea in the population, a test sensitivity of 96%, and a specificity of 100%, the calculated VE estimates using both the traditional and test-negative control groups closely approximated the true VE for all values from 30% to 100%. As true VE decreased, the traditional case-control approach slightly overestimated the true VE and the test-negative case-control approach slightly underestimated this estimate, but the absolute difference was only ±0.2 percentage points. Field VE estimates from 10 evaluations that used both traditional and test-negative control groups were similar regardless of control group used.
  
  
  CONCLUSIONS
  The use of rotavirus test-negative controls offers an efficient and cost-effective approach to estimating rotavirus VE through case-control studies.
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Tate
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Manish M
authors.initials: MM
authors.lastname: Patel
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Cortese
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Payne
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Lopman
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Yen
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Umesh D
authors.initials: UD
authors.lastname: Parashar
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D035061:Control Groups; D003967:Diarrhea / Q000209:etiology* / Q000517:prevention & control / Q000821:virology; D005260:Female; D005759:Gastroenteritis / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007118:Immunoassay; D000071497:Immunogenicity, Vaccine; D015994:Incidence; D007223:Infant; D008297:Male; D012401:Rotavirus / Q000276:immunology* / Q000302:isolation & purification; D012400:Rotavirus Infections / Q000175:diagnosis / Q000517:prevention & control* / Q000821:virology; D022243:Rotavirus Vaccines / Q000191:economics / Q000276:immunology*; D016896:Treatment Outcome; D064166:Vaccine Potency; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated
keywords: rotavirus vaccine effectiveness; test-negative controls; vaccine effectiveness