Estimating Strain‐Specific and Overall Efficacy of Polyvalent Vaccines Against Recurrent Pathogens From a Cross‐Sectional Study

• Published in: Biometrics Vol. 69; no. 1; pp. 235 - 244
• Main Authors: Auranen, Kari, Rinta‐Kokko, Hanna, Halloran, M. Elizabeth
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishers 01.03.2013; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: bacterial colonization; BIOMETRIC PRACTICE; Biometrics; biometry; carrier state; Carrier State - immunology; Carrier State - microbiology; Case-control studies; Clinical trials; Computer Simulation; Conjugate vaccines; cross-sectional studies; Cross-Sectional Studies - methods; Cross-Sectional Studies - standards; Datasets; Disease transmission; Estimators; Humans; Infant; Microbial colonization; Models, Statistical; Multiple colonization; nasopharynx; Nasopharynx - immunology; Nasopharynx - microbiology; Pathogens; Pneumococcal Infections - immunology; Pneumococcal Infections - microbiology; Pneumococcal Infections - prevention & control; Pneumococcal vaccine; Pneumococcal Vaccines - immunology; Pneumococcal Vaccines - standards; Pneumococcus; Polyvalent vaccine; Randomized Controlled Trials as Topic - methods; Randomized Controlled Trials as Topic - standards; Recurrent infection; Risk-set sampling; Simulations; Statistical estimation; Strain interaction; Streptococcus pneumoniae; Streptococcus pneumoniae - immunology; Vaccination; Vaccine efficacy; Vaccines; Vaccines, Conjugate - immunology; Vaccines, Conjugate - standards
• ISSN: 0006-341X; 1541-0420; 1541-0420
• DOI: 10.1111/j.1541-0420.2012.01826.x

Evaluating vaccine efficacy for protection against colonization with bacterial pathogens is an area of growing interest. Colonization of the nasopharynx is an asymptomatic carrier state responsible for person‐to‐person transmission. It differs from most clinical outcomes in that it is common, recurrent, and observed only in its prevalent state. To estimate rates of acquisition and clearance of colonization requires repeated active sampling of the same individuals over time, an expensive and invasive undertaking. Motivated by feasibility constraints in efficacy trials with colonization endpoints, investigators have been estimating vaccine efficacy from cross‐sectional studies without principled methods. We present two examples of vaccine studies estimating vaccine efficacy from cross‐sectional data on nasopharyngeal colonization by Streptococcus pneumoniae (pneumococcus). This study presents a framework for defining and estimating strain‐specific and overall vaccine efficacy for susceptibility to acquisition of colonization () when there is a large number of strains with mutual interactions and recurrent dynamics of colonization. We develop estimators based on one observation of the current status per study subject, evaluate their robustness, and re‐analyze the two vaccine trials. Methodologically, the proposed estimators are closely related to case–control studies with prevalent cases, with appropriate consideration of the at‐risk time in choosing the controls.