Case-control vaccine effectiveness studies: Preparation, design, and enrollment of cases and controls

• Authors: Jennifer Verani, Emory University; Abdullah H Baqui, Johns Hopkins Bloomberg School of Public Health; Claire Broome, Emory University; Thomas Cherian, WHO; Cheryl Cohen, National Institute for Communicable Diseases; Jennifer L Farrar, Centers for Disease Control and Prevention; Daniel R Feikin, Centers for Disease Control and Prevention; Michelle J Groome, University of Witwatersrand; Rana A Hajjeh, Centers for Disease Control and Prevention; Cynthia Whitney, Emory University
• Journal Title: Vaccine
• Volume: Volume 35, Number 25
• Publisher: Elsevier Sci Ltd | 2017-06-05, Pages 3295-3302
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.vaccine.2017.04.037
• Subjects: Health Sciences, Immunology; Health Sciences, Public Health
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Medicine, Research & Experimental; Research & Experimental Medicine; Vaccines; Case-control studies; Evaluation studies; PNEUMOCOCCAL CONJUGATE VACCINE; PENTAVALENT ROTAVIRUS VACCINE; RADIOLOGICALLY-CONFIRMED PNEUMONIA; HEALTH-CARE UTILIZATION; TEST-NEGATIVE DESIGN; ROUTINE IMMUNIZATION; BACTERIAL PNEUMONIA; SURVEILLANCE DATA; YOUNG-CHILDREN; DISEASE

Abstract

Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under ‘real world’ conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential.