Case-Control Study of Rotavirus Vaccine Effectiveness Compared to Test-Negative Controls or Hospital Controls

Abstract

Background Selection of test-negative controls takes less time and costs less than traditional control selection for evaluating vaccine effectiveness (VE). Here, rotavirus VE was evaluated using hospital controls and compared with test-negative controls to determine whether using the latter can substitute for the former. Methods We recorded gastroenteritis in children from 2 months to 2 years of age at six medical facilities in Saga City between January 4th and May 31st, 2014. Stools from all identified acute gastroenteritis patients were tested for rotavirus using immunochromatography. Rotavirus gastroenteritis (RVGE) cases had test-positive stool, whereas test-negative controls had gastroenteritis but no rotavirus infection; hospital controls were outpatients visiting the same facility for indications other than gastroenteritis. Vaccination status was verified by inspecting maternal and child health records, and demographic data were obtained from a questionnaire completed by the patients’ guardians or from the medical records. Unconditional logistic regression analysis was used to adjust for possible confounding factors. Results Sixty-four RVGE cases, 260 test-negative controls, and 589 hospital controls were enrolled. The characteristics of the two control groups, including RV vaccination history, were similar. The RVGE cases were more likely to have used daycare services than children from either of the two control groups. The VE against RVGE estimated using hospital controls was 86.6% (95% confidence interval [CI], 55.9–96.0%), very similar to the VE using test-negative controls (84.9% [95% CI, 49.6–95.5%]). Conclusions The estimated VE using test-negative controls and hospital controls is similar. Therefore, test-negative controls are considered appropriate for establishing VE.

Determinants of self-paid rotavirus vaccination status in Kanazawa, Japan, including socioeconomic factors, parents’ perception, and children’s characteristics

“…In Japan, Rotarix® and RotaTeq® became available on the private market in November 2011 and July 2012, respectively. Because of the high effectiveness of these vaccines [11,12] and their impact on reducing hospitalization from RVGE [13][14][15][16], rotavirus vaccine will be included in Japan's NIP in October 2020; however, vaccination is self-paid at present. Additionally, vaccination coverage in Japan is unclear because Japan has no vaccination registry.…”

Potential Test-Negative Design Study Bias in Outbreak Settings: Application to Ebola vaccination in Democratic Republic of Congo

“…This design estimates vaccine efficacy from the odds ratio for test outcome conditional on vaccination status, and has lower misclassification bias than traditional case-control studies (23,24). TNCC studies have been used estimate the efficacy of vaccines against influenza (25), rotavirus (26)(27)(28), pneumococcus (29), and other pathogens (30,31). The design can also assess interventions such as vector control and risk-factor management (32)(33)(34).…”

Commentary: Test-Negative Design Reduces Confounding by Healthcare-Seeking Attitude in Case-Control Studies

“…Hospital-based case-control studies employing the “test-negative design” have been used recently, with the intention of reducing confounding by healthcare-seeking attitude in the evaluation of vaccine effectiveness (VE) for some diseases with specific characteristics, such as influenza and rotavirus infection. 1 – 3 Araki and colleagues investigated the effectiveness of rotavirus vaccine for children in a case-control study with this design. 1 In this highly sophisticated study, the mechanism of reducing confounding by healthcare-seeking attitude may seem complicated, so it would be helpful for general readers for us to briefly summarize the principle as well as the benefits and cautions related to its application.…”

“…1 – 3 Araki and colleagues investigated the effectiveness of rotavirus vaccine for children in a case-control study with this design. 1 In this highly sophisticated study, the mechanism of reducing confounding by healthcare-seeking attitude may seem complicated, so it would be helpful for general readers for us to briefly summarize the principle as well as the benefits and cautions related to its application. Figure 1 shows the temporal flow of vaccination and course of development of the target disease; it also summarizes the evaluation of VE in observational epidemiological studies.…”

“…5 In Araki’s test-negative study regarding rotavirus VE, they also emphasized that the pathogenic test should be applied to all eligible patients visiting with pre-defined symptoms. 1…”