| Title: |
Evaluating the Test-Negative Design for COVID-19 Vaccine Effectiveness Using Randomized Trial Data |
| Authors: |
Andrews, Leah IB; Halloran, M Elizabeth; Neuzil, Kathleen M; van der Laan, Lars; Huang, Yunda; Andriesen, Jessica; Patel, Mayur; Fisher, Leigh H; Janes, Holly; Rouphael, Nadine; Walsh, Stephen R; Theodore, Deborah A; Tieu, Hong-Van; Sobieszczyk, Magdalena; El Sahly, Hana M; Baden, Lindsey R; Falsey, Ann R; Campbell, Thomas B; Kelley, Colleen F; Healy, Catherine Mary; Immergluck, Lilly; Luft, Benjamin; Hirsch, Ian; de Bruyn, Guy; Truyers, Carla; Priddy, Frances; Sumner, Kelsey M; Flannery, Brendan; Follmann, Dean; Gilbert, Peter B; Abad, Vanessa; Abalos, Karina; Abate, Getahun; Abbas, Anum; Accini, Jose; Ackerman, Ronald; Ackerman, Jamie; Ackermann, Jeremy; Adams, Atoya; Adams, Michael R; Adams, Mark S; Adams, Michael; Adelglass, Jeffrey M; Afework, Sarah; Ahmad, Nina; Akamine, Christine; Ake, Julie A; Albert, Gary; Alcaide, Maria L; Alderson, Nathan; Aleman, Lily; Alemán, José O; Al-Ibrahim, Mohamed S; Allaw, Mohammed; Allen, Leland N; Allen, Mary; Aloysia, Naveena; Alvarado, Hilario; Alvarez León, Winniberg Stephany; Amador, Carmen; Amuasi, John Humphrey; Andersen, James; Anderson, Evan J; Anderson, Corey G; Anderson, Victoria R; Andes, David R; Andrasik, Michele P; Andree, Stephanie; Andrews, Jeb; Andriesen, Jessica G; Andriulis, Victoria; Áñez, Germán; Angeles Ceregido, Maria; Ansah, Nana Akosua; Ansel, Jessica L; Anthony, Codi M; Antony, Johannes; Antwi, Mohammed; Arduino, Roberto C; Aristy, Florida; Arnold, Valerie K; Arrazcaeta, Alicia; Arroyo, Hugo Macareno; Asante, Kwaku Poku; Atmar, Robert L; August, Allison; Avworo, Ayoade; Bacher, Christina; Bäcker, Martín; Baden, Lindsay R; Badillo, Diana; Bainbridge, Emma; Baka, Michele; Baker, Sherrie; Balani, Bindu; Ball, Brandy; Baron, Mira; Barouch, Dan H; Barranco-Santana, Elizabeth; Barrat Hernández, Alejandro Quintín |
| Source: |
JAMA Network Open, vol 8, iss 5 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2025 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); Infectious Diseases (rcdc); Clinical Research (rcdc); Emerging Infectious Diseases (rcdc); Prevention (rcdc); Vaccine Related (rcdc); Immunization (rcdc); Coronaviruses (rcdc); Clinical Trials and Supportive Activities (rcdc); 6.1 Pharmaceuticals (hrcs-rac); 3.4 Vaccines (hrcs-rac); 3 Good Health and Well Being (sdg); Humans (mesh); COVID-19 Vaccines (mesh); COVID-19 (mesh); Vaccine Efficacy (mesh); Randomized Controlled Trials as Topic (mesh); SARS-CoV-2 (mesh); Adult (mesh); Female (mesh); Male (mesh); Middle Aged (mesh); Research Design (mesh); COVID-19 Prevention Network (CoVPN); 42 Health sciences (for-2020) |
| Description: |
Importance: The test-negative design (TND) has been widely used to assess postmarketing COVID-19 vaccine effectiveness but requires further evaluation for this application. Objective: To determine whether the TND reliably evaluates vaccine effectiveness against symptomatic COVID-19 using placebo-controlled vaccine efficacy randomized clinical trials (RCTs). Design, Setting, and Participants: This secondary cross-protocol analysis constructed TND study datasets from study sites in 16 countries across 5 continents using the blinded phase cohorts of 5 harmonized phase 3 COVID-19 Prevention Network RCTs: COVE (Coronavirus Vaccine Efficacy and Safety), AZD1222, ENSEMBLE, PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax Trial COVID-19), and VAT00008. Participants included adults who received the intended number of doses, experienced COVID-19-like symptoms, and obtained SARS-CoV-2 testing. Start dates ranged from July 27, 2020, to October 19, 2021; data cutoff dates ranged from March 26, 2021, to March 15, 2022. Statistical analysis was performed from May 11, 2023, to February 25, 2025. Interventions: Participants received vaccines consisting of messenger RNA-1273 (COVE; 2 doses 28 days apart), ChAdOx1 nCoV-19 (AZD1222; 2 doses 28 days apart), Ad26.COV2.S (ENSEMBLE; 1 dose), NVX-CoV2373 (PREVENT-19; 2 doses 21 days apart), CoV2 preS dTM-AS03 (VAT00008; D614) (2 doses 21 days apart), or CoV2 preS dTM-AS03 (D614 plus B.1.351) (VAT00008; 2 doses 21 days apart) or placebo. Main Outcomes and Measures: Main outcomes were symptomatic COVID-19 according to each trial's primary efficacy definition and the Centers for Disease Control and Prevention definition. Vaccine effectiveness was estimated using targeted maximum likelihood estimation under a semiparametric logistic regression model and ordinary logistic regression. Noncase exchangeability, a core TND assumption for unbiased estimation, was also assessed by estimating vaccine efficacy against non-COVID-19 illness. Results: Among the 12 157 participants ... |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
qt6pn6p9gr; https://escholarship.org/uc/item/6pn6p9gr |
| DOI: |
10.1001/jamanetworkopen.2025.12763 |
| Availability: |
https://escholarship.org/uc/item/6pn6p9gr; https://doi.org/10.1001/jamanetworkopen.2025.12763 |
| Rights: |
CC-BY-ND |
| Accession Number: |
edsbas.45915CCD |
| Database: |
BASE |