@article{Voysey_M-2021_8054,
title = {Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK},
author = {Voysey, M. and Clemens, S. and Madhi, S. and Weckx, L. and Folegatti, P. and Aley, P. and Angus, B. and Baillie, V. and Barnabas, S. and Bhorat, Q. and Bibi, S. and Briner, C. and Cicconi, P. and Collins, A. and Colin-Jones, R. and Cutland, C. and Darton, T. and Dheda, K. and Duncan, C. and Emary, K. and Ewer, K. and Fairlie, L. and Faust, S. and Feng, S. and Ferreira, D. and Finn, A. and Goodman, A. and Green, C. and Green, C. and Heath, P. and Hill, C. and Hill, H. and Hirsch, I. and Hodgson, S. and Izu, A. and Jackson, S. and Jenkin, D. and Joe, C. and Kerridge, S. and Koen, A. and Kwatra, G. and Lazarus, R. and Lawrie, A. and Lelliott, A. and Libri, V. and Lillie, P. and Mallory, R. and Mendes, A. and Milan, E. and Minassian, A. and McGregor, A. and Morrison, H. and Mujadidi, Y. and Nana, A. and O'Reilly, P. and Padayachee, S. and Pittella, A. and Plested, E. and Pollock, K. and Ramasamy, M. and Rhead, S. and Schwarzbold, A. and Singh, N. and Smith, A. and Song, R. and Snape, M. and Sprinz, E. and Sutherland, R. and Tarrant, R. and Thomson, E. and Török, M. and Sorio, G. and Sorley, K. and Sosa-Rodriguez, T. and Souza, C. and Souza, B. and Souza, A. and Spencer, A. and Spina, F. and Spoors, L. and Stafford, L. and Stamford, I. and Starinskij, I. and Stein, R. and Steven, J. and Stockdale, L. and Stockwell, L. and Strickland, L. and Stuart, A. and Sturdy, A. and Sutton, N. and Szigeti, A. and Tahiri-Alaoui, A. and Tanner, R. and Taoushanis, C. and Tarr, A. and Taylor, K. and Taylor, U. and Taylor, I. and Taylor, J. and te Water Naude, R. and Themistocleous, Y. and Themistocleous, A. and Thomas, M. and Thomas, K. and Thomas, T. and Thombrayil, A. and Thompson, F. and Thompson, A. and Thompson, K. and Thompson, A. and Thomson, J. and Thornton-Jones, V. and Tighe, P. and Tinoco, L. and Tiongson, G. and Tladinyane, B. and Tomasicchio, M. and Tomic, A. and Tonks, S. and Tran, N. and Tree, J. and Trillana, G. and Trinham, C. and Trivett, R. and Truby, A. and Tsheko, B. and Turabi, A. and Turner, R. and Turner, C. and Ulaszewska, M. and Underwood, B. and Varughese, R. and Verbart, D. and Verheul, M. and Vichos, I. and Vieira, T. and Waddington, C. and Walker, L. and Wallis, E. and Wand, M. and Warbick, D. and Wardell, T. and Warimwe, G. and Warren, S. and Watkins, B. and Watson, E. and Webb, S. and Webb-Bridges, A. and Webster, A. and Welch, J. and Wells, J. and West, A. and White, C. and White, R. and Williams, P. and Williams, R. and Winslow, R. and Woodyer, M. and Worth, A. and Wright, D. and Wroblewska, M. and Yao, A. and Zimmer, R. and Zizi, D. and Zuidewind, P.},
month = {jan},
year = {2021},
abstract = {Background: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.},
pages = {99-111},
volume = {397},
issue = {10269},
journal = {The Lancet},
publisher = {Elsevier},
url = {http://dx.doi.org/10.1016/S0140-6736(20)32661-1},
}
