Publication El Sahly H, N Engl J Med, 2021
Dates: 2020-07-27 to 2020-10--23
Funding: Public/non profit (Office of the Assistant Secretary for Preparedness and Response, National Institute of Allergy and Infectious Diseases (NIAID / NIH), Biomedical Advanced Research and Development Authority (BARDA / U.S. Department of Health and Human Services))
Conflict of interest: Yes
Multicenter / United States |
Follow-up duration (months): 5.3
|• 100 mcg mRNA-1273 (n=15209)
• Placebo (n = 15206)
2 IM doses of 100-mcg mRNA-1273 D0/D27
2 IM doses of saline placebo, D0/D27
|Characteristics of participants|
Type of participants: Healthy volunteers
Pregnant women: 0
Mean age: 51.3
Age range: 18-95
|Description of participants|
Healthy adults with no known history of SARS-CoV-2 infection in 99 centers in the US
|In the register|
1. Number of Participants with a First Occurrence of COVID-19 Starting 14 Days after Second Dose of mRNA-1273 [ Time Frame: Day 29 (second dose) up to Day 759 (2 years after second dose) ];
2. Number of Participants with Adverse Events (AEs) or Medically Attended AEs (MAAEs) Leading to Withdrawal [ Time Frame: Up to Day 759 (2 years after second dose) ];
3. Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: Up to Day 8 (7 days after first dose) and up to Day 36 (7 days after second dose) ];
4. Number of Participants with Unsolicited AEs [ Time Frame: Up to Day 57 (28 days after each dose) ]
|In the report|
Vaccine efficacy in preventing a first occurrence of Covid-19 with onset at least 14 days after the second injection
Yes. In English
Yes, With publication of the final study results in 2022
|Risk of bias
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
In addition to the two published reports (El Sahly HM, N Engl J Med, 2021 and Baden LR, N Engl J Med, 2020), the FDA and sponsor briefing documents, the trial registry, protocol, supplementary appendices and sponsor media statement and trial website were used in data extraction.
Based on the Baden LR et al report: Mortality in the FDA and sponsor briefing documents vs in the published article were not the same. The publication reported on the fatal unsolicited adverse events 28 days after any injection while the FDA and sponsor briefing documents reported mortality that resulted from serious adverse events, up to December 3rd, 2020. Furthermore, we now report data for withdrawal from the study due to adverse events taken from unsolicited adverse events 28 days after any vaccination in the overall safety set. We are requesting information (particular of the denominators) from the authors concerning similar data presented in Table 16 of the sponsor document.
There were no substantive differences between the publication or FDA/sponsor briefing documents and the trial registry and protocol in population, procedures and interventions. The outcomes and timepoints reported were appropriate for an interim analysis of safety and efficacy of a large trial with follow up planned to continue up to two years.
Quote: "The case-driven study design required 151 COVID-19 cases to trigger the final scheduled efficacy analysis. Two interim analysis timepoints were pre-specified; the first upon accrual of 53 cases and the second upon accrual of 106 cases."
"The initial EUA request was based on data from the pre-specified interim analysis (November 11, 2020 data cutoff) with a median follow-up duration of 7 weeks after dose 2; this interim analysis data is the primary basis of this EUA review and conclusions. Data and analyses from a November 25, 2020 data cut with a median duration of at least 2 months follow-up after completion of the 2-dose primary vaccination series was submitted as an amendment to the EUA request on December 7, 2020. The FDA has not independently verified the complete safety data from the primary analysis, aside from all new deaths (including those reported through December 3, 2020) and SAEs."
This trial was updated on October 11th 2021 with results from the El Sahly et al report which reports data from a cutoff date of March 26, 2021.
This trial was further updated on September 2nd, 2022 after publication of immunogenicity results.