The National COVID Cohort Collaborative (N3C) Consortium is a US national enterprise to “aggregate and harmonize EHR data across clinical organizations in the United States”. The consortium comprises more than 600 individuals and 100 organization.

In a study led by Jing Sun, N3C was employed to investigate the effectiveness of COVID-19 vaccines. The study found that full vaccination provided a 24% improvement over partial vaccination for the prevention of COVID-19. The study also showed that hospitalized unvaccinated patients were at greater risk of severe disease than hospitalized full vaccination patients.

However, the original intent of the study was also to include an estimate of vaccine efficacy; the rate of COVID-19 diagnosis in the unvaccinated vs the rate in the fully vaccinated. That is apparent from a statement from the author in a comment to the article. However, no estimate of vaccine efficacy was provided in the article. Nor did the authors disclose the change to the protocol in the article. Furthermore, the trial protocol was not registered in ClinicalTrials.gov.

As mentioned above, the protocol deviation was disclosed in a comment to the article by the author, Jing Sun. I posed the following question to the author:

“Why not also compare the prevalence of COVID-19 in the pre vaccination and full vaccination groups? Such a comparison would provide an independent estimate of vaccine efficacy.”

Sun responded:

“Thank you for your comment and interest in our research. In an ongoing study, we are evaluating the vaccine efficacy in N3C. The current study was completed and submitted before all components evaluating vaccine efficacy were available.”

Note the “pre vaccination” group in this article refers to the “unvaccinated” group. The discussion then continued by email with the author.

“I commented on your recent article in JAMA Internal Medicine. Do you intend to publish the results of the study on vaccine efficacy?” (Yim)

“Thanks for your comments. Yes, the study is ongoing and we do plan to publish it.” (Sun)

“You say that the study is ‘ongoing’, yet the study data collection period was December 10, 2020 to October 14, 2021. What exactly is it about the study that is ongoing?” (Yim)

Sun did not respond.

The omission of the vaccine efficacy result from N3C study is a troubling protocol deviation. It’s also troubling that a clinical trial of this magnitude (664,722 subjects) was conducted without registration of the protocol. There needs to be a full accounting. More importantly, the N3C vaccine efficacy result needs to be publicly disclosed.

Biography: Peter J. Yim, PhD is a computer scientist and educator. He has written extensively on COVID-19 science and policy. This includes a broad perspective on US government handling of COVID-19: Separation of Science and State.