Before Phase 3 Trial results got published

Post #1063

Phase 3 trial results for COVID shots began being public in November 2020, when the researchers sent trial data to the FDA. But before that, in October 2020, a study was published showing what to expect. It was a study about how it is that you can go about performing a phase 3 trial on COVID shots, particularly which markers to use.

The kicker is that these other researchers already knew that COVID was not virulent enough to cause a lot of severe COVID cases in the phase 3 trial participants:

“However, severe COVID-19 constitutes a relatively small portion of COVID-19 cases, and incidence varies widely by age, underlying risk, and ethnicity (19–21), implying that statistical power to demonstrate adequate vaccine efficacy against the severe COVID-19 endpoint may be lower than that for an endpoint that includes reduction in nonsevere COVID-19.”

Knowing that COVID was not a very lethal disease for most people — i.e., that it was no more than twice as lethal as a bad flu would be — they presented an estimated number of severe COVID cases to be expected out of examining 10,000 unjabbed (placebo group) trial participants (number at top-right):

With 19 expected cases of severe COVID from 10,000 people, that hypothesized severe COVID case rate works out to 190 severe cases per 100,000 people. But using a measure for flu that estimates severity — i.e., using “flu hospitalizations” — the 30-week flu season of 2017/18 had a hospitalization rate more than half as high as that:

At 102.5 flu hospitalizations per 100,000, the hypothesized severe COVID case rate of 190 per 100,000 would be 85% worse than bad flu. Note how being twice as bad as flu would have meant that it was 100% worse than flu. Later on, a review of studies revealed that the hospital death rate for COVID was similar to the 2014/15 flu:

“For general patients admitted to the hospital (excluding critical care-only studies) the mortality rate of the COVID-19 was 11.5% (95% CI 7.7; 16.9, I2 = 96.7%).”

Notice the lower bound on the confidence interval of a 7.7% death rate for those admitted to hospital with COVID. That’s lower than the central estimate of 8.7% hospital death for the 2014/15 flu season (cell K7 below):

[click to enlarge]

It looks like, even before phase 3 trial results got published, that it was known that COVID was not more than twice as fatal as a bad flu season would be. This calls into question those mathematical modeling studies claiming up to 14 million COVID deaths prevented in a single year.

Being no more than twice as bad as a bad flu, COVID could not possibly even create that many deaths in a year. It would only be capable of creating under 160,000 deaths in a year in the USA (no more than twice as bad as bad flu).

Reference

[COVID not virulent enough to use “severe COVID” as a phase 3 trial endpoint] — Mehrotra DV, Janes HE, Fleming TR, Annunziato PW, Neuzil KM, Carpp LN, Benkeser D, Brown ER, Carone M, Cho I, Donnell D, Fay MP, Fong Y, Han S, Hirsch I, Huang Y, Huang Y, Hyrien O, Juraska M, Luedtke A, Nason M, Vandebosch A, Zhou H, Cohen MS, Corey L, Hartzel J, Follmann D, Gilbert PB. Clinical Endpoints for Evaluating Efficacy in COVID-19 Vaccine Trials. Ann Intern Med. 2021 Feb;174(2):221-228. doi: 10.7326/M20-6169. Epub 2020 Oct 22. PMID: 33090877; PMCID: PMC7596738. https://pmc.ncbi.nlm.nih.gov/articles/PMC7596738/

[flu hospitalization rate of up to 102.5 per 100,000 — i.e, more than half as bad as COVID] — Gantenberg JR, McConeghy KW, Howe CJ, Steingrimsson J, van Aalst R, Chit A, Zullo AR. Predicting Seasonal Influenza Hospitalizations Using an Ensemble Super Learner: A Simulation Study. Am J Epidemiol. 2023 Oct 10;192(10):1688-1700. doi: 10.1093/aje/kwad113. PMID: 37147861; PMCID: PMC10558190. https://pmc.ncbi.nlm.nih.gov/articles/PMC10558190/

[general COVID hospital fatality not statistically different from bad flu] — Macedo A, Gonçalves N, Febra C. COVID-19 fatality rates in hospitalized patients: systematic review and meta-analysis. Ann Epidemiol. 2021 May;57:14-21. doi: 10.1016/j.annepidem.2021.02.012. Epub 2021 Mar 2. PMID: 33662494; PMCID: PMC7920817. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920817/pdf/main.pdf