A commentary published on Medscape.com, April 29, 2021, claims that COVID-19 vaccine clinical trials were too brief to judge outcomes using absolute risk reductions (ARR), and that extending a clinical trial’s length of time can increase the ARR, thereby reducing the number needed to vaccinate to prevent one infection. Why Number Needed to Treat Can Be Misleading for Vaccines (medscape.com). The author’s argument in the commentary may be technically correct under certain assumed conditions or considered “contextual points,” but the argument is clinically meaningless at best.
The Pfzier/BioNTech vaccine’s absolute risk reduction is 0.7%, and the vaccine efficacy or relative risk reduction (RRR) is 95.1% Medicina | Free Full-Text | Outcome Reporting Bias in COVID-19 mRNA Vaccine Clinical Trials (mdpi.com). Published results from the Pfzier/BioNTech phase 3 clinical trial covered the period from May 2020 to November 2020, having a trial length of 6-7 months; more than just “a few weeks” claimed by the Medscape.com commentary. Inside the Pfizer/BioNTech COVID-19 vaccine trial: Insights on speed, agility and digital development (biopharma-reporter.com).
To follow the author’s argument in the commentary, let’s double the Pfzier/BioNTech phase 3 trial from seven months to 14 months, and also assume that cases in the vaccine group and the placebo group double. Under these circumstances, as the author indicated, the ARR will now double from 0.7% to 1.4% while the RRR remains the same at 95.1%. But how much has the ARR improved compared to the RRR? Not much. Let’s double the cases and trial time again. The ARR at 28 months is now 2.8% compared to the RRR of 95.1%…still pretty low. Get the point? The effect of length of time on the ARR compared to the RRR is relatively meaningless from a clinical and public health point of view.
Just out of curiosity, how long would it take for the ARR to catch up to the RRR under these “contextual” conditions? At 56 months the ARR is 5.6%; 112 months: 11.2%; 224 months: 22.4%; 448 months: 44.8%; 896 months: 89.6%…it would take over 75 years for the ARR to reach the RRR level under assumed conditions of consistent vaccine efficacy!
But let’s get back to reality. The more important point is that the relative risk measures, ARR and RRR, are both valid only for the actual length of the clinical trial. One cannot assume that the effectiveness of the vaccine in the “real world” would continue at the same efficacy rate beyond the trial length without supporting evidence. If you think you might get a better ARR with a longer trial, then the only proof is a longer trial. But basic principles of pharmacodynamics suggest the opposite is just as likely to occur.
Pharmacotherapies have limited real life effectiveness over time, including vaccines for influenza-like illnesses. Pharmaceutical companies rely on time-limited benefits to promote annual sales of seasonal influenza vaccines and booster shots. Additionally, the mRNA vaccines’ alleged biological mechanism of stimulating additional spike protein biosynthesis can theoretically only provide therapeutic benefits as long as the additional spike proteins remain active in the body. No protein remains in the body indefinitely as proteins are eventually catabolized and eliminated.
In conclusion, the argument in the Medscape.com commentary, that a vaccine’s ARR increases indefinitely with increasing length of time, is invalid because it assumes vaccine efficacy will continue at the same rate beyond the clinical trial length, without providing any strictly controlled experimental evidence to support this assumption.