When clinical trials are planned, a stopping rule is often pre-specified in order to preserve integrity. Back in the early 2000’s, a trial of the now-removed anti-inflammatory drug, VIOXX (rofecoxib), had begun — but without a pre-specified stopping rule:
Nevertheless, they found a 92% increase in cardiovascular adverse events, and it was enough to shut the trial down:
Even without a stopping rule, they realized that it is counter-productive to administer a medication that makes serious adverse events 92% more likely to occur (i.e., almost doubles the rate of serious adverse events). The accumulated incidence of medically-confirmed thrombotic events for VIOXX (rofecoxib) became signficantly higher:
That being said, it would also be true for when the lower bound of a confidence interval represents a 100% increase in risk, such as in this study regarding COVID shots:
[purple markings added]
This screenshot, taken from a report cited by Nic Hulscher, reveals that COVID shots have “crossed the Rubicon” into the territory where it is normally the case that a Stopping Rule engages and the whole project gets shut down out of an abundance of caution. It is not medically ethical to continue a product known to double your risk.
Because of the high basline rate of cardiovascular events, whenever you double the risk for them, you increase the harm immensely. The 92% increase in cardiovascular risk, just from VIOXX, is suspected to have led to the premature death of 38,000 people:
But the estimate for COVID shots would be even higher than 38,000 people killed prematurely, because there have been more people exposed to COVID shots — and for more total person-years — than there were for those exposed to VIOXX. It could be that the number of premature deaths are quadruple or even quintiple that for VIOXX.
That’s an awful lot of premature deaths to be causing in people, much higher than the total number of deaths of Americans for the entire 10 years of the Vietnam War. But medical interventions should not “cause more death than wars.” The VIOXX researchers knew this, but what has changed?
With food and dietary supplements, the Food & Drug Administration (FDA) will pull a product if it is found to have over 2 milligrams of lead per kilogram of product (2 ppm of lead):
But when it comes to drugs, FDA has been at least sometimes willing to “look the other way” even after strong statistical significance of a “risk doubling” has been shown — as is currently being illustrated by the COVID shot fiasco. Hopefully, things will change at the FDA with the new administration.
For as long as we have “gatekeeper” regulation (where FDA decides who stays and who goes), we can close our eyes and imagine a time and a place where products shown to double your risk of very serious medical conditions get quickly and decisively pulled from the market.
p.s. If we didn’t have gatekeeper regulation, new avenues of information would spring up quickly to replace the service that the FDA had been providing. In other words, in a completely-free market, consumer watchdogs would find a way to profit off of saving people’s lives with early-warning systems. They’d get rich off of saving lives.
Reference
[stopped study, due to an almost doubling of serious cardiovascular events] — Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA; Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005 Mar 17;352(11):1092-102. doi: 10.1056/NEJMoa050493. Epub 2005 Feb 15. Erratum in: N Engl J Med. 2006 Jul 13;355(2):221. PMID: 15713943. https://www.nejm.org/doi/10.1056/NEJMoa050493
[38,000 suspected of being killed by VIOXX] — https://www.npr.org/2007/11/10/5470430/timeline-the-rise-and-fall-of-vioxx
[FDA recalls] — https://datadashboard.fda.gov/ora/cd/recalls.htm