The US Buries Its Head While the UK Turns to Early Treatment

The UK Has Admitted the COVID-19 Vaccines Has Failed and It’s All Hands on Deck for Treatment. When Will the US Wake Up?

The University of Oxford has published results which show that early treatment with inhaled budesonide shortens recovery time by a median of three days in patients with COVID-19 who are at higher risk of more severe illness and are treated in the community.

This research, which found an average 3-day recovery time to non-hospitalized COVID-19 patients, was conducted as part of a series of Platform Randomized Trial of Treatments in the Community for Epidemic and Pandemic Illnesses (PRINCIPLE) studies, is an example of the increasingly embarrassing strange avoidance of studies of budesonide and other widely available drugs and therapies in the US. ClinicalTrials.gov lists 3 studies in the US that mention budesonide: two timid studies (one UPMC and one at the Mayo Clinic in Rochester) examining the effect of the therapy on the loss of smell. The third study is an anticipated observational study that will study a multimodal approach and lists budesonide as one of many options. Ivermectin is included among those options. There are an additional nine studies listed that focus on budesonide being conducted in other countries.

In March 2021, the UK also completed a Phase III trial of SaNOtize’s nitric oxide nasal spray. This therapy clears the SARS-CoV-2 virus in 95% of patients – regardless of how severe their symptoms – in 24 hours, and in 99% of patients in 72 hours. (Popular Rationalism has no financial affiliation or interest in the Canadian company SaNOtize or the product ENOVID, available online here).

Anyone can walk into any pharmacy in Israel and pick up a bottle of ENOVID. So why don’t we have widespread medical practice and advice on how to effectively manage COVID-19 in the US? Most studies conducted on inexpensive therapies are either observational or small randomized trials. This is the product of failed prioritization of funding for therapies for which real world data and data from smaller, but successful trials have shown promise. It has become clear that the reliance on large randomized clinical trials is a stop gap mechanism in place which ensures that only entities that can afford large-scale randomized clinical trials can produce results considered to be “credible”.

However, the way clinical studies are conducted in the US and elsewhere is backwards. The ability to detect a reliable, significant effect of a treatment is determined by a study’s statistical power, which everyone assumes is based on the sample size – the number of people in a study. But other factors also influence our ability to detect a significant effect – and one of those is the size of the effect itself. Smaller studies can, in fact, have high power if the effect size is large – and many of the therapies have had very large effects. Power of proposed studies can be calculated using effect size estimates from past studies – and until this changes, sufficiently powered studies that find compelling results in spite of their small size will be dismissed.

We now know that we can expect a rather large effect in outcome variables such as hospitalization and death from treatments such as Ivermectin – and the UK trial of 3 days’ recovery time of patients on budesonide tells us a major effect can reasonably be expected in other studies that look at the same or correlated outcome variables.

Clinical studies should base their recruitment efforts to accrue patients based on power analyses using the effect size of prior studies of the same treatment – or of treatments for the same condition. Currently, they are not required to do so, and this needs to change. The data safety monitoring board determines when the data are sufficient to be analyzed, and that process is neither transparent nor free from political pressure. The sample size needed to detect an effect should be locked in place by the IRB approval process using power curves that show the statistical power response to increased sample size, noting where on that curve the effect size of past studies. A safety margin of adding 20% more patients than the power calculations say is required would be a good new standard.

This very simple step will put a stop to the abuse of successful studies that have been reproduced by those who claim that only “large” RCTs are valid and who dismiss highly reproducible results like those found in the studies of Ivermectin.

US Buries Its Head on Innate Immune Therapies

For other therapies that hack the innate immune system, the US is burying its head in the sand. Here are some examples (data from ClinicalTrials.gov):

Ozone therapy (blood ozonation) – US (0 studies), other countries (10 trials) (Spain, Italy, Turkey, Belgium, UK)

Iodine (mouth rinse, nasal application, gargle) – US (4 studies), other countries, (20 studies)

Hydrogen peroxide (mouth rinse, gargle) – US (4 studies), other countries, (10 studies)

Vitamin D (oral) – US (2 studies), other countries (50 studies)

Quercetin (oral) – US (1 study), other countries (13 studies)

The vast majority of the studies listed in the US are not randomized clinical trials. The fact that the US is unable to conduct studies focused on reproducing hospitalization and mortality from therapies and treatments that are not highly profitable for pharmaceutical companies reflects an errant and broken value system in the persons in key positions at the primary US research funding agency, the NIH. The person who has stop-gapped and failed to prioritize essential research on potentially life-saving treatment options is, of course, Anthony Fauci.

On an episode of Unbreaking Science, Dr. Pierre Kory and I discussed this failure by Fauci to prioritize research focused on saving human lives and the premature adoption of remdesivir followed by the unseemly celebration of a press release touting molnupiravir based on interim results. We also discussed flaws in translational research and drug repurposing, among other things, like the sociopathologies afflicting clinical and translational research.

This is Dr. Kory’s second round on Unbreaking Science. Dr. Kory had some mic problems, so it sounds a bit like he’s speaking through a vacuum hose at times. But if you can ignore that and listen to what he’s saying, you’ll find that the fight for bona fide, effective, inexpensive therapies is the only ethical way forward. You can support UBS via Patreon.