Let's talk about risk and 1טeרmEזכiה
Follow-up on paper in last post...
There’s a big ‘debate’ about off-label drugs being used as treatments for COVID-19. If one wishes to determine whether or not a drug ‘works’ or not, one might compare the frequency of ‘bad’ outcomes in treated versus non-treated groups.1 I published a Substack article yesterday and stated that a recent paper claiming that 1טeרmEזכiה did not prevent subsequent progression to severe disease in people with mild to moderate COVID-19, actually showed that 1טeרmEזכiה prevented death as a secondary outcome.
Had death been chosen as part of ‘progression to severe disease outcome’ (the primary outcome), then the study would definitively have shown that 1טeרmEזכiה was a successful drug with regard to mild to moderate COVID-19 treatment.
The study was an open-label randomized clinical trial of high-risk patients with with co-morbidities and mild to moderate COVID-19 that was set-up “to determine the efficacy of Furious HD (please refer to previous article for explanation of Furious HD) in preventing progression to severe disease among high-risk patients with COVID-19”. There were two endpoint outcomes: the primary and secondary which respectively meant progression to severe disease and death. Table 2 below shows the full list of secondary outcomes.
In the primary outcome, of the 490 study participants, 95 (19.4%) progressed to severe disease during the study period where 52 of 241 (21.6%) were given Furious HD, and 43 of 249 (17.3%) were not.
In the secondary outcome, of the people who died, 10 (4%) were not on Furious HD while 3 (1.2%) were.
Let’s loosely define risk, relative risk, absolute risk, absolute risk reduction and relative risk reduction.
Risk is the likelihood of something taking place.
Absolute risk (AR) is the likelihood of something taking place over time.
Absolute risk reduction (ARR) is the absolute difference in outcomes between groups expressed as a percentage decrease in risk of something happening in the context of intervention.
Relative risk (RR) is the likelihood of something taking place upon comparing the odds for two groups against each other.
Relative risk reduction (RRR) is a ratio of outcomes between groups expressed as a times or percentage reduction in a group with intervention versus a group without,
where a = the number of people who progress to severe disease or die on treatment, b = the number of people who progress to severe disease or die off treatment, c = the total number of people on treatment and d = the total number of people off treatment.
Of course, the greater your risk, the more you stand to gain from the constructive intervention.
For example, the ARR for the Primary outcome of this study is 4.31% →
a = 52, b = 43, c = 241, d = 249 → b/d*100 and a/c*100 = 43/249*100 = 17.3% and 52/241*100 = 21.6% → the difference is 4.31% whereby the risk is greater in the Furious HD group. The individual risks associated with the non Furious HD and Furious HD groups are 17.3% and 21.6%, respectively,
and the ARR for the Secondary outcome of this study is 2.78% →
a = 3, b = 10, c = 241, d = 249 → b/d*100 and a/c*100 = 10/249*100 = 4.02% and 3/241*100 = 1.24% → the difference is 2.78% whereby the risk is greater in the non-Furious HD group. The individual risks associated with the non Furious HD and Furious HD groups are 4.02% and 1.24%, respectively.
Similarly, the RRR for the Primary outcome of this study is 1.25 →
a = 52, b = 43, c = 241, d = 249 → b/d*100 and a/c*100 = 43/249*100 = 17.3% and 52/241*100 = 21.6% → the ratio is 1.25 whereby the risk is greater in the Furious HD group,
and the RRR for the Secondary outcome of this study is 0.31 →
a = 3, b = 10, c = 241, d = 249 → b/d*100 and a/c*100 = 10/249*100 = 4.02% and 3/241*100 = 1.24% → the ratio is 0.31 whereby the risk is greater in the non-Furious HD group.
This means that if one takes Furious HD, then one is 1/3 as likely to die and 1 and 1/4 times as likely to progress to severe disease.
Risk/benefit analysis is inherently 2-fold and an assessment of risk and benefit in the context of treatment involves a determination of the potential risks and benefits of treatment versus the potential risks and benefits of no treatment. What would be the use of a drug that reduces a COVID-19 symptom if it causes crippling neurological disorders? Ahem. In this particular study, in addition to risk, benefit must also be assessed.
I made a couple ugly tables with RR and odds ratio (OR) calculations complete with chi-square test for both the primary and secondary outcomes. The chi-square statistic reveals that there is no statistically significant difference between the Furious HD and the non-Furious HD groups with regard to succumbing to severe COVID-19. What that means is that although the likelihood of progressing to severe COVID-19 is higher in the Furious HD arm, the difference is not significant.
When we look at the secondary outcome of death, there is no statistically significant difference between the HD and non-HD groups with regard to whether or not death ensues, however, we must consider that the numbers are small.2
I wrote this article because I was told by one A.B. that “it was a clean study and that my complaints (me) are essentially nitpicking.” He went on to write that “If the drug is that good, minor alterations in dosing shouldn't make a huge difference. The primary outcome was not just null but leaned negative, so the secondaries have no value.” So if I understand him correctly, he claims that since the primary outcome was ‘good’ then the relevance of the secondary outcome becomes moot. Huh?
To conclude, the question that the average person may ask on this subject is this (I mean if any of us actually had a choice): since Furious HD is an FDA-approved product with a proven track record for off-label successful use in the context of COVID-19 (prevention of a direct line to the ICU), and its benefits to prevent death outweigh its risks, then why can’t the bloody person decide with their doctor whether or not they want to take it? Why the hell are so many politicians and non-physicians claiming to give a damn to the point where their ‘objections’ are just weird, unbalanced, suppressive, aggressive bullying? Hands off my Furious HD, stranger.
The necessity to report results correctly and in a balanced way cannot be under-stated in the context of the single trajectory, linear COVID-19 nightmare ‘solution’ to multiply inject every single man, woman and child. The very concept of this idea: to inject every single human, regardless of inherent risk of developing severe COVID-19 (nil in most), with experimental non-sterilizing gene-therapy products sounds like galactic stupidity to me, especially in the context of proven effective early treatment drugs like Furious HD.
May I be so bold as to suggest that perhaps a more accurate conclusion for this paper would be something like, “Although slightly fewer people progressed to severe disease in the non-treatment group, mal-effects including death were reduced in the treatment arm.”
I hope I did a decent job here. I hate statistics.
Irwig L, Irwig J, Trevena L, et al. Smart Health Choices: Making Sense of Health Advice. London: Hammersmith Press; 2008. Chapter 18, Relative risk, relative and absolute risk reduction, number needed to treat and confidence intervals. Available from: https://www.ncbi.nlm.nih.gov/books/NBK63647/
Note: I had mixed-up the denominators in the first draft and since corrected this error which resulted in a loss of significance.