Coronavirus -- HCQ, RCT, politics

This article, title Hydoxychloroquine: A Morality Tale, is sort of long (> 15,000 words), but well worth reading. It is about the drug (HCQ), randomized control trials (RCT), facing a pandemic due to a novel virus, and how they have been so politicized.

Remdesivir has been politicized, too, but not as much. Many people on the political left favor it. Its success in treating Covid is modest. Some had a change of heart when they assumed the FDA was unduly influenced by the Trump administration when the emergency use authorization was broadened for remdesivir. See my September 1 post.  

The article gets philosophical: "We live in a culture that has uncritically accepted that every domain of life is political, and that even things we think are not political are so, that all human enterprises are merely power struggles, that even the idea of “truth” is a fantasy, and really a matter of imposing one’s view on others. For a while, some held out hope that science remained an exception to this. That scientists would not bring their personal political biases into their science, and they would not be mobbed if what they said was unwelcome to one faction or another. But the sordid 2020 drama of hydroxychloroquine—which saw scientists routinely attacked for critically evaluating evidence and coming to politically inconvenient conclusions—has, for many, killed those hopes." 

Coronavirus – clinical trials #3

Yesterday’s post was about a clinical trial for a coronavirus vaccine and Mill’s Method of Difference. In this post I consider a clinical trial for a Covid-19 cure and Mill’s Method of Difference.

A clinical trial for a cure for Covid-19 would enroll patients who already have Covid-19. There is no contingency analogous to becoming infected like there is for a coronavirus vaccine clinical trial. On the other hand, there are a lot more variables – a variety of patients’ ages, each patient’s health status, degree of infection, and so forth. Dosage amounts may also differ, for which the logic is also Mill’s Method of Concomitant Variation.

Dr. Anthony Fauci often invokes the “gold standard” for clinical trials (randomized double blind placebo control studies) when he comments on any drug doctors might prescribe to treat patients. This standard is mainly for new drugs, but may also be used for already FDA approved medications for treating medical conditions outside the scope of prior approval, e.g. remdesivir for Covid-19. These are often called “off label” uses. It is also called repurposing. The FDA has relaxed its standards for drugs to treat Covid-19 patients. The FDA has made emergency use authorizations (EUA). The FDA may grant Investigational New Drug (IND) permission to test a drug. To my knowledge no drugs – even Remdesivir, which Fauci personally approves -- have passed the “gold standard” for treating Covid-19.

The following are the NIH guidelines for the treatment of Covid-19 with four different drug therapies.  Remdesivir.  Chloroquine and Hydroxychloroquine.  Hydroxychloroquine Plus Azithromycin.  Dexamethasone.

Conspicuously non-existent are web-pages for (1) Hydroxychloroquine (HCQ) Plus Zinc and (2) HCQ Plus Zinc Plus Azithromycin, especially with outpatients. Several doctors who recommend using HCQ for Covid-19, mainly with outpatients, have said zinc is a necessary enabler and without zinc the HCQ is minimally effective. Note that the NIH's web-page for HCQ + Azithromycin page concerns only trials with inpatients (hospitalized).

Dr. Anthony Fauci still approves using remdesivir. Regardless, it falls far short of a cure for Covid-19. Like the above web-page shows, some clinical trials have shown at best that remdesivir reduced  recovery time compared to a placebo. Other trials have shown no observed improvement or the data is insufficient. I would not call that passing the “gold standard.”

Dr. Fauci and the NIH recommend dexamethasone for some patients. The web-page above says clinical trials have shown significant mortality reduction in patients requiring supplemental oxygen, with or without a ventilator. On the other hand, no benefit of dexamethasone was observed in patients who did not require supplemental oxygen. Does this mean that dexamethasone passed the “gold standard”? Arguably 'yes' in some cases, but a cure? Many who got the drug still died during the trial.

Despite the many unknowns about the coronavirus and Covid-19 and the long time frame of clinical trials, Dr. Fauci often appeals to the “gold standard” as an argument against anything that doesn’t meet his or the FDA’s approval. In effect, he has little regard for individual judgments of practicing physicians to prescribe drugs absent his or the FDA’s approval, despite the lack of “gold standard” drugs for curing Covid-19 or halting its progress.

Dr. Fauci also consequently has shown little regard for giving placebos to patients who are seriously ill with Covid-19. Assume such patients participate in a clinical trial hoping to be cured and they later learn – if they survive – they were given a placebo and other patients in the trial who got the drug benefited. I suspect they would not be content.

Coronavirus – clinical trials #2

My previous post posited that the logical basis of clinical trials is Mill’s Method of Difference. The following is a simple example of a clinical trial based on Mill’s Method of Difference. Suppose there are N patients with disease D and the clinical trial is to treat some, e.g. two-thirds, of the N patients with medicine M and give the other one-third a placebo. Assume the later result is that the patients who are given M are cured of D, but the patients who are given the placebo are no better off than at the start. Then one could conclude that M is a cure for D. Call this the SDMT (for simple disease medicine trial).

A real world clinical trial is probably rarely as clear-cut as SDMT. It also seems to me that a clinical trial for a vaccine against the coronavirus would be far less clear-cut, for at least the following reasons.

1. The SDMT has a huge advantage over the coronavirus vaccine trial at the start. The participants at the start of the vaccine trial presumably have all tested negative for the coronavirus.* Some get the vaccine and the rest get a placebo. Then they wait to see if they do become infected by the virus to some degree. If they do become infected, and the vaccine protects against Covid-19, whereas those given the placebo get Covid-19, then the vaccine justifiably worked. However, many of the participants may not become infected any by the virus. They provide no basis for any conclusion about the efficacy of the vaccine. Presumably, such a vaccine trial must have many, many more participants than a SDMT kind of trial to make up for the probability of not becoming infected.

2. Those given the placebo might get infected, but their natural immune system might protect them from testing positive for the coronavirus or getting very ill from Covid-19 anyway.

3. Some participants may become only mildly infected and others far more so. This might come about due to the extent of precautions they take while in the trial, such as wearing a mask, keeping a safe distance from others, and washing hands. 

4. Some given the vaccine may be infected and the vaccine works. Others given the vaccine may be infected and the vaccine doesn't work or works poorly.

For all these reasons, and more not stated, a clinical trial for a coronavirus vaccine falls far short of all factors being the same except for one key difference for ideally applying Mill’s Method of Difference. It makes me quite skeptical about achieving a “gold standard” vaccine clinical trial per the wishful Dr. Anthony Fauci.

*The trial might also include groups of people who tested positive and are (a) asymptomatic or (b) have mild symptoms. They should be considered as separate trials.

Coronavirus – clinical trials #1

The coronavirus pandemic has pushed the concept and use of clinical trials into the mainstream media. Searching the Internet for {coronavirus clinical trials news} or {coronavirus clinical trials method} or {clinical trials logic} yields many results about clinical trials underway, but very little about the logic behind such trials. For example, this web-page is about clinical trials for a Covid-19 vaccine. The title says “here’s what you need to know”, but none of it is about the logic behind such trials.

When I became aware of clinical trials, I supposed that such trials are an application of John Stuart Mill’s Method of Difference. Researching it very recently, I found this web-page which supports the supposition. Despite that, it doesn’t link the logic of clinical trials directly to the influence of John Stuart Mill himself. Another web-page addresses the direct influence of Mill, but such influence is sketchy.