We must keep our scientific hats on when poring over an analysis of treatments relating to the recent pandemic, writes Terry Maguire
I have tried really hard not to fall down any rabbit holes when it comes to Covid-19 in case I resurface in a land of crackpots, antivaxxers, and delusional conspiracy theorists. I am a pharmacist and therefore I consider myself a scientist. I should be able to make some sense of the data provided on the safety and efficacy of medicines, including Covid-19 treatments.
Interventions to protect public health when the pandemic struck in early 2020 were threefold: non-pharmaceutical interventions (lockdowns, masks, and socials distancing); repurposed drugs (dexamethasone, ivermectin, and hydroxychloroquine); and vaccines. With the exception of dexamethasone, few drugs were found to be effective in reducing the risk of infection and disease transmission or in reducing the impact of the disease, specifically hospitalisation and death. Ivermectin, discovered by Donegal man Bill Campbell, is an effective animal dewormer and treatment for river blindness, and has been discussed before in these pages with the conclusion that it is largely ineffective as a treatment for Covid-19. Cochrane, the trusted reference on drug safety and efficacy, updated its assessment on ivermectin in June 2022, and this is what they say.
“For outpatients, there is currently low?to-high-certainty evidence that ivermectin has no beneficial effect for people with Covid?19. Based on the very low-certainty evidence for inpatients, we are still uncertain whether ivermectin prevents death or clinical worsening or increases serious adverse events, while there is low-certainty evidence that it has no beneficial effect regarding clinical improvement, viral clearance, and adverse events. No evidence is available on ivermectin to prevent SARS-CoV-2 infection.”
In other words, there are trials and studies assessing the benefits of ivermectin in Covid-19 treatment and prevention, but they are quite poorly designed, so it is very difficult to say with any degree of certainty that ivermectin works. But it is certainly not the wonder drug it was claimed to be at the start of the pandemic.
Vaccines
When it comes to the vaccines produced at lightning speed at the end of 2020, they are very safe and highly effective. Indeed, the studies used to obtain an Emergency Use Authorisation (EUA) in the EU and the US suggested 95 per cent efficacy against Covid-19 infection and 100 per cent efficacy against death. These are the statistics we as pharmacists report to our patients in support of vaccination, and most of us continue to do so as we complete the winter vaccines service. But how correct are they?
For the Pfizer vaccine, the pivotal study by F Polack and colleagues, published in NEJM at the end of 2020, provided the data on Covid cases. The Pfizer application to the US Food and Drug Administration had the additional data on Covid deaths and all-cause mortality but it is less well known. The data are summarised in Table 1:
Table 1
When we look at the number of Covid-19 deaths, it is, you may agree, a bit of a stretch to claim 100 per cent efficacy in avoiding deaths when it is based on three patients out of 44,000 persons. The main goal was, of course, to avoid Covid infection and this outcome seems more robust in the raw data presented.
Put simply, Polack’s study states that if no vaccine was used, then out of about 22,000 people 162 would catch Covid and two would die. But use of the vaccine reduces the number of Covid-19 infections down to eight, which is 4.9 per cent of 162, therefore a relative risk reduction of 95.1 per cent and this is why we all quote this figure. Deaths fall from two to one and for some reason this is a relative risk reduction of 100 per cent (my very poor mathematics makes this a 50 per cent reduction but who am I?)
What was not reported in this study is that there were an additional 34 deaths from all-cause mortality; 20 died in the vaccine group and 14 died in the placebo group. Of the 20 who died in the vaccine group, five of them were due to cardiovascular causes compared to zero in the placebo group. However, for some reason, this was not considered an issue by regulators.
Controversial
Robert F Kennedy Jr, a 2024 US presidential candidate and nephew of President John Fitzgerald Kennedy, wrote a controversial book The Real Anthony Fauci: Bill Gates, Big Pharma, and the Global War on Democracy and Public Health, published in late 2021, and it became an instant bestseller in the US. In this large and impressive tome, Kennedy makes the case that the repurposing of drugs in the pandemic was deliberately blocked by Anthony Fauci because it allowed him to seek and obtain an Emergency Use Authorisation (EUA) for the drug remdesivir (the monoclonal antibody drug), and new vaccines based on the novel mRNA technology in which he, according to Kennedy, had a considerable vested interest.
Had ivermectin, or another repurposed drug, proved effective in reducing the impact of the disease – reducing hospitalisations, for example – then this non-patented medicine would have become widely used. From Kennedy’s point of view, this would have stopped an EUA application for both remdesivir and Covid vaccines as there would already have been an effective remedy and therefore no urgent public health need. Remdesivir and the vaccines would then have been required to go through the normal rigorous assessment required by regulators for any new drugs and perhaps, just perhaps, when all the data was known it might have been less of a rosy picture for monoclonal antibodies and the emerging mRNA vaccine technology.
Kennedy is a tort lawyer and his book unfortunately reflects his strength in pleading in a legal rather than a scientific forum. He has also been accused of lacking ‘intellectual modesty’ by his critics and Fauci has said he is “a very paranoid and disturbed person”. That said, Fauci himself and others are not well known for their intellectual modesty either.
Kennedy is a tort lawyer and his book unfortunately reflects his strength in pleading in a legal rather than a scientific forum.
Kennedy uses and cites references not for their scientific rigour but because they suit his case. For example, when discussing ivermectin he describes one “powerful” study as showing a “dramatic” effect. The study he cited is a very small unblinded trial that involved a comparison of 12 patients in an ivermectin arm and 12 patients in a placebo arm. The belief that this study can add anything to scientific understanding is just laughable.
Kennedy also cited a study to back his claim of the significant toxicity of vaccines, but failed to quote a section of the paper that stated that vaccines are 90-99 per cent effective against hospitalisation, 90-95 per cent effective against mortality, and 65-99 per cent effective against symptomatic disease.
His reference sections always seem impressive, but on closer inspection are found to contain many gossip items and TV channel discussions with unscientific and unsubstantiated claims that back the case he is trying to make.
I suppose my learning from my near fatal trip into Kennedy’s rabbit hole is that I am not the sharp scientist I assumed I was. The scientific studies that give us our understanding of the real world and the Covid-19 pandemic need close study and careful interpretation. It’s too easy to bamboozle and use slight-of-hand statistics that manipulate even the well-informed.
Much remains to be uncovered about the pandemic that we have just come through. More will become known as more data and better information becomes available. Vaccines for Covid-19 are unlikely to prove as effective against all end points as was claimed when they were licensed using a EUA, and they certainly will have side effects.
Meanwhile, the monoclonal antibody drug remdesivir licensed with a EUA is not very effective. According to Cochrane, “remdesivir probably makes little or no difference to deaths after 28 days, after 60 days, or to deaths in hospital during 150 days. It probably raises the chance for patients to get better slightly, and it probably lowers the risk of getting worse. The rates of unwanted effects of any severity were similar between the compared groups”. Reading Kennedy’s book, I also learnt the danger of expecting black-and-white answers from science. This is what Kennedy tries to do. Science has to deal with uncertainty, and the truth is not easily arrived at in one, two, or even myriad well-designed studies. He might turn out to be right on a few things. All the people in the Polack study were vaccinated immediately after the study ended. This means that it is not possible to use this cohort to study potential long-term side effects of the vaccine. Ethically, this decision was dubious even when manufacturers claimed it was unethical not to vaccinate the control group. But a non-vaccinated cohort was the only way to look for unusual side effects given that mRNA technology is new and largely untested. Absence of that data is indeed cause for concern but not a justification to jump back down the rabbit hole.
