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By Mark Devonish
The Nature Research Journal succinctly captured in three profound analytical lines what most of us make of President Trump’s anti-science predisposition. For this citation from an academic journal is beyond astute and meritorious of a verbatim quote-“The US president’s actions have exacerbated the pandemic that has killed more than 200,000 people in the United States, rolled back environmental and public-health regulations and undermined science and scientific institutions. Some of the harm could be permanent.” Make no mistake, this anti-science predilection underpinning the public verdict on President Trump, reflects a thinking that is not intellectually align with modern day evidence based science. For it is without doubt that the outgoing President of the United States, dangerously and intentionally misled his supporters by repeatedly stating, without any evidence, that America is turning the Covid corner. Without question, any rational mind confronted with such an illogical pronouncement is likely to be rendered speechlessly befuddled as to what corner President Trump was calling attention to. For the statistics on this deceptive corner speak to a Covid which is deadly, contrary to President Trump’s argumentation- Counting in excess of 250,000 deaths with over 11M severely injured. But these ghastly numbers, birth out of Trump’s disinformation, must be contextually examined to appreciate the magnitude of the medical cataclysm that Trump has singlehandedly orchestrated. For it is on President Trump’s watch that his America, which has 4% of the global population disproportionately has over 20% of the Covid cases. It is on President Trump’s watch that America leads the World Covid league death table. It is on President Trump’s watch that from the Institute of Health Metrics and Evaluation modelling, they extrapolated that if he had shown leadership in promoting facial covering, then that simple act could have saved up to 100,000 Americans lives. It is on President Trump’s watch that more than 120,000 new cases of Covid and more than 1000 Covid deaths are being registered daily which continue to exponentially increase. So I humbly ask, is that turning a corner as Trump asserts or simply turning a blind eye?
And notwithstanding the nightmarish devastation that eventuated from his White House, President Trump continued to staggeringly dispense his propofol laced Kool-Aid to his gullible supporters, anaesthetising them into a state of irrational stupor in which they readily misbelieve that face coverings are ineffective, Covid will grow wings and miraculous go away, social distancing must be social distanced, injected disinfectant will efficiently eradicate the deadly virus from their bodies and hyroxychloroquine is the best medicine known to man. So with this level of debased thinking, not unexpected I may add, under President Trump’s leadership it is of little surprise that America has expeditiously plummeted from the stratospheric heights of global leaders in science to the global leaders in delusional jumbie in the dark conspiracy theories.Thankfully, President Trump has been directed to the exit but unfortunately he left behind the ginormous paranoia he created. For this paranoia he did feed and nurture with regular diets of conspiracy theories, with anti-science delicacies his preferred desert and politicisation of vaccination his favoured stupefying alcoholic beverage, which has resulted in universal suspicion about anything Covid. And it this suspicion, that found fertile ground in millions of skulls, germinating into a vibrant anti-vaccine movement which resulted in large percentage of the population aborting their confidence and common sense, in the Covid vaccines. For today my medical mission is to, with surgical precision, excise that fear and implant functional faith in Covid vaccines, with basic pharmaceutical research principles as the foundation.
Celebrating Covid vaccines
Over the past week, two world renown pharmaceutical companies, Pfizer and Moderna made public, data from their Phase 3 Covid clinical trial.These data compilation, which were independent of the pharmaceutical companies, revealed that both Covid vaccines have an efficacy of approximately 95%. Using the 50% efficacy influenza vaccine as a comparator, must undoubtedly make it easier to appreciate the euphoria of many on publication of these, never before seen type of data. Undeniably these data have resulted in a paradigm shift in benchmarking pharmaceutical validation- For the FDA, which is the American drug regulatory body, had set a benchmark of 50% efficacy for any Covid vaccine approval. Therefore, 95% efficacy, albeit preliminary for Moderna, is that light at this menacingly dark Covid pandemic tunnel. That light which is very much evident today, has it’s genesis from a very dark tunnel universally known as the Thalidomide Scandal.
The thalidomide Scandal
Clinical trials as an avenue to establish the safety and efficacy of pharmaceuticals are recent development in the field of pharmaceutical science. It’s genesis was birth out of an International catastrophe that opened the proverbial eyes of health care professionals. For pharmaceuticals predating clinical trials, were centred on curative outcomes with little or no extrapolation to potential patients’ burden adverse effects. But this all changed, disquietingly so, as a result of the thalidomide scandal. For thalidomide was a recognised curative treatment for vomiting in pregnancy. And I must state for the purpose of emphasis, that the use of the word ‘curative’ is not only descriptive of function but also to bring to the fore the limitation or myopic view of pharmaceutical companies in those dark days, with only a tunnel vision for cure but blind eyes for adverse effects. It is without doubt that these adverse effects alluded to, were worldwide reflecting the pervasive dispensing of the offending thalidomide. And it was theorised that these pervasive prescriptions did numerically amplify the adverse effects. For historically, this medical catastrophe cited did transpired before the days of pharmaceutical guardrails in the period 1950-1960. And the devastating numbers are- Over 10,000 newborns who had varying degrees of physical deformities that were painfully augmented by thousands of preventable miscarriages. But from this catastrophe many lessons were learnt which informed many recommendations that served as the underpinnings for practices aimed at minimising the probability of a reoccurrence. For these recommendations, which were far reaching, can be summed up in two lines; “medicines needed to not only satisfy efficacy criteria but more importantly safety parameters.” And these recommendations birthed the establishment of regulatory independent bodies to validate pharmaceutical research data before approval. These pharmaceutical research can be binary stratified as Pre-clinical and Clinical Trial. With the Clinical Trial, which I will expound on, being a process of three phases; Phase I-III.
Clarifying clinical trials
The first time a new pharmaceutical is tested in humans, it is usually given to a small group of volunteers(<10). The principle objectives are to:
1. Make sure that the new pharmaceutical presents no major safety issues.
2. Establish that it can reach the targeted body area and remain there long enough to deliver its benefit
3. Gain preliminary evidence that it could offer therapeutic value, or prevent the disease or condition
At this stage, the performance of the medicine in one group of volunteers is compared with another group of volunteers receiving a placebo or an existing treatment. A placebo is a treatment that looks the same as the potential new medicine, but has no active ingredients. In this way a reference group is established against which the performance of the new medicine can be judged. It is important wherever possible that neither the patients nor the researchers have any idea which volunteers receive which treatment. This is known as double blind control, and is a way to minimise bias in the reporting of the results. In phase II, <100 volunteers are used. If phase II is successful, approval will then be sought for a trial involving a larger group of people. Phase II trials aim to establish:
1. Effectiveness in treating the condition
2. Effectiveness in preventing the condition.
3. Appropriate dosing levels
If the results from phase II are encouraging, then the researchers can seek to start a phase III trial. This will be a much larger trial, often involving hundreds, possibly thousands of participants coming from a range of different countries. To be of medical success, a new pharmaceutical needs to offer the prospect of better outcomes for patients than any established pharmaceuticals that are already available. In the case of Covid, where no other vaccine is available, the comparator was a placebo. Generally, Phase III trials may last several years but in the case of the Covid vaccines, this was safely expedited because of the urgency of a pandemics. If a new pharmaceutical completes phase III with positive results, the pharmaceutical company may seek regulatory approval to make it available in a range of countries or regions. In the case of a new pharmaceutical, regulators will determine how it should be used and which patients should qualify for it, based on all the evidence from clinical and pre-clinical studies. This is known as a medicine’s indication. So what can be established, beyond reasonable doubt, is the rigorous testing pharmaceuticals undertaken before they are deemed safe for a large patient population. The principle objectives in phase III are to:
1. Demonstrate the safety and effectiveness of the new pharmaceuticals in the typical patient likely to use it.
2. Confirm effective dosing levels.
3. Identify side effects or reasons why the treatment should not be given to people with another condition (known as ‘contraindications’).
4. Build knowledge of the benefits of the medicine or vaccine and compare them with any risks.
5. Compare results against any currently achieved by existing treatments.
Pfizer and Moderna data appraised
As earlier alluded to, data from Moderna and Pfizer Covid vaccines indicate a 95% efficacy albeit preliminary for Moderna. And these data will now be to examine individually.
Pfizer registered 43,500 healthy volunteers in their Covid Phase 3 trial. From this cohort, half were randomly assigned to receive the vaccine while other half the placebo. The volunteers were then closely monitored. Of this 43,500 volunteers,170 developed coronavirus infection. Of the 170 who acquired coronavirus infection, 162 had the placebo while 8 had the vaccine. Therefor this translates to a efficacy of 95%. This efficacy was consistent across age groups with the over 65yrs having 94%. Further there were 10 severe cases of coronavirus infections with 8 out of the 10 volunteers being from the placebo arm. Adverse effects were headache and fatigue which occurred in less than 2% of the volunteers.This is the final analysis for Pfizer but they will continue to follow up these patients for two years. On Friday they have applied for Emergency Use Authorisation(EAU) in America. They will likely do the same in other countries. The EAU would involve two further detailed independent reviews and scrutiny of their data before agreeing to emergency use. If at all they agree.
Moderna phase 3 trial has 30,000 healthy volunteers with half being randomly assigned to the vaccine arm and the other the placebo. Thus far, based on preliminary data, 95 healthy volunteers developed coronavirus infection. Only 5 of the coronavirus cases were in the vaccine arm of the research while 90 were in the placebo arm. This translates to a vaccine protection of 94.5%. Their data also shows that there were 11 cases of severe coronavirus infections in the trial, but none in the volunteers who were immunised.
It should be noted that The Data Safety and Monitoring Board, an independent body in America would have securely kept all the data from the trials. In the case of the Pfizer 170 coronavirus infected volunteers and Moderna 95, the independent body would have first unblinded the data for both volunteers and researchers then shared the data with Moderna and Pfizer.
It is likely that Covid vaccines will be available to the general public by mid-2021. Despite this estimation, a few questions remain unanswered. It is likely that these questions, which are part of the end points of the trial, will be answered at the completion of the research and lengthy follow up. These unanswered questions are:
1. Will the vaccination immunity be life long?
2. How frequently will vaccination be required?
3. Will the vaccination protect against severe infections
4. Will the vaccination prevent the carriage and transmission of the virus?
5. What is the efficacy of vaccination in the elderly population?
Another factor that needs to be considered when procuring is storage. Pfizer vaccines need to be stored at minus 75 degrees Celsius. These are not standard temperatures in hospital freezer and may turn out to be a limiting factor for Pfizer. Moderna vaccine can be stored at minus 20 degrees Celsius which is much more practical.
Lessons for Guyana
Many countries have seen the Covid vaccine industry as an opportunity for lucrative investment, therefore it is of critical importance that Governments undertake transparent due diligence before procurement. The logical conclusion stemming from the aforementioned statement is that not all vaccines manufacturers will satisfy safety and efficacy standards since many will cut corners during their clinical trials. For example, China Covid vaccine trial was recently discontinued in Brazil because of severe adverse effects. Further, despite the trial being incomplete and of questionable safety, China had unethically started vaccination of their citizenry with said vaccine. India also has their hands in the Covid vaccine market but unfortunately no trial data is publicly available hence we are none the wiser as it pertains to safety and efficacy. Russia is also capitalising on the Covid vaccine market but shockingly they aborted Phase 3 trials to start distribution and vaccination of their population.
Four square pegs placed in a round hole
Finally, I do feel compelled to provide a polite reminder of the desperate need to avoid all Covid complacency. It is beyond imperative that we conscientiously utilise face coverings, religiously practice social distancing, diligently excercise good hand hygiene, unflaggingly avoid gatherings, strictly comply with WHO quarantine guidelines and patriotically follow self isolation. Unfortunately, adhering to these life saving measures have attained much greater importance since the PPP Government has raised the surrendering white flag at any attempts to impede the exponential increases in Covid cases and deaths under their watch. For sadly, if these Covid cases and deaths continue along this very trajectory, which is likely to be the case, then a much more painful 2021 awaits us all. Regrettably, the poor or absent management of Covid is reflected in the hundreds of other health conditions, with the vulnerable in our society having to face the brunt of it. Sadly, even with four de facto Ministers of Health, I have no confidence in any improvement soon since the issue is not quantitative but qualitative. For if one square peg is ineffective in a round hole, why the visionless thought four will produce a more desirable outcome?