Most readers will be aware of the rumpus that has characterized the rollout of vaccines in an effort to bring this pandemic under control. These concerns have mainly surrounded the COVID-19 vaccine that was developed through a collaboration between scientists from Oxford University and Anglo-Swedish pharmaceutical company AstraZeneca. The rumpus started with reports that some patients who had been vaccinated had developed blood clots; with others found to have lowered platelet counts.
Though the number of reported cases were few, the occurrence of fatalities led several countries in mainly Europe to pause the use of these vaccines whilst investigations were carried out to establish if there was a causal relationship between the vaccines and these rare blood clots. The anxiety that followed the decision to pause and investigate these events led to many people having misgivings.
As at the time of writing, the World Health Organization (WHO), the European Medicines Agency (EMA) and the Medicines and Health Products Regulatory Authority (MHRA) of the United Kingdom had reported the findings of their independent reviews and concluded that the Oxford-AstraZeneca vaccine was safe, efficacious and protected against SARS-CoV-2. If this debate rested simply on the science of vaccine research and development as well as regulatory licensure of pharmaceutical products, these independent findings should have settled this matter. However, in the world of vaccine hesitancy, driven by a mixture of lack of education and anti-vaccination campaigners, this has not been the case.
We, therefore, set out to explain why there should not be cause for alarm.
We start from the premise that for any medicinal product to be approved for use by a medicine’s regulator, a benefit-risk analysis would have to be undertaken. This is a tacit acceptance that there is no pharmaceutical product in current use globally that is devoid of side effects or Adverse Drug Reactions (ADR). An ADR is an undesired or harmful effect resulting from the use of a medication or other medical intervention. If the ADR is judged to be secondary to the main effect of the therapy it is termed a side effect.
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For example, if a person received a COVID-19 vaccination and then experienced headache, fever, raised temperature or inflamed lymph nodes, these are considered side effects. This is an indication that the immune system has responded to the vaccine and that antibody production has commenced. These effects may last for up to two days and wane off on their own or following the use of analgesics. However, the development of a blood clot, if linked to vaccination, will not be considered a side effect; as it has no secondary correlation to the desired therapeutic effect. Such occurrences are seriously reviewed, and if attributable to the pharmaceutical product, could result in a withdrawal of the said product under certain circumstances.
To obtain information to make these decisions, medicine’s regulators undertake post-market surveillance to track the performance of existing and new medicines in the general population. In the United Kingdom, for example, new medicines are denoted as black triangled, requiring a black triangle to appear after the trade name. For such medicines, all ADRs must be reported. Similar protocols exist for most countries where medicines regulation is a priority.
The United States National Cancer Institute (NCI) has standardized a way to measure the seriousness of an adverse event. This is called the Common Toxicity Criteria for Adverse Events (CTCAE). This standardisation grades ADRs on a scale from 1 to 5. Grade 1 adverse events are mild and generally not bothersome. Grade 2 events are bothersome and may interfere with doing some activities but are not dangerous. Grade 3 events are serious and interfere with a person’s ability to do basic things like eat or get dressed. Grade 3 events may also require medical intervention. Grade 4 events are usually severe enough to require hospitalization. Grade 5 events are fatal. ADRs of Grade 3 and higher are often a cause for concern. The reported blood clots led to Grade 4 and 5 events and hence were the cause of the initial red flags that were raised.
The raising of red flags is the first step in reviewing the frequency and probability of occurrence of the particular ADR. If the probability of it occurring in those using the medicinal product exceeds that of the general population, most regulators will institute a review of the newly licensed medication and restrict its use further. If the concerns are significant, leading to the benefits of use being outweighed by the risk of ADRs, the use of the product is paused. Such a pause could either lead to product recall or the issuance of further guidance for use in a particular age group, gender or race. Such reviews are what resulted in Aspirin not being licensed for use in people below the age of 16-years.
Available evidence suggests that, on average, 1 or 2 people in every 1000 in the general population (0.2%) will develop a blood clot or lowered platelets, without any medical intervention or vaccination. Also, for people hospitalised with infections of SARS-CoV-2, 1 in 6 (16.67%) will have blood clotting irregularities. Of the data reviewed from over 17 million people from the United Kingdom and the European Union who had received the AstraZeneca vaccine, it was found that approximately 0.00035% developed a blood clot or lowered platelets. More importantly, a direct causal relationship has not been established by any of the regulators between the receipt of the vaccine and the development of these blood clots. In the strictest sense, these events could be said to be unrelated and not classified as ADRs attributable to the Oxford-AstraZeneca vaccine.
As we indicated in a previous article, most of the COVID-19 vaccines in current use reported the development of blood clots amongst a very small percentage of volunteers during their clinical trials before Emergency Use Authorisation (EUA) was granted. Furthermore, most have reported the occurrence of such events during the current global mass vaccination drive. This is why we believe the pauses issued by these countries were not backed by science and have only succeeded in increasing vaccine hesitancy. More importantly, they have slowed down the global match towards herd immunity and worsened the plight of citizens in some of these countries. Furthermore, these actions would potentially lead to avoidable deaths. When the pause is lifted, there is further constrain on the global vaccine supply chain since manufacturing, after being paused, will struggle to meet the sudden increase in demand. We are of the view that the main driver of these unfortunate events was geopolitics. Also, we cannot discount the dark hands of pharmaceutical manipulation in a quest to drive up the cost of vaccines.
We hold these positions based on a leaked letter indicating that some vaccine developers were in discussions to hike their prices. Their claim, rather erroneously, made was that with the discovery of vaccines, this pandemic was over. How this conclusion was reached is one we will leave to the imagination of our readers. The timing of these discussions around the pause of the AstraZeneca vaccine gives us cause for concern as well . Although, the AstraZeneca vaccine is the cheapest available due to the United Kingdom absorbing most of the research and development investments made, many perceive it as low quality. Thus an attempt to discredit the Oxford-AstraZeneca vaccine, and subsequently hike up the price of their vaccines, could make countries perceive them as the vaccine of a choice from a value for money and cold chain logistical standpoint. This for us is what this turf war is all about.