Like cigarette companies, Big Pharma has become skilled at satisfying the letter of the law by including long lists of ‘possible’ side effects in promotional materials and instructions for its products. Sometimes, however, it shifts gear into a more directly persuasive mode, even to the point of using bogus arguments for convincing well-intentioned health authorities of the safety of—or at least the need for—its products. A case in point: recent AstraZeneca (AZ) arguments for the safety of its COVID vaccine in the face of mounting concerns that, in some cases, the vaccine causes fatal blood-clotting events. I criticise two of the arguments that AstraZeneca has marshalled in defence of its vaccine: (1) the fallacious statistical argument that if the bad effects that are observed in the mass trial of X occur no more frequently than in the population at large then the product is safe; and (2) a question-begging utilitarian argument that the vaccine’s bad effects on the few are necessary for the good of the many. I also draw upon recent evidence of a causal relation between the AZ vaccine and serious blood-clotting events; and, on the basis of the phenomenon of EDTA-dependent-PTCP, suggest that the EDTA ‘excipient’ (filler) in the vaccine may be a (hitherto unrecognised) villain in the piece.
Let’s begin with the joint statement by the World Health Organization (WHO) and the European Medical Agency (EMA) advocating the use of the AZ vaccine in a mass vaccination campaign. It puts forward a brutal but apparently straightforward utilitarian argument, framed as a choice between two and only two possibilities. These are (1) not use the AZ vaccine, with the certain knowledge that many people will die from COVID-19 who, had they been vaccinated, would have lived, or (2) use the vaccine, knowing that the fatal effects of using it are restricted to a very few—’the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects’ (EMA). In short, the decision is the classic utilitarian choice that frames medical ethics in situations of scarce resources: namely, a decision between death for the few and death for the many. By framing the possibilities in this way, I will argue, the WHO-EMA implicitly (one might say question-beggingly) tips the balance in favour of using the vaccine.
I reject the WHO-EMA’s utilitarian calculus of death not only because of its brutality but also because, by focusing upon the AZ vaccine’s large-scale effects, it forecloses precautionary modifications to the current regime for administering it and, in so doing, biases the decision in favour of using the vaccine. Let me suggest two possible precautionary modifications that upset this morbid utilitarian argument.
First, a Norwegian team of scientists recently identified a few cases in which administering the vaccine had a direct causal relation to fatal blood-clotting events via the production of antibodies that trigger the agglutination of platelets. The Norwegian team recommends continuing to use the vaccine, but in combination with a follow-up to check for any signs of clotting effects and, if such effects are detected, providing immediate sustained treatment ‘by giving [patients] intravenous immunoglobin, which targets the [platelet-clumping] antibody and blood thinners’. Up to the time of writing this article, no such precautions have been instituted on a national basis.
Second, the AZ vaccine contains an excipient EDTA (‘Ethylendiamine’ for short) that is used extensively—and safely—as a ‘filler’ in orally ingested medications, in foods, and as a stabiliser for the in vitro (test-tube) blood samples that are the bread and butter of standard bloodwork tests. It is well known, however, that in a small percentage of people (0.1 to –2 per cent) EDTA causes an in vitro clumping of their blood platelets, leading to a reduced platelet count. In itself this familiar effect, called EDTA-dependent-PTCP (‘ETA-dependent-Pseudothrombocytopenia’ or simply ‘EDTA-PTCP’) is not considered a pathological condition. Instead it is the result of a harmless tendency, in a small percentage of people, for blood platelets to clump in vitro in response to exposure to EDTA, together with an artifact of the automatic counting of platelets by machines that cannot distinguish between platelet clumps and single platelets.
Now combine these facts with two other well-known facts: (a) blood clots form by the coagulation/clumping of blood platelets and (b) on post-mortem analysis, people who have either died from cerebral blood clots (CVST) or experienced other serious blood-clotting events within two weeks of receiving an AZ vaccine have exhibited the same surprisingly low machine readings of their blood-platelet counts that people with PTCP exhibit. On the basis of these facts, it seems a distinct possibility that the in vivo injection of EDTA has something to do with—perhaps even triggers—the fatal blood-clotting episodes. It would thus seem reasonable to remove individuals with PTCP from the pool of candidates for the AZ vaccine and instead allot them other vaccines. Up to the time of writing this article, to the best of my knowledge, no such precautions have been instituted (perhaps, one might speculate, because growing concerns about the AZ vaccine have led to a scarcity of the other vaccines).
Apart from the usual generalised warnings about allergies to vaccines, AZ’s response to this situation has been a strong denial of any fatal side effects of its vaccine, reinforced by somewhat more ambiguous denials to the same effect from the WHO and EMA. These denials, I now argue, have been grounded in a bogus statistical form of argument that is prevalent not only in the AZ debate but also more generally in arguments by Big Business in order to establish the safety of new products that it is mass marketing.
Let’s look in more detail at AZ’s response to increasing public concern about the safety of its vaccine, specifically the increasing concerns that it contributes to fatal blood-clotting events. In agreement with the EMA and WHO, AZ argues that the incidence of blood clots in the aftermath of people getting their vaccine is no greater (indeed some of the data suggests that it is actually less) than the expected incidence of blood clots in the general population.A recent careful article in The Lancet confirms this claim, although the article is careful to add that it considered blood-clotting episodes in general, rather than the fatal cerebral CVSTs upon … Continue reading On this basis, AZ (unsurprisingly) concludes that its vaccine is not a factor in contributing to the serious, sometimes fatal, clotting events that have been observed in the aftermath of administering it.The EMA and WHO apparently concur: ‘The European Medical Agency joined the WHO by saying that the numbers of blood clotting in vaccinated people seems not to be higher than that seen in the general population, combined with the reassuring conclusion… As of today, there is no evidence that the incidents [of clotting] are caused by the [AZ] vaccine’.
This sort of statistical argument is all too familiar in the mass marketing of new products in cases where there are safety concerns: for example, a new drug is deemed safe because the incidence of pathological effects after taking it is no greater (perhaps even less) than in the population at large. But the fallacy in this argument is apparent: it is not only wrong to infer a causal connection from a statistical correlation, but it is also wrong to make the reverse inference from the absence of a statistical correlation to the absence of a causal connection.
Such bogus arguments serve a double purpose: they justify assertions of causal independence, thereby helping to dismiss bad effects. But also, by focusing attention on large-scale statistical patterns as a basis for establishing causal relations, they deflect attention from the significant details of the causal relations. Specifically, they deflect attention from the variations in background conditions that, hidden within the large-scale patterns of events, steer the initial causes in radically different directions.
An example, a childhood trauma may well be a cause of future adult behaviour, but the direction that this future behaviour takes depends critically upon the background conditions in which it unfolds. Specifically, it depends upon what may be quite subtle differences in children’s subsequent upbringing, so that one traumatised child ends up a sociopathic criminal, whereas another ends up a law-abiding good citizen. This does not mean that the childhood trauma is causally irrelevant, however. On the contrary, the trauma is the primary cause that sets the scene for what comes later—and this primary causal relation may be reflected in statistical correlations of various sorts (for example, a high correlation between sociopathic behaviour and childhood trauma). But—and here is my main point—the burden of how a particular child’s adult behaviour comes to be fleshed out falls neither upon the initial traumatic cause, nor upon large-scale statistical correlations, but rather upon the particular background conditions under which the particular child subsequently develops. To put it in a nutshell, macro-statistical patterns take us only so far in our analysis of causes and effects, but as always (one might argue), the devil is in the detail—in particular, in what philosophers call ‘the ceteris paribus clause’ that details the supplementary background conditions that decide the direction in which a cause’s effects unfold.
And similarly, I argue, in particular cases the burden of the particular effects of the AZ vaccination falls upon the particular background conditions, which steer the effects of the vaccination, whether it is in the direction of (1) fatal blood clots or (2) in the opposite direction of a healthy, COVID-free life. The key question, then, is not the large-scale statistical question of the correlation between AZ vaccination and fatal blood clots upon which the WHO, the EMA and (to its advantage) AZ place our focus. Instead, I argue, the key question is in the details from which this large-scale statistical question distracts us: namely, which conditions will encourage the effects of the AZ vaccination to develop in the second direction, of a healthy, COVID-free life, rather than in the deadly direction of a CVST. And, I suggest, a good start in answering this key question is to advocate for the removal of people with EDTA-PTCP from the pool of candidates for AZ vaccination. Why? Because the EDTA-PTCP condition indicates a tendency for platelet clumping upon in vitro exposure to EDTA. On theoretical grounds (backed by some empirical facts), and since EDTA is a primary ingredient of the AZ vaccine, this, in turn, suggests that the injection of the AZ vaccine in vivo runs the risk of creating blood clots. A key part of my argument here is that, unfortunately, focus upon the issue of the large-scale correlation between blood clots and the AZ vaccination totally distracts us from even considering this suggestion, which, I argue, is central to developing a humane and useful answer to the question of how (or even whether) to use the AZ vaccine. (In the context of these remarks, I note with interest that AZ does include TCP—thrombocytopenia—among the list of rare dangerous side effects of its vaccine. But, perhaps understandably, it does not take the further, more radical step of counting the fake-relative of TCP, namely PTCP—pseudothrombocytopenia—among the vaccine’s risk factors.)
The upshot of these critical considerations is that, from a public-policy point of view, it is not, as the WHO-EMA put it, a simple choice between, on the one hand, not using the AZ vaccine and therefore facing the death of the many from COVID-19, and, on the other hand, using the vaccine while, for the greater good, putting up with the death of a few who happen to react fatally to the vaccine. Instead, there are other—dare I say ‘more humane’—choices: first, the choice to use alternative vaccines for pseudothrombocytopeniacs and their ilk, for whom the AZ vaccine may be dangerous; second (the Norwegian recommendation) to follow up more closely the AZ vaccinated for signs of clotting; and, third (we may add), investigating the possibility of alternative excipients for the AZ vaccine, other than EDTA. (At this point in my story, I should heap praise upon an individual doctor and an individual administrator of the Austrian Public Vaccination Service, who, upon being told that my wife had PTCP—and acting entirely upon their own initiative—insisted that she switch from being vaccinated with the readily available AZ vaccine to listing her for the scarce Pfizer vaccine.)
In the context of these considerations it is comforting to see that despite, it seems, buying into the statistical fallacies that I have criticised, the WHO-EMA does not agree with totally ruling out the possibility that the AZ vaccine contributes to serious blood clotting: ‘They [the World Health Organization and the European Medicines Agency] couldn’t establish whether the vaccine caused the [few observed] cases of CVST [cerebral venous sinus thrombosis] or DIC [disseminated intravascular coagulation]. But they couldn’t rule out the possibility, either’. Although, what is less comforting is that the WHO-EMA seem totally committed to making the brutal utilitarian decision that it is better to risk the lives of a few clotters than to restrict the circulation of the AZ vaccine: ‘The World Health Organization and the European Medicines Agency independently reviewed all the data in detail and, in the end, urged countries to quickly resume use of the [AZ] vaccine. Both agencies concluded that the risks of severe disease and death from Covid-19 clearly outweighed the exceedingly rare risk of blood clotting events’. My gripe with this argument is not only with its utilitarian brutality but also with its foreclosure of more nuanced answers to the question of how (not simply whether) to use the AZ vaccine.
Finally, let me return to my starting point: Big Business, specifically Big Pharma, is skilled at including low-profile, effectively unreadable hazard warnings with many of its products. On occasion, however, it goes even further in putting profits before its customers’ safety: namely, by not expanding the list of warnings to include ultra-rare or less than fully certain dangerous side effects, particularly when the effects in question are fatal. Surely people deserve better than this—especially now, amid the COVID-19 pandemic, when the stakes are so high. AstraZeneca and the relevant health authorities need to investigate, and circulate prominently, information about even the rarest conditions under which the AZ vaccine may have dangerous, even fatal, effects (among which I have suggested we may, perhaps even should, include EDTA-dependent-PTCP). Rather than relying on bogus statistical arguments or inhumane justifications, AstraZeneca and authorities such as the WHO and the EMA need to prioritise the development and setting in place of tests to help determine the AZ vaccine’s safety in individual cases.Update: A recent BBC report relays the opinion: ‘evidence is growing that the blood clot events are “causally related” [to taking the vaccine] although…the benefits of taking the AstraZeneca … Continue reading
Special note: please do not read what I am saying as anti-vax. Vaccines are a key element in any public health policy. But the public deserves not to be put at risk when simple precautions can be taken to screen for and guard against possible bad side effects of vaccines, however rare these side effects might be.
Although the development of a COVID-19 vaccine broke records for speed, never before have virtually limitless financial and scientific resources suddenly been made available.
|↑1||A recent careful article in The Lancet confirms this claim, although the article is careful to add that it considered blood-clotting episodes in general, rather than the fatal cerebral CVSTs upon which public attention has come to focus.|
|↑2||Update: A recent BBC report relays the opinion: ‘evidence is growing that the blood clot events are “causally related” [to taking the vaccine] although…the benefits of taking the AstraZeneca vaccine still far outweighed the risks of not getting the jab’. The report goes on to comment on ‘the unusual nature of the clots…including low level of platelets’ [which, I have pointed out, indicates the possible presence of an EDTA-PTCP effect]. The point to which I draw attention in this quotation is not merely the mounting evidence that the AZ vaccine causes blood clots but rather the continuing reliance of even the most well-intentioned scientists and media reporters upon forms of argument that, I have argued, are both bogus and inhumane.|