Update, February 13, 2021: The first incoming data from Israel show that infections among the elderly have decreased whereas those among the younger have increased, respectively are unchanged. Since the elderly received the vaccination whereas the younger did not, this has been interpreted to be a consequence of the vaccination, not of the lockdown. However, we cannot conclude as such, because there is no control group. In other words, we do not know what would have happened had the vaccines not been given. One plausible explanation for differential dynamics of infections between the young and the old during the lockdown would be, for instance, that compliance is lower among the young than among the old. However, I would not dispute that the vaccines have an effect. The question is not if they do, the question is rather how strong is the effect? To assess this, i.e., to learn about the relative effectiveness of the vaccines, we need control groups. Even if the vaccination leads to an absolute reduction of infections, only knowing its relative effectiveness would enable us to make statements about a risk benefit trade-off. Therefore, the arguments in my blog that to date too little is known about the relative effectiveness of the vaccines for the old and frail continues to hold.
Update, February 08, 2021: In response to feedback from policy makers I trace out three policy implications from my blog below, two of which are explicit from the text, the third is a compromise between my suggestions and the status quo:
- Independent expert committee: Take serious the warnings about potential long-run negative health consequences from adverse immunological reactions and form an independent expert committee to investigate these warnings.
- Modify objective: Modify the goal from achieving herd immunity from the vaccination to taming the epidemic by proceeding with the covid-19 vaccinations as with the regular flu vaccination (which does not mean that covid-19 is a regular flu). Accordingly, if policy makers conclude on the basis of existing data that vaccinating the elderly (and the frail) can be done without health concerns, then recommend vaccination only to people above age 50 or age 60. The younger can, of course, also receive the vaccination but only if accompanied by appropriate education on risks and benefits. Under no circumstances should there be any pressure to get vaccinated – neither of a legal nor of a moral form.
- Statistical data analysis: As a compromise of my suggestion to interrupt the vaccination program to collect data in controlled trials and of the status quo, one alternative is to proceed in parallel, i.e., conduct controlled trials while the vaccines are already in the field. Another – inferior – alternative is to form an expert group of biometricians, statisticians, and econometricians to accompany the current field experiments with data analyses using sophisticated empirical methods. Collect data on socioeconomic characteristics from the treated, and, if feasible, also from control groups who do not receive the vaccination. It is indispensable to learn about the true effectiveness of the vaccines, in particular among the elderly and frail, in order to accompany the vaccination programs with additional measures to protect this group in the population. Notice that I have in mind measures along the lines of the recommendations of the German virologist Hendrik Streeck, and not measures in the spirit of extended lockdowns, see my blog with the provocative title “Zero Covid, Zero Sense”. Also notice that the incoming raw data from Israel cannot be directly explored to extract the needed information on the effectiveness of the vaccines, because there is no control group. Thus, also for this data, sophisticated data analysis is called for.
I should stress that I do not have any vested interests in writing this blog, also not in regard of item 3 of my above suggestions, because I am not a micro-econometrician, and I would therefore not be part of such a group of data experts.
Blog, February 02, 2021
In my view, we do not have a sufficiently deep discussion on the risk-benefit trade-off of the novel vaccines. Could it be that governments expose their citizens to too large of a risk? Do the risks outweigh the benefits? On the one hand, there exists the possibility that the vaccines are particularly dangerous in the longer run for those who need them the most, namely the elderly and vulnerable. On the other hand, too little is known regarding the effectiveness of the vaccines for that group. Furthermore, the young and healthy – who face a very low risk from the virus, but who do face an unknown risk from the vaccination – may still pass on the virus, and thus there may be no positive externality from the vaccinated in this group of the population to others. So, could it be that for this group the individual risks of the vaccination outweigh the social benefits?
Neither am I a biologist nor do I have any medical experience. However, as a scientist committed to the truth, I am concerned, hereby speak up and urge government officials, in particular in Germany, to interrupt the vaccination program in order to collect more data in controlled trials and to form an independent expert committee to investigate recent warnings on potentially serious adverse effects from the vaccines.
My concerns began when I first heard of the test results and of the finding that the high and truly amazing 95% effectiveness of the Biontech/Pfizer vaccination would not vary by age. I could simply not believe that samples were large enough to conclude with such statements. This concern was confirmed from Table 8 of the RKI bulletin, which shows that confidence bands for the effectiveness for the 75 and older range from -13% to 100%. In this group, there were only some 780 test persons, out of which only 5 were infected in the placebo – the control – and zero in the test – the treatment – group. In addition to this huge uncertainty regarding the effectiveness, if samples are so small, how can we have sufficient knowledge on potential (short-run) negative side effects? Of course, we know even less about potentially harmful long-run side effects of the new types of vaccines, because the horizons of the test phases are simply too short, but there is reasons to be concerned, see below.
One can also read from that table that there were only 4 cases of severe illness in the control group and 1 in the treatment group. Point estimate of 75% effectiveness but huge confidence bands. What can we learn from a handful of observations on the effectiveness of the vaccination against a serious disease? Very little.
Next, came the information from a commentary by Peter Doshi in the British Medical Journal which basically states that, in the Biontech/Pfizer trials, suspected but not confirmed covid-19 cases had been excluded. Peter Doshi presents a calculation that including these cases would reduce the relative effectiveness to at most 30%, way below the 50% threshold for authorization of the vaccine on the market. The study also concludes that we need more data, a statement I can only underscore.
Finally, I learned about cell biologists, hermatologists, imunologists and neurologists raising their concerns about high long run risks from the vaccines. Among those warnings are that serious illnesses and deaths will occur as a direct consequence of taking the COVID-19 vaccines because of adverse immunological reactions. For instance, the immunologist Hooman Noorchashm warns in a public letter sent to the US FDA dated January 26 of the immunological dangers of the novel Pfizer vaccine, most especially to those who are elderly, frail or have significant cardiovascular risk factors. Despite this, Mr. Noorchashm states that “I do believe that it is the patriotic duty of every American who can reasonably and safely be vaccinated, to do so – in order that we save our nation from this pandemic peril that is threatening our very existence.”
I reach a different conclusion. Neither the data uncertainty nor these warnings must be ignored. I urge government officials – and the German government in particular – to interrupt the vaccination program and to instead conduct extended controlled trials. We need more data, and we need independent expert committees who investigate the aforementioned possibility of adverse immunological reactions. Of course, tracking the current field experiments on the population is in the hands of the European EMA, and in Germany of the STIKO, but I am convinced that we need a break in order to buy time to investigate more in controlled trials and not to continue with this field experiment on the population.
In its recent update of January 29 the STIKO states that, in contrast to the Biontech/Pfizer and Moderna mRNA based vaccines, the vector based AstraZeneca vaccine shall only be offered to persons of age 18-64, whereas the mRNA based vaccines can also be offered to people above age 65. From my reading of the above mentioned RKI bulletin, I do not understand why the STIKO concludes that, in the case of the Biontech/Pfizer vaccines, there are instead enough observations for the elderly? The STIKO also recommends that formerly recovered should receive a vaccination no earlier than six months after their recovery in order to avoid excessive side effects. In light of potential risks of the vaccines and since a partial immunity is already achieved through an infection and since an existing study on influenza viruses concludes that “vaccines incorporating variants of pandemic viruses seem to provide little benefit to those previously immune”, does the recommendation to vaccinate the formerly infected really reflect an appropriate resolution of the trade-offs between risks and benefits?
It is my understanding that, since the novel vaccines are developed by a very different technology than conventional vaccines are, people who received the vaccination – or, the treatment – may still pass on the virus. In fact, as of now, there is not any evidence that this would not be the case. This is why vaccinated people still have to wear masks. Thus, positive externalities from vaccination – that the non-vaccinated are partially protected by the vaccinated – are far from clear, and the so-called sterile immunity may be out of reach. Why would then a caring government expose the young and healthy part of its population – who face a low risk of dying from the corona virus conditional on being infected – to unknown long-run risks from the vaccination, if the social benefits are so unclear? Would that not require first a controlled trial – see below – before carrying out such a huge experiment with the, as intended, entire population? On the other side, regarding the elderly population, it seems that we simply do not yet have enough data, and for the vulnerable, risks from side-effects and adverse immunological reactions later might be too high. Is it not then that a caring government should conclude that the risks potentially outweigh the benefits and thus this vaccination experiment on the population at large should not be carried out until we have more data from controlled trials? The most recent development is the intention to also vaccinate children. In light of the above arguments: Why? In sum, conditional on establishing effectiveness among the elderly and conditional on finding that long-run risks are not a concern, would it not be better to proceed as with the flu vaccination and to only recommend the vaccination above age 60 (or age 50, where the conditional mortality risk from corona in Germany exceeds one percent)?
What would additional controlled trials have to achieve? If the goal is taming the pandemic – which I personally regard as sufficient –, then the trials need to recruit those at high risk (such as the frail and elderly) and be powered to detect reduction in hospitalization, ICU use and death. Given the hypothesis of a 95% efficacy, it would not take large trials to confirm this benefit in that population, if it exists. If the goal is herd immunity, then the trials need to study prevention of infection and onward transmission, which is way more difficult to investigate.
Interrupting vaccination programs now to conduct at least the first type of controlled trial does not imply that we need to go into a prolonged lockdown – the current lockdown in Germany is anyway inappropriate. We have other means to contain the virus and to protect the elderly and vulnerable, e.g., through widespread use of rapid testing and improved treatment. Of course, following such a path requires chutzpa by politicians and may imply – in case the matter is resolved against the vaccination – that a large chunk of taxpayers’ money is lost. In case it will be, this will, however, be just a classical example of sunk costs. At a minimum, the vaccination programs must be accompanied by a better education about risks involved. For sure, there should be no pressure to get vaccinated, neither of a legal nor of a moral form.
I therefore regard the slow start of the vaccination programs in continental Europe as a virtue. In my view, governments should further slow it down to collect and to analyze more data in controlled trials.
Deutsche Übersetzung folgt