A Canadian Behavioral Study of Obedience on Vaccines
Or: A lesson in how to learn nothing about risk management, ever.
Thalidomide was first marketed in the late 1950s and used to treat nausea in pregnant women. It led to 10,000 children with birth defects. This tragedy was averted in the United States because approval was withheld by Dr. Frances Kelsey of the Food and Drug Administration. She was concerned about the potential effects a biologically active drug could have on pregnant women for which no long term test data existed1. Her concerns were dismissed by experts because testing on rats had shown no harms. Dr. Kelsey was ultimately awarded many times over as a heroine, including receiving a President's Award for Distinguished Federal Civilian Service in 1962 from President Kennedy and the Order of Canada in 2015, the latter because she was born, raised, and educated in Canada. Her commitment to rigor and data over expert opinion and political pressure saved many children and is credited with bringing about modern systematic long-term testing protocols.
COVID-19 vaccines have not yet completed such testing. They were approved in Canada under an Interim Order2, not because they have proven long-term safety but:
“predicated on the Minister's determination that the evidence provided supports the conclusion that the benefits outweigh the risks associated with the drug, taking into account the uncertainties related to the benefits and risks, as well as the urgent public health need caused by COVID-19.”
According to the regulatory decisions on each vaccine3 4,
“One limitation of the data at this time is the lack of information on the long-term safety and efficacy of the vaccine. The identified limitations are managed through labelling and the Risk Management Plan. The Phase 3 Study is ongoing and will continue to collect information on the long-term safety and efficacy of the vaccine.”
Labelling means the risk is managed by informed consent of the patient who takes responsibility for the risks. The Risk Management Plan describes how the outcomes on the public will be monitored, reported, and updated in the product monograph, after the fact, so that health officials can make any necessary changes to approvals and so future vaccine recipients can base their informed consent on up-to-date information. The vaccine monographs report5 6,
“The safety and efficacy of [the vaccine] in pregnant women have not yet been established; It is unknown whether [the vaccine] is excreted in human milk. A risk to the newborns/infants cannot be excluded. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for immunization against COVID-19.”
Risk mitigation by informed consent allows us to diversify risk, recognizing that the risk-benefit varies with individual age, gender, local case frequency, and natural immunity from prior COVID-19 infection7 8 9 10 11 12. However, this risk mitigation plan is changing. The Prime Minister has declared all federal employees must get vaccinated. For them, the government has decided the risk-benefit calculations for all individuals are the same as the overall drug approval, and risk mitigation by diversifying the risk should be eliminated. Risk information has not yet been actively shared with federal employees but perhaps being informed is moot without the ability to give consent.
I've seen this style of risk management before. In 1986 NASA Shuttle Program Manager Lawrence Malloy overruled Thiokol engineers worried about O-rings in cold temperature on the Space Shuttle Challenger. “My God, Thiokol,” he said in the pre-launch call, “when do you want me to launch, next April?”13 Malloy's objections: not enough data to demonstrate the risk, and a schedule to keep.
In 2003 NASA Mission Management Team Chair Linda Ham cancelled a request from the Debris Assessment Team to the Department of Defense for on-orbit imaging of Columbia's left wing. They were worried about damage from a high velocity fuel tank foam impact. Ham's objections: foam impacts had been deemed an “accepted risk” and imagery would unduly delay the mission schedule14. The Columbia Accident Investigation Board noted ongoing confusion between overall pre-flight “accepted risk” and case-specific “not a safety-of-flight problem”, much like an overall interim approval “benefits outweigh the risks” to allow that anyone can use a drug might be confused with case-specific risk-benefit calculations, or that everyone should use it. These aren’t the same risk-benefit calculations.
Certainly there are other objections to a vaccine mandate. We are often reminded that absence of evidence is not evidence of absence, but they do sound similar. The Canadian Charter of Rights and Freedoms, Section 7, precedence includes rights on bodily autonomy, choice of medical treatment, and limitations on government imposition. Section 15 addresses identical yet inequitable treatment. But I have no standing. I am not a secluded young female with prior COVID-19 immunity. I am middle-aged in a major city. I have been double-vaxxed for months. I recommend it for most people. I also recognize the risk-mitigation value, and rights, of individuals deciding their own medical treatment.
Despite my vaccination status, I've found myself wondering about the unknown long-term risks, the underlying ethics15, and game theory analysis16 suggesting this might be a bad idea. I've even considered the 1960s Milgram experiments simulating public obedience to authorities and experts17, showing how a large portion of society will actively harm others and rationalize it as merely following and trusting orders. I've wondered if we might need a Frances Kelsey.
Then I realized that Canada doesn’t have a Frances Kelsey. We never did. Thalidomide was approved in Canada in 1961. Kelsey saved American children. We eventually embraced Kelsey out of national pride but we have not embraced her essence. We are a nation of Malloys and Hams. We dismiss and mock those who don't fall in line and fail to get with the program. We have a schedule to keep, an election to win, and no evidence of long-term harms18. Our highest political authority has decreed that all we have to do for a successful mission is to merely follow orders.
Update 2021-09-20. The Interim Order expired on September 16, 2021. In Canada the order is now replaced by transitory regulations as outlined in the Canada Gazette dated March 31, 2021 which also notes the expiration date of September 16. The process has changed somewhat but the information and conclusions in this article remain the same.
Under the transitory regulations, way down at the bottom, continues the approval of the Interim Order. As part of this transition, the Government of Canada also approved name changes for the vaccines. As of September 16, 2021, the four approved vaccines are Moderna Spikevax COVID-19 vaccine, Pfizer-BioNTech Comirnaty COVID-19 vaccine, AstraZeneca Vaxzevria COVID-19 vaccine, and Janssen (Johnson & Johnson) COVID-19 vaccine.
As an example, clicking the Comirnaty vaccine details gives you a summary. Under the heading of “Vaccine review, approval and monitoring” is a link for Pfizer-BioNTech Comirnaty® vaccine regulatory information. Under the ‘Consumer’ tab (default), lists the link for “(New) Regulatory Decision Summary (Food and Drug Regulations)” dated September 16, 2021. If you click on ‘Why was the decision issued’, it unrolls the details. Near the bottom it re-states the same as before:
“An important limitation of the data is the lack of information on the long-term safety and effectiveness of the vaccine. The identified limitations are managed through labelling and the Risk Management Plan RMP).
The RMP is designed to describe known and potential safety issues, to present the monitoring plan and when needed, to describe measures that will be put in place to minimize risks associated with the product. Upon review, the RMP was considered to be acceptable and identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures based on the safety profile of the product. This included providing information in the product monograph and identifying populations where more data are needed.”
If you go back to the vaccine regulatory information and click on the tab ‘For health care professionals’, it has a link to the (Updated) Product Monograph dated September 16, 2021. In that monograph, Section 7, it makes the following statements:
“It is unknown whether COMIRNATY has an impact on fertility.”
“The safety and efficacy of COMIRNATY in pregnant women have not yet been established.”
“It is unknown whether COMIRNATY is excreted in human milk. A risk to the newborns/infants cannot be excluded. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for immunization against COVID-19.”
There are similar results for the other vaccines. So, even as of September 20, 2021 (today), the analysis remains unchanged.
James H. Kim, Anthony R. Scialli, Thalidomide: The Tragedy of Birth Defects and the Effective Treatment of Disease, Toxicological Sciences, Volume 122, Issue 1, July 2011, Pages 1–6, https://doi.org/10.1093/toxsci/kfr088
Government of Canada, Explanatory Note, Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19, Implications Section.
Government of Canada, Regulatory Decision Summary - Pfizer-BioNTech COVID-19 Vaccine - Health Canada.
Government of Canada, Regulatory Decision Summary - Moderna COVID-19 Vaccine - Health Canada.
BioNTech Manufacturing GmbH, Product Monograph Including Patient Medication Information, Pfizer-Biontech COVID-19 Vaccine, Section 7.1, page 12, retrieved Aug 19, 2021.
ModernaTX, Inc., Product Monograph Including Patient Medication Information, COVID-19 Vaccine Moderna, Section 7.1, page 8, retrieved Aug 19, 2021.
Government of Canada, COVID-19 daily epidemiology update, last retrieved version Sep 3, 2021.
Cohen et al. Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells. Cell Rep Med. 2021 Jul 20;2(7):100354. doi: 10.1016/j.xcrm.2021.100354. Epub 2021 Jul 3. PMID: 34250512; PMCID: PMC8253687.
Trinité et al. SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity. Sci Rep. 2021 Jan 28;11(1):2608. doi: 10.1038/s41598-021-81862-9. PMID: 33510275; PMCID: PMC7843981.
Ivanova et al. Discrete immune response signature to SARS-CoV-2 mRNA vaccination versus infection. medRxiv [Preprint]. 2021 Apr 21:2021.04.20.21255677. doi: 10.1101/2021.04.20.21255677. PMID: 33907755; PMCID: PMC8077568.
Radbruch A, Chang HD. A long-term perspective on immunity to COVID. Nature. 2021 Jul;595(7867):359-360. doi: 10.1038/d41586-021-01557-z. PMID: 34127832.
Hall et al. SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN). Lancet. 2021 Apr 17;397(10283):1459-1469. doi: 10.1016/S0140-6736(21)00675-9. Epub 2021 Apr 9. Erratum in: Lancet. 2021 May 8;397(10286):1710. PMID: 33844963; PMCID: PMC8040523.
Report of the Presidential Commission on the Space Shuttle Challenger Accident, Volume 5, February 26, 1986 Session.
Report of Columbia Accident Investigation Board, Volume I, Chapter 6.
Specifically, various versions of the Trolley Problem whereby you reduce the risks for some people by increase the risks for others.
Ahn, T.K., Lee, M., Ruttan, L. et al. Asymmetric payoffs in simultaneous and sequential prisoner’s dilemma games. Public Choice132, 353–366 (2007). https://doi.org/10.1007/s11127-007-9158-9. Retrieved from https://papers.ssrn.com/sol3/papers.cfm?abstract_id=932675
Milgram, Stanley (1963). "Behavioral Study of Obedience". Journal of Abnormal and Social Psychology. 67 (4): 371-8.
Or safety. There is an absence of evidence one way or the other, not evidence of the absence of long-term harms.