In 2022, students at North American universities with third-dose COVID-19 vaccine mandates risk disenrolment if unvaccinated. To assess the appropriateness of booster mandates in this age group, we combine empirical risk-benefit assessment and ethical analysis. To prevent one COVID-19 hospitalisation over a 6-month period, we estimate that 31 207–42 836 young adults aged 18–29 years must receive a third mRNA vaccine. Booster mandates in young adults are expected to cause a net harm: per COVID-19 hospitalisation prevented, we anticipate at least (...) 18.5 serious adverse events from mRNA vaccines, including 1.5–4.6 booster-associated myopericarditis cases in males (typically requiring hospitalisation). We also anticipate 1430–4626 cases of grade ≥3 reactogenicity interfering with daily activities (although typically not requiring hospitalisation). University booster mandates are unethical because they: (1) are not based on an updated (Omicron era) stratified risk-benefit assessment for this age group; (2) may result in a net harm to healthy young adults; (3) are not proportionate: expected harms are not outweighed by public health benefits given modest and transient effectiveness of vaccines against transmission; (4) violate the reciprocity principle because serious vaccine-related harms are not reliably compensated due to gaps in vaccine injury schemes; and (5) may result in wider social harms. We consider counterarguments including efforts to increase safety on campus but find these are fraught with limitations and little scientific support. Finally, we discuss the policy relevance of our analysis for primary series COVID-19 vaccine mandates. (shrink)

In times of crises, public health leaders may claim that trials of public health interventions are unethical. One reason for this claim can be that equipoise—i.e. a situation of uncertainty and/or disagreement among experts about the evidence regarding an intervention—has been disturbed by a change of collective expert views. Some might claim that equipoise is disturbed if the majority of experts believe that emergency public health interventions are likely to be more beneficial than harmful. However, such beliefs are not always (...) justified: where high quality research has not been conducted, there is often considerable residual uncertainty about whether interventions offer net benefits. In this essay we argue that high-quality research, namely by means of well-designed randomized trials, is ethically obligatory before, during, and after implementing policies in public health emergencies (PHEs). We contend that this standard applies to both pharmaceutical and non-pharmaceutical interventions, and we elaborate an account of equipoise that captures key features of debates in the recent pandemic. We build our case by analyzing research strategies employed during the COVID-19 pandemic regarding drugs, vaccines, and non-pharmaceutical interventions; and by providing responses to possible objections. Finally, we propose a public health policy reform: whenever a policy implemented during a PHE is not grounded in high-quality evidence that expected benefits outweigh harms, there should be a planned approach to generate high-quality evidence, with review of emerging data at preset time points. These preset timepoints guarantee that policymakers pause to review emerging evidence and consider ceasing ineffective or even harmful policies, thereby improving transparency and accountability, as well as permitting the redirection of resources to more effective or beneficial interventions. (shrink)

The COVID-19 vaccine has been a miraculous, life-saving advance, offering staggering efficacy in adults, and was developed with astonishing speed. The time from sequencing the virus to authorizing the first COVID-19 vaccine was so brisk even the optimists appear close-minded. Yet, simultaneously, United States’ COVID-19 vaccination roll-out and related policies have contained missed opportunities, errors, run counter to evidence-based medicine, and revealed limitations in the judgment of public policymakers. Misplaced utilization, contradictory messaging, and poor deployment in those who would benefit (...) most—the elderly and high-risk—alongside unrealistic messaging, exaggeration, and coercion in those who benefit least—young, healthy Americans—is at the heart. It is important to consider the history of COVID-19 vaccines to identify where we succeeded and where we failed, and the effects that these errors may have more broadly on vaccination hesitancy and routine childhood immunization programs in the decades to come. (shrink)

The U.S. Food and Drug Administration's drug advisory committees provide expert assessments of the safety and efficacy of new therapies considered for approval. A committee hears from a variety of speakers, from six groups, including voting members of the committee, FDA staff members, employees of the pharmaceutical company seeking approval of a therapy, patient and consumer representatives, expert speakers invited by the company, and public participants. The committees convene at the request of the FDA when the risks and harms of (...) novel products are not immediately clear, and their final decisions carry significant weight, as most therapies that receive advisory committee approval are subsequently approved by the FDA. In recent years, across a series of diverse publications, the financial conflicts of interest of each category of participants in the meetings have been investigated. Here, we summarize these findings and their ethical implications, focusing on the FDA Oncologic Drugs Advisory Committee, and we suggest ways to move toward more transparent and impartial advisory committee meetings. (shrink)

We thank Leo Lam and Taylor Nichols for their response 1 to our paper ‘COVID-19 vaccine boosters for young adults: a risk–benefit assessment and ethical analysis of mandate policies at universities’. 2 In our paper, we demonstrate that the risk–benefit calculus to mandate boosters for young adults aged 18–29 is a net risk intervention. The authors assert that we have made three inappropriate comparisons of benefits versus risks of the mRNA vaccine booster dose in this age group. We provide our (...) response to each below. We erred on the side of overestimating benefits of the booster dose against severe COVID-19 in this age group and still found net harms to outweigh net benefits. The conclusion of our paper holds, and university booster mandates for young people were—and remain—unethical. COVID-19 hospitalisations prevented versus booster serious adverse events (SAEs) For the first comparison, we weighed predicted hospitalisations prevented... (shrink)

Many physicians are involved in relationships that create tension between a physician's duty to work in her patients’ best interest at all times and her financial arrangement with a third party, most often a pharmaceutical manufacturer, whose primary goal is maximizing sales or profit. Despite the prevalence of this threat, in the United States and globally, the most common reaction to conflicts of interest in medicine is timid acceptance. There are few calls for conflicts of interest to be banned, and, (...) to our knowledge, no one calls for conflicted practitioners to be reprimanded. Contrast our attitudes in medicine with public attitudes toward financial conflicts among government employees. When enforcement of rules against conflict of interest slackens in the public sector, news organizations investigate and publish their criticism. Yet even when doctors are quoted in the media promoting specific drugs, their personal financial ties to the drug maker are rarely mentioned. Policies for governmental employees are strict, condemnation is strong, and criminal statutes exist (allowing for corruption charges). Yet the evidence that conflict is problematic is, if anything, stronger in medicine than in the public sector. Policies against conflicts of interest in medicine should be at least as strong as those already existing in the public sector. (shrink)

Many physicians are involved in relationships that create tension between a physician's duty to work in her patients’ best interest at all times and her financial arrangement with a third party, most often a pharmaceutical manufacturer, whose primary goal is maximizing sales or profit. Despite the prevalence of this threat, in the United States and globally, the most common reaction to conflicts of interest in medicine is timid acceptance. There are few calls for conflicts of interest to be banned, and, (...) to our knowledge, no one calls for conflicted practitioners to be reprimanded. Contrast our attitudes in medicine with public attitudes toward financial conflicts among government employees. When enforcement of rules against conflict of interest slackens in the public sector, news organizations investigate and publish their criticism. Yet even when doctors are quoted in the media promoting specific drugs, their personal financial ties to the drug maker are rarely mentioned. Policies for governmental employees are strict, condemnation is strong, and criminal statutes exist. Yet the evidence that conflict is problematic is, if anything, stronger in medicine than in the public sector. Policies against conflicts of interest in medicine should be at least as strong as those already existing in the public sector. (shrink)