Risky Business

In the 1950s, after two miscarriages, my late mother was prescribed a drug – DES – that was thought to help women carry pregnancies to term. Thereafter she gave birth to seven healthy children, of whom I was the fifth.

The medical community later determined that DES may not have helped the women who took it with their pregnancies and that it had sometimes horrific side effects on the women who had taken it and – just as horrifyingly – on their daughters (https://www.cancer.org/cancer/cancer-causes/medical-treatments/des-exposure.html). The FDA told doctors to stop prescribing it, and a campaign was begun to inform those who had taken it of the heightened risks to themselves and their daughters.

This was precisely the sort of experience that conditioned the FDA to adopt a policy of extreme caution with regard to drug approvals. As one whose mother and sisters were unknowingly exposed to terrible risks by an ineffective and dangerous drug, I can hardly disagree with the FDA’s risk-averse stance with regard to drug approvals. Indeed, as a general matter, I take comfort from it.

Even so, it strikes me as astonishing that the earliest possible date for legal distribution of a possible vaccine for the Coronavirus that has – maybe – already established itself as the first truly global pandemic is this December (https://www.foxnews.com/media/john-price-coronavirus-vaccine-greffex). HHS Secretary Azar has pronounced himself pleased with this expedited approval timeline (https://www.foxnews.com/media/alex-azar-coronavirus-vaccine-timeline). Count me as less than enthusiastic about it.

As we all know, there is much that we don’t know about the new Coronavirus. We don’t really know the mortality rate among those who have been exposed to it; we don’t know how long asymptomatic people can pass it along; we don’t know its long term effects on survivors; we don’t know why some people who seem to have recovered from it relapse and die. What we do know is that it’s often deadly, highly communicable and spreading quickly – and that containment efforts thus far have failed.  We also know that given how widely it has already spread and how many carriers are asymptomatic, it appears likely to continue to spread even in the face of heroic containment efforts.

It may be that the virus’s mortality rate will prove to be as, or nearly as, low as a normal flu because orders of magnitude more people may have the virus than we already know (thus increasing the denominator, with virus-related deaths as the numerator). Or the pessimistic view expressed by the WHO a few days ago that virus-caused deaths might amount to 3.4% of those who get it (vs. roughly .1% of flu victims) might be right. We just don’t know.

If the more pessimistic view proves to be correct and if the number of afflicted people continues to expand exponentially with the passage of weeks, the numbers of people at risk of death between now and final FDA approval of a new vaccine in December could be staggering.


Drug approval processes should be thought of as balancing risks. One risk is embodied in a known problem – acne, say, or carrying difficult pregnancies to term (two very different kinds of problems, to be sure); on the other side of the equation is the risk that a possible solution to the particular problem being addressed will just not work as anticipated or have devastating, unanticipated side effects, or both.

The FDA now has a well-established institutional habit of erring on the side of caution in approving new drugs – which is why we have had few repeats of the DES disaster. In recent years this structural conservatism on the part of the FDA has been challenged in certain cases by a “right to try” movement which advocates allowing terminally ill patients to try experimental drug therapies that have been through phase one FDA testing, but not the full regimen. After all, what do such patients have to lose? This movement has made political and legal progress, including garnering verbal support from President Trump.

Granting analogous, expedited approval rights (and presumably protection to producers of quickly-approved drugs against litigation in the event of failure) to a possible vaccine is quite different from the right to try movement, though, because doing so would cover the use of a possible vaccine by those who are not yet ill – and may never become so with or without a vaccine.  

Such a change might, however, be justifiable in some circumstances – e.g., for vaccines judged to be effective by the medical community after limited, phase-one trials where there is the risk of millions of deaths that could flow from an uncontained pandemic.

What’s worse, the possibility of unexpected side effects from taking a vaccine that is judged highly likely (but not certain) to be effective, or the probability that society will experience exponentially increasing deaths from a pandemic? The only possible answer to that question is: it depends on careful – though necessarily fraught with risk, because based on imperfect information – guesswork about the relative risks. Sometimes in the midst of battle, decisions need to be made in a fog.

Before I move on to making a recommendation, allow me to mention one more set of risks to allowing the drug approval process to play out along its customary, ultra-careful and time-consuming path: the economic – and thereby human – costs of the virus if it were to run unchecked for the next eight months could be gigantic. International trade is already being severely impacted; hotels, travel companies, restaurants, live entertainment venues, schools and places of worship are now emptying out. Think about all the people whose livelihoods depend on these communal aspects of our customary patterns. What will they do if they lose their jobs?


If I were President Trump, I would be asking Congress for the authorization to bypass existing FDA protocols to approve a Coronavirus vaccine on a super-expedited basis if, in the judgment of my medical advisers a) the vaccine to be approved in this manner looks highly likely to succeed in stopping the virus b) seriously adverse side effects are not expected and c) not approving such vaccines on an expedited basis would likely result in deaths far out of proportion with any adverse, unanticipated side effects of the uses of the vaccine.

With such a process, we might have an effective vaccine in one month instead of eight, and millions deaths might be prevented. It’s also possible, of course, that there would be severe unanticipated side effects from the vaccine, or even that the vaccine might prove ineffective, but even so, those might be risks worth taking given the magnitudes of the risks on the other side of the equation.

The decision on whether or not to take such risks shouldn’t be made on a de facto basis by protocols developed in a normal, risk averse environment, but based on judgments made by elected (and, we hope, well-informed) leaders based on the unique circumstances we find ourselves in.

We elect our leaders to make the rules – and sometimes, to change them. Sometimes they even have to make tough choices.

M.H. Johnston               

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