Vaccine Week: Will it be good enough?

Will any vaccine be good enough to solve The Pandemic Information Gap?

Welcome to Plugging the Gap (my email newsletter about Covid-19 and its economics). In case you don’t know me, I’m an economist and professor at the University of Toronto. I have written lots of books including, most recently, on Covid-19. You can follow me on twitter (@joshgans) or subscribe to this email newsletter here.

This week I am looking at whether, even under the most favourable of circumstances (a safe and effective vaccine appearing by early 2021), a vaccine will be the ‘silver bullet’ to end the virus at that point. The other day, I argued that because of supply chain issues (it takes time to produce doses) and distribution issues (it takes time to work out who gets earlier doses), that there will be a long process by which the vaccine is given to enough of the population to have an impact on the course of the pandemic. Today, I am going to look at how effective a vaccine needs to be in order to generate its desired prize — a return to normality. The answer is much more effective than the levels that will satisfy regulators.

There are two ways to think about vaccines. First, if I take a vaccine, then it protects me from the virus. Second, if I take a vaccine, then it protects others from getting the virus. The problem, however, is that a vaccine may only be partially effective in protecting me, it may only be partially effective in protecting others and how effective it is at one or the other may not be related.

The way I want to examine this in terms of the pandemic information gap. Recall that gap arises primarily because we do not know who is infectious and, as a result, we do not have the information required for a decision to isolate individuals and individuals do not have information as to how safe it is for them to interact with others. In its ideal state, a vaccine can resolve this problem. If I have a perfect vaccine, then I know I cannot get it from others and so can go about my business. If I know that you are vaccinated, under perfect circumstances, I know that you are safe to interact with. It is this latter effect that gives rise to the idea of immunity passports. You get the vaccine or are otherwise certified as immune and you can produce the passport to be allowed to interact with others regardless of whether they are immune or not. If you can’t produce that passport, then you are only allowed to interact with those who do have it.

In other words, by turning uncertainty into certainty, a vaccine can solve the pandemic information gap and normality. But what happens if it goes only part of the way there?

Imperfect immunity

The FDA has said that they will approve a vaccine for use if it is only 50% effective. Others have said that they will be very pleased if a vaccine is available that is 70% effective. For people who require tests to match levels of performance above 90%, this seems surprising. But it is born of experience.

Some vaccines have great efficacy; that is, the reduction in the chance of contracting the disease in question. Measles vaccines prevent the disease in 95% of those who take the vaccine. For the flu, it varies between 60% in a good year to less than 20% in a bad year. So when the FDA says it wants 50% efficacy, that means that your probability of being protected from Covid-19 will be half what it is if you didn’t have the vaccine. Of course, that is in the lab. In the wild, this effectiveness tends to be even less.

What does an imperfect vaccine do to the pandemic? A study published in July in the American Journal of Preventative Medicine did the maths using a standard epidemiological model.

[W]hen vaccination prevents infection and occurs after 5% of the population has already been exposed, the peak can only be reduced by, at the most, 86% when R0 is 2.5. Vaccine efficacy has to be at least 60% to reduce the peak by 85% when coverage is 100%. This vaccine efficacy threshold increases to 80% when coverage drops to 75% (86% reduction) and 100% when coverage drops to 60% (85% reduction). However, while reducing the peak, the number of cases averted continues to increase, not reaching the maximum until both vaccine efficacy and coverage are 100%.

If a vaccine is 50% effective, then we may not wipe out the virus even if everyone is vaccinated. With lower coverage, a vaccine has to be more effective to do its job. To be sure, the scale of the reductions even with a less effective vaccine are great and worthwhile. The problem is that the virus remains with us.

Those scenarios, of course, are based on the raw aggregate assumptions using models that don’t take into account people’s behaviour. The hope of the vaccine is the hope it will give us the confidence to go about our previously normal activities.

Here is the question to ask yourself: if you take a vaccine that is only 50% effective, what changes will this make to your life?

If you are like me, you are trying to avoid ever getting Covid-19. As I noted in an earlier post, at the moment, in Toronto, my chance of catching Covid-19 on any given day is about 0.002%. If I am vaccinated, that drops to 0.001%. But my ability to manage risks by changing my behaviour at such low probabilities is limited. My confidence to say, go to a movie theatre, restaurant or travel somewhere where the virus is more prevalent does not change appreciably. The best I can say is that I will likely move my behaviour back to normal more quickly as the virus abates.

If you are one of those people who is socially distancing only because of legal restrictions, then it is likely that being vaccinated and being able to avoid those restrictions will cause larger changes in behaviour. With 50% efficacy, this means that the less risk-averse members of the population will get out and about. This suggests that we might see a spike in infections as that happens but hopefully, it won’t last long.

Either way, even as it is distributed, a vaccine is more likely to be disruptive initially and will take some time to work itself through to eliminating the virus. From the perspective of the economy, there is no magic bullet here. Instead, the end may well be in sight but we will have to be patient.

Imperfect protection

On that note of slight optimism, there is a problem. The above calculations assume that taking a vaccine will protect you and will protect others from you. For some vaccines, such as that for polio, that is a reasonable assumption. Someone who is immune from the disease is also unable to carry and transmit the disease. For other vaccines, that isn’t the case. That is going to matter for our calculations.

Let’s look at why there is a discord between immunity and potential infectiousness. From two infectious disease specialists:

Doctors usually explain vaccines to patients and the parents of young children by describing how those protect us from a particular disease: An attenuated form of a pathogen, or just a bit of it, is inoculated into the human body in order to trigger its immune response; having learned to fight off that pathogen once, the body will remember how to fend off the disease should it be exposed to the same pathogen later.

A vaccine’s ability to forestall a disease is also how vaccine developers typically design — and how regulators typically evaluate — Phase 3 clinical trials for vaccine candidates.

Yet the best vaccines also serve another, critical, function: They block a pathogen’s transmission from one person to another. And this result, often called an “indirect” effect of vaccination, is no less important than the direct effect of preventing the disease caused by that pathogen. In fact, during a pandemic, it probably is even more important.

That’s what we should be focusing on right now. And yet we are not.

Thus, we are developing vaccines to protect people from the virus but not from each other.

This changes the risk and epidemiological properties of a vaccine. If a vaccine prevents you from being able to transmit the virus, this has a big effect on transmission rates. If you take our 50% effective vaccine discussed above, while your protection is at 50%, if the vaccine also prevents being a source of transmission, this actually reduces your probability of getting the virus by more than that. To get the virus, you have to encounter someone infectious and you have to be unprotected. Thus, if you encounter another person, you chance of having them transmit the virus is 0.5 times 0.5 or 25% of the probability you faced prior to everyone being vaccinated. This is actually something we get from the HPV vaccine.

The Haemophilus influenzae type B (Hib) conjugate vaccines were designed, and licensed in the early 1990s, to prevent young children from developing serious infections such as meningitis. Soon enough an unexpected and welcome side benefit became clear: The vaccine interrupted the bacterium’s transmission; after its introduction, occurrences of the disease dropped also in groups that had not been vaccinated.

The human papillomavirus (HPV) vaccines were developed to prevent cervical cancer and genital warts in women. They have proved immensely effective among the women to whom they are administered — and up to 50 percent effective at preventing genital warts among unvaccinated men, according to a 2017 study of the health insurance records for 2005-10 of some nine million people in Germany.

However, if the vaccine is only 50% effective in protecting you, then it is only halving the probability of transmission. That makes a big difference in the reproduction rate of a virus following vaccination and on the personal risk calculations discussed above.

Why is there this discord?

To understand why this is the case, remember what it takes for you to become ill from a pathogen, be it a virus or a bacterium.

First, you are exposed to it. Then it infects you. While you are infected, you may infect others. In some cases, the infection develops into a disease. In other cases, it doesn’t: Though infected, you remain asymptomatic.

One way that vaccines can interrupt a pathogen’s transmission cycle is by preventing the pathogen from causing an infection in the first place. This is how many common vaccines — against measlesmumpsrubella and chickenpox — operate.

Other vaccines — like the ones against meningococcal meningitis or pneumonia brought on by the pneumococcus bacterium — can block the transmission of the pathogen by interfering with the infection or by decreasing either the quantity of pathogen that the infected patient sheds or the duration of the shedding period.

Some recipients of the pneumococcal pneumonia vaccine simply don’t get infected with the bacterium; others do get infected and carry the bacterium in their nose, but in smaller amounts and for shorter periods of time than if they had not been vaccinated.

Currently, producing a vaccine with these better properties is not a priority. It is not an FDA requirement and the candidates in trials aren’t really focussing on even measuring it.

But with imperfect vaccines, it will matter.

Conversely, a vaccine that, let’s say, offers older adults only modest protection against developing a disease might nonetheless be very effective, when administered to healthy adults or children, at curbing a pathogen’s transmission in a population overall.

This is the case with the pneumococcal conjugate vaccine. A 2015 study published in the New England Journal of Medicine found that the vaccine reduced the occurrence of pneumonia in inoculated adults age 65 or older by only about 45 percent. Yet, according to a study last year by researchers at the Centers for Disease Control and Prevention and Stanford University, the immunization of infants and toddlers reduced ninefold the incidence of pneumococcal disease in the elderly.

The point of all of this is not to discredit the good work being done to give us a vaccine. Instead, it is to caution us on what news of ‘success’ might mean. What it does not mean is a return to normal. What the vaccine becomes is just another tool in our kit on how to reduce transmission rates and protect people from Covid-19. We should view it like that and, indeed, not make presumptions that we might end the economic and health damage from the virus in any clear way.

In terms of our policy judgments, this surely means that relying on a vaccine to achieve large outcomes is a mistake. We should, instead, develop a plan that could eliminate the virus sans vaccine.

What did I miss?