Vaccines in Canada

This is certainly a contentious topic. And there are certainly critics abounding everywhere.

For me, I think that when the dust settles that Canada's approach to vaccines will be seen as one of the best. And I have felt this for quite some time. I also think that this reality has very little to do with who is in charge and a lot more to do with circumstances. So, please, do not try to interpret this in any sort of political context.

One of the supposedly controversial things Canada did with it's vaccines was to prioritize 1st doses, pushing the 2nd dose off months outside of the manufacturers schedule. That being said, the most at risk populations did, by and large, get a much more timely 2nd shot. And this is where I think the good lies.

Before I dive in I'm going to sum up my points:

• The hard limit on 2nd doses is dictated by the number of first doses. (You cannot mathematically achieve more 2nd doses than you did 1st ones).
• A first dose, generally speaking, is more beneficial to the public at large.
• Both delay of first doses and acceleration of second doses seem to contribute to hesitancy.
• It is difficult to get the same degree of testing for randomized durations and mixed doses as it is for a single series over a fixed timeline.
• Science supports both delaying vaccines and mixing vaccines, but, for the above reason the hard evidence is not present yet.

So yeah, the first point is pretty obvious; if only 100 people get their first vaccine you cannot magically have 101 who have gotten their second vaccine. And with that out of the way, one can understand numerous reasons why it might be important to get 1st doses done with some degree of priority. It can help manage resources for second doses, inform planning and many other aspects of distribution. But, this alone doesn't make prioritizing first doses an overall smart idea. It just makes it an efficient one from a certain perspective.

The next point however adds some teeth. The mRNA vaccines in particular have a reasonably strong immune response after just 1 dose, with the key metric (reduction in hospitalization and deaths) being potentially as high as 70% and with the protection seemingly lasting for at least months. And while a second dose boosts that up to an incredible 95%+  the math is clear; every 1st dose is twice as effective in the general population as each second dose. If you're not already at an elevated risk of hospitalization or death then it actually makes a lot more sense to continue to prioritize 1st doses until demand dries up.

Which leads into the next point. The longer it takes to get a first dose the more likely restrictions are to be eased by the time your turn comes. This is because more people have had both 1st and 2nd doses and politicians aren't really doing a good job of handling things. And that means the more likely it is someone won't want to take the shot thinking that the pandemic is over and they don't need to be concerned. And, as mentioned before, a person who opts not to take their first shot, can never take their second shot.

A lot of these decisions have also lead to some hesitancy. Many complain that we are engaged in an active experiment. To which I would say "sure, it's called life". But, seriously... the problem here is really more a lack of understanding in the general population. We may never see the volume of evidence required to categorically prove the effectiveness of the strategies being used today.

But, that actually makes a lot of sense when you put it in context. Medical trials isolate for a large number of variables. They are doing a fixed number of doses of a single product over a fixed time period. And these tests use tens to hundreds of thousands of participants to bear out the results. And then the results are applied to millions or even billions of people. And, each person who participates in that trial, or follows that schedule cannot participate in another trial.

Thus, in addition to the sheer volume of people required. The pool available also goes down every day. And, we are introducing a much wider range of variables. We are mixing vaccines with different 1st and second doses and we are using many different intervals. The Pharmaceutical companies are not going to condone any of this. They could be sued if they do and the results are not good. And the sheer number of data points required to match the quality of testing done by the Pharmaceutical companies is an astronomical undertaking.

So, will we ever see high quality, peer reviewed data which supports the use of Pfizer for a first dose and Moderna for a second dose at an 8 week interval? Unlikely. As unlikely as any other combination. More than likely we will eventually see enough aggregate data to say something like "Any full course vaccination, mixed or not and administered within a timeframe of X-Y weeks provides a minimum Z% efficiency".

In short, we're a lot more likely to get enough data to draw larger conclusions by pooling data than we are to be able to effectively zero in on a specific strategy's effectiveness if it isn't one which was validated in a controlled clinical trial. 

However, I do feel that is where we will end up. The science does, more broadly, support the idea of mixing and matching and that alternate schedules will still be more beneficial than a single dose alone. And preliminary data is certainly backing this up. 

So, will a 16 week interval offer the same protection as a 3-4 week interval? I don't know. It should be better than a first dose alone. But, beyond that it could be more effective or less. What I don't think people recognize is that in these cases the companies aren't making these interval recommendations based on exhaustive testing to determine the best interval. They simply chose a value within a range which preliminary testing would have indicated had the best odds of success. They don't have the time or money (or desire) to test all possible intervals. Which means that it is actually quite likely that the optimal interval is something other than the manufacturer recommended one.

And mixing vaccines? Well, the science actually tends in favor here again. Multiple vaccines means introducing your immune system to more variations of the same spike protein or attenuated virus. And this should result in your immune system being more likely to identify the real thing as a threat and sooner as well as helping to amplify the immune response.

Once again though, Pfizer is not going to waste money testing whether using Moderna or AstraZeneca as either a 1st or second dose in conjunction with their own is effective. It makes no sense at all for them to do so. They want you to buy both. So, pretty much all of the clinical trial data will be from populations on a single series.

Though, the science (and preliminary evidence) would seem to indicate that this actually is quite a bit more effective when you factor in variants when compared a full series of a single vaccine.