Hi, I’m back as Robin-Schoenthaler-the-Boston-cancer-doctor-who-writes-about-Covid.
(And it’s okay with me if you want to share.)
Today I’m going to talk about vaccines.
(And here are two things I’m not going to talk about: school re-openings, which are way too complex for me; and long-haulers, about whom we just don’t know enough yet. But we will, and I will.).
Massachusetts continues to have low positivity rates — now steadily under 1% — and all the other metrics remain good. Cases in the US are also going down as are deaths, except in a few midwestern states.
The Boston college scene has many Bostonians on edge (will they bring Covid in? Will they party?) Testing is going great guns.
–BC has had 37 positive tests out of 22K (last week was 10/15K)
–Northeastern has 28 positive individuals out of almost 53,800 tests (was 7/17K).
–BU has 75 positives and they did over 68,600 tests (was 39/28K)
–Harvard has 28/31,000
–MIT has 18/44K (I’m pretty sure of this. Their dashboard was very complex LOL).
— Brandeis has 6/16K, Tufts 19/20K
(These colleges all have public dashboards for the data-geeks amongst us.)
So let’s talk a bit about vaccines.
There are three Phase 3 vaccine trials going on in the US and over a dozen around the world. Phase 3 trials are the gold standard of clinical research —randomized clinical trials (RCTs) —and if they show the vaccine is effective and safe they are the last step before “approval” or licensing by the FDA. Effective and safe are the key words here.
All of these vaccines already went through Phase 1/2 trials where they showed their product appeared to be effective (people made antibodies) and safe (some fever, achy muscles, sore arms, but nothing catastrophic).
So once they had successful Phase 1/2 trials with small numbers of patients, they have proceeded to three big Phase 3 trials in the US, each aiming to get about 30,000 patients, aka 90,000 people we need to volunteer.
If you are a brave and wonderful participant — what I call our Valorous Volunteers — you go through a long screening process where, among other things, you are tested to be sure you don’t have Covid and never did. Then they separate you into groups by age, gender, ethnicity, chronic medical problems, all that.
Then they randomly pick half of you to get a shot containing a Covid vaccine. The other half gets a shot that is just salt water or some other kind of placebo.
Then a month later you get a second shot of whatever you got before. You don’t know if it’s real or salt water; neither do the shot-givers.
After that, the researchers test you for the next few months to see if you develop Covid antibodies — proof the vaccine can help teach your body how to fight off Covid (please note the declared goal isn’t necessarily to never get Covid or never spread it — it’s to be able to fight it).
Simultaneously the researchers carefully watch both vaccine and placebo people to see if they develop Covid symptoms and/or become Covid positive. They figure each trial needs about 150 cases of Covid to give an accurate idea of the vaccine’s effectiveness.
For this part, geography matters. If you are part of these trials in a place like Boston with its very low positive test rate (<1%), it could take months to get 150 cases of Covid. Whereas if you’re in a surge area, trial participants have a higher chance of being around people with Covid and the trial will move along faster. (So trials are being held all over the place.)
Participants are also being monitored for short term side effects. Did you get a sore arm, a fever, a trip to the ER? Did you get a worsening of a prior condition the day or the week of the shot? And, of course, safety also needs to be monitored in the long term — weeks and months out.
Once a certain number of people have gotten Covid (eg 150), the researchers will start comparisons. Did fewer people in the vaccine arm get Covid? Did they get milder cases? Did they more or less frequently end up in the hospital/ventilated/dying?
In addition the researchers will be checking on how different groups do. Did the vaccine work better in certain groups? Patients of color? People over 65? People with diabetes or heart disease or who have had cancer? (The one group they’re not studying right now is kids. Also not pregnant women yet, although that is to come.).
And what does this mean for November? Is there anything you can rush, any aspect you can speed up?
Some things yes, but some things absolutely no. There are some “Facts Are Facts Just The Facts, Ma’am” biological considerations for these trials:
The volunteers have to get two shots a month apart (29 days to be exact).
–It takes time to develop antibodies (several weeks).
–It will take time for our Valorous Volunteers to develop the number of Covid cases that can statistically show a difference between the vaccine and the placebo, eg 150) (weeks to months)
–It will take time to see the different severity in illness (weeks) and deaths (months).
And of course over the long-term:
–It will take time to get all 30,000 people in these trials so the trials are fully powered (months)
–It will take time to see if there is a difference in long-term side effects (a year)
These things are biologically immovable. We simply have to let a certain amount of time pass and have a certain number of patients enrolled before we can know for sure about whether any vaccine is effective or safe.
You just can’t outrun biology.
Let us look at the numbers in one trial. Of the 30,000 planned patients, so far only 6000 people have gotten both shots. That means 24,000 people have still only had one shot (or not yet been enrolled, even worse).
That trial is a long ways away from having enough people ready for evaluation (ie, had both shots), and here it is September. How could we possibly know if this is a safe or effective vaccine by November?
Some people have suggested looking at early numbers. There has been talk about doing an early statistical analysis in October — at 32 cases. If that happens and it’s even remotely positive, you will see headlines galore about that vaccine. And maybe you’ll even see pressure to approve that vaccine.
But we need to remember. That’s statistics. That’s headlines. But it’s not science.
Science is waiting. Science is finishing up what you started. Science is looking at the completed data with an unbiased eye.
Again, the only scientifically appropriate way to be sure of a vaccine is with:
— detailed analysis of antibodies and illness in a wide variety of patients to see if it’s effective
— both short AND long-term follow-up to see if it’s safe
If shortcuts are taken, science can sink. The only way we can honor all the work that’s gone into these vaccines, the deaths of so many loved ones, and the incredible contribution our Valorous Volunteers are making is to follow the rules and wait for the science.
Covid’s already shown us again and again and it’s doing it again now: you just can’t outrun biology. Not by wishing, not by headlines, not by decree.