The last three represent clinical trials of vaccines to fight the virus. That is, the potential vaccine must go through three types of trials, each of which is more comprehensive and comprehensive than the previous one. It is only after passing those tests that the vaccine can be put on the market for widespread use. With this unique virus, efforts are underway worldwide to find a vaccine, and others are now launching Phase 3 trials.
This means the vaccine will be available soon. Or. There is no doubt because it actually has to go through phase 3 attempts, and we have no idea what is going on. But we have no doubt, we do not have a vaccine yet. Oh, there are those who tell you differently. They may try to sell you a “cure” for the virus, which will give you a “100% recovery”. Until it goes to those tests, consider such “cures” as snake oil.
But put the snake oil aside. Anyway, what do those tests do?
Say you run a lab that has been working with the corona virus for weeks with fevers, peering under a microscope. You have made progress. You have identified its harm and put together a cocktail of chemicals to attack them. At least in your petri dishes and under your microscope, the cocktail can neutralize or destroy the virus. It’s time to try it on humans, you believe.
Thus Step 1. This is when you recruit some healthy volunteers – usually the first people to offer them a trial and cocktail that a few dozen people ask for. Why is it healthy? Think about it: the first priority with the new drug is to make sure it does not cause completely different problems in healthy people. This is especially important when the virus is causing so many infections that there is already unnecessary pressure on health care systems.
However, the questions you would like to answer in Step 1 are: Are there any side effects to the vaccine? If so, does the magnitude of the dose make a difference to the side effects? Is it safe? In fact, does it seem to be working?
Also, with any new drug, with minimal side effects, you will want to find the right dose for it. So the first few volunteers are given in very small doses and closely watched. If the side effects are minor, the next volunteer will receive an overdose. When causing acceptable side effects, this cycle is repeated until a working dose strength is found. The potential vaccine is called the “maximum tolerable dose”.
When stage 1 tests indicate that the new medicine is safe, it is time for stage 2. This time, you will call a large number of volunteers, probably a few hundred. Although not all of them are infected with the virus, there are many. As noted in step 1, they are treated with dosage doses up to the maximum tolerable dose.
Again, there are questions that need answers. How effective is medicine in preventing the virus from infecting healthy people and treating those who are already infected — that is, does medicine work as a preventive vaccine and cure? Is there an “optimal dose” that we can detect – does medicine affect the immune systems of volunteers and if so how? How do factors such as age and gender affect its effectiveness?
Usually in stage 2, a group of patients is given a placebo at once – i.e. it looks similar to treatment at trial, but has no value drug values and does nothing by treatment. The point here is to establish a standard, indication that the performance of a new drug against it can be measured. In the absence of such a “control” indication, how can you be sure that the medicine is working?
If you come to that decision, you will probably start the 3rd phase endeavors. By this time, you have a good idea of the final chemical composition of your cocktail and the appropriate dose to give to healthy and infected people.
So now, medicine is being given to many thousands of people – a Phase 3 trial of a potential corona vaccine in the US, for example, enrolling 30,000 adult volunteers. Typically, Phase 3 volunteers come from different countries and living conditions. It is also generally maintained in conditions and environments similar to the procedure used when fully approved. Again, some volunteers are treated with placebo, so they are a control group.
If your cocktail exceeds Step 3 attempts, you can apply for a license to approve and distribute it.
Now, this is a broad and essentially definitive outline of these trials. But perhaps you are wondering: what does it mean to conduct these trials, and what does it mean to “pass” a specific new vaccine? Well, other than giving doses and monitoring patients, these tests have a reason to interest me. Its taste here; I will leave a more detailed search for a future column.
One thing is, how do you determine if a medicine has side effects? Suppose there are 100 volunteers in your Phase 1 trial. Of those, two begin to limp after taking the drug. Is it noticeable? 60 What if you start limping? I mean, at what point do you decide that limping is the downside of this new drug?
Also, since you are choosing healthy volunteers for Phase 1, you are not collecting a bunch of random people. Automatically means that these tests may suffer from a well-known problem when analyzing numbers. Who selects volunteers, and how?
To make this clear, you deliberately, for your own reasons, choose volunteers who are already infected and recovering. Thus, volunteers who are now immune. How does this “choice bias” affect your trial?
Consider the administration and “control” of placeboss as a group of volunteers. Suppose a physician who is already convinced that the drug medicine works is conducting this investigation. Knowingly or not, he may try to help volunteers who appear sicker than others. They are in a group receiving real treatment rather than placebo. Apparently, this distorts the test results. So we need to make sure that volunteers or researchers do not know who to treat. Control.
Finally, how does a test pass these tests? If 50% of our Phase 3 volunteers recover from an infection, will it not pass? Should this be allowed to be promoted as a cure? 50% of users will it actually recover? The answers to such questions take into account concepts such as “sample size” and “confidence interval” for our results.
The phrases quoted in the last few paragraphs are mathematical – really, statistical – words. They give signals that phase tests are essentially math exercises. That is why confidence in the drugs we use increases. That’s why these efforts fascinate me so much.
Dilip D’Souza, once a computer scientist, now lives in Mumbai and writes for his dinners. His Twitter handle is DeathEndSfun