Clinical trials and data for laypeople, Part 2

The foundation of science is this: that we can determine how adding or removing something changes a scenario by comparing it to what happens when we do not nothing.

Sunblock is a very simple example of this. In order to see what sunblock does, or does not do, we first keep track of what happens when a person doesn’t use sunblock, and then replicate that situation with the only change being that person now using sunblock. It is important to keep everything else the same: if the person we are testing normally drinks three cups of coffee before noon, wears make up, and doesn’t get enough sleep, we want that person to keep doing those things while we study what the sunblock does.

The reason we want this is because if lots of things change at once, how can we know that the sunblock causes any changes we see? For example, let’s say this person often has an upset stomach. If she suddenly stops drinking coffee when she starts using sunblock, and this improves her upset stomach, the data might indicate that wearing sunblock helps with upset stomach even though that’s not really the case.

Most people think that clinical trials do what I just described: that they compare the effect of a therapy to people who think they are getting the therapy but are actually getting the placebo. While this does sometimes happen, that is almost never the case for people with advanced life threatening diseases or rare diseases. This is a complex topic so I’m going to unpack this in a series of posts so that I can answer questions as they come up.

The first thing to understand is that there are phases of clinical trials. Understanding the phases will help you to know what the data means when the results are released.

For trials that are supervised by the American FDA, there are four phases. They are cleverly called Phase I, Phase II, Phase III, and Phase IV.

Phase I is the first and most preliminary. Phase I trials are safety and dosing trials. I have never seen a phase I trial with more than fifty people. Most of the ones I see involve 10-20 people. This is the first real contact a new treatment (drug or biologic) has with patients that the therapy is intended to treat. It is literally to see how the human body reacts when it is given any amount of this substance.

Phase I trials are to see what adverse events present with this therapy. Adverse events are basically side effects and complications. They are the risks you accept when using the therapy. Some are serious, and some are not.

Dosing trials are just what they sound like: they give different people different doses in order to figure out the lowest effective dose. This is because we want to give as little of this substance as possible because this usually gives the lowest risk for complications. So we will split our phase I group into smaller groups called cohorts. Cohort is just the science term for a group of patients that have things in common that we are studying.

For example, let’s say we have a phase I study for Klimasonium, a drug that is taken once daily and cures mast cell disease. (I super wish for Klimasonium.) Let’s say I gather up 30 patients with MCAS for Klimasonium. (Please do not think this is real thing.) In order to determine what doses we should use to treat patients, I would break up my 30 patients into 3 groups, also called cohorts. Cohort 1 would take one tablet a day. Cohort 2 would take two tablets a day. Cohort 3 would take three tablets a day.

At the end of the trial, I would look at what side effects and complications patients had, and if their disease got worse or better, and in what ways. Based upon this information, I will pick a dose that helps the disease while causing the fewest complications. I will also have to report any and all side effects or complications to the FDA so that the risks of this therapy are recorded and patients who take this drug at any time will be made aware.