Variable Fragment

Clinical trials are the statistical testing of new drug molecules in human patients to determine safety and effectiveness. You frequently hear about drugs having “promising results after Phase II clinical trials” and you may not know exactly what that means.

First, to be clear, a great deal of development effort goes into a candidate molecule before it ever enters a person. There will have been extensive lab tests, tests in animal models (an animal, such as a rat, which has a condition that mimics the human disease of interest) as well as toxicity tests in animals. In general, perhaps 1 in 1000 molecules makes it all the way to phase 1 trials. In biotech, the ratio is probably higher, but that should give you an idea. And once you enter into clinical trials, the majority (perhaps the great majority) of candidate drugs fail at each phase.

A quick summary is:

1. Phase I – is it safe?
2. Phase II – does it work?
3. Phase III – fully, statistically define the drug

The trials themselves are statistically designs, very careful experiments to determine the effect and safety of new drugs. They can last 8 years and cost many millions of dollars to perform. And most drug candidates fail to pass the test criteria.

Phase I
This is the first time the drug will have been administered to a human. The goal of Phase 1 testing is to test for safety in a small group of healthy people before you ever give it to a sick person. You might give 50 volunteers doses of the drug and monitor their response to it (how rapidly it’s metabolized, cleared from the body etc).

in the case of serious, life threatening diseases sometimes sick people are used in phase 1 trials. In this case it is deemed more ethical to try the drug on volunteers who have no other treatment choice available, rather than to withhold the treatment from them. In non-life-threatening situations it is probably more ethical to avoid adding risk to these patients by giving them unproven drugs.

Phase II
This is the first trial designed to look at the effectiveness of a new drug. You might administer the drug to a couple hundred sick patients and monitor their health and response. Of course the safety component is still monitored throughout phase 2 and 3.

Phase III
This is a large study of perhaps 2000 people which is intended to be your final stack of data proving to yourself and to the world regulatory bodies that your drug is safe, and that it does what you say it does.

As a side note, sometimes phases II and III can be extended if a significant benefit is being seen, so that patients can continue to receive the drug until it is approved for sale.

Each of those phases can last 1-2 years. Development of the phase 3 process and technology and production of phase 3 material must take during the phase 2 trials, so if the phase 2 trial fails, all of that development effort is wasted. The total timeline can take 6-8 years from the time a drug enters clinical trials until it is approved for sale.

Clearly clinical trials are a very expensive and time consuming part of the drug development process, but it’s something that is critical to get right. An incorrectly designed trial can allow a harmful drug onto the market. The FDA does “fast-track” some drugs which are especially urgently needed, and allowances are made for patients to remain on trial drugs when they respond to treatment. But an understanding of clinical trials is important to understanding the economics of the drug industry.

If you are in the position of considering participating in a clinical trial, I encourage you to read this article by the American Cancer Society explaining in more detail the issues you may need to consider. This article also goes into greater depth than my summary above, so if you’d like to read further this may be a good starting point.