As I have mentioned the FDA and its UK counterpart in several posts, as overseers of new drug applications and approvals, I wanted to share a couple of highlights from today's talk.
This is not all new information (I have talked about the different phases before, for example) but it may be a more detailed explanation or in one case, a correction of past postings.
I will start with the correction. I thought in order to have a new drug approved, the new drug had to treat a condition that was not being treated at all, or treat a condition better than an existing drug, OR treat the condition similarly but with less side effects or less inconvenience. That is NOT true - in the USA. I do think that Europe has a different rule. Dr. Grimes did say that one deterrent for not creating a new drug just to add it to the market is because doctor's don't like to switch patients to new drugs for no reason.
What IS true is that the new drug has to show a benefit. The benefit has to be measurable. This measurement has to be identified in the protocol. The drug company has to say how the effect will be measured and what outcome from the drug is considered success. For example, a new drug will lower cholesterol by at least 3 mg/dL which will be determined by a blood test. Or a drug will reduce depression as measured by the average score a person gets on a test that measures feelings.
The research has to include a risk to benefit analysis and proof that it is safe and effective.
We have talked about phase 1-3 trials before - but I think I left out a stage. Actually I referred to Phase 1 as the non human participant part, but the stage that does not include human subjects is called the Pre Clinical phase.
In the pre clinical stage, the drug is created and tested in the lab with test tubes, petree dishes and animals.
Clinical trials are the ones that include people.
Phase 1 includes healthy volunteers who do not have the condition that the drug is supposed to treat. The scientists just want to know how the drug works in the body and what happens when different doses are tried.
Phase 2 is the main efficacy stage - does it work? Risk is also assessed in this stage, but efficacy is the main concern. The drug is tested in people who have the condition.
Phase 3 is the large full scale trial that is specifically intended to capture the risk profile. As Dr. Grimes said - chemicals always DO something - the drug does things we want it to do and things that we do not want.
Before a drug can be approved, the scientists also have to prove adequate exposure. There have had to have been enough people in the various phases to assess the effect and risk. There is a standard.
- At least 100 people have had to been on the drug for at least a year,
- between 300 and 600 have had to been on it for 6 months, and
- 1500 people have had to have had at least one dose.
The process of testing - pre clinical, phase 1-3 and FDA assessment can take 12-16 years and cost a billion dollars.
"biocreep" - the term for when less effective drugs get approved - some fault of the system when a drug does not have to be compared to a placebo.
Types of Studies:
A superiority study attempts to prove that the new (investigative) drug is better at treating a condition than a placebo.
A non inferiority study is intended to show that the investigative drug is at least as good as an existing drug (for that condition).