Question: how many trials do you have to do on the drugs before you are sure they are successful?

David Foley answered on 19 Nov 2014:

Hi Louisa.

Clinical trials in humans are conducted in 3 stages.

The first, Phase 1, usually takes 10 healthy male volunteers (for ethical reasons don’t perform trials on children, the elderly or women of child bearing age). Each subject recieves incrementally bigger doses, starting at about 1,000 times less concentrated then the highest tolerated does in animals (scaling for weight differences). The dose is increased until side-effects become apparent – this becomes the MTD (maximum tolerated dose). This trial only determines if the drug is crudely “safe”. You also hope that the MTD gives sufficent exposure of the drug to be effective based on your in vitro and animal studies.

Phase 2 is the first time the compound is tested in patients against the disease. It usually numbers around 500-1000 patients. Here the dose is defined by the trail, as are the endpoints for success. The trial is usually conducted “double blind” meaning neither patients nor the doctors know which subjects are getting the drug and which the placebo. This eliminates bias on behlaf of both the patient and the doctor. This trial determines if your drug actually works and most drugs fail here – about 80%.

The final trial, Phase 3, involves up to 10,000 patients. It usually compares your drug to the current standard of care. A drug has to be better than what we have already if it is to be allowed onto the market. This trial begins to detect rare side-effects associated with the compound. About 50% of Phase 3 trials fail, at a cost of some 1 billion dollars.