The press reports the results of clinical trials, but the reports rarely explain what is involved in conducting a clinical trial.  Clinical trials test drugs on human subjects to determine if they are safe for humans to take, and whether they are effective in slowing, preventing or reversing the course of a disease.  The trials also monitor the side effects of the drugs. The FDA will not approve a drug for sale without confirming the results of clinical trials.

 

THE THREE PHASES OF A DRUG TRIAL

Clinical trials go through three carefully constructed phases to determine safety and efficacy.

Phase One – The first phase of a drug trial is to establish whether a drug is safe for humans. The sponsor enlists a small number of healthy people who take the drug and are observed for side effects or other adverse outcomes.

Phase Two – If the drug passes Phase One, Phase Two determines efficacy and proper dosing levels. The subjects enrolled will have the medical condition that the drug is supposed to treat. Typically the number of subjects will be 2 to 3 times larger than the number involved in Phase One.  Subjects may be divided into groups that receive different doses of the drug to determine appropriate dosing ranges.  This phase continues to tracks adverse side effects and safety.

Phase Three –  If the drug passes Phase Two, the trial moves to Phase Three, which involves many more subjects, all of whom have the disease.  It is common to expand the trial to multiple sites, under the administration of different groups of physicians, to insure that the results are consistently replicated when conducted by different institutions in different geographic regions.

 

THE RANDOM DOUBLE BLIND PLACEBO TRIAL: THE “GOLD STANDARD”

Although not all Phase Three trials are structured in the same way, scientists and regulators have the most confidence in the results of Phase Three trials that divide the subjects randomly into two groups, one of whom receives the drug, the other receiving a placebo.  To eliminate bias in interpreting interim results, neither the researchers nor the subjects know which group is receiving the medication, hence the term “random double blind placebo.”

 

At the end of this trial, the sponsor and the FDA review the outcomes for hundreds of patients and assess whether the drug offers a treatment that is safe and effective, and if effective, the optimum dosing levels. The entire process involves hundreds of subjects and may take many years to complete. However, without this painstaking process, the public would not have confidence in pharmaceuticals. Understanding the process provides insight on why it takes so long for new drugs to come to market, and the disappointment of patients and drug manufacturers when a clinical trial fails.