Suggested Changes in Phase One Clinical Trials
First, let's have a quick review of the structure of clinical trials in the United States. There are three phases (there are actually four defined phases, but the 4th is rarely done in the US) of all clinical trials that are described this way in a fact sheet from the NIH:
Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.
Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase III: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.
Additional Resource Information on clinical trials can be found at http://clinicaltrials.gov/info/resources
The guidelines were last reviewed in 1997, and ASCO has published a statement strongly supporting a revision of the Phase 1 rules. Per the explanation above, Phase 1 trials have traditionally been about safety; can this drug be given to a human being without horrible side effects? Later trials have been focused on the value of the new drug. The current argument is that so much progress has been made in molecular medicine that much of the guesswork has been eliminated from identifying people who are likely to benefit from a new treatment. That is, keeping in line with the movement of science towards individualizing treatments and developing targeted therapies, it is increasingly possible that people may benefit from a Phase 1 trial. If this is true, does it not make sense to eliminate some of the barriers and make it easier for patients to qualify and participate?
Here is the start of a summary from Medscape about the proposals. I give you an excerpt and then a link:
Forget 1997: ASCO Modernizes Phase 1 Trials Policy
Phase 1 clinical trials now offer a greater potential for clinical benefit than in the past because molecular medicine has taken a lot of the guesswork out of picking optimal participants, according to the American Society of Clinical Oncology (ASCO).
And for that reason — and others — ASCO has issued a policy statement about the trials, which are also referred to as "first-in-human" studies of new agents.
ASCO's first policy update in this area of oncology since 1997 was published online today in the Journal of Clinical Oncology.
The forces behind the new effort were summarized by ASCO President Peter Paul Yu, MD, from the Palo Alto Medical Foundation in California. "With new agents that target specific abnormalities in a patient's tumor, better tests to identify those abnormalities, and more sophisticated clinical trial designs, today's phase 1 trials in cancer offer patients a greater likelihood of benefit than ever before," he said in a statement.
An update is especially needed because "significant barriers discourage patient enrollment in research," according to an ASCO statement.
The policy has five broad recommendations aimed at modernizing the participation of the five major stakeholders in clinical trials.