Phase 1 clinical trials begin the process of moving a potential medication from the laboratory to the patient. Unlike the later types of studies, the focus of Phase 1 investigations is to clarify the appropriate dose of the agent, define a preliminary toxicity profile, and describe its pharmacokinetics.
“Phase 1 studies are the first link between the laboratory and the patient,” says Jill Buyon, MD, professor of medicine at New York University School of Medicine and founder of the systemic lupus erythematosus (SLE) clinic at the Hospital for Joint Diseases in New York City. “It is the ultimate transition of discovery to the patient.”
Initial phase trials can be broken into subgroups. One type uses healthy volunteers, the other stable patients with the specific disease under study. Many of the early trials currently underway in the area of rheumatology focus on SLE.
“Research in SLE is exploding and there are several promising agents moving through the pipeline that will need to be tested,” says Cynthia Aranow, MD, associate investigator at the Feinstein Institute for Medical Research in Manhassett, N.Y. “Making sure these trials are completed and done well is really important.”
Participants Not Always Clear on Efficacy Considerations
In addition to the ethical considerations inherent in any clinical trial (see “Are You Informed About Consent?” p. 1, May 2008), Phase 1 trials add concerns about how well the potential participant understands the reasons for undertaking these kinds of studies—to look at safety rather than efficacy.
“Although Phase 1 studies are mostly designed to look at initial uses and safety issues, a majority of patients think they are in a therapeutic trial and are going to benefit,” says Eric Matteson, MD, professor of medicine and chair of the division of rheumatology at the Mayo Clinic in Rochester, Minn. “Special care needs to be taken by the doctors and others charged with obtaining informed consent to make sure the participants know this difference.”
Although the new agent under investigation in these early trials may have extensive data on toxicity in animal models, it is not always clear how these translate to humans. Thus, it is hard to describe during the informed consent process exactly what the concerns are going to be.
“One of the risks that needs to be stressed to a potential subject is that we just don’t know what all the risks are going to be,” says Dr. Aranow. “Although inherent in all studies, unknown risks are a huge part of the Phase 1 trials. There is more uncertainty [in Phase 1 trials] for the investigator who is asking patients to put themselves at risk.”
Investigator Should Know the Molecule’s History
To help the participant understand what may happen, it is the duty of the investigator to know the history of the molecule up to that point. The experts interviewed here suggest asking many questions of the basic science experts at the pharmaceutical company. One of the first questions to ask is why the company picked this potential medication out of the entire pipeline for the very expensive clinical trials phase. Why was this one so special?
