Next would be to understand the proposed mechanism of action. More importantly, does the mechanism make sense from a pharmacokinetic and biological standpoint? “I am also interested in knowing if the sponsor is interested in the mechanistic impacts of the molecule in addition to just safety parameters,” says Dr. Aranow. “We are exposing people to a new agent. To not learn as much as possible while exposing them to risk would be a crime.”
Finally, discuss what the animal studies have shown to be toxicity concerns. Also, ask about what has been discovered about the toxicity profiles of similar molecules. “To me it is a belief in the mechanism and belief that the company will continue to move the molecule forward if the safety looks good,” says Dr. Buyon. “It is a partnership between the investigator, the sponsor, and the participant.”
What happens after the study is over is an ethical concern that should be discussed at length with a participant. Although Phase 1 trials are not specifically focused on efficacy, the potential for efficacy remains, or the molecule would not a viable candidate for study. So, what happens if there is a therapeutic benefit to an individual? It is not always possible from a protocol perspective to include those participating in the Phase 1 trial in later-stage trials. Thus, another part of the informed consent is to make sure that subjects know they may not have access to the drug unless it reaches the market as much as a decade later.
“These are mainly short-term trials lasting six to 12 weeks at the most,” says Christine Barr, RN, CCRC, clinical research coordinator at the Center for Rheumatology in Albany, N.Y. “In reality, many with chronic illnesses get into these studies to find some relief. What comes after is an important consideration that should be addressed early in the process.”
Family and Patient Concerns Sometimes Conflict
Taking into consideration the personal concerns of the patient’s family with the needs of the study is an especially tricky balancing act. What should happen when the potential participant is eager, but a spouse or adult child is hesitant?
“When this occurs, I speak to the family members and ask what their concerns are,” says Dr. Aranow. “Much of the time, it will be that there was something the family member misunderstood and the objections go away with the misunderstanding. Sometimes the family just doesn’t want the study participant to take part in any kind of research, period.”
