When it comes to planning and conducting Phase 1 clinical trials, every possible measure to prevent risks and deviations should be taken at the earliest stages.
Phase 1 trials set the groundwork for the entire clinical development process of new treatments, thus, it makes sense to prioritize identifying any possible risks associated with that new treatment in preparation for further stages of development. Phase 1 sites should be engaging in extensive Risk Mitigation exercises in order to identify these risks, as well as plan resolutions should those risks be unavoidable.
Risk Mitigation in Phase 1 Clinical Trials
Risk Mitigation can be broken down into many areas, and ultimately, includes anything that could be a possible risk or deviation during Phase 1 clinical trials. Here are some of the main areas where risks could be identified:
- Volunteer Recruitment and Retention
- Screening Period
Risks in the Protocol
The protocol should be the first place to look at to identify risks in Phase 1 clinical trials. Three areas in particular should be assessed and considered:
- Inclusion/Exclusion Criteria: The inclusion and exclusion criteria outlines what requirements the volunteer must meet in order to participate. When incorporating special patient populations, there may be comorbidities and potential risks associated with the disease state.
- Procedures: Are there risks associated with the procedures outlined in the protocol? Are they complex or potentially dangerous to the volunteer?
- Drug History: Does the drug have a profile that is potentially dangerous to the volunteer? Is it known to cause changes in blood pressure or other symptoms?
Risks in Volunteer Recruitment and Retention
Does the inclusion and exclusion criteria create a difficulty in recruiting the population? For example, when doing an ethnic sensitivity study, does the protocol require recruiting Asian populations with unusually high BMIs? Trying to recruit healthy elderly populations is also difficult. This could present a risk for enrollment and overall completion of your study.
Perhaps your study has two dosing periods with a short wash-out period in between—if there are adverse events (such as nausea or vomiting, very common AEs in Phase 1 clinical trials), will your volunteers want to participate in the second half of the study? Sites should have a plan to mitigate that risk and prepare contingencies as well.
Screening Period Risks
During the screening period, where physical exams are conducted and lab samples collected, there is a risk in that you may have patients with abnormal labs or positive drug screens. While these are unavoidable, how will this risk be accounted for in your recruitment plan?
Suppose the Phase 1 unit has 30 ECG machines available, but at the time that they are needed, only half of them are functioning properly—does the site have a way to resolve this issue in a fashion that won’t delay any of the other procedures or cause any timepoints to be missed?
What will be the experience level of the staff handling your study? Will you be receiving the Phase 1 unit’s A team or their B team or below due to conflicts with other studies being performed at the site? Even if you are being assigned the A team, perhaps one of those staff members has an emergency and cannot be available for study procedures, does the Phase 1 unit you are using have a plan to resolve that issue while still maintaining the same level of quality with a replacement? Are there difficult procedures involved with your study? If there are, the staff assigned to those procedures will have a significant impact on the level of risk associated with those procedures. If the site makes use of agency staff (such as a phlebotomist) that may not be used to research settings, or has to resort to on-call staff that are out-of-practice, that presents a greater risk to the success of your study and the safety of the volunteers.
While this is not a complete list of areas where risks could be identified in Phase 1 clinical trials, this list does provide a groundwork for more detailed consideration. When selecting Phase 1 sites for your upcoming clinical development programs, you should ensure that they are going through these considerations and proactively identifying potential risks for every study which they are assigned.