Phase 1 clinical trials with healthy volunteers are typically conducted in order to determine safety and tolerable doses and performed with anywhere between 20-100 patients.
When it comes to selecting clinical Phase 1 units for large normal healthy volunteer studies, Sponsors and CROs usually make their selections by determining whether or not a site fulfills a set of standard criteria, which will ultimately determine if the site is equipped to conduct the study at all.
Clinical Phase 1 Units Standard Selection Criteria:
1. Experience of the Principal Investigator and Nursing Staff: The Principal Investigator and the Nursing Staff will ultimately be responsible for ensuring the success of your study and the safety of volunteers, so you’ll want to ensure that these key staff clinical Phase 1 units are well trained and highly experienced not only in practicing medicine, but in overseeing clinical trials. Furthermore, are the PIs therapeutically aligned with the investigational product being tested? Even though most Phase 1 studies aren’t conducted in patients, a PI that understands how the treatment is likely to interact with the body is an important factor in ensuring patient safety and being able to predict any potential risks that may occur with it.
2. Bed Space: Perhaps the site checked off every other item on the list, but it has a limited bed space, causing your study to need to be prolonged in order to assess all of the necessary volunteers. Additionally, it would be naïve to assume that the site will be able to dedicate its entire facility to your study alone. So, even if the site has enough bed space to cover a significant amount of volunteers, will it still be enough in order to complete your study within your desired timelines, as the unit will likely be housing other studies concurrently?
3. Access to the patient population: Even though Phase 1 studies are conducted in healthy volunteers, exact protocol requirements can vary. You’ll want to make sure that the site can adequately fill the study with its database and identify subjects which satisfy the boundaries set by the protocol’s Inclusion and Exclusion criteria.
4. Access to the necessary equipment: If your study requires some more complex procedures, does the Phase 1 unit have the equipment necessary to perform that procedure? Furthermore, does the site have staff that are adequately trained in operating and maintaining this equipment? Does the site have the equipment as a standard, or will it need to use a vendor to rent or lease the equipment? All of these factors can significantly impact the success and cost of your Phase 1 trial.
5. Experience in similar studies: Does the site and its staff have an understanding of the type of treatment being evaluated and the procedures necessary to conduct the study? If the site doesn’t have experience in similar types of studies, the site may require more training which will require more time. Additionally, if the Phase 1 unit doesn’t have experience, there is a heightened chance of safety risks due to an unfamiliarity with the study drug and procedures necessary to conduct the study.
6. Geographic location: Is the site located in an area that will easily be able to recruit the volunteers? If the area is not densely populated, it may be difficult to enroll enough patients for your study, especially if it is a large one.
7. Enrollment capability: Especially for larger studies, whether or not the site can enroll volunteers within the necessary timelines is of the utmost importance. Furthermore, does the site have a concrete plan for retention? Multiple follow-up visits are common for phase 1 clinical trials, so the site must be able to keep these volunteers all the way through study completion, in order to produce the best results possible. How is the site going about enrollment? Does the site have a database of active, qualified volunteers? Does it have the staff necessary to handle high volume enrollment, screening, and retention efforts? These questions must be asked early on, for without an adequate amount of volunteers, studies can easily fail or undergo significant delays.
8. Regulatory history: Has the site received any 483s from an FDA audit? Nearly every Phase 1 unit has received a 483 at some point, but the reality is that the repercussions of 483s can vary greatly depending on the severity of the issue. Sometimes, the issue can be fairly benign, and the truly important factors are how the site responded to the 483. Was the issue resolved? Did the site learn from it and improve their operations or procedures? Or was it received for something very detrimental that the site wasn’t able to improve upon? While ultimately, you don’t want your sites to have ever received a 483, realistically, a site with no 483s issued may indicate a site that isn’t very experienced in conducting Phase 1 studies at all.
9. Contract/Budget negotiation structure: Is the site taking into account the volume of patients for large studies and identifying where costs can be reduced due to efficiencies and eliminating redundancies? Or is the site simply charging a per-patient fee regardless of procedures or staff necessary? Does the site offer discounts for multiple studies contracted or for using the same study teams for subsequent programs, decreasing costs overall? These are important questions to ask your site as they should be willing to evaluate their pricing and look for ways in which to provide more value to their Sponsors.
10. Cost: Last, but certainly not least, what is the cost of running the study at that site? At the end of the day, the cost of Phase 1 clinical trials will be a huge factor in determining where to conduct the study. The cost will be determined by a number of factors, including size of the study, location of the site, as well as whether or not the site had done a detailed analysis of their internal costs and staffing practices. Typically, this is not something that is done by standalone clinical Phase 1 units; the result is that oftentimes the site may be submitting a budget in the wrong (usually higher) amount to the Sponsor or CRO. We’ll discuss this in more detail in a future article.
If clinical Phase 1 units can fulfill these criteria, then it is likely they will be selected to conduct the Phase 1 study at their site. However, there are factors to consider beyond these above listed qualities which Sponsors and CROs should be paying close attention to, in order to ensure they are receiving the most value from their current and potential Phase 1 units.