Selection of Clinical Sites
Clinical trials commonly run behind schedule, with sub-optimal site selection being one of the main culprits. Sponsor companies often become too focused on “brand name” centers and investigators, and lose sight of what actually gets a study across the finish line. The best way to prevent this is through building a balanced portfolio of clinical trial sites based on qualities vital to your trial. This article outlines our recommended process for narrowing down and selecting sites.
Step 1: Define the Patient Population
Prepare a one-sentence version of the general patient population targeted by your study. Examples include “Patients undergoing catheter ablation of atrial fibrillation for the first time,” or “Patients hospitalized for heart failure at your institution within the past six months.” While this may seem like a trivial exercise given the detailed inclusion/exclusion criteria listed in your protocol, this simple phrase will serve multiple purposes throughout the duration of the trial. First, it will standardize comparisons of patient populations and procedure volumes during site selection. Second, this definition should be printed verbatim on your Screening Log, to give coordinators a clear understanding of exactly which screen-failed patients they should provide information on. As such, down the road it will help you hold sites accountable for screening the number of patients they committed to during site qualification.
Step 2: Objective List of Site Requirements
The next step in site selection is to create an objective list (for internal use) of the site attributes desirable for your study. This organizes abstract ideas about what a ‘good site’ looks like into concrete measurables, and includes greater depth than a site assessment questionnaire.
While sponsor companies commonly prioritize “who are the KOLs (key opinion leaders)” and “what are the highest volume institutions?” there are other worthwhile considerations: site resources, expertise, and historical trial participation. Here are some ideas to inspire your list of site requirements:
- Patient Population
- What is their monthly volume of the general patient population defined above? What is it after all the study-specific inclusion/exclusion criteria are applied?
- Are there other studies competing for the same patient population? A high volume institution with multiple competing studies may not be desirable.
- Research Infrastructure
- Does the site have dedicated study personnel, specifically full-time coordinators? How many hours per week will they be able to devote to supporting your study? Provide them with the expected number of hours site personnel will need to spend per screened/enrolled subject.
- How many other studies will the coordinators be balancing? Try to judge if they are spread too thin.
- Patient Management Style
- How and when is screening performed at their site? Does the Investigator or Coordinator typically introduce and review potential studies with patients?
- Will the design of your protocol fit into their patient management style? (Once you start gathering this data, it’s a great opportunity to reevaluate whether your protocol should be modified to fit real-world practice.)
- Expertise and Interest
- Is the Investigator genuinely interested in the investigational technology and willing to comply with the structure of the protocol?
- Would the Investigator be willing to collaborate with fellow Investigators for developing best practices, ways to overcome enrollment challenges, and recommendations for future device design iterations?
- Site Location
- Is site location reasonable for field clinical support, shipping logistics, etc?
- How far do most patients live from the site? If your trial requires multiple follow-up visits, driving distance for patients should be considered.
- Site Startup
- What is their average time to activation, historically?
- Which type of IRB is used for the site: local or central?
Step 3: Site Qualification Questionnaire
Create a site qualification questionnaire using relevant topics from your list of site requirements, noting that not all topics are suited for the questionnaire. Send it to potential sites to garner interest and compatibility. Always obtain extensive data about the patient population; specifically ask for concrete data (e.g., the number of patients over each of the past six months that met the general patient population and/or specific criteria) rather than estimates of how many subjects they think they’ll enroll. This is your best chance to set up the trial for success by determining which sites have the patient population and research-infrastructure to successfully execute your study.
Step 4: Site Assessment Visit
The in-person site assessment visit may be the most critical step in determining the truth of a site’s capabilities. As such, we recommend that someone very closely tied to the site’s performance during the study (such as the Study Manager or FCE) be the one(s) to conduct the visit. Dig deeper into unconvincing responses seen on the site qualification questionnaire, and also ascertain the items from your list of site requirements that weren’t well-suited for the questionnaire (such as genuine investigator interest). Address potential challenges and concerns around how your protocol will fit into the site’s standard of care practices, patient management style, enrollment plan, available resources, and facilities. This is your final chance to evaluate any remaining items on your list by observing site dynamics and having transparent dialogue on the site’s executability of and interest in the protocol.
Step 5: Selecting Diverse Sites
Now that the list of potential sites has been narrowed down, try to consider the remaining sites as a portfolio rather than individually. Diversification of clinical sites in accord with specific trial nuances is the key for a high-performing group. While the top teaching hospitals have many thought leaders and are active at conferences, they are often slower to enroll due to competing studies and slower to get activated due to institutional bureaucracy. Private practices tend toward quicker activation and higher enrollment, but are they equipped with the appropriate resources and expertise for your study? Ideally, the clinical sites selected will be a mixture of academic centers, private practices, and some government-funded centers. A wide geographical spread is recommended for multi-center Pivotal Studies, but proximity to the home office may be preferred for Feasibility Studies. Don’t forget to diversify across different strengths and weaknesses from your objective requirements list. Your end goal is a balanced portfolio of clinical sites encompassing a diversity of physicians, practices, and patients, to resemble where and how the technology will be utilized once commercially available.
We cannot stress enough how impactful site selection is on your study. This early stage of the process is your one chance to get it right. FCE Source can aid with the definition of your patient population, the development of your objective list of qualifications, the site qualification questionnaire, and assist with conducting site assessment visits and site selection. Tap into our twenty plus years of collective clinical trial experience. Reach us at firstname.lastname@example.org.