Selecting Study-Appropriate Clinical Sites in 3 Steps
In the industry we often hear staggering statistics about the number of trials that are delayed or fail to meet their goals. For example, you may have heard 45% of clinical trials are completed late, 70% of trials experience study start-up delays1, and approximately 80% of trials fail to meet their initial target enrollment on time2. Part of a major risk mitigation strategy to avoid some of these challenges is selecting clinical sites that fit the unique needs of the study – because when it comes to clinical research one size does not fit all. Selecting sites that match the specificities of the protocol and the sponsor’s regulatory goals and strategies, has a direct impact on the quality of data collected, study timelines, and overall project finances.
Surveys show sponsors tend to reuse the same clinical sites for their studies: in general, only 30% of sites in any given multi-center trial were previously used by the sponsor company3. While there are operational and strategic advantages that come with reusing sites, such as start-up time savings due to existing contract templates, study team structure, and relationship with the site, reusing a site does not necessarily predict performance on a different trial. For these reasons, a thorough process that incorporates the following three steps should systematically take place to ensure an objective analysis, and therefore optimal site selection.
Step 1: Define Site Requirements and Selection Criteria
One of the most cited inefficiencies in the industry regarding site selection is the lack of information about the protocol when starting the process.3
The first step to selecting appropriate sites for a study is to identify key site criteria from the study design as this data provides the fundamentals that will guide site selection. Important points to define before the site identification and selection can start include participant population profile, staffing and facilities requirements, enrollment targets and period, study duration, desired geographical area (if applicable), and target start up timelines.
Clearly defining evaluation criteria before the process starts will not only help identify sites that are suitable for the study, but also supports an objective comparison between eligible sites to select the best ones for a specific trial. The most important assessment points to incorporate in the evaluation plan to support the ultimate selection decision include:
- Staff Qualifications: staff availability, specialty, credentials, experience in clinical research and the studied indication, including their performance as it relates to regulatory compliance.
- Facilities and Equipment: adequate facility space, drug/device storage space and security, types of source documents, and equipment needed for the study.
- Site Profile and Timelines: site types (e.g., hospitals or clinics, academic centers, Veteran Affairs facilities, non-profit, government, and private sites), site’s Institutional Review Board (IRB) meeting timeframe, and typical contract negotiation timeline.
- Population Profile and Access: eligible participants’ availability and proximity, disease/condition incidence, ongoing trials recruiting similar patients, and recruitment capabilities including resources for conducting outreach.
- Past Performance: clinical trial experience including in trials with similar enrollment timelines, enrollment target, and complexity, and past enrollment rates.
- Competition: concurrent trials in the same indication or targeting the same population profile that are ongoing or scheduled to start during study conduct.
This initial step should involve defining as many criteria and sub-criteria as necessary to answer the study and sponsor business needs in terms of timelines and finances. It’s also important to prioritize and define the non-negotiable items as some criteria are absolute must-haves while others may be flexible. Assigning a weight to each criterion supports a better evaluation of the sites’ strengths and weaknesses and allows for an objective comparison. Later on, when data are collected, they may be added to a scoring system such as a simple spreadsheet or, for more complex projects, a visualization dashboard that lets users analyze the data from different perspectives.
Step 2: Identify Sites and Gather Initial Information
Once the criteria are defined, site identification can start. Sites can be identified through diverse paid and free tools such as:
- The sponsor’s internal database of previously utilized sites
- External database through a Contract Research Organization (CRO) that has its own list of potential sites
- A Site Network Organization that owns a network of sites, oftentimes with various experience
- Online and offline directories
- Publications of recent clinical trials in the studied indication
- Clinicaltrials.gov postings
- Word-of-mouth and references
The most helpful tools for pre-selecting sites are the ones that provide filtering functionalities (e.g. site size, location, specialty, etc.), and detailed datasets about past experience and performance which provide initial insights on the site’s compatibility for the study.
Once a potential site is identified, the first step is to send the PI an inquiry for clinical trial participation which includes a study synopsis to assess initial interest and request their CV. If the PI is interested and the site is new to the sponsor or CRO, the next step is to set up a Non-Disclosure Agreement (NDA) before divulging further study details. Once completed, the study protocol can be shared with the PI and a survey that includes specific questions that address each of the pre-defined criteria can be provided to the site. Questions should be unambiguous and generate answers that can be scored. The questionnaire can be submitted and answered through an online survey system. This allows to establish specific rules (e.g., create mandatory fields), obtain standardized answers that can be more easily compared, and produces results that can be easily exported to a spreadsheet and analyzed.
Questions/answers may need clarification, and additional documents may be requested. However, sites lack of or delayed response is often cited as a main reason for site selection inefficiency3. As a result, keeping a contact log that includes the contact information of the point person at the site, an indication about the last time a site was contacted, and notes about pending items or questions, helps staying on top of the progress made and follow ups needed.
Step 3: Evaluate and Select the Sites
Studies report that 11% of sites selected for a study are in fact never activated, the main reason being due to contracting issues.3
It’s important to involve site administration staff in charge of contracting and budgeting early in the conversation, to understand their timeline and expectations. Setting expectations from the start will ensure more efficient start-up and study conduct. In addition, if the sponsor does not have a pre-defined cost per patient, the site should provide a forecast budget that includes study setup cost, study conduct charges, closeout fees, and overhead percentage. Providing a standard budget template to the sites will ensure that all line items are accounted for and facilitate budget comparison.
Prestudy visits (PSVs), also called Site Selection Visits (SVSs) or Site Assessment Visits (SAVs), are then conducted by Site Monitors, especially if the site is new to the sponsor or indication, or if key site staff has changed since their last participating trial. A meeting is scheduled to establish a relationship with the PI and site staff, explain the study in more detail to the staff including study objectives, overall design, procedures, and endpoints, and communicate the sponsor expectations. The visit is essential for the sponsor to verify that the investigator has the personnel, motivation, time, subject population (if possible, as demonstrated by review of the site’s patient database), and facilities and equipment to adequately conduct the study. Providing the visit agenda ahead of time helps ensure appropriate staff are available and enough time is allotted to cover every aspect. A written report is provided to the sponsor detailing visit findings and the Monitor’s recommendations for final consideration of the site.
After all the information is gathered, reviewed, and evaluated, an objective comparison and decisions can be made. Additional support in the areas of Good Clinical Practice (GCP) training, subject recruitment tools (advertising, etc.) may be considered for sites with otherwise adequate qualifications. After such full consideration, the final sites are notified of their selection for the trial. Subsequently, Clinical Trial Agreements (CTAs) are sent to each site, and documents in support of 21 CRF 312.53 can be formally prepared and organized.
To select the optimal sites for a given study, an unbiased and systematic process that consists of conducting an analysis of the site’s compatibility with the study needs, must take place. Proper planning to define study-mandated evaluation criteria, and using the right tools to gather information and facilitate communication, are absolute musts to make the right decisions. However, essential, proper site selection is not the sole factor for site performance and study success. External forces and challenges often affect study conduct (e.g., protocol design such as unclear or difficult-to-meet inclusion/exclusion criteria, supply chain delays, cultural and technological considerations such as in the case of trials conducted in resource-challenged areas, etc.) and require additional planning and mitigation strategies. TRI is a full-service CRO+ with 37+ years of experience supporting all aspects of clinical trials in all aspects from site identification/selection and clinical operations, to strategic planning and risk management. Learn more, here: www.tech-res.com
- Federal Policy for the Protection of Human Subjects; Final Rule, 82 Fed. Reg. 7149. (2017, January 19). Retrieved from https://www.federalregister.gov/documents/2017/01/19/2017-01058/federal-policy-for-the-protection-of-human-subjects
- Federal Policy for the Protection of Human Subjects; Proposed Rules, 80 Fed. Reg. 173 (2015, September 8). Retrieved from https://www.federalregister.gov/documents/2015/09/08/2015-21756/federal-policy-for-the-protection-of-human-subjects
- Analysis of Public Comments on the Common Rule. (2016, May 9). Retrieved from http://www.cogr.edu/Human-Subjects-and-Animal-Research
- Common Rule Overview. (2017, February 1). Retrieved from http://www.cogr.edu/sites/default/files/Summary%20of%20Changes%20to%20the%20Common%20Rule_COGR.pdf
- Disapproval of Regulations by Congress: Procedure under the Congressional Review Act. (2001, October 10). Retrieved from https://www.senate.gov/CRSpubs/316e2dc1-fc69-43cc-979a-dfc24d784c08.pdf
- H.R.21 - Midnight Rules Relief Act of 2017. (2017, January 5). Retrieved from https://www.congress.gov/bill/115th-congress/house-bill/21
- H.R.26 - Regulations from the Executive in Need of Scrutiny Act of 2017. (2017, March 29). Retrieved from https://www.congress.gov/bill/115th-congress/house-bill/26
- Memorandum for the Heads of Executive Departments and Agencies. (2017, January 20). Retrieved from: https://www.whitehouse.gov/the-press-office/2017/01/20/memorandum-heads-executive-departments-and-agencies
About the Author
Jessica Fair is a Human Subjects Protection Specialist with experience in regulatory affairs and clinical research operations. Her areas of expertise include bioethics, regulatory affairs, clinical operations, and public health.