Site identification and selection can feel like a grueling process. The process of finding dedicated sites with skilled clinicians/principal investigators and research teams poses many challenges, but this toolkit may help guide you through the process.
1. Examine the site(s)’ current and past research portfolio, specifically, investigator-initiated trials and industry-sponsored trials.
An investigator-initiated trial is led by non-pharmaceutical company researchers, like individual investigators, institutions, collaborative study groups or cooperative groups1. These studies may be funded by the federal government, private organizations, non-profit groups, or may not be funded at all. The overall design, execution, and data collection is under the purview of the investigator and his/her research team (as applicable).
An industry-sponsored trial is funded by a pharmaceutical or device company that has contracted with a faculty member to conduct a clinical trial. For most industry-sponsored clinical trials, the industry organization designs the trial and owns the protocol.2
Understanding the percentage of investigator-initiated versus industry-sponsored effort in a research portfolio can be an indicator of overall funding, academic interest, dedicated research investigators and support staff, complexity of trials previously completed, and overall institutional support.
Questions to consider:
- How many active trials are currently up and running?
- How many trials do you have in your pipeline?
- How many Principal Investigators are currently participating in research?
- Are there any centers of excellence or therapeutic specialties at the site?
2. Inquire about staffing and staff qualifications.
Before committing to a particular site, it is essential to understand the principal investigator, co-investigator (if applicable) and research staff’s previous experience with clinical trials. In addition to obtaining CVs and training certificates, one should understand how the trial-related tasks are delegated to active members of the research team. Depending on the complexity of the trial and drug indication, a sponsor may be heavily dependent on staff expertise.
Questions to consider:
- How many research coordinators are typically assigned to one trial?
- Does the site have dedicated research nurses or phlebotomists?
- Are research staff members trained in specific therapeutic areas?
- Are regulatory/Institutional Review Board specialists available to support clinical trials?
3. Recognize the research differences between a community hospital versus an academic medical center.
There are many differences between a community hospital versus an academic medical center. For the purposes of the toolkit, I’ve identified a few of the major differences.
Typically, a community hospital may not have a large pool of active investigators, making complex trials challenging to implement. The limited number of PIs may be attributed to competing demands between clinical care and dedicated research time afforded to clinicians in this type of care setting. Community hospitals are not traditionally known for receiving large amounts of federal support for conducting research. Without funding, research teams may be faced with limited human capital and other research-specific resources necessary to carry out a trial.
Academic medical centers, on the other hand, are known for robust research enterprises, affiliated with a medical school and heavily support graduate medical education. Due to its commitment to education and federal support, academical medical centers are oftentimes better equipped to execute trials.
Keep in mind, there are pros and cons to both types of research environments. For example, community hospitals may have a smaller research portfolio, but that may enable the research team to balance fewer studies and therefore stick to timelines more efficiently. Fewer studies to balance across therapeutic areas also allows for more effective recruitment as studies are not cannibalizing the population of interest.
Researchers from academic medical centers may be balancing numerous trials resulting in less attention towards each individual trial.
Depending on the geographic location and surrounding population, investigators who are affiliated with community-based hospitals versus an academic medical center may be exposed to characteristically different populations (e.g., complex, rare diagnoses or diseases versus more acute, stable conditions). Given these differences in the research landscape, academic medical centers in comparison to community-based hospitals may have varying levels of staffing and resources available.
Questions to consider:
- How many trials is the current PI supporting?
- How many of the trials are actively recruiting, in start-up, in data-analysis only, or in closeout?
- How many of the trials are supported through industry versus federal funding?
4. Understand Institutional Review Board requirements (IRB) and timelines
Sites may have their own local IRB that is the preferred IRB of record. Before finalizing site selection, one should understand the timelines associated with this local authority.3 Local IRBs often take up to two times longer to activate a trial due to resources, meeting schedules, and feedback from reviews.
Central IRBs such as WIRB-Copernicus Group (WCG) or ADVARRA are well-equipped to handle large, multi-center studies as well as single-site studies by ensuring all sites (as applicable) are using the appropriate protocols/Informed Consent forms (version control), staff meet the necessary qualifications, and oversight is efficient. Because meeting schedules are not an issue faced by central IRBs, feedback from reviews can be completed in days to weeks, rather than months.
Questions to consider:
- Does the site need local approval before relying on a central IRB?
- Are there local implications for relying on a central IRB?
- What are the costs associated with central IRBs versus a local IRB?
- Does the site require site-specific language to be included in the ICF?
5. Consider recruitment practices
According to the NIH, over 80% of clinical trials struggle to meet recruitment goals and 19% of clinical trials close early due to these challenges.4 Because recruitment practices may vary from site to site based on the populations served, the sponsor must make careful decisions based on the information provided by each site under consideration. If a site has previous experience with the given indication, the sponsor should inquire about average termination rates and screen-fails. Depending on the timeline of the clinical trial, staffing may need to be able to provide 24/7 coverage to enhance recruitment potential. Additionally, if there are multiple trials with the same indication and similar inclusion/exclusion criteria, the PIs will be competing from the same patient population thus cannibalizing other trials.
Questions to consider:
- Will the site be recruiting from a repository?
- Does the site plan to advertise? If so, what is the anticipated conversion rate?
- If a multi-center trial, how many patients does the site staff anticipate contributing?
- How many competing trials are active?
Summary
There are many elements to consider when choosing a research site. Understanding the research portfolio, staffing experience and expertise, site characteristics (community hospital versus an academic medical center), IRB/regulatory implications, and recruitment practices are only a few of the primary considerations in formulating the decision. Dependence on the therapeutic area/indication, may help narrow down the preliminary search, but the finer details will support the final decision-making process. Once sites are activated, monthly reporting of recruitment will help the sponsor understand how well sites are performing and if additional support or site changes are required. The sponsor should be proactive and prepared with additional sites on standby in the event unforeseen challenges occur throughout the clinical trial.
References
1. https://www.roche.com/research_and_development/who_we_are_how_we_work/investigator-initiated-studies-portal.htm?tab_id=types-of-iis-eligible-for-support
2. https://www.iths.org/investigators/handbook/set-up-the-study/industry-sponsored-clinical-trials/
3. https://www.biopharmadive.com/spons/six-practices-of-high-performing-clinical-research-sites/529344/
4. https://credevo.com/articles/2020/03/31/how-to-improve-patient-recruitment-in-clinical-trials/
About the author
Jenna Brager, PhD, RN, MS, is the director of regulatory affairs at MyMD Pharmaceuticals®. Prior to joining MyMD, Dr. Brager served as the Director of Clinical Research for LifeBridge Health and was a clinical investigator at Johns Hopkins Hospital. Dr. Brager received her B.S. in Nursing from the University of North Florida, graduating cum laude and received her Ph.D. from the Johns Hopkins University School of Nursing.
Dr. Brager welcomes comments, questions, and requests for future blog topics. Please email jbrager@mymd.com.