Best Practices for Clinical Site Selection

Overview

Clinical trials are expensive and labor-intensive. Failures within the clinical trial process result in a huge loss of valuable resources and time. [1] These challenges can stall a clinical trial and delay life-saving medical therapies and devices from entering the healthcare marketplace. Statistics indicate that an overwhelming 80% of clinical studies are not able to meet their enrollment timelines and objectives because of recruitment difficulties. [1,6]

By implementing a series of best practices for clinical site selection, study sponsors can mitigate potential problems. This is accomplished by carefully navigating several key factors involving population profiles, safety, recruitment strategies, funding [5], and regulatory controls. [1] Notably, industry experts cite a strong correlation between meeting recruitment goals and clinical site selection. [6]

Globally, more than 80% of trials fail to enroll on time resulting in an extension of study and or addition of new study sites. [13]

Subsequently, principal investigators and sponsors place heavy emphasis on identifying site locations with ample resources, such as staff expertise and access to the target subject population. [1,2,3] Principal investigators work to optimize clinical trial volunteer engagement and improve protocol adherence, thereby ensuring a successful trial experience for study subjects. Successful clinical sites benefit from past experiences, as survey-based studies indicate that repeated use of clinical sites is common. [3,6] This is especially true if the clinical trial site can demonstrate a  track record of meeting enrollment targets and successfully completing studies. [2,3]

Implementing Best Practices in Clinical Site Selection

Research sites are ramping up their efforts to combat the many challenges associated with site selection by using prior knowledge, proven practices, and enhanced technology. Taking strategic steps to determine early site feasibility [8] is recommended and should include the following:

Practical and Protocol Considerations

• Geography [9]
  • Is the study site situated in an accessible location for study participants?
  • Can study visits be decentralized and brought closer to participants?
  • Are there measures in place to lower premature dropout rates due to distance?
• Population Profiles [1,3]
  • What strategies are in place to identify patient eligibility?
  • Is there a correlation between the subject population and the disease or condition under study?
• Study Design Assessment [1,3]
  • Is the study protocol too complex?
  • Is there a clinical site monitoring plan in place?
• Ethical Considerations [4,11,12]
  • Are vulnerable populations involved, such as the elderly, pediatric, or disabled? If so, will they have access to post-trial medical care?
  • Are there economic or cultural aspects related to the potential clinical trial site that may deter eligible subjects from participating?
  • Are fair selection practices being upheld?
  • How are inclusion principles and disparity concerns being addressed?
• Study Timelines and Objectives [13]
  • What are the enrollment objectives and allotted timeline?
  • What is the maximum time allotted for study completion?
• Partnerships, Competitors, and Staffing/Team-members [1,3]
  • Are there any competing or similar studies being conducted either at the same site or at another location?
  • What historical takeaways from previously used clinical sites/teams need to be considered?
  • Are there avenues for partnering with medical or social community members to help with recruitment efforts?

Facilities

What site resources are important in a clinical trial site?

Sponsors must assess potential clinical trial sites for suitable facilities and resources. This is normally accomplished by conducting pre-site visits (PSVs) or site selection visits (SSVs). In preparing for a clinical trial, the details matter, such as maintaining the overall appearance of the potential site to ensure it is professional and welcoming to potential participants. Additionally, an ideal site will have adequate storage space, all needed clinical equipment, privacy options, and an attached or nearby research pharmacy. Flexible site access is also an integral component; participants favor facilities with weekend and late-evening appointments. [1,3]

Recruitment and Retention Strategies

Can staffing placements make a difference in clinical trial site selection?

Staffing appointments (existing and new) can significantly impact clinical trial site selection. Essential to the process, clinical site staff should be well-versed in Good Clinical Practice guidelines, federal and state regulations, and institutional policies. They should also demonstrate sincerity and compassion with trial participants. Because site coordinators and research nurses are tasked with vital duties such as data collection, they are often in constant contact with participants.

Patients’ perceptions regarding staff availability or interest (as well as having to meet with unfamiliar staff) can greatly impact recruitment and retention. [2] Patient satisfaction surveys suggest that the interactions between participants and clinical staff members play an influential role in clinical trial recruitment and overall experience. [7] Establishing patient trust by using consistent methods of communication and follow-thru often results in better participation and adherence.

Regulatory Considerations

Is there a risk to using clinical sites with internal site management teams already in place?

Studies concluded that clinical sites with a history of demonstrated site management operations offer the best results in terms of data collection and regulatory compliance. Regulatory duties may be outsourced to companies specializing in clinical site management. Although there is a tremendous benefit to streamlining the clinical process, the challenge of staff inconsistencies and turnover is ever-present. Common pitfalls include high investigator turnover (approximately 40% each year) because of a stressful site environment and burdens related to maintaining regulatory compliance. [10]

Conclusion

Research illustrates how clinical site selection can affect the success of a clinical study or trial. With many overlapping elements, staffing considerations affect multiple areas, including recruitment, retention, regulatory compliance, and overall patient experience. Utilizing best practices alongside a strategic pre-clinical site management plan is key when trying to meet recruitment objectives and study timelines.

As more technological enhancements come into play, we can expect more industry outsourcing to help manage data collection and reporting, in addition to incorporating biometrical data to help improve trial outcomes. While there are many benefits associated with outsourced clinical site management, research sponsors should approach each new potential clinical trial site selection with a fresh lens.

Industry thought leaders emphasize that there is no one-size fits all approach to site selection. By choosing clinical sites carefully and using proven practices, a study sponsor can increase the opportunities for a successful clinical trial.

References:

1. Hurtado-Chong, A., A. Joeris, D. Hess, and M. Blauth. 2017. “Improving site selection in clinical studies: a standardized, objective, multistep method and first experience results.” BMJ Open. 12;7(7): e014796. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734283/.
2. Fogel, D.B. 2018. “Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: A review.” 2018. Contemp Clin Trials Commun. 11:156-164. doi: 10.1016/j.conctc.2018.08.001.; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092479/.
3. Dombernowsky, T., M. Haedersdal, U. Lassen, et al. 2019. “Criteria for site selection in industry-sponsored clinical trials: a survey among decision-makers in biopharmaceutical companies and clinical research organizations.” Trials 20;708. https://doi.org/10.1186/s13063-019-3790-9
4. Feyman Y., F. Provenzano, and F.S. David. 2020. “Disparities in Clinical Trial Access Across US Urban Areas.” JAMA Netw Open. 3(2): e200172. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049079/.
5. DiMasi, J.A., H.G. Grabowski, and R.W. Hansen. 2015. “The cost of drug development.” N. Engl. J. Med. 372:1972. https://www.nejm.org/doi/10.1056/NEJMc1504317.
6. Bose, S.K., A. Sandhu, and S. Strommenger. 2017. “Clinical trials: A data driven feasibility approach.” Pharmaceutical Outsourcing. Blog. Feb. 1, http://www.pharmoutsourcing.com/Featured-Articles/333830-Clinical-Trials-A-Data-Driven-Feasibility-Approach/.
7. Thoma, A., F. Farrokhyar, L. McKnight, and M. Bhandar. 2010. “How to optimize patient recruitment.” Can. J. Surg. 53:205–210. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878987/.
8. Rajadhyaksha V. 2010. “Conducting feasibilities in clinical trials: an investment to ensure a good study.” Perspect Clin Res. 1(3):106-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146075/.
9. McMurray, J.J. 2016. “Site Selection and Performance in Clinical Trials.” Circulation: Heart Failure. 9: e003490. https://www.ahajournals.org/doi/full/10.1161/CIRCHEARTFAILURE.116.003490.
10. Getz, K.A., and M.J. Lamberti. 2013. “Global site landscape remains highly fragmented with variable performance.” Tufts Center for the Study of Drug Development Impact Report. 2013; 15 (1-3). March/April.
11. Miller J. and J. Millum. 2022. “Ethical considerations in international clinical trial site selection.” Global Health 7: e008012. https://gh.bmj.com/content/bmjgh/7/4/e008012.full.pdf.
12. Giutis, K., R.G. Hammermesh, and M. Krasnow. 2021. “Addressing demographic disparities in clinical trials.” Harvard Business Review. https://hbr.org/2021/06/addressing-demographic-disparities-in-clinical-trials.
13. Desai M. 2020. “Recruitment and retention of participants in clinical studies: Critical issues and challenges.” Perspect Clin Res. 11(2):51-53. doi: 10.4103/picr.PICR_6_20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342339/.