Infectious Disease Research: Importance of Site Location in Clinical Trials
June 18, 2021
Site location plays an important role in clinical trials. The impact of location comes into play for most therapeutic areas. In the same way that allergy studies need to be planned with respect to the allergens studied, infectious disease clinical trials have to take place where those diseases are prevalent.
Natural Selection Amongst Pathogens
Pathogens tend to thrive in specific ecosystems, and ancient history reflects that connection. Researchers Karlsson, Kwiatkowski, and Sabeti (2014) explain that connection: “this ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders.” While globalization and industrial development have eroded some of those borders, the interactions between hosts and pathogens are important in the development of therapies as well as the management of infectious disease.
Diversity of Trial Populations
Diversity also has to come into play as well. In 2021, Nephew published commentary detailing the importance of more diverse demographics in infectious disease studies. A vaccine tested and approved in one community may not have the same efficacy or safety in another. With this disparity in mind, the FDA published a report in late 2020: Enhancing the Diversity of Clinical Trial Populations-Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry (you can access the report here). That guidance is meant to encourage researchers to consider both demographic (e.g., age) and nondemographic (e.g., comorbidities) when selecting participants to prevent populations from being underrepresented.
Criteria for Site Selection
Selecting sites for clinical trials needs to be more than a function of availability of participants for the study to produce quality data. Dombernowsky et al (2019) looked at the criteria that pharmaceutical companies and contract research organizations (CROs) use when designing studies. They found that 88% were primarily focused on reaching enrollment goals and most would work with an inexperienced site if it meant access to a larger or more interested patient population. The researchers also concluded that data entry, fast startup times, and the presence of a study coordinator were each significantly more important than site costs.
Vaccine Trial Design for Emerging Infections
Timing is a consideration as well, especially when looking at emerging infections. Researchers Kahn et al (2018) explain that “the 2014–2016 Ebola epidemic highlighted variations in the design of randomized trials to evaluate investigational vaccines in an emergency setting.” They advocate for starting trials at the same time for all participants in a parallel rollout to maximize the scientific and social value of the study.
Site Location in Infectious Disease Trials
Site selection is critical in conducting sound clinical trials within infectious diseases and vaccines. Natural selection of pathogens and diversity of trial participants are important site selection criteria, but timing also matters.
Administration UFaD, (2020). Enhancing the diversity of clinical trial populations-eligibility criteria, enrollment practices, and trial designs guidance for industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enhancing-diversity-clinical-trial-populations-eligibility-criteria-enrollment-practices-and-trial
Dombernowsky, T., Haedersdal, M., Lassen, U., 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
Kahn, R., Rid, A., Smith, P.G., Eyal, N., and Lipsitch, M., (2018). Choices in vaccine trial design in epidemics of emerging infections. PLoS Med 15(8): e1002632. https://doi.org/10.1371/journal.pmed.1002632
Karlsson, E., Kwiatkowski, D. & Sabeti, P., (2014). Natural selection and infectious disease in human populations. Nature Reviews Genetics 15, 379–393. https://doi.org/10.1038/nrg3734
Nephew, L.D., (2021). Accountability in clinical trial diversity: The buck stops where? The Lancet: EClinical Medicine 36 (100906), June 1, 2021. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00186-3/fulltext
Simpson, S., Kaufmann, M.C., and Glozman, V. (2020). Disease X: accelerating the development of medical countermeasures for the next pandemic. The Lancet Infectious Diseases 20 (5), E108-E115, May 1, 2020. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30123-7/fulltext