Systematic site assessments

Sponsors should systematically assess potential sites and develop a targeted response to identified weaknesses.

A robust site selection process is required to ensure appropriate sites are selected and equipped to manage a clinical trial. The process should consider patient population (recruitment potential), clinical expertise (ability to manage participant care), microbiology expertise, nonclinical expertise (for example project management and regulatory knowledge and experience) and the adequacy of physical infrastructure (such as that of lab, pharmacy, and information technology).

In STREAM, site selection began with a desk-top analysis of recruitment potential based on burden of disease and competing trials at the site. For potentially eligible sites, the Sponsor approached the NTP to determine their support for the trial. MRC CTU at UCL, ITM and, sometimes Sponsor pharmacists then visited the site to assess its facilities and expertise. While these visits were quite good at confirming clinical expertise and identifying required changes to infrastructure, they were less effective at assessing non-clinical capabilities. As a consequence, there were sometimes delays in identifying gaps and weaknesses related to aspects such as project management, logistics and regulatory expertise. For example, a trial site in India had significant experience with the primary trial regulator (the DCGI), but less experience with secondary regulatory requirements under the country’s biodiversity legislation applicable to the export of trial samples. A more thorough upfront assessment of expertise by the Sponsor could have identified and addressed this gap through additional staff hiring or by contracting local consultants or experts.

Careful review of all regulatory components as part of the site assessment, such as import/export requirements, can help mitigate delays and other challenges in trial implementation.

Vital Strategies, STREAM Sponsor

In most cases, however, the STREAM site selection process worked very well to ensure trial sites were well-equipped to conduct the trial. Excellent sites were selected, and the assessment process effectively identified gaps and weaknesses. At many sites, assessment visits successfully identified infrastructure improvements needed for storing trial medicines in appropriately controlled environments. In Mongolia, the initial assessment concluded that STREAM was among the most complex clinical trials ever conducted in the country and, therefore, would necessarily raise novel regulatory issues for the national ethics committee to consider. In response, trial timelines and resources were adjusted to account for the extensive interactions required with the ethics committee and regulators to ensure their concerns and questions regarding the trial were adequately addressed by the Sponsor and the site. In India, some sites received more intensive GCP training to address their limited experience with phase III USFDA regulated clinical trials. Site assessments also helped identify laboratories where ITM conducted pre-initiation trainings on trial-specific techniques for staining and culturing of Mycobacterium tuberculosis.

Recommended best practices

Ensure clinical trial sites are equipped to successfully manage the trial through the following measures:

  • Implement a systematic site evaluation and selection process that assesses the full range of criteria relevant to successful implementation of the trial and includes clear selection criteria

  • Clearly document site assessments and targeted responses to identified weaknesses

  • Implement responses to identified weaknesses, including infrastructure improvements and capacity building at site as well as systems level

  • Share information about site readiness with sponsors of future trials to simplify site selection