Standard processes at sites

Sites should develop and document standard processes (SOPs) in line with the trial protocol for key aspects of trial implementation.

Regulated clinical trials must meet the highest standards related to participant safety and data integrity. To do so, key trial requirements are set out in the trial protocol, with details of implementation typically left to sites so that local conditions can be considered in site-level processes. Too little site level systematization of processes can mean key aspects of the trial are not implemented in accordance with the trial’s requirements (per the protocol, lab manual, etc.).

In STREAM, more systematized implementation at sites would have improved trial performance related to central laboratory testing. All of the trial’s safety testing and some microbiology analyses were conducted by central laboratories. A complex supply chain was required to permit the import of lab kits and the export of samples to central labs in Singapore, Belgium, South Africa and the UK. Sites were required to manage various aspects of the supply chain, including import and export licenses, customs/duties clearance and kit inventory management, but were not required to document their processes for managing these issues (although some elected to do so). In some cases, that resulted in high levels of kit wastage, kit stock-outs, and/or delays in sample shipment; these could have been avoided if site-level processes for inventory and shipment management had been developed.

When we learned the trial would require central lab testing with imported bespoke kits, we knew we needed to put in place a process to make sure we didn’t run out of kits and didn’t order too many. So, we decided that we would keep strict records of the kits, with information about visit and expiry date. When we place an order, we make sure to consider the number of visits during the period, the type of visit, and which kits will be needed depending on the structure of the visit according to the protocol.

Site Principal Investigator, STREAM Trial

In contrast, the trial’s response to the COVID-19 pandemic demonstrated the impact of well-developed processes. Early in the pandemic, the Sponsor developed a strategy for ensuring continuity of care for participants and minimizing loss of trial data. This strategy prioritized continuity of treatment first, then protocol-mandated safety assessments for those still on treatment and finally minimization of data loss. This was communicated to sites and rapidly implemented by site PIs. While the principles were developed centrally, each site developed processes adapted to local circumstances – for example, where participants were unable to travel to the trial site due to lockdown restrictions, study teams made home visits; where participant travel was permitted, participants were transported to/from trial sites for key visits in a private vehicle to reduce exposure risk. Because sites developed clear processes to manage these issues, all trial treatment doses were properly dispensed to participants, even during COVID-19 lockdown restrictions.

Recommended best practices

Systematize key site-level processes through the following measures:

  • Require sites to develop a minimum set of site-specific SOPs that cover key implementation issues, including informed consent processes (including documentation of inclusion and exclusion criteria), drug dispensing frequency and logistics to directly observed therapy (DOT) centers, trial visit scheduling, local and central laboratory testing logistics, onward reporting of protocol deviations and safety events to local ethics committees and regulatory authorities

  • Provide sites with template site-level SOPs for key processes that can be adapted to local conditions

  • Develop flow charts and job aids for sites around key trial processes, such as eligibility assessments and inclusion/exclusion criteria

  • Review metrics around key site processes including but not limited to protocol deviations, regulatory non-compliances, kit wastage, failed tests, delays in sample shipments in order to revise and improve site-specific SOPs as required