Risk-based monitoring strategy

Implement a well-designed, risk-based monitoring strategy.

Oversight of a clinical trial requires a well-designed, risk-based monitoring strategy that is flexible enough to account for the different experience/expertise levels of trial sites. While much of the oversight can be conducted remotely, onsite visits are required to build personal relationships, effectively carry out capacity building, review sensitive participant records and observe site facilities and activities. In STREAM, the trial’s main implementation partner, MRC CTU at UCL, made in-person monitoring site visits in response to identified issues, but generally oversaw the trial remotely. In Stage 2, in recognition of the need for further onsite oversight, the frequency and scope of onsite monitoring increased and included regular onsite visits by a contract research organization (typically one visit/site/month), the trial’s microbiology lead (typically one visit/site/year) and the trial’s pharmacists (typically one visit/site/year).

At sites with prior experience of running multi-site trials (e.g., some of the South African sites), this approach worked well because they had experienced principal investigators and clinical trial/research units to support less-experienced trial team members and understood when to escalate issues to the sponsor/partners. However, some less experienced sites initially reported more serious protocol deviations – including some related to the informed consent process and reporting of safety events – indicating that a more comprehensive monitoring approach was needed for inexperienced sites.

The role of the local country based monitor is very important in bridging the gaps of understanding context at a site level between sponsors and site staff. Site visits from the sponsor could have been more frequent and if not possible, skype calls or regular feedback sessions on study progression to address concerns as they came up would have been very useful for new sites.

Site Principal Investigator, STREAM Trial

As issues were identified, monitoring strategies were adjusted to incorporate more intensive onsite monitoring (particularly in the early stages of participant recruitment), additional site audits, and development of corrective action and prevention (CAPA) plans. At the less-experienced India sites, a New Delhi-based sponsor representative made frequent onsite visits to identify challenges and provide support. In addition, later in the trial, CRO visits were timed to ensure an initial visit just after the first few participants were recruited in order to confirm site compliance with the informed consent process and participant eligibility requirements. This helped control major protocol deviations and identify training and/or process changes required at sites.

Recommended best practices

Identify and respond to quality issues through the following measures:

  • Develop a clear, risk-based monitoring system that accounts for differing experience levels at trial sites

  • Implement more intensive and in-person monitoring during the initial recruitment period to identify and resolve major quality issues

  • Develop and implement a risk-based audit plan that prioritizes higher risk sites (e.g., inexperienced or high recruiting sites)

  • Ensure frequent and regular communication channel between sponsor and site team