Sponsors, contract research organizations (CROs), and sites should immediately introduce “emergency interim measures” to help sustain clinical trial monitoring as the coronavirus (COVID-19) continues to impact day-to-day life in the United States and much of the world, says the Association of Clinical Research Organizations (ACRO) in a new policy statement issued Monday (March 16).
ACRO says its recommendations should be considered in the following situations:
- When sites have suspended or restricted all visitors (including clinical research associates [CRAs]) from accessing medical facilities, but where patient visits are still occurring.
- When local health officials have implemented regional quarantines.
- When local CRAs are unable to travel to the sites (for personal health reasons or because of travel restrictions).
Specifically, ACRO is recommending increased use of centralized monitoring tools already in place and enhanced by a set of practices and tools that “do not require any additional sophisticated analytical tools or dashboards.”
“Care should be taken that any remote monitoring activities implemented are proportionate to the risks identified,” ACRO says. “Further, they should not place any extra burden on clinical trial sites.”
Among ACRO’s recommendations addressing clinical trial oversight:
- Utilize regular site telephone contacts to monitor the situation and status of patient participation at the sites.
- Increase the frequency of already programmed patient profiles or listing reviews.
- Use existing key risk indicators (KRIs) and key performance indicators (KPIs) to assess the impact on early termination, electronic data capture (EDC) data entry backlog, deviations, the volume of missed subject visits, adverse event (AE) reporting cadence, etc. KRIs and KPIs should be used to identify any trends that may require temporary interventions. Identified trends should be assessed for scale of impacts across sites, which may require discussions across the project team/sponsor to mitigate risks to accommodate investigational product shortages, missed endpoints, alternative methods of monitoring subject safety, etc.
- In the event that onsite monitoring visits cannot be completed, consider implementing remote review of subject visit data via the EDC system, with a focus on data most important to subject safety and data quality. While this will not cover the review of source documentation, this process can still alert the CRA to the following:
- Eligibility violations visible in medical history, scales, electronic patient-reported outcomes, eDiaries, physical exam findings, and concomitant medications.
- Protocol noncompliance with visit windows, gaps in investigational product administration, dose taper and dose titrations, serious AE reporting, adherence to withdrawal criteria, etc.
- Safety concerns through the assessment of labs, AEs, and other assessments reported in the EDC system (or lack thereof).
ACRO also offers guidance on how to document the results of these remote reviews. “Subsequent site follow-up can be managed through remote interim monitoring visit reports,” it says. However, ACRO does not recommend accessing electronic health records remotely (unless the process was already established with appropriate privacy and access controls) or requesting that sites fax source documents for remote review.
“If you choose to adopt any of these interim measures, we recommend following your company’s procedures (e.g., planned deviation or Monitoring Plan addendum) to document the effective date of the interim measure,” ACRO says. “We also recommend that you document the date of when routine monitoring practices have resumed.”
Before routine monitoring is resumed, strategies on how data are monitored in this interim period should be discussed with the sponsor and then documented, ACRO says. ACRO’s position is that it will not be necessary to perform 100% source document review and source data verification of all subjects, visits, and data. When routine monitoring resumes, a risk-based approach should be applied to subjects being monitored.
Author: Michael Causey