QRTI Newsline --- Wednesday September 8, 2010

Using Monitoring Reports to Actively Manage Clinical Trials

By Phyllis B. Kent

What is the best tool to use to show inspectors that we are actively overseeing clinical trials? Monitoring reports provide an effective tool to assist with oversight of monitoring as long as they are complete, accurate and timely.Documentation of who, what, when, and where in monitoring is industry standard in order to document that sponsors are complying with monitoring requirements. Typical reports include the name and address of the site and names of all persons involved in the visit both from the site and from the sponsor/CRO and when the visit was conducted. The reports document study enrollment and which subjects' records were source verified. Additionally, reports should document the compliance with informed consent requirements, SAE review and reporting, investigational product accountability and maintenance of the required regulatory documentation. All of these items are documented by responding to questions on the form or filling in blanks. So what are the issues?

• Training Monitors to document and address site issues.
  Many monitors have never received training beyond completing the checklists. They do not understand the importance of documenting any problems noted at the site and the actions taken to gain resolution of issues noted. In addition, comments boxes are frequently left blank on the reports. How does a Clinical Manager reviewing these reports have assurance that the monitor addressed issues? How will FDA be assured?
• Using a spreadsheet attachment to the Monitoring Visit Report.
  Most companies have an attachment to their monitoring reports, or sometimes have a list of action items imbedded in the reports. These lists are usually spreadsheet style to capture the observation date, the issue, space to enter a resolution and the date of resolution. Some forms may include the person responsible for the resolution, e.g., study coordinator. Others enter a plan of action, (e.g., study coordinator will obtain the approval letter from the IRB). When the monitor has verified the correction, the resolution date or date completed is entered. I like to see the plan and, of course, prompt resolution.
• FDA expects to see issues identified by monitors and that the resolution is documented.
  Use of spreadsheet attachments results in fewer issues being overlooked or accidentally dropped off the follow-up list by the monitors. There is also better documentation that the issue is resolved, including when it was corrected and by whom. It allows managers the ability to follow the progress toward resolution. Avoid a mess from the management/QA oversight perspective. A spreadsheet should not be cumulative. Once an issue is documented as resolved, it should be removed from the report. Some companies use cumulative reports that become 20+ pages in length and it is difficult to identify the open issues or resolutions since the last visit. This is very inefficient from the management/QA oversight perspective since additional time is required to review the lengthy reports and managers are more likely to miss outstanding issues. Open issues and current resolutions are all that should be in the list.
• SOPs should specify a resolution timeframe.
  Serious issues should be resolved immediately, that is, before the next monitoring visit. Monitors/sites should not wait for the next visit to address these items. Other items should be resolved by the second return visit. An action item listed for 3 visits is an audit finding. The SOP can address steps to be taken when items are not corrected by the site (e.g. management involvement, telephone call to the PI, direct IRB contact, etc.) This is where the liability in an FDA inspection lies ...issues that remain outstanding for months without resolution. The monitoring reports provide FDA with documentation that the monitoring was not effective in obtaining corrective action.
• Generating a separate report of action items to be resolved is not advisable.
  Too much additional work is involved. The issues need to be followed and tracked during the site visit and this is the most appropriate place to document them. Documentation in the monitoring visit report provides immediate proof to an FDA inspector that issues were identified, addressed and resolved.
• Managers are also responsible for ensuring corrective action.
  Managers reviewing monitoring reports have a responsibility for oversight of the issues identified by the monitor. If issues remain open and uncorrected on several monitoring reports, it is incumbent upon the manager to take steps to see that corrective action is taken. Managers can provide guidance to the monitor, provide additional resources to enable more monitoring, or can intervene by contacting the investigational site directly to get resolution. Managers can also stop enrollment until the site corrects the problems. Failure to act can result in an audit or inspectional finding of inadequate supervision of monitors.
  
  

  © 2010 Quality Research Training Institute