eClinical Forum Risk Based Monitoring Taskforce Offers Best Practices

This is an excerpt from a peer-review article titled "Risk-Based Approaches" from the July/August issue of Applied Clinical Trials, which will be available mid-month.

It is important to emphasize that monitoring plans are not unique to the CRA role but also can provide an overall cross functional plan that emphasizes what must be done in order to assure that the data received from clinical research sites are of high quality and integrity. The monitoring plans include not only what is expected to occur at a site level, but also within the data system and program level.

A quality monitoring plan, which can be part of the clinical monitoring plan, may include information from traditional plans that had previously been separated into role or task based activity, for example, each therapeutic area may be different so several quality plans may be needed on that basis. In considering the monitoring plan, adequate risk assessment must be performed prior to the start of the study, in order to ensure patient protection as well as the quality and integrity of data. Our recommendation is that monitoring plans should exist at the program, protocol, and site levels, and outline what will be included in on-site monitoring as well as central monitoring.

Program level plans.
This plan addresses overall quality aspects of the program and should be developed at the start of the clinical program. Risks that are known or anticipated for the disease population and investigational product under study should be documented and clear instruction given as to what, why, and how those risks should be monitored. As a general outline, a program level plan could minimally include the following:

• Planning—a priori identification of risks of the investigational product.

• Design—define protocol eligibility criteria, efficacy, and safety risk factors during design; for inclusion in the eCRF and edit build, as well as define key protocol deviations anticipated for study.
• Execution—clear direction in the oversight and monitoring of parameters leading up to study endpoints, integrated study level monitoring plan, clear direction on evaluating fraud.
• Analysis—clear definition of data measurement and reporting, defined elements of statistical analysis of protocol endpoints, safety, etc.
• Disclosure—publish outcome data, bringing all the above together in the clinical study report (CSR).

Companies may wish to consider creating standard quality checks pertinent to all programs, and which may also include therapeutic area specific sections to be selected as relevant. Ensuring that the entire study team understands the principals and purpose of the program level monitoring plan will help avoid duplication and encourage study teams focus effort where it is most effective.

This is an ideal opportunity to take a step back from familiar routines and look hard at current processes; assess what is valuable and what is not; invest in processes that bring most value from a quality perspective. The goal is to develop an integrated clinical data monitoring plan, based on compound and historical knowledge, which can respond proactively to data signals during trial execution.