To learn more about the updated guideline, Outsourcing-Pharma.com talked with Helen Howitt, director, process quality management at INC Research.
What does the adoption of the new ICH E6 (R2) monitoring protocol mean for the industry?
As an industry, we need to focus on the data and processes that ensure subject protection and the reliability of trial results. This starts with avoiding unnecessary complexity of our clinical trial protocols and considering the operational feasibility of our trial designs.
By doing so, we reduce the burden on site staff and clinical trial subjects while maximizing our opportunity to recruit both. At the same time, we maintain compliance with the protocol and GCP, protect our clinical trial subjects, and ensure we generate high-quality data.
We also need to move away from treating all data and processes associated with trials with equal importance, instead focusing on the data and processes that really matters in a risk-proportionate manner relative to the phase, indication, and complexity of the trial.
In other words, we must focus on the data and processes which are directly linked to subject safety, rights, and welfare, as well as the key efficacy variables.
What are some of the key considerations for assessing an organization’s readiness?
The areas of the addendum with the biggest impact on the industry are those related to Quality Management (section 5.0), and the Extent and Nature of Monitoring (5.18). Organizations should consider the maturity of their risk-based quality management system and the extent to which Quality by Design principles are implemented in their clinical trials.
Can they demonstrate the seven steps of quality risk management throughout the clinical trial lifecycle, and are these used to inform the manner in which the trial is monitored?
To what extent does the organization take a holistic, cross-functional approach to monitoring the clinical trial data, utilizing technology to surface anomalies in the data and to inform when to perform on-site monitoring? Or is the organization still largely attached to traditional on-site monitoring activities?
In addition, an organization should ask itself whether its Computerized System Validation (CSV) and Trial Master File (TMF) processes and activities are fully aligned with the new addendum requirements.
How can companies maximize the opportunities provided by advances in technology and in risk-based monitoring approaches?
Technology is a key enabler to performing effective Risk Based Monitoring (RBM). By focusing monitoring activities on the critical data, critical processes and identified risks, effort is spent on value-added activities that directly support subject safety and the reliability of trial results.
Technology solutions underpin this by enabling near real-time access to the data, meaning that risks and issues can be identified and addressed early on in the study, before they become endemic.
How can they reduce the challenges that may pose a threat to a successful implementation?
In the past, one of the barriers to success has been a resistance from organizations and individuals to let go of conducting 100% source data verification of all data. By demonstrating through the critical data and process evaluation which data are of most importance, and identifying how best to monitor and review those data during the trial, sponsors can reassure their own staff, site staff, and auditors/regulators that the appropriate control measures are in place to ensure subject rights and safety, as well as data integrity.
Cultural change management and messaging is also central to the successful implementation of the ICH E6 (GCP) addendum. It is important to reassure all those concerned (clinical monitoring staff, auditors, and site staff) that taking a risk-based approach is not about cutting costs, transferring more responsibility to investigator sites, or reducing quality or subject safety; rather, it serves to achieve the opposite.
Lastly, it is critical that auditors and inspectors also adopt a risk-proportionate approach, evaluating the appropriateness of the monitoring strategy applied and compliance with that strategy. If auditors and inspectors continue to check every data point, it may undermine the efforts of the industry to modernize and drive a continued conservative approach to the management of clinical trials.
What does the new ICH E6 R2 GCP addendum mean for sites specifically?
Sites are impacted both directly and indirectly. Directly, requirements related to investigator qualification, delegation, and oversight of third parties, as well as to the collection and maintenance of source documents, are all reinforced by adding them to the Investigator section of ICH E6 directly.
Previously, these items were only designated as the Sponsor’s responsibility to check. Indirectly, sites can expect to see a change in the way sponsors and CROs interact with them. There will likely be a shift away from fixed interval monitoring visits and movement towards triggered on-site monitoring visits based upon, among other things, the volume of subjects, the complexity of the trial protocol, the level of risk associated with the study, the investigational product and site experience and compliance. Sites can also expect an increase in remote (centralized) monitoring activities.