The International Council for Harmonisation (ICH) on Thursday opened for comment a new reflection paper on Good Clinical Practice (GCP), part of a plan to modernize ICH guidelines on clinical trial design, planning, management and conduct.
The scope of the revisions includes the current E8 General Considerations for Clinical Trials and further revision to the E6 Guideline for Good Clinical Practice, which is already undergoing modernization with the recent development of ICH E6(R2).
The goal of such revisions is to provide updated guidance to address the increasing diversity of study types and data sources that are being employed to support regulatory and other health policy decisions.
The changes come as concerns were recently expressed by some research organizations and an international consortium of health researchers in a February 2016 letter to ICH, conveying concerns that the current ICH E6 guideline fails to sufficiently recognize variations in the level of risk for participants in different types of trials and allow corresponding flexibility in managing the risks. Another major concern was related to E6’s limited scope. It was felt that a guideline entitled “good clinical practice” should more holistically address the planning and conduct of clinical trials.
The proposed renovation would address the broader concern about the principles of study design and planning for an appropriate level of data quality through revision to the current ICH E8, based on the recognition that data quality fundamentally depends on the quality of the study that generates that data, and that many aspects of study design affect the reliability of the study conclusions.
ICH is proposing that E8 would be revised and modernized to better identify “1) aspects of a trial that are critical to generating reliable data (e.g., relevant critical-to-quality (CTQ) factors) and 2) the strategies and actions that could effectively and efficiently support quality in these critical areas. The document could identify a basic set of CTQ factors generally relevant to the integrity and reliability of study conclusions and patient safety that sponsors should consider, to determine which factors stand out as critical and need to be explicitly addressed in a risk-based management and monitoring plan.”
ICH’s revisions to its E6 guideline also would “preserve a key role for the current focus on traditional interventional trials conducted in a clinical trial setting while also addressing the other types of data sources or decision contexts.”
That revision would focus on overarching principles, including elements of human subject protection and data quality, using a risk-based approach to study oversight and monitoring.
“Recently, there has been a further shift to leverage the large amounts of available data from the ‘real world’ (e.g., electronic health records, hospital discharge summaries, claims data, patient/disease registries, etc.), collected and stored for other purposes, that could inform regulatory decision-making…Other possible sources of real world data include electronic medical records (EMRs) sometimes referred to as electronic health records (EHRs) generated by ongoing patient care, as well as health care administrative data sources. However, it should be noted that there are no universally accepted standards currently in use for formatting data from these different real-world sources, and this is probably the single biggest impediment to large-scale use of existing health care records in clinical trials. The adoption of standardized electronic formats for health care administrative data, and patient EMRs will greatly improve the ability of researchers to use these data to address health care and policy questions,” ICH added.
The council also seeks to lay out three annexes (Proposed Annex 1: Traditional Interventional Trials of investigational unapproved or approved drugs; Proposed Annex 2: Non-Traditional Interventional Trials and/or data sources; Proposed Annex 3: Non-Traditional Trial Designs) to attach to the new E6 guideline, each of which would address in more detail a particular type of study and/or data source to which E6 could be applied, and provide a more detailed workup of the CTQ factors that should be considered.
Stakeholders are invited to submit any comments to email@example.com. by 11 March and the council said its aim “is to proceed with initiating needed renovation work as soon as practical, for example, within the next year.”
ICH Reflection on “GCP Renovation”: Modernization of ICH E8 and Subsequent Renovation of ICH E6