Amended ICH GCP Guideline Addresses Evolution of Trials Landscape

The International Conference on Harmonization (ICH) has amended its good clinical practice (GCP) guideline with the aim of helping industry address the increasing scale, complexity and cost of clinical trials.

The evolving use of technology and new risk management processes offer opportunities to increase efficiency, ICH says. The updated guideline is intended to provide a unified standard for the regulatory authorities in the EU, Japan, US, Canada and Switzerland to facilitate the mutual acceptance of clinical data.

"This guideline has been amended to encourage implementation of improved and more efficient approaches to clinical trial design, conduct, oversight, recording and reporting while continuing to ensure human subject protection and data integrity," the amended guideline says. "Standards regarding electronic records and essential documents intended to increase clinical trial quality and efficiency have also been updated."

Quality Management

The longest addendum to the guideline is centered on a sponsor's quality management, which includes the efficient design of trial protocols, data collection tools and procedures, and the collection of data essential to decision making.

The broad ICH recommendations call on sponsors to identify processes and data "that are critical to assure human subject protection and the reliability of study results." And as for risks, ICH says they should be considered at both the system level (e.g., facilities, standard operating procedures, computerized systems, personnel, vendors) and clinical trial level (e.g., investigational product, trial design, data collection and recording).

Risks should be evaluated by considering: (a) the likelihood of errors occurring, given existing risk controls; (b) the impact of such errors on human subject protection and data integrity; and (c) the extent to which such errors would be detectable.

Trial Monitoring

In addition to quality management, sponsors should develop a systematic, prioritized, risk-based approach to monitoring clinical trials, ICH says. The group advocates for a flexible approach intended to improve the effectiveness and efficiency of monitoring.

"A combination of on-site and centralized monitoring activities may be appropriate," though sponsors "should document the rationale for the chosen monitoring strategy," ICH says.

As far as why centralized monitoring processes are important, ICH says they can complement and reduce the extent and/or frequency of on-site monitoring by such methods as:  Routine review of submitted data; identification of missing data, inconsistent data, data outliers or unexpected lack  of variability and protocol deviations that may be indicative of systematic or  significant errors in data collection and reporting at a site or across sites;  using statistical analyses to identify data trends such as the range and consistency of data within and across sites; and analyzing site characteristics and performance metrics.

Other Addenda

ICH also updated the guideline, among other topics, on the responsibilities for supervising any delegated or outsourced study tasks conducted at a trial site, as well as how to maintain adequate and accurate source documents and trial records.

ICH GCP Guideline