Common Rule Checklist

by Aarthi Iyer

ICH Modernization and What it Means for You

Twenty years after the International Council for Harmonisation (ICH) released international guidelines for good clinical practice (GCP), ICH has issued an addendum to their original guidance which aims to:

  • Account for modernization within clinical trial practice
  • Expand the scope of roles and responsibilities of all involved parties
  • Address concerns from past GCP regulatory inspections, especially around data management and monitoring activities

Specifically, the Addendum (formally known as ICH GCP E6 [R2]) has introduced 26 new items spanning all areas of clinical research, including sponsor and investigator responsibilities, electronic data capture systems, and data management and monitoring.

The Addendum is arguably overdue, but will provide valuable guidance for sponsors and investigators as they continue to consider and adapt the powerful new technologies and capabilities offered by the 21st century.


How the ICH Addendum Impacts Your Research

Formalized Quality Management

The Addendum now includes comprehensive compulsory quality management criteria for GCP in accordance with the recent policies of the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

Sponsors are obligated to manage quality throughout the design, conduct, recording, evaluation, reporting, and archiving of clinical trials, and they are encouraged to focus on study-related tasks essential to ensuring human subject protection and the reliability of trial results. ICH specifically promulgates the use of a risk-based approach to monitoring, where sponsors will need to detail how to identify, evaluate, control, review and report risks through quality management systems.

While responsive to results from inspections, these revisions walk a fine line between requiring sponsor hypervigilance with regards to quality management (thereby slowing down research timelines) and more focused targeting of those activities that are likely to have the biggest impact on the quality of clinical trials.

Data Management

The Addendum clearly states that its stringent recordkeeping criteria apply equally to electronic data capture programs and paper records. Under the modernized GCP, all clinical trial source data must be:

  • Attributable
  • Legible
  • Contemporaneous
  • Original
  • Accurate
  • Complete

Plus, changes to data collected must be traceable (via audit logs).

Additionally, sponsors must have written procedures in place for all electronic systems used in research, with SOPs drafted to address validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. The responsibilities for the use and training of the electronic systems must also be clearly defined.

These revisions are a clear effort by ICH to keep up with the increased utilization of electronic data capture systems in clinical trials, and while utilizing electronic platforms in research is relatively common, sponsors now must routinely engage experts in information technology, information security, systems engineering, and so forth when developing and overseeing electronic documentation and data capture systems.

For any sponsor lacking in these essential functions and expertise, the GCP Addendum means a significant investment in data infrastructure and staffing.

CRO and Vendor Oversight

Given the pace at which research is moving and the complexity of modern clinical trials, greater reliance has been placed on contract research organizations (CROs) and vendors in carrying out clinical trials. Consequentially, many integral study-related tasks have been delegated to third parties. In the wake of audits that identified regular lapses in such monitoring, questions were raised whether sponsors have taken enough care to ensure they retain an ability to effectively monitor their own research.

The Addendum stresses that sponsors are responsible for the ongoing management of their clinical trials and must maintain appropriate oversight over its vendors, including ensuring documented approval of any research-related duties assigned to CROs and other third party vendors.


Historically, GCP has remained largely silent on how to resolve incidences of noncompliance. Indeed, typically noncompliance has been met with minimal steps, usually only involving retraining of implicated parties.

Through the Addendum, GCP now includes utilization of root cause analysis (RCA) and implementation of corrective and preventive actions (CAPA).

Sponsors are additionally responsible—if required by local authorities or regulations—for notifying regulatory authorities on:

  • Serious breaches of protocol,
  • Violations of GCP standards, and
  • Noncompliance that significantly affects human subject protection or clinical trial results.

These procedural changes will, in many cases, demand that sponsors and investigators become more knowledgeable and proactive in identifying incidents of noncompliance as well as resolving them through RCAs and CAPAs.

Adequate Resources and Recordkeeping

The Addendum tasks investigators with assuring that there is a suitable monitoring plan in place to supervise the site research personnel. Further, it falls on the investigator to ensure that any third party is qualified to perform contracted study tasks, including implementing procedures to ensure the integrity of the study tasks performed and any data subsequently generated.

The investigator must also maintain records for all critical processes and clear documented evidence of his or her oversight and involvement in the trial.

While the new Addendum provides more depth and breadth to an already existing framework, its requirements should not be new to investigators, as it underscores longstanding human subject protections principles.


Meeting Modern Expectations

The ICH GCP E6 is the worldwide standard by which clinical trials are conducted, and the new R2 Addendum ensures these standards stay current with advances in clinical trial implementation, data capture, and outsourcing while continuing to prioritize compliance with human subject protection principles and participant safety. Not only is this move in line with modernization efforts from other agencies, it is a necessary step to ensuring that the rights, safety, and welfare of participants remain protected.

It is now up to sponsors and investigators to ensure their research programs rise to the GCP’s new expectations, including engaging with regulatory and technical experts as needed.


Executive Insight

Mitchell Parrish, JD, RAC, CIP, VP of Legal and Regulatory Affairs


ICH GCP’s new Addendum largely flew under the radar since its release coincided with the 58th presidential election.  No matter the administration or any nationalist sentiment, the world is a global market with significant success achieved through cooperation. ICH GCP is a prime example of this cooperation and has helped foster the development of beneficial drugs in the U.S., Europe Union, Japan, and elsewhere. It is easy to overlook the new Addendum, given the two behemoths impacting clinical trials in the U.S.: the 21st Century Cures Act and the new Common Rule.

However, for a significant portion of those conducting drug research in the U.S., and to IRBs reviewing that research, compliance with the new Addendum is a reality not to be overlooked.

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