Janice Stack

As commonly defined, Good Clinical Practice (GCP) is an international ethical and scientific quality standard for the design and conduct of clinical trials involving humans. The primary objectives of GCP are to protect the safety, rights, and welfare of subjects, and to ensure the credibility of trial data and resulting reports. The need for ethical standards in clinical practice came about in response to instances of data fraud and other scientific misconduct, and as a result of numerous examples of violations of human rights in research such as those committed in the Tuskegee syphilis study where subjects were never told they had syphilis and were never treated for it.  

The Food and Drug Administration has had GCP regulations in place since the 1970s and these were expanded in 1997 with the addition of E6 GCP to the Federal Register. E6 GCP states that individuals performing clinical research must be qualified by training and experience (21 CFR 312.53: Selecting Investigators and Monitors; ICH E6 5.18.2: Monitoring; ICH E6 5.5.1: Trial Management Data Handling, Record Keeping), although specific standards of GCP training are not referenced. 

Pharmaceutical companies initially responded to E6 GCP by placing more emphasis on implementing GCP training for investigator sites. Basic training was (and is) offered at investigator meetings, but it often includes nothing more than a high-level overview and, because it is often time constrained, it may not include all of the critical elements. There is typically no knowledge check or completion documentation at the end of these sessions, so it may not qualify as GCP certification.  

As the need for improved GCP training was recognized, many pharmaceutical companies developed intensive, instructor-led, in-house courses for their clinical operations staff. Although many of these courses included practical application exercises, there was often no knowledge check, so the value was greatly diminished. This is also a costly method of instruction for companies if decentralized staff members are expected to attend in person. For this reason, many companies progressed to web-based programs or other methods of training for both investigational and operational staff. In addition to in-house or web-based instruction, sponsor companies and CROs may use an independent GCP training consultant to implement company-specific GCP training or may send staff to a clinical research, professional society, or commercial training course. Some companies offer only a slide review followed by a knowledge check to document their training.  

Current GCP expectations are that principals investigators and sub-investigators are trained in GCP and that this training is documented and tracked. It is expected that sponsors' clinical operations staff members are also trained in GCP, but there are varying requirements for refresher courses, documentation, and tracking. Regulatory agencies may have a reasonable expectation that clinical staff members are GCP-qualified, but currently there is no guidance that specifically defines what topics GCP training should include.  

Typically, courses available from professional societies include topics such as the history of GCP, sponsor and investigator responsibilities, informed consent, good documentation practices, safety, essential documents, audits, and inspections. This training is often static and may not cover current issues related to evolving technology, security/confidentiality, corrective and preventative actions (CAPA) and recent agency warning letters. Additionally, there is no defined time frame for refresher training, which can be a valuable component of actually delivering GCP. Ideally, refresher training would provide updates from practical audit and inspection experience such as warning letters as well as new regulations and regulatory guidance.  

There are many challenges involved with effective GCP training, not the least of which are adverse effects on sponsor/staff relationships that can occur when staff members are required to complete different GCP courses for multiple sponsors. With time frames for start-up decreasing, ensuring completion of GCP training can be a factor that delays the start of the study.  

If GCP training is to keep pace with the ever-changing regulatory environment, a method of standardizing its implementation must be developed that can answer questions such as these:  

Is it acceptable to just offer a GCP course once at the time of onboarding or must refreshers be required? 

Who is responsible for documenting the training and what is the appropriate amount of documentation needed?  

Is it enough to provide a completion date or should participants be tested? 

If they are tested, what is the passing threshold?  

Who is the appropriate audience for GCP training? Should study coordinators, medical writers, data management staff, and people fulfilling other roles involved with clinical trials also be trained?  

To solve the inconsistencies in GCP training, a centralized group representing global regulatory agencies and clinical research associations should be charged with designing and implementing a standard GCP course that can be offered to all appropriate individuals across all regions.  

A web-based course that includes comprehensive testing and practical application scenarios could work best. All parties would have access to the training 24/7, and the course would be updated as new information becomes available. To make sure GCP training remains effective, a standard interval for retraining would be established and maintained through a central database. Investigator and site staff as well as clinical operations staff would benefit by completing and being certified in a single course that applies to all studies from all sponsors.  

A standardized methodology is more efficient on many levels, including cost, scheduling, and time invested in completing the training. The initial cost to develop the standard training may be high in order to satisfy requirements of all countries and regions, but the downstream benefit is incalculable in terms of reduced training time, standardization of knowledge, and credible certification of clinical staff available to all sponsors.  

Since its inception in 1990, the ICH has evolved the standards that constitute GCP. The ICH could be the logical international body to take the steps necessary to design and implement a universal GCP training program and a global database of certified clinical personnel. 

— Jeanne Green is Senior Director of Clinical Operations and Janice Stack is the Training Director both at ExecuPharm.

Articles

The primary objectives of GCP are to protect the safety, rights, and welfare of subjects, and to ensure the credibility of trial data and resulting reports.

Janice Stack

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The Case for Universal GCP Education