Good Clinical Practice or GCP

Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects.  These standards are consistent with the principles that have their origin in the Declaration of Helsinki , one of the best known international reference codes of medical research ethics, first established in 1964.
In 1962, the Drug Amendment Act was approved in the United States.  This became the Food and Drug Administration (FDA) Regulations governing clinical research.  These regulations became a framework for legislation and guidelines covering the majority of clinical research that are now in place in almost every country in the world.
Guidelines for the conduct of medical research were subsequently developed in a number of European countries during the 1970s and 1980s, with some harmonization occurring in 1990. The Nordic GCP guidelines were also developed during this time.  Meanwhile, other regions of the world, Canada, Israel and Japan also developed GCP guidelines and the World Health Organization (WHO) issued their own set of GCP guidelines in 1993.  By that time, it was apparent that a global standard for GCP was required.
In 1991, the International Conference on Harmonization (ICH) recognized this need and formed an Expert Working Group to draft a guideline on GCP.  In May, 1996, this guideline was issued as final and referred to at the “ ICH E6 GCP Consolidated Guideline”. This guideline was then adopted by the three main ICH regions – Europe, the United States and Japan.  In countries and organizations outside the three ICH regions, the ICH GCP guideline quickly became the most widely accepted and followed GCP guideline, with many countries and regions implementing legislation which requires that the ICH GCP guidelines (among other things) be followed.


Even though the ICH-GCP Guidelines describe the responsibility for the investigator, sponsor and ethics committees, the intent of this presentation is to focus on your responsibilities as the Principal Investigator.

With the understanding that you may delegate some responsibilities, it is always the Principal Investigator who has the overall responsibility for all clinical trial activities conducted at the study site.

Some of the key responsibilities that we will review are:

• Medical care of subjects during the trial
• Required communication with the Ethics Committee 
• Protocol compliance 
• The need for providing study information to the study subjects and obtaining informed consent 
• The handling of clinical supplies, including drug storage and accountability
• Collecting protocol specified data, including the execution of any required protocol procedures
• The evaluation, review and reporting of the results related to the study subjects during the study
• Adverse experience assessment and reporting and finally,
• Maintenance of study documentation related to the clinical trial at the study site.

A clinical trial involves many tasks and activities.  Typically,  the Principal Investigator delegates some of these tasks and activities to other individuals.  Any delegation of study-related tasks must be to individuals who are qualified by education and/or training. The delegation of all study tasks and procedures must be documented on the Site Signature and Responsibility Log.  The intent is always to identify all study staff at your site and their delegated responsibilities.

When an individual either begins or ends responsibility for a designated activity during the course of a study the start and stop dates should be clearly indicated on the form.

All trial-related medical decisions are made by a qualified physician.  Therefore, you as the Principal Investigator may not delegate these responsibilities to a Nurse Care Practitioner or Physicians Assistant.  Examples of trial-related medical decisions include:

• Review and interpretation of ECGs and laboratory results
• Causality assessment of adverse experiences

Before initiating a trial, written approval from your local ethics committee  must be obtained.

Minimally, your ethics committee must approve: the trial protocol, the patient informed consent form and subject recruitment procedures as well as any other written information that will be provided to the study subjects. As Principle Investigator, you are responsible for ensuring that all ethics committee approvals have been appropriately obtained prior to initiation of the study at your site

As Principal Investigator you are responsible to report any deviations, changes or revisions to the approved protocol to your ethics committee.

You are required notify your ethics committee of all site-specific serious adverse events in accordance with the ethics committee requirements and/or local regulations.

Ethics committee requirements for these responsibilities vary and should be clearly understood prior to the start of the study. Please discuss any questions you may have with your Clinical Research Associate.

It is expected that all participating investigators will review the appropriate study documents, including the full protocol and Confidential Investigator’s Brochure (CIB).  By signing a protocol, you, as the Principal Investigator, accept responsibility for adhering to the protocol requirements. Remember, if, a deviation to the protocol occurs at your site, you must report the deviation to Merck and your ethics committee.

As noted previously, it is essential that  prior to carrying out any study related procedures at your site, the Ethics Committee have reviewed and approved the protocol and associated study documents