Good clinical practice (GCP) guidelines govern important aspects of clinical trials to ensure patient safety and scientific integrity. “GCP” is a quality standard which refers to the document put forth by the International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The ICH is a group made up of regulatory officials from the United States, Europe, and Japan, as well as representatives from the pharmaceutical industry. Additionally, a similar of guideline, ISO 14155:2011 has also been established by the International Organization for Standardization (ISO) and is used throughout the European Union and generally accepted globally. While not regulatory documents in themselves, these two guidelines serve as the basis for legislation in many countries around the world.
Foundations of GCP
GCP guidelines have their roots in the Nuremberg Code, which were 10 ethical principles established at the end of World War II in response to Nazi experiments. The focus of this code covered three main areas:
- Informed consent
- Risk minimization
- Study rationale
Later on, the 1964 Declaration of Helsinki further defined ethical research conduct, urging researchers to state: “The health of my patient will be my first consideration.” This document has since gone through numerous revisions with the seventh and most recent update in 2013. While the Declaration of Helsinki has formed the backbone of regulations regarding human subject research, a 2000 update limiting the use of placebos and increasing the responsibilities of trial sponsors toward research participants lead to the FDA removing references to the document.
Obtaining Informed Consent
To comply with GCP standards, written informed consent must be obtained before enrollment and trial-specific screening activities. Exceptions are made for urgent, life-threatening situations as defined by the protocol. Consent must be freely given with no coercion or pressure for the patient to participate and the right to withdraw at any time without detriment. For patients who cannot read or write, an independent witness must be present throughout the process.
In certain populations, special ethical considerations are necessary to ensure patients are protected. For these groups, a legally authorized representative may sign consent forms on the patient’s behalf. These groups include patients who are:
- Unconscious due to illness or injury
- Otherwise seriously ill
- children under the age of legal consent
- Cognitively handicapped
- Mentally ill
However, in these cases, the participant should still be informed as much as possible within his or her ability to understand.
According to ISO standards, study patients — and their authorized representatives when applicable — must be provided with the following information about the trial before consent can be given:
- A description of the clinical investigation and its objectives
- Potential benefits of participation
- Possible risks and inconveniences for the patient
- Alternative procedures
- Any associated costs for which the patient is responsible
- Right to withdraw
- Role of the sponsor’s representative
- How important new information will be communicated
- Notification methods for personal physicians
- The conditions and processes of study termination
- Various additional statements to protect study patients, including their rights as human research subjects
Drafting Study Protocols
The content and format of study protocols — or clinical investigation plans, as they are termed in medical device trials — are well-defined by both ICH GCP and ISO standards. Some key aspects include:
- Well-defined dose rational, including route of administration and duration of treatment, that is based on either early phase trials or preclinical data
- Adequate safety monitoring and reporting, including follow-up after the trial’s conclusion
- Inclusion/exclusion criteria that concretely define the study population
- Main and possible secondary objectives of the trial
Other Important GCP Standards
Study sponsors are responsible for ensuring GCP standards are followed. When GCP-related activities are outsourced, the sponsor must demonstrate adequate oversight. This includes mandatory pre-assessment visits to each investigator site to assess capabilities, followed by site selection and initiation visits.
While declaration of conflicts of interest are not mentioned in ICH GCP itself, these are a basic regulatory requirement in many countries. In the U.S., an FDA financial disclosure form must completed by all investigators. Additionally, some countries, such as the U.K., require that sponsors and all relevant parties must be insured prior to starting trial.