Good Clinical Practice (GCP)

Good Clinical Practice is defined as a “standard for designing, conducting, recording and reporting trials that involve the participation of human subjects” ^{[1, 2]}.

References to ‘GCP’ can sometimes be confusing because some research professionals use the term generically as a way to define how research is conducted, whereas others are actually referencing a specific guidance document on GCP.  The concept of GCP is, however, much broader than a single guidance document. Rather, GCP is “an attitude of excellence in research” ^[5] that encompasses the principles and obligations set forth in the various documents and regulations that guide the conduct of human subject research.

In other words, GCP is a compilation of the underlying principles described in the Nuremberg Code, Declaration of Helsinki, Belmont Report, Code of Federal Regulations (Department of Health & Human Service [HHS] and Food & Drug Administration [FDA]), International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice, and International Standards Organization (ISO) 14155 Clinical Investigation of Medical Devices for Human Subjects – Good Clinical Practice ^{[3, 4, 5, 6,]}.

Common among these documents are standards (i.e., GCPs) related to:

• Conducting scientifically sound research that is of benefit to society;
• Ensuring a favorable risk:benefit ratio of the research;
• Ensuring subject safety prevails over societal benefit;
• Selecting subjects equitably;
• Obtaining independent ethics committee (i.e., Institutional Review Board [IRB]) approval;
• Protecting vulnerable populations;
• Conducting research in accordance with the approved study protocol;
• Obtaining voluntary informed consent;
• Limiting involvement in the conduct of research to those with adequate qualifications and experience;
• Appropriately accounting for investigational product;
• Protecting subject privacy and maintaining the confidentiality of the data;
• Assuring data integrity and quality; and
• Appropriately documenting the research.

The regulations and policies you’re required to comply with depend on the nature of your research and will vary from study to study based on who initiates the research, the interventions, procedures and risks involved, and the funding source.

From a regulatory standpoint, per institutional policy, all research conducted at the University of Rochester with human subjects must minimally comply with HHS regulations (45 CFR 46).  If the research also involves a test article (drug, biologic, device [including in vitro diagnostic devices] or supplement) or is funded by the FDA, study staff must further comply with applicable FDA regulations (21 CFR 11; 21 CFR 50; 21 CFR 54; 21 CFR 56; 21 CFR 312; 21 CFR 812).  Additional regulations that may apply include:

• Regulations set forth by different HHS agencies such as the Department of Defense or Department of Education, when an HHS agency funds the research or when the agency imposes requirements based on the study population (e.g., students);
• Regulations defined by the Health Insurance Portability & Accountability Act, when the research involves the use and/or disclosure of protected health information by a covered entity;
• Tribal law, when the research is conducted in a setting governed by tribal law; and
• Regulations from other countries, when the research is conducted abroad.

Beyond regulatory compliance, study staff must also minimally comply with institutional policy, policy set forth by the Reviewing IRB, and the IRB-approved study protocol.

Guidance documents provide recommendations and best practices for how to comply with regulations; they are not, by definition, regulation. In fact, most guidance documents related to the conduct of human subject research published by HHS or the FDA state that the ‘guidance represents the current thinking’ of the agency and the information provided is not legally binding ^[1].

So, when asked the question ‘do I have to comply with guidance?’ the answer is technically no. However, given the variation in how regulations can be interpreted, following the advice provided in guidance documentation is strong encouraged.

Study teams should equate guidance documents to a play book or treasure map; if someone provided you a play book that enhanced your ability to ‘play the game’ or a map of how to reach your goal, wouldn’t you follow it? Following the recommendations provided in published guidance documents betters your chances of protecting subjects, collecting quality data and minimizing non-compliance.

There is, of a course, a caveat to this, most notably in regards to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice (hereinafter ICH GCP) and the International Standards Organization 14155 Clinical Investigation of Medical Devices for Human Subjects – Good Clinical Practice (hereinafter ISO 14155). These guidance documents set forth international GCP standards for investigational products; ICH GCP has been adopted as guidance by the FDA and ISO 14155 has been recognized as a consensus standard. These international GCP standards were developed to streamline the drug and device development process and facilitate mutual acceptance of international clinical data by corresponding regulatory authorities (e.g., as support for a marketing application, the US FDA will accept data collected by a trial conducted in Japan, provided the study was conducted in accordance with ICH GCP). As such, study sponsors will often require compliance with ICH GCP and/or ISO 14155 (commonly identified in study protocol, on the protocol signature page or in the investigator agreement).

To reiterate, if your study protocol, clinical trial agreement, or any other study-specific documentation indicates that compliance with ICH GCP, ISO 14155 or any other regulation or guideline is required, then the study team is responsible for complying with such requirements.

Despite the word ‘clinical’ in the phrase Good Clinical Practices, the general principles considered to be GCP (bulleted in the ‘What is GCP?’ FAQ above) still generally apply to social-behavioral research.

Remember, as stated previously: GCP encompasses standards across several potential sources of compliance, including ethical principles and federal regulations that apply to social-behavioral research. Moreover, guidelines identified specifically as ‘GCP’ guidance define best practices for reaching your study’s aims and conducting sound research. Those recommendations within the guidance that don’t apply to social-behavioral research (e.g. test article accountability), simply don’t apply, though many do (as validated by a survey conducted by Murphy, et al.).

While the University of Rochester has not implemented a policy requiring GCP training for study staff (only human subject protection training is required), GCP training may be required for study staff:

• Sponsors, Department Chairs and Administrators/Supervisors may require GCP training.
• Most industry sponsors conducting research involving investigational products (drugs, devices, and biologics) will require GCP training.
• The National Institutes of Health (NIH) require all “investigators and staff who are involved in the conduct, oversight or management of clinical trials” to complete and maintain GCP training. Of note, NIH’s definition of clinical trials includes trials that are behavioral in nature; the policy defines a clinical trial as “as research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related or behavioral outcomes.”

All new and inexperienced research personnel, including investigators and study staff, are strongly encouraged to complete GCP training regardless of whether it is required.

GCP training is available for all University of Rochester faculty, staff and students through the Collaborative Institutional Training Initiative (CITI). To add GCP training to your training curriculum, reference CITI’s How to Add/Remove Courses. Note: When adding the course, trainees can opt to complete either a US FDA-Focused or Social-Behavioral-focused GCP course.

In lieu of CITI GCP training, sponsors may also accept training completed via another mutually recognized GCP training platform, as identified through Transcelerate BioPharma, Inc.’s ‘Mutual Recognition Program (reference a list of acceptable courses recognized in the program). Questions regarding whether a certain type/platform for GCP training is acceptable should be directed to the party/entity requiring the training.

1. Food & Drug Administration (FDA) Guidance for Industry – E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R2). (2018, March). Retrieved March 30, 2020 from the FDA
2. International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) – Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2). (2016, November 9).  Retrieved March 30, 2020 from the ICH
3. Moran, J., Stevens, E. & Statzel, J. (2013, May 09). Good clinical practice: Where ethics and quality meet. Regulatory Affairs Professional Society.
4. Murphy, S. L., Byks-Jazayeri, C., Calvin-Naylor, N., Divecha, V., Anderson, E., Eakin, B., Fair, A., & Denton, L. (2017). Best practices in social and behavioral research: report from the Enhancing Clinical Research Professional’s Training and Qualifications project. Journal of clinical and translational science, 1(1), 26–32. DOI source
5. Silver-Kessler, R. (n.d.) The Fundamentals of Good Clinical Practice [white paper published by IMARC Research]. Retrieved March 30, 2020 from IMARC Research.
6. York, R. (n.d.) Good Clinical Practice: from review to application [white paper published by IMARC Research]. Retrieved March 30, 2020 from IMARC Research.