Clinical trials and Good Clinical Practice (GCP)
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Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting clinical trials that involve the participation of human subjects.1
Regardless of whether a clinical trial is a large, multi-centre study in patients or a small clinical pharmacological study in healthy subjects, the relevant GCP standard should be followed by the sponsoring company of the healthcare product, the investigators, the ethics committees and any clinical research organizations.
Companies undertaking a clinical trial must follow certain procedures and practices
Companies undertaking a clinical trial should develop written procedures for implementing GCP.2 Such procedures may include, but are not limited to, the following:
- Investigator site selection
- Regulatory document collection, review and submission
- Financial disclosure
- Investigator site initiation
- Investigational product distribution and tracking
- Clinical monitoring of investigator site
- Investigator site close-out
- Safety reporting
- Quality assurance audits
- Required documents for study master file and document retention
- Vendor qualification and oversight (for example, contract research organization)
- Indemnity, compensation and insurance
Good Clinical Practice and the International Conference on Harmonisation
Prior to the GCP guidance document developed by the International Conference on Harmonisation (ICH), different jurisdictions had different guidelines relating to the conduct of clinical trials. With the introduction of ICH GCP, the conduct of clinical trials globally has become more uniform and practicable. Today, the implementation of ICH good clinical practice in most jurisdictions is reasonably similar and the vast majority of the regulations are the same.
Despite the effort of ICH, there still exists some local differences. For example, the US no longer adheres to the Declaration of Helsinki in its entirety, because the declaration considers placebo-controlled trials unethical in cases where an active drug is available. New privacy regulations in the EU and the financial disclosure requirements in the US are also making the clinical trial landscape more complicated.3,4 Healthcare product developers should therefore work to ICH in the context of local regulations.
GCP principles for clinical trials
The regulations, guidance and industry standards that make up Good Clinical Practice are intended to provide assurance that the rights, safety and well-being of clinical trial subjects are protected. GCP is also intended to assure that the research yields quality scientific data. 5-7 Fundamentally, Good Clinical Practice requires:
- Oversight of the local ethics committee(s)
- Verification of the investigator’s qualifications
- A study protocol, investigator’s brochure,* informed consent, and the documentation that is essential for undertaking a clinical trial
- Monitoring of the clinical trial
- Submission of reports and maintenance of records
The ICH GCP lays out the responsibilities of the ethics committees, sponsors and investigators.
The core principles of ICH Good Clinical Practice are presented below1,5.
Thirteen core principles of GCP
| Ethical principles: Declaration of Helsinki | Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with GCP and applicable regulatory requirement(s). |
| Favourable benefit(s) vs. risk(s) | Before a clinical trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A clinical trial should be initiated and continued only if the anticipated benefits justify the risks. |
| Subject’s rights | The rights, safety and well-being of the trial subjects override the interests of science and society. |
| Adequate supporting data | The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial. |
| Scientifically sound protocol | Clinical trials should be scientifically sound and described in a clear, detailed protocol. |
| Independent ethics committee oversight | A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval or favourable opinion. |
| Medical care by qualified investigator | The medical care given to subjects, and the medical decisions made on their behalf, should always be the responsibility of a qualified physician or, when appropriate, a qualified dentist. |
| Qualified personnel | Each individual involved in conducting a clinical trial should be qualified by education, training and experience to do their respective task(s). |
| Informed consent | Freely-given informed consent should be obtained from every subject prior to participation in the clinical trial. |
| Record-keeping | All clinical trial information should be recorded, handled and stored in a way that allows its accurate reporting, interpretation and verification. |
| Subject confidentiality | The confidentiality of records that could identify subjects should be protected―respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s). |
| GMP manufacturing of the investigational product | Investigational products should be manufactured, handled and stored in accordance with applicable Good Manufacturing Practice (GMP). They should be used in accordance with the approved protocol. |
| Quality assurance & monitoring | Systems with procedures that assure the quality of every aspect of the clinical trial should be implemented. |
GCP: Related regulations and guidance documents
For further reading, key documents related to GCP are listed below.
- International Conference on Harmonisation (ICH). ICH E6(R1) Notice for Guidance on Good Clinical Practice: Consolidated Guideline
- US Code of Federal Regulations, Title 21:
- Part 50, Protection of Human Subjects
- Part 54, Financial disclosure by clinical investigators
- Part 56, Institutional review board
- US Code of Federal Regulations, Title 45, Part 46, subtitle A, Protection of Human subjects
- US Health Insurance Portability & Accountability Act (HIPAA): US Code of Federal Regulations, Title 45 Part 160, and Subparts A and E of Part 164.
- EU Clinical Trials Directive (2001/20/EC)
- EU GCP Directive (2005/28/EC)
- Health Canada. Regulations amending the Food and Drug Regulations (Schedule No. 1024 – Clinical Trials). Division 5. Drugs for Clinical Trials Involving Human Subjects.
- Department of Justice Canada. Personal Information Protection and Electronic Documents Act
- ISO 14155. Clinical investigation of medical devices for human subjects―Good clinical practice
* A product information brochure, package leaflet or labelling may be an appropriate alternative as permitted by regulatory agencies.
Summary: Companies undertaking a clinical trial should follow Good Clinical Practice (GCP), an international ethical and scientific quality standard for clinical trials involving human subjects.
Disclaimer
The information presented in these articles is intended to outline the general processes, principles and concepts of the healthcare product development lifecycle. Since regulatory requirements are ever-changing, it is current only as of the date of publication and not intended to provide detailed instructions for product development. Every healthcare product is unique and therefore so is its associated product development lifecycle. Specific advice should be sought from a qualified healthcare or other appropriate professional.
Published: October 17, 2012
References
- Tobin, J.J. & Walsh, G. (2008). Chapter 5. Clinical trial. In Medical product regulatory affairs. Pharmaceuticals, diagnostics, medical devices. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA.
- Buckley, B. & Blanks, R. (2008). Chapter 8. Overview of the GxPs for the regulatory professional. In Pisano, D.J., Mantus, D.S. (Eds.), FDA regulatory affairs. A guide for prescription drugs, medical devices and biologics. (2nd ed.). New York: Informa Healthcare.
- Darwin, K.L.R. (2009). Chapter 7. Conduct of clinical trials: Good Clinical Practice. In Griffin, J.P. (Ed) The textbook of pharmaceutical medicine. (6th ed.). West Sussex: John Wiley & Sons Ltd.
- Kolman, J., Meng, P. & Scott, G. (1998). Introduction. In Good clinical practice: Standard operating procedures for clinical researchers. West Sussex: John Wiley & Sons Ltd.
- International Conference on Harmonisation. (1996, June). E6(R1): Good clinical practice. Retrieved July 12, 2012, from http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_R1__Guideline.pdf.
- Becker, K.M. & Whyte, J.J. (2006). Clinical evaluation of medical devices. Principles and case studies. (2nd ed.). Totowa: Humana Press.
- Brody, T. (2012). Clinical Trials: Study Design, Endpoints and Biomarkers, Drug Safety, and FDA and ICH Guidelines. London: Academic Press.