"Conducting Clinical Trials A-Z"

What regulations and guidelines must be followed?

In addition to ethical considerations, the Federal Government provides a statutory framework of legal standards pertaining to clinical and human subject research.

Code of Federal Regulation (CFR) – laws enforced by the Food and Drug Administration (FDA) detailing the processes and procedures for conducting clinical research. The FDA provides guidance websites for conducting clinical trials with investigational drugs and information for compliance with the regulations of the Food and Drug Administration.

Specific law is Title 21, Chapter 1 (8 volumes)

Good Clinical Practices (GCP) are Parts 50 (responsibility for informed consent)

          Part 50 - Responsibility for Informed Consent
          Part 54 - Financial Disclosure by Clinical Investigators
          Part 56 - IRB
          Part 11 – Electronic records
          Part 312 – IND – Investigator Responsibilities Drug Reserch
          Part 314 – NDA – New Drug Approval
          Part 812 – IDE - Investigator Responsibilities Device Research
          Part 814 – PMA – Pre Marketing Approval

DHHS 45 CFR 46 deals with Protections of Human Subjects with subparts for special populations

A –core requirements Common Rule – refers to the US federal policy that provides regulations for human subject protection

Sixteen government agencies that conduct regulate or fund human research have signed on to comply with the provisions of the common rule.

B – fetuses/Pregnant Women
C – Prisoners
D – Children (adopted also by FDA)

The University of Kentucky has a federal wide assurance FWA of compliance with common rule for all research.

State Law & Institutional Policy

State laws can have implications on human subject research. 

In addition, be aware of institutional policies that may affect research conduct, such as UK hospital policy 06-09 on signature of legal representatives.

Regulatory agencies continue to work toward harmonization of guidelines; however there are some differences in specificity, detail and application.  In addition, local institutional policies such as detailed IRB policies will typically supersede the more general federal regulations. In these instances, the best practice will be to follow the strictest interpretation.

The International Conference of Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. 

Worldwide standard for conduct of clinical trials –

Was a joint project between regulatory authorities from Europe, USA, and Japan along with industry to improve the process for developing and registering new medical products.  Harmonization would “standardize” the rules so that studies conducted in one ICH region could be used by others in evaluating new drugs.

GCPs are basically the rules for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials.  They provide assurance that data and results are based on sound scientific and ethical research. They are a broad set of requirements, standards, and recommendations that apply to thousands of highly specific tasks.

In the US, GCPs are defined by federal law and enforced by the FDA

THE PRINCIPLES OF ICH GCP

2.1 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 the applicable regulatory requirement(s).

2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.

2.3 The rights, safety, and well-being of the trial subjects are the most important
considerations and should prevail over interests of science and society.

2.4 The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.

2.5 Clinical trials should be scientifically sound, and described in a clear, detailed protocol.

2.6 A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favorable opinion.

2.7 The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.

2.8 Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s).

2.9 Freely given informed consent should be obtained from every subject prior to
clinical trial participation.

2.10 All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification.

2.11 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).

2.12 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.

2.13 Systems with procedures that assure the quality of every aspect of the trial should be implemented.

TITLE 21, CODE OF FEDERAL REGULATIONS (CFR)

STATEMENT OF INVESTIGATOR – FDA Form 1572