Clinical Regulations

Clinical Regulations

• Clinical trials are a critical stage in the regulatory process, establishing the safety and efficacy of a drug in humans.
• Regulations governing clinical trials ensure the safety, welfare, and rights of subjects participating in the trials are protected, and scientifically useful and valid data are collected.

Clinical Trials

• Purpose: Establish a drug therapy that is safe and effective in humans, with an acceptable risk-benefit relationship.
• ICH definition: Investigations in human subjects to discover or verify clinical, pharmacological, and/or pharmacodynamic effects of an investigational medicinal product.
• Process: Phase I, Phase II, and Phase III; Phase IV: Safety studies (may be conducted post-approval).

Clinical Trial Design

• Key element: Ensure scientific validity and objectivity, demonstrating a positive benefit to risk outcome.
• Studies can be broadly divided into two types: confirmatory studies (to prove or disprove pre-defined hypotheses) and exploratory studies (where outcomes may not be clear in advance).
• Designed to minimize potential sources of bias, e.g., blinded trial designs.

Good Clinical Practice (GCP)

• Must be conducted in accordance with GCP principles, an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials.
• Ensures the rights, safety, and well-being of trial subjects are protected, and clinical trial data are credible.
• Harmonized guidance document on GCP developed by ICH (ICH E6).

The Sponsor

• Initiates the process of conducting clinical trials, responsible for initiation, management, and/or financing.
• Ensures trials are conducted according to regulations and GCP principles.
• Responsible for documenting, analyzing, and reporting data according to established SOPs.

The Investigator's Brochure (IB)

• Compilation of available clinical and non-clinical data on the investigational medicinal product.
• Includes a description of the physical, chemical, and pharmaceutical properties of the drug substance and product.
• Provides investigators with sufficient information to facilitate their understanding of the trial protocol.

The Investigator

• Responsible for the conduct of the trial at the trial site.
• Must be a doctor or other appropriately qualified medical personnel.
• Manages recruitment of subjects, administration of drugs, and monitoring and recording of responses.
• Ultimate purpose is to guard the health and welfare of subjects.

Clinical Trial Application (CTA)

• Submission to the competent National Regulatory Authority for obtaining authorization to conduct a clinical trial in a specific country.
• Provides necessary information on investigational medicinal products.

Independent Ethics Committee

• Focuses on ensuring the rights, safety, and welfare of human subjects involved in a trial are protected.
• Generates public confidence in the process.
• Consists of both healthcare professionals and lay members.

Amendments to Clinical Trials

• Sponsor may need to amend a clinical trial due to new information.
• Notifies the Competent Authority and the Ethics Committee using a Trial Amendment Form.
• Ethics Committee has 35 days to approve the amendment.

Case Report Forms (CRFs)

• Record all protocol-required data at the trial site.
• Data for individual subjects are recorded on separate CRFs.
• Used to transfer trial data to the sponsor for analysis and evaluation.

Adverse Event Reporting

• Serious adverse event or reaction: any untoward medical occurrence or effect that results in death, is life-threatening, requires hospitalization, or results in persistent or significant disability.
• Suspected Unexpected Serious Adverse Reactions (SUSARs): reported to the Ethics Committee and the Competent Authority within 7 days (fatal or life-threatening) or 15 days.

Annual Safety Report

• Sponsors submit a safety report to the Competent Authority and the Ethics Committee once a year throughout the clinical trial.
• Covers SUSARs, other serious adverse reactions, and an analysis of the subject's safety during the trial.

Monitoring of Trials

• Sponsor appoints clinical trial monitors to oversee that trials are conducted and correctly documented in accordance with the protocol and GCP.
• Monitors regularly visit the trial site to verify that related laboratories or sponsor's facilities are conducted in accordance with applicable protocols, procedures, regulations, GCP, and GLP.

End of Trial

• Sponsor must inform the Competent Authority and the Ethics Committee of the end of a trial within 90 days of its completion.