GLP and GCP notes

Good Laboratory Practice (GLP)

GLP ensures the quality, integrity, and reliability of non-clinical laboratory studies, particularly preclinical safety studies submitted to regulatory authorities. Originating in the 1970s due to fraudulent activities, GLP provides a framework for planning, performing, monitoring, recording, reporting, and archiving lab studies. It helps assure regulatory authorities that data accurately reflects study results for risk/safety assessments.

Key principles based on OECD guidelines:

  • Test Facility Organisation and Personnel: Clear structure, defined roles, and documented training.

  • Quality Assurance Programme: Independent QA system for GLP compliance through inspections and audits.

  • Facilities: Suitable facilities designed to prevent contamination.

  • Apparatus, Materials, and Reagents: Maintained equipment and clearly labeled materials.

  • Test Systems: Proper biological or chemical test system conditions.

  • Test and Reference Items: Clear identification, storage, and documentation of test substances and reference materials.

  • Standard Operating Procedures (SOPs): Documented procedures for routine tasks.

  • Performance of the Study: Detailed study plan with documented amendments.

  • Reporting of Study Results: Accurate reports including raw data, deviations, and QA statements.

  • Storage and Retention of Records and Materials: Secure archiving for required periods.

Good Clinical Practice (GCP)

GCP is an international ethical and scientific quality standard for designing, recording, and reporting trials involving human subjects. Compliance ensures the protection of subjects' rights, safety, and well-being, and the credibility of clinical trial data. Key elements include IRB/IEC assessment, qualified investigators, and a responsible sponsor.

ICH GCP Principles:

  1. Ethical principles from Declaration of Helsinki.

  2. Weighing risks against benefits.

  3. Prioritizing subject rights, safety, and well-being.

  4. Adequate non-clinical and clinical information on the investigational product.

  5. Scientifically sound protocol.

  6. Compliance with IRB/IEC-approved protocol.

  7. Medical care by qualified physician.

  8. Qualified research staff.

  9. Informed consent.

  10. Accurate data recording and handling.

  11. Confidentiality of records.

  12. GMP for investigational products.

  13. Quality systems.

Clinical Trial Phases

  • Phase 1: Assesses safety and tolerability in healthy volunteers.

  • Phase 2: Evaluates drug's effectiveness and optimal dosage in patients with the condition.

  • Phase 3: Confirms effectiveness, monitors side effects, and compares the drug to placebos.

  • Phase 4: Post-market studies to answer further questions about effectiveness and safety.

Combination Trials

Drug trial phases are sometimes combined to streamline development, reduce costs, and accelerate approval.

  • Phase I/II Trials

  • Phase II/III Trials

  • Phase I/II/III Trials

Clinical Trial Designs

  • Allocation methods: Non-randomized vs. randomized controlled trials.

  • Awareness: Single-blind vs. double-blind studies.

  • Expected outcome: Superiority vs. non-inferiority trials.

Clinical Trial Design classificiations:

  • Absence/presence of control group

  • Participant allocation method

  • Participants'/investigators' awareness of treatment group

  • Significance of expected result between groups

  • Treatment structure

Power in Clinical Trials

Power refers to the probability of correctly detecting a treatment effect if one exists. It measures the study’s sensitivity and is usually set at a pre-specified level (e.g., 80%, 90%) before the study begins.

Clinical Trial Designs Details

  • Uncontrolled Trials: Medication efficacy/toxicity compared without a control group, common in Phases I and II.

  • Controlled Trials: Compared to a control group (placebo or another treatment), common in Phase III.

  • Non-Randomized Trials: Investigator allocates participants.

  • Randomized Controlled Trials: Participants randomly assigned.

Blinding

Blinding seeks to eliminate source of bias.

A study may be designed so the patient is unaware of the treatment being administered. This is a single blind study.

A study may be designed so that neither the patient nor the invesigators are aware of the treatment being administered. This is a double blind study.

Parallel group trial design

In parallel group randomisation, after randomisation, each participant stays in their assigned treatment arm for the duration of the study.

Cross-over trial design

Cross-over randomisation is when participants receive a sequence of different treatments

Matched-pair design

In the matched-pair design, participants are first matched in pairs according to certain characteristics. Then, each member of a pair is randomly assigned to one of the two different study subgroups.

Withdrawal trials

In a withdrawal trial, the participant receives a test treatment for a specified time and are then randomised to continue either with the test treatment or a placebo (withdrawal of active therapy).

Factorial design

Factorial clinical trials test the effect of more than one treatment. This allows assessment of potential interactions among the treatments