Clinical trials and Drug DIscovery PSY2003

Biblical Origins

Early anecdotal example of dietary comparison—vegetarians appeared healthier than meat eaters after 10 days.

James Lind (1747)

First controlled trial on sailors with scurvy; identified citrus fruits (oranges and lemons) as effective treatments.

Edward Jenner (1796)

Developed the first experimental vaccination (cowpox against smallpox). While unethically conducted by today's standards, it laid the foundation for modern immunisation and clinical validation.

Intro to Placeba (1800's)

First defined as medicine given more to please than to treat. Used by Austin Flint in rheumatism trials.

First Double-Blind trial (1943)

Medical Research Council (UK) tested Patulin for the common cold.

First Randomised Curative Trial (1946)

Streptomycin for tuberculosis introduced systematic randomisation and blinding. This study set global standards and led to the development of regulatory frameworks.

Clinical Trial Definition

A medical research study involving people, used to:

Prevent disease

Improve treatment and cure rates

Enhance quality of life

Test diagnostic methods or lifestyle interventions

Clin Trial Steps

Systematic Review

Trial Design and Protocol Development

Ethical Approval

Sponsorship

Recruitment and Informed Consent

Trial Execution

Publication and follow up

Phase 1

Safety, small group (healthy volunteers)

Phase 2

Larger group, assess side effects and initial efficacy

Phase 3

Hundreds/thousands; compare to standard treaments, monitor side effects

Phase 4

Post-marketing surveillance; long-term risks and effectiveness

Controlled Trial

Compares a treatment group with a control (standard treatment or placebo).

Blind Trial

Participants are unaware of their treatment group.

Double-Blind

Neither participants nor researchers know the treatment allocation.

Randomisation

Participants are randomly assigned to groups, often via computer, to prevent selection bias.

Informed Consent

Participants (or guardians) must be fully informed of the trial's purpose, risks, and procedures and agree voluntarily.

Academics and Researchers

Design trials, conduct experiments, collect and analyse data.

Ensure research is ethical, valid, and meaningful.

Adhere to Good Laboratory Practice (GLP).

Trial Sponsors

Can be NHS Trusts, universities, or pharmaceutical companies.

Responsible for funding, compliance, and risk management.

Patients

Voluntarily participate after informed consent.

May benefit from early access to new treatments or contribute to scientific knowledge.

Ethics Committees

Review study protocols to safeguard participant welfare and ensure scientific validity.

Trial Managers and Statisticians

Coordinate logistics, manage data collection, ensure accuracy in analysis.

Institutions

Provide infrastructure, personnel, and insurance.

Ensure governance and adherence to national and international regulations.

Discovery stage

Identify promising compounds through:

-Disease mechanism insights

-High-throughput screening (HTS)

-Repurposing of existing drugs

-Novel delivery systems (e.g., across blood-brain barrier)

Pre-Clinical Development

In vitro (cell-based) and in vivo (animal) studies to assess:

-Absorption, distribution, metabolism, excretion (ADME)

-Toxicity and interactions

-Mechanism of action

Good Laboratory Practice (GLP)

Ensures standardisation and ethical conduct:

-Trained personnel

-Validated equipment and facilities

-Quality assurance and documentation

Transition to Clinical Trials

Only a few compounds make it past discovery into clinical testing.

Known as the "Valley of Death" due to high cost and failure rate (only 1 in 10 drugs succeed).