Clinical trial

[Wikipedia:"Clinical trial"]

Types of trials

Clinical trials and observational studies

Clinical trials = investigators manipulate the administration of a new intervention and measures the effect of that manipulation

Observational studies = Investigators observe associations/correlations between treatments experienced by participants and their disease/health

Phases of clinical trials

Clinical trials use human as test subjects.

Pre-clinical development involves drug being tested on animals.

Pre-clinical development

Main goal is to determine:

• Pharmacodynamics and pharmacokinetics
  * Including ADME (absorption, distribution, metabolism, excretion)
• Toxicity

Phase I

Small group (20-80) of healthy volunteers

Purpose of phase I

• Safety
• Tolerability
• PK and PD

May also include dose-ranging studies to refine doses for clinical use

Single-ascending dose (SAD) studies

A group of 3-6 patients is given a small dose, and if no adverse effects, give a new group a higher dose.

Maximum tolerated dose is determined when intolerable side effects start to appear

Multiple-ascending dose (MAD) studies

A group of patients initially receives a small dose, then dosage gradually increases to a predetermined level.

Used to improve understanding of the PK and PD of the drug

Phase II

Larger (20-300) group of patients

Purpose of phase II

• Assess clinical efficacy of the therapy in highly controlled environment
• Continue phase I assessments on a larger group

NB:

Often development fails in phase II due to discovery of poor efficacy or toxic effects

Phase IIA and IIB

Phase IIA = Specifically designed to assess dosing requirements

Phase IIB = Specifically designed to study efficacy

Phase III

Large patient group (300-3000 or more)

Double-blinded randomised controlled trials

Purpose of phase III

• Definitive assessment of efficacy, in comparison to gold standard treatment
  * In conditions of typical use

NB:

Regulatory submission is made after Phase III is completed

Phase IV

Involves post-launch safety surveillance and ongoing support of a drug.

May result in withdrawal or restriction of a drug
* e.g. rofecoxib (vioxx)