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Clinical trials come in a great variety and many forms. Simply put they are scientific studies related to the use of treatments or some medical intervention in humans. The term "clinical" relates to the use in a healthcare setting as opposed to a pre-clinical (e.g., cell or animal subject) study. The term "trial" relates to it being a planned scientific study.

Traditionally, clinical trials of drugs have been categorised by the phase of trial (I to IV), where each phase has a different design emphasis and overall objective as more is learned about the drug. The key areas of interest relate to the safety and efficacy, which is the therapeutic effect, of the treatment.

Characteristics of the four trial phases
Phase I Phase II Phase III Phase IV
Main objective

Dose determination

Escalation and safety

Preliminary assessment of efficacy and safety Confirmatory assessment of efficacy and safety Post-marketing surveillance
Size Circa 20-80 Circa 100-300 Circa 1000+ Unknown
Population Healthy volunteers / patients (maybe FIH) Subset of clinical population thought to benefit Clinical population thought to benefit Treated population
Design Usually single-arm, one centre Often controlled, maybe randomised, possibly multicentre Randomised, multicentre Typically passive, population
Key outcomes

Recommended dose

Maximum tolerable dose (MTD)


Disease activity

Clinical surrogate

Patient-orientated outcomes Adverse events

In simple terms for a new drug (see the figure above), a phase I study focuses on initial safety testing, and often first use in humans, phase II on dose optimisation, phase III on efficacy and safety in a relevant patient population, and phase IV on evaluation of use in routine clinical care. A phase I study of a new drug may be small in size, with say 20-80 participants, while a phase III trial may have 1000 or more participants. Phase IV studies can be much larger still (but perhaps only focussing on those who receive the drug), and phase II studies are somewhere in between a phase I and III trial. However, there are no strict rules on the design or size of trials in each phase, or indeed the number of trials. It varies from situation to situation and particularly where a non-drug intervention (e.g., surgery) is being evaluated or where an existing drug is being evaluated for another use.

In-terms of study design these vary through the phases with Phase I studies often only having treated patient ("single arm") with no control, phase II perhaps involving a control group (may be randomised) but phase III being a randomised controlled trial (RCT). Some common RCT designs are considered here. Phase IV studies are often fairly passive studies collecting adverse event data where the number being evaluated not strictly controlled (within the study protocol).

The outcomes of main interest typical vary according to the phase of the study and reflect the relative focus on safety and/or efficacy.