Clinical Trials – Phases
What are Clinical Trial Phases?
The phase of a clinical usually refers to how far a drug is down the research pipeline, and how much data has been collected for the compound in question previously. There are 4 main phases which we will analyse (phase I, phase II, phase III and phase IV), each with their own investigative purposes. The clinical trial pyramid is a great visual aid when wrapping your head around why each phase exists and why they must be performed in a strict order –
The primary aim of phase I clinical trials is to assess the safety profile of the drug within humans. This will include any toxicities or side effects and optimising the dose in line with the data received. In order to do this, low doses of the experimental compound are often administered initially. Depending on observed side effects, this may be continually scaled up until the optimal dose is reached (usually the highest dose with minimal side effects). This research may also focus on how a drug is metabolised within the body, and how it may be best administered to provide the greatest therapeutic effect whilst minimising toxicity. As this is the first phase of human trials with a certain compound, enrolled subjects are generally monitored thoroughly, as this is the ‘riskiest’ stage of research.
The number of human subjects studied during this phase tends to be small, normally under 100.
If a drug is deemed to have an acceptable safety profile from the data collected/patient observation during phase I, then it may progress onto phase II. This is generally where early research into the efficacy of the drug is conducted for a specific disease state. The criteria for patient enrolment may be far more specific than in phase I due to the specificity of the study design. The optimal dosage range that has been predetermined from phase I becomes the starting point for therapeutic intervention, although further monitoring of side effects also takes place for one main reason – the sample size! The larger study population of a phase II clinical trial allows researchers to ascertain whether any uncommon side effects exist that may not have been realised, within the smaller population size of phase I.
100-300 subjects normally comprise a phase II trial.
This is the final phase that a drug must successfully navigate to be considered for approval, should it have proven a certain degree of therapeutic efficacy during phase II. Here, the drug under investigation is usually compared to existing treatments in order to determine which works best! The research at this stage is what people normally associate with clinical trials. Simplistically, one group of participants will receive treatment in the form of an existing drug, whilst another group receives the drug under investigation – another group receiving a placebo may be used at this point to give baseline data values for comparison. The efficacy of all treatments (according to a specific set of study parameters) is then analysed.
Further observation of potential side effects that may have slipped the radar during phase I and II trials are undertaken here. The sample sizes of phase III trials generally exceed 1000-2000 participants, and are often multicentered. This gives any positive data more validity and gives a truer indication of how the results can be extrapolated into the wider population.
Should a drug pass phase III successfully, it may then be submitted for approval to the FDA. Although this may take several years.
These studies tend to be very large and are designed to further assess drug safety within the wider population, over a longer period of time. This allows us to gain a understanding of how a drug may affect the body after long-term use, as well as potentially assist in refining dosage or future administration techniques. They are conducted after a drug has been approved following successful navigation of phase III.