Phases of clinical trials


If you are asked about joining a clinical trial or if you are reading about scientific studies in the media, it’s important to know what stage the research is at. Early-stage research, like animal studies and phase I trials, cannot show whether a new drug, vaccine or cure strategy is effective. Larger, late-stage studies known as phase III trials are needed for that. Most of the clinical trials reported on this website are phase III trials.

Pre-clinical research screens or synthesises possible drugs or vaccines, and picks some to try in computer simulations, then in cells in a lab dish, and then usually on animals. Thousands of different compounds may be screened and dozens tried on animals before advancing one to human trials.  

Phase I trials give the substance to a small number of people (about 20-30) who may not necessarily have the disease in question and are at low risk of it, to screen out products that are toxic or just inactive. Typically one in ten candidates may be advanced from phase I.

Phase II trials give it to a larger number of people – typically a few hundred at most – who do have the condition or are at risk of it, under tightly controlled conditions. The substance’s ability to cure, control or prevent the condition is measured and if this is significant, a dose is chosen to take forward. A number of promising candidates may fail at this stage due to low efficacy, poor absorption or intolerability.

Phase III trials give the substance to a large number of people (from several hundreds to tens of thousands) in relatively ‘real world’ conditions to find out if it actually has efficacy in treating, curing or preventing the disease in a high enough proportion of people. Because phase III trials are expensive, researchers have to be reasonably confident that a drug or vaccine may work. Trials of prevention methods such as vaccines or PrEP often have to be especially large (and expensive) as by definition, many people in the trial would not have caught the disease anyway.

There is also ‘phase IV’: this is post-marketing surveillance, when the developers of a drug or vaccine undertake to monitor its effects for a certain time after a drug licensing authority allows it to be prescribed to the public. Specific phase IV requirements may be attached to the licence to prescribe. However, phase IV commitments are not always well enforced and may fail to spot unexpected side effects that may emerge only after licensing: an example is lipodystrophy, eventually found to be caused by certain HIV drugs of the NRTI class.   

The process from animal and phase I studies to efficacy always involves eliminating numerous unsuccessful candidates and approaches. It can also take years or decades. This is one of the reasons there have only ever been eight phase III HIV vaccine trials.

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