Clinical trials - the four phase process

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Much of the focus on managing and ultimately containing COVID-19 has naturally centred on the successful development of vaccines to protect people from the onset of infection. 2020 has seen an extraordinary race in the biomedical and pharmaceutical industries to find suitable candidates which can be deployed for public health programmes. Central to this process is the time taken to test drug for efficacy and safety - for the COVID vaccines, a process which normally proceeds over  years has taken only months.

Prior to proceeding to a clinical trial, compounds which constitute the drug are screened at a laboratory setting using computer modelling, tissue samples and pathology to assess which are likely to function with humans. The compounds are tested in at least two species of animals to establish performance, how they are metabolised and any side effects. After this preliminary stage, a candidate drug typically proceeds through a four stage process -

Phase 1: After approval from a human clinical trial ethics committee, and the appropriate health authority (Food and Drug Administration or FDA in the US, and the Therapeutic Goods Administration or TGA in Australia), the drug candidates which are the most promising are tested in small groups of healthy volunteers, usually young to lower middle age, non-smoking and normal body weight. For Phase 1 trials targetting life threatening diseases such as cancer, terminally ill patients as test drug recipients are included. Only one in five Phase-1 tested drugs are successful and proceed to being available for use.

Phase 2: The candidate drug is tested on a larger group of people with an illness to evaluate whether it works and to confirm safety, tolerance for patients and dosage requirements.

Phase 3: The trial is expanded for testing with hundreds or thousands of patients often in multi-institutions in various countries in what is termed a 'randomised controlled trial'. Some patients receive placebos (such as harmless sugar pill) while others receive the test drug itself. Neither doctors nor patients know whether they are using the placebo or the drug which enables an unbiased analysis of the response to the treatment and any side effects. This stage also enables measurement of how effectively the drug works in comparison to existing therapies, the economics of treatment and in quality-of-life terms.

Phase 4: Drug receives regulatory approval and is included in routine clinical practice. Ongoing surveillance studies may reveal any rare side effects or extra benefits.

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