A new drug registration must be approved for use by the regulatory and ethics committee before clinical trials are conducted. Studies are conducted in strict accordance with an approved study protocol, which describes the types of volunteers and patients who may enter the study, the schedule of tests and procedures, drugs, dosages, duration of study, and the outcomes to be measured.
A strict process of receiving informed consent must be followed for each volunteer.
Clinical trials comprise different, specific, phases referred to as phase I, phase II, phase III, and phase IV. Each phase is designed to answer questions regarding the safety, efficacy and use of the target molecule.
Different phases of clinical trials
Phase I clinical trials or safety studies
This stage is intended collate pharmacokinetic safety data following the administration of pre-set doses of the target molecule enabling the maximum tolerated dose (MTD) to be determined. These trials are usually conducted with a limited number of healthy volunteer participants.
Multiple ascending dose (MAD) studies improve understanding of the pharmacokinetics, and pharmacodynamics effects. Groups of patients receive multiple low doses of the candidate molecule, while samples are collected at various time points to determine drug processing kinetics information.
Phase II clinical trials
Data gathered at this stage assesses how well a drug works and continues phase I safety assessments in a larger group, usually 20-300 volunteers including patients. Most new drug candidates tend to fail to progress beyond phase II studies due to unplanned or toxic effects.
Phase III clinical trials or pivotal clinical trials
This stage is designed to be the definitive assessment of how effective the drug is, in comparison with current ‘gold standard’ treatment. Phase III studies are blind, randomised, controlled, multicentre trials, on a large subject population of 300 to 3,000+ volunteers and patients, over a long period of time.
These are the most expensive, time-consuming, and difficult trials to design and run, especially in therapies for chronic medical conditions. Full cGMP must be in place by the time phase III studies are performed.
Phase III trials will often continue while the regulatory submission is pending, allowing patients to continue to receive possibly lifesaving treatment until the drug is approved and can be obtained by purchase.
If these trials prove satisfactory the results are usually combined into a comprehensive description of the methods and results of human and preclinical studies, manufacturing procedures, formulation details, and shelf life. This collection of information makes up the “regulatory submission” submitted in eCTD format.
Phase IV or post-marketing trials
This phase follows product licensure and involves the safety surveillance, pharmacovigilance, and ongoing technical support of a drug. This will typically be communicated as the post approval commitments to the relevant board of health and be designed to detect any rare or long-term adverse effects over a much larger patient population and longer period.
Phase V
This stage refers to comparative effectiveness research and community-based research. This helps new clinical treatments become integrated in widespread public health practice. cGMP must also be considered throughout the clinical development stage as it must be implemented prior to phase III clinical trials.