Phase I studies can last anything from a few days to a few weeks. In most cases the medicine will be tested on around 20 to 80 healthy volunteers or closely-monitored patients. These studies are used to collect information about the metabolism of the medicine in human subjects. The information is used to establish the dose which will be used at the next stage of testing. The nature and severity of any side effects are recorded.
Phase II studies involve patients (between 100 and 300), who are affected by the target disease. The efficacy of the medicine will be studied here in terms of its effects on symptoms and signs of the disease, and further information obtained regarding the safety of the medicine.
In some trials, the new medicine is compared with the best currently available treatment, in others it is compared with a placebo (an inactive substance). In either case, the trial will often be carried out in a ‘double blind’ manner, meaning that neither the patient, nor the doctor, knows whether they are taking the new medicine or not. This helps to differentiate between the physical effects of a medicine and any other effect that might occur as a result of a patient believing a medicine will produce a particular effect and consequently actually experiencing it (placebo effect).
Issues that may need to be investigated further in subsequent studies are also identified. This helps establish the dosing plan for the final round of clinical trials before licensing of the new medicine is applied for.
Phase III trials are carried out on a much larger scale. A decision to begin this stage is made once the results from the previous phases have been documented and have been seen to indicate that the medicine is potentially efficacious, and its safety profile has been established as far as possible.
Phase III trials are designed to gather evidence of efficacy in specific indications and to more fully understand the safety profile of the medicine. Patients are allocated to the treatment they will receive through a randomised code, some will receive the new medicine, others an existing treatment or placebo. Typically during this phase, which can take several years to complete, the medicine is administered to thousands of patients.
The numbers required are dictated by statistical considerations so that a comparison of the new medicine with existing medicines or placebo is placed on a sound footing. The results of these trials provide support for claims concerning efficacy and safety and the pivotal evidence required by the regulatory authorities before the new medicine can be licensed.
All the information that has been obtained must be put into a database for analysis and subsequently summarised by data management specialists. This data is then submitted to the regulatory authorities so that approval to market the medicine can be granted on the basis of its proven safety, efficacy and quality. Only then will the medicine go into full manufacture and be available for treating patients suffering from specific conditions studied in the Phase III trials.
Further trials may be carried out post-marketing to gather additional data on the long-term benefits, to add additional indications for the medicine, or to include recommendations for use in special groups, such as children.
As you would expect, safety procedures in the development of medicines are extremely rigorous. All clinical research is governed by Good Clinical Practice, which covers four main areas:
There are a large number of other governmental regulatory and clinical trial protocol requirements to be met as well. Therefore, to work in clinical trials you need to be able to combine excellent organisational skills with a focussed, methodical approach and close attention to detail.
Before a trial can start, a lot of planning takes place. The trial design needs to be considered to ensure that the correct scientific questions are asked and that as much relevant information as possible will be obtained. A protocol is drafted, with input from regulatory experts, physicians, clinical researchers, statisticians and others, that sets out what the trial is aiming to achieve. Patient record forms are designed to record the treatment given and effects of that treatment, and sites where trials will be conducted need to be identified. Sites are chosen where a doctor, the clinical investigator, will have access to a sufficient number of patients who might be suitable for enrolment in the trial.
Approval for trials to be carried out is required, not just from the regulatory authority, but also from a research ethics committee. Trial documentation can be inspected at any time during the trial, or after it has been completed.