Phases of Clinical Research
Clinical research is conducted in phases, each with aims and objectives that help to answer questions or hypotheses posed by the investigators.
Each phase is treated as a separate clinical trial.
Randomized clinical trials compare a standard treatment to a new therapy or a modified version of the standard treatment. This is gold standard research.
Standard treatment is the best known treatment for a particular stage of a specific disease. Clinical research generates knowledge that continually improves standard treatment.
The safety and activity of a particular treatment is assessed in a selected (usually very small) group of patients. These studies risk selection bias, limiting value of the findings.
Studies may be retrospective (medical records are examined to assess outcome), or prospective (patients are given a particular treatment and the outcome is documented). Case series may be consecutive (all cases are included), or non-consecutive (cases are selected).
Most clinical trials divide patients into two or more groups (arms), comparing standard treatment with experimental therapy. A computer randomly assigns the child to one arm, preventing bias.
Uncontrolled randomized trials involve two arms (standard and experimental). Controlled trials involve 3 or more arms, and the group receiving standard treatment becomes the control. They enable investigators to scientifically compare the two experimental arms.
Laboratory experiments are conducted to gather preliminary information about a treatment’s efficiency, toxicity and action. The data helps researchers decide whether a particular treatment is worth investigating clinically.
Initial testing of an experimental therapy evaluates safety, establishes a safe dose range, and identifies side effects. 20 to 100 patients are involved, usually they have failed all other therapy.
This phase evaluates how well the treatment works, while further assessing safety and side effects. Some Phase II trials are case series. Most are randomized clinical trials, and between 20-300 people are enrolled.
If a new therapy fails, this usually occurs during Phase II when it is found to be inefficient or toxic.
This is considered definitive assessment of the treatment’s efficiency. Randomized multicentre trials enrol 300 – 3,000 participants. The protocol is further tested to validate effectiveness, track side effects and assess safety, compared with current ‘gold standard’ treatment
Phase III trials are the most costly, time-consuming and challenging to design and run. This is especially so for rare cancers like retinoblastoma as close international collaboration is required to conduct effective research.
Continued monitoring provides further information on risks, benefits, and optimal use of the therapy. Safety surveillance is designed to detect rare or long-term adverse effects. Harmful effects discovered in Phase IV may result in a treatment being withdrawn or its use restricted.