Clinical Trials

R&D in the pharmaceutical industry is both expensive and time consuming, and thus entails considerable uncertainty.

All potential pharmaceutical products go through two major stages of development before a product registration can be granted: non-clinical and clinical.

In non-clinical testing, potential compounds are tested comprehensively to determine whether they are safe to administer to humans. This stage of development involves investigating the effects of the compound on various body functions as well as studying its absorption, distribution, metabolism and excretion in selected species.

In clinical development, clinical trials are commonly classified into three phases (I, II, and III), and the development of new medical imaging agents usually proceed through all three stages over 6-8 years. If the new agent successfully passes through the Phases I, II, and III, it will usually be approved for use in the general population.

Phase I trials are the first-stage of testing in human subjects. Normally a small (40-120) group of healthy volunteers is selected. This phase includes trials designed to assess the safety, pharmacokinetics (distribution, metabolism and elimination of the active ingredient), and pharmacodynamics (contrast enhancement properties) of ascending doses of the new imaging agent.
For diagnostic radiopharmaceuticals, organ and tissue distribution data are usually collected over time in Phase I studies to optimise subsequent imaging protocols and calculate radiation dosimetry.

In Phase II studies, the medical imaging agent is given to a larger group of people (200-500) to see if it is effective, to further evaluate its safety and to gather additional information regarding the safe dose range. Several doses of the agent are tested and compared in terms of contrast enhancement properties and incidence and severity of adverse events.

The general goals of Phase II studies of medical imaging agents include:

• Refining the agent's clinically useful mass dose and radiation dose ranges or dosage regimen (e.g., bolus administration or infusion) in preparation for Phase III studies
• Answering outstanding pharmacokinetic and pharmacodynamic questions
• Providing preliminary evidence of efficacy and expanding the safety database
• Optimising the techniques and timing of image acquisition
• Developing methods and criteria by which images will be evaluated in Phase III testing.
• In Phase III studies, the agent is given to large groups of people (800-1,500) to confirm its effectiveness, monitor side effects, compare it to commonly used agents (if available) and collect information that will allow the agent to be used safely. The general goals of Phase III efficacy studies for medical imaging agents include confirming the principal hypotheses developed in earlier studies, demonstrating the efficacy and continued safety of the medical imaging agent, and validating instructions for use and for imaging in the population for which the agent is intended.