The assessment of whether it is worthwhile and feasible trying to move an academic discovery from demonstration of activity in a laboratory experiment into clinical trials requires that many issues be addressed that are not always obvious to the academic researcher :
- Is the drug candidate effective at doses that are not toxic?
- Is there an animal model of the target disease suitable for evaluation of efficacy?
- Are the pharmacokinetics in the animal model favourable to demonstration of efficacy ?
- Can production of the drug candidate be scaled up sufficiently to meet the potential need, at reasonable cost and with sufficient purity and reproducibility ?
- Are the pharmacokinetics favourable in humans to maintaining an effective dose in the patient for long enough to achieve a cure or alleviation of symptoms?
Permission to administer a treatment to a patient comes only after a rigorous review of the answers to the above by regulatory authorities. The guiding principle is a determination that the potential benefit outweighs the potential risk. To make this assessment the regulators need to be supplied with extensive documentation to support the potential therapeutic benefit – this usually comes from proof-of-concept experiments with the drug candidate in animal models of disease. Often there are “gold-standard” models that are preferred by the regulators. For example, for potential treatments for influenza, the gold standard model is ferrets because they exhibit symptoms similar to humans – sneezing being one. In other cases Ebola virus infection, for example, demonstration of effectiveness in a primate model of infection may be required.
Evidence to support safety at the proposed dose and regimen is essential. This is usually extrapolated from toxicity studies in animals. In some cases, regulators may require that for drug candidates that have not been in humans before, the initial safety determination is through dose escalation to establish an MTD – maximum tolerable dose.