About Clinical Research
While clinical trials form the basis of the approval process for medical treatments, research into new therapies begins years before these clinical trials get underway. Before a new therapy can be considered for testing in humans, it must show therapeutic promise in animal models of the disease, as well as undergo extensive testing to assure a wide safety margin. These studies are collectively defined as preclinical (i.e., occurring prior to clinical testing) or more often nonclinical (i.e., testing outside the scope of human tests). Scientists test potential therapies in animals that have diseases or other pathology that resembles human afflictions (called animal models), attempting to find effective doses that produce no toxicity or unwanted side effects. It typically takes many years of research before results accumulate to justify an application to the FDA for advancing into testing in humans.
Clinical Trials
Once a company accumulates credible evidence that a new therapy could potentially safely benefit people, it then applies to the FDA, for investigational new drug (IND) status. With this IND approval, the experimental treatment can now be tested in human clinical trials.
For the safety and protection of the people who volunteer to participate in clinical trials, the FDA has strict protocols and guidelines for conducting these medical studies. First, the treatment enters Phase 1 clinical trials where establishing safety is the key focus, though other aspects of the treatment, such as method of administration, dosage and tests for preliminary evidence of efficacy (or effectiveness in treating the disease) might also be assessed. Phase 1 clinical trials typically take many months to a couple of years to complete, depending on the complexity of the disease and novelty of the product. In the case of neurological disorders, such as those for which Ceregene develops treatments, the experimental administration of the therapy begins with one surgical procedure and continues with routine and detailed examinations of the patient for at least a year. Ceregene continues to perform follow-up examinations of its patients for several years after treatment, whenever feasible, in order to accumulate long-term data on our treatments’ safety and preliminary effectiveness.
Once sufficient evidence of safety and preliminary evidence of efficacy is obtained, the product candidate can advance to Phase 2 testing. In Phase 2, the primary objective is assessing the efficacy to treat the disease, though further tests for safety in larger numbers of patients are also very important. Usually much greater numbers of patients receive the treatment, providing a large enough sample size to reach statistically valid conclusions. The additional time required to generate results for neurological treatments in Phase 2 amounts to years of dedicated work on the part of the medical researchers and commitment by the patient volunteers who received the treatment.
If a potential product successfully completes the Phase 2 clinical trials, it moves on to the third and usually final phase of clinical testing prior to submission for FDA approval. The Phase 3 clinical trial is intended to provide clear and reliable evidence of safety and efficacy of the product. This requires testing in hundreds to thousands of patient volunteers, often for extended time periods (i.e. one year or more). An appropriate control group (i.e. one not given the treatment) is included to assure that any improvement seen in the disease is due to the specific treatment and not possible placebo effects, experimental bias, or numerous other factors that could produce a “false positive” result. The FDA typically requires at least two such controlled clinical trials before they consider whether to approve the new product for marketing, though a well-controlled Phase 2 clinical trial, together with a larger Phase 3 clinical trial, can sometimes satisfy this requirement.