Before Human Trials
Before human trials begin, the process starts in the laboratory, where it takes years of sifting through thousands of potential treatments to find a handful that were fit for testing in clinical trials.
Basic Research/Drug Development
New potential treatments* are discovered at this stage. At this point, the investigators test their ideas at the laboratory bench and in machines or “test tubes,” but the experiments can also involve cells and specially-bred animals. The potential treatments can be made from all sorts of materials, including natural or synthetic chemical compounds and bioengineered or biological materials, like antibodies. Some are “repurposed,” meaning that they have been approved for treatment of one or more disease(s) and are being tested for their potential to treat another disease.
Much of this basic research is done to determine more details about the disease studied and what proteins, genes or system processes contribute to the development and/or progression of the disease. These clues to potential avenues for treatment are essential to be able to design drugs for further testing. The clues can also help with designing large “high-throughput” drug screening techniques.
Only potential treatments that have the best evidence for potential safety and effectiveness in animals and humans move forward to Pre-Clinical/Translational Research. The list of treatments is whittled down to much smaller numbers as some make it past the tests and others do not.
The potential treatments* identified to have therapeutic potential in the Basic Research stage are then tested in animals for their ability to be delivered to the target organ(s) and tissue(s), to determine how well they are cleared from the system, and to determine their toxicity, safety, and effectiveness. Many potential treatments that do not pass certain tests may be “dropped” at this stage, since they may seem too risky for further development for use in patients.
Normally, one of the Pre-Clinical tests must involve a type of animal that has a condition similar to one or more symptoms held by human patients of the particular disease for which a treatment is being pursued.
Translational Research involves studies that give evidence that the effectiveness shown for a particular treatment has a good chance that similar results could occur in humans. Essentially, the research must show that the results can “translate” into helping patients who have the disease or condition.
Once the trial sponsor has identified a promising treatment, they prepare and send an Investigative New Drug (IND) application to the FDA, for them to review the evidence that a potential treatment is appropriate for testing in human clinical trials. The FDA wants to assure that the proposed drug does not put humans at an unreasonable risk for harm.
At this point, the sponsors also submit their plans for future clinical trial testing. The FDA requires that the trial volunteers will have proper protection and informed consent (i.e. participants will be given enough information about the relevant medical facts and potential risks of the proposed treatments, as explained in easy-to-understand language). If a treatment or clinical trial design does not meet the FDA’s standards or requirements, the sponsor will not be given permission to proceed with this treatment to human clinical trials.
*Treatment: Although we are using the word "treatment," clinical trials also involve medical research studies in which people participate as volunteers to test new methods of prevention, screening, and diagnosis of disease.
U.S. Food and Drug Administration (FDA); National Institutes of Health (NIH); Center for Information & Study on Clinical Research Participation (CISCRP); Pharmaceutical Research and Manufacturers of America (PhRMA); Tufts Center for the Study of Drug Development [Updated Outlook 2010 and original referenced paper (DiMasi, Joseph A., Ronald W. Hansen and Henry G. Grabowski (2003) “The Price of Innovation: New Estimates of Drug Development Costs,” Journal of Health Economics 22(2):151-85, March)]; and a paper comparing the costs of different studies (Morgan, Steve, et al. “The cost of drug development: A systematic review” Health Policy 100 (2011) 4–17).