Clinical Trials

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Clinical research is key in the exploration of whether a new medical strategy, or treatment, is safe and effective and will work better than current treatments for humans. The regulation around new drug development and clinical research can be found in the U.S. Code of Federal Regulation (CFR), Title 21 Food and Drugs, Chapter 1 Food and Drug Administration (FDA), Subchapter D Drugs for Human Use, Part 312 Investigational New Drug (IND) Application. Specifically part 312.3 defines “Investigational new drug means a new drug or biological drug that is used in a clinical investigation.” Further defines, “Clinical investigation means any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects. For the purposes of this part, an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice.”

Clinical trials are the final step in a long and vigilant process that usually begins with (licensed) research in a lab. If an approach seems promising, the next step may involve animal testing to show how the approach affects a living body and whether it’s harmful. However, an approach that works well in the lab or in animals does not always work well in people. Thus, research in humans is needed.

Once a investigational product (IP) is ready to be studied in humans, an FDA Investigational New drug Application must be filed (see guideline for pre-clinical data requirements), to review that the development of the IP or preclinical studies meets Current Good Manufacturing Practice (cGMP) standards. Unless placed on a clinical hold, the IND is considered approved 30 days after the application is received by the FDA (unless notified earlier) per part 312 subsection C. For safety purposes, clinical trials start with small groups of patients to find out whether a new approach causes any harm. In later phases of clinical trials, researchers learn more about the new approach’s risks and benefits.

FDA’s primary objectives in reviewing an IND are, in all phases of the investigation, to assure the safety and rights of subjects, and, in Phase 2 and 3, to help assure that the quality of the scientific evaluation of drugs is adequate to permit an evaluation of the drug’s effectiveness and safety. Therefore, although FDA’s review of Phase 1 submissions will focus on assessing the safety of Phase 1 investigations, FDA’s review of Phases 2 and 3 submissions will also include an assessment of the scientific quality of the clinical investigations and the likelihood that the investigations will yield data capable of meeting statutory standards for marketing approval.

The purpose of clinical trials is research, so studies must follow strict standards called the principles of good clinical practices (GCPs), including adequate human subject protection (HSP) which are universally recognized as a critical requirement to the conduct of research involving human subjects. The FDA’s regulations for the conduct of clinical trials, address both GCP and HSP. The official FDA regulations and guidance are available via the FDA website, including the International Conference on Harmonisation (ICH) GCP guidance which FDA collaborated on and adopted as an official FDA guidance. These standards protect patients and help produce reliable study results to help move drugs from development to market.

The U.S. National Institutes of Health’s (NIH) , National Cancer Institute (NCI), organizes trials into four different types:

  • Treatment trials: Most cancer clinical trials are treatment studies that involve people who have cancer. These trials test new treatments or new ways of using existing treatments, such as new drugs, vaccines, approaches to surgery or radiation therapy, or combinations of treatments. Some treatment trials involve testing cancer cells for the presence of specific molecular markers. These markers can include changes in certain genes or proteins. These changes may help to further classify cancers and certain treatments may target them. So it is important to know whether they are present.
  • Prevention trials: Cancer prevention trials are studies involving healthy people. In most prevention trials, the participants either do not have cancer but are at high risk for developing the disease or have had cancer and are at high risk for developing a new cancer. These studies look at cancer risk and ways to reduce that risk.
  • Screening trials: The goal of cancer screening trials is to test new ways to find disease early, when it may be more easily treated. An effective screening test will reduce the number of deaths from the cancer being screened.
  • Quality-of-life/supportive care/palliative care trials: These trials look at ways to improve the quality of life of cancer patients, especially those who have side effects from cancer and its treatment. They find new ways to help people cope with pain, nutrition problems, infection, nausea and vomiting, sleep disorders, depression, and other health problems.