In Clinical Trials: What You Need to Know, Part One, we discussed types of trials which are conducted as biomedical or health-related research in human beings. These trials, including interventional studies and observational studies, are designed to follow a pre-defined protocol.
A protocol is a type of study plan by which clinical trials are based. The plan, which may be designed with the help of the FDA, is carefully designed to protect the health of the participants as well as answer specific research questions. A protocol outlines what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study.
Ideas for clinical trials usually come from researchers or the research sponsors. After researchers test new therapies or procedures in the laboratory (in vitro) and in animal studies (usually with mice), the experimental treatments with the most promising laboratory results are moved into clinical trials (involving people).
Clinical trials are sponsored or funded by organizations or individuals such as physicians, medical institutions (such as Johns Hopkins or Mayo Clinic), foundations (see Myelin Repair Foundation), voluntary groups (such as the National MS Society), and pharmaceutical companies. Federal agencies such as the National Institutes of Health, the Department of Defense, and the Department of Veteran's Affairs also fund clinical trials. Over the past two years, nearly $10 million have been secured for MS research through the Congressionally Directed Medical Research Programs (CDMRP), a Department of Defense (DOD) program which is funded annually through the Defense Appropriations Act.
The US Food and Drug Administration (FDA) requires that new therapies undergo three phases of trials before they can be approved for a particular indication. Each phase of a clinical trial has a different purpose and help scientists answer different questions:
Phase I trials (safety trials): Researchers test an experimental drug or treatment in a small number of healthy volunteers or persons with MS. The investigators determine how the human body reacts to the therapy, evaluate its safety, determine a safe dosage range, and identify side effects.
Phase II trials: The experimental study drug or treatment is given to a larger group of people to determine its effectiveness (efficacy) in people with MS and to further evaluate its safety. Depending upon the study protocol and purpose, these studies may last several months or several years. If the study is "controlled," one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo.
Phase III trials: The experimental study drug or treatment is given to large groups of people (often hundreds) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely. These multi-center studies can span several years and be conducted in several countries. Data from Phase III trials form the basis of the marketing application submitted to the FDA for approval.
Special Protocol Assessment: Sometimes between Phase II and Phase III trials, the sponsoring organization (likely a pharmaceutical company) will ask to meet with the FDA to receive a Special Protocol Assessment (SPA). The SPA is requested for the purpose of reaching an agreement on the design and size of clinical trials, including primary endpoints and the method of measurement, intended to satisfy the marketing application.
Phase IV trials: Following FDA approval, post-marketing studies may be conducted to assess long-term safety and effectiveness. Phase IV trials help to obtain additional information including the drug's risks, benefits, and optimal use.
Expanded Access Protocol: Most human use of investigational new drugs take place in controlled clinical trials like those described above. Sometimes patients do not qualify for carefully-controlled trials because of other health problems (comorbidities), age (too young or too old), or other factors (such as disease which is too far progressed or use of specifically excluded medications).
Patients with a life-threatening or serious disease who may benefit from the investigational drug, but who don't qualify for the trials, may apply for "expanded access" to the drug. Specific FDA regulations allow the manufacturer to provide study drug in exceptional circumstances to those patients who have no other treatment options.
Expanded access protocols are only allowed if clinical investigators are actively studying the experimental treatment in well-controlled studies, or if all studies have been completed. If the drug might expose patients to unreasonable risks due to the severity of their disease, then the trial sponsor can deny expanded access.
Understanding Clinical Trials from ClinicalTrials.gov
Clinical Trial Basics from National MS Society
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