A clinical trial is a research study. It is an organized way of testing a new investigational treatment to determine if it is safe and effective to use. The participants in clinical trials are human patients who volunteer for this opportunity to obtain a treatment that otherwise wouldn’t be available to them.
The results that these clinical trials generate are considered to be the most robust data in the era of evidence-based medicine. Ideally, clinical trials should be performed in a way that isolates the effect of treatment on the study outcome and provides results that are free from study bias.
A common approach by which to achieve this aim is through randomization, whereby patients are assigned to a treatment group by random selection. Patients and trial personnel are deliberately kept unaware of which patient is on the new drug. This minimizes bias in the later evaluation so that the initial blind random allocation of patients to one or other treatment group is preserved throughout the trial.
Clinical trials must be designed in an ethical manner so that patients are not denied the benefit of usual treatments. Patients must give their voluntary consent that they appreciate the purpose of the trial. Several key guidelines regarding the ethics, conduct, and reporting of clinical trials have been constructed to ensure that a patient’s rights and safety are not compromised by participating in clinical trials (Declaration of Helsinki, 2005; Altman et al., 2001).
Biomedical clinical trials of experimental drug, treatment, device or behavioral intervention may proceed through four phases:
Phase I clinical trials test a new biomedical intervention in a small group of people (e.g., 20-80) for the first time to evaluate safety (e.g., to determine a safe dosage range, and to identify side effects).
Phase II clinical trials study the biomedical or behavioral intervention in a larger group of people (several hundred) to determine efficacy and to further evaluate its safety.
Phase III studies investigate the efficacy of the biomedical or behavioral intervention in large groups of human subjects (from several hundred to several thousand) by comparing the intervention to other standard or experimental interventions as well as to monitor adverse effects, and to collect information that will allow the intervention to be used safely.
Phase IV studies are conducted after the intervention has been marketed. These studies are designed to monitor effectiveness of the approved intervention in the general population and to collect information about any adverse effects associated with widespread use.
Trials are designed to answer the following questions about the new treatment:
• Is it safe?
• Is it effective?
• Is it more effective than standard treatment?
• Does it provide any benefit or advantage over standard treatment?
Clinical trials play an important part in whether new drugs and medical devices eventually get to market. The U.S. Food and Drug Administration (FDA) requires any new drug or device to be approved before being sold. To gain FDA approval, the manufacturer or distributor of the drug or device must submit full reports of the studies carried out to show that the drug or device is safe and effective for its intended use. Clinical trials act as the primary way for manufacturers to prove that their product is safe and effective.
Sponsors of Clinical Trials
Sponsors of a clinical trial can be either a commercial company (industry-sponsored trial) or a clinical investigator/physician (non-industry trial). The former comprises pharmaceutical and biotechnology companies, while the latter comprises medical schools, biomedical research institutes, government institutions or clinical trial networks. Depending on the body, non-industry trials are referred to as non-profit, non-industry-sponsored, investigator-initiated, or institutional-initiated trials.
The sponsor initiates a clinical trial and has a number of responsibilities such as protocol development, financing the trial and quality assurance. The sponsor will seek permission for trial initiation from the drug regulatory authority or authorities if more than one country is involved in conducting the trial.
Where are clinical trials conducted?
Clinical trials are conducted throughout the world at university hospitals, cancer centers, medical centers and hospitals, and doctors’ offices and clinics. The National Cancer Institute sponsors or co-sponsors the majority of clinical trials in the United States and it does so through its clinical trials cooperative groups and consortia, cancer centers and clinical grant programs.
How are the final results of a trial made known?
After all patients have been treated and followed for the prescribed length of time, the results are analyzed. It is the sponsor’s obligation to distribute the results as quickly and widely as possible. In reality, this can take months or even years. However, as electronic communication becomes more commonplace, this information is being shared more rapidly.
Trial results are made known in several ways:
• A poster or presentation at a scientific meeting
• An article published in a scientific journal (this may take months before the article appears in print; some journals make available electronic versions of the article as soon as they are reviewed)
• Electronic bulletins from NCI
• New trials citing results of the prior study
• An application to the FDA for an New Drug Application (NDA)
• Word of mouth among the researchers or sponsors
• News media reports, press releases, etc.
Defining Clinical Trial Outcome/Endpoint
A clinical trial outcome/endpoint is an indicator measured in a participant or in a sample taken from the participant to assess the safety, efficacy or other objective of a clinical trial. The endpoint measure of a trial can be of various types. Efficacy, safety and quality of life are the most common and widely accepted indicators:
• Efficacy is simply an estimate of how effective the test medicinal product is in eliminating/reducing the symptoms or long-term endpoints of the condition under trial. Efficacy measures can be of many kinds, such as blood pressure, tumour size, fever, liver function test or body mass index.
• Safety of the test treatment is as important to the trial as the treatment efficacy. All negative adverse reactions or events that a trial participant experiences during the conduct of the trial should be documented. The investigators monitor for adverse reactions or events to determine safety during a clinical trial. The information is used to describe the safety profile of the test treatment. Adverse events can be mild, such as local short-term reactions and headaches, or serious such as stroke and death.
• The measurement generally referred to as quality of life (QoL) in clinical trials is now a well-established term. QoL includes physical, mental and social well-being, and not just the absence of disease or illness. There are broad QoL measurements that are not very specific for the disease or condition – general well-being – and there are disease-specific questionnaires that are more sensitive to treatment and disease influences. All questionnaires must be validated properly before they are used as a valid trial endpoint.