Medical research is a carefully planned process that enables scientists to find safer and more effective ways to prevent, diagnose, and treat diseases. The process starts in the laboratory, where many detailed experiments are carried out to develop drug candidates, and only the most promising new molecules arising from laboratory research become experimental medicines for further evaluation in those persons who are living with the targeted disease.
Clinical trials are typically conducted in a series of steps called “phases.” Each successive phase has a different purpose and helps scientists and doctors to answer a different set of questions. The knowledge gained from each phase is carried forward to the next.
The goal of the first phase of clinical research is to identify the optimal dose and schedule of the medication being tested. This type of trial is often called a “dose escalation” study or trial.
In this type of trial, patients are divided into small groups, called cohorts. The first cohort receives a dose of the new drug. If this cohort does not experience any dose-limiting serious side effects, then another cohort receives a higher dose of the study medication. The dose increases with each new cohort until the optimal dose for future clinical testing has been determined. Usually, new drugs are tested alone at first to understand the potential for side effects at different doses, and this is called a Phase 1a clinical trial. Then, the new drug is combined with standard-of-care cancer drugs to find out what dose is best tolerated in combination. This is called a Phase 1b clinical trial.
Phase 1 trials usually enroll small numbers of people (typically 15 to 30) who have advanced disease that cannot be treated effectively with the standard treatments or for which no standard treatment exists. Although evaluating the efficacy of the experimental medication is not a primary goal of the trial (determining an optimal, safe dose level and schedule is the goal), the investigators nevertheless evaluate each patient to see how their disease is responding to treatment, as well as to determine tolerability to the drug candidate or combination treatment.
This second phase of clinical trials is designed to evaluate the efficacy of the medication in a specific disease condition, for example multiple myeloma. A Phase 2 clinical trial will also continue to assess the safety of the medication.
Unlike the small patient populations in Phase 1, Phase 2 clinical trials may include 50 to several hundred patients, depending on the specific goals and design of the clinical trial. Sometimes, the results of a Phase 2 clinical trial may be used to gain approval for marketing from the U.S. Food & Drug Administration (FDA), and other regulatory authorities outside the U.S. More often, continued evaluation in a Phase 3 clinical trial is needed.
Phase 3 clinical trials are large-scale studies designed to compare the safety and efficacy of the study medication with that of the current therapeutic standard-of-care.
These trials may include several hundred to several thousand patients and can be conducted either nationally or internationally. Patients in these trials are typically randomized into treatment comparison groups called treatment arms. Most often, there are two treatment arms in a Phase 3 clinical trial:
The control group
The experimental or investigational group
The majority of Phase 3 clinical trials are double-blinded, which means that neither the patient nor the study investigators (i.e. the physicians, nurses, and sponsor) know who is receiving which medication. The purpose of this blinding is to reduce the risk of bias.
The FDA uses the findings from these studies to decide whether the experimental medication should be approved for use in a specific disease indication outside of clinical trials.
Not everyone will be eligible to participate in clinical trials. Your doctor will assess whether or not you are qualified for the trial based on the stage of your disease and your previous treatment history, as well as other factors about your overall health status and medical history.
Inclusion and exclusion criteria for a particular clinical trial are intended both to protect the safety of individual patients and to enhance the quality of the clinical trial results. Please speak with your health care provider to find the clinical trials and/or standard-of-care treatments that best meet your needs. For an up-to-date listing of current clinical trials in the U.S., visit www.clinicaltrials.gov.
There are many advantages to joining a clinical trial. The most significant benefit is that clinical trials offer patients early access to new treatments. Trials also enable patients to:
However, clinical trials are not without some risks. For example, the experimental medicine may not be effective or it may lead to serious side effects. In addition, participating in a clinical trial may interfere with your daily life as it may require frequent visits to the trial site, ongoing tests, and a more complex dosing schedule than standard-of-care treatment.
Information is going to be your most valuable resource as you make your decision whether to participate in a clinical trial. To get the information you need, ask many questions.
Here are some questions you can ask your doctor and other healthcare providers to help you make your decision:
Answers to many of these questions can also be found in the Patient Informed Consent document, which must be reviewed and discussed with your physician before enrollment in a clinical trial.