The Food and Drug Administration, or FDA, only allows the use of drugs that it knows to be safe and effective. At the same time, it is impossible to be sure whether a new chemical is truly safe and effective until it has been tested on patients. Drug developers and regulators bridge this gap with clinical trials, carefully regulated experiments that test the impact of new drugs on volunteers. While the phrase “clinical trials” can describe studies examining medical devices, tests, procedures, or changes to participants’ behavior (e.g., diet), this page will focus on clinical trials studying new drugs.

Once a new drug is ready to be tested, standard FDA procedure prescribes three phases of clinical testing:

  • Phase 1: The first trial tests a drug in a small number of volunteers, generally between 20 and 80, and focuses on toxicity.
  • Phase 2: The second trial involves dozens to hundreds of volunteers and tests a drug’s effectiveness in treating a disease.
  • Phase 3: The third trial is the largest, often involving hundreds to thousands of volunteers. This trial gathers additional information on safety and effectiveness, as well as data about appropriate dosing and interactions with other medicines.

Some drugs also require post-market studies to further confirm safety, efficacy, and optimal use. As a drug gets closer to market, its trials demand a greater investment of human, structural, and financial resources. Only a small portion of all potential drugs are sufficiently safe and effective to be worth the high cost of Phase 3 testing.

 

Clinical Trial Design

The primary goal of a clinical trial is to determine whether or not a therapy is safe and effective. Developers and the FDA also attempt to ensure that promising new treatments reach patients in need as efficiently as possible, both by expediting their path to market and by maximizing their availability during clinical testing. The FDA must balance these goals against the unique needs of different drugs (e.g., a drug that attempts to increase longevity over five years in patients with a rare form of lung cancer should be tested differently from a drug that attempts to promote blood coagulation within a few minutes in hemophiliacs). As a result, there is a great deal of variety among clinical trial structures and designs. Here are a few major elements of clinical trial design:

  • Number of Patients: The more patients enrolled in a clinical trial, the greater that trial’s statistical power, or ability to accurately predict a drug’s effects. This is why Phase 3 trials, which offer the final study of a drug’s impact before it’s submitted to the FDA for approval, tend to be so large. Some drugs have unique attributes, such as very small target populations, that make large trial sizes impractical or impossible. In these cases, developers have to find ways to achieve statistical confidence with fewer enrolled patients.
  • Controls: Developers and regulators can’t study a drug’s effects in a vacuum. If every patient in a trial were given the same drug and the resulting data were studied in isolation, it would be impossible to tell which benefits or harms had been caused by the drug and which had occurred due to unrelated factors. Data on a drug’s impact are only useful when compared with that of a control group–an otherwise similar group of patients who did not receive the new drug. In clinical trials, control groups generally receive either treatment at level of the standard of care or a placebo in cases where the new drug aims to address an unmet medical need. Each group of patients receiving a distinct treatment in a clinical trial is referred to as an “arm.” Often, if it becomes clear that one arm of a trial is producing superior results, the trial will be stopped to minimize the number of patients receiving the less beneficial treatment.
  • Randomization: If researchers are directly comparing an experimental drug to a control, they must assign the two drugs to patients at random. This helps to prevent bias on the part of those selecting patients, which would compromise the accuracy of the study. Where trials involve small target populations, randomization can be impractical. In these cases, researchers may employ a “single-arm” trial, in which all patients receive the experimental therapy.
  • Blind, Double-Blind, and Non-Blind Trials: Bias can also result from the behavior of patients and researchers who know which patients are receiving an experimental drug and which are receiving a control. A study is said to be “blind” if patients are unaware of which drug they are receiving. In a “double-blind” study, researchers are also unaware of which drugs patients are receiving and only the pharmacist knows which drugs have been assigned to which patients. “Non-blind” or “open-label” trials can be unavoidable in cases where the administration of two drugs is radically different (e.g., if a medication is being compared with physical therapy).
  • Endpoints: An endpoint is the outcome that researchers measure during a clinical trial in order to determine whether or not an experimental therapy is effective. Researchers select endpoints based on clinical trial design, the nature of the condition being treated, and the anticipated effect of the drug being tested. Many trials testing cancer drugs, for example, measure how long a patient survives on a particular drug (Overall Survival) or whether a drug improves a patient’s quality of life. Other common endpoints include Response Rate, Progression Free Survival, and Disease Free Survival.

Clinical trials are the most expensive and time-consuming aspect of drug development. Developers, regulators, and patient advocates are constantly looking for ways to design more efficient trials without jeopardizing safety or accuracy. One novel approach is the Master Protocol trial design, which aims to test several drugs simultaneously by screening a central group of patients for biomarkers and assigning them to the drugs most likely to impact their unique conditions. (Read more about the Master Protocol trial design HERE.)

 

Participating in a Clinical Trial

Clinical trials rely on the voluntary participation of patients. While clinical trials involve more risk than FDA-approved treatments, they offer volunteers close supervision by researchers and access to cutting-edge drugs that have yet to reach the market. Clinical trial participants have the opportunity to advance medical research on behalf of future patients and to contribute to the most vital part of drug development.

The first step in getting involved in a clinical trial is to talk to your doctor about what trials might be available and right for you and your family.

For additional information about clinical research, visit http://clinicaltrials.gov/ct2/home

The Astellas Clinical Trials website offers education to patients, their caregivers, as well as the public and healthcare professionals about the clinical trial process: https://www.clinicaltrials.astellas.com/