How Clinical Trials Work

Clinical trials are essential for the development of safe and effective treatments.

A clinical trial is a research study designed to answer specific questions about a new treatment or a new way of using a current treatment. Clinical trials are used to establish whether a potential new treatment reliably produces the intended medical benefit and is safe.

Trials typically begin with the development of a clinical protocol, which outlines how the trial will be conducted, including the objectives, design, methodology and organization. The design looks to eliminate bias on the part of the participating researchers and doctors. Laws and regulations governing clinical trials differ from country to country, but reputable clinical trials share important criteria, including respect for participants’ rights, strong scientific evidence, oversight by independent committees and compliance with appropriate laws and regulations concerning research on human subjects.

Sometimes, in attempting new surgical techniques or where a disease or condition is rare, test treatments may be tried on just one or two people outside the confines of a clinical trial. In these cases, standard patient protections should still apply.

How do clinical trials work?

A clinical trial includes a comparison to determine whether or not the treatment is having an effect. Clinical trials formally compare the efficacy and safety of an experimental treatment or procedure with a control. A control may be an existing, approved treatment or a placebo, if no alternative exists. Participants in the experimental group, or test group, of a trial receive the treatment, and those in the control group receive no treatment, a placebo or the standard of care.

Participation in a clinical trial may be randomized, meaning participants are randomly assigned to either the experimental or the control group. In an open label trial, both the participants and the investigators know who is in the experimental and control groups. In a single-blind trial, participants don’t know whether they are getting the test treatment or not but the investigator does know. In a double-blind trial, neither the participants nor the investigators know who is in the test or the control group. This helps to reduce bias on the parts of those conducting the trial and double-blind trials are therefore considered the most reliable.

A well-designed trial will use one or more endpoints, which are outcomes that can be objectively measured to determine whether the investigational treatment is beneficial. These end points are determined in advance of the study and are used to generate credible evidence about efficacy and safety.

During the clinical trial process, there are a number of checks to protect the rights of patients.

Fundamental to the process are:

• Monitoring of experimental treatments for patient safety and ethical practice. Before beginning, trials should be carefully reviewed by a group of people who together have broad expertise and experience in research, medicine and ethics. These groups, often called Institutional Review Boards (IRBs) or medical ethics review committees, evaluate a number of factors, including the potential risks weighted against the potential benefits.

• Oversight by regulatory agencies. National oversight agencies, such as the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA) or Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), authorize and monitor the development of new treatments. The nature of regulatory agencies and their responsibilities vary from country to country, but most enforce a code of conduct or guidelines for researchers and clinicians to follow to promote safe and effective medical practice.

Phases of Clinical Trials

Clinical trials typically start with a small number of people and are focused on testing safety. As the procedures are perfected and the risks evaluated, the number of participants is gradually increased and the effectiveness of the treatment is more closely examined. The steps through which trials progress are called phases. While the terminology might vary between countries, the idea of a progressive building of knowledge remains consistent.

Phase 1: Is it safe?

Researchers test an experimental drug or treatment in a small group of people (20-100) for the first time. The researchers evaluate the treatment’s safety, determine a safe dosage range, and identify side effects.

Phase 2: Is it safe to continue testing and does it work?

The experimental drug or treatment is given to a larger group of people (up to 300) to see if it is effective and to further evaluate its safety.

Phase 3: Is it safe and effective in a broader population?

The experimental study drug or treatment is given to large groups of people (300-3,000). Researchers 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.

Phase 4: What are the long-term benefits and risks?

Post-marketing studies, which are conducted after a treatment is approved for use by the FDA, provide additional information including the treatment or drug’s risks, benefits, and best use.

The structure of the clinical trial process varies from country to country, as do the laws and regulations governing trials and the standards of proof required for the approval of new treatments.

However, reputable clinical trials follow a process similar to that illustrated above and generally have these things in common:

• Respect for participants’ rights and protection for their well-being

• Evidence-based treatment supported by lab research with cells, tissues and animals

• Approval, review and oversight by an independent committee, board or agency

• Compliance with appropriate laws and regulations concerning research on human subjects