Why Are Clinical Trials Important?

Robert L. Ferris, MD, PhD

Clinical trials are a key research tool for advancing medical knowledge and patient care. Clinical research is done only if doctors do not know whether a new approach works well in people and is safe and which treatments or strategies work best for certain illnesses or groups of people. In cancer of the head and neck, many clinical trials are available, but new medicines or devices are only FDA approved every 5-10 years, reflecting the difficulty of bringing new treatments to patients and the need for cooperation with patient advocacy groups to move the field faster.

Clinical trials are important for discovering new treatments for cancer (and other diseases) as well as new ways to detect, diagnose, and reduce the chance of developing the disease. Clinical trials can demonstrate to researchers what does and doesn’t work using humans that cannot be learned in the laboratory or using animals. Clinical trials also help doctors decide whether the side effects of a new treatment are acceptable when weighed against the potential benefits. Researchers don’t know what the results of clinical trials will be. (If they did, they wouldn’t have to do the trials!) This uncertainty can make it difficult for a patient to decide whether to participate in a clinical trial. While in rare cases, patient volunteers have been hurt by the treatment or procedure in a clinical trial, millions of people have been helped because other people before them chose to participate in a trial that resulted in a new, more effective treatment.

While clinical trials are important, the choice to participate in one is very personal and depends on your unique situation. When presented with a clinical trial, you and your doctor need to weigh the benefits against the risks and decide what’s best for you. According to the American Cancer Society, about 1,000 potential medications are tested before one makes it to clinical trials. On average, new cancer treatments have been studied for at least 6 years (and sometimes many more) before a clinical trial is started. Usually by the time a treatment makes it to the stage of a clinical trial, it has been found to be safe and to have some chance of being effective. In some cases, a treatment is safe and already FDA-approved and standard practice in one disease (like lung cancer), and the clinical trial is simply testing it in another type of cancer (like cancer of the head and neck).

How Clinical Trials Work

If you take part in a clinical trial, you may get tests or treatments in a hospital, clinic, or doctor’s office. In some ways, taking part in a clinical trial is different from having regular care from your own doctor. For example, you may have more tests and medical examinations than you would otherwise. The purpose of clinical trials is research, so the studies follow strict scientific standards. These standards protect patients and help to produce reliable study results.

Clinical Trial Protocol

Each clinical trial has a master plan called a protocol, which explains how the trial will work. The trial is led by a principal investigator (PI), who usually is a doctor. The PI prepares the protocol for the clinical trial. The protocol outlines what will be done during the clinical trial and why. Each medical center that does the study uses the same protocol, which is reviewed and approved by various committees, whose job it is to ensure patient protections, and some potential of learning new information or benefitting patients who have the disease. Key information in a protocol includes, how many patients will take part in the clinical trial, who is eligible to take part in the clinical trial; what tests patients will get and how often they will get them; what type of data will be collected during the clinical trial; and detailed information about the treatment plan. The researchers doing clinical trials take steps to avoid bias. “Bias” means that human choices or other factors not related to the protocol affect the trial’s results.

Comparison Groups

In most clinical trials, researchers use comparison groups. This means that the patients taking part in a trial are assigned to one of two or more similar groups. Each group will receive different medical strategies. For example, one group may get the current standard treatment for a condition, while another group gets a new treatment. Researchers can then compare the results to see whether one group has better outcomes than the other.

Using comparison groups also ensures that no one in a study is left without treatment for the sake of research. Sometimes, when no accepted standard treatment exists for a condition, people in one group may receive a placebo (inactive pill that looks like the test product). You’ll be told if a placebo will be used in a study before you agree to take part.


Some clinical trials that have comparison groups use randomization. This involves assigning patients to different comparison groups by chance, rather than choice. This method helps to ensure that any differences observed during a trial are due to the different strategies being used, not to preexisting differences between the patients. Usually, a computer program makes the group assignments.

Possible Benefits and Risks of Clinical Trials

Taking part in a clinical trial can have many benefits. For example, you may gain access to new treatments before they’re widely available. If a new treatment is proven to work and you’re in the group getting it, you might be among the first to benefit. If you’re in a clinical trial and don’t get the new strategy being tested, you may receive the current standard care for your condition. This treatment might be as good as, or better than, the new approach. You also will have the support of a team of health care providers, who will likely monitor your health closely.

In late-phase clinical trials, possible benefits or risks of a treatment can be identified earlier than they would be in general medical practice. This is because late-phase trials have large groups of similar patients taking the same treatment the same way. These patients are closely watched by Data and Safety Monitoring Boards. Even if you don’t directly benefit from the results of the clinical trial you take part in, the information gathered can help others and add to scientific knowledge. People who take part in clinical trials are vital to the process of improving medical care. Many people volunteer because they want to help others.

Clinical trials do have risks and some downsides, such as the following…

The new strategies and treatments being studied aren’t always better than current standard care. Even if a new approach benefits some participants, it may not work for you. A new treatment may have side effects or risks that doctors don’t know about or expect. This is especially true during phase I and phase II clinical trials. The risk of side effects might be even greater for trials with cutting-edge approaches, such as gene therapy or new biological treatments. Health insurance and health care providers don’t always cover all patient care costs for clinical trials. If you’re thinking about taking part in a clinical trial, find out ahead of time about costs and coverage. You should learn about the risks and benefits of any clinical trial before you agree to take part in the trial. Talk with your doctor about specific trials you’re interested in.

Scientific Oversight

Institutional Review Board
Institutional review boards (IRBs) help to provide scientific oversight for clinical trials. An IRB is an independent committee created by the institution that sponsors a clinical trial. IRB members are doctors, statisticians, and community members.

The IRB’s purpose is to ensure that clinical trials are ethical and that the participants’ rights are protected. The IRB reviews the trial’s protocol before the study begins. An IRB will only approve research that deals with medically important questions in a scientific and responsible way. The IRB also checks on results during the trial. All U.S. clinical trials are required to have an IRB.

Office for Human Research Protections
The U.S. Department of Health and Human Services’ (HHS’) Office for Human Research Protections (OHRP) oversees all research done or supported by HHS. The OHRP helps protect the rights, welfare, and well-being of research participants. They provide guidance and oversight to the IRBs, develop educational programs and materials, and offer advice on research-related issues.

Data Safety Monitoring Board
Every National Institutes of Health (NIH) phase III clinical trial is required to have a Data and Safety Monitoring Board (DSMB). This board consists of a group of research and study topic experts. The NIH also requires DSMBs for large trials comparing alternative strategies for diagnosis or treatment. In addition, the NIH requires DSMBs for some earlier phase trials that involve high-risk procedures (such as gene therapy) or vulnerable patients (such as children).

A DSMB’s role is to review data from a clinical trial for safety problems or differences in results among different groups. The DSMB also reviews research results from other relevant studies. These results may reveal unknown patient risks, or they may even answer the NIH study’s research question. Scientific oversight informs decisions about a trial while it’s under way. For example, some trials are stopped early if benefits from a strategy or treatment are obvious. That way, wider access to the new strategy can occur sooner. Sponsors also may stop a trial, or part of a trial, early if the strategy or treatment is having harmful effects.

Food and Drug Administration
In the United States, the Food and Drug Administration (FDA) provides oversight for clinical trials that are testing new medicines or medical devices. The FDA reviews applications for new medicines and devices before any testing on humans is done. They check to make sure that the proposed studies have proper informed consent (see below) and protection for human subjects.
The FDA also provides oversight and guidance at various stages throughout the studies. For example, before large-scale phase III trials begin, the FDA provides input on how these studies should be done.

Patient Rights

Informed Consent
Informed consent is the process of giving those who participate in a clinical trial all of the facts about the trial. This happens before they agree to take part and during the course of the trial. Informed consent includes details about the treatments and tests that they must receive and the benefits and risks they may have.

Before you decide whether to enroll in a clinical trial, a doctor or nurse will give you an informed consent form that presents the key facts of the study. If you agree to take part in the trial, you’ll be asked to sign the form. You can and should ask questions about the trial to make sure you understand what’s involved. Here are some questions to ask before enrolling in a clinical trial:

• What is the purpose of the study?
• Who is sponsoring the study, and who has reviewed and approved it?
• What kinds of tests, medicines, surgery, or devices are involved? Are any procedures painful?
• What are the possible risks, side effects, and benefits of taking part in the study?
• How might this trial affect my daily life? Will I have to be in the hospital?
• How long will the trial last?
• Who will pay for the tests and treatments I receive?
• Will I be reimbursed for other expenses (for example, travel and child care)?
• Who will be in charge of my care?
• What will happen after the trial?

The informed consent document is not a contract. You have the right to withdraw from a study at any time, for any reason. Also, during the trial, you have the right to learn about new risks or findings that emerge. If researchers learn that a treatment harms you, you’ll be removed from the study. Taking part in a clinical trial is your decision. Talk with your doctor about all of your treatment options. Together, you can make the best choice for you.

Editors Note: Robert L. Ferris, MD, PhD is currently the UPMC Endowed Professor, Vice-Chair and Chief of Head and Neck Surgery, and Fellowship Director in Head and Neck Oncologic Surgery. At the University of Pittsburgh Cancer Institute, he is Co-Leader of the Cancer Immunology Program and Associate Director for Translational Research. Dr. Ferris serves on the Editorial Boards of JNCI, Clinical Cancer Research, Cancer Immunology Research and Section Editor for Cancer, and Head and Neck. He is Editor in Chief of Oral Oncology (the highest impact factor journal dedicated to Head and Neck Oncology). Dr. Ferris has published over 250 peer-reviewed manuscripts and was elected co-chair of the NCI Head and Neck Steering committee to facilitate prospective clinical trials.

Dr. Ferris’ NIH-funded laboratory is focused on reversal of immune escape and immunotherapy using monoclonal antibodies and cellular vaccines. Dr. Ferris is leading several prospective randomized trials, including ECOG 3311, testing radiation dose-reduction after transoral robotic surgery (TORS) for HPV+ oropharynx cancer, and several randomized phase II-III trials of anti-PD-1 and anti-CTLA-4 immunotherapy. Dr. Ferris co-led the first positive phase III randomized trial of anti-PD-1 immunotherapy (nivolumab) in head and neck cancer, contributing to FDA approval of this class of therapies. He is Principal Investigator of the University of Pittsburgh Specialized Program of Research Excellence (SPORE) grant for translational head and neck research, and a T32 training grant, “Training of Head and Neck Oncologists,” both funded by the National Cancer Institute until 2020. Dr. Ferris has authored numerous book chapters and helped co-edit two textbooks with Dr. Eugene N. Myers, MD, Salivary Gland Disorders and Master Techniques in Head and Neck Surgery.

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