What Are Clinical Trials?

Clinical studies are research studies performed in people as a way to understand new medicines, devices, procedures, and treatments. The objective is to determine if they are safe and effective. Such studies are sometimes also called “Clinical trials”. Often a clinical study is performed to evaluate if a new medication or treatment method is more or equally effective and/or has fewer or less harmful side effects than the existing treatment.

A clinical study performed in the United States must be submitted to the U.S. Food and Drug Administration (FDA) and approved by the Institutional Review Board (IRB) of the hospital or center where the study is being performed. Both must affirm the study to be ethical, as safe as possible, and valuable to patients and science in the future. Every patient who is entered into a study must sign an “informed consent” (permission) form to be entered into the study after being given a thorough explanation of the study, both verbally and in writing. Studies performed in minors must have parents or guardians give their approval.

What Are the Phases of Clinical Research?

Clinical research includes four phases to test a potential treatment’s effectiveness, find the appropriate dosage (or amount of the drug that works best), and to understand the potential side effects that people might experience when taking the experimental treatment.

Before even starting a Phase I first-in-human study, researchers must conduct “preclinical studies” to see if there is a potential benefit of the new treatment for a specific disease by testing the treatment in animals (or other models). These preclinical studies must show the experimental treatment at doses to be tested in humans has a positive benefit-risk assessment to allow for its use in the experimental setting of a clinical study. The FDA must agree with the preclinical study results to move forward.  

1. Phase I Studies test an experimental medication or treatment on a small group of often healthy people (generally 20 to 80) and preferably with an equal number of men and woman representing various major races, if possible, to judge the drug’s safety, to understand any major side effects and to estimate the correct drug dosage (amount that works best) and the ideal frequency of use.
2. Phase II Studies use more people (100 to 300). While the emphasis in Phase I is on safety, the emphasis in Phase II is on effectiveness (how well it works) along with safety. This phase aims to obtain preliminary data (information) on whether the drug works in patients who have a specific disease and often includes further evaluation of doses for future study. These studies also continue to study safety, including short-term side effects. It is preferred that men and women are equally represented and that all races be adequately represented.
3. Phase III Studies gather more information about safety and effectiveness of the medication or treatment in a much larger population. Importantly, the Phase III study compares the new drug against the standard of care from an efficacy and safety perspective. It may also be compared to use of no other drug or a “placebo” (a pill that looks the same but has no drug inside it). The patients are randomized to get the experimental treatment to avoid bias in patient selection. This decision may be hidden (“blind”) from the investigator or known to the investigator (“open”). The study and control patients should have equal representations of race, gender, age, and defined disease conditions. Some studies may evaluate different dosages of the drug or use the drug in combination with other drugs. The number of people participating in this phase is defined upfront to deliver statistically valid data and reach a well-defined conclusion. The number of patients in Phase III trials range from several hundred to thousands of subjects. To give the experimental drug final approval, the FDA must agree that the drug is efficacious and has an acceptable safety profile. [ML1] In addition, the study must be performed precisely as described and the result recorded accurately.

• Phase IV Studies take place after the FDA approves the use of the drug. The purpose is to assure the safety of the drug in a larger number of patients over a longer period of time. A drug’s effectiveness and safety are monitored in large, diverse populations. Sometimes, the side effects of a drug may not become clear until more people have taken it for a while. In addition, Phase IV studies are often used to collect additional efficacy and safety data in broader sets of patient populations.

Why Participate in a Clinical Study?

Some people join a study because the treatments they have tried for their health problem did not work or there is no treatment for their health problem. Some studies are designed to help find better ways to prevent, treat, or manage a disease. For example, a goal can include finding a treatment with fewer side effects or an improved quality of life.

Many people say participating in a clinical study is a way to play a more active role in their own health care. Other people say they want to help researchers learn more about certain health problems. Whatever the motivation, when people choose to participate in a clinical study, they become a partner in scientific discovery. And this contribution can help future generations lead healthier lives. Major medical breakthroughs could not happen without the generosity of clinical study participants.

How Do You Find and Enroll into a Clinical Study?

Individuals can find information about ongoing clinical studies through their doctors or health care providers. They can also search online or sign up for a matching service to get connected to a study of the treatment of their disease in the area where they live. Studies are often conducted at more than one research center and may require the patient to live / stay within a certain distance from the center where the study is conducted.

To enroll into a clinical study, the patient must contact the clinical study investigator or study coordinator to schedule a screening appointment to see if he/she qualifies. At times, study teams may contact potential patients to invite them for a visit to see if they are interested in participating in the study. If the patient is interested in participating, they will participate in an initial study visit to explain the protocol (what will happen in the study), obtain patient consent, and recruit the patient. There are certain specific inclusion / exclusion criteria for each patient.  Age, stage of disease, gender, genetic profile, family history, need for other drugs that may interfere with the tested drug, and whether or not the patient has a study partner who can accompany him/her to future visits are examples of inclusion / exclusion criteria. Exclusion criteria might also include specific high risk health conditions. Importantly, a patient may only participate in one research study at a time.

The screening process includes both a thorough history (what has happened to a patient with their health over their entire life) and a comprehensive physical examination, as well as cognitive (mental) tests. Often, one first completes a questionnaire or a survey online, which is followed by a phone call with the study coordinator. Then, an in-person screening visit at the study site with an investigator and/or the study coordinator might include a physical examination and review of candidate’s medical history. Laboratory testing (e.g. blood tests, urine test) and/or special diagnostic testing (e.g. x-ray, MRI, CT scan) may also be required.

Before any laboratory/diagnostic tests are performed or any screening documents are completed, the candidate must review and sign a participant information sheet and an informed consent form. This document is not a contract; it represents an agreement to participate in the study and an understanding of what it will involve. For example, it will outline the purpose of the study, what participation is required of the candidate (how long it lasts, initial visits, follow-ups procedures), risks / benefits, compensation, confidentiality, and more). You may withdraw your consent and leave the study at any time.

What Happens to You During a Clinical Study?

If accepted into the study, you will then be randomly assigned (“blindly” or “knowingly”) to the treatment group or to the control group. The control group does not receive the experimental treatment, which permits the study staff to compare the results in patients who receive the experimental item versus those who do not receive the medication being tested. The control group may receive a placebo (inactive pill or injection), or the standard of care treatments generally administered to the patients with the disease being studied. Some studies are partially/single-blinded, meaning that either you or the study staff do not know which group you are in, or double-blinded, meaning both you and the study staff do not know which group you are in. This helps remove any biases when analyzing the results of the treatment at the conclusion of the study.

Throughout the duration of the study, the candidate must adhere to the study procedures and protocols, and report any issues, deviations, or concerns to researchers (these are known as adverse events and adverse reactions). You may be asked to visit the research site at regularly scheduled times to receive treatment and/or for new cognitive (mental), physical, or other evaluations and discussions with the study staff. At these visits, the research team collects information about effects of the treatment and about your safety and well-being. You continue to see your regular physician for usual health care throughout the study.

What Happens When a Clinical Study Ends?

Once a clinical study has ended, the researchers will collect and analyze the data to determine what subsequent steps are needed as a result of the findings in the study. The analysis of the results are generally posted on the website clinicaltrials.gov within 12 months of the completion of the study, at which time a press release may be issued announcing the results. In most cases, the findings will also be presented at a scientific meeting and published in a scientific journal. The study findings, together with the protocol and other documents, will be filed with the FDA for their review with the goal of having the new drug (or its new use) approved and licensed for use. Upon approval, the drug can be launched and promoted. As a participant, the candidate should be informed before entering the study about whether he or she will continue to receive the study treatment if appropriate and desirable after the study closes (ends), and how to be kept informed about the results of the study. 

This article is made possible by the support of ITB-MED LLC. 

Glossary of Definitions

Adverse event: Any health problem that happens during the study.

Adverse reaction: A health problem that happens during the study and is possibly caused by the study treatment.

Assessment: Information that is collected and analyzed from a study participant.

Clinical benefit: A health change that researchers measure to find out if the study treatment helps the study participants.

Clinical research: A controlled way to study health and illness in people.

Clinical study (trial): A way to study new drugs, devices and treatments to see if they are safe and work in people.

Confidentiality: Protecting personal information from people who should not have access.

Consent form: A document used to explain the details of the research study.

Control group: People in a study who do not have the condition being studied.

Data: Information collected from or about people taking part in a research study.

Discontinue: To stop a study treatment or stop being a participant in the study.

Double-blind study: A study that is set up so that participants do not know which study treatment they are getting, and researchers do not know either.

Efficacy: How well a study treatment works in the study.

Eligibility criteria: The reasons a person can be included in, or excluded from, a study.

Endpoint: A measure of the expected effect of the study treatment (for example, lower blood pressure or reduced sleeplessness).

Enroll: Agree to join a study as a study participant.

Exclusion criteria: A list of reasons a person cannot be included in a study.

Inclusion criteria: A list of requirements a person must meet to take part in a study.

Informed consent: The process of learning and discussing the details of a research study before deciding whether to take part.

Institutional review board (IRB): A team of people who review studies to protect the rights and welfare of study participants.

Investigator: A person who leads a research study.

Phase: A step in the overall clinical research process to test a new drug or treatment.

Placebo:  A substance or treatment which is designed to have no therapeutic value, a so called “sugar pill”.

Preclinical study: A study to test a treatment in the lab or in animals before testing it in people.

Protocol: A complete description of the research plan and procedures.

Randomization: A way to use chance to place study participants into different study treatment groups.

Side effect: A health problem that is likely caused by an approved treatment.

Single-blind study: A study that is set up so that participants do not know which study treatment they are getting.

Standard of care: Treatment usually given to patients for an illness.

Study design: The way a study is set up to answer the study question.

Study participant: A person who joins a research study.

Study population: All the participants in a study.

Withdraw: To stop being a participant in a study.

Sources and more information:

• https://mrctcenter.org/clinical-research-glossary/
• https://www.nia.nih.gov/health/what-are-clinical-trials-and-studies

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