The Basics
Understanding Clinical Trials
What is Clinical Research?
To better understand clinical trials, the National Institutes of Health says you must first understand clinical research. Clinical research is medical research involving people. There are two types of clinical research:
Observational Studies
Observational studies observe people in normal settings. Researchers gather information, group volunteers according to broad characteristics, and compare changes over time. For example, researchers may collect data through medical exams, tests, or questionnaires about a group of older adults over time to learn more about the effects of different lifestyles on cognitive health. Studies like these can help identify new possibilities for clinical trials.
Clinical Trials
Clinical trials are experiments done in clinical research. These biomedical or behavioral research studies on human volunteers are designed to answer specific questions about biomedical or behavioral interventions, including new treatments and known interventions that warrant further study and comparison. Clinical trials generate data on the safety and effectiveness of a therapy or drug. They are conducted only after they have received permission from the health authority in the country where approval of the therapy is sought.
Video Credit: American Society of Gene & Cell Therapy
How Do Clinical Trials Work?
Clinical trials are a type of research designed to answer specific medical questions such as, is this treatment safe for patients or how well does the treatment work?
The idea for a clinical trial often starts in a laboratory. After researchers test new treatments or procedures in the lab and in animals, the most promising treatments are moved into clinical trials to find out how well they work in humans.
Clinical trials follow a very strict plan known as a protocol. The protocol must address risks and benefits to trial participants as well as answer specific research questions. Sections of the protocol include:
The goal of the study; who can be in the trial; How participants are protected from risks; What information do the researchers want; Details about tests, procedures, and treatments; How long the trial will last
Study sponsors send the protocol to an Institutional Review Board (IRB) for approval. The IRB consists of doctors, researchers, patient advocates, data analysts, etc. and their job is to make sure the proposed trial passes legal and ethical standards. No trial takes place without approval from an IRB.
Once approved, the principal investigator and research team recruit trial participants and begin their study. Most clinical trials belong in a certain “phase” that dictates how many people can be in the trial and the purpose of the trial. While you may join a phase I trial, it’s more likely that you will join during phase II or phase III.
Clinical Trial Phases
(In the rare disease setting, these Phases are very often combined or overlap)
Phase I
An experimental treatment is given to a small number of participants (20-80). Research staff want to identify the drug/device/treatment’s most common and serious side effects. This phase focuses on safety and how the team can adjust the treatment to make it better for the participant.
Phase II
Information learned in Phase I is applied to the treatment in Phase II. The focus then turns to the specific research question, disease, or condition being tested (100-300 people).
Phase III
The experimental treatment, drug, or device gets compared to the standard treatment or product. The investigation explores variables like age, dosage amount, race, health status, etc. to identify areas of success or failure and confirm its effectiveness (1,000-3,000 people).
Phase IV
The drug or treatment must receive approval from the FDA. Once approved, the drug becomes available to the public and researchers monitor its safety in the general population. Data about the benefits, best use, or issues related to the treatment are collected and analyzed by the research team.
After a clinical trial ends, the researchers carefully review information collected during the study. The results drive the decision to continue or stop the clinical trial. For example, after a phase I or phase II study, the researchers may choose to stop the process because the new treatment was unsafe or did not help the patient. On the other hand, they may move on to phase III because results from the first two rounds were so promising.
Once a new drug/device/treatment is proven safe and effective in a clinical trial, it may become a new standard of medical practice.
What is a Placebo?
In undertaking a clinical trial, researchers don’t want to leave anything to chance. They want to be as certain as possible that the results of the testing show whether or not a treatment is safe and effective. The standard for testing interventions in people is the “randomized, placebo-controlled” clinical trial. That means volunteers are randomly assigned—that is, selected by chance—to either a test group receiving the experimental intervention or a control group receiving a placebo or standard care. A placebo is an inactive substance that looks like the drug or treatment being tested.
Comparing results from the two groups suggests whether changes in the test group result from the treatment or occur by chance. In many trials, no one—not even the research team—knows who gets the treatment, the placebo, or another intervention. When participants, family members, and staff are all “blind” to the treatment while the study is under way, the study is called a “double-blind, placebo-controlled” clinical trial.
“Placebos in Clinical Trials.” National Institute on Aging, U.S. Department of Health and Human Services, www.nia.nih.gov/health/placebos-clinical-trials.
Types of Research
Clinical research helps find new and better ways to detect, diagnose, treat, and prevent disease. The most common types of clinical research include:
Translational
Applying basic scientific knowledge to identified medical needs in hopes of creating a new drug, therapy, or treatment for people, i.e. translate scientific data into a solution.
Genetic
Identify and understand the relationship between genes and illness. This information can help predict the genetic structures most likely to develop a particular disorder.
Observational
Studies in which people are followed (observed) by researchers over a period of time to determine health outcomes.
Epidemiological
Examination of specific populations to clarify how often a disease occurs or is found in a given group, the individual factors that can make the disease worse, and the types of lifestyle decisions the people make.
Interventional/Clinical Trials
Evaluate and test the usefulness or safety of new interventions such as medication, treatment method, or device. There are several kinds of clinical trials, including:
Prevention trials look for better ways to prevent a disease or condition from occurring in people who have never had the disease. They also explore how to prevent the disease from returning. Approaches may include medicines, vaccines, or lifestyle changes.
Screening trials test new ways of detecting diseases or health conditions.
Diagnostic trials study tests or procedures designed to diagnose a particular disease or condition.
Treatment trials test new treatments, drugs, combinations of drugs, or new approaches to surgery or radiation therapy.
Behavioral trials evaluate or compare ways to promote behavioral changes designed to improve health.
Quality of life trials explore and measure ways to improve the comfort and quality of life for people with certain conditions.
Clinical research provides scientists an effective way to find answers to important questions and use that knowledge to create new treatments, and maybe a cure, for common and rare diseases.
What is Inclusion and Exclusion Criteria?
According to the National Institutes of Health, factors that allow someone to participate in a clinical study are called inclusion criteria, and the factors that disqualify someone from participating are called exclusion criteria. They are based on characteristics such as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions.
Each clinical trial wants to answer a specific question. That’s why researchers provide a list of eligibility requirements and only people who meet the guidelines may be enrolled in the trial. Each study is different so it’s possible to qualify for one trial but not another.
What is Informed Consent?
Once you are approved for a clinical trial but before any treatment begins, the study organizers will give you an informed consent document. Informed consent is the process of agreeing to participate in a clinical trial after learning all the details of the study.
The informed consent document provides details (including, but not limited to) of the trial including:
How the study will be conducted
What the purpose of the study is
What other treatment options you may have if you do not participate in the study (e.g. physical therapy)
Who will get to see your medical records under the study
Specific participant requirements
Risks and benefits of participation
Study duration
Cost to you, if any
Payment to you, if any
Names and phone numbers of key contacts
After reviewing this information and asking any questions, you sign the consent form if you wish to proceed with the study. Make sure you understand what will happen during the trial, what is expected of you, and the possible risks and benefits before you sign the consent form. If you decide not to continue with the trial, return the document to the organizers without signing it.
Taking part in a clinical trial is voluntary. You can leave the study at any time, for any reason – even if you sign the consent document and change your mind later.