What are the Types of Clinical Trials?

What are clinical trials?

The term “clinical trial” refers to the study of the effects of experimental drugs, vaccines, devices, and other interventions on people. Clinical trials help find new ways to treat, diagnose, and even prevent disease. They can also be used to identify “risk factors” for disease, such as genetic mutations or lifestyle habits that might make an individual more likely to develop a specific disease or condition later in life. In some countries, clinical trials are also called “clinical studies” or “clinical research studies” or simply “trials.”

Understanding Clinical Trials

Navigating your way through clinical trial information can be a daunting task. One of the largest online databases of clinical studies, ClinicalTrials.gov, contains records for more than 400,000 research studies conducted in 220 countries around the world. Each of these studies is unique in its purpose and its design. There are other public registries (for example, https://www.clinicaltrialsregister.eu/, https://euclinicaltrials.eu/home, http://www.chinadrugtrials.org.cn/, https://jrct.niph.go.jp/, and others) that include information on clinical studies in specific countries or regions of the world. It’s helpful to start with some basic knowledge of different types of clinical studies.

Interventional Studies (Clinical Trials)

Interventional studies, also known as treatment studies or clinical trials, are a type of clinical study that is carefully designed to evaluate the effects of a specific intervention on a specific group of people. Before a clinical trial starts, the trial sponsor works with researchers to decide:
  • what questions the trial will try to answer,
  • how the results will be measured,
  • who can enroll in the trial,
  • what treatments and other medical care the participants will receive,
  • and how long the trial will last.
Here are some examples of questions that may be asked and answered during clinical trials:
  • Did Drug X help lower blood sugar in participants with diabetes?
  • Did participants with lung cancer who added Drug Y to standard chemotherapy live longer than participants who received standard chemotherapy alone?
  • Did participants with migraine headaches who took Drug Z as a nasal spray report greater treatment satisfaction than participants who received the same drug as an injection?
The information collected in clinical trials is needed to gauge whether experimental treatments work, how safe they are, and if they offer advantages over what is currently available. Health authorities such as the Food and Drug Administration (FDA) use the results of clinical trials to decide which experimental treatments should be approved for use by the general public.

Clinical Trial Phases

When an experimental treatment is studied in clinical trials, it is tested in stages, or “phases.” Clinical trials are often described by their phase (for example, a Phase 2 study). The trial phase gives you an idea of what the trial is designed to learn and how many participants will be enrolled. During an early phase (Phase 1), researchers may study the effects of an experimental treatment in a trial that includes a small number of participants. During the later stages (Phase 3 or Phase 4), researchers may study the long-term effects of an experimental treatment in a clinical trial that includes thousands of participants with a specific disease or condition. Each phase is designed to learn more about how an experimental treatment works and how safe it is.

Clinical Trial Designs

A clinical trial is also described by key parts of the trial design. Understanding some of these more common terms used to describe types of clinical trials can help you navigate the clinical trial landscape.
  • Randomized controlled trials: Randomized trials typically have at least 2 treatment groups. The experimental group is assigned to receive the intervention being tested, while the other (often called a “control group”) is the comparison or “usual care” group. The control group may receive another treatment or no treatment at all. In a randomized trial, participants are randomly assignedto one of these treatment groups by a computer program. Neither the trial doctor nor the participant chooses which treatment group the participant will be assigned to. This helps make sure the treatments are assigned fairly and the treatment groups are well balanced with respect to factors that could affect the trial results, such as a participant’s age or disease severity.
  • Placebo-controlled trials: A placebo-controlled trial also has at least 2 treatment groups. The experimental treatment is given to one group, and a placebo is given to the other. A placebo looks exactly like the experimental treatment but contains no active ingredients. People who receive the placebo follow the same steps and receive the same care as people who get the experimental treatment. Researchers use a placebo to make sure that any effects of a clinical trial treatment they find in the trial are actually caused by the treatment being studied.
  • Single-blind trials: In single-blind trials, the participants typically do not know which treatment they are receiving, but the trial doctors and other site staff know. This is done to reduce the chance of errors. Some participants may have responses that are due simply to knowing that they are or are not getting a certain treatment. This response is called a placebo effect.
  • Double-blind trials: In a double-blind trial, neither the trial doctors nor the participants know which treatment each participant is receiving. Some trials are done this way because knowing which treatment someone is getting can influence how the trial doctor observes and interprets the results. Because the trial doctor does not know who got which treatment during the trial, there is less of a chance of introducing bias. At the end of the trial, the results are “unblinded” so that researchers can look at outcomes for the different treatment groups.
As an example, a Phase 3, randomized, double-blind, placebo-controlled trial would be a late-stage study (the drug has already been studied in smaller trials and is now being studied in a larger population) in which participants are assigned randomly by a computer program to receive the experimental treatment or a placebo, and neither the trial site staff nor the participant will know their treatment assignment during the trial.

Observational Studies

Observational studies are studies in which people are observed, and researchers keep track of specific outcomes. There is no intervention (treatment) given in an observational study. An example of an observational study is the Nurses’ Health Study (NHS). The original NHS started in 1976. This study and the related studies that followed (NHS 2 and NHS 3) have gathered data from more than 275,000 participants. Researchers use data collected from NHS participants about their diet, physical activity, and other lifestyle habits to identify which lifestyle factors might be risk factors for major chronic diseases later in life.

Medical Records Research

Researchers can sometimes use patient medical records (a patient’s medical history, including diagnoses, test results, physician observations, and medicine usage) to study risk factors for a disease or its prognosis (the likely outcome). If patients agree to share their medical records for research purposes, their data can be anonymized (to protect the patient’s identity) and shared with researchers for this purpose. For example, researchers with access to medical records for a large group of people with migraines can look at the treatments these people took and identify which treatments were associated with better outcomes or, alternatively, more side effects.

Weighing the Evidence in Clinical Research

Interventional studies (clinical trials) are typically considered the gold standard in research. They offer us the strongest evidence of an experimental treatment’s effectiveness and safety because clinical trials study a treatment in a “controlled” setting. These trials have predefined rules about who can enroll and what will be measured. A well-designed clinical trial is one in which any differences observed between treatment groups are likely to be due to the treatments themselves rather than other factors that might have influenced the data. Consider this example: A medical record review of patients with breast cancer might show that patients who received Drug A had a shorter survival time than patients who received Drug B. However, it’s possible that people with certain risk factors might have been more likely to get a prescription for Drug A by their doctor, so the shorter survival time observed with this drug was due to variables other than the drug itself. In a controlled clinical trial designed to compare these 2 drugs, researchers would ensure that the risk factors were well balanced between the 2 treatment groups. While clinical trials set the standard for strength of evidence, observational studies and medical records research still play important roles. For certain patient populations, such as people with a rare disease, it can be difficult to find enough participants to conduct a controlled clinical trial. In cases like these, a review of medical records may offer researchers valuable access to larger datasets.