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What Is a Clinical Trial?

Contributor: Bob Herman
10 minute read
A smiling male researcher interviews a female study subject in his office.

Lifesaving treatments don’t just suddenly appear inside a doctor’s office or a hospital. Years before a doctor writes a prescription, orders a test, or fits a device, a researcher asks a simple question:

“How can I improve the health of tomorrow’s patient?”

While the answer often begins in a laboratory, researchers rely on a series of tests to move solutions into the hands of doctors and patients. These tests, called clinical trials, evaluate the effects and safety of a medical intervention on humans.

Mass General Brigham is actively involved in numerous clinical trials, conducting many studies across the health system. These trials, led by our experts, hold the potential to expand the number of FDA-approved therapies in the coming years.

“Clinical trials help bridge the gap between lab bench and patient bedside,” says Bob Herman, director of clinical research at Massachusetts General Hospital. “The people who sign up for these trials are guiding medicine into a brighter future.”

He explains the different types of clinical research, the risks of clinical trials, and what questions you may consider before signing up for a trial.

What is clinical research?

Clinical research is the study of health and illness in people. It improves the way doctors treat and prevent illness.

Findings may explain how:

  • The body works.

  • Illnesses develop.

  • The body responds to a treatment.

  • Behaviors affect health.

All the data in the world may show that this pill can stop the progression of Alzheimer’s in a mouse. But mice are not humans. Even if evidence suggests humans may respond in a similar fashion, we can’t rely on the treatment until we’ve ruled out the other dangerous side effects. We need as close to absolute certainty as possible.

Bob Herman

Director, Clinical Research

Massachusetts General Hospital

Types of clinical studies

Researchers use two types of studies.

1. Observational studies

Researchers observe a situation. They monitor people in normal settings, collect data, and compare changes over time. Data may include the health, habits, or environments of the observed people.

Types of observational studies include:

  • Case study or series: A detailed description of one or more patients

  • Ecological study: Rates of a disease or condition compared among groups of people

  • Cross-sectional study: A group, or groups, studied at a specific moment in time

  • Case-control study: One group with a condition compared to another without the condition

  • Cohort study: A large group observed over time

Findings may uncover a health-related problem or trend. While researchers may propose an explanation or a solution, they put neither to the test.

A researcher may examine the diets of patients with liver cancer, for example, and notice advanced tumors only among patients with diets high in fat and sugar.

“Researchers may predict that their patients’ cancers will begin to improve if their diets do, too,” says Herman. “But, as soon as they adjust their diets, the study no longer becomes observational. The researcher has intervened, which makes the study a clinical trial.”

2. Clinical trials

Clinical trials evaluate how people respond to an intervention, whether medical, surgical, or behavioral.

Examples of interventions include:

  • Drugs, such as medications for high blood pressure, or hypertension

  • Exams, such as blood tests that diagnose diseases

  • Devices, such as a pacemaker

  • Behavior changes, such as following a diet for weight loss

Those who take part in a clinical trial do so voluntarily. Participants agree to follow the terms outlined in a trial protocol. The research team responsible for the trial writes the protocol, which explains:

  • Who can sign up

  • Test and procedure schedules

  • Tested drugs, devices, or diagnostic exams

  • Drug dosages (if applicable)

  • Length of study

  • Trial goals

Clinical trial process

Prior to a clinical trial, researchers test their proposed intervention in a controlled environment. They may test the intervention on animals or donated human organs. During these experiments, researchers gather data to demonstrate that their intervention works. However, researchers do not know how a typical patient will respond under ordinary circumstances unless they test the intervention on a living human.

Herman uses a hypothetical Alzheimer’s medication as an example.

“All the data in the world may show that this pill can stop the progression of Alzheimer’s in a mouse,” says Herman. “But mice are not humans. Even if evidence suggests humans may respond in a similar fashion, we can’t rely on the treatment until we’ve ruled out the other dangerous side effects. We need as close to absolute certainty as possible.”

When introducing an intervention to humans, those leading the trial must prioritize the health and safety of its participants. A group of experts called an ethics review committee, or Institutional Review Board, weighs the benefits and risks of the trial. They determine if the risk to patients is as low as possible and acceptable enough for the trial to proceed.

In the United States, government agencies, such as the U.S. Food and Drug Administration (FDA) and the Office of Human Research Protections (OHRP), also regulate trials for safety. These agencies often review data submitted by researchers. They then decide whether the intervention is safe enough for further testing.

Clinical trial stages

Clinical trials occur in 4 stages, or phases. Each phase minimizes the risk to participants by enrolling the minimum number needed to answer a research question.

  • Phase 1: Researchers test the safety of an intervention, and its side effects are observed. Fewer than 100 people typically take part in this phase.

  • Phase 2: Researchers test whether the intervention works. They gather data on how it affects a certain disease or condition. Typically, 100 to 300 people participate. Researchers observe new side effects.

  • Phase 3: Researchers prove whether the intervention works among a diverse set of participants spanning different populations. The total can exceed 1,000 participants. Researchers compare the intervention to different drugs or treatments. When studying a drug, they may study the effects of different dosages.

  • Phase 4: Researchers market the intervention, and researchers continue to gather information on its effects. Thousands of people take part in phase 4.

Drugs and medical devices need to pass certain requirements before the FDA approves them for broader clinical use. The FDA typically requires a drug or device to pass phase 1, 2, and 3 trials before granting approval. They may visit the trial site to inspect safety protocols.

Research suggests fewer than 1 in 10 drug development projects makes it all the way from phase 1 to approval. Overall success rates ranged from 5% to 26% by specific drug type.

Who benefits from a clinical trial?

Clinical trials can benefit:

  • Individual patients and families: Sometimes an approved treatment option doesn’t work, or a patient can’t tolerate its side effects. A clinical trial provides another option. Clinical trials may offer payment, too.

  • Health providers: New exams can help doctors diagnose an illness faster and with more accuracy. Clinical trials can also make testing more accessible. At-home tests approved by the FDA, like pregnancy tests, do not require a doctor visit.

  • Society: Those who volunteer for a clinical trial could help a new drug reach its final stages of approval. If a vaccine proves effective with few side effects, its broader use could make a dangerous illness less harmful or likely to spread. The COVID-19 vaccines, for example, can help build immunity from severe respiratory illnesses in communities worldwide.

What are the risks of a clinical trial?

Clinical trials are not for everyone. Consider several risks before signing up:

  • Side effects: In a worst-case scenario, the new intervention causes serious side effects or discomfort.

  • Effectiveness: The intervention may not work. Participants may receive less benefits than from standard care.

  • Control groups: Many clinical trials randomly assign participants to a control group. Participants in the control group receive a standard treatment. Only those randomly selected into the experimental group receive the tested intervention. Participants do not know which treatment they receive.

  • Inconvenience: Trials may take too much time to complete. You may need to travel to the trial site multiple times a week or month or stay at a hospital. Some trials can last months or years.

How can I participate in a clinical trial?

Protocols detail who is eligible for a trial. Researchers determine eligibility based on the trial goals. They may need patients with a specific:

  • Family health history

  • Disease and disease stage

  • Sex

  • Age

  • Height

  • Weight

  • Race or ethnicity

  • Lifestyle

  • Prescription medication

Certain conditions or characteristics may disqualify participants. A single factor can jeopardize the health of the participant or the integrity of the experiment.

“If I’m a researcher trying to see how a new anti-depressant works, I may not want to enroll someone who just started another anti-depressant medication,” says Herman. “There may be no clear way to tell which drug is responsible for improvement or regression, or whether an improvement may just be the result of the two drugs working together.”

Likewise, he adds, a patient with an irregular heartbeat, or atrial fibrillation (aFib), or constant chest pain may not qualify for clinical trials requiring high-intensity exercises. The exercise may put the participant in an unnecessarily harmful situation.

What questions should a patient ask before joining a clinical trial?

Before signing up, determine whether a clinical trial is right for you. Contact the health care team conducting the trial and your primary care provider (PCP).

Ask:

  • What happens during the trial?

  • What type of care will you receive?

  • What costs can you expect?

  • What are the benefits and risks of the intervention?

How can I participate in clinical research?

Academic research hospitals, including those across Mass General Brigham, regularly invite volunteers to participate in clinical trials. You can also find trials through government agencies, such as the National Institutes of Health (NIH), FDA, and National Cancer Institute (NCI).

The Gene and Cell Therapy Institute (GCTI) at Mass General Brigham is a hub of innovation and collaboration, uniting more than 400 researchers and clinicians dedicated to advancing gene and cell therapy. The GCTI accelerates groundbreaking research, conducts clinical trials, and facilitates the development of FDA-approved treatments.

The Mass General Brigham Biobank offers another opportunity to participate in clinical research. The biobank collects biological material and health information from patients. Mass General Brigham researchers then use the information to study how genes, the environment, and lifestyle affect human health.

Participation in the biobank is completely voluntary. To date, more than 135,000 people have donated samples, and more than 450 research studies have used its data. The studies have covered topics including:

Explore clinical research at Mass General Brigham (opens external link in new tab)
Bob Herman

Contributor

Bob Herman
Director, Clinical Research