Clinical Trials

Clinical trials are carefully planned research studies that assess new drugs, devices, procedures, biologics (for example, vaccines or targeted therapies), diagnostic approaches/tools.

These studies also test interventions that might help prevent another heart attack or slow the progression of diseases (for example, cardiac rehabilitation or team-based care, etc.).  

Research studies look at specific drugs or treatments to determine:

• If they are safe (and to identify what, if any, side effects might occur)
• If they work
• How they compare with current treatments (called usual or standard care)
• Optimal doses (amounts) and frequency of treatments

Cardiovascular studies help answer scientific questions and find new ways to:

• Prevent  
• Detect and diagnose
• Treat
• Manage symptoms of heart and vascular diseases

Often during research, the best standard treatment or procedure is compared with the best standard treatment + new drug or intervention.

Research studies also can be designed to look at large populations of people (called observational studies) and to identify important trends in heart disease over time.

Researchers also plan trials to evaluate how certain lifestyle habits such as diet or exercise influence outcomes. For instance, the DASH diet plan was shown in a clinical trial to lower blood pressure, especially among Black patients.

Each clinical trial follows a specified protocol that spells out how the trial will be conducted. Think of the protocol as the rules that must be followed to ensure the results are consistent and reliable.

Among other details, the study protocol clearly defines:

• The reason for doing the trial: What question needs to be answered.
• How many people are needed: The number of people required to give the trial enough power so that the findings apply to those who would use the treatment being studied.
• Who can and cannot take part in the trial: These are called eligibility criteria.
• The treatment plan/intervention: This describes the medication or device under study, including when, how and at what dose it will be given.
• How patients will be assigned to each study group: For randomized trials, participants in the treatment and control groups are similar at the start of the study and most, if not all, other factors are kept the same; this way, researchers have good reason to believe that if the outcomes differ among study groups it is because of the treatment.
• Who is in the know: Trials are often double-blinded, meaning that neither the participant nor the researcher knows which therapy is being given to whom.
• What tests and follow up will be done, how often and for how long
• What type of data or information will be collected and how often: For example, the protocol lists which measures will be tracked, such as blood pressure or cholesterol levels and/or whether someone has a cardiac event or goes to the hospital during the study period.

This plan is especially important when there are multiple sites and researchers involved. It helps ensure the research is done in the same way across each facility. Studies are bound by strict regulatory and ethical standards.

New medicine and devices have to advance through four phases of study. While each phase has a different goal, each one builds on the next.

Researchers start by studying the treatment in a small group of patients. They will invite more people to enroll once there is clear evidence that the therapy being tested causes no harm.

Participants can drop out of a clinical trial at any time. The study can also be stopped midway through if there is any indication that the study treatment is harmful

Trial Phase	Main Focus	People Enrolled *	How Long
Phase 1	Is it safe? What’s the best dose (amount) to give?	20-100 healthy people with the condition	Several months
Phase 2	Does it work? Are there side effects?	100-300 people with the disease	Several months to 2 years
Phase 3	How well does it work? How does it compare with existing treatments?	300-3,000 people	1-4 years
Phase 4	Post-marketing studies that look at how the drug works in a large population of patients over an extended period of time. Is there continued safety and efficacy?	Several thousand

_{* Studies that enroll people with rare diseases—conditions that affect fewer than 200,000 Americans—often will include fewer patients at each stage of study.}

Not all drugs or devices progress to the next phase of study either because they do harm, are found to be ineffective or other reasons.

FDA also has fast-track and breakthrough therapy designations to help speed up the development and study of drugs that treat serious or life-threatening conditions or that fill an unmet medical need.

A number of people and institutions are involved in clinical trial research.

• Trial sponsors: organization, institution or company that funds the trial
• Trial sites: place where the study happens (for example, in hospitals, universities, doctors' offices or other clinics)
• Principal investigator (PI): doctors or clinicians who oversee the trial
• Research team: group made up of individuals who support the PI including other clinicians, as well as the study coordinators, research assistants, nurses and biostatisticians who measure how volunteers respond to new drugs and devices
• Participants: people who volunteer their time to enroll and help advance science
• Food and Drug Administration: government agency that sets the standard of how trials should be conducted and evaluates the safety of drugs and medical devices and how well they work
• Institutional Review Boards: these ethics committees, called IRBs, and other drug and safety monitoring boards, help protect patients’ rights and safety
• Contract research organizations: group that provides support to pharmaceutical, biotechnology and medical device companies to coordinate trials across multiple locations

Clinical trials rely on volunteers. Many clinical trials are delayed and some never happen because there aren't enough volunteers.

People might decide to join a clinical trial for many reasons. For example, to help:

• Improve their own condition with closer monitoring, and for access to health professionals and a promising new therapy that is not available for public use
• Learn more about their disease
• Advance science and treatment
• Potentially save lives

Historically, certain groups—women, people 75+ years old and certain racial/ethnic minorities, in particular—have not been well represented in clinical studies. Yet, we know certain treatments work differently in men and women, as well as in people from different racial/ethnic backgrounds.

Many of these groups also have a heavier burden of cardiovascular disease and risk factors. New therapies need to be tested in a wide variety of people to truly gauge how well they work within the general population. If a drug is studied only in adult white men, it is not necessarily applicable in general to others.

“A wide range of people should have the opportunity to participate in trials both to have access to new therapies and to have the chance to contribute to better treatment of everyone,” said Keith C. Ferdinand, MD, professor of medicine, Tulane University, New Orleans. “It’s an important altruistic goal for many Americans.”

Martha Gulati, MD, stresses that volunteers are the foundation of clinical studies. “We will only know if and how a therapy works in men and women, and different racial/ethnic groups, if we study these interventions in everyone,” she said.

Only a small fraction of people with heart or vascular diseases actually take part in clinical trials. But of those who do participate, many say they would join one again. Unfortunately, there are barriers or hesitations to participate. People may:

• Be unaware of clinical trials (their health care providers may not have talked with them about this as an option)
• Lack access to clinical trials (travel and time)
• Not meet the study’s inclusion criteria
• Worry about side effects or that the new treatment will not be equal to or as good as standard care
• Worry that they will get the placebo
• Be worried that their insurance won’t cover clinical trials

“Clinical research does not pay participants in research studies but often will help with travel costs, and the volunteers benefit form uncovering how new drugs and devices will work for all patients,” Dr. Ferdinand said. “If a major breakthrough therapy is discovered, the new therapy is sometimes offered as compassionate, extended free therapy.”

Depending on your condition, Dr. Gulati says it’s important to ask about clinical trials as a potential treatment path so you know all of your options. These studies aren’t only for people with late stage heart or vascular diseases.

It’s important to talk with your health care team about how you are feeling and if your current treatment plan is working for you. A lot of research us underway, so taking part in a clinical trial may be or become an option for you in preventing or treating heart disease.

If you’re thinking about participating in a clinical trial, here are a few questions you might want to ask:

• Is a clinical trial the right option for me given my medical history and prognosis?
• How do I find a clinical trial that might benefit me?
• How long will the study last?
• What are the risks?
• What does randomized mean?
• What are the costs?

Here are some sources to find more information about clinical trials:

U.S. Food and Drug Administration
Drug Trials Snapshots: Provides consumers with information about who participated in clinical trials that supported the FDA approval of new drug

U.S. National Institutes of Health Clinical Trial Registry
ClinicalTrials.gov

Centerwatch—allows you to search and find clinical trials

• CenterWatch.com
• Information on volunteering 

National Institutes of Health
Patient Bill of Rights