Clinical Research

Clinical trials are carefully planned research studies that assess new drugs, devices, procedures, vaccines, or tests or screenings.

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).

The 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.

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 needed so that the research findings about the treatment are meaningful.
• Who can and cannot take part in the trial: These are called eligibility and exclusion 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 conclude 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 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 heart event or goes to the hospital.

This plan is important when more than one site and several researchers are involved. It helps ensure the research is done in the same way at each site. 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 sign that the study treatment is causing harm.

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 people in the U.S. – often will include fewer patients at each stage of study.}

Some drugs or devices don't progress to the next phase of study because they do harm, are found to be ineffective, or for 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.

Clinical research involves a number of people and institutions:

• 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

Another type of clinical research involves researchers gathering information from participants or examining information that has already been collected. This is called an observational study.

In this type of study, researchers do not assign a particular intervention to participants.

These research studies often are designed to look at large populations of people. Observational studies help identify important trends in heart disease over time.

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

People might decide to join a clinical study 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 older than 75, and people from certain racial and ethnic minority groups – 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 or 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 find out how well they work within the general population. If a drug is studied only in adult white men, the research findings may not apply to people of other backgrounds.

“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, associate director of the Barbra Streisand Women Heart Center in Los Angeles, stresses that volunteers are the foundation of clinical studies. “We will only know if and how a therapy works in men and women, and people of different races or ethnic groups, if we study these interventions in everyone,” she said.

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

• Be unaware of clinical studies (their health care providers may not have talked with them about this as an option)
• Lack access to clinical studies (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 studies

Participants in research studies may receive a small compensation, which can help cover travel or other costs.

"Also, volunteers can benefit from 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 studies 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.