Increasing Diversity in Clinical Trials

Heart disease remains the No. 1 killer of men and women. Yet, estimates are that it is 82 percent preventable through lifestyle and efforts to stay heart healthy, according to the National Institutes of Health.

What’s more, women, racial and ethnic minorities are more vulnerable to developing cardiovascular diseases. They also continue to lag behind when it comes to health outcomes, including heart attacks, stroke and related death. African Americans, for example, tend to have higher rates of diabetes, obesity, high blood pressure and untreated high cholesterol—all very powerful risk factors for cardiovascular disease and poor outcomes. As a result, African Americans have the highest rates of heart disease. Until recently, women have also had higher rates of deaths due to cardiovascular disease. When compared to men, women are less likely to survive a first heart attack, and young women have the poorest outcomes after a heart attack.

More: Understanding Clinical Trials

So what’s behind these trends?  A number of factors may contribute to the health disparities among gender and racial/ethnic groups. For example:

  • Few research studies are designed to look specifically at heart and vascular diseases in women, older adults (75+), and among racial and ethnic minorities, yet we now know these diseases and their treatments play out differently among these groups.
  • Clinical trials have largely enrolled white men. Historically, participation has been low among:
    • Women
    • Adults ages 75 and older
    • People of certain racial/ethnic groups

A typical cardiovascular clinical trial often includes many more men than women. In fact, very few studies have an enrollment that is half women. Even when research studies include women, there is evidence that sex-related differences are often not examined, even in deeper analyses of the data. In addition, more than half of trials for coronary heart disease over a decade failed to enroll any patients over 75 years old.

Other factors are at play, too, including a lack of:
  • trust in research studies, and questioning whether the clinician has their best interest in mind
  • fear of unintended outcomes, not wanting to be a “guinea pig”
  • care that factors in someone’s cultural values and beliefs (called culturally competent care)
  • minority leadership in clinical trial investigations (only 1% of all principal investigators at NIH are African American)
  • access to preventive care or specialty care centers, which translates into more instances of heart disease, stroke and cancer, and fewer opportunities for being referred to clinical trials
  • access to safe open spaces or fresh fruits and vegetables (“built environment”)
  • physician awareness about the different risks (one study found only 17% of cardiologists correctly identified that women have a higher risk for heart disease than men)

“It would be great if everything we learn from clinical research could be applied to everyone. In reality, cardiovascular disease and many other conditions are not the same across genders and racial and ethnic groups, and neither are their responses to treatment.”—Martha Gulati, MD

Making Sure History Doesn’t Repeat Itself

Historically, older patients, women and racial/ethnic minorities have been underrepresented in trials. As a result, it’s often not until a large number of people start using these medications after they are approved by the Food and Drug Administration (FDA) that differences in how they work in various patient groups come to light.

Some drugs appear to affect men and women differently. Also, race and ethnicity can make a difference. For instance, to treat high blood pressure, angiotensin-converting enzyme (ACE) inhibitors have been shown in some studies to be less effective in African American patients than in white patients. There is also some evidence that our genes play a role as well, often interacting with our diets and environments. For example, it seems that African Americans may be more sensitive to the effect of salt, which raises the risk of developing high blood pressure. The same salt sensitivity has been described in patients with obesity and chronic kidney disease.

At times, the FDA has required changes to drug labels because of differences in how these medications work in men and women. For example, doses of a common sleep aid were halved in women due to its more potent effects. These differences are why it’s important to test drugs on diverse patient populations, and to pursue trials that identify unique risk factors.  

“We know treatments work differently in different people, so to get a complete picture of the benefits and risks of a particular therapy, people involved in clinical trials ideally need to represent everyone who is likely to use the treatment or intervention being studied” said Keith C. Ferdinand, MD.

Research studies pave the way for new and better therapies. In recent years, the FDA has called for wider representation of people of different ages, races, ethnic groups and gender in clinical trials. The goal is to ensure medical products are safe and effective for everyone.

It Comes Down to Numbers

Researchers need a large enough sample of patients to be able to draw conclusions, and it seems we have a long way to go to add more diversity into clinical research.

In 2011, African Americans made up 12% of the U.S. population, yet only 5% of clinical trial participants, according to the FDA. Hispanics made up 16% of the population, but only 1% of studies. Meanwhile, whites were overrepresented: They accounted for 83% of participants in clinical trials and 67% of the U.S. population.

“Ignoring the racial/ethnic diversity of the U.S. population is a missed scientific opportunity to fully understand the factors that lead to disease or health.” —PLOS article
Why It’s important

Race, ethnicity, sex and age may play a defining role in how heart disease and stroke develop, how they are detected, in some cases, and how we might respond to different treatments. There are:

  • Genetic variations in heart and vascular disease,  and how it develops across ethnic groups
    • 75 percent of Pacific Islanders are unable to convert clopidogrel, a drug used to prevent heart attacks and strokes, into its active form
  • Higher rates of certain diseases across certain populations
    • African Americans have a greater risk of death from heart disease than whites, yet they are underrepresented in studies of potentially lifesaving drugs
  • Females have a 1.5-1.7 fold greater risk of having a bad reaction to medications compared with their male counterparts; several drugs have been withdrawn from the market or the doses have been scaled back because of women’s adverse reactions.
  • African Americans have more  angioedema, a potentially life-threatening condition , with ACE-inhibitors and dual ARB/sacubutril used to treat patients with heart failure  
  • The reason diverse races may respond differently from others is unknown. In addition to genetics, people respond to drugs based on body weight, diet patterns and lifestyle factors.

How to Get Involved-Closing the Research Gap

Many people who have participated in a clinical trial say they would do it again. Among the reasons to take part include helping to make sure treatment options continue to advance and benefit future generations.

If you or a loved one wants to learn more about clinical trials as an option for treatment, talk with your health care team. You might want to ask:
  • Would a clinical trial be a reasonable option for me?
  • Will it affect my usual care?
  • How does the study treatment differ from what’s currently available?
  • How much time will it take?
  • What are the risks?
  • Can I drop out?
  • How will you keep my doctor informed about my treatment?
  • Are there reimbursements for travel/child care?
  • Will this research help others like me in the future?

Resources /How to Find a Clinical Trial

CardioSmart.org
To learn more about your heart condition or risk, CardioSmart.org has a wealth of resources and tips. Visit our condition centers.

U.S. Food and Drug Administration

Office of Women’s Health
WomensHealth.gov

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

Centerwatch

National Institutes of Health
Patient Bill of Rights


Published: April 2017
Medical Reviewers: Keith C. Ferdinand, MD, FACC, FAHA; Martha Gulati, MD, MS, FACC, FAHA

Infographic: Clinical Trials

Patient Resource

CardioSmart Benefits

  • Get personalized newsletters and email alerts
  • Track key health indicators and physical activity
  • Bookmark news articles, fact sheets and questions to discuss with your doctor 
  • Take quizzes to improve health and earn prizes

Questions about a drug?

Featured Video

Serious threats to your health can occur when your medication regimen is skipped, modified, or ignored.