What Are Clinical Trials and Why they are important to all of us

Clinical trials are medical research associated with a specific drug or treatment. They are conducted utilizing everyday people to determine the effectiveness and safety of medical and surgical treatments. Every medication, surgical treatment, and diagnostic study used today has undergone rigorous investigation in animals and humans to determine if these interventions are safe and perform as intended. As new treatments are developed, researchers conduct clinical trials to determine if a new treatment is more effective than an existing treatment and if it has more (or fewer) side effects than the standard treatment. This is how the science of medicine evolves.

Some clinical trials are focused on the study of new diagnostic tools. They may involve studying methods of early detection of a particular disease before it is symptomatic. Other clinical trials may look at new treatments to help prolong life for patients suffering from life-threatening diseases or improve the quality of life for those suffering from chronic health problems. Today’s most advanced medical treatments and devices, like robotic surgical platforms, wireless glucose monitors, and insulin pumps, would not exist without clinical trials.

The FDA will not approve a clinical trial without compelling data from many laboratory tests and animal studies that test a potential treatment’s safety and efficacy. If these preliminary studies meet the very high bar set by the FDA, researchers will receive approval for the new medical treatment (or diagnostic) to be tested on people.

 

How Clinical Trials Work
There are four phases of clinical trials that new treatments must advance through to determine their safety and efficacy before being marketed to the public:

• Phase 1 trials – These are typically tests of the new treatment on a small number of participants (20 to 80 individuals) to evaluate their safety, side effects, and the correct dosage to be used in Phase 2.

• Phase 2 trials – These trials will usually involve 100-300 participants. Phase 2 trials are used to determine how well the drug or intervention works in people who have the targeted disease or condition and can last for several years. As always, they continue to monitor safety, including side effects.

• Phase 3 trials -These studies aim to expand the information about a new treatment’s safety and effectiveness (efficacy). These trials study the drug or treatment in different populations at different dosages, sometimes using the drug in combination with other rugs. These are much larger trials conducted in several hundred to several thousand people. If the treatment successfully executes this phase and the results are favorable, the experimental drug or device will be approved by the FDA.

• Phase 4 trial – These studies are conducted after a drug or device has received FDA approval and is being used by treating physicians in patients with the target disease or condition. The device or drug’s safety and effectiveness are monitored in large and diverse populations. This longer follow-up period will sometimes identify side effects that become evident only with time.

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Why Clinical Trials are Important

Clinical research is critical in the modernization of medical diagnostics and treatments. For instance, it may be hard to believe that only a few decades ago, the primary treatment for advanced prostate cancer was the “surgical” removal of the patient’s testicles. Through aggressive clinical research, physicians can now treat advanced prostate cancer with medications and allow patients to keep their testicles. Breast cancer clinical research showed that many types of breast cancer could be successfully treated while enabling women to keep their breasts. After nearly 40 years, these advancements in cancer treatment continue to benefit patients and provide the building blocks for even more medical advances.

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Inclusion and Diversity in Clinical Trials: Why is it important?

It is a well-known fact that racial and ethnic disparities exist in the access to and delivery of healthcare in the U.S. The COVID-19 pandemic has highlighted this. Indeed, racial disparities in clinical outcomes continue to persist in several common diseases, such as obesity, high blood pressure, diabetes, and limb amputation. Even more concerning is the fact that when studies have adjusted their patient samples for socioeconomic status, insurance coverage, equal access to care, co-morbid conditions, etc., the disparities remain! These disparities drive unacceptable sickness and death rates among African Americans and other people of color. Many scholars believe that the low numbers of BIPOC people participating in clinical trials are a crucial determinant of the racial differences in healing and death. For example, if the effective dosage of a drug is mainly tested on Caucasians, will that same dose be safe or effective for other racial groups? Moreover, if a specific cancer gene or heart disease gene is more common in one racial group and they aren’t fairly represented in a trial, then how can the behaviors of that gene be adequately evaluated?

The result is continued high morbidity and mortality for African Americans and other BIPOC patients from cancers and chronic illnesses. Does the underrepresentation of BIPOC people in clinical trials put these populations at risk? Is what is deemed an effective dosage of a drug that has only been studied in a large population of white patients the same effective dosage that should be used in African American, Asian or Hispanic patients? These important questions can only be answered through clinical trials with representative numbers in appropriate numbers of patients from these minority populations.

Pharmaceutical and biotech companies are looking to prioritize inclusion of racial and ethnic groups in all of their clinical trial for safety reasons. Studies have shown that there are differences in how certain medications are broken down (metabolized) by people of different racial groups. This can lead to different dosing requirements in African American, Asian and White patients. Atypical drug responses and unexpected side effects have been seen with medications used to treat high blood pressure and psychiatric disorders in patients of diverse
racial and ethnic backgrounds. One area of concern is the use of generic medications instead of brand-name drugs. This is now very common with some insurance plans, especially Medicaid, which serves the poor. This has a disproportionate impact on African American patients. There is significant evidence in the medical literature that shows these “substitutions” place minority patients at greater risk. This is because a drug’s effectiveness and side effects (or toxicity) can vary amongst different racial and ethnic groups. The effective dosage of medication may require dosage adjustments to achieve the desired effect or to reduce the risk of certain side effects. These determinations should be made during the clinical trial process, not after a drug has been approved for use.

Many complex factors may be responsible for racial variations in response to certain medications and treatments. These factors could be environmental, cultural, psychosocial, and genetic. These are the reasons why diversity and inclusion are so important in the development of new drugs and other treatments. I find it disturbing that African Americans have seen little improvement in disease-related morbidity and mortality over the past 40 years as other groups in the U.S. have from the many advancements in medicine. We must participate in medical research and clinical trials to reap the benefits of improved quality of life and longevity. We must also take advantage of the pharmaceutical and biotech's current interest in improving diversity in clinical trials, both in patient recruitment and in the inclusion of BIPOC physician researchers.

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References

1) V. Burroughs, et al. Racial and Ethnic Differences in Response to Medicines: Towards Individualized Pharmaceutical Treatment. Journal of the Natl Med Assoc. Vol 94, No. 10 (suppl), October 2002
2) CC Lang, et al. Attenuation of isoproterenol-mediated vasodilation in blacks. N Engl J Med. 1995;333:155-160.
3) WB Lawson. Clinical issues in the pharmacotherapy of African-Americans. Pyschopharmaco Bull. 1996;32:275-281.

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