Pharmacologist presents plan to improve equity in drug development

In a new perspective article published in the Feb.5 issue of Science, pharmacologist Namandje Bumpus, Ph.D. – who recently became the first African-American woman to head a department at Johns Hopkins University School of Medicine and is the only African-American woman to head a Department of Pharmacology in the country – describes the molecular origins of the differences in the functioning of certain drugs between distinct populations. It also presents a four-part plan to improve equity in drug development.

Human beings are more similar than we are different. Yet even the slightest variations in our genetic material can cause big differences in how drugs work in our bodies. It’s not a new idea. “

Namandje Bumpus, Ph.D. Pharmacologist, Johns Hopkins University School of Medicine

Genetic variants may be more likely to occur in some ethnic groups than in others, and as a champion of scientific diversity, Bumpus argues that these differences make increasing diversity in clinical trials even more important. new drugs and therapies. Still, many clinical trials continue without diverse participation, which can lead to poor outcomes for people of color and reduced access to emerging therapies.

Some drugs available today, such as warfarin, used to thin the blood, have been shown to be less effective in people of African descent; and, according to previous studies, one in five new drugs approved by the FDA showed differences in effectiveness between ethnic groups.

Today, as new treatments and vaccines take us to a critical juncture in a pandemic that has disproportionately affected people of color, the need for better standards of diversity in clinical trials is greater than ever, Bumpus says , EK Marshall and Thomas H. Maren Professor and Head of the Department of Pharmacology and Molecular Sciences at Johns Hopkins University School of Medicine.

But increasing the number of underrepresented minorities in clinical trials is not enough to solve systemic problems, she adds.

Bumpus’ framework for better drug development includes a four-part plan involving laboratory research of cell and animal models to study genetic variability; better hiring practices to diversify the scientific workforce; diversity requirements for funding agencies; and requirements for diversity reporting on clinical trial demographics in articles published in scientific journals.

By implementing diversity requirements that demand diversity among clinical trial participants and in study design, funding agencies would ensure accountability – and scientific journals would increase transparency for their audiences, Bumpus says. At the research institute, biotechnology and pharmaceutical company level, Bumpus advocates for recruiting practices to build a more diverse workforce. With a diverse workforce, there is diversity of thinking, she says, and a greater likelihood that researchers will be better able to incorporate genetic variation into their studies.

She notes that animal models can be genetically engineered to reflect variations that occur between ethnic groups, potentially to “enhance predictability of drug outcomes and provide a mechanistic basis for understanding disparities.”

Genetic variations related to drug response are often associated with a family of enzymes vital for drug metabolism, called cytochromes P450. This family of enzymes in humans processes around 75% of clinically available drugs.

Still, subtle genetic differences can alter the enzyme in people, and some gene variants are more prevalent in specific ethnic groups. The modified enzyme could affect the way drugs are processed and used by the body, so what works for one person may be ineffective or toxic for another.

Since most clinical trials of these drugs have included people of European descent and few people of African descent, the differences in drug efficacy are often not immediately known.

Bumpus says the framework may force the field of drug development to take steps toward a future where “treatments are most likely to work for all” and “existing health disparities are not yet exacerbated.”