This week’s newsletter looks at the dire consequences of when research is focused on only one swath of the general population (white men) and the ramifications of that practice. First, we will look at the ways that male-dominated research has impacted women’s health historically. Then, we will look at the ways that researchers are trying to diversify when searching for those willing to be part of a vaccine trial. The issue has pressing significance as we look toward the development of a vaccine for COVID-19 which has affected Black and brown communities at a disproportionate rate.
A brief history of women’s participation in clinical trials
The history of pharmaceutical research has, until the past 25 years, excluded women and minorities leading to misunderstanding of the different ways that drugs impact individuals. Early clinical research typically used white men as subjects. Why? It is hard to know, but some of the reasons given in the past include researcher bias, the fact that women’s hormones fluctuate throughout the month possibly interfering with results, the danger of testing on pregnant women (see the thalidomide debacle of the 1960s), and the expense of looking at a variety of races and genders. But as more and more drugs hit the market, researchers discovered that women and minorities experienced different levels of side effects than White men. For example, Ambien left women with severe grogginess in the morning preventing them from driving and working. This was because the dosage had only been tested on male subjects.
In a National Institutes of Health (NIH) review of the history of clinical research, we see a call to include more women in clinical research. Diseases that are more prevalent in women were not being researched adequately. Additionally, some diseases like sexually transmitted ones express themselves differently in women than in men. It is important to understand these differences. Fortunately, “in 1998, the FDA issued a final rule entitled “Presentation of Safety and Effectiveness Data for Certain Subgroups of the Population in Investigational New Drug Application Reports and New Drug Applications”. This regulation specifically states that New Drug Applications (NDA) must present safety and efficacy data for important populations, including sex, age, and racial subgroups.”
Brian Prendergast, a professor at the University of Chicago's Department of Psychology, studied the impact of pharmaceuticals on women’s bodies and brains. His June 2020 study in Biology of Sex Differences found 86 drugs with more adverse side effects for women, including nausea, seizures, and cardiac arrhythmias. The study concludes with this recommendation. “The common practice of prescribing equal drug doses to women and men neglects sex differences in pharmacokinetics and dimorphisms in body weight, risks overmedication of women, and contributes to female-biased adverse drug reactions. We recommend evidence-based dose reductions for women to counteract this sex bias”. So, even though researchers are studying the differences between how drugs affect men and women, they are still writing dosages based on the results for men!
While the 1998 rule is good news and has helped to make great strides in clinical research for women, we must be vigilant when it comes to the COVID-19 vaccine. Nicole Woitowich, associate director for the Women's Health Research Institute at Northwestern University, was disappointed when she saw preliminary research statistics for the early phases of the vaccines. While women were included in the studies, the breakdown by sex was not available. Woitowich is hopeful that they are being analyzed by sex so that women can be confident that the vaccine is safe for them at the dosage given.
Finally, the NIH has also published research outlining the ethical issues that arise when deciding whether to include pregnant women in vaccine trials. I invite you to read the study to find out more about this topic, but their conclusion is that pregnant women should have the autonomy to decide whether to enter a clinical trial after being informed of any possible dangers.
COVID-19 Vaccine Development and Minority Populations
So how are things going in the COVID vaccine research for minorities? Well, if we look at phase 1 and 2 data, it is not promising. In a Moderna phase 1 trial, out of 45 subjects, 40 were white. But, in phase 3 trials, all of the pharmaceutical companies involved claim that diversity within the research cohorts of over 30,000 people will be of paramount importance. To make sure that they get the representation of women and minorities, the companies have several tools. The first is to actually ask those populations to participate. Historically, communities of color and women have not been approached for participation. According to Linda Goler Blount of the Black Women’s Health Imperative, “The No. 1 reason Black people and Brown people don’t participate in clinical trials is because nobody asks them.” When they are approached, the discrepancy narrows or disappears. Another tool is to take a mobile clinic to where your desired participants live. Dr. Richard Novak, the lead investigator at the University of Illinois at Chicago for Moderna’s Covid-19 vaccine trial, is planning to take a mobile clinic to African-American churches and communities where they can enroll many people at once.
But one problem that researchers may come up against in minority communities is a suspicion of researchers rooted in racist history. Given that the Tuskegee experiment, where Black men were told they were receiving treatment for syphilis but were really being observed to see the progression of the disease over 40 years, is still in the memories of living people, it is no wonder that there is distrust. Henrietta Lacks’ cells were used to develop all sorts of drugs and treatments used today without her family’s knowledge or permission. Researchers have a heavy lift in convincing minority communities that they have their best interests at heart.