Clinical trials are a vital stage in the development of any drug for market. However, they can have weaknesses, and a common one is the demographic makeup of the trial population.
In some cases, a narrow patient group is needed, but in others, especially vaccine trials, you need as diverse a population as possible to ensure that the drug works in all groups. Traditionally, in the U.S., ethnic minorities are underrepresented in clinical trials, with Caucasians tending to dominate. This is particularly the case for African-Americans. For example, for 24 cancer drugs approved between 2015 and 2018, less than 5% of the subjects were African-American, even though several of the drugs were for conditions that disproportionately affect them.
In some trials, women are also underrepresented, although there is often a clinical reason for that.
WHY ARE MINORITIES UNDERREPRESENTED?
There are a number of reasons why minorities and women may be underrepresented in clinical trials. Here are some of the most common:
- Trial designers may sometimes exclude women because they do not want anyone in the trial population who is pregnant.
- Native Americans are hugely underrepresented, in no small part because of the logistics of accessing healthcare in general from reservations.
- Minority providers tend not to participate in clinical trials.
- African-Americans tend to have a historical distrust of the healthcare system, especially when it comes to “experiments.” The Tuskegee Study is still sometimes cited as a reason for avoiding participation in trials; the experiment was an utter disaster, with participants not properly informed as to the purpose of the study and were not offered appropriate treatment.
- Trial data and materials are not always available in languages other than English, resulting in lower representation amongst non-English speaking immigrants.
- Trans and non-binary patients may be reluctant to sign up for trials if they are not treated with courtesy and their gender and pronouns respected.
- Study designers will sometimes exclude non-whites, and unconscious bias may come in when race is concerned.
So, all of this results in a bias towards white males when recruiting trial populations. Does it matter? The short answer is, yes.
WHY DOES DIVERSE PARTICIPATION MATTER?
Age, sex, and ethnic background call all impact how somebody responds to a drug. Some drugs may work better, or worse, in African-Americans, For example, in treating cardiovascular conditions, it’s been discovered that Blacks respond slightly better than whites to CCBs and diuretics, while whites respond better to ACE inhibitors and beta blockers.
Additionally, some conditions disproportionately affect different ethnic groups. While some of these differences are socio-economic, others do appear to be real. Native Americans generally have a higher risk of colorectal cancer, and while white people are at higher risk of skin cancer, African-Americans tend to have worse outcomes (partly because it can be harder for both doctors and patients to identify problems on darker skin).
Women, of course, can have quite different reactions from men, and trans people can have different reactions again. Very few drugs are tested on trans men who are taking testosterone, or on trans women who are taking estrogen, on testosterone blockers, or have had an orchidectomy.
Ensuring that the study population is diverse can help identify drugs that might be prescribed preferentially to different groups, or drugs which might be risky for certain populations.
The focus on white men, which is both deliberate and accidental, can potentially result in worse outcomes for other groups, or in a study missing something which might help a certain population.
In many cases, drugs are approved based on a narrow patient population and then problems show up later when they are given to a broader patient group.
HOW CAN DIVERSITY BE IMPROVED?
There are two key aspects to improving diversity:
This can happen at both the study design level and the logistical level. Applying “quotas” to ensure a diverse population can be used to ensure that trial administrators include different backgrounds and ask more people from minorities to participate. Other things which can be done include:
- Recruiting and training more minorities as clinical investigators. This both improves trust and ensures that diverse populations are remembered.
- Translating trial materials into other languages.
- Understanding cultural barriers and acting appropriately. For example, many Hispanics prefer not to have providers enter their homes.
- Using mobile providers to bring the trial to the participants, especially in rural areas.
- Collaborating with community leaders. For example, Black churches have proven useful in working with their communities to recruit more African-American participants.
- Providing cultural sensitivity training to providers working in trials, and providing translators into both foreign languages and sign when needed. Ideally, point of care providers should be of the minority concerned, but this is not always possible. Training should also include reaching out to and working with the LGBT community, who also tend to be underrepresented.
REACHING OUT TO PATIENTS
Trial investigators don’t always ask the right patients. Involving providers in minority communities can make a huge difference. In many cases, members of ethnic minorities seek out medical providers of the same ethnicity, and are more comfortable with them. Most people find out about clinical trials through their point of care providers.
This makes these providers essential to reach out to patients and encourage them to join trials. Training these providers in trial recruitment is key, as is bringing more minorities in as clinical investigators.
Patients also need to be educated and reassured that the goal of recruitment is not to have them carry a burden for white people, but rather to help them get the same benefit from research discoveries. Studies also show that increasing access to clinical trials is associated with improved healthcare access in general.