The American Medical Association (AMA) announced last week a new policy for including more women and sexual and gender minority (SGM) populations in clinical trials and medical research—including within the ophthalmic field.
First up: Define SGAs.
Accounting for an estimated 4.5% of the U.S. population, the SGM population is comprised of (but certainly not limited to) the following individuals who identify as:
- Lesbian
- Gay
- Bisexual
- Asexual
- Transgender
- Two-spirit
- Queer
- Intersex
In regards to clinical research: The National Cancer Institute (NCI) has noted that a growing body of evidence suggests members of SGM populations experience higher rates of certain cancers and worse physical and mental health after diagnoses vs non-SGM populations.
The barrier: A lack of systematic and standardized sexual orientation and gender inclusion (SOGI) data collection in surveillance, research, and clinical settings.
What else?
This population’s participation in clinical trials has also not historically been representative of the general population—with these individuals omitted entirely as a category for clinical research, even when they are a high-risk population, according to the AMA.
Now explain how women are impacted.
Despite the creation of the National Institutes of Health (NIH) Revitalization Act in 1993, both women and SGM populations in clinical research have been grossly underrepresented.
Note: This act sought to increase the clinical trial inclusion of diverse populations in order to decrease the imbalance of health care disparities.
- Zeroing in on women: Prior to the Revitalization Act, FDA regulations established in 1977 had barred all women of child-bearing age from clinical trial participation—apart from life-saving medication—due to a fear of birth defects from a medicine similar to thalidomide (an antineoplastic for cancer originally discovered to have a high risk of severe/life-threatening risks in the 1950s).
- Later: This 1977 exclusion was later updated in 1986 when the NIH passed a policy to encourage women’s participation in clinical research.
Let’s talk about the issue.
This exclusion from clinical trials and medical research has led to “unnecessary health inequities” and negatively impacted the care these populations receive, according to AMA Board member Toluwalase Ajayi, MD.
- Even more so: “Without this important data, there’s no way to know whether medications and medical devices are not only safe, but effective, for use in women and SGM populations,” stated Dr. Ajayi.
The proposed solution: Increasing the number of women and SGM participants (as well as researchers) in clinical research in order to develop more targeted and effective medications and medical devices for their needs.
Tell me more about this new policy.
The policy amends AMA's 2023 Council on Science and Public Health (CSPH) report: Sex and Gender Differences in Medical Research to include three additional clauses:
#1: The policy advises that the AMA will support the FDA in requiring drug and device sponsors in order to develop “actionable clinical trial diversity action plans” that feature both women and SGM populations.
#2: The AMA is expected to aid the FDA in its conditioning of drugs and device approvals on post-marketing studies “that evaluate the efficacy and safety of products in women and SGM populations” when these populations are not properly represented in drug/device clinical trials.
Go on …
#3: The AMA will also be promoting more funding from the NIH (plus other grant-making organizations) to support post-market research into pharmacodynamics and pharmacokinetics for generic drugs that didn’t originally include proper clinical trial representation from women/SGM participants.
Why this is key: Such prioritization is particularly critical for drugs in which women/SGM populations account for a significant number of patients or reported associated adverse events (AEs).
Note: The final language for this new policy is still being finalized prior to becoming publicly available on the AMA website.
So why make this a priority now?
While policies (like the Revitalization Act, mentioned earlier) and programs have sought to address the misrepresentation of these patient demographics, a 2021 study analyzing their inclusion in NIH-funding trials identified two key findings:
- Only 26% used sex as a variable for analysis
- Over 70% did not include sex as a variable
In fact: Despite the NIH announcing a policy in 2014 that required NIH-funded preclinical research to account for sex as a biological variable (SABV), the analysis found that clinical researchers misunderstood the requirements.
- For example: Some misused the terms “sex” and “gender” in regards to the policy, while others thought it applied only to human clinical trials (not preclinical research) and a number questioned the need for such differentiation.
I’m listening ...
Even further, a recent AMA Council on Science and Public Health report found that SGM population participation in clinical trials is not representative of the population.
Case in point: Individuals that identified as “gay, lesbian, transgender, gender non-binary, or gender expansive, having been historically [were] omitted entirely as a category for clinical research, even when they are a high-risk population,” according to the AMA.
And in ophthalmology specifically?
Research published in JAMA Ophthalmology in 2022 evaluating sex or gender reporting in ophthalmology-specific studies of FDA drug approvals (1995 to 2022) found that:
- Over 75% of trials conflated sex and gender
- Over 66% of trials lacked sex- and gender-based analysis
Yikes. So what’s the intent behind this new policy?
“Despite changes in the regulatory environment, inequities in clinical trial participation and outcomes persist today,” Dr. Ajayi stated. “We commend the FDA’s work to date and we are committed to furthering efforts to improve equity in patient outcomes.”
As such, greater representation among clinical research data is key to providing more accurate clinical data indicative of all participant demographics—a critical need in all medical fields, including eye care.