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Medical Education as a Tool to Increase Representativeness in Clinical Research

Sacha Sharp PhD, MA,

Vice Chair for Strategic Engagement

Director of Medical Education Innovation

Assistant Professor of Medicine

Division of General Internal Medicine

Indiana University School of Medicine

Presentation Developed with Support From:

Lauren D. Nephew MD, MA, MSCE

Associate Vice Chair for Health Equity

Assistant Professor of Medicine

Indiana University School of Medicine

Division of Gastroenterology and Hepatology

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Questions

How pervasive is the problem of racial disparities clinical trial enrollment?
Are there solutions?
How can medical education be used to drive solutions?
Why is clinical trail representativeness important for health equity?

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How pervasive is the problem of racial disparities in clinical trial enrollment? �

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Recently started requiring capture of data on clinical trial race & ethnicity�

2007: FDA Section 801 required US phase 2-4 trials to report results in ClinicalTrials.gov.
2017: The FDA Final Rule required reporting race/ethnicity data.

Figure 1

Turner BE, Steinberg JR, Weeks BT, Rodriguez F, Cullen MR. Race/ethnicity reporting and representation in US clinical trials: a cohort study. Lancet Reg Health Am. 2022 Jul;11:100252.

Pre 801

27.6%

After 801

44.4%

After Final Rule

90.1%

Proportion of Clinical Trials Reporting Race/Ethnicity Data by Period

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Rates of Reporting all 5 Racial and Ethnic Groups Remained Low

Figure 2

The Lancet Regional Health – Americas 2022 11DOI: (10.1016/j.lana.2022.100252)

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Under Enrollment of Minority Groups

Figure 3

The Lancet Regional Health – Americas 2022 11DOI: (10.1016/j.lana.2022.100252)

*Distribution only includes trials that reported data for all five racial/ethnic groups. Census calculations reflect 2010 US Census data..

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Why is clinical trial diversity important?�

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Ethical Imperatives in Research

https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html

Respect for Persons

All persons have rights to make their own choices.
Protect those with diminished autonomy (i.e prisoners).

Beneficence

Maximize benefits and minimize harms

**Justice

Those who do not receive the benefits of research should not bear its burden
Nor should research provide opportunities only for those who can afford to participate.

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Inability to Achieve Therapeutic Goals

Therapeutic Goal	Without Diversity
Effective therapy	Lack of generalizability in diverse populations
Minimize side effects	Lack of safety data in diverse populations
Reduce health disparities	Failure to access investigational, potentially lifesaving therapies

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Generalizability

Definition: The degree to which you can apply the results of a study to a broader context.
Many groups underrepresented and excluded in clinical research can have distinct disease presentations or health circumstances that affect how they will respond to an investigational drug or therapy.
Representation by self-identified race and ethnicity is important to generalizability of study findings, but interpretation requires clarity of thought.
Racial categories are socially constructed and do not have a biological basis.

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Transportability

Definition: approaches that extend inferences made based on the study population to the representative target.
It is essential for researchers to be able to extrapolate clinical research results to the targeted populations for generalizability purposes, thus informing clinical decisions and public health.
Transportability cannot be assessed if a population is not represented in the research, therefore, participants from minoritized populations are essential to facilitate transportability to the general population.

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Minimize Side Effects

Some genetic factors that may result in heterogeneity in drug response may be more common in certain ancestral populations, which may be associated with self-identified race. (i.e. Warfarin identified in 1951)
Self-identified race and ethnicity may also be associated with lived experiences that themselves result in specific biological manifestations that are not genetic in origin.

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Lack of Access to Interventions

Approval of new interventions are often limited to the demographics of the populations included in clinical trials.
Example: Pre-exposure prophylaxis (PrEP), the company included only cisgender men and transgender women.
This exclusion requires a marketing insert that says the drugs are not for use in those assigned female sex at birth.

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Cost of the Failure to Reduce Healthcare Disparities��

Economic modeling to estimate the social cost of groups that have been underrepresented in clinical trials.
Presumption is that disparities could have been mitigated if clinical trials had been more inclusive:

Quantity of life (life expectancy)
Quality of life (measured by disability-free life)
Working life (years in labor force)

In aggregate, health disparities will cost society more than $5 trillion through 2050

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Are there solutions to the problem of racial disparities in clinical trial enrollment?�

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It Can Be Done! Phase III Study Participation COVID vaccine trials

	Total US Population Age 16+	Pfizer Phase 3	Moderna Phase 3
Total	258 million*	37,706	30,351
Race (%)
White	60.1	82.9	79.2
Black	12.2	9.3	10.2
Asian	5.6	4.3	4.6
Native American or Alaska Native	0.7	0.5	0.8
Native Hawaiian or Pacific Islander	0.2	0.2	0.2
Multiracial	2.8	2.3	2.1
Other/Missing		0.6	3.0
Ethnicity (%)
Hispanic or Latinix	18.5	28.0	20.5
*Race and ethnicity considered together in the KFF Census Bureau’s American Community Survey

Nephew, L. D. (2021). EClinicalMedicine, 36. https://doi.org/10.1016/j.eclinm.2021.100906

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Overcoming Patient & Provider Barriers

Sheikh SZ, Wanty NI et al. J Clin Med. 2019;8(8):1245.

Access to providers with knowledge
Transportation
Insurance

Access

Awareness about clinical trials
Providers to refer to clinical trials

Opportunity

History of exploitation in research
Fear of side effects
Concerns of feeling like a “guinea pig”

Mistrust

Lack of disease knowledge
Misunderstanding about randomization and placebo
Belief that clinical trials have no benefit

Health Literacy

Excluding family members in enrolment and participation can deter certain ethnic groups (Latino)
Lack of patient-provider relationship

Cultural

Lack of access to clinical trial information, sites and investigators
Lack of familiarity with inclusion criteria

Awareness

Belief minority patients wont adhere to protocol
Belief patient not interested or wont understand
Concern will lose patient to clinical trial practice

Implicit Bias

Lack of time to discuss trials
Lack of patient provider relationship
Distance to clinical trial sites

Logistics

Patient

Provider

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Ecosystem Efforts

The FDA issued updated guidanceon enhancing the diversity of clinical trial populations in 2022. [No longer available on their website]. Also issued nonbinding industry recommendations for enrollment of populations most impacted by COVID-19, specifically minoritized populations.
The Multi-Regional Clinical Trials (MRCT) Center of Brigham and Women’s Hospital and Harvard formed an MRCT Center Diversity Workgroup in February 2018 and published a guidance documentin 2020 and a toolkitin early 2021.
Pharmaceutical Research and Manufacturers of America (PhRMA) and its member companies published the first-ever industrywide principles on clinical trial diversity in November 2020, These principles became effective in April 2021, and they implemented an Equity Initiative in 2022.
The National Academies of Sciences, Engineering, and Medicine published a report titled "Strategies for ensuring diversity, inclusion, and meaningful participation in clinical trials in 2020.�

https://www2.deloitte.com/us/en/insights/industry/life-sciences/lack-of-diversity-clinical-trials.html

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Can medical education drive solutions?

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Relevant Foundations of Medical Education

	UME	GME
Patient Care and Procedure Skills	Demonstrates evidence-informed, equitable patient centered care	Provides equitable, appropriate, and effective treatment
Medical Knowledge	Integrates foundational knowledge	Demonstrates evolving, biomedical, clinical, epidemiological, and social-behavioral knowledge
Practice-Based Learning	Integrates feedback, evidence, and reflection to adapt behavior and foster improvement.	Demonstrates the ability to investigate and evaluate care, appraise and assimilate scientific evidence, and continuous improvement.
Interpersonal and Communication Skills	Effectively communicates to contribute high-quality patient center care	Demonstrates interpersonal and communication skills that results in the effective exchange of information and collaboration.

AAMC, AACOM, ACGME. Foundational Competencies for UME. 2024

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Overcoming Barriers

Incorporate clinical trial information at the start of weekly conferences or morning reports

Awareness

Offer didactics on bias mitigation
Standardize clinical trail recruitment as part of H&P in clinical years

Implicit Bias

Learners have more time to discuss trails
Rely on patient care competency to strengthen relationships

Logistics

Learners and Trainees

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Curricular Enhancements

Expand evidence-based medicine requirements

Definition: the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.

Prioritize experiential learning

Definition: a holistic model of learning consistent with adult learning theory that emphasizes the role an experience plays in the learning process.

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What’s the impetus to create such infrastructure? Whose problem is this?�

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Mission of Academic Medicine

Medical Education - prepare future physicians to meet societies future needs. * Note: According to Brookings and the Census, minoritized populations will be the majority by 2045.
Medical Research – in alignment with policy and advocacy initiatives, innovation in research is what saves lives and transforms health.
Health Care – medical schools and teaching hospitals are the conduit for research implementation, as well as help improve quality, safety, value, and equity of care.
Community Collaborations – partnerships with the community anchored in trust are what fuel the education mission areas.

https://www.aamc.org/about-us/mission-areas

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Regulation and Accreditation can Build Accountability & Enables Innovation

To catalyze innovation, government regulatory agencies and medical school accreditation teams can:

Develop and streamline regulations and guidances
Incentivize best practices
Promote industry best practices

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Towards Health Equity

What is still needed:

Investment in a network of clinical trial sites in underserved communities in non-traditional locations like FQHC by Industry. Possibly collaborating with student outreach clinics.

Consistency in government!!! Funding agencies to require anti-discrimination training for all medical learners, researchers, and research staff.

Sustained collection of demographic data.

Scientific journals require ALL race and ethnicity information; explanations for low enrollment and implications in the discussion.

High-impact journals declining to publish papers with low DRIVE scores.

Increased budgets to pay for weekend and evening hours, shared ride vouchers, translator services, and incentives.

Incentivize involvement for learners to support their future career goals.

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Conclusion

How pervasive is the problem of racial disparities in clinical trial enrollment? Why is it an issue?

Pervasive; and potentially underreported.

Are there solutions?

Yes, medical education can be a part of this solution.

How can medical education be used to drive solutions?

Through curricular enhancements and reliance on the core competencies of medical education.

Why is clinical trail representativeness important for health equity?

Health equity is a fundamental part of the mission of academic medicine. We must continue to transform health to achieve better outcomes from everyone, especially the members of society who have been historically disadvantaged.

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I would like to start off refreshing your epidemiology with a discussion about the nuts and bolts of prospective cohort studies, the assumptions, the advantages and disadvantages, so that we can think about how they can be leveraged for disparities research.

Certainly a large barrier to prospective cohort studies in disparities can be recruitment, so we will spend some time reviewing some of the data around minority participation in clinical trials as well as strategies for recruiting.

Finally, I will review on famous disparity prospective cohort study, as a model of what I think can be done to explore disparities in cirrhosis and end stage liver disease, and that’s the Southern Community Cohort Study.

Finally, I would like to encourage the junior investigators in the group like myself. All prospective cohort studies may not be as large and expansive as the SCCS. So I will share with you a smaller scale prospective study that I am working on in Indianapolis.

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Thank you!

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