Clinical Researcher—August 2023 (Volume 37, Issue 4)

PEER REVIEWED

Nadine H. Spring, PhD, CCRC; Jeanne Connors, PhD;
Michael Schwab, PhD; David O. Anderson, PhD

 

 

Clinical trials play a crucial role in making new medical treatments and devices available. However, historically, these trials have lacked diversity in participant representation, posing challenges in determining the safety and efficacy of treatments for specific populations. This qualitative phenomenological study explored the experiences of clinical research principal investigators (PIs) in addressing diversity in clinical trials. The PI respondents, recruited through social media and professional networks, shared their insights through interviews. Thematic analysis revealed several emergent themes, including passion for clinical trials, increased awareness of the importance of diversity in clinical trials over time, frustration with eligibility criteria, recognition of the need for diversity among staff, awareness of barriers to diversity, concerns about the lack of formal training, and optimism for future strategies and solutions. The study’s findings have implications for social change by guiding efforts to attract underrepresented minorities to participate in clinical trials, ultimately promoting diversity, reducing health disparities, and improving health equity.

Background

According to the U.S. Food and Drug Administration (FDA), a clinical research study is an investigation or research that involves one or more human subjects that is undertaken to assess or evaluate the safety or effectiveness of a medical device.

Clinical research studies are conducted to test the safety and efficacy of promising, novel treatments and diagnostic tests. The findings from clinical research studies fill knowledge gaps by providing new information about ways to treat, prevent, and diagnose diseases. Studies are needed to advance medicine and healthcare as well as to optimize outcomes. (Umscheid, et al., 2011)

Volunteers join these studies and contribute to the data. In many of these studies, the diversity of the participants is not representative of the general population. (Selker, et al., 2018) Some populations, such as African Americans and Hispanics, are disproportionately underrepresented in medical research studies. (Occa, et al., 2017) Evidence has indicated that outcomes, such as adverse reactions and efficacy, can differ by certain patient characteristics, such as gender and ethnicity. (Stronks, et al., 2013) Clinical research studies need to consider diversity when the goal is to improve care and outcomes for all patients.

There is a gap in research where the volunteer patients evaluated in the clinical trials and the target patient populations differ. In the real world, outside trials, this creates an issue where the data about the general population are lacking. This difference in the knowledge about treatment effects in diverse patient populations is widespread in medical practice and occurs with some of the most prescribed medications. (Selker, et al., 2018)

According to Kennedy-Martin, et al. (2015), when the external validity of randomized control trials in the fields of cardiology, mental health, and oncology were examined, it was found that more than 70% of the patient participants included in these trials were not representative of the patients encountered in routine clinical practice.

Racial and ethnic minority groups are routinely disproportionately affected by health conditions such as Type II diabetes mellitus, cardiovascular disease, stroke, HIV/AIDS, and many types of cancer. (Noonan, et al., 2016) Many studies of diseases, such as different forms of cancers, neurologic diseases, and cardiovascular disease, have revealed that the study populations are not representative of the racial and ethnic make-up of those who are most affected by these diseases. (Amorrortu, et al., 2018) The population difference between the trials and real-world practice could significantly impact the external validity of randomized clinical trial findings. (Kennedy-Martin, et al., 2015) The lack of a diverse patient participant pool and a shortage of publicly available data means that healthcare providers and patients often cannot discern which medications and devices are safe and effective for specific demographics. (Fox-Rawlings, et al., 2018)

Methodology

The methodology of this study involved conducting semi-structured interviews with PIs in clinical research. The population for this study included PIs with at least two years of experience conducting clinical trials in the United States. These PIs had experience in academia, industry, or government agencies with medicines and devices. Experience in any of the four phases of clinical trials was considered. Respondents were screened for eligibility based on their experience in conducting clinical trials in the United States (see Table 1 for demographics).

Recruitment was done through social media platforms by posting recruitment flyers. Purposeful sampling was employed to identify potential respondents. A demographic questionnaire and interview guide were used during the study, providing baseline information, and focusing on research questions.

The interviews were conducted from June 2022 to October 2022. Respondents provided informed consent and received a $25 Amazon gift card after each interview. Interviews were audio-recorded, transcribed, and reviewed for accuracy. Data analysis was conducted using NVivo Qualitative Research Software, Version 12. Saturation was reached when no new data, themes, or codes emerged from the interviews. The interviews ceased when saturation was achieved, which occurred at 15 respondents.

Results

The preliminary coding of the 15 transcripts yielded 86 nodes. The next step was categorizing these nodes into 12 major categories and subcategories by grouping. Sorting was completed based on concepts that emerged that were the same or similar. Some nodes were merged or deleted because they were repetitive.

The last phase of the data analysis process involved reviewing the categories in NVivo and manually producing themes based on recurrences in the data from the transcripts of the 15 respondents. The result was seven primary themes and several subthemes that revealed the lived experiences of the PIs when addressing diversity in clinical research studies (see Tables 2 and 3).

Table 1: Demographic Information for Respondents

Respondent Number	Gender	Race	Ethnicity	Experience (years)	Specialty	Type of practice
001	Female	Asian	Non-Hispanic	2	Optometry	Private medical practice
002	Female	Asian	Non-Hispanic	8	Pulmonology	Academic medical center
003	Female	Other	Hispanic	10	Rheumatology	Academic medical center
004	Female	White	Non-Hispanic	2	Endocrinology	Academic medical center
005	Female	Other	Unknown	11	Family medicine	Clinical research center
006	Male	White	Non-Hispanic	25	Internal medicine	Clinical research center
007	Female	Asian	Non-Hispanic	2	Internal medicine	Clinical research center
008	Female	Asian	Non-Hispanic	15	Emergency medicine	Industry
009	Female	White	Non-Hispanic	36	Internal medicine	Clinical research center
010	Female	Black or African American	Non-Hispanic	3	Rheumatology	Academic medical center
011	Female	Other	Hispanic	4	Rheumatology	Academic medical center
012	Male	Asian	Non-Hispanic	2	Neurology	Academic medical center
013	Female	Other	Non-Hispanic	5	Rheumatology	Academic medical center
014	Female	Black or African American	Non-Hispanic	12	Rheumatology	Academic medical center
015	Female	Asian	Non-Hispanic	2	Rheumatology	Academic medical center

 

Table 2: Themes for RQ1—What are the lived experiences of clinical research PIs regarding diversity in clinical research?

Theme	Number of respondents	Percent (%)
Theme 1: Passionate about working in clinical trials	9	60
Theme 2: Increased awareness over time	10	67
Theme 3: Frustration with stringent eligibility criteria Subtheme: Perceived belief that sponsors can do more Subtheme: Link diversity goals to funding Subtheme: Partner with patients	9	60
Theme 4: Perception that increased diversity among staff is needed	7	47

 

Table 3: Themes for RQ2—What do clinical research PIs identify as concerns for diverse participants in clinical trials?

Theme	Number of respondents	Percent (%)
Theme 5: Knowledge and awareness that there are multifaceted barriers to having diverse participants in clinical research Subtheme: Meet the needs of underrepresented populations Subtheme: The role that race and mistrust plays Theme 6: Concerns that no formal training exists	14         14	93         93
Theme 7: Optimism for the future with strategies and solutions	15	100

 

Respondents were prompted to share what attracted them to serve as a PI on clinical research studies. Serving as a PI can be a challenging role; respondents shared that they enjoyed the innovative components and the medical aspects of being involved in clinical research studies. They enjoyed being a part of the process of helping their patients and bringing new therapies to the market.

The PIs who participated in this study have an average of nine years of experience, and over the course of their career they have seen some changes as it relates to diversity in clinical research. There is more awareness about the need to have representation in clinical trials. There are now recommendations from government entities urging pharmaceutical companies to address this. Respondent 010 indicated that the COVID-19 pandemic has helped to shape some of the conversations around this “since the pandemic has started and since…people’s eyes have been open[ed] to social justice issues in this country.”

The respondents seemed frustrated that study criteria often don’t match those of the average patient in their practice with the condition of interest. The eligibility criteria for some clinical trials can be so strict that it is difficult to get the average patient with the condition into the study. Study Respondent 003 stated “…although I see primarily Hispanics and African Americans, sometimes these patients do not meet criteria for some of my studies.”

The PIs indicated that the field of clinical research itself isn’t diverse or representative of the population served. Respondent 001 suggested a potential solution would be to have more diversity amongst PIs, and that “just having more doctors of diversity…as your [PI] would be, I think, a huge thing. Because…when you see someone who looks like you, it does make an impact.” Respondent 003 stated, “Change the makeup of the workforce.”

In their answers to the prompt “In your experience, tell me about challenges towards recruiting diverse populations into clinical research studies,” the respondents reported there are countless barriers faced and experienced by PIs as related to increasing diversity in clinical research studies. These barriers include difficulty in reaching these patients due to difficulty in accessing diverse patient populations. There are concerns with care responsibilities for dependents of the study participants, barriers tied to time commitment, concerns with improper consent, language barriers, cultural differences, an absence of diversity among the research staff, mistrust of the medical research process, and a fear of being used as a “guinea pig.”

Race and mistrust emerged as a subtheme to the knowledge of the barriers to having diverse participants in clinical research studies. Many respondents alluded to what happened with the Tuskegee Syphilis studies as well as to present-day atrocities such as injustices in the judicial system, educational system, and healthcare. These include “It is difficult to get these groups into clinical research studies when they do not trust the system.”

Study respondents expressed the urgency of improving diversity in clinical research studies. The push came from their employers, pharmaceutical companies, and from government entities such as the FDA and National Institutes of Health. However, they expressed frustration at being unable to find and attend formal training on this topic. The respondents expressed that they received numerous trainings to become a PI, but nothing on recruiting underrepresented populations. To become PIs, respondents expressed that they received training and certifications and, in some instances, research mentorship.

While all the respondents expressed that they enroll underrepresented populations into their research studies, none have had any formal training on how to successfully enroll these populations into clinical research studies. For example, Respondent 001 stated, “I will have to be honest with you, I got zero training in that.”

The PIs in this study were optimistic and hopeful that we are heading in the right direction. They expanded on strategies that could help to address increasing diversity in clinical research studies. Study Respondent 013 indicated this can be approached by tackling language barriers and improving the research infrastructure.

Discussion

There were notable findings from interviews with 15 PIs in clinical research. Due to time constraints and funding, many medical schools do not routinely prepare students and physicians for clinical research. (Adams, et al., 2017) The fact that these PIs pursued additional training exemplifies their level of commitment and dedication to the clinical research process.

These investigators expressed awareness of the importance of diversity in clinical trials, driven by existing mandates and new recommendations from government agencies. They are optimistic about achieving diversity and have already implemented solutions at their research sites. They expect pharmaceutical companies to do more and desire training on approaching ethnic and underrepresented populations for trial participation.

The passion of the investigators for their work and the positive impact on patients’ lives stood out. They acknowledged the challenges but expressed dedication and commitment to the research process. Over time, they have become more aware of the need for diversity and have implemented strategies to attract underrepresented groups.

Frustration was expressed regarding eligibility criteria that often exclude the average person with the condition under study and the reliance on laboratory test results developed based on European American norms. The investigators emphasized the need for diversity in the clinical research staff to effectively serve and enroll underrepresented populations. The findings align with those of previous studies, highlighting the importance of establishing advisory panels and increasing recruitment from underserved groups in the research field. (Bodicoat, et al., 2021)

Further Considerations

Further considerations for this study include conducting a larger, mixed-methods exploration of PIs’ efforts to address underrepresentation in clinical research. This would involve a more diverse group of participants from various practice settings. The study revealed a need for formal training on attracting and retaining underrepresented populations, indicating the potential for future research and the development of training programs in this area. Exploring effective patient partnerships and expectations from pharmaceutical companies are additional areas for future study. Recommendations include expanding the participant population, exploring different practice settings, and examining the pharmaceutical industry’s role.

Public health practitioners can utilize the study findings to develop targeted, culturally congruent programs addressing health equity and disparities in underrepresented populations in clinical trials. The study’s insights offer potential solutions and strategies for addressing the needs of underrepresented populations in clinical research.

Limitations

This study faced several limitations. The small sample size of 15 respondents constrained the generalizability of the findings. The strict eligibility criteria further restricted the findings to a specific group of U.S.-based, English-speaking researchers. The demographics of the respondents, with only two males and a predominant Asian representation, may have introduced biases. The use of purposeful sampling resulted in self-selection bias. Recruitment through social media excluded PIs not on social media, potentially affecting the representativeness of the sample. The COVID-19 pandemic affected participation. The study design, being qualitative, focused on the experiences of PIs and did not seek statistical significance or a large sample size. Finally, this study was developed as an academic thesis by the lead author, and her personal biases may have influenced data collection and analysis, although steps were taken to minimize bias.

Conclusions

This study has implications for positive social change and advancing care for underrepresented populations. The recommendations for creating training programs could contribute to designing programs and training that are relevant and culturally appropriate for increasing diversity in clinical research studies. This implementation alone could result in more representation in the research studies, having more data and safety and efficacy profiles of many therapies for ethnic minority groups, improving health equity, and reducing health disparities. Furthermore, this study’s respondents revealed innovative recommendations for future researchers and public health practitioners to promote positive outcomes.

Finally, this situation of underrepresentation in clinical trials is critical. Diversity in clinical trials is needed and it’s needed now—the advancement of care, medicine, and science for underrepresented groups depend on it. Now, imagine a world where certain groups are not disproportionately affected by certain conditions. Imagine a world where there are no health disparities. Imagine a world where there is health equity. This study has shown us that we still have so much to do, and that there are so many layers to address. It won’t happen overnight, but achieving representation in clinical trials can help to get us to that world.

References and Resources

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Bodicoat DH, Routen AC, Willis A, Ekezie W, Gillies C, Lawson C, Yates T, Zaccardi F, Davies MJ, Khunti, K. 2021. Promoting inclusion in clinical trials-a rapid review of the literature and recommendations for action. Trials 22(1):880. https://doi.org/10.1186/s13063-021-05849-7

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Nadine H. Spring, PhD, CCRC, (nadine@springwell360.com) is Director of Operations at SpringWell360 LLC. The full version of this study, “Clinical Research Principal Investigators’ Perspectives of Improving the Diversity of Clinical Research Participants,” serves as her doctoral dissertation at Walden University and will be available online on ProQuest in late April 2024.

Jeanne L. Connors, PhD, is a Contributing Faculty Member, Walden University.

Michael Schwab, PhD, is a Core Faculty Member, Walden University.

David O. Anderson, PhD, is a Contributing Faculty Member, Walden University.