Emily Botto

Although we have witnessed increased inclusion of diverse populations in COVID-19 vaccine

 trials over the past two years, in nearly all other disease indications, representation of BIPOC

 populations—black, indigenous, and peoples of color—in clinical trials remains comparatively low, particularly in world regions where most clinical trials are currently conducted

 and where demographics are becoming increasingly more diverse (i.e., North America and Western Europe).

A variety of factors help explain the lack of racial and ethnic representation among clinical trial volunteer participants. Low clinical research literacy, poorly targeted communications, and limited access to clinical research facilities are among top factors mentioned.

 Many note that racial and ethnic representation among the research workforce is essential in reducing barriers to clinical study volunteer participation among historically underrepresented populations.

 A 2008 study conducted by the Tufts Center for the Study of Drug Development (Tufts CSDD) found that a physician’s race and ethnicity can influence the race and ethnicity of clinical trial volunteers. The study also found that incidence of participation in clinical research among BIPOC physicians was well below that observed among white physicians. Although interest in becoming a clinical investigator was high among all physicians surveyed, BIPOC investigators tended to conduct and initiate fewer trials annually. In that study, BIPOC investigators also reported fewer infrastructural resources and support compared to white investigators.

More than a decade has passed since the 2008 study. During that time, public and clinical research stakeholder awareness and interest in improving the proportional representation of volunteer participants by race and ethnicity in clinical trials has intensified. Several recent initiatives underscore these changes. The FDA Reauthorization Act of 2017, for example, expanded the FDA’s authority to address barriers to participation in clinical trials (SEC.610.Expanded Access).

 In 2020, FDA issued guidance for the broadening of volunteer eligibility criteria and the enhancement of diversity in clinical trial participation.

 In April 2022, FDA issued draft guidance recommending the development and submission of plans—with each new IND application—for achieving diversity targets, as well as retaining study participants.

 Separately, The Lancet issued a diversity pledge to reinforce its commitment to diversity

 and the New England Journal of Medicine conveyed the importance of diversity in clinical research in a recent editorial.

In late 2020, Tufts CSDD conducted a new study to revisit, characterize, and more deeply examine the relationship between investigative site personnel diversity and study participant diversity.

This research began with the formation of a large Working Group

 of biopharmaceutical companies, contract research organizations (CROs), and one global professional association. The Working Group supported the development of two extensive online global surveys that were distributed between April and July of 2021. These were reviewed and approved by the Tufts University IRB and the university’s General Data Protection Regulation (GDPR) expert reviewer.

The first survey targeted medical professionals, regardless of their involvement in the clinical research process. Its purpose was to gather data about medical professionals regarding their awareness of, access to, training, and involvement in clinical research. The second survey targeted clinical research professionals working at various types of clinical research sites. Its purpose was to gather data on staff diversity at investigative sites, the infrastructure and support available to clinical research staff, and staff perceptions about Diversity, Equity, and Inclusion (DEI).

Definitions of race and ethnicity were presented to respondents participating in both surveys as shown in Table 1. These definitions are consistent with those reported in a 2021 study looking at race and ethnicity of COVID-19 patients participating in 68 studies worldwide.

 Race and Ethnicity—Definitions Presented to Respondents

Survey one: Awareness of, access to, training in, and involvement in clinical research among medical and allied health professionals

In total, 611 respondents participated in the online survey aimed at medical professionals regardless of their involvement in clinical research. Of these, 54% were in North America (US & Canada) and 46% were in Rest of World (ROW). Regarding their education levels, 62% had a doctoral or medical degree, 24% had a nursing degree, and 14% had achieved other educational levels, such as a bachelors or high school diploma. Respondents to the survey were 56% female and 44% male. Racial and ethnic identities were reported as follows: 68% White, 15% Asian, 10% Other (including mixed race/ethnicity), 4% LatinX, and 3% Black.

The survey results show that most medical and allied health professionals who are involved in clinical research believe that mentors made them more comfortable with (1) the clinical trial process (93%), and (2) referring and screening patients for clinical trials (91%). Most medical and allied health professionals involved in clinical research (87%) also believe that mentors helped them find greater access to clinical trials.

The survey findings also indicate that a high proportion of medical and allied health professionals first became exposed to clinical research at the invitation of a peer or mentor. Differences in exposure through a mentor or peer were also observed between BIPOC and white professionals, with 42% of white professionals reporting becoming involved in clinical research in this manner compared to only 30% of BIPOC professionals. Other differences in exposure among BIPOC and white professionals were found when respondents were asked if they first became exposed to clinical research by proactively contacting a pharmaceutical company about opportunities to participate as staff supporting or leading clinical trials. Thirteen percent of BIPOC professionals reported becoming involved in clinical trials by being proactive compared to 6% of white professionals.

Further, differences in access to clinical research opportunities and infrastructure were identified between BIPOC and white medical and allied health professionals who have not been involved in clinical trials. Table 2 shows the barriers to involvement in clinical trials as reported by Physicians, PhDs and nurses who have not been involved in clinical research worldwide.

 Barriers to Involvement in Clinical Research as Reported by Professionals Without Clinical Trial Experience (Global)

Survey two: Investigative site diversity, infrastructure, and support available to clinical research site staff

The primary aim of the second survey was to understand current racial and ethnic representation among research professionals at clinical research sites supporting clinical trials funded by pharmaceutical and biotechnology companies, and the elements that influence staff diversity at these sites. These elements include (1) the types of communities served (i.e., urban, suburban, and rural), (2) the income levels of the patient population served, (3) staff’s access to technologies, (4) training and support available to site staff, and (5) the site’s infrastructure. To that end, in addition to the definitions shown in Table 1, respondents to this survey were also provided with the definitions included in Table 3 below.

 Site Characteristics—Subgroup Definitions

In total, 3,462 respondents—representing an estimated 3,340

 unique sites—participated in this global

 online survey. Of these respondents, 40% were principal investigators, 36% were site directors and managers and other administrative staff, and 25% were clinical research coordinators (CRCs) or clinical research nurses. Respondents to this survey were 61% female and 39% male. Racial and ethnic identities were reported as follows: 69% White, 12% LatinX, 8% Asian, 6% Mixed, 4% Black, and 2% Other.

In addition, survey respondents were asked to estimate the racial and ethnic breakdown/composition of the staff working at their respective sites. Table 4 shows this breakdown by world region and type of research institution. Overall, BIPOC populations were not widely represented among staff at clinical research sites globally. When comparing BIPOC percentage representation by type of institution in North America, higher representation was observed in private sites and site networks compared to academic medical centers and large healthcare systems. When comparing BIPOC percentage representation by type of institution in Europe, significant differences in representation were not observed among private sites, site networks, academic medical centers, and large healthcare systems. BIPOC representation was higher among staff at research sites located in ROW.

 Distribution of Investigative Site Staff by Race and Ethnicity

Clinical research sites were also classified into one of two groupings: ‘High’ Staff Diversity Sites and ‘Low’ Staff Diversity Sites. Sites in the US were classified as High Staff Diversity if their staff was at least 60% BIPOC. Sites in the US were classified as Low Staff Diversity if their staff was 40% or less BIPOC. Sites in locations outside of the US were classified as High Staff Diversity Sites if representation by any one race or ethnicity was 40% or lower; they were classified as Low Staff Diversity Sites if representation by one race or ethnicity was 60% or higher. Sites that fell outside of these parameters (i.e., the 50th percentile) were excluded from supplementary analyses. It is important to note that less than 1% of European sites met the criteria for the High Staff Diversity grouping—this includes sites in Eastern Europe as well as the UK, Germany, Spain, France, and other parts of Western Europe.

Clinical trial volunteer diversity is strongly associated with diversity in the clinical research workforce

Racial and ethnic representation among the clinical research site workforce is associated with racial and ethnic representation in clinical trial volunteer enrollment. To explore the strength of this relationship, respondents were asked to estimate the racial and ethnic breakdown of patients enrolled in their recently conducted clinical trials. These estimates were then cross tabulated against the groupings for High Staff Diversity Sites and Low Staff Diversity Sites, and chi-square tests were conducted to determine statistical significance. As shown in Table 5, the enrollment of BIPOC patients was significantly higher at High Staff Diversity Sites, including all site types. This result was statistically significant.

 Relationship Between Staff Diversity in Diversity in Patient Enrollment in Trials (Global)

The relationship between diversity in patient enrollment and investigative site staff diversity has important implications for the development of DEI plans and policies. If the aim is to increase representation among clinical trial volunteers, policies and plans must also prioritize improvements in representation of BIPOC populations among investigative site staff; thus, understanding the basic characteristics of sites that show High Staff Diversity is a meaningful starting point for future initiatives in this space.

Characteristics of investigative sites reporting higher staff diversity

This study sheds light on the characteristics of sites reporting higher levels of staff diversity—though it also uncovers barriers faced by those sites reporting lower levels of staff diversity. Sites reporting higher racial and ethnic diversity among their staff tended to be in urban areas, service low-income communities, and have centralized clinical trials offices to support research teams—in greater proportion than sites reporting lower staff diversity levels. As shown in Table 6, two of these findings were statistically significant.

 General Characteristics of Investigative Site Staff by Diversity Subgroup

Clinical research sites reporting High Staff Diversity levels also reported greater use of technologies and infrastructure to support the execution of clinical research compared to Low Staff Diversity sites, as shown in Table 7. The difference in use of Patient Management Systems at High Staff diversity sites compared to Low Staff Diversity sites was statistically significant. Additionally, provision of adequate access to Patient Management Data was higher at High Staff Diversity sites. The analysis also revealed that, prior to the pandemic, remote communication platforms were used in higher proportion at High Staff Diversity sites compared to Low Staff Diversity sites, and that the overall current use of these platforms was higher at High Staff Diversity sites.

 Use of Technology and Infrastructure by Diversity of Investigative Site Staff

Not least, this research revealed that High Staff Diversity Sites tended to offer better access to diversity and inclusion, unconscious bias, and inclusive behavior SOPs to its staff. The offering of inclusive behavior SOPs was notably higher at High Staff Diversity sites.

 Presence of Diversity SOPs by Diversity of Investigative Site Staff

The Tufts CSDD Investigative Site Personnel Diversity Study results demonstrate association between reported levels of racial and ethnic diversity among personnel at investigative sites and racial and ethnic representation among volunteer participants enrolled in clinical trials. This finding suggests that increased diversity within the clinical research workforce facilitates the racial and ethnic representation of study volunteers in clinical trials at individual research sites.

This study also offers new understanding about shared characteristics among sites reporting comparatively higher staff diversity and offers insight into the paths followed by medical and allied health professionals toward becoming involved in clinical trials. These elements are key considerations and may be important strategies supporting improvements in racial and ethnic representation among clinical trial volunteers.

Specifically, our results suggest that expanding exposure to clinical research opportunities to all medical and allied health professionals can lead to greater overall staff participation in clinical investigation. Our results show that 87% of all professionals involved in clinical research believe that mentors helped them find greater access to clinical trials, and over 90% of all medical and allied health professionals involved in clinical research report that a mentor made them feel more comfortable with the clinical trial process, as well as in referring and screening patients for trials. However, only 30% of BIPOC medical and allied health professionals first became involved in clinical research by invitation by a mentor or peer compared to 42% among their white counterparts. This last result highlights a disparity in access to mentors in clinical research and the benefits that accompany such connections. Mentorship and other research socialization programs are therefore expected to be effective in increasing overall and BIPOC staff participation in clinical research.

The study findings indicate that the presence of DEI-specific materials and SOPs may play a role in supporting workforce diversity and, in turn, foster diversity and inclusion among study volunteers. First, a strong relationship was identified between High Staff Diversity sites and the availability and use of Diversity and Inclusion, Unconscious Bias, and Inclusive Behaviors SOPs. Second, High Staff Diversity Sites reported access to these SOPs in higher proportion compared to Low Staff Diversity sites. Third, approximately half of staff at clinical research sites—across site types and locations—believe that SOPs for Diversity & Inclusion, Unconscious Bias, and Inclusive Behaviors help increase participant diversity at sites. Our results set the stage for drug development stakeholders to collaborate in the development and dissemination of materials, policies and procedures that elevate awareness and understanding of the importance of inclusive behaviors and minimizing biases. This collaboration is not just isolated to the level of the investigator site, but also can benefit from involvement of sponsoring organizations and CROs to support such efforts to increase DEI awareness.

Altogether, our research demonstrates that a diverse clinical research workforce is associated with diversity among clinical trial volunteers, shows that diversity in the clinical research workforce still falls short of reflecting the diversity of the global patient population, and identifies key areas that can support increased racial and ethnic representation among site staff: offering mentorship in clinical research to medical and allied health professionals, as well as SOPs and educational materials related to diversity and inclusion, unconscious bias, and inclusive behaviors.

, MA, Research Consultant and Senior Analyst, Tufts CSDD, Tufts University School of Medicine, 

, BA, Research Analyst, Tufts CSDD, Tufts University School of Medicine, 

, PhD, Strategic Feasibility Manager, UCB, 

, Senior Director, Global Feasibility, Labcorp Drug Development Inc., 

, PhD, Senior Director Patient Insights and Solutions, Portfolio Transformation and Insights, Biopharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 

, Director Oncology Hematology, Janssen Research & Development, LLC,

, MBA, Executive Director and Professor, Tufts CSDD, Tufts University School of Medicine

 for his contributions. The authors also thank representatives from the following organizations for providing research grants and support to this study: AbbVie, Amgen, Association of Clinical Research Professionals, AstraZeneca, Biogen, Bristol Myers Squibb, Covance (now Labcorp Drug Development), CSL Behring, Eli Lilly and Company, EMD Serono, ICON, IQVIA, Janssen, Merck, Otsuka Pharmaceuticals, Parexel, Pfizer, Sanofi, Seagen, Syneos Health, Takeda, UCB, and Genentech, a member of the Roche group. Additionally, the authors wish to thank the following for their assistance: Philippine Nurses Association of America, Asian American Pacific Islander Nurses Association, Taiwan Clinical Research Association, Academy of Physicians in Clinical Research, European Society for Clinical Investigation, ARMA UK, ARCS Australia, Hong Kong Medical Association, the Israeli Medical Association, and the Society of Clinical Research Sites.

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The Tufts CSDD Investigative Site Personnel Study Working Group included the Association of Clinical Research Professionals (ACRP), five contract research organizations (Covance—now Labcorp Drug Development, ICON, IQVIA, Parexel, Syneos Health) and 17 biopharmaceutical companies (AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, CSL Behring, Eli Lilly and Company, EMD Serono, Janssen, Merck, Otsuka Pharmaceuticals, Pfizer, Sanofi, Seagen, Takeda, UCB, and Genentech, a member of the Roche Group).

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This estimate is based on an analysis of 12 unique variables included in the dataset and on the application of a 3.4% duplication rate. The number of sites represented here accounts for approximately 40% of the total number of unique investigative sites involved in FDA-regulated clinical trials in 2020.

Sixty-two countries were represented. Fifty percent of sites were in the US and Canada, thirty-two percent were in Europe, ten percent were in Central and South America (including Mexico), four percent were in Asia and Pacific, and four percent were in ROW (rest of world).

Articles

2020 Tufts CSDD study examines relationship between investigative site personnel diversity and study participant diversity.

Improving Diversity in Clinical Trial Volunteer Participation by Addressing Racial and Ethnic Representation Among the Clinical Research Workforce

Women in drug development continue to be underrepresented in leadership roles. Although various reasons have been given for this disparity, one possible explanation concerns gender-based microaggressions experienced by women in the workplace. To investigate this proposed cause of gender disparities in the drug development workforce, Tufts Center for the Study of Drug Development conducted 26 interviews among a diverse group of women professionals in drug development. These interviews focused on participants’ experience with microaggressions in the workplace and the effect of these microaggressions on teamwork and communication. The research team found that gender-based microaggressions in the drug development workplace can negatively impact collaboration among teams and can affect retention of women employees.

Drug development is among the many areas within Science, Technology, Engineering, and Math (STEM) where women professionals continue to be underrepresented. Although the gender diversity in the drug development industry has improved over the years, women, and particularly women of color, are still noticeably underrepresented in leadership roles. Only 30% of all C-suite positions are filled by women, with a mere 4% of this group representing women of color.

 There have been many reasons put forth to explain this gap, including perceived role incongruity between women and male-typed jobs,

 and deeply entrenched systemic barriers.

 Another contributing factor to this gap are gender microaggressions, defined as subtle behaviors and comments that most often unintentionally demean or denigrate individuals based on their gender.

 Though subtle, microaggressions are ubiquitous, occurring daily in the lives of women in the workplace. Though some argue that microaggressions are harmless, amounting to nothing more than minor insults,

 the emerging research on workplace gender microaggressions has demonstrated their deleterious effects on both cognitive and affective outcomes on women professionals.

Naturally, we wondered how gender microaggressions might manifest in drug development and what impact they might have on women professionals navigating this industry. To shed light on this topic, Tufts Center for the Study of Drug Development recently conducted a qualitative study to examine how gender microaggressions manifest among different work teams in drug development. We interviewed a total of 26 women across different areas, including sponsor organizations, contract research organizations (CROs), vendors, and academic research centers, representing a variety of different functions, levels, and work experience. Importantly, our sample was also racially diverse: 50% were women of color representing Asian, Black, Latina and multi-racial women, allowing us to capture nuanced ways gender microaggressions manifest for women of color.

Of the different types of microaggressions that we uncovered, devaluation emerged as a common form of slight that women encountered on a regular basis. Devaluation describes behaviors or comments that put down or diminish a woman’s input or contribution, the most common example being interrupting women while they speak or misattributing their work to a male colleague. These experiences were shared unanimously across the diverse sample of women we interviewed.

Our study’s racially diverse sample provided important nuance to how gender microaggressions manifest for women of color. Women of color not only had to contend with the usual forms of gender microaggressions, such as devaluation and misattribution of work, but also had to navigate an added layer of microaggressions that intersected their gender and racial identities. These included unsolicited comments that otherized different aspects of their racial and ethnic identity (i.e., colleagues repeatedly mispronouncing their names and being mistaken for another woman of color). Important distinctions also emerged within our racially diverse sample. Black women shared how they felt otherized by belabored comments from colleagues about their hair that made them feel uncomfortably spotlighted. Assumptions of incompetence and lack of intelligence for Black and Latina women also emerged. Conversely, Asian women were assumed to be overly competent, which was often accompanied by the assumption that they do not need resources or help or that they are naturally experts in data analysis even if they were not.

The potential impact of gender microaggressions on team productivity

Regularly experiencing these types of slights were linked with cognitive depletion, emotional exhaustion, and behavioral changes, including overcompensation as well as withdrawal. Importantly, constantly navigating these dynamics was also associated with lowered productivity and team performance, stemming largely from lowered trust towards and a tendency to limit one’s interactions with the aggressor. Naturally, this can pose a challenge to team productivity and effectiveness, which we detail below.

Lowered trust towards one’s colleague can lead to decreased information sharing and communication, which are hallmarks of effective teams.

 This is particularly worrisome within the context of drug development given the collaborative nature of many cross-functional teams whose success depends on effective communication and idea sharing.

Moreover, several of the behaviors that women encountered, such as interruptions or misattribution of their work were directly linked to lowered productivity. In one example, a project manager (PM) described a situation in which the Principal Investigator (PI) would constantly email her male colleague about her project. Repeated incidents such as this created redundancy and delays in the project, all of which could have been avoided had the PI reached out to the correct PM, in this case, the woman.

Such interactions that we have described so far may seem minor at first blush. However, when experienced on a regular basis at work among one’s colleagues, the psychological and emotional toll can be taxing. In fact, the growing research on workplace microaggressions has linked these interactions to emotional and cognitive exhaustion as women manage their emotions while they decipher the meaning and intent behind many of these often-unintentional slights that are committed unbeknownst by the aggressor.

 Though unintentional, these micro interactions have the potential to have macro effects if left unchecked. In fact, many of the women in our sample talked about their intent to leave the organization, and many of them had, at the time of the interview, recently left what they viewed as toxic and exclusionary teams and organizations. Losing talent is the ultimate cost to teams and organizations as it can result in a “brain drain” of diverse, high potential talent.

What then can organizations do to address these all-too-common forms of team dynamics? The solution is creating an inclusive organizational culture where individuals, regardless of their background, feel welcomed and have the potential to develop and grow. However, creating such an environment is easier said than done. While many organizations have heeded the calls for more inclusive workplaces by organizing Diversity, Equity, and Inclusion (DEI) panels, talks, and workshops, etc. such efforts will fall short if they are not accompanied by an intentional and systematic way of benchmarking progress. After all, how does one know there is a problem when one does not measure it? How does one know there is improvement if there are no metrics to track over time? While tracking personnel data, such as turnover statistics, is vital, such statistics would be well paired with antecedent indicators that can help predict and prevent the loss of diverse talent.

We propose measuring the occurrence of these dynamics within organizations and teams to identify areas that need resources related to training and dialoguing. We believe that microaggressions are best addressed through conversation and perspective-taking. The ability to measure and track these dynamics can serve organizations well as they can “get ahead of the problem.”

Cross collaboration is increasingly necessary for producing high quality science.

 Microaggressions, however, can hinder team effectiveness by stifling communication, trust, and cohesion among teams. Further, these dynamics can signal exclusion, ultimately contributing qualified women to leave such organizations or quit the industry altogether in search of more inclusive environments. Thus, the ability to identify, measure, and benchmark these dynamics can help organizations take a more proactive approach to ensure that they are creating an inclusive environment where all individuals, regardless of their social identity, can thrive.

Corresponding Author, Tufts Center for the Study of Drug Development, Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111. 

This study was conducted through a research grant from PhRMA.

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26 interviews conducted by Tufts CSDD found that gender-based microaggressions can negatively impact collaboration and affect retention of women employees.

The Impact of Gender Microaggressions on Team Performance in Drug Development

Since the release of the first ICH E6 Good Clinical Practice guidance in 1996, outlining international standards in the design, recording, and reporting of clinical trial data, technological advances in drug development have made it possible to conduct more clinical trial activities remotely and in patients’ homes. Although a revision to this earlier guidance was released in 2016 (ICH E6 R2), there has since been increasing adoption of decentralized clinical trials, as well as more use of technology given the COVID-19 pandemic. As investigative sites conduct more decentralized and hybrid trials, data collection is increasingly falling to the patient (e.g., wearable devices, smart phones). Stakeholders have expressed concerns about the impact of this trend on protocol complexity and patient participation burden during trials. The principles and guidelines in ICH E6(R2) influence the complexity of trial protocols and, by extension, the burden of data collection, validation, and reporting on investigative site staff and patients. Although the ICH E6(R2) guidance is meant to protect the “rights, safety, and well-being of trial subjects,” it does not sufficiently address the patient’s growing role or the roles of the many vendors and third parties that have entered the market.

The ICH E6 guidance is currently being revised (ICH E6 R3), and the industry has yet to see how this new iteration will approach oversight of these emerging external stakeholders. The goal of this study is to provide insight on ICH E6 revisions that could improve clinical trial operating activity by incorporating the patient’s changing role and those of the many stakeholders, including new entrants into the pharmaceutical industry.

The Tufts Center for the Study of Drug Development (Tufts CSDD) conducted a study in collaboration with MaxisIT, a technology solutions provider.* In early 2021, Tufts CSDD examined and identified areas in the ICH E6(R2) guidance document that fall short in accommodating the role of patients/study volunteers as partners in clinical data collection. To gather in-depth perspectives on these topics, Tufts CSDD facilitated three 2-hour virtual listening sessions in March 2021 among 20 clinical operations, data management, and regulatory affairs executives. A 2-hour virtual roundtable discussion was later held in mid-June 2021 to review the results of the listening sessions, gather additional insights from listening session participants, and add new voices and perspectives to the research. A total of 26 individuals attended the roundtable. Finally, Tufts CSDD interviewed six roundtable attendees during the summer of 2021 with relevant and extensive backgrounds in clinical trial regulation and development to expand upon the findings from previous discussions.

One pervasive issue that emerged during the interviews and discussions is the increased patient and study staff burden when unfamiliar technology is utilized for a trial. Although awareness and knowledge among the general public surrounding basic technology has grown exponentially in the last 10 years, patient and study staff burden can increase when the technology is sophisticated or has an interface that is unfamiliar. As a result, patient and study staff capabilities differ by trial, site, and geographic area, so the use and type of technology should be centered around the individual patient as well as the site capabilities.

One suggestion for decreasing knowledge-based patient burden when patients are oversight partners in a trial is adhering as much as possible to existing standards of care. For example, a diabetes patient participating in a diabetes-related clinical trial will have certain familiarity and capability around medical instruments and procedures more than a “healthy participant.” Whenever possible, responsibilities placed on the patient should adhere to the existing standard of care for the given disease.

Collecting feedback from trial participants and sites is another important way to prevent burden in future trials or improve the level of burden in ongoing trials. Some sponsors have struggled to effectively collect feedback from patients due to confidentiality concerns, or simply do not have feedback mechanisms available. A few participants from larger sponsor companies discussed channels in place for some trials that collect feedback from patients and sites during the study design process, throughout the treatment duration, and following the end of the trial. Such feedback channels can potentially decrease patient burden by adhering to what the patients believe is burdensome. However, these feedback channels have not been widely implemented and it will take time for sponsors to not only establish these mechanisms but also to learn to accurately interpret and cater to the patients’ needs.

A consistent theme surrounding patient burden and data collection is to only collect data that is critical to the trial and avoid extraneous protocol data collection. Although guidance in this area has been established, further clarity surrounding the restriction of extraneous data collection in ICH E6(R3) could decrease burden for the patient and the site. Other basic guidelines that currently exist may contribute to resolving this issue, such as ICH E8, which encourages patient feedback and input into study design.

During trials in which patients collect their own data and provide oversight, monitoring professionals still must review all patient activities and data. Discussions and interviews revealed concerns about how monitoring professionals can identify relevant data; validate the data; and integrate new technology in this process. Though we have yet to see how many companies will revert to on-site monitoring after the pandemic and how many will continue with decentralized models, multiple participants stated that they think many companies will return to on-site monitoring. Some of these are smaller sponsors without the technology to continue remote monitoring. Others might have a new system that relies on CRO partners, and internal staff may not be familiar with the technology. If on-site monitoring returns, the development of a remote monitoring process that allows monitoring professionals to overcome the challenges that accompany patient-collected data and patient oversight practices could be delayed until the use of decentralized trial models is more established among both large and small sponsor organizations.

Training and technological solution standardization were proposed as resolutions for decreasing burden on both patients and study staff and was discussed extensively throughout the listening sessions, roundtable, and interviews. Although there were mixed thoughts on the effectiveness of training in patient data collection and incorporating new technology systems, most participants agreed that training helps, but it should not be the only solution when confronted with these challenges. The simplicity and clarity of processes and systems, among others, are also important factors.

ICH E6(R3) should focus on data quality and patient engagement—in this case, patient engagement could mean patients have input into study design or aspects of data quality and verification. Additionally, throughout this study participants have discussed the detrimental focus on 100% SDV among sites. ICH E6(R3) should further highlight risk-based monitoring over 100% SDV, as monitoring and validating patient-collected data with 100% SDV would be difficult to carry out and would increase burden on the site and the patient.

Many participants discussed lack of system standardization across sponsors and its effect on the site’s ability to collect data and conduct trials quickly and effectively. Systems can also differ across sponsor organizations or departments within the same organization, creating confusion and additional burden for sites that have to navigate learning various systems for the same purpose. Although select vendors’ products are commonly used by most sites, there is rarely only one system that sites and patients are required to use.

Some participants in the roundtable and interviews did not see any resolution to the lack of standardization and vendor agnostic** solutions. The discussions clarified the different needs and operations across sponsors and sites, which has led to adoption of hybrid technology solutions. According to participants, implementing one system with the same capabilities across every site has not been feasible, as some level of customization is necessary for most trials. Participants expressed a need for integration and standardization of systems, however, and sponsors have not yet made the move to adopt or build centralized data platforms to improve their ability to maintain oversight and collaborate. Despite various limitations and evolving scenarios, standardization is still an important topic, and some steps can be taken to minimize the cost and time burden as well as potential risks resulted from delayed data that lack of standardization causes. One of these steps involves focusing on strategy or more efficient processes for using vendor agnostic technology when attempting to standardize systems. For example, sponsors could potentially standardize their processes so sites can more easily train for and adhere to methods across sponsors. Technology solutions should then be able to support these new methods. This process has occurred previously with GCP/ICH training, where study staff training with one sponsor can be applied to multiple sponsors across trials.

Participants did not think standardization was applicable to ICH E6, and in fact some were concerned that addressing this problem in the guidance could hinder innovation and make it more difficult for sites to operate. Standardization must occur among sponsor organizations with the focus of alleviating site burden. However, the guidance can help by implementing guidelines around topics such as third-party vendor oversight that encourage standardization of processes among sponsors, which could potentially lead to system standardization.

Leaving room for innovation in ICH E6 guidance

A common thread of conversation throughout the course of the research was maintaining simplicity and flexibility in the ICH guidance in order to be widely applicable across sites. However, a more general version of the guidance may result in variation of its interpretation among sponsors and sites. Some participants said that misinterpretation can increase burden because sites do not know what the regulator will look for during inspections. This confusion over the requirements influences the implementation of 100% SDV and other unnecessary and time-consuming tactics.

Regulators can prevent misinterpretations by providing transparency around the focus of inspections, making it easier for sites to adhere to these requirements. Additionally, industry groups and institutions can contribute to a general understanding of the guidance that will help those sites or sponsors struggling to achieve clarity in the interpretation.

The ICH E6(R3) guidance that is being developed is currently a collaborative effort with professionals from a variety of clinical trial fields incorporating their insights. This effort could contribute to a more widely interpretable document. Providing transparency on the guidance’s base principles while not being too didactic or restrictive can also leave room for innovation within the space of clinical research.

The main barriers to incorporating patients as oversight partners in clinical trials—and the acknowledgement of patients as stakeholders in the ICH E6 guidance—include the absence of technology standardization between and within sponsors and sites, protocols that overburden patients or require gathering extraneous data, and industry silos. The pharmaceutical industry is unlikely to adapt quickly to the needs of remote and hybrid trials and patients overseeing their own data collection because these barriers prevent quick turnaround. Therefore, it will take time and multiple research initiatives for the idea of patients as oversight partners to become commonly accepted and implemented throughout the industry.

ICH E6(R3), which is scheduled for release later this year, is expected to address the rapid innovations in technology and design that impact the conduct of trials. The guidance can also help encourage adaptation by considering the needs of sponsors and sites and allowing for flexibility in conducting trials. According to participants in this study, innovation is not driven by regulations. Instead, regulations create a minimum standard of quality and care in a clinical trial, and the more flexible regulations are, the more space there is for innovation among sponsors and sites.

Efforts to incorporate patients as oversight partners while addressing these potential drawbacks include training, collection of patient feedback, system standardization, vendor agnostic data platforms and maintaining an open channel of communication between the site and the patient. Although these solutions also contribute to mitigating the increase of patient and study staff burden, many sponsors have not, or state that they are not currently capable of, implementing them. Additionally, despite the higher use of digital processes and remote trial solutions during the COVID-19 pandemic, participants in this study anticipate that many sponsors will likely return to pre-pandemic standards as a result of lack of infrastructure and resources. Although patient oversight approaches have a strong place in the future of clinical trial technology, progress must be made before the industry is ready to adopt.

*This research study was funded by MaxisIT.

** In this article, vendor agnostic solutions/technology refers to a solution/technology that is generalizable, so it is interoperable among various systems.

Note: The authors would like to acknowledge Monique Garrett of PrismWorks for her contribution to this article.

Research Analyst, Tufts CSDD and School of Medicine Development, 

Professor and Associate Director, Tufts CSDD and School of Medicine Development, 

Deputy Director, Research Professor, Tufts CSDD and School of Medicine

Improving receptivity and response to the evolving nature of clinical trial patient oversight.

Emily Botto

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