Mary Jo Lamberti, PhD

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

Articles

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

Assessing Sponsor and CRO Awareness

Remote and virtual clinical research team collaboration has been a defining characteristic of global drug development activity during the pandemic. This article, based on research conducted between September 2020 and April 2021, summarizes how organizations approached adapting to remote operating models and the associated experiences and effectiveness of clinical research professionals managing their roles and responsibilities.

The goal of this article is to provide insight into lessons learned, and to guide considerations about the future of remote team collaborations within biopharmaceutical companies and other stakeholders in the clinical research enterprise.

The results reveal that drug development professionals have been mostly satisfied with their organizations’ remote preparedness and responsiveness and feel supported by their managers and organizations. In addition, clinical research professionals operating remotely during this global health crisis perceive that their productivity and effectiveness levels have been high, and the majority wish to continue to work remotely. The results also show that there are areas requiring attention: 55% of respondents reported feeling burned out and 42% reported that connections with colleagues had deteriorated.

Tufts CSDD research conducted early in the pandemic

 captured the variety of remote and virtual approaches being utilized. As expected, communication technologies—including video conferencing, cloud-based file sharing and telehealth—were the predominant approaches being used by clinical teams. Other widely used solutions—largely out of necessity—supporting clinical trial activities included eConsent and remote monitoring. 

A study conducted at the Cleveland Clinic Cancer Center

, revealed some key benefits of remote work and its impact on the execution of clinical research. The findings are based on analysis of productivity data sourced from a remote research coordinator (RC) pilot program that started one week prior to the onset of the pandemic. By March 25, 2020, all research coordinators at the Cancer Center were part of the program and working from home. The data collected revealed that the productivity and efficiency of RCs during at-home days was higher compared to in-office days. The program allowed for higher and better data entry, an increase in the number of trials initiated, and a reduction in trial times to initiate a trial compared to a similar time-period in 2019. An uptick in team morale was also observed. Nearly all members of the 60-person team expressed gratitude for their ability to work at home. Notable benefits included reduced stress and burden from commuting, parking, and fuel costs. Additionally, the work-from-home model correlated with reductions in team turnover.

Employee reports of productivity across industries during the pandemic have been extremely positive. Several studies suggest, however, that although organizations adapted well to remote operating models, many did not provide adequate communication and support. A study by Marsh McLennan among 256 employees, for example, found that one-third gave mixed reports of their manager’s preparedness and effectiveness in implementing company-wide response to the pandemic.

In another cross-industry study conducted among 5,043 full-time employees, high levels of anxiety were observed among personnel whose organizations did not clearly state their plans, policies and vision for remote work. The study, conducted by McKinsey & Company, also found that most employees would like to see their organizations adopt flexible and/or hybrid virtual working models after the pandemic has ended. More than 50% of participants in the survey would like to work from home at least three days per week in the future; those with young children are more likely to prefer fully remote working models.

Tufts Center for the Study of Drug Development collaborated with the Bill and Melinda Gates Medical Research Institute (Gates MRI) and undertook a global study in early 2021 to understand the attitudes, experiences and effectiveness of remote teams specifically within the clinical research enterprise. This study afforded the opportunity to gather more granular data and more targeted insights.

Tufts CSDD and Gates MRI teams established a working group of organizations comprised of stakeholders across the clinical research enterprise in order to solicit comprehensive and diverse input. A total of 26 organizations participated in this working group including representatives from patient advocacy groups, medical research foundations, academic medical centers, government agencies, pharmaceutical and biotechnology companies, contract research organizations and investigative sites.

Based on a working group discussion, a 69-question online survey was developed. In addition to questions assessing detailed respondent characteristics (e.g., demographics, organizational characteristics), the survey focused on specific steps taken to adopt remote work practices before and since the pandemic began, organizational support in the transition to remote work, employee wellness, capacity for work, diversity and inclusion, and the impact of remote approaches to work. Respondents were also asked about their perceptions surrounding clinical trial performance and the future of remote work.

Survey responses were fielded globally between January 27, 2021 and April 9, 2021. A total of 344

 unique responses were gathered and reflected high survey response completeness and variation.

 The results of our analysis are presented below. 

We analyzed twelve different subgroups (see Exhibit 1) to understand personnel experiences adapting to and operating remotely.

Exhibit 1: Characteristics of Respondents

Our sample includes respondents from more than 50 countries across five continents, as well as a wide range of races and ethnicities. More than half of respondents live in the US & Canada and self-reported white, female, and between the ages of 35 and 54. Most respondents also indicated having caregiving responsibilities and one or more children. Nearly six-out-of-ten respondents reported that they are employed by large organizations.

The vast majority of those working at academic medical centers and research institutions reside in the US and Canada.

Whereas some significant differences were observed across all twelve subgroups, significant differences (p

.05) were most commonly observed by organization type and geographic area.

Approximately four-out-of-ten (43%) respondents indicated that their productivity was unchanged since the pandemic began, while 35% reported that their productivity had increased. A lower proportion—19%—noted that their output had declined and 3% were not sure. Respondents working in pharmaceutical and biotechnology organizations were more likely to report higher productivity than respondents working in other types of organizations (p 

.05). US and Canadian respondents were more apt to report higher productivity levels since the pandemic began compared to European, UK, and Latin American respondents. Differences by respondent age were also observed; those between 35 and 54 reported higher productivity compared to respondents in younger or older groups (p 

Respondents’ self-reported assessments of their remote performance was high: 71% indicated ‘very effective’ and 26% ‘somewhat effective’. Similarly, more than three-fourths of remote team managers evaluated their teams as being ‘very productive’ (76%) and one-fifth (21%) as ‘somewhat productive’ since the pandemic began, reflecting alignment between the perceptions of team managers and individual team members (see Exhibit 2).

Exhibit 2: Self-reported remote performance vs. team productivity rating

Respondents from biopharmaceutical companies and contract research organizations (CRO) were more prone to report that they were either ‘very’ or ‘somewhat effective’ in their remote roles compared to those working at academic medical centers or research institutions (p

 .05). In addition, those without children tended to report that they were more effective (‘somewhat’ or ‘very’) doing remote work compared to those having one or more children. In comparing women and men, women had an increased likelihood of reporting that they were ‘very’ or ‘somewhat effective’ performing remotely compared to men (p 

The vast majority (93%) of respondents indicated they were satisfied with their organization’s preparedness in transitioning to remote work, 95% reported satisfaction with their organization’s responsiveness, and 57% reported satisfaction with provision of resources by their organization. European and UK respondents were more likely to report satisfaction with their organization’s preparedness and responsiveness (p

.05). In contrast, Latin American respondents were less likely to report satisfaction with provision of resources compared to those in other geographies. Individuals working at biopharmaceutical organizations were also more likely to report satisfaction with preparedness, responsiveness, and provision of resources when compared to other types of organizations (p 

Three-out-of-four (74%) respondents indicated that their organizations had a remote work policy in place prior to the pandemic and 66% reported that their remote work policies changed once the pandemic began. Some of the changes reported include financial support for better home office setups, allowance for relocation “beyond reasonable commute” areas, increased number of virtual meetings, and greater flexibility. In addition, respondents also reported increased quality and scope of information technology (IT) support, expansion of the existing remote policy to include roles that were previously not included, and a shift to permanently remote setups, among other changes.

A higher proportion of CRO respondents worked at organizations that had a remote work policy in place before the pandemic began. Biopharmaceutical respondents were more likely to say their remote work policy changed during the pandemic compared to other types of organizations (p 

A higher percentage of US and Canadian respondents reported that their remote work policy had changed since February of 2020 compared to respondents located in other geographies (p 

.05). Most respondents also reported that their respective organizations provided access to the basic elements of remote work such as laptops/desktops (89%), paid access to communications platforms (88%), and stable compensation (85%).

Notable differences were observed in levels of provision of resources by organization type, with pharmaceutical and biotechnology companies and CROs providing most resources to their staff at higher levels. Respondents from biopharmaceutical companies were more likely to report access to computer monitors and hardware such as mouses, keyboards, and headphones when compared to other types of institutions (i.e., non-profits, etc.) (p <.05). We found that a higher percentage of CRO respondents reported receiving paid access to high-speed internet compared to other types of organizations (p <.05). We also observed that higher proportions of respondents from academic medical centers, research institutions, and pharma/biotech companies reported access to updated standard operating procedures (SOPs) and regulatory compliance training during the pandemic.

Interestingly, significant differences were not observed in the importance rating given by respondents to each of the resources we enquired about. Most respondents agreed that paid access to high-speed internet and virtual communication platforms were highly important to the effectiveness of remote work, and yet these resources were not provided at similar levels across the various types of organizations included in this study.

Overall satisfaction with organizational approaches to remote work was very positive; 92% of respondents indicated they were ‘very’ or ‘somewhat’ satisfied with the approach implemented by their organization (see Exhibit 3). Respondents expressed satisfaction with their organization’s approach to cybersecurity (94%) and access to communication platforms (90%).

Exhibit 3: Satisfaction with organization’s approach to remote work since February 2020

Female respondents were more likely to be satisfied (95%) with their organization’s approach compared to males (90%). Biopharmaceutical companies and CROs were also more satisfied than were other types of organizations. These results were statistically significant (p 

Impact of remote work: burnout, inclusion, and social support

The Tufts CSDD/Gates MRI global survey also detected adverse effects of remote team activity. More than half (55%) of respondents reported feeling burnt out, while 9% of respondents said they were unsure. Burnout was primarily attributed to factors such as frequency of virtual meetings, added work responsibilities, restlessness, and uncertainty in work demands. The latter factor is consistent with findings reported in other recent studies.

Other factors contributing to burnout include feelings of loneliness and hopelessness, caretaking difficulties, and inadequate access to tools. Many respondents also reported facing emotional burden due to the US political environment in 2020, deterioration of co-worker relationships, and the inability to travel.

Respondents aged 18-34 were more likely to report burnout compared to those 35 and older (p 

.05). Female respondents were also more likely to report burnout compared to males—at 57% and 51% respectively (p value 

.05) A striking number of respondents within academic medical centers and research institutions—71%—said they have felt burnout since February 2020. This proportion is nearly 1.5x higher compared to respondents in biopharmaceutical companies, CROs, medical research foundations, patient groups, and government agencies. Not surprisingly, respondents who were in roles with frequent patient interaction were more likely to report feelings of burnout (61%) compared to those in roles without patient interaction (54%).

Among the 18-34 age group and those with caregiving responsibilities, the factors causing higher relative reported burnout included frequency of work-related meetings, added work-related responsibilities, uncertainty and variability in work-related demands, and feelings of hopelessness (see Exhibit 5).

Respondents in Latin America were almost 4x more likely to say that feelings of hopelessness were a major or moderate factor in their feeling burned-out compared to respondents in other geographies. Rest of world (ROW)—Asia, Australia, Africa—respondents were more inclined to report frequency of work-related meetings as a major or moderate factor in their burnout.

Exhibit 5: Differences in reported causes of burnout across age groups, geography, and whether they were caregivers

A high majority (82%) of clinical research professionals indicated that their feelings of connection to their colleagues had deteriorated since February 2020, with four out of ten saying they felt less connected to their colleagues. Loss of connection with colleagues was most observed among those in patient-facing roles (55%). Interestingly, 87% of survey participants said they felt somewhat or very supported by their colleagues, while 86% indicated they felt supported by their managers and leadership. Those working at pharmaceutical and biotechnology organizations were more likely to say they felt supported by colleagues, managers, and leadership, compared to those employed by academic medical centers and research institutions (p <.05); 90% of respondents from biopharmaceutical companies reported feeling supported compared to 82% at academic medical centers and research institutions.

Eight-in-ten (80%) respondents reported that the greatest benefit of remote work and collaboration was increased flexibility followed by gained time from not having to travel or commute to work (12%). Better relative participation within and across teams was also a key benefit mentioned.

The vast majority of respondents (89%) felt that they were either ‘extremely’ or ‘somewhat’ likely to embrace adopting a mostly remote work model, and a similar percentage of respondents (84%) indicated a high probability that their organization’s leadership would accept continued remote work models (see Exhibit 6).

A mostly remote work model was defined as having 60% of staff working remotely at least 60% of the time. Females were more apt than males to support this model and US and Canadians were more prone to accept working primarily remotely compared to their European, UK, and ROW counterparts (p 

Exhibit 6: Likelihood of management to permanently embrace a ‘mostly-remote’ work model

Most respondents (86%) indicated support for their organization’s current remote model—or a similar version—to continue when the pandemic ends. Respondents over the age of 35 compared to other age groups; and females with one or more children at home were the most likely to support their organization’s current remote model after the pandemic ends (p 

Those in the US, Canada, and Latin America indicated support for their company’s remote work model compared to European, UK and ROW (Asia, Australia, Africa) respondents (p 

 .05). And pharmaceutical and biotechnology company representatives expressed a higher likelihood to want to continue in their organization’s current remote work model compared to those working in other organizational settings (p 

The results of the Tufts CSDD/Gates MRI Remote Clinical Research Team Experience and Effectiveness study indicate that clinical teams have transitioned to remote collaboration models well facilitated by employers who are generally supportive and prepared. Remote clinical teams report performing their roles effectively, but a high percentage are feeling burned out and experiencing deterioration in their connections with their colleagues. 

Gaps were identified in respondents’ perceived importance of resources in select areas compared to organizations’ provision of these. Wide gaps were especially seen in the perceived importance of high-speed internet access and external computer monitors compared to their provision, suggesting that additional investment may be required by certain organizations in select areas to sustain their remote work activity.

Biopharmaceutical company and CRO respondents reported a greater likelihood of perceived effectiveness in their remote roles compared to those working at academic medical centers or research institutions. This result may also be tied to (1) differences in investment in resources at other types of organizations, and (2) that academic medical centers and research institutions may require greater support from sponsors and other stakeholders to conduct clinical research effectively using remote approaches.

Global differences also were observed in self-reported productivity; respondents in the EU, UK, and Latin America reported lower levels compared to their counterparts in the US and Canada. This finding suggests that there may be geographic disparities in the level of remote support provided. Further study is needed to examine this area. 

Substantial burnout was observed globally with the primary causes identified as frequency of virtual meetings, added work-related responsibilities, variability and uncertainty and feelings of restlessness. Younger workers, women, and respondents from academic medical centers and research institutions were more likely to report burnout. Retaining younger workers could become a greater issue as the pandemic ends with those workers leaving for organizations that return to the workplace or offer more opportunities to interact and collaborate face-to-face with co-workers. In addition, workers who were younger than 35 were also less likely to endorse a remote model in the future. Women, however, were more likely than men to support a future remote model, suggesting that more support might need to be established for women who continue to work remotely to avoid experiencing burnout. More effective and less frequent virtual communication may help address burnout while improving connectivity among workers.

Despite some of the subgroup differences, the vast majority of respondents support a version of their organization’s remote model when the pandemic ends. This finding underscores the importance of establishing operating models that can accommodate a variety of options simultaneously for employees who prefer to continue to work from home and those who prefer a mix of home—and office—based activity, especially younger workers and women. Offering flexibility to those who have responsibilities outside of work is critical and has been characterized in other studies.

The Tufts CSDD/Gates MRI study focused on the impact of remote clinical team collaboration experience at the beginning and in the earlier stages of the pandemic. We will continue to examine and draw lessons and insights on remote team experience and effectiveness long after the pandemic is behind us. As organizations adjust and adopt policies to accommodate and support a global remote and hybrid workforce, newer models and opportunities to drive innovation and employee satisfaction will no doubt emerge.

, MBA, is Deputy Director and Research Professor; all of Tufts Center for the Study of Drug Development, Tufts University School of Medicine.

Alexander, De Smet, Langstaff, Ravid. What employees are saying about the future of remote work. McKinsey and Company Report. April 1, 2021. 

Cleveland Clinic’s Cancer Research Team Sees Increased Productivity During COVID-19. Cleveland Clinic. December 7, 2020. 

Jenkins, Zabor, Mooney, et al. Increased Productivity and Efficiency Among Cancer Center Clinical Trials Workforce during the COVID-19 Pandemic. 

LeBreton, Lamberti, Dion, et al. COVID-119 and Its Impact on the Future of Clinical Trial Execution. Applied Clinical Trials, October 22, 2020. 

Caputo, Hyland. Employee Concerns about COVID-19. Marsh McLennan Report. 2021. 

344 surveys were submitted with fully signed and completed consent forms.

For nearly every question, approximately 15 respondents chose not to answer.

A summary of how organizations approached remote operating models and the experiences and effectiveness of clinical research professionals in their roles and responsibilities during the COVID-19 pandemic.

Remote Clinical Research Team Experience and Effectiveness During the COVID-19 Pandemic

The COVID-19 pandemic caused major disruptions to clinical trial execution in the U.S., impacting key stakeholders across the industry. Investigative site capabilities experienced upheaval, driven by staff furloughs, social-distancing protocols, financial losses, and concerns over patient safety. Sponsors, CROs and other organizations that support drug development shifted to remote working environments. An estimated 80% of non-COVID-19 trials were stopped or interrupted as a result of the COVID-19 pandemic.

An April 2020 study suggests investigative sites demonstrated flexibility and ingenuity in adopting new approaches in order to cope with challenges presented by COVID, with over half of investigative sites transitioning to virtual approaches to interact with patients. More recently, follow-up studies performed in August 2020 have identified persistent impact of COVID, with over 60% reporting an “average” or greater level of impact on ongoing trials and initiation of new trials. Respondents specifically highlighted challenges in patient enrollment and recruitment.

Recent FDA guidance (March 2020 and updated July 2020)

acknowledged that the impact of COVID-19 may require companies conducting clinical trials to consider virtual patient visits or put new processes in place regarding their current protocols. Therefore, there are now more opportunities for using remote healthcare including conducting virtual or decentralized trials, site-less clinical trials and use of other non-traditional approaches that do not involve in-person visits. This shift, driven by the effects of the pandemic, prompted the team at the Tufts Center for the Study of Drug Development to conduct a qualitative study researching the impact of COVID-19 on clinical trial execution. 

The study examined the effects of COVID-19 on clinical trials by gathering insights and perceptions from clinical operations professionals at pharmaceutical companies in the United States. The goal was to understand the modifications that organizations have made in response to the pandemic, especially with regard to remote or virtual approaches. In addition, the study explored how companies have approached planning and implementing remote and virtual approaches to trials, as well as their experience and lessons learned. Last, Tufts researchers sought to understand initial perspectives on how COVID-19 will impact trial execution in the long-term.

A total of 25 interviews with pharmaceutical and biotechnology executives within the clinical operations department from unique companies were conducted using Zoom. All executives worked in the United States and played a role in U.S. clinical operations. Participants were selected from Tufts CSDD proprietary lists of contacts who work in clinical roles and through other collaborations on prior studies or from professional conferences and meetings. Participants were recruited via email from June to early August and have extensive experience conducting clinical trials across diverse therapeutic areas. Interviews were 30 minutes in duration and were conducted by Tufts CSDD researchers using a comprehensive discussion guide encompassing the following areas: (1) COVID-19 Impact on Ongoing Trials, (2) Organizational Preparedness, (3) Trial Amendments and Remote Technologies, (4) Role of Regulatory Agencies (5) Role of Third-Parties, (6) Long-term Impact of COVID-19.

Interviews were conducted with U.S.-based staff at 25 organizations comprised of pharmaceutical, biotechnology, and non-profit research institutions. There were 15 large organizations represented and 8 mid-sized or small companies based on R&D spending.* Two were non-profit organizations. These were included given they often sponsor government-funded clinical research.

Eleven organizations halted ongoing trials and enrollment for at least one month. Shutdowns were most frequently driven by concerns that patients would not be able to safely travel to and receive care at research centers. These concerns were especially poignant in indications that were considered “high-risk” for COVID infection (e.g., cardiology, pulmonology, immunology) or indications where patients had difficulty traveling or for example, had neuromuscular and/or neurodegenerative conditions. In these cases, studies often resumed only once patient safety was assured and R&D organizations had amended protocols to include suitable pandemic contingency plans. An interviewee discussed the impact of COVID on their ongoing trials:

“We put our entire portfolio on hold for two months—it became clear we were not ready to move to a virtual situation.”

Another 12 organizations reported moderate impacts on ongoing trials, most frequently citing delayed enrollment as the primary challenge related to COVID. Several factors may have reduced impact on ongoing trials. Trials in indications such as dermatology and psychiatry may have faced less severe disruption, given more frequent use of telehealth in clinical practice prior to COVID or relative ease of transitioning collection of outcome measures to remote methods (e.g., measuring skin lesion size over telehealth). Additionally, organizations that demonstrated a higher level of pre-COVID preparedness or greater organizational agility tended to report lower impact. Finally, organizations with modest impact often reported partial, geographically isolated closures or understaffing at select sites, rather than full shutdowns reported by those experiencing greater impact. The impact on an organization’s investigative sites is described by a respondent: 

“Many of our sites were partially closed, and we had to incur additional cost to sustain our study. We are maybe approximately 25% behind on enrollment as a result.”

Most R&D organizations that reported some level of COVID impact suggested that the ability of sites to respond to the pandemic was a key indicator of the level of impact. Given COVID-19 outbreaks occurred regionally in the U.S., differences in site response emerged based on location and time period. Respondents identified four key factors that tended to influence sites’ abilities to respond to the pandemic. First, staffing furloughs were often site-dependent, and often resulted in delays in data processing, as well as scheduling and execution of patient visits. Additionally, many patients felt hesitant to visit research centers, especially in harder-hit regions, with select organizations citing higher rates of patient withdrawal from studies. Sites with poor or non-compliant IT faced significant challenges pivoting to telehealth visits, providing access to EMR to investigators, or completing CRA site visits virtually. Finally, sites set different restrictions based on hospital- and state-imposed protocols (e.g., no lab-only visits, additional PPE needed, etc.) that resulted in potential deviations from protocol or delays.

Figure 1. 23 of 25 organizations reported some level of impact on ongoing trials due to COVID-19.

A couple of organizations (n = 2) reported experiencing small or no disruptions. These organizations were often running early stage trials (e.g., Phase I) where clinical follow-ups to identify adverse events could easily be performed over telehealth. An interviewee conducting studies in early phases noted that “there is a fairly large dichotomy between early phase and late phase—the impact for Phase I and Phase II is a little less.” Organizations with less disruptions also were often running trials in disease areas where patients required urgent treatment and/or had few options for treatment (e.g., oncology, rare disease).

Organization response: successes and failures

R&D organizations reported a spectrum of success in responding to the challenges presented by COVID. R&D organizations that self-reported “successful” responses to COVID-19 often demonstrated at least one of four key success factors: organizational agility, prior investment in remote technologies, development of COVID-19 task forces, and/or strong R&D capabilities in Asia-Pacific (APAC) regions.

Five organizations cited organizational agility as a key factor in the success of their COVID response. Smaller, flatter organizations were less hindered by bureaucracy, and were able to rapidly implement changes to studies.Decisions were made at a study-team level and upper management were informed of decision-making. In these cases, it was critical that leadership trusted their employees to execute trial changes without significant oversight.

Another 5 companies were piloting remote technologies and services prior to COVID and reported transitioning more easily to “virtual” trials.Several organizations were piloting telehealth, remote data monitoring, home health, and other virtual approaches in ongoing studies. Comfort with existing remote infrastructure allowed for rapid expansion into indications that did not initially leverage but could benefit from virtual approaches (e.g., measurement of skin lesions over telehealth in dermatology trials). The trend of shifting to a more remote model was explained by an interviewee:

“We were already in the process of things becoming more virtual anyway. This has definitely accelerated the process because we’ve had to adapt.

We are thinking more about how we collect data, verify data from a remote perspective.”

Establishment of a task force was instrumental for larger companies to prepare and rapidly amend trial designs to include remote modalities, with 5 of interviewed organizations reporting implementing such task forces. For larger organizations, the creation of response teams was critical to preparing for COVID’s impact. Organizations that successfully adapted trials to COVID-19 typically had upper leadership that trusted their task force to execute without significant oversight. In select cases, leadership indicated desire to press forward with additional changes to future trials, in order to continue building upon the trend toward virtual trials. The COVID-19 task force typically encompassed representatives from all key trial functions. Experienced team members with backgrounds in operations, regulatory, and data management were all required for implementation of novel remote technologies. Following general guidelines from the COVID-19 task force, study leads often were responsible for managing direct COVID-19 impact. Study leads needed to consider each investigative site separately, given variable COVID-19 activity across regions in the U.S. Task forces that took a study-by-study and site-by-site approach reported greater success than those that attempted a “uniform” approach. The importance of a relatively independent task force that could communicate with study teams and leadership was explained by two interviewees:

“There wasn’t a one-size-fits-all approach to our trials, given they were in different therapeutic areas and geographic regions. Thus, it was important to allow study teams to make recommendations that we could then adopt.”

“Communication with leadership was important to keep them informed of changes to our trials. They really just let us run with it. Now that we have a plan, leadership is pushing to make ‘the next step’ and make sure we COVID-proof our trials going forward. This includes leveraging more virtual approaches.”

A minority of organizations (~2) reported leveraging their organizations’ R&D capabilities in China and Japan, who had early COVID experience, to prepare ongoing studies in the U.S. Select global R&D programs indicated that their colleagues in China and Japan warned them about the impact COVID may have on trial execution, which allowed them to prepare for COVID and begin to develop protocols in case sites were shut down. Of note, this was a benefit that was not reported consistently by global R&D organizations and may be dependent on specific colleague-colleague relationships.

Adoption of remote monitoring technologies and decentralized approaches

Interviewed stakeholders implemented a wide range of novel remote monitoring technologies and decentralized approaches to make trials more patient-centric in the COVID era.

Figure 2. Telemedicine and eConsent were the most frequently utilized remote technologies, while home health was the most frequently utilized remote service.

Telemedicine and eConsent were the most frequently mentioned technologies adopted during COVID-19. Telemedicine was implemented by the majority of respondents, with 19 interviewed organizations reporting use of telehealth in ongoing trials. Telemedicine was most frequently used for routine follow-ups to identify adverse events, especially in Phase I studies. Telehealth was also used to measure select objective outcome measures (e.g., lesion size in dermatology or plaque psoriasis). Though investigators recognized the potential to collect other measures via telehealth (e.g., depression scales), they expressed concern that the method is not validated and requires proof of concept before regulators would accept data generated through telehealth. eConsent was used by 10 companies and was perceived to be one of the simplest innovations to implement. Respondents highlighted the potential for eConsent to facilitate communication with patients, by leveraging novel modalities such as video explanations, quizzes to assess understanding, etc. Interviewees offered their insights on remote technologies:

“I expect eConsent and telemedicine will become routine and integral parts of clinical trials. They are pretty straightforward steps towards a more patient-centric trial, and could easily be adopted in most, if not all, protocols.”

“We had piloted eConsent on a couple of studies and it (COVID) moved us out of the pilot very quickly. We’re trying telemedicine even more. How do we ‘hybridize’ a trial even outside of COVID to reduce patient burden?

Broader use of telemedicine may encourage enrollment and make trials more patient-centric.”

ePRO was the next most frequently utilized technology, with eight companies citing use. Notably, ePRO was already used in ongoing trials prior to COVID. However, in an effort to further reduce patient burden, research organizations opted to allow patients to use their own devices.

Use of data integration was perceived to be highly useful to R&D organizations, given R&D organizations could access trial data in real-time. Additionally, utilization of EMR provided opportunities for R&D organizations to supplement clinical research data, as potential alternatives to monitor adverse event and clinical care patterns. However, only select companies (n = 4) actually leveraged real-time integration of trial data or EMR during COVID. Several respondents cited challenges with implementation of integrated EMR, given poor investigative site IT infrastructure, investigative site preferences, or challenges with CRO staffing or capability to visit sites. Privacy restrictions, interoperability and compatibility challenges represent additional key barriers to utilization of these technologies. One interviewee discussed the barriers that have emerged in monitoring due to COVID:

“Monitoring is our biggest challenge right now and we’re trying to get back out to sites. Across the board we have major Phase III database locks and we cannot get to some of the final sites that have data. If we don’t have access to their EMR is there another way? We are discussing remote approaches and technologies that can be implemented.”

A number of respondents expressed interest in the future use of integrated EMR, and suggested they were actively seeking CRO partners to implement the technology once sites reopened. In addition to novel technologies, respondents adopted a range of approaches to decentralize trials and minimize patient exposure to investigative sites in the face of COVID-19. Overall, nearly half of respondents implemented at least one approach to decentralize ongoing trials.

Approximately seven organizations implemented some method of home health in their ongoing trials to ensure patients that were unable or unwilling to travel received IV medications and were able to provide blood samples. Rare disease trials reported greater use of home health, given the long distances patients may have to travel to access the investigative site and the need for frequent IV infusions. However, investigators also noted that home health was “hit-or-miss,” given some patients resided in locations inaccessible to home health while others refused to allow nurses in their home due to concerns with the spread of COVID-19. “Home care and direct-to-patient drug delivery are steps to move towards a more patient-centric trial design,” commented one interviewee. Direct-to-patient drug delivery was implemented by five companies and perceived to be a relatively low-risk method to transition trials to be more patient-centric, especially for oral agents with safer expected toxicity profiles.

Decentralized lab work was utilized by five organizations. Many sites did not allow “lab-only” visits during COVID-19, presenting challenges to collecting biomarker-related outcomes in oncology, cardiology, diabetes, etc. Investigators allowed participants to have blood work done at local labs, and in select cases provided co-pay cards to cover the cost of lab work (e.g., via Scout). Decentralized lab/blood work was perceived to be highly effective for oncology and rare disease patients, especially for those that had to travel longer distances to investigative sites.

Overall, remote technology adoption was more extensive than adoption of remote services. One might speculate that remote technology adoption has been more extensive not only because companies had prior experience with these technologies (e.g., piloting) but also because remote personnel and drug delivery require more lead time to set up, more extensive logistics and certification planning.

More than half of organizations interviewed (13 companies) cited leveraging FDA guidance at the start of COVID-19 to adapt and amend clinical trials. Interviewees cited published guidance on home-dosing and telemedicine as being especially helpful at the start of COVID. Interviewees also perceived the FDA to be responsive and accepting of the need for flexibility, so long as the integrity of trial data was preserved, and patient safety was ensured. Several interviewees spoke directly with the FDA and rated the experience as positive and informative.

However, interviewees also noted that regulators’ stances on how or if they would accept data that had been gathered in amended trials was unclear, and how the utilizations of remote technologies would impact filing. Specifically, several interviewees expressed concerns that select outcome measures may not be accepted without proof of concept (POC) demonstrating that collection via remote technology was the same as in a physician practice, given current FDA standards on how data should be measured.

Perspectives on long-term impact of COVID

Ultimately, 20 of the 25 interviewees believed that COVID-19 would permanently accelerate use of remote technologies in clinical trials. Most interviewees perceived increased use of remote technologies as a “silver lining” to COVID-19. Respondents often cited telehealth, e-consent, and EMR/data integration as the approaches that would most likely continue to persist past COVID. Additionally, respondents mentioned that they would aim to streamline the data collected from trial protocols, seeking to provide greater flexibility to investigators while removing “nice-to-have” outcome measures from protocols. Meanwhile, high upfront investment cost and unclear regulatory stance drove several interviewees to predict that trials would return to “normal” post-COVID-19. This perspective was especially clear for oncology and rare disease, where stakeholders believed in-person care was critical. Ultimately, most interviewees acknowledged that while use of remote technologies had been accelerated by COVID, use would not persist without concerted effort from industry and regulators to continue momentum. Change would focus on convenience for the patient as highlighted during an interview:

"We were forced to dip our toes in the water; we will not return to status quo. Patients are likely to expect some of these technologies now to make their lives easier.”

Challenges to adoption of remote technologies

Interviewed stakeholders identified several barriers to the adoption of remote technologies and services. Several interviewees (n = 5) suggested that preference for care at investigative sites would delay implementation of remote technologies. Patients, especially in rare diseases, may prefer to receive care at investigative sites from an in-person key opinion leader (KOL) rather than via telehealth. Others (n = 4) suggested site-specific protocols would hinder adoption. Select sites demonstrated resistance to adoption of new technologies or had specific IT protocols that were barriers to adoption of novel approaches (e.g., poor security delayed remote EMR access). Finally, 8 companies perceived regulators to pose a significant barrier to adoption. Interviewees believe there is low incentive to adopt new technology, given high early investment cost and unclear guidance from the FDA on how they will interpret these technologies during filing. Thus, a firm stance is needed from the FDA to promote utilization of remote technologies post-COVID.

Steps to continuing progression to “patient-centric” trials

Industry, regulators, and investigative sites will need to take several steps to cement the role of virtual approaches and promote patient-centricity in future clinical trials. A strong regulator stance on the use of virtual and remote technologies in clinical trials is necessary to promote adoption by industry. Currently, lack of clarity from regulators on how remotely-generated data will be accepted leads to hesitancy to adopt novel technologies. Published FDA guidance expressing standards for e-Consent, telehealth, and other tools or decentralized approaches may be necessary for organizations to invest in remote technologies. Conversely, POC may be required for regulators to publish such guidance, resulting in a dilemma for companies. 

Additionally, it is critical that all stakeholders including patient advocacy groups and investigative sites be on board in order to move decentralized models forward. Several interviewees perceived that select patients enroll in trials to get “better” care at academic centers. Patient perspectives must be incorporated into trial design in order to balance the patient-centric and cost-related benefits of remote technology with the preferences of patients. Additionally, investigative sites may not have the budget nor the expertise to implement novel remote technologies (e.g., EMR integration, telehealth, e-consent). Industry may need to support sites by investing in technologies and trainings to ensure standardization across investigative sites.

, Research Anlayst; all from Tufts CSDD; 

, MBA, is Deputy Director and Research Professor, 

, both based in Boston, MA. Email: kenneth.getz@tufts.edu 

Dorn, A. V. (2020). COVID-19 and readjusting clinical trials. 

(10250), 523-524. doi:10.1016/s0140-6736(20)31787-6

Medidata. (2020, August 18). COVID-19 and Clinical Trials: The Medidata Perspective. Retrieved from 

https://www.medidata.com/wp-content/uploads/2020/08/COVID19-Response8.0_Clinical-Trials_2020824_v1.pdf

United States of America, Food & Drug Administration. (2020). 

FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency

*Categories of R&D spending based on large companies (R&D >$1Billion); mid-sized (R&D $100 Million - $1 Billion); and small (R&D < $100 Million)

Findings from a Tufts study examining the effects of COVID-19 on clinical trials.

COVID-19 and Its Impact on the Future of Clinical Trial Execution

	The development of new therapies is not possible without volunteers to participate in clinical trials. Recruiting study participants is extremely challenging regardless of demographic background. Challenges to potential participants include time away from work and loss of income, travel to a site and reimbursement, and the potential risks of a trial. There are, however, unique barriers for minority and underrepresented populations who participate in clinical trials, including mistrust, inadequate communication, and significant fear of the research process. Some of these barriers are rooted in the ethical failures of the history of clinical trials. Most notably, the Tuskegee Syphilis study conducted between 1932-1972 which promised black male participants free medical care but did not treat them once the cure became available in 1947.

	There is ample evidence in the literature indicating that the primary factor associated with low participation by underserved groups in clinical trials is a lack of trust in research and in the healthcare system.

Unethical practices, and disclosure and transparency failures are two examples of factors that have led to widespread distrust.

Poor access to clinical trials and the low relative availability of experienced minority clinical investigators are also cited as barriers to minority patient participation.

Recently, significant strides have been made to build the trust between minorities and trial investigators by the National Institutes of Health (NIH), FDA, and among industry stakeholders. The 2019 draft guidance released by FDA on enhancing the diversity of clinical trials reflects the perceived importance of having adequate minority representation in clinical trials.

	            Tufts Center for the Study of Drug Development (Tufts CSDD) and Biogen recently conducted a study to inform growing interest in improving diversity of clinical trial participation.  Tufts CSDD conducted ten in-depth interviews with investigative site staff during July and August 2019 and co-moderated two advisory boards with 11 clinical research professionals in Atlanta and Phoenix. The primary aim of the advisory boards was to understand investigative site experiences and barriers that hinder minority participation. The results of this research provide key insights into increasing the community of minority investigators and study staff and presenting greater access to clinical trials among minority study volunteers.

	The advisory boards noted that trust should exist at both the individual level (e.g., physician, healthcare provider) and the institutional level (e.g., healthcare or medical system) with the coordinator and/or investigator acting as a critical liaison.  Advisory board members expressed:

“In dealing with minority populations, the coordinator needs to know how to address the issues of trust and the distrust of the medical system, and distrust in research.”

“You have to know where that fear and distrust comes from, and then you have to know how to address it appropriately.”

“I usually tell them straight out we don’t have enough African Americans in research, and we’re giving you all this information on medications that are not tailored for us. It’s tailored to Caucasians.”

	Prior research supports the concept of establishing trust at the individual and institutional level. Trust in a physician or researcher is typically based on the quality of personal interactions, while trust in the medical research enterprise  is often based on the reputation of an institution.

One strategy to increase trust at the individual level is through strengthening a patient’s relationship with their healthcare provider. 

	Establishing trust between a healthcare provider and patient requires recognition of diverse patients’ needs, which commonly involves awareness of language preferences. Unfortunately, many sponsors and study teams often overlook language inequity as a barrier to recruitment of diverse participants. Individuals who speak English “less than very well” are considered to be of limited English proficiency (LEP) and constitute 8.5% of the total U.S.population or 25 million people over the age of five.

The population of LEP people continues to grow, and research shows this population to be more likely to live in poverty, have poorer health outcomes, and be underrepresented in clinical research.

Limited participation by LEP patients greatly diminishes the social benefits and generalizability of clinical trial outcomes. The advisory boards noted that the development of culturally and linguistically appropriate educational interventions geared toward LEP communities are critically needed to explain the risks, benefits, and practices of clinical research.

	One solution recommended to address language inequities was to recruit bilingual site staff; however, the availability of multi-lingual coordinators is extremely limited and remains an urgent need. To overcome shortages of multi-lingual staff, sites offer cultural competency training and language courses to interested employees. Technology can also be leveraged to translate materials into grammatically correct language. Ad board participants recognized that materials should be inclusive of distinct dialects and languages. Information must be accurately translated to reflect the idiomatic characteristics of the target population. Another common misconception is that someone of Hispanic/Latinx background has the ability to speak one language over another or has the literacy level to understand in their preferred language. Whenever possible, both the English and Spanish versions of materials should be included in one document. Study coordinators related examples of patients who enroll or discontinue studies based on a family member’s advice. Bilingual materials are also beneficial for family members who are involved in the patients’ healthcare and decision-making. As the role of family and tradition are highly valued among diverse populations, including the patient and their family early on in the recruitment process is key to improving participant adherence to the study protocol. 

“The thing is, a patient goes home and explains in a way that’s not going to be the same as what was explained to them during their visit because it’s just–they explain whatever they absorbed, and it might not–to the family, it might sound like an experiment, which is what a lot of patients say, versus someone who is trained to explain it to the family member.”

“A lot of times we’ll have a woman come in, we’ll give her the consent form and talk to her about it, and she’ll say, ‘My husband has to read it,’ or ‘I have to talk to my husband.’ Men will do the same thing, ‘I have to talk to my wife.’ Sometimes they’ll bring their wife or their husband. Then it just makes it a little bit easier, because they’re both there.” 

	Establishing a safe participation environment

	Fear of deportation among undocumented immigrants who become involved as research participants was identified by the Phoenix ad board as a source of concern leading to greater mistrust and fear.  Participant misunderstandings about what they are committing to may occur due to a potentially limited knowledge of the research process. As a result, there is a critical need during the recruitmentprocess to provide and communicate detailed study policies regarding the reporting of undocumented immigrants. Enlisting the aid of community-based groups and clinics that are trusted by migrant communities help guide these conversations. 

“Working with a lot of folks that may have mixed legal status in their family, we had a really difficult discussion around this with our team about our level of comfort of actually having to present that to these families and how much of a deterrent that could be. 

“A lot of our folks are working two jobs, have limited transportation. Then if they’re going to show up and be surprised by: ‘You have to fill out this W-9,’ which basically, if you leave this part blank, is saying something about your status, that absolutely is a: ‘I don’t want to participate.’”

	In addition to ensuring sympathetic translations, partnering with the community may avoid engendering stereotypes or confusion by researchers or sponsors based on potential cultural, socio-economic (e.g. poverty), or linguistic differences. Successful intersections and engagement include investigators and staff from study participants’ own communitiesto increase rapport and build trust.One participant established an group of community leaders to develop targeted and appropriate materials; and ensure consent forms were written at the sixth-grade level. In addition, the group provided on-the-job training and “lay training” for community board members. The “lay training” served as an alternative to the current CITI training that is geared for training researchers and may pose challenges for a non-researcher. The training provided community members with a better understanding of medical research at all stages, including patient recruitment, enrollment, and retention.

	Other strategies that foster community collaboration and facilitate trust are researchers’ active participation in the community,for example, by attending and hosting health fairs, or disseminating the results of prior research studies. A recommendation for sponsor companies is to build lay language results into their patient engagement plans. Contrary to popular belief, churches may no longer be the best form of communication and outreach for minority patients. While churches still play an important role and act as a location for community events, it may have shifted as the main/sole source of communication and outreach as younger generations seek other outlets. Including a variety of community stakeholders from the start to the close of a trial has revealed other recruitment strategies,such as “refer-a-friend,” that may ease the recruitment process of specific subpopulations.

“We’re talking about having that trusted visual in the community. When I go in as a member of a university [in the state of Georgia]. I’m introduced to the community through these entry points, these agents, and the gates are automatically open to me.”

“I’ll notice that more of our Hispanics come from maybe refer-a- friend versus our traditional      methods. We have flyers and they’re not putting ‘flyer,’ they’re putting ‘my sister’ or ’my friend,’            things like that. It’s much more refer-a-friend than anything else.”

	Participants strongly encouraged the use of technology for overcoming not only language and literacy barriers, but also for broadening the reach of diverse trial participants. Remote or virtual trials have become more common and their usage is increasing across the industry.

 These trials use wearables, mobile apps, videoconferencing,or other tools to ease the burden for both the sponsor and study participants. Despite significant progress made in virtual trial technology over the past decade, research sites continue to play a vital role in moving clinical research forward. One site shared use of an app-based digital storytelling intervention to engage minority groups and facilitate the informed consent process. Sites also offer Uber and/or Lyft ride credits to improve access to participation.

“The app sends push notifications [to their cell phones] and asks patients to answer questions. It prompts them to watch the story they’re supposed to be watching. It’s working really well for us. It’s geared towardsHispanic patients, but everything-the story, the video-is in Spanish, and includes subtitles in Spanish, too. We also have them set to English, so that if you have a mixed language family, everybody can understand, hear, or read it.”

	Strategies that consider the culture and diversity of a population are effective among investigators and research staff. The advisory board discussions revealed that sitesdo not feel prepared or equipped to serve underrepresented populations. Providing adequate compensation, resources, and allocation of additional time for investigators (of all backgrounds) to prepare and learn about appropriate strategies for recruitment and retention of diverse participants alleviates “burnout” and improves staff retention to ensure continuity of community interventions.

Tangentially, providing clinical research education early in an individual’s career increases their awareness and opportunity to be a clinical investigator or study coordinator. 

“If you want to design a study, the site should be equipped with all the materials on all the populations of interest (e.g.,Spanish-speaking patients). The sponsor has to be ready to provide that to sites so that they feel prepared for the patients.” 

	The group noted that additional investments and incentives by institutions (e.g., universities, hospitals) and other organizations (e.g., professional associations) could potentially increase the numbers of diverse investigative site staff and improve minority participation. This investment could be used to stimulate hiring, support underrepresented study coordinators and investigators, and create a supportive and comfortable environment for diverse investigators. Participants offered ideas for incentives and strategies to motivate researchers and investigators to participate, including publication opportunities, promotions, awards and recognition for minority-serving institutions, supportive infrastructure (i.e. mentorship), and carving out time for primary investigators (PIs) to conduct research. 

“Need good mentorship (not sure if through the same race or not) and institutional support. The institution must provide a level of security that they can do this work and it won’t all come crashing down if they lose a grant cycle.” 

	It is widely known that marginalized groups must overcome large barriers in the clinical research process and in order to establish a solid foundation for diversifying trials and research teams, there are critical areas that still need to be addressed. Mistrust of clinical research and of the medical establishment, and low ethnic/racial representation of investigators, site staff, and study volunteers are factors that perpetuate fear and lack of participation in clinical trials. Community-based partnerships with trusted representatives serve to increase awareness of clinical trials and provide extensive information about the process. It was apparent that this group of diverse coordinators and investigators have been working to include underrepresented participants in trials and are willing to forge stronger partnerships with sponsors and other organizations to promote sustainability of their diversity and inclusion efforts. 

		Acknowledge that the HCP role is influential in developing trust with a patient and can help to increase a patient’s comfort level with clinical trials; explain the science of clinical research,including the risks and benefits of participation;,and offer support during the process.

		Resolve language equity issues in clinical research both through the elimination of research-specific language and through providing appropriate translations. Hire additional bilingual staff at sites.

		Recognize the role of family and tradition and include a patient’s family early on to support the decision-making process.

		Promote community involvement by local leaders within the community to build trust and promote awareness of clinical research.

Tufts Center for the Study of Drug Development and Biogen recently conducted a study to inform growing interest in improving diversity of clinical trial participation. The results of this research provide insights into increasing the community of minority investigators and study staff and presenting greater access to clinical trials among minority study volunteers.

Mary Jo Lamberti, PhD

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