Executive Director and Research Professor, Tufts Center for the Study of Drug Development, Tufts University School of Medicine

Kenneth Getz, MBA

The past decade has seen a proliferation in the number of investigational therapies and the number of companies sponsoring active clinical trials. At the same time, an unprecedented number of collaborations between patient advocacy groups and biopharmaceutical companies have formed to not only reach and recruit patients into clinical trials but also to shape clinical development plans, to ensure outcomes relevant to patient communities are reflected in drug development activity, and to support access to clinical trials for historically underserved communities.

Patient advocacy groups are often considered the trusted partner in a patient’s health journey, supporting patients and their caregivers. And advocacy groups are interested and may invest in clinical research activity but, for many, their primary mission is not to conduct clinical trials. Biopharmaceutical companies, on the other hand, are focused on expediting and improving the clinical trial process and in bringing new therapies to market.

In recent years, through forums like FDA Patient-Focused Drug Development meetings and social media, patient communities and their families are calling upon their advocacy organizations, health care providers, drug developers and the clinical research enterprise to communicate and collaborate more effectively in order to accelerate the development of new therapies, with the ultimate goal of increasing access to life-saving treatments.

While well-intentioned, with few exceptions, collaborations between patient advocacy groups and industry have been limited in their effectiveness in making clinical research faster and more efficient. This is largely due to wide variation and inconsistency in collaboration expectations, processes, and practices. A major opportunity exists to standardize and structure these R&D-driven collaborations to optimize their impact and reduce the risk of repeating past mistakes. Specific optimization opportunities include:

improving understanding of respective operating processes; objectives; restrictions; needs; priorities; and timelines.

establishing standards for contractual arrangements and fair market value language.

increasing transparency around effective organizational and governance structures, training, operational support, monitoring and evaluation/assessment.

improving understanding of funding request and delivery cycles.

improving early communication to anticipate short- and long-term mutual interests and promote effective planning of resources and timelines.

developing mechanisms to apply lessons learned and measure value and impact to improve future collaborations

The good news is that all of the underlying conditions and opportunities to optimize collaborative efficiency and effectiveness are addressable. Biopharmaceutical companies and patient advocacy groups have devoted significant attention, effort and financial investment to establishing partnerships. However, there has been limited attention and investment devoted to determining and communicating ‘how’ industry and patient advocacy groups can best collaborate and to establishing an accessible repository of resources, standardized practices and lessons learned.

Recognizing this opportunity, in the spring of 2023, Sanofi provided thought-leadership and funding to launch a pre-competitive, disease-agnostic Consortium whose mission is to optimize advocacy group-industry collaboration to ultimately accelerate the pace of medicines development. Over 20 charter groups launched the Consortium to collectively develop:

common foundations that improve industry and advocacy R&D-focused collaborations;

guidance and trainings for advocacy and industry representatives on how to implement patient- and caregiver-informed R&D approaches;

measures to improve diversity in clinical trials through best-practice sharing across industry;

awareness programming aimed at educating and connecting patients to clinical trials; and

knowledge-sharing across therapeutic areas to reduce silos and maximize learnings.

As of May 2023, current members of the PALADIN Consortium include:

Merck, known as MSD outside of the United States and Canada

Michael J. Fox Foundation for Parkinson's Research

The Tufts Center for the Study of Drug Development (Tufts CSDD), part of Tufts University School of Medicine, is providing project management support for the Consortium including assistance with governance and operating activity; planning and execution of work streams; meeting facilitation; development and production of work products; and a communication strategy to ensure broad dissemination of the work of the Consortium.

Consortium members have collectively created a charter and chosen PALADIN — Patient Advocacy Leaders And Drug (Development) Industry Network — for the Consortium’s name with the mission of Inclusive and Optimal Collaboration Accelerating Drug Development.

In its first year, PALADIN will focus on four primary work streams. These areas have been identified as essential and fundamental to collaborative success:

Common Foundations, Processes and Approaches

Guidelines for Optimizing Patient Engagement and Clinical Trial Participation

Guidelines for Transparent Solutions that Work

Each work stream will meet approximately once per month to develop their respective work products. To ensure that insights, recommendations, and resources are relevant and useful, each work stream will be comprised of, and co-chaired by, representatives from patient advocacy groups and industry. During this launch period, the Consortium’s governance will include one member of each participating patient advocacy group and biopharmaceutical company. All Consortium, work stream activity and deliverables will be consensus-driven.

The key to PALADIN’s success in the first year will be establishing the highest level of engagement, collaboration and consensus among member organizations and creating best-in-class resources (i.e., standard practices, guidelines and skills training). Success also depends on Consortium resources being recognized, applied and adopted by the broader community of patient advocacy and drug development organizations.To this end, PALADIN plans to publish updates and articles on its progress and to provide easy access to finished work products.

The launch of PALADIN is an exciting and important step to establish more effective relationships between patient advocacy groups and industry. We look forward to working together to develop consensus-based guidelines, training, resources and competencies that will optimize patient advocacy group- biopharmaceutical company collaborations. Ultimately, we believe PALADIN’s impact will enable more consistent, effective and efficient engagementsthataccelerate the development of new medical therapies and better align medicines development with patient needs.

It is our hope that PALADIN will continue to innovate and support advocacy-industry collaborations well beyond its launch year. While the focus for year one is on the US ecosystem, the Consortia members believe there will be a future opportunity to leverage learnings to other countries and adjust for local regulations and laws.

If your organization would like to learn more about PALADIN, please contact 

The authors acknowledge suggestions and insights from Silvia Cerolini, Roslyn Young-Daniels, Mary Elmer, De De Gardner, Sara Loud, Colin Rock, Michael Spigler, Wendy Vargas, Len Valentino, Anthony Yanni

*Corresponding author to whom inquiries should be directed: Patricia.davidson@tufts.edu

PALADIN is funded by Sanofi US and authors Victoria A. DiBiaso,

Sanofi, 1 Avenue Pierre Brossolette, Chilly Mazarin, France

Sanofi, 55 Corporate Dr, Bridgewater, NJ, USA

Articles

First-of-its-kind consortium dedicated to accelerating new medicines development through optimizing patient advocacy group—industry collaboration.

Introducing PALADIN

There have been a number of occurrences of late signaling that the adoption of decentralized clinical trial (DCT) technologies is far from a fait accompli. To name a few:

A February 2023 assessment of ClinicalTrials.gov listings conducted by IQVIA found that only 1% of industry-sponsored clinical trial starts are using DCT solutions.

This spring, DCT providers reported stalling revenue, cited market resistance, and announced layoffs and restructurings.

A recent Tufts Center for the Study of Drug Development (Tufts CSDD) study found that sponsor-reported use of virtual and remote solutions in active clinical trials had fallen well below the levels reported by sponsors during the first year of the pandemic.

Lengthy and bumpy timelines associated with the adoption of any innovation supporting clinical trial execution are not new. Tufts CSDD research has shown that the typical adoption cycle for a single company takes a full six years; 20+ years for the drug development industry to achieve wide-spread adoption, defined as 67% or more of companies routinely using an innovative solution.

This article reflects on Tufts CSDD’s research characterizing the innovation adoption process in drug development to shed light on and share insights into what we can more realistically expect for DCT solutions adoption moving forward.

A pair of conceptual frameworks—Everett Roger’s Innovation Diffusion Model and the Gartner Group’s Hype Cycle—set the stage for understanding the dynamic nature of innovation adoption. The former, introduced in 1962, suggested that within companies and across an industry, there are varying levels of opportunistic behavior and aversion to risk.

Individuals and organizations that are highly receptive to risk, keenly aware of and willing to act quickly on the need to innovate are called “pioneers” and “early adopters.” Those organizations that are highly risk averse, lacking awareness and slow to act are characterized as “late majority” and “laggards.”

The Gartner Hype Cycle, introduced in 1995, focused on the evolution of expectations associated with a given innovation. Individuals and companies first look at an innovation with unrealistic and exuberant expectations that contribute to initial adoption perceptions. As organizations gain real-world experience with an innovation, their expectations plateau at the “peak of inflated expectation” and fall precipitously into the “trough of disillusionment” where they must temper and revise their expectations. Over a protracted period of time, expectations align with reality when organizations begin to realize the true benefits and value of an innovation.

Drug development professionals have noted the unprecedented—and, for some,—irrational —level of excitement that followed early use of virtual and remote solutions at the beginning of the COVID-19 pandemic.

In 2022, Tufts CSDD undertook an empirical study to gather granular data on innovations supporting all aspects of clinical trial execution, including protocol planning and design; investigative site selection and management; study initiation, ongoing trial management and closeout; patient screening, enrollment and retention; administration of protocol procedures; and data collection, management, analysis, and reporting. Innovations in biomedical science and pharmacology fell outside the scope of this study as they occur largely within scientific functions and do not require cross-functional changes, integration, and coordination in operating practices, procedures, and processes.

A working group of 17 companies provided input into defining areas of focus; designing an interview guide and survey instrument; and discussing preliminary study results and their implications. Tufts CSDD conducted a global survey that yielded 631 total responses from approximately 225 distinct companies—90% biopharma; 10% contract research organizations(CROs). Among respondents, there was good representation by company size, geographic location of company headquarters, and therapeutic area(s) of focus (e.g., 62% focus on oncology; 25% on immunology and infectious diseases, 16% on cardiovascular diseases, 14% on neurological disorders, and 7% on rare diseases). Nearly half of respondents indicated having a role in a clinical operations function. The highest percentage (54%) operates within a large pharmaceutical company, 28% in mid-sized, and 18% in small companies. Half (49%) are based in Europe and 39% are based in North America.

The overall time to adopt an innovation supporting clinical trial execution is 70 months, on average, or 5.8 years. Approximately 20% of the total time—13.8 months—is spent in the initiation stage where organizations are identifying and characterizing an operating need, gauging organizational interest and initiating plans to assess an innovation. One-out-of-10 respondents rates this as the most difficult stage, citing major challenges associated with building cross-functional support and coordination and the absence of regulatory clarity. Another challenge cited is the misalignment of incentives that dissuade personnel and functions from embracing risk and novel solutions.

In the next stage—evaluation—organizations identify, qualify, and engage solution providers; and pilot and evaluate various innovative solutions. This stage takes, on average, 15.7 months, or 23% of the total adoption cycle. A similar one-out-of-10 rates this stage as the most difficult. Poorly designed and executed pilots, the failure to gather sufficient evidence to assess and compare innovative solutions, and the inability to generalize across the portfolio and demonstrate ROI are cited as the largest challenges in this stage.

Industry observers and insiders have noted that the rapid adoption of DCT tools necessitated by the pandemic substantially compressed the initiation stage and invariably skipped the evaluation stage. In the wake of the pandemic, organizations have regrouped and are looking to conduct considerably more thorough evaluation and ROI assessment.

The third stage involves making the decision to move forward and fully adopt an innovative solution. In the adoption decision stage, organizations review their pilot experience, build internal consensus to move forward with, and announce an enterprise-wide implementation. Arriving at an adoption decision takes nearly 17 months, or one-quarter of the total innovation adoption cycle time. One-third of respondents believe that this is the most difficult stage, citing uncertainty and internal dynamics and politics associated with having insufficient “evidence” to support management’s decision to implement.

The final stage—full implementation—takes, on average, two years and represents one-third of the total time to adopt an innovative solution. This stage entails implementation planning, roll-out, communication, training, monitoring, and continuous improvement. Nearly half (47%) of all respondents rate this stage as the most difficult, citing several major challenges, including the lack of senior management and cross-functional support and engagement; poor regulatory clarity and support resulting in substantial concern and resistance from regulatory and legal affairs functions; the absence or late preparation of a comprehensive change management plan to guide the organization through full implementation; and failure to provide the necessary investment of time and resources to fully support the transition from adoption decision to full implementation.

Mid-size companies take the longest time—on average, 6.6 years—to complete the innovation adoption process. Small companies are nine months faster than larger companies and nearly two years faster (21 months) than mid-size companies. CROs are able to complete the innovation adoption process in nearly half the time—3.1 years compared to 5.8 years for pharma companies (see Table 1 below). Indeed, a significant speed advantage and much lower variation around mean durations are observed among CROs at each innovation adoption stage compared to that of pharma companies.

Small companies—and most notably CROs —bring speed advantages to the innovation adoption process but for different reasons. They are generally more nimble than their larger counterparts with less siloed functional relationships and with personnel often responsible for cross-functional activities. With more constrained capital and resources, and pressure from outside investors, smaller companies must often take more risks and arrive at decisions faster. For CROs, executional innovation is central to their ability to differentiate their services and capabilities and retain their clients. 

A much higher proportion of mid-size and small companies rates the initiation and evaluation stages as “most difficult.” Mid-size companies in particular are more likely to positively rate their ability to complete each stage in the process.

Whereas 10 years ago a larger proportion of companies centralized their innovation adoption functions, only 15% of companies today report using a centralized, dedicated function to drive innovation adoption. The majority (85%) reports using a decentralized approach today, relying on individual functional areas to promote, pilot, and evaluate new operating innovations.

Lastly, most companies are harsh self-critics of their ability to adopt innovative solutions supporting clinical trial execution. Approximately one-third (31%) rate the overall adoption process within their organization as “poor” or “very poor.” Nearly 80% perceives that the process takes “somewhat’ or “much” longer than expected and 61% believes that the process for their organization takes longer than it does for their peers. Larger companies are more likely to perceive this.

The drug development industry has long placed a premium on innovations that drive differentiation and competitive operating and performance advantages. As stakeholders throughout the clinical research enterprise look in earnest to accelerate drug development timelines, the ability to quickly, efficiently, and effectively adopt novel solutions supporting clinical trial execution and improve patient engagement is paramount. Although the stages in the adoption process —from initiation to full implementation—are rational and necessary, the relative speed of small pharma and CRO companies offers insight and indicates opportunities to optimize the innovation adoption process.

Study uncovers realistic goals in efforts to embrace decentralized clinical trials.

Optimizing the Process for Adopting DCT Solutions

The COVD-19 pandemic and changing global economies have impacted the clinical research workforce resulting in attrition, shortages, and staffing challenges. Current workforce shortages have posed numerous hurdles for clinical research stakeholders, including sponsors, investigative sites, contract research organizations (CROs), and industry associations.

 The role of the clinical research associate (CRA) has been especially affected as high rates of turnover and vacancies proliferate. CRA turnover rates have been reported as high as 30% in the US with similar rates noted globally.

Recent research has examined current approaches to CRA training, performance assessment, and experience. The results of a global survey of 661 clinical research professionals, including 52 CRAs, assessing their own competencies indicated that respondents with more post-secondary education reported higher levels of self-confidence in their research skills and those professionally certified by the Association of Clinical Research Professionals (ACRP) and/or Society of Clinical Research Associates (SOCRA) compared to those who were not. Self-confidence also increased with the level of academic degree.

 Researchers used a Joint Task Force (JTF) for Clinical Trial Competency Framework to assess respondents on eight competency domains. The results are consistent with prior research conducted in 2016.

The JTF for Clinical Trial Competency framework as discussed by ACRP “objectively defines the knowledge, skills, and attitudes necessary for conducting safe, ethical and high-quality research.”

 Although common practice is currently to hire CRAs with two years of experience, high demands, vacancies, and attrition in the industry have led researchers to recognize a need to address the two years of required experience for those entering the clinical research workforce. Proposed solutions include conducting outreach to raise awareness of the profession, capturing measures of experience and transferable skills as well as add to competency-based training and innovative recruitment and retention approaches to attract candidates to the field.

An examination of the entry-level shortage of CRAs cites several factors including the requirement of a minimum of two years of work experience, high CRA turnover, increasing numbers of open CRA positions, and clinical trial growth and complexity. An assessment of a monitoring simulation of 579 CRAs from a global CRO indicates no difference in performance regardless of CRA seniority and years of experience.

 The research also discusses that addressing the requirement of two years of experience for CRA roles would alleviate the current shortages in the workforce.

Given the impact of the changing clinical research industry on CRAs, Tufts CSDD investigated the current role of the CRA and critical issues including shortages and turnover, and approaches to CRA training and required experience. Also, the study examined the industry practice of two years’ experience as a hiring requirement and its relationship to CRA performance and recruitment and retention practices.*

*This research study was funded by Virb, Inc.

The research used a dual methodology comprised of a web survey of pharmaceutical, biotechnology and CRO executives and an executive roundtable with industry experts. Tufts CSDD conducted an online survey prior to the meeting to gauge perceptions and insights about the role of the CRA based on a small group of clinical research professionals from the US Areas examined included years of experience required to become a CRA and type and effectiveness of training provided. In addition, the survey gathered perceptions about CRA shortages and attrition, most successful recruitment approaches and frequently used retention strategies. CRA assessment and performance were also investigated.

A roundtable meeting was held in October 2022 with 33 participants from biotechnology and pharmaceutical companies, CROs, academia, consulting, and technology. Participants provided their insights and perceptions across a broad range of topics including CRA assessment and training and the industry standard of requiring two years of work experience as a prerequisite to hiring. Other areas explored included recruitment and retention practices; the investigative site perspective; and the impact of outsourcing models, technology, and economic factors on the CRA role.

The survey was distributed via a link to an e-mail invitation using Qualtrics software to industry executives in the US primarily working in clinical operations or clinical development. A total of 55 responses were collected between August and September 2022. Respondents represented a mix of company types with over half (56%, n=31) representing pharmaceutical or biotechnology companies; more than one-fourth (27%, n=15) from CROs and 16% (n=9) from other company types. The mean number of company employees was 17,581 with companies ranging in size from 4 to 95,000 employees. Respondents had 21 years of experience on average and an overwhelming majority (91%, n=50) identified their functional area as clinical operations or clinical development.

Survey responses varied regarding the number of years of experience required to become a CRA at respondent organizations with less than half (44%, n=15) indicating less than two years of experience, while more than one-third (35%, n=12) reporting two years of experience. A smaller percentage (15%, n=5) noted more than two years were needed, and a few respondents (6%, n=2) provided other responses. A majority (69%, n=22) reported that their organization has hired a CRA with less than two years of experience, while fewer (28%, n=9) did not or were considering this option (3%, n=1).

One area that emerged from the discussion was whether the current metrics used by organizations are useful and how to accurately measure CRA competency. The group discussed the implications of published data revealing that newer CRAs performed better on a simulation than experienced CRAs.

 The results also indicated that when comparing more experienced CRAs to newer CRAs, experienced CRAs may demonstrate complacency in their roles. A meeting participant discussed the need for CRA performance metrics:

“We don’t measure much coming from CRAs. The simulation is an exciting tool. It may not be perfect, but we need something like that to give a Pass/Fail, or at least a target. Those results are miserably low. You want to see over a two-to-three-year period that your CRAs moved up in performance and then you’re looking at performance in terms of FDA audits and CRA breaches. If we don’t start, we’ll never get to that point. We’ve been looking at this for years and years.”

Using years of experience as the primary criteria for promotions and not performance was brought into question and participants discussed replacing years of experience as an overall performance metric.Although years of experience is currently the primary determinant of promotions, 61% (n=14) of respondent organizations have not examined CRA performance by CRA experience or job level, while fewer (9%, n = 2) have, with 30% (n = 7) planning to in the future. Enhanced pressure by organizations to promote top performing CRAs is common to prevent attrition. Focusing on other key performance indicators (KPIs), such as site satisfaction or evaluating soft skills acquired through maturity and experience were also proposed.

The group acknowledged that various therapeutic areas and phases of studies may pose different challenges for entry-level CRAs. For less experienced CRAs, trials in oncology, rare disease and gene therapy as well as larger phase III trials could potentially be difficult. Therefore, evaluating CRAs within the same therapeutic areas or phases or within one protocol might be more effective. Attendees also discussed giving CRAs access to their assessments, and building them into the CTMS system, so they can use them as a guide for improving their performance.

The investigative site perspective on the role of the CRA

Sites face multiple hurdles in evaluating CRA performance, one of which is achieving consistent performance given the difficulty with gathering metrics from newer CRAs. An added burden is that CRAs and site staff may lack training or specific skill sets required for their roles. Sites expect a CRA to provide a single point of contact to ensure responsiveness to inquiries despite CRAs often being overburdened with work.

One participant discussed the challenges to the CRA role on-site and the impact on studies:

“Study de-prioritization is a real thing that happens at sites. I can tell you this by experience. Calling CRAs and they never pick up the phone, it always must escalate to a director or manager and even then, they’re overwhelmed. Talking about site relationship managers, I have not seen one on any of our studies and the reason why sites de-prioritize a study is the sponsor or the CRO are absent. There are other sponsors who are more connected to the sites than other sponsors. If they aren’t responding or it’s taking too much effort, just put it in the back burner and let it sit.”

CRA turnover also impacts sites and may slow recruitment or cause study delays or terminations. Estimates of the average annual turnover rate of CRAs at organizations varied according to survey respondents. One-quarter (n=8) projected turnover between 15-20%; 22% (n=7) between 0-10%; and 16% (n=5) indicated 20-25% turnover. More than three-quarters (77%, n=23) reported that average time before turnover was more than two years.

A participant discussed “the challenge with sites is that the CRA must be the expert at all things, that resource, and it takes a CRA nine months to be proficient but they’re at a two-year cycle then that turnover is disruptive.” Senior coordinators support new CRAs and are influenced by turnover placing an even greater burden on the investigative site. A proposed solution is to have line managers work with CRAs on-site to improve rapport and teamwork.

In examining where CRAs typically receive training, a greater percentage of survey respondents indicated CRAs were trained by academia (62%, n=21) or company training programs (59%, n=20). Nearly 40% (38%, n=13) reported that ACRP provided training, while fewer (36%, n=12) noted specific programs or other types. The remainder (21%, n=7) mentioned SOCRA or Regulatory Affairs Professionals Society (RAPS). More than one-third of respondents (33%, n=11) reported that new CRAs receive three to four months of training at their organization.

The survey also asked respondents to evaluate the most effective forms of training. An overwhelming majority of respondents (84%, n=26) reported that peer support or mentoring was the most effective training while more than three-quarters (77%, n=24) indicated in-person training was most valuable.Over half noted (52%, n=16) either observational or web-based training models were most beneficial, with 42% (n=13) reporting scenario based and 39% (n=12) experiential training. Three percent felt other trainng types were effective.

Entry-level CRA training varied at participant organizations. Some comprised large in-house training programs, while others included transitioning new college graduates from clinical study administrators to CRAs or shifting clinical research coordinators into CRA roles. Programs ranged from 12 weeks to 9 months and emphasized co-monitoring, mentoring, and training with both senior CRAs and line managers. The training also included quality assessments and use of ACRP assessments.

One participant related the details of their in-house training program:

“The demand for CRAs is growing. There’s definitely an appetite for creative ways to bring people in, we are doing that through partnership programs where you’re turning global study administrators into CRAs through a training program, including a classroom portion that is taking about three months and then actually turning into their day jobs and in another three months they’re doing on-site visits and getting that on-scene perspective.”

Companies have also established global recruitment programs for US based CRA jobs through partnerships with Mexico and Japan. A newer focus of company training emphasizes trust in partnerships. Softer skills such as communication or collaboration also comprise training and may be transferable from other roles if a candidate is new to the field.

A few alternative training approaches were proposed. One strategy included the use of chatbots for CRA questions to clarify issues and conduct training through use of behavioral data. Other methods discussed were utilizing the protocol and training documents as resources or experiential support and training.

Some general training techniques can be specifically applied to train CRAs including critical mistakes analysis of performance. This approach involves training learners on real world challenges with high stakes. Another was the use of spiral design, a training strategy intended to begin with the least complex version of a task and continue to challenge the learning with similar tasks that increase in complexity.One participant noted that “the CRA role isn’t one where individuals improve over time, but rather through training.” Attendees considered that quality of monitoring could potentially be improved through spiral learning.

Industry guidance (ICH E6R2) does not specify number of years of work experience for a CRA but stresses clinical trial specific training and experience. Nevertheless, a two-year requirement has been the industry standard and often incorporated into sponsor-CRO contractual agreements. One participant discussed that the “threshold of two years is a barrier if sponsors are not willing to take the time to train so they can provide their own help with the deficit today.” Many CROs do not have the resources to fill positions and training requires a large investment. Participants unanimously agreed that a commitment to industry training was critical.

In evaluating primary CRA recruitment approaches, larger numbers of survey respondents reported using recruiters (86%, n=25), websites or social media (69%, n=20) and staffing companies (59%, n=17). Additional approaches included professional networks or associations (45%, n=13); universities or colleges (41%, n=12); and other methods (28%, n=8). Lesser numbers recruited CRAs through training programs (24%, n=7) or conferences (17%, n=5).

The greatest number of respondents indicated recruiters (52%, n=15) were the most successful methods of recruiting CRAs while 38% (n=11) used referrals from internal staff, recommendations or appplications. Fewer(31%, n=9) reported that staffing companies, training programs (21%, n=6), professional networks or associations (17%, n=5), universities or colleges (17%, n=5) and conferences (7%, n=2) were successful.

Academic-Industry partnerships are significant to CRA recruitment and provide extensive training through internships and fellowships. Several universities have also established clinical research programs and with demonstrated success in placing students in permanent positions. A participant from a university noted:

“We focus on getting organizations to offer cooperative education opportunities which are paid internships for preparing students not just for the working environment, but also for acquiring soft skills such as preparing their resume, write their cover letters, getting in front of companies, and engaging in the dialogues of what their experiences were.”

There is, however, a pervasive lack of awareness among undergraduate students about clinical research as a profession and of the role of a CRA. In a survey of more than 200 university students in both the US and UK, not a single one had heard of clinical research as a career.

 Recruitment by companies on college campuses over the past five years has led to some increased awareness. A meeting participant in support of recruiting new graduates explained that “the next generation wants to work for a higher purpose and what greater higher purpose than helping humanity and saving lives?” Mentoring students is also critical however, and some universities are unable to fill faculty positions due to the massive pay disparity between industry and academia.

CRA retention and perceptions about industry shortages

The primary reasons for CRAs leaving their positions were for higher salaries (74%, n=23); followed by better growth opportunities (45%, n=14) and burnout (29%, n=9).The top two strategies implemented by organizations were flexible work schedules (65%, n=20) or higher salaries (55%, n=17).

The growth opportunities that CRAs seek are in part impacted by the rapidly changing clinical research industry and by economic factors. Both factors influence retention of CRAs and may inhibit growth opportunities. Yearly salary increases are not sustainable, and they typically leave these roles for higher paying positions.An attendee suggested that other career paths allow a CRA to stay in the industry yet be able to advance:

“We should think about as an industry, career opportunities. What else is next? Central monitoring, data monitoring, regulatory.All require quality whether or not the role is a CRA. We want to keep CRAs while promoting, because that skill set is very valuable as a monitor.”

A CRA may experience disconnectedness from staff on-site for a number of reasons: burnout from having a large work burden; working on complex studies too soon; and managing multiple technologies and systems. One participant described the gap in the support that may contribute to a CRA feeling disconnected: “there is more separation between MDs and clinical teams, and they are not connected with the CRAs on the ground.” In addition, a CRA may currently spend less time on site and more on remote monitoring.

Company outsourced models can also influence retention of CRAs. While CROs are the primary organization that staff CRAs, pharmaceutical organizations are increasingly using internal or headcount CRAs. Participants offered mixed opinions on full service, functional service provider and freelance models. One attendee with headcount CRAs reported that turnover was less than 5%, and another indicated that functional service providers (FSP) resulted in high turnover. A third participant found no differences in performance between headcount and FSP CRAs.

An overwhelming majority of survey respondents (88%, n=28) reported a shortage of CRAs in the industry while 13% (n=4) did not.Opinions were mixed about whether the shortage was getting worse (43%, n=14) or staying the same (57%, n=18), however no respondent felt the situation was improving.

The results of the survey and executive roundtable confirm that organizations are currently accommodating CRAs with less than two years of experience and establishing novel approaches to training. In addition, solutions are currently being implemented or planned to alleviate the impact of CRA shortages and turnover, and these include the following:

Re-examining experience in relationship to performance through using innovative strategies to gather alternative metrics on CRA performance, such as evaluating site satisfaction or assessing soft skills.

Organizations are also planning to link specific metrics such as FDA audits to experience or job level. In addition, evaluating CRAs with similar workloads and providing access to their assessments for self-improvement are strategies being considered. Novel approaches to gathering metrics are still in the early stages of implementation, however, and follow up studies will be critical.

Addressing the shortage of CRAs through raising awareness of clinical research as a profession at the university level.

Recruitment by companies on college campuses and offering university internships have led to permanent placements for students after graduation. Academic-industry partnerships also provide new graduates with valuable real-world experience before entering the workforce.

Mentoring and working collaboratively on-site with managers can address CRA disconnectedness and facilitate teamwork as well as build trust.

Mentoring programs provide an increased level of support for CRAs beyond training programs. In addition, dedicated line managers working on-site offer critical training. These approaches can alleviate burnout and provide the critical groundwork for encountering challenging studies.

Providing growth opportunities to increase retention and address issues of complacency among senior CRAs as well as offering varied incentives to remain within the industry.

A competent CRA can easily transition into other positions where comparable skills are valued and would be able to fill roles in regulatory, trial management, and central or data monitoring. Many organizations support career development of CRAs to increase staff retention.

Given increasing use of technology and growth of decentralized trials, proposing sustainable solutions that tackle industry and global change is critical.

Solutions should address changing organizational models as well as economic factors. In response, some companies are developing in-house training programs. Other organizations are examining the impact of outsourced models on CRA performance as well as their onboarding processes and training programs to implement crucial changes to current practices.

Consider experiential training approaches based on spiral learning that may prepare CRAs to perform effectively without two years’ experience.

The aviation industry trains pilots using simulation, scenarios, and real-time coaching by expert pilots and may be a useful model from which we can learn when designing curricula for training and preparing CRAs to actually monitor clinical trials in the field.

, PhD, associate director and research assistant professor, 

, executive director and research professor; all with Tufts CSDD

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https://acrpnet.org/2016/12/01/global-self-assessment-of-competencies/

Barriers to Bridges: Addressing the Urgent Need for a Diverse, Research-Ready Workforce within the Clinical research profession. ACRP Whitepaper. September 2022 p. 7. Available at: 

https://acrpnet.org/barriers-to-bridges-addressing-the-urgent-need-for-a-diverse-research-ready-workforce-within-the-clinical-research-profession/

Alsumidae M. Entry-level CRA shortage still crippling trials. 

. Published online March 2, 2022. Available at: 

https://www.appliedclinicaltrialsonline.com/view/entry-level-cra-shortage-still-crippling-clinical-trials

Alsumidae M. CRA Skills Lack in Critical Areas. 

. Published online May 22, 2018. Available at: 

https://www.appliedclinicaltrialsonline.com/view/cra-skills-lacking-critical-areas

Survey conducted by Connelly Partners Health for Virb, Inc., March 2022.

Study by Tufts CSDD uncovers potential reasons behind CRA shortages, turnover, experience requirements, and more.

An Examination of the Role of the Clinical Research Associate and Factors Impacting Performance and Experience

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, 

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

Kenneth Getz, MBA

Articles

Introducing PALADIN

Optimizing the Process for Adopting DCT Solutions

An Examination of the Role of the Clinical Research Associate and Factors Impacting Performance and Experience

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

Quantifying Protocol Deviation Experience by Clinical Phase

Measuring Patient Satisfaction as a Primary Outcome for Patient-Centric Initiatives