Abigail Dirks

During the past several years, in the wake of the COVID-19 pandemic, investigative sites have faced unprecedented challenges executing clinical trials. In additon to administering more complex protocols, finding patients under more stringent eligibility criteria, and retaining patients under more onerous participation requirements, sites have had to accommodate the use of a variety of remote and virtual technologies to collect and manage clinical trial data. At the same time, chronic operating challenges including inadequate study budgets, protracted contract negotiations, punitive hold-back payments, and poor CRA quality and continuity have continued to plague investigative sites. And recently, investigative sites have encountered higher levels of staff turnover and shortages.

The Tufts Center for the Study of Drug Development (Tufts CSDD) recently conducted a survey to understand the current mindset, experience and outlook of a global community of investigative sites. The survey endeavored to garner the perspectives of the “typical” investigative site and to understand variation in perspectives and experience by site type and by personnel function.*

This article presents highlights of the survey results and offers insights into ways that sponsors and CROs can strengthen their relationships with sites in this current, post-pandemic clinical trial operating environment.

Survey methodology and data characteristics

The survey was conducted online between October and December 2022. To reach a global community of investigative sites, Tufts CSDD used proprietary contact lists and partnered with the Association of Clincial Research Professionals. A total of 205 responses were collected.

The majority of respondents are employed by integrated clinical care/research sites (81%), and the remaining (19%) are employed by dedicated sites/site networks. 64% of respondents held a clinical site staff role and 36% held an administrative role. Clinical staff included roles such as PIs or Sub-Is, Clinical Research Coordinator (CRCs), and Clinical Research Nurses (CRNs) whereas administrative staff included site directors, research managers or equivalent roles.

Overall,respondents were experienced with a mean tenure in clinical research of 17 years with a range of less than one year up to 50 years working in the industry.

While the majority (70%) of respondents is employed in North America/Central America, 16% are employed in Europe, 10% in Asia (10%) and 4% in other regions of the world (Table 1). 

In general, the majority of respondents reports that many study start-up, execution and other operating activities have worsened substantially over the last 5 years (Table 2). Some of these challenges are related to the COVID-19 pandemic whereas others are long-standing issues.

Hiring and retaining staff topped the keylist of primary challenges with budgets and contracts as well as study initiative activities a close second and third. Interestingly only 42% of respondents feel that implementing new technology had worsened somewhat or greatly. These findings are in contrast to some other recent site surveys where technology-related factors appear to have a bigger impact on site operations.

No significant differences are observed by site type, although it is noteworthy that only 20% of respondents from dedicated sites/site networks feel that interacting with sponsors had worsened compared to 35% of respondents from sites where research is integrated with clinical care. Administrative staff hae more positive views about sponsor interactions than do clinical staff.This could perhaps be a result of the investments sponsors have made engaging sites through professional research sites through various industry collaborations such as through SCRS, ACRP, TransCelerate, and the type of site staff who participate in these initiatives.

Perceived change in site operating activities during the past five years by site type and role

Unsurprisingly, site staff who feel that things have worsened substantially over the last 5 years have a more pessimistic view of the future outlook of clinical research at their site in the next five years. Conversely, site staff who feel these operating activities have not worsened greatly or somewhat over the last 5 years, have a more optimistic viewpoint.

Site optimism and factors driving the optimism

The results also reveal that nearly 80% of respondents hae a ‘Somewhat’ or ‘Very Optimistic’ view of the future (Table 3).

Optimism* for the future overall and by site type and respondent role

*Question: My outlook for the future of clinical research at my investigative site over the next five years

No significant differences are observed by site type or role although administrative staff reports being very optimistic in somewhat higher proportion compared to the clinical staff. One interesting finding is that site staff with less tenure have a more positive outlook than more experienced staff although the differences are not statistically significant (Figure 1). This may be explained by the fact that less experienced staff have a limited baseline on which to compare trends. Similarly, more seasoned veterans may have become more jaded in their attitudes or are more frustrated with the lack of progress in some areas.

Viewpoints based on tenure of clinical research experience

The most astonishing finding however, was the degree to which sponsor-site relationships affect positive or negative perceptions; specifically the degree to which sponsors seek, value, and apply site feedback is significantly related to site optimism about the future. Higher percentages of respondents who agree that sponsors seek (87%), value (86%), and applied (87%) site feedback are optimistic about the future (Table 4).

Relationship between site optimism and perceived degree that sponsors seek, value and apply site feedback

Those that felt that sponsors they work with value input even if they are unable to apply it are over 4 times more likely to be optimistic about the future. Similarly, those that perceive that the sponsor applies site feedback and those that feel the sponsor seeks out site feedback are over 3 times more likely to be optimistic about the future. Several respondents underscored this point, noting that:

“Soliciting and implementing changes based on the feedback of experienced sites would help sites succeed in implementing study protocols and likely would prevent many failed trials.”

“Sponsors who do not ask for feedback from study coordinators regarding study design and feasibility generally have poorly designed, non-feasible studies. Sponsors should seek consultation from study coordinators, as we are the ‘boots on the ground’ and can tell a sponsor if something does not appear to be doable or will be too much burden on participants and/or study staff.”

—Clinical research coordinator/site director

Even if site feedback cannot be incorporated, respondents value hearing from sponsors that their feedback was considered.

Patient centricity and site centricity are one and the same

Overall sites feelthat more traditional patient-centric services such as pre-paid debit cards and transportation assistance programs have a much greater impact on a volunteer’s willingness to participate in clinical trials than some of the newer approaches (Figure 2). Over half of the respondents feelthese had a greater influence compared to remote visits, home-health services or local pharmacy-based visits.

Solutions that greatly enhance volunteer participation

Nonetheless, respondents feelthat overall, any of the DCT-related solutions aimed at enhancing volunteer participation also enhance site implementation success (Figure 3). These findings suggest that if the site perceives a solution will enable their success and if they are bought-into the solution, then it may translate into enhanced volunteer participation. Or, at a minimum, a perceived positive influence on participation rates.

Perceptions of impact of DCT-related solutions on participation and site implementtion

One industry expert noted that “the most patient-centric thing sponsors can do is to be site-centric.” The results of the Tufts CSDD survey support that observation.

Supporting healthy sponsor-site relationships by tackling age-old issues

Nearly every industry survey on site perceptions reinforces the importance of addressing the enduring challenges of study budgets, CRA quality and study complexity.

 The results of this study were no exception (Figure 4).

Top factors that greatly enhance site sustainability

When asked which factors would greatly enhance the site’s likelihood of remaining in business going forward, the number one factor, reported by two-thirds of the respondents, is ensuring that study budgets reflect the true work efforts of the site. This is likely related to the intensity and complexity of the study as well with nearly half of the respondents suggesting that reduced intensity could facilitate better study implementation and future site viability. As one respondent noted:

“The resources to implement procedure-intensive studies are just so limited it would be great to have sponsors think carefully about what matters in getting the drug approved.”

Similarly, over half of the sites also reinforce the qualifications of the CRAs/monitors as having a great influence on the viability of clinical research operations in the future. This was reinforced by another respondent who commented:

“If we were able to significantly increase the number of competent monitors for clinical trials, I think a large number of the issues that we face would dissipate.”

There were some significate differences noted between clinical and administrative staff for each of these factors with administrative staff ranking all of these factors as having a greater influence than the clinical staff. This speaks to importance of tailoring site interactions to address the needs of the different roles.

While these themes were reinforced through a vast number of qualitative responses, one site director summed it up most succinctly:

It stands to reason that sites who feel respected and heard by sponsors will have a more optimistic view of the future. What may be less intuitive however, is the importance of pairing investments in new technologies with investments in behaviors that foster relationship quality with site staff, particularly more seasoned veterans. Simply focusing on novel approaches to conducting trials or implementing new technologies will only go so far in terms of becoming the sponsor of choice or accelerating clinical trials. Site staff who feel heard and that their experiences are valued, may withstand any number of burdensome procedures, novel technologies and procedure-intensive studies.

The results of this survey suggest that it may be less about the complexity of the study design, implementation model, or use of a given technology and more about the relationship the sponsor has with the site (in general) and specific roles at the site (administrative versus clinical staff).In addition, focusing on persistent challenges related to the adequacy of study budgets and CRA quality may have a greater impact on both the quality of the site relationship, as well as study performance.

In upcoming research, we hope to further explore the extent to which the qualitative aspects of sponsor-site relationships impact site performance and the adoption of new solutions supporting clinical trial execution.

*For this study, Tufts CSDD differentiated two site types: one that integrates research activities withing clinical care settings including not-for-profit clinics, hospitals, health systems, academic and government-affiliated hospitalsystems, and for-profit clinics and hospitals that provide clinical care and also conduct clinical research studies; and the other that conducts clinical trials within a dedicated site(s) / site networks and that derives the majority of their income from industry-funded clinical trial study grants.

We would like to acknowledge the following individuals who provided input into the survey design or shared their insights on the results:

Jessica Fritter; associate faculty, clinical instructor of practice, The Ohio State University College of Nursing, and partner, BJE Consultants

Victoria DiBiaso; global head, patient informed development & health value translation, Sanofi

Joseph Kim; chief strategy officer, ProofPilot

Therica Miller; executive director, enterprise cancer clinical research, Tisch Cancer Institute at Mount Sinai

We would also like to acknowledge the Association of Clinical Research Professionals (ACRP) for distributing the survey to their members.

Scott, J. Sites Name Tech Acceptance as Essential Factor in Selection of Sponsors, Survey Finds. CenterWatch. 2018. Published online: January 16, 2023.

AVOCA, ACRP. Becoming a Sponsor or CRO of Choice – A Site Perspective. White paper published online: September 2018.

SCRS. Site Perspectives on Decentralized Clinical Trials. White paper published online: 2022.

Articles

Tufts CSDD survey finds fostering healthy relationships with site staff is key to a positive outlook.

Assessing Investigative Site Outlook and Operating Experience Post-Pandemic

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

Hill M. Clinical research sites share cash and workforce shortage concerns. 

. Published online July 21, 2022.Available at: 

https://www.clinicalleader.com/doc/clinical-research-sites-share-cash-workforce-shortage-concerns-0001

Wieland A. What is really behind the CRA shortage in clinical trials? A root causes analysis. Published online May 18, 2020. Available at: 

https://www.clinicalleader.com/doc/what-s-really-behind-the-cra-shortage-in-clinical-trials-a-root-cause-analysis-0001

Sonstein S, Samuels E, Aldinger C et al. Self-assessed competencies of clinical research professionals and recommendations for further education and training. 

Therapeutic Innovation and Regulatory Science

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Sonstein S, Silva H, Thomas-Jones C et al. Global self-assessment of competencies, role relevance, and training needs among clinical research professionals. Clinical Res. 2016;30(6):42-9. Available at: 

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

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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

Decentralized clinical trials (DCTs) have accelerated in response to the pandemic and continue to evolve. As a result, sponsor companies and contract research organizations (CROs) working in collaboration have been re-evaluating their relationships, especially in terms of structure, costs, and effectiveness. Much of the research examining DCTs and hybrid trials has tracked increases in usage but has not specifically addressed the impact on sponsor-CRO relationships. In an examination of worldwide trials, researchers noted a 50% increase in global drug trials with a DCT or virtual element from 2020 to 2021 and a 28% increase from 2021 to 2022.

Other surveys have noted growth in the implementation of DCTs, but greater usage projected for three years out.

Research conducted with pharmaceutical industry professionals on the use of DCTs and hybrid elements after the COVID pandemic found that in a survey of 245 investigators, 104 investigators in the U.S. indicated that telemedicine (74%), remote patient monitoring (77%), and remote site-initiation visits (63%) would increase.

 Other studies report increasing use of electronic health records or prevalence and use of DCTs in numerous therapeutic areas.

Various challenges to the use of DCTs have been cited including data standards, country-to-country regulations, and the need for clarity in regulatory guidance. Data privacy issues are also notable considerations. Other hurdles are seen in data quality for apps, wearables and ePRO which require clinical and technical validation. Another barrier is patients’ lack of familiarity with technology which can hinder implementation.

Pricing models, approaches to the implementation of DCTs, and management of vendors impact sponsor-CRO partnerships. Research has been sparse on this topic, with a few published articles addressing the critical need for partnering with the right CROs and vendors.

 In addition, the need for novel partnerships to streamline processes and improve upon data sharing have been cited.

 Others have noted the need for multi-stakeholder collaboration across the biopharmaceutical industry to promote best practices and drive adoption.

 As sponsor-CRO partnerships expand their collaboration, the need grows to examine the impact of DCTs and hybrid trials. To assess this impact and gather additional research, Tufts CSDD initiated a study in collaboration with ten biopharmaceutical organizations and CROs.

The study assessed how approaches to decentralized and hybrid trials disrupt sponsor-CRO relationships including evaluating strategies and approaches to oversight and performance. The study was comprised of a two-part methodology including an assessment of the current landscape through interviews with the working group and a global industry survey. The interviews identified the primary sponsor-CRO relationship areas that were most disrupted by DCT solutions, while the survey assessed the current landscape and gathered insights into how organizations are responding and adapting to these relationships. Tufts CSDD researchers conducted interviews with representatives of the working group companies in the summer of 2021 and the results informed the development of the survey.

A global web survey examined the overall impact of decentralized and hybrid trials including implementation of specific technologies and solutions and those that organizations have most effectively implemented. Definitions were provided at the beginning of the survey.* Pharmaceutical and biotechnology respondents evaluated a CRO’s ability to manage specific solutions and technologies indicating the degree to which their oversight was executed satisfactorily and their opinions about the cost of implementation. In addition, the survey examined pricing models and areas of challenge implementing decentralized or hybrid trials with CROs and vendors. The survey also assessed metrics and performance, training, and overall perceptions about the future of trials.

The survey was launched in February 2022 to a diverse group of clinical research professionals and in coordination with DTRA (Decentralized Trials and Research Alliance, dtra.org) and 

An e-mail invitation containing a link to the survey was distributed. The survey closed in April 2022 with 80 completed responses. Three-quarters of respondents represented pharmaceutical, biotech companies and CROs (Table 1). A majority (60%) worked in clinical operations or clinical development roles and in mid-sized or small companies (59%), while 41% were from large companies.​

Respondents reported that on average, their organizations conducted 84 trials in 2020 and 88.5 trials in 2021 (Table 2). An estimated 21% were identified as DCTs or hybrid trials in 2020 and 30% in 2021. The percentage increase in decentralized or hybrid trials from 2020 to 2021 was not statistically significant.​ Three-quarters of the pharmaceutical/ biotechnology survey respondents indicated that they were decision-makers in the process of selecting DCT CROs and vendors and 90% of those reported using at least 3 preferred providers.

Usage and implementation of DCT and hybrid solutions and technologies

Prior to the pandemic, the largest number of respondents reported usage of ePRO (n=35), eDiaries (n=34) and eCOA (n=33) (Table 3). Currently, remote monitoring (n=38), ePRO (n=36) and eConsent (n=35) are the DCT technologies used by the greatest number of respondent organizations. The DCT technologies most frequently reported as effectively implemented were ePRO (n=30), eCOA (n=29), and remote monitoring (n=29).

A majority (40 of 50 respondents) indicated that remote monitoring impacted their organizations and would remain the predominant approach after the pandemic (29 of 54 respondents). The fewest respondents rated the following solutions as effectively implemented (Table 4): home health services (n=15), wearables or sensor data collection (n=9), and electronic medical record (EMR)/electronic health record (EHR) data integration (n=7). More respondents planned to use EMR and EHR data integration (n=22), wearables or sensor data collection (n=21), direct-to-patient or home IP drug shipments (n=21), and eConsent (n=20).

A high percentage of pharmaceutical and biotechnology respondents indicated that CROs were able to manage decentralized lab work including local labs (n=47 of 54 respondents), direct-to-patient (home IP drug shipments) (n=45), and eConsent (n=45) satisfactorily (‘Very Well’ or ‘Somewhat Well’). In implementing DCT and hybrid trials with CROs and vendors, major or moderate barriers commonly identified were country challenges (n= 49 of 54 respondents); different site capabilities (n=45); and data collection challenges including quality, integrity, oversight, and ownership (n=45). Other obstacles included resistance to change (n=44) and managing multiple vendors (n=43).

In evaluating the costs of DCTs compared to traditional trials (Table 5), 28 (of 52 respondents) indicated that DCTs are more expensive, while 17 felt they are about the same and 7 reported they are less expensive. Asked about the future of DCTs, 23 respondents (of 51) indicated they expected the cost to increase, 13 expected the cost to remain about the same, and 15 expected the cost to decrease.

A comparison of the top five outsourced expenses in the time period from before the pandemic to the top five outsourced expenses in early 2020 (Table 6) yielded the same expenses, although remote monitoring moved up from fifth to second most expensive in the ranking in early 2020.

Pricing models reported by respondents before and after COVID appear to be mixed with fixed unit pricing (i.e., pricing based on completion of tasks) (26 before COVID and 23 respondents currently using) and fixed pricing (i.e., pricing that guarantees a fixed budget) at the study level (25 before COVID and 21 respondents currently using) as most prevalent. Fewer respondents indicated using incentive-based pricing or fixed pricing at the portfolio level.

A majority of pharmaceutical and biotech respondents (n=44) gave favorable ratings of CROs, indicating CROs were either somewhat or very proactive in DCT adoption (Table 7). Only 18 respondents indicated that CROs were not proactive. Fifty respondents perceived that DCTs or hybrid trials had a moderate or significant positive influence on sponsor-CRO collaborations, while 12 believed they had a moderate negative influence.

Similarities emerged among the key performance indicators (KPIs) used to evaluate sponsor-CRO relationship effectiveness and vendors implementing DCT solutions. The top performance metrics for sponsor-CRO relationships were patient compliance, study startup, first patient first visit, enrollment, and last patient last visit to data base lock. For DCT vendors, the top performance metrics were enrollment, final actual contract as a percent of initial contract value, first patient first visit, last patient last visit to database lock, study startup, and study startup to last patient last visit.

Training responsibilities were also consistent for sponsors and CROs/vendors with approximately three-quarters of respondents noting that sponsors and CROs/vendors were responsible for training site staff, study teams, or both. There were no differences found among respondents by company size. The results also showed preferences for online and virtual approaches (n=60) as well as written documents and manuals (n=42) over in-person sessions (n=29).

In examining perceptions about outsourcing DCTs and hybrid trials over the next three to five years, 38 (of 51 respondents) indicated that outsourcing would likely increase due to advanced technologies (Table 8). Seven indicated usage would remain the same and four felt it would likely decrease due to complications and challenges. Similarly, 44 respondents (of 52) anticipated the use of CROs and vendors that implement DCT solutions will increase as more solutions become available. Only four believed usage would likely decrease as companies consolidate, and three felt that outsourcing would remain the same.

Respondents offered varied opinions about the role of the CRA in the future. Nearly half of respondents (24 of 51) indicated that CRA roles will increase with remote work, while 20 felt that the numbers would decrease. Of those indicating a decrease, 14 felt more technological expertise and skills will be required and 6 perceived travel benefits would be curtailed. Few respondents reported increased CRA turnover due to burnout and additional time on the job, or that the role would remain unchanged.

Although remote monitoring, ePRO and eConsent were the DCT technologies currently used by the greatest number of respondents, the results also indicated that only slightly more than half of those responding rated ePRO, eCOA and remote monitoring as effectively implemented by their organizations. This finding may reflect challenges with implementation or investments required early on in the study. Published research indicates that assessing ePRO technology to ensure its usability and acceptability for patients is critical.

 Further, eCOA has numerous logistical considerations and may require added time and funding upfront, especially in terms of determining scientific requirements and qualifying suitable vendors.

Looking at the same DCT technologies, a surprisingly small number of respondents indicated that they planned to use the technologies in the future. While the current study shows that fewer than half of respondents planned to use any individual technology in the future, surveys conducted during the pandemic indicated that the vast majority of respondents expected to use these technologies in future studies.

 It may be that the general excitement surrounding these technologies is waning as organizations encounter the challenges of implementation and costs.

Relatively small numbers of respondents rated their company’s implementation of home health services as effective. Staffing shortages due to the pandemic have impacted these services and wide variation in costs could affect usage. Respondents’ ratings of the effectiveness of telemedicine were also fairly low relative to other technologies assessed. This finding could perhaps be due to decreasing usage with easing COVID restrictions. There could, however, be other factors that hinder efficiencies such as requirements of swift reporting of adverse events, necessary documentation and follow up.

The primary barriers reported with implementation of DCT and hybrid trials by CROs and vendors include country challenges, varied site capabilities with respect to novel technologies, and data collection. These challenges are consistent with published data on this topic (2,3,6). Resistance to change and managing multiple vendors were also among the top five implementation hurdles. The latter are expected given that much of the technology is novel, and the disruption brought about by a multitude of innovative solutions, especially at investigative sites could be staggering. In addition, the number of CROs and vendors which companies must manage has increased substantially. With the expansion of solutions globally and variation in country regulations, there are additional considerations such as data privacy and security, lack of regulatory frameworks and harmonization, and legal policies that can hinder implementation. Use of multiple data sources can also challenge the integrity of data and clarity regarding ownership of data.

The majority of biopharma respondents rated CROs favorably for maintaining a proactive role in DCT adoption. In addition, respondents indicated that DCTs or hybrid trials had a significant or moderate positive influence on sponsor-CRO collaborations. Although viewed as currently more expensive with anticipated cost increases, the majority of respondents indicated that both outsourcing of these trials will increase as well as the use of CROs and vendors that implement such solutions.

Follow up research can potentially identify specific examples of relationship models due to disruptions by hybrid and decentralized trials. An in-depth study of use cases across organizations would be invaluable and could clarify ways in which these sponsor-CRO partnerships continue to transform.

Decentralized clinical trials use technologies and other solutions to create options for participation outside of conventional clinical settings, improving access and convenience.

Hybrid trials use a mix of elements from traditional clinical trials and decentralized clinical trials

Remote monitoring is conducted off-site. A remote evaluation that is carried out by sponsor personnel or representatives at a location other than the sites at which the clinical investigation is being conducted.

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Laaksonen N, Bengtstrom M, Axelin A. et al. Success and failure factors of patient recruitment for industry-sponsored clinical trials and the role of the electronic health records—a qualitative interview study in the Nordic countries. 

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https://www.tlggconsulting.com/whitepaper/TLGGConsulting-DCT-WhitePaper.pdf

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https://www.statnews.com/2021/01/29/decentralized-clinical-trials-more-collaboration-needed-to-expand/

Aiyegbusi, O.L. Key methodological considerations for usability testing of electronic patient-reported outcome (ePRO) systems. 

https://doi.org/10.1007/s11136-019-02329-z

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Tufts CSDD study in collaboration with ten biopharmaceutical organizations and CROs examines sponsor/CRO relationships.

Abigail Dirks

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