Mary Jo Lamberti, PhD

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

Articles

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

The Impact of Decentralized and Hybrid Trials on Sponsor and CRO Collaborations

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

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

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

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

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

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

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

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

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

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

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

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

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

Leaving room for innovation in ICH E6 guidance

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

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

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

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

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

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

*This research study was funded by MaxisIT.

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

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

Research Analyst, Tufts CSDD and School of Medicine Development, 

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

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

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

Assessing Sponsor and CRO Awareness

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

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

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

Tufts CSDD research conducted early in the pandemic

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

A study conducted at the Cleveland Clinic Cancer Center

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

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

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

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

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

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

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

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

 The results of our analysis are presented below. 

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

Exhibit 1: Characteristics of Respondents

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

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

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

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

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

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

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

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

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

Mary Jo Lamberti, PhD

Articles

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

The Impact of Decentralized and Hybrid Trials on Sponsor and CRO Collaborations

Assessing Sponsor and CRO Awareness

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

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

Understanding the Complexities of Diversifying Clinical Trials