Clinical Researcher—February 2024 (Volume 38, Issue 1)

SPECIAL FEATURE

Elisa Cascade, MBA; James Wurdeman

 

 

 

Adoption of technology by clinical trial sites has increased significantly over the past decade, especially amongst organizations that perform more than five research studies annually. Technology systems considered core to a clinical research site’s operations include:

• Clinical trial management system (CTMS): A CTMS is responsible for managing all operational aspects of a clinical trial from study start-up to closeout. Critical features include, but are not limited to, study milestone tracking, review/sign-off workflows, calculation of subject visit schedules, financial billing/tracking, billing compliance, and task management.
• eRegulatory management (eReg) system: An eReg system contains the electronic final copy of site-level essential documents related to study startup and amendments, training documentation, delegation of authority log, and other items needed for audit or inspection. The system also manages subject-level documents such as screening/enrollment log, list of subject identification codes, and signed consent forms. Other items include, but are not limited to, protocol deviations/exceptions, safety (adverse events/serious adverse events) log, as well as correspondence with the sponsor, contract research organization (CRO), or monitor.
• eSource/electronic data capture (EDC): eSource and EDC systems capture source data in an electronic format. While there are many similarities between eSource and EDC, eSource will capture every piece of information potentially needed from a standard of care, research, and workflow perspective. Another important aspect is remote monitoring functionality, as this is the dataset generally monitored during source data verification (SDV). EDC is often a subset of eSource because it does not collect protected health information (PHI).

The primary goal of these systems is to facilitate the research process at the clinical trial site, regardless of funding source—industry-sponsored trials, research grants, or investigator-initiated studies. Through use of technology, in combination with development of standard processes and associated training, research sites are able to address many of the common U.S. Food and Drug Administration (FDA) inspection findings, such as protocol compliance, source documentation, and regulatory documentation for activities including adverse events and informed consent.{1} Also important are integrations with site systems such as those to support staff resource planning (e.g., human resource systems) or to drive efficiency (e.g., labor to generate and record invoices).

Sponsors and CROs looking for process automation, higher quality study delivery, and transparency into study status are also investing in technology related to such activities and features as essential document collection, learning management systems (LMSs), eConsent, patient recruitment tracking, and many more. Thus, it is not surprising that in the 2023 Advarra Study Start-up Survey,{2} sites reported that setup and training on sponsor technology is the most burdensome start-up activity, with 55% rating this activity as very or extremely burdensome. Further, the situation is worsening, as 67% of sites reported that the burden associated with sponsor technology has grown over the past five years.

In this paper, we provide a summary of the technology needs of different types of sites (i.e., not all sites are created equal) and highlight barriers to implementing sponsor/CRO technology from the perspective of sites that currently have technology.

Variance of Technology Needs by Type of Clinical Trial Site (i.e., Not All Sites are the Same)

Site technologies such as CTMSs, eRegulatory management systems, and eSource/EDC systems are used by a variety of clinical research sites. As mentioned above, because the needs of each type of site organization differ slightly, it is unlikely that a “one size fits all” technology solution will work. A high-level overview of types of clinical research organizations and requirements for clinical research technology follows.

Academic medical centers (AMCs)

AMCs typically manage between 500 and 2,000 studies per year—inclusive of industry-funded studies, research grants, and investigator-initiated trials. These institutions often have a central research office that coordinates technology system purchase, implementation, and reporting.

A CTMS is critical for these AMCs to coordinate all aspects of study delivery including, but not limited to, patient visit scheduling across various departments (e.g., clinic visits, diagnostic imaging) in compliance with the protocol schedule of events, billing clinical research vs. standard patient care, and facilitating the workflow for ethics submission in cases where the AMC requires review by a local institutional review board (IRB). The CTMS also allows for tracking of key performance indicators (e.g., patient enrollment and retention), both for progress monitoring dashboards and a historical record of operational metrics. Integrations are common between the CTMS system and a median of six specific hospital systems (e.g., electronic medical/health records [EMRs/EHRs], Human Resources, Finance),{3} and a primary reason why clinical research sites can’t just use a CTMS provided by the sponsor/CRO, a question often asked by sponsors/CROs who lack familiarity with site systems.

For the 72 organizations that meet the standards for research of cancer prevention, diagnosis, and treatment from the U.S. National Cancer Institute (NCI),{4} a CTMS is also critical for application to and review of Nationally Designated Cancer Center status.{5}

Having invested in CTMS, these AMCs are next likely to purchase an eRegulatory system to collect documents associated with each clinical study. While the volume of studies varies across type of clinical research site, the institution-specific requirements for eRegulatory binder systems are similar and integration with a site’s CTMS is desirable for pre-population of standard study information and personnel across systems.

Finally, AMCs may also choose to invest in an EDC system to capture information on single-site studies (e.g., grants, investigator-initiated studies). For industry-sponsored studies, the sponsor/CRO will typically provide an EDC to the site for use on that study, so site-specific EDC is used outside of industry-funded studies. eSource use by AMCs is less common, because their own institutional EMR/EHR system is typically source for the clinical study.

Non-academic hospitals/health systems/clinics

Like AMCs, non-academic hospitals/health systems/clinics typically provide clinical research services in addition to patient care, and thus have their own EMRs/EHRs that serve as source for a clinical study. Another similarity with AMCs is the need for a CTMS to organize all aspects of study delivery across approximately 200 to 800 clinical studies per year. However, the non-academic site’s needs tend to be simpler than the AMC’s because these sites typically do not have a local IRB process to coordinate, nor do they participate in as much research grant or investigator-initiated studies. Performance tracking dashboards and access to historical operational metrics are of value to the non-academic centers, particularly in larger institutions that conduct research across departments.

Due to the high volume of studies per year, these non-academic hospitals/health systems/clinics may also invest in an eRegulatory system. As mentioned above, requirements are somewhat standard across sites with a desire for pre-population of study information from CTMS. Because they have their own EMR/EHR and participate primarily in industry-sponsored studies, use of eSource and EDC is not common.

Standalone clinical trial sites and networks

Many of these stand-alone clinical trial sites and networks are dedicated to clinical research, and thus lack the practice management system and/or EMR/EHR systems seen at AMCs or non-academic hospitals/health systems/clinics that also provide patient care. Large clinical trial sites may perform as many as 40 studies per year, and site networks may oversee an aggregate of 200 to 500 studies across regional—and increasingly multinational—clinical trial sites.

Similar to other types of sites, a CTMS is often the first technology system purchased by independent sites, and this is particularly important in the case of site networks that have a central office that monitors study progress (e.g., performance metrics) and provides centralized services for individual sites (e.g., business development, feasibility, billing/invoicing, patient payments). In the case of site networks, technology is typically purchased by the central office to facilitate cross-site and cross-study project management, as well as to capitalize on technology purchasing power. In addition to a CTMS, sites/site networks will next typically invest in an eRegulatory management system, and eSource may be purchased by the site network as a third supporting technology, particularly in cases where no EMR/EHR system is available.

Implementing Sponsor/CRO Technology in Technology-Enabled Sites

Barriers to adoption of sponsor/CRO technology by clinical research sites are well documented and include, but are not limited to, too many systems with different login credentials, duplication of training, systems require too much time and/or detract from patient care, and the systems are not easy or intuitive to use.{6}

Technology-enabled sites experience these barriers, but have additional challenges to using their own technology in combination with sponsor/CRO provided technology, as described below.

Duplicate activities:

• Issue: Sites choosing to invest in CTMS and eRegulatory management systems already automate many clinical trial activities covered by sponsor/CRO technology, such as sending participant visit reminders (CTMS), collecting/storing documents needed for study start-up (eRegulatory), and/or capturing electronic participant signature in informed consent (eRegulatory). When sponsors/CROs provide these types of tools to sites in the context of a single study, technology-enabled sites either don’t use the functionality (resulting in incomplete data/lack of transparency for sponsors/CROs) or, in cases where use of the tool is mandatory for study participation, sites require added work to perform the activity in two unconnected systems.
• Potential solutions: Integration across site and sponsor technology to form a connected ecosystem is one way to overcome this barrier. In a 2023 survey by Advarra, more than 70% of sites rated integration of their eReg system with sponsor tech as extremely or very valuable. Selecting technology providers that have already established integrations with site technology is one way that sponsors and CROs can ease site burden. Another action that sponsors/CROs should consider is selecting technologies that enable navigation with single sign-on between site and sponsor technology using the site’s own credentials. Using the site’s own credentials to access sponsor technology was rated as extremely or very valuable by more than 80% of sites.{2}

Unified site reports/dashboards:

• Issue: As mentioned above, one of the primary drivers in an organization’s decision to invest in site technology is the need for transparency across all ongoing studies. While this is helpful to all sites, unified reporting/dashboards are critical to operations for some types of sites. One example is AMCs that are not only working on studies across sponsors/CROs, but also working on non-industry–funded studies. National Cancer Institute–designated cancer centers are another example of where reporting is critical to attaining and maintaining certification. Unified reports and dashboards are also extremely important for site organizations with a central office that requires transparency to deliver central activities (e.g., recruitment support) and/or provide clinical trial oversight/management. Examples include a central office across all sites in a site network, or a central office across all research departments in an AMC.
• Potential solutions: Support the site’s use of its own tools and associated reporting/dashboard functionality to deliver centralized activities and track important study and participant milestones across all studies. This can be facilitated through point-to-point integration with each technology, or even better, for a more modern technology configuration with near real-time data sharing from the central data warehouse. Many of the larger sites (especially AMCs) and site networks have sufficient internal information technology capabilities to support data amalgamation for unified dashboards/task lists, a tool rated as very or extremely useful by 77% of sites in Advarra’s 2023 survey.

Site processes/standard operating procedures (SOPs):

• Issue: To facilitate new employee onboarding and deliver high-quality, regulatory-compliant research, sites have developed SOPs, work instructions, and other process maps that incorporate use of site technology. Having a scalable way to manage onboarding and oversight of clinical research site staff has been critical to maintaining study operations in recent years, with site networks having experienced double the usual staff turnover rate (increase from 10% to 37% pre-COVID-19 to 35% to 61% after).{7} Introducing new technologies often requires deviation from and/or modifications to standard site process and associated change management activities (e.g., staff training, job aids). This may impact both staff efficiency and study delivery quality.
• Potential solutions: Selecting technologies with streamlined user experiences is paramount to minimizing site burden. Discussions with sites, sponsors, and CROs suggest wide variance in the ease of use across sponsor technology vendors. For example, one sponsor that recently switched start-up technology vendors reported a decrease in site support calls from 150 to three over the same timeframe due to ease of use. For sponsors or CROs selecting to adopt the same technology across their entire portfolio, there is an opportunity to partner with very large sites to offer change management support prior to start-up.

Conclusion

In speaking with study sponsors and CROs, there appears to be a disconnect as to why sites need their own technology and can’t use the technology provided to them by a sponsor/CRO for a particular study. As described in this paper, the unique features required by sites to operate a study combined with the need for integrations to other systems in the organization pose serious challenges to sites using the same technology as a sponsor or CRO. Further, for CTMS in particular, finding a single system that can meet the needs of all site customer types—AMCs, other health systems and clinics, and sites/site networks—adds even greater complexity.

Understanding that sites will continue to use their own technology, sponsors, CROs, and technology providers all need to strive to minimize site burden when adding sponsor/CRO technology for a study. While some of these challenges are universal to all sites, others are specific to technology-enabled sites, including the real potential for duplicate work, compliance risk due to process change, and the need to preserve unified data tracking and reporting. Sponsors and CROs can help by considering the site technology experience when selecting the portfolio of technology systems used within a study. Integration for data and document flow, navigation with login using the site’s credentials, data access for consolidated reporting, and a simple, intuitive user experience are all important factors for consideration for our sites.

Press releases, websites, and participation of sponsors and CROs in clinical trial workforce associations such as the Association of Clinical Research Professionals all point to a strong desire to decrease site burden, but there’s not always a clear, actionable path for sponsors and CROs to address the problem. Sponsors and CROs that are truly site centric will be looking for ways to reduce friction so that technology isn’t just an additional challenge to a workforce that is already suffering from a widening gap between the supply of and demand for trained staff.{8} Recognizing that experienced sites are already struggling to achieve workforce levels to keep pace with industry clinical trial volume, anything sponsors and CROs can do to decrease burden will have a positive impact on the clinical trial industry—within and beyond an individual trial.

References

1. Cascade E, Yawman K. 2024. How to Improve Quality of Study Delivery? Work with Technology-enabled Sites. Applied Clinical Trials. https://www.appliedclinicaltrialsonline.com/view/how-to-improve-quality-of-study-delivery-work-with-technology-enabled-sites
2. Advarra 2023 Study Activation Report. Advarra.com. https://info.advarra.com/study-activation-eb.html
3. Advarra analysis of data provided by 28 OnCore CTMS customers. May-June 2023.
4. National Cancer Institute: NCI-Designated Cancer Centers. National Cancer Institute. https://www.cancer.gov/research/infrastructure/cancer-centers#:~:text=Find%20an%20NCI%2DDesignated%20Cancer%20Center,-NCI%2DDesignated%20Cancer&text=There%20are%2072%20NCI%2DDesignated,edge%20cancer%20treatments%20to%20patients
5. Advarra Case Study: Markey Cancer Center Earns NCI Designation with Help of OnCore. 2021. Advarra.com. https://info.advarra.com/rs/291-FFI-055/images/Markey%20NCI%20Designation%20-%20OnCore%20Case%20Study.pdf
6. Society for Clinical Research Sites. 2019. Impact Assessment of eClinical Technologies and Industry Initiatives on Sites. https://myscrs.org/uncategorized/scrs-releases-research-report-on-the-impact-of-eclinical-technologies-and-related-initiatives-on-sites/ and https://www.oracle.com/a/ocom/docs/dc/em/scrs_research-report_09oct2019_final.pdf
7. Open Letter to Sponsor and CRO Colleagues Regarding the Workforce Retention and Inflationary Pressures Affecting Clinical Research Sites. 2022. MySCRS. https://myscrs.org/workforce-challenges-letter/
8. Freel SA, Snyder DC, Bastarache K, et al. 2023. Now is the Time to Fix the Clinical Research Crisis. Society for Clinical Trials. https://doi.org/10.1177/17407745231177885
9. Kingsley J. 2018. Sites Need Technology, Infrastructure Improvements to Improve Clinical Trials. Clinical Leader. https://www.clinicalleader.com/doc/sites-need-technology-infrastructure-investments-to-improve-clinical-trials-0001

Elisa Cascade, MBA, is Chief Product Officer at Advarra and the 2024 Chair of the Association Board of Trustees for ACRP.

James Wurdeman is Senior Vice President for Technology Strategy and Innovation at Advarra.