Page 6 – Advarra

Since early 2020, clinical research sites – like many industries – experienced profound COVID-19 impacts. Specifically, sites had to maneuver restricted access, pivot their research priorities, and move procedures they’ve traditionally performed on-site to a virtual or remote format. Curious to further understand these impacts, Advarra conducted The Future of the Clinical Research Workforce survey in Summer 2021. Our survey found while sites tended to have similar habits prior to the pandemic, individual organizations are approaching the “next normal” differently.

In order to effectively analyze survey results, it’s helpful to know the demographic we are talking about further. Representing 70% of survey respondents, we found research site staff worked for the following types of organizations:

Independent research sites: 41%
Academic medical centers (AMCs): 28%
Hospital/health systems: 23%
Cancer centers: 9%

We also asked respondents how many protocols they work on each year. AMCs had larger clinical research portfolios, with 34% stating their organization managed 500 or more protocols. The majority of independent research sites – 83% – reported working on fewer than 50 trials yearly. Cancer centers and hospital/health systems varied across all portfolio sizes. We found 95% of cancer centers had portfolios of at least 10 protocols, while hospitals and health systems were distributed across all sized portfolios.

Sites are Facing Staffing Shortages

Survey results showed us staff shortages are occurring industry-wide. Overall, 28% of our site respondents indicated they anticipate staffing shortages in “numerous areas” of their organization or “widespread” staffing shortages, as opposed to having “enough” staffing, or shortages in a few areas in their organization.

However, this varied by site type. About 49% of independent research sites indicated they had “enough research site staff” and only 3% said they would experience a widespread shortage. Over 10% of respondents from other site types reported there would be widespread shortages. Conversely, AMCs were the least confident, with only 15% stating there would be enough research staff over the next 12 months and 19% respondents indicating they will experience “widespread” shortages.

When adding shortages in “numerous” areas to the respondents anticipating widespread shortages, the gap widens with only 12% of independent research sites giving one of those two responses versus 51% of respondents from AMCs (31% for cancer centers and 28% for hospitals/health systems).

Work Locations are Changing

Due to the frequency of interacting with participants through visits, research site staff have traditionally worked on-site almost exclusively. In fact, prior to the pandemic, 85% of site survey respondents indicated they worked fully on-site, as opposed to working a hybrid format, or a remote schedule including travel. Of the 85% working fully on-site, 45% indicated their organization will not bring them back fully on-site. This will force many to work remotely with some time each week on-site.

However, this seems to be in line with how staff would like to work moving forward. Many respondents who previously worked fully on-site would like to move to a hybrid or fully remote work scenario (63%). The remaining 37% of staff who worked fully on-site prior to the pandemic would like to remain fully on-site.

No matter where someone wants to work, all organization types are expecting a change in how their employees work. At AMCs, 66% of respondents expect their work location to become more remote or more on-site. Independent research sites were the least likely to report a difference in their work locations, with only 27% reporting a change from pre-pandemic. Cancer centers and hospital/health systems reported they’re expecting a shift in their work location at 47% and 58%, respectively.

Independent research sites showed the smallest change in work location scenarios pre-pandemic to the next stage. Of those respondents, 69% expect to return fully on-site, compared to the 84% working on-site pre-pandemic. Other site types are shifting many employees to hybrid weekly on-site/remote locations, including:

51% of AMC respondents
41% of cancer center respondents
44% of hospital/health system respondents

This shift is gaining traction because it’s shown the clinical research industry it is possible to effectively conduct remote research. However, a key component to productive remote workflows is communication. While important to facilitate successful in-person interactions, communication is crucial to ensure safe and compliant research.

In our survey, we asked people where they thought they would primarily work versus where they would like to work. About 25% of respondents from independent research sites wished for a different work scenario than what their organization wants. For the remaining organizations, between 40%-50% of respondents indicated they wanted a different work scenario than the one they think their organization wants.

Communication is Key

Even though many organizations are still in the midst of figuring out what the “next normal” will look like, remote work is here to stay. Many site types are finding ways to incorporate non-traditional work locations to meet the needs for their site, participants, and staff members. With a lot of unknowns still in the air, it’s more important than ever to keep open communication. Leadership as well as independent contributors need to initiate communication sooner rather than later to ensure a satisfying and efficient workplace. The more visibility staff have into future changes – no matter how small or seemingly insignificant – the more they will feel valued and included. This also will contribute to a higher work morale and greater buy-in from staff as everyone navigates the unknowns.

To learn more about Advarra’s findings about the “next normal”, download the Advarra Trend Report: The Future of Work in Clinical Research.

How can we embrace industry changes to become more patient-centric? As we’ve seen a shift in remote modalities to accommodate COVID-19 restrictions, there’s an increased need for a heightened participant experience in trials overall. However, it’s important to understand remote and virtual are not inherently patient-centric. It takes intentional design, adoption, and implementation to ensure remote tools are used in the most patient-centric way possible.

However, adopting a patient-centric mindset in trials benefits more than just the patient. ACRP reported, “patient-centric trials took almost half the time to recruit participants, recruited double the numbers of patients, and the drug was 19% more likely to be launched.” With this in mind, how can sites begin to become more patient-centric?

Components of Patient Centricity

When striving to become more patient-centric, there are a few components sites can focus in on and refine to create a better patient experience.

Study Design

Supporting the patient experience should be top of mind throughout study planning, designing, and execution of a study. Adopting a patient-centric mindset doesn’t just affect the beginning of a trial when you are recruiting potential participants. It’s imperative to keep the participants in mind as they move through the trial, helping them to stay engaged and more likely to stick through a trial in its entirety.

Retention

When designing a study with participants in mind, there are a few things to consider. It’s important, to the best of your ability, to fit the trial to the participant’s schedule and daily life. Bringing the trial to them via their home or on their own device are ways to incorporate the trial into where the participant is. When meeting with participants, only collect necessary endpoints – avoid anything extraneous in the interest of their time.

Communication

Keep communication between you and the participant direct, thoughtful, and easy to understand. Saying what you mean and meaning what you say opens up opportunities for a healthy dialogue between you and your participants, helping them stay engaged in a trial. Additionally, creating a positive trial experience through consistent communication goes a long way as well. Participants want to feel valued, and they want to know their time and efforts are contributing to something meaningful, whether that’s through science, therapies, advancing research, or something else. Through consistent communication, it will help them feel like their effort is worthwhile.

How eConsent Aligns with Patient Centricity

A way to become more patient-centric is to enable eConsent at your site. An electronic consenting tool, eConsent, enables research organizations to improve compliance, better educate patients and measure participant comprehension, increase communication options, and cater to a variety of learning styles. By adopting an eConsent technology, sites have the ability to enhance the participant experience and increase trial success.

Enhancing the Participant Experience

Utilizing an eConsent platform can improve ease of use and overall comprehension in a clinical trial. Participants can use the devices they are already familiar with and consistently have on them to review study materials and discuss questions with site staff without having to visit the research site. This also enables parts of the consent process they can do remotely, and gives them time to read the consent at their own pace and discuss with family members on if participation is right for them.

A major benefit to adopting eConsent is supplementing the text with multimedia elements, such as video or links, to appeal to those who may learn best visually. It’s also easy to test for comprehension in an eConsent platform, including quizzes throughout the ensure participants understand the material they are learning about. Providing a glossary for complex terms and their definitions also increases comprehension, helping participants further understand the trial in its entirety.

Increasing Trial Success

Informed consent is more than a simple box to check off on the enrollment checklist. It can have a considerable impact on the success and safety of your study. Ensuring true informed consent while managing materials, documentation, and updates of consent information is easier said than done. This is evidenced by top issues frequently found in Food and Drug Administration (FDA) audits:

Incorrect consent version
Not re-consented when required
Consent not dated by subject
Check boxes and initials on pages left blank
Subject was not provided a copy of consent
Original consent missing
No HIPAA authorization

By leveraging an eConsent platform designed to streamline workflows for site staff and supports patients throughout the trial, your organization can reduce audit findings. Through eConsent, participants are presented with the most up-to-date version of an institutional review board (IRB)-approved informed consent form (ICF), and research staff are notified when re-consents are required. This significantly improves version control maintenance by centralizing and deploying the accurate ICF. The ICF is also time stamped as signatures are captured, signed documents are automatically emailed to participants, and stored electronically. If a participant requires multiple documents’ worth of signatures, all documents are presented to them.

Quality greatly improves as well – eConsent enables FDA-compliant processes and documentation, helps eliminate deviations and audit findings, and increases both efficiency and ICF data quality.

Many research and development (R&D) organizations across the industry have limited access to a quality department in the early stages of development. It’s imperative for organizations to be agile and flexible during each development stage and often organizations interpret quality management systems and quality functions as imposing too much rigidity which may hinder this fast-paced development.

Performing R&D activities well enables researchers to gain the most knowledge in the least amount of time. This also allows an organization to easily move through development stages while efficiently delivering the investigational drug product. By performing good science in an efficient manner, organizations are matching the definition of quality.

What is Quality?

Achieving customer satisfaction and meeting requirements are the key principles of quality. Implementing quality early in the discovery phases supports the development and evolves the subsequent development stages. In the pre-clinical development stage, we find more guidance and regulations. Developmental success then leads to the onset of the clinical program and applied good clinical practice (GCP), for which expanding regulatory documentation is referenced. With the onset of investigational drug product manufacturing for any kind of development study, the need for good manufacturing (GMP) arises.

Established quality principles allow for well-supported processes and a culture embracing procedural aspects. This also fosters an understanding of effectively driving activities forward, rather than policing or limiting them.

The Challenge of Implementing a Clinical Trial Quality Management Plan

Like many aspects of research, organizations may face challenges, especially for growing companies. Quality management system support connects company development and product development.

As a company’s organizational development grows, they will see an increase in activities, staff members, functions, and the need for developed processes. This is usually a linear growth pattern. Conversely, a product’s development path can occur in different stages and is not so linear – product development can jump back and forth or leave the organization at different stages, requiring a great amount of flexibility.

Implementing a Clinical Trial Quality Management Plan that is the Right Size

Whether an organization is growing or has recently merged, it’s imperative to strengthen their processes through a systematic approach with the foundation of quality. This can be done by effectively implementing a QMS tailored to meet the organization’s needs and supporting the adoption of this approach. A staged approach to building a QMS sets a strong foundation, allowing for growth to support the investigational product’s development phases.

Conclusion

The pharmaceutical industry continually relies on quality in all research activities. Because of this, it’s important to make quality a foundational element of a company, ranging from operations to culture, to organizational functionality.

When looking for a partner to assist with your quality management system assessment or development, it’s important to find one who will collaborate with your organization to develop a tailored, fit-for-purpose approach that does not over-burden your company. The strategy should include assessing and developing curated, regulatory compliant documents, focusing on important, critical-to-quality issues and implementation to ensure compliance.

Additionally, finding the expertise to support the development program, internal teams, and elevate the organizational understanding of critical quality indicators will also give your organization the advantage it needs to improve and enhance quality operations.

While most research institutions don’t face the same financial scrutiny seen at more commercially-driven sites, there is still pressure for these academic organizations to sufficiently fund a wide variety of research initiatives. As research is dependent on investments from the clinical enterprise, it’s paramount to receive the appropriate resources to carry out your mission.

How do you ensure your institution receives the resources and revenue it needs to succeed? In our recent webinar, Leveraging Data to Lead and Manage the Research Mission: Data-Driven Decision Making at all Levels of the Organization, University of Michigan’s Teri Grieb and Kate Huffman discuss how they use data at their institution to drive the research enterprise and day-to-day research.

Form a Strategic Plan

In order to understand exactly what your institution needs to succeed, you need the appropriate resources. To understand these resources, your institution needs to create a strategic plan. In the case of the University of Michigan, this included focusing on key areas of their strategic mission related to maintaining a best-in-class, high-impact research organization.

Ask the Right Questions

Asking questions enables you to best align resources and talents with priorities at your institution. This also serves as a way to jumpstart your strategic planning by allowing your team to be on the same page about your institution’s needs. Ask questions such as:

What can we be the best at?
How are we uniquely positioned to make a difference?
What do we need to do to be competitive?
How do we differentiate ourselves?
How do we have the largest impact within the resources we have?
What measures would indicate we are on track to achieve our goals?

From there, you can group together activities you’re currently doing into themes or topic areas, and evaluate whether or not they are what your organization should do. By getting a holistic picture of where your institution is at and where it can go, it positions you well to come up with an actionable and intentional plan to get there.

Involve Multiple Organizational Levels

In order to really solidify a research mission and understand how it ties back to strategy, it’s helpful to track performance and involve leadership in the process. This gives leadership an opportunity to come together, view enterprise opportunities, and understand where their staff are giving time and effort. Grieb and Huffman said at the University of Michigan, they provided a dashboard for leadership to look at. This allows for a quick and easy way to view sources, a central location for source information, and helped with connectivity from leaders, to managers, to individual contributors.

Learn about the Advarra Insights reporting and analytics platform

These operational dashboards provided real-time visibility into daily business processes and an integration of data from multiple independent systems. By connecting decentralized units into a common ecosystem, it puts trial information at your fingertips, saving time when reporting. This also increases transparency throughout the organization, allowing everyone to understand the metrics more clearly and understand how to work toward organizational goals.

Ask More Questions

Once others are involved, start asking “why” in order to get to the root cause of the problem. Involving study coordinators is a great way to understand how metrics are affected during the activation since they are the ones making it come to fruition. This also changes the conversation between leadership and coordinators, and forces better communication with the coordinators to really understand what is going on.

Additionally, asking “why” can help your organization make data-driven decisions. By looking at the data available, it allows you to identify trends and make decisions based off of them. However, it also allows you to re-evaluate if your decisions are the correct ones for your organization. Measuring success at your organization may look like asking questions such as:

Did you achieve the results you wanted?
Did you collect the right data?
What is the quality of this data?

Use Data to Drive Daily Work

In their presentation, Grieb and Huffman noted their portfolio managers pull data from multiple locations to ensure IRB, contracting, and budgeting departments are reaching their activation goal. Since these data are in different dashboards, the central location also helped provide an overview of the project as a whole from this perspective.

This same data is then converted to a task list for completed steps in the activation process. Additionally, it becomes the basis for a bi-weekly pre-award meeting at the University of Michigan, driving communication between the finance team and the portfolio managers. The communication also identifies the action needed to make sure the activation process progresses as expected, and empowers staff to see how their work directly impacts the bigger picture.

Grieb and Huffman found this central dashboard increased data literacy, transparency, and governance. Through data dictionaries, staff knew how to better interpret the data they were looking at. Paired with an increase in who could view the data, staff members are now empowered to make timely decisions as needed.

However, even with increased transparency, Grieb and Huffman noted there needed to be a level of governance in order to quickly correct data. To establish staff buy-in for the dashboard, Grieb and Huffman knew data needed quick corrections if there were ever errors.

This central dashboard also created trust among teams since the data needed to be consistent, accurate, timely, and traceable. Grieb and Huffman found through these dashboards, the University of Michigan is able to provide their faculty with access to the data they need to measure their progress, make informed, strategic decisions, and ensure their trials impact their community.

When conducting research, in some cases sponsors and contract research organizations (CROs) may involve a data safety monitoring board (DSMB), also referred to in regulatory documentation as a data monitoring committee (DMC). Per US Food and Drug Administration (FDA) guidance, DSMBs are supposed to be independent of the party who is conducting the research. This blog outlines when a sponsor or CRO can enlist a DSMB’s help, and why DSMB independence is critical to a successful study.

What’s a DSMB’s Role in Research?

First, let’s define what a DSMB is. A DSMB or DMC is an independent group of experts who conduct a periodic review of accumulated worldwide clinical data during a clinical trial. Their primary purpose is to report early evidence of benefit or harm found in a study, accounting for participant safety and data integrity and validity.

DSMBs are not typically formed for every single study; there are particular protocols where it is helpful to enlist one. Common types of studies with DSMBs include:

Studies with placebo controls or studies where the investigator and/or sponsor are blinded
Protocol is done on a high-risk population, such as pregnant women or the elderly
Studies done in the oncology and/or cardiology field
The product under investigation may have something that causes some type of harm or serious side effect

You can learn more about when a DMC or DSMB is necessary in our infographic When Do I Need a DMC?

Why is DSMB Independence Important?

FDA and European Medicines Agency (EMA) guidance is very clear – DSMBs should be independent of the folks who are conducting the research. The best way to accomplish this independence is to have a trusted third party administer the DSMB. In order for a DSMB or DMC to be most effective, it must be independent from individuals sponsoring, organizing, or conducting research. This is so the independent oversight body can provide an opinion without the appearance of implied bias.

Eliminating the Perception of Bias

Sponsors or CROs organizing and conducting the research can have a perceived bias toward showing an investigational drug works as expected. Having a stakeholder in this position also fill the DSMB role calls into question the true independence of such a committee. To address potential bias, guidance from the FDA and EMA suggests that an entity independent of the study sponsor provide this oversight.

An independent DMC can help erase bias perception and improve trust with regulators and the general public. Regulators especially recognize an impartial, third-party DSMB enables appropriate independence from those sponsoring, conducting, and organizing the research at hand. Additionally, sponsors and CROs can assure the general public that the study was done fairly and without any hidden agendas.

What is Charter Development?

The DSMB or DMC charter is a key part of establishing the committee, defining in advance how the DSMB will maintain independence from the sponsor.

Serving as a roadmap for trial oversight, a charter includes what exactly the DSMB will review, how often it will be reviewed, secure data flow, open and closed meeting procedures, and more. By laying out a step-by-step roadmap with information in terms of how the DMC will conduct itself and how the sponsor will interact with the DSMB, the charter helps describe roles and responsibilities, drawing clear lines between the sponsor and the independent review.

Not only does the charter keep everyone involved on the same page, but it is also useful for the sponsor when interacting with the FDA. A charter will become part of a DSMB record, so when the sponsor needs to provide information during an FDA filing, they can easily provide the charter to the FDA, along with specific meeting reports.

By ensuring the DMC is truly independent from study conduct, sponsors make trial data more trustworthy to regulatory authorities and clinicians and enhance public trust with patients.

Informed consent, a cornerstone of ethical research, involves describing important elements of research in a way that permits participants or potential participants to comprehend those elements and make a voluntary choice about research participation. For individuals who speak languages other than English, or who possess limited English proficiency (LEP), informed consent may require an interpreter and a translated consent form.

Facilitating enrollment of individuals with LEP gives the research community an important chance to foster clinical trial diversity and inclusion. However, careful forethought is needed to anticipate logistical challenges and balance the importance of fostering diversity with the costs of translation services.

Regulatory Parameters and the Challenge of Inclusion

Both Food and Drug Administration (FDA) and Health and Human Services (HHS) regulations state during informed consent, “the information that is given to the subject or the representative shall be in language that is understandable to the subject or representative.” FDA further advises, “When the study subject population includes non-English speaking people or the clinical investigator or the IRB anticipates that the consent interviews will be conducted in a language other than English, the IRB should require a translated consent document to be prepared and assure that the translation is accurate.”

Because translation and interpreter services incur costs and can be time-consuming, sponsors and sites may choose to limit enrollment to people with English proficiency, rather than providing translation services. Indeed, there are several empirical studies supporting the conclusion that people with LEP are excluded from research participation at surprisingly high rates—often through an explicit requirement stating participants must read and/or understand English.

While the costs and feasibility of translation services are important considerations, there are a number of factors that make exclusion of people with LEP less than optimal and important practical solutions that should be explored first.

Access, Justice, and Scientific Value

From an ethical and participant-centered perspective, considerations of access and justice support the inclusion of people with LEP in research, which are reflected in the regulatory requirement for institutional review boards (IRBs) to ensure equitable participant selection (21 CFR 50.27 (b)(2)). Underlying this principle is the idea of sharing the benefits of research equitably across groups and members of society, and that people should not be denied access to research based on medically or scientifically irrelevant characteristics, such as limited proficiency in English.

Another consideration stems from the importance of enrolling diverse and representative study populations, which ensures that the research conclusions can be generalized widely across all segments of society. While LEP is not itself a scientifically relevant variable, it can overlap with such features, including increased co-morbidities and polypharmacy, due to the unfortunate fact that individuals with LEP are more likely to be economically vulnerable and more susceptible to negative social determinants of health.

Translation Processes

Sponsors and investigators should anticipate which non-English speaking populations they are likely to encounter for enrollment and proactively translate consent materials into those languages. Indeed, consent materials may always merit translation into prominent non-English languages, such as Spanish. The IRB should confirm translation accuracy, which may be done via an attestation from a third-party translation service or another certified translator. Researchers may also want to check with their IRB of record to ensure they understand any other IRB translation requirements.

US regulations also make specific provision for unanticipated situations where study-specific translated consent materials are unavailable. In these cases, researchers may use what is known as a “short form” consent in tandem with an oral interpreter to conduct the consent process (21 CFR 50.27 (b)(2), 45 CFR 46.117 (b)(2)). The short form consent is a document containing general, key elements of research translated into the participant’s native language. Since the short form consent does not contain study-specific information, it is best practice for participants enrolled in this way to receive the full consent document translation as soon as it is available.

An Opportunity for the Research Community

As the research community pays greater attention to access and equity considerations, facilitating the inclusion of individuals with LEP is a concrete way to advance these goals. Including people with LEP will require commitment from sponsors and researchers, both in terms of facilitating informed consent at enrollment and ensuring non-English speaking participants can adequately communicate with study staff and complete study requirements as the study unfolds.

While inclusion of individuals with LEP may carry operational costs, these costs can be justified by the goods of ensuring fair access to clinical trial opportunities for people with LEP and diversifying clinical trial samples. Excluding people from research based on the language they speak is, in many cases, ethically questionable, especially when regulatory provisions exist to minimize the burdens of translation. The research community has an excellent opportunity to advance diversity and inclusion in practice by finding ways to facilitate the enrollment of people with LEP.

The landscape of data privacy is certainly dynamic and, at times, imposing. In particular, transferring data across borders can be difficult to navigate. Does your journey to responsible and compliant data governance seem daunting? Let’s explore some of the data privacy implications and their impact on research.

What is Brexit’s Impact on Organizations with GDPR Exposure?

In addition to the need for a lawful basis for processing personal data subject to the General Data Protection Regulation (GDPR) [1], directly regulated and contractually obligated entities must also have a basis to transfer personal data outside the European Economic Area (EEA). Valid transfer mechanisms include:

A blanket decision made by the European Commission (EC) that the destination jurisdiction maintains an adequate level of data protection [2]
Conformance with appropriate safeguards such as standard contractual clauses (SCCs) [3] or binding corporate rules [4]
Utilization of derogations such as informed consent from the data subject [5]

As the name implies, however, derogations should be limited exceptions rather than standard practice.

While the UK exited the EU on January 31, 2020, a grace period for the existing regulatory framework governing data privacy extended through December 31, 2020. [6] The flow of personal data from the UK to the EEA (and to those countries that were the subject of an adequacy decision by the EC at the time of Brexit [7]) was never in jeopardy. [8] However, a measure of uncertainty existed over the future state of EEA-to-UK transfers. The status quo of limbo persisted for another six months. [9] Then, on June 28, 2021, the EC adopted an adequacy decision ensuring the lawful transfer of personal data from the EEA to the UK. [10]

How does this Impact Data Transfer to the United States?

Litigation known as Schrems II [11] (July 16, 2020) resulted in the invalidation of the EU-U.S. Privacy Shield, [12] which served as an adequacy determination. The Court of Justice of the European Union (CJEU) judgement, though rendered after Brexit, remains authoritative in the UK, as well as in the EEA. Consequently, the Privacy Shield can no longer be used as a tool for data transfers from either the UK or the EEA to the US, and entities that self-certifying under the framework must decide whether to renew or abandon their related obligations (with associated costs), at least until a new paradigm for adequacy is established.

Furthermore, Schrems II has implications for relying on the appropriate safeguards for data transfer, including SCCs. Additional due diligence is required beyond contractual terms execution to demonstrate accountability. Essentially, the private entities involved in the transaction are responsible for ensuring an adequate—or GDPR equivalent—level of data protection throughout the voyage. These contractual terms cannot be susceptible to subversion along the way, given the actual circumstances in any particular destination.

What are Supplementary Measures?

The European Data Protection Board (EDPB) published recommendations on adopting and implementing supplementary measures necessary to legitimize transfers, including pursuant to SCCs. [13] The recommended steps are as follows:

Map data flows
Identify basis for transfer
Assess effectiveness of transfer tool(s)
Adopt supplementary measures, as necessary
Consider process for implementing supplementary measures and documentation, as necessary
Re-evaluate periodically

Foremost, organizations should map expected data flow, considering any onward transfers after the initial one outside the EEA. Then, organizations must assess local law and practice, conduct a risk/impact assessment, and implement any additional safeguards (contractual, technical, or organizational measures) for each implicated jurisdiction, given the particularized circumstances of the transfer. [14] This process based on relevant, objective, reliable, verifiable, and accessible information should be documented, with a rationale as to how the measures adequately safeguard the transfer. It is not necessary to repeat the assessment when transferring a specific data type to the same jurisdiction. This documentation must be available to supervisory authorities upon request.

It may be possible to avoid implementing supplementary measures if the implicated organizations, based on individual and broader experience in the relevant sector, conclude there is no reason to believe that any identified problematic legislation, [15] regulation, or practice will compromise the subjects’ fundamental privacy rights in the data transferred. More specifically, for example, parties involved in the transfer should conclude public authorities do not have disproportionate access to data, without notice, and private entities are adequately regulated so as not to inhibit adherence to the requirements of the SCCs. However, such a determination and the rationale need to be thoroughly documented and vetted.

Finally, organizations conducting international transfers of personal data have a continuing obligation to monitor changes in local circumstance and should have established processes to act accordingly.

To assist, the EC issued new SCCs in June 2021. [16] While the former SCCs may continue to support new data transfers until September 2021, all transfers must be based on the revised SCCs by December 2022. Importantly, the SCCs consider the fallout from Schrems II. To this end, per Clause 14:

The Parties warrant that they have no reason to believe that the laws and practices in the third country of destination applicable to the processing of personal data by the data importer […] prevent the data importer from fulfilling its obligations under these Clauses.

Moreover, to fulfill this warranty, any internal documentation supporting conclusions (e.g., practical experience with prior instances of requests for disclosure from public authorities, or the absence of such requests, covering a sufficiently representative timeframe) must be derived from a process of continuous evaluation and certified at senior management level. This documentation too must be made available to a supervisory authority upon request. As distinct from modifications to the SCCs themselves, adopting supplementary measures does not trigger an authorization by a competent supervisory authority. Consequently, these measures can be incorporated in the contract as long as they do not directly or indirectly contradict the SCCs.

Returning to the impact of Brexit, the new SCCs have no force and effect in the UK. [17] The Information Commissioner’s Office (ICO) advised UK controllers to continue to use the former EU SCCs. Organizations may make changes to the former EU SCCs so they are relevant to the UK, while not disturbing the substantive legal meaning of the clauses. Much the way Switzerland maintains its own SCCs, the UK intends to publish its own SCCs for transfers from the UK. The ICO warned after the Schrems II decision, organizations should conduct the same sort of assessment and adoption of additional safeguards to ensure sufficient data subject protection.

Illustratively, from a GDPR perspective, if clinical trial data is transferred from France to the US and, finally, to a commercial entity in Canada, the onward transfer from the US to Canada could be made pursuant to the applicable EC adequacy determination. The transfer to the US could rely upon SCCs, provided parties have performed the requisite due diligence and perfected all relevant documentation. Effective supplementary measures could include pseudonymization, where:

The US-based entity is contractually prohibited from re-identifying or receiving codes enabling re-identification of the subjects to whom the data pertains, and
an assessment concludes third parties would not be able to identify the subjects with other available information. [18]

It is important to also consider individual US states, not only federal laws. Colorado, as of July 2021, joins California and Virginia in having GDPR-like laws on the books.

Ultimately, organizations do not want to compromise their obligations or their data, and it certainly is no longer enough to adopt a reactive position. Instead, organizations can proactively establish an infrastructure and culture to support good data stewardship. Purposeful and strategic execution, such as implementing supplementary measures where appropriate, will help meet the complex regulatory landscape’s demands and mitigate today’s inherent risk involved in international personal data transfer.

References:

[1] Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation).

[2] Id. at Art. 45.

[3] Id. at Art. 46.

[4] Id. at Art. 47.

[5] Id. at Art. 49. See also European Data Protection Board, Guidelines 2/2018 on derogations of Article 49 under Regulation 2016/679 (May 25, 2018), https://edpb.europa.eu/sites/edpb/files/files/file1/edpb_guidelines_2_2018_derogations_en.pdf.

[6] European Commission, The EU-UK Withdrawal Agreement, https://ec.europa.eu/info/relations-united-kingdom/eu-uk-withdrawal-agreement_en.

[7] See European Commission, Adequacy decisions, https://ec.europa.eu/info/law/law-topic/data-protection/international-dimension-data-protection/adequacy-decisions_en.

[8] Information Commissioner’s Office, International transfers after the UK exit from the EU Implementation Period, https://ico.org.uk/for-organisations/guide-to-data-protection/guide-to-the-general-data-protection-regulation-gdpr/international-transfers-after-uk-exit/.

[9] European Commission, The EU-UK Trade and Cooperation Agreement, https://ec.europa.eu/info/relations-united-kingdom/eu-uk-trade-and-cooperation-agreement_en.

[10] Commission implementing decision of 28 June 2021 pursuant to Regulation (EU) 2016/679 of the European Parliament and of the Council on the adequate protection of personal data by the United Kingdom, https://ec.europa.eu/info/sites/default/files/decision_on_the_adequate_protection_of_personal_data_by_the_united_kingdom_-_general_data_protection_regulation_en.pdf.

[11] C-311/18, Data Protection Commissioner v. Facebook Ireland LTD, Maximillian Schrems, ECLI:EU:C:2020:559 (July 16, 2020) (holding Section 702 of the U.S. FISA does not respect the minimum safeguards resulting from the principle of proportionality under EU law and cannot be regarded as limited to what is strictly necessary, and the level of protection of the programs authorized by Section 702 is not essentially equivalent to the safeguards required under EU law.)

[12] Privacy Shield Framework, Privacy Shield Overview, https://www.privacyshield.gov/Program-Overview.

[13] European Data Protection Board, Recommendations 01/2020 on measures that supplement transfer tools to ensure compliance with the EU level of protection of personal data (June 18, 2021), https://edpb.europa.eu/system/files/2021-06/edpb_recommendations_202001vo.2.0_supplementarymeasurestransferstools_en.pdf (superseding draft recommendations available at https://edpb.europa.eu/sites/default/files/consultation/edpb_recommendations_202001_supplementarymeasurestransferstools_en.pdf) [Hereinafter Supplementary Measures].

[14] European Data Protection Board, Frequently Asked Questions on the judgment of the Court of Justice of the European Union in Case C-311/18 – Data Protection Commissioner v Facebook Ireland Ltd and Maximillian Schrems (July 23, 2020), https://edpb.europa.eu/sites/default/files/files/file1/20200724_edpb_faqoncjeuc31118_en.pdf.

[15] “‘Problematic legislation’ is understood as legislation that 1) imposes on the recipient of personal data from the European Union obligations and/or affect the data transferred in a manner that may impinge on the transfer tools’ contractual guarantee of an essentially equivalent level of protection and 2) does not respect the essence of the fundamental rights and freedoms recognised by the EU Charter of Fundamental Rights or exceeds what is necessary and proportionate in a democratic society to safeguard one of the important objectives as also recognised in Union or EU Member States’ law, such as those listed in Article 23 (1) GDPR.” Supplementary Measures, supra n. 13 at 22 n. 63, https://edpb.europa.eu/system/files/2021-06/edpb_recommendations_202001vo.2.0_supplementarymeasurestransferstools_en.pdf.

[16] Commission Implementing Decision (EU) 2021/914 of 4 June 2021 on standard contractual clauses for the transfer of personal data to third countries pursuant to Regulation (EU) 2016/679 of the European Parliament and of the Council, https://eur-lex.europa.eu/eli/dec_impl/2021/914/oj?uri=CELEX:32021D0914&locale=en.

[17] Information Commissioner’s Office, Standard Contractual Clauses (SCCs) after the transition period ends, https://ico.org.uk/for-organisations/guide-to-data-protection/guide-to-the-general-data-protection-regulation-gdpr/international-transfers-after-uk-exit/sccs-after-transition-period/.

When it comes to selecting a clinical trial management system (CTMS) for your research organization, there dozens of factors to consider before making your final decision. Does the pricing model make sense for my company? Will the system provide a fast return on investment? Does the system provide the necessary functionality to get the job done?

All of these relevant questions to ask, but there are a few more questions to consider during the selection process. While the system itself is the often the most exciting part of the process, failing to ask questions about other aspects of the solution provider can help prevent you from selecting a vendor that is not a good fit for your company. Here are four questions to ask during the selection process to offer more insight into your future success with the selected vendor.

What is your Customer Retention Rate?

Understanding a CTMS provider’s customer retention rate is critical to ensuring you pick the right system. CTMS providers often highlight about how many customers they have, but don’t readily share any information on retention. It’s important to understand this because it indicates how much value the vendor brings to the table for the research organization. If a large number of people sign up but then don’t renew their subscription, it should pose a red flag. What is happening after the sale that is causing discontent? Was the system oversold on its capabilities? Is support not available?

How Frequently do you Release Software Updates?

The past few years have brought near-unprecedented change to the clinical research industry. For a CTMS system to continue to properly serve a research organization, it must adapt to meet the ever-changing needs of researchers. In today’s fast-paced world, CTMS vendors need to be quick in order to provide the best experience for researchers. This is why it’s critical to understand the release cycle for the CTMS vendor you select. Make sure your selected vendor releases three to four updates per year. This way, changes to the industry are accounted for in a very short period of time.

What New Functionality are you Working on for Future Releases?

Not only should a CTMS vendor provide releases on a regular schedule, but the content of those releases should be relevant to the users. During the CTMS selection process, be sure to ask what the company is currently working on for future releases, and how they determine which features are included in a release. This is often a good indication of your vendor’s marketplace awareness. Additionally, it helps ensure you select a vendor who understands trends and develops software to help keep you successful in the ever-changing research industry.

How Many Service and Support Personnel do you Employ?

The level of customer support your CTMS vendor provides to its customers is almost as important as the system itself. If you face a problem or have a question, you want to know you will receive answers in a timely manner. This is why it’s important to ask how many service and support personnel the CTMS vendor employs. There should be a sufficient number of staff available to handle calls in a timely manner and ensure users are up and running in no time.

Ultimately, thinking of questions such as these when choosing a vendor will help your organization in the long run. By understanding how a vendor holistically could fit into your organization, you are poised to select the best one for your organization’s needs.

Decentralized clinical trials (DCTs) are becoming one of the most dynamic ways to conduct clinical research. The ability for research sites to deploy remote trials elevates opportunities easily and effectively, priming them for increased sponsor awards and participant engagement. In order to capitalize on all the benefits DCTs have to offer, clinical research sites must embrace the myriad of technologies making remote trials possible. This blog covers three must-have decentralized trial tools to efficiently and compliantly implement remote modalities at your organization.

Remote Workflow Capability

A main concern regarding successful remote trial work is preserving source document workflows, critical approval processes, and CRF completion. If a research site doesn’t have processes or technology in place to address these concerns, sponsors may not select them for remote research. Even if a site transitioned to mostly remote workflows, leveraging tools like a clinical trial management system (CTMS) or an eRegulatory management system demonstrates a site’s ability to effectively and compliantly manage remote workflows. However, the process of transitioning to remote data capture and case report form (CRF) completion is challenging. In order to keep the process moving and provide timely access to avoid unnecessary delays to remote principal investigators (PIs) and monitors, sites need an effective eSource system. eSource not only captures screening and visit data effectively, but also empowers team members, reviewers, and approvers working remotely to leverage 21 CFR part 11 compliant eCRF workflows instantaneously.

Electronic Consent Management

Maintaining updated hard copy consent documents are complicated for site-centric clinical research models, but they are especially impractical for remote trial work. Electronic consent, also known as eConsent, systems digitize the process of facilitating and obtaining initial and ongoing informed consent. While this is a necessity for all trials, it’s especially critical when participants never physically enter a site. Entering consent forms directly into the system increases information accuracy and completeness, helping boost sponsor satisfaction and ensure audit preparedness. Due to its dynamic digital nature, eConsent systems provide diverse engagement tactics via images, audio, video, and other eLearning elements to ensure informed consent and increase participant comprehension. Digitizing the process of obtaining consent can increase the chances of a positive participant experience and boost retention.

Video

Remote trials help remove a significant barrier to participating in research: frequent travel to a brick and mortar research site. However, requiring fewer in-person visits opens the door for improved research access and new participant engagement tactics. In order to maximize the remote participant experience, decentralized trials require technology to facilitate virtual visits, designed with both sites and participants in mind. Secure video conferencing is a critical component for remote trial model success, as it allows sites to complete study visits virtually, increases site revenue, and reduces in-person monitoring costs. Convenient video solutions don’t require special app downloads or installation, making it easy for participants and clinicians to gain access. They should also support multiple attendees to join, in case participants have home health care or family members who are involved in their trial participation. In addition, integrated video capabilities with your Clinical Trial Management System (CTMS) or EHR system further centralizes your workflows and eliminates multi-system visit data entry.

Explore more resources about how these tools can help your site succeed in the new remote research landscape:

The clinical research landscape is likely forever altered by the COVID-19 pandemic, especially regarding trial continuity and the potential for business development. According to the Lancet, 80% of non-COVID trials were suspended, forcing all major pharmaceutical companies to delay current or planned trials. In May 2020, BioPharmaDive reported nearly 240 trials experienced disruptions, which lead to potentially devastating financial gaps for research companies. While COVID-19 trials made up for some of the losses and other trial work is now mostly back on track, the situation underscored the need for constant attention to the business pipeline.

Keeping trial types and designs diverse, as well as understanding important metrics, helps research companies mitigate the negative effects of trial delays. Increasingly, sponsors want to ensure performance is monitored and reported upon accurately. Having the right technology to provide sponsors with predictability and reliability sets an organization apart, leads to growth, and helps sites secure a position as a loyal partner of choice. Through this, sponsors should understand how sites can provide predictable, reliable trial results. A site can further differentiate and demonstrate how their team approaches enrollment – especially how they track, record, and organize data.

Another ramification of COVID-19 trial work is the demand for increased speed to market from sponsors and communities. The time from the start of the pandemic to the approval of a vaccine was remarkable, but also will likely affect the public’s view of what is possible. Not only will sponsors look to partner with clinical research sites to offer more efficient trials, but the public will also likely demand quicker cures to known diseases.

The first hurdle of speedier trial execution is having the right recruitment tools in place, including social media integration for campaigns. Recruiting with a fully capable clinical trial management system (CTMS) also allows sites to track metrics easier and verify study participant enrollment goals are reached. Tracking recruitment efforts and outcomes can play a strategic role in deciding how to recruit for future trials. Perhaps more importantly, this encourages early enrollment for participants in studies still in the request for proposal (RFP) process.

Easily and effectively deploying remote trials will elevate opportunities for research sites and prime them for increased sponsor awards and participant engagement. In order to capitalize on all the benefits of these trials, clinical research sites must embrace the myriad of technologies making remote and hybrid trials possible. These include texting, video, electronic consent, remote monitoring, and decentralized workflow capabilities.

Maintaining a robust clinical trial pipeline for any type of trial a sponsor may offer includes tracking data collection, analytics, and reporting supported by comprehensive CTMS and eClinical systems. Successful sites have the tools and understand how to measure the return on investment (ROI) of these investments, deploying them thoughtfully to align with growth and revenue goals.

At the core of clinical research, the safety of all stakeholders is paramount. To guide the safe and ethical execution of research, the U.S. Food and Drug Administration (FDA) oversees extensive regulations supported by pharmacovigilance teams. Although necessary, complex safety regulations can not only be difficult to understand but also challenging to implement across your research operations. This blog outlines IND safety reporting required under FDA 21 CFR 312.32(c), challenges faced in adhering to the regulation, and strategies to ensure compliance across your research program.

What is FDA 21 CFR 312.32(c), IND Safety Reporting?

Broadly, FDA 21 CFR 312.32(c) outlines detailed requirements for sponsors to communicate potentially serious risks of an Investigational New Drug (IND) to participating principal investigators. In detail, under 21 CFR 312.32(c), the sponsor is required to notify all participating investigators in an IND safety report (i.e., 7- or 15-day expedited report) of potentially serious risks from clinical trials or any other source as soon as possible, but no later than 15 calendar days after the sponsor receives the safety information and determines that the information qualifies for reporting. Participating investigators include all investigators to whom the sponsor is providing a study drug or under any investigator’s IND (21 CFR 312.32(c)(1)). This includes all investigators participating in clinical trials under an IND, at U.S. and non-U.S. sites, for the investigational drug, and any investigators conducting a study under their own IND for whom the sponsor provides the investigational drug.

The FDA recently drafted new guidance to help sponsors comply with expedited safety reporting requirements. Subscribe to receive resources on major regulatory updates.

The Considerations of IND Safety Reporting

Sponsors are responsible for communicating and tracking IND safety reporting. As sponsors, what should you consider when ensuring necessary measures are in place to remain compliant? Especially with increasingly complex studies conducted across a global footprint, this question becomes even more essential yet difficult to execute. When establishing processes to support compliance or exploring technologies to assist your communication, consider these elements:

How quickly is your study team alerted to serious risks in your clinical trials?
How does your study team evaluate serious risk and determine the information qualifies for reporting?
How does your study team compile the safety report, and how quickly and confidently can it be distributed to all your participating investigators?
How do you record, track, or prove that the report was distributed?
Where do you store receipt of the report?
Where can you minimize redundant or duplicate effort across all participating investigators and multi-study programs?
In what ways can you utilize other systems your team uses to execute IND safety reporting?

When establishing or evaluating safety reporting processes, consider the questions above to ensure your safety reporting strategy is compliant, reliable, and efficient.

Technology to Support IND Safety Reporting

To confidently ensure compliant and efficient safety reporting, it is best to implement a centralized approach that leverages pre-existing communication channels with investigators, Part 11-compliant signatures, and document storage. Systems like Advarra’s Study Collaboration, which already has an established line of communication with investigators and monitoring, ensure a tested and compliant process for dissemination, tracking, and reporting of IND safety letters.

Many contract research organizations (CROs) and sponsors collect metrics on site performance for their specific use, often requiring sites to provide the information using a variety of tools and formats. However, many of these efforts are of little value to sites because the metrics don’t truly capture the operational realities of conducting clinical trials. The metrics collected and the methods by which they are collected are determined with a top-down perspective of what the sponsors and the CROs want, rather than the sites.

For some sites, metrics are synonymous with the mandated collection of seemingly arbitrary data for reporting to sponsors and CROs. Yet, the true value of metrics is to measure operational performance in order to improve internal processes. In clinical research, this is highly beneficial when applied where the work is conducted: at the sites.

The Need to go Beyond Sponsor-Driven Metrics

Most metrics initiatives are geared toward sponsors and CROs and are oftentimes inconsistent among organizations. What’s essential and worth tracking for a sponsor is different from what the site finds valuable. Of course, some site and sponsor metrics are similar, but others may set benchmarks and measure two completely different aspects of the same process. By looking exclusively at the site perspective with their needs in the forefront, real improvements can be made based on their own workflows and associated operational data.

The ultimate use of metrics is to bring data into conversations to inform one another and create an efficient, effective partnership that will work well in the long term. This doesn’t mean a one-sided dynamic but instead having sites advocate for themselves. Focusing on what’s happening at the sites can uncover ground-level realities. After all, sites can collect more data than sponsors/CROs about their own performance, including data potentially revealing delays involving the sponsor/CRO or data more useful for internal purposes. With a thorough understanding of the complexity of site processes, it’s also critical to make tracking metrics as easy as possible for sites by leveraging the data they have on hand.

Examples of Site-Driven Clinical Data Management Metrics

While it may be tempting for sites to focus on metrics tied to revenue and other financial performance indicators, it’s essential to build a holistic data and analytics strategy based on the operational metrics that matter most to your organization.

Some examples of key site metrics include:

Accrual to date versus target enrollment
Institutional review board (IRB) submission to approval
Participant diversity over time
Days since the last participant enrolled
Staff time spent on protocol per task

Effective analytics strategies built at your research organization have the ability to greatly impact your research operations, enhancing overall trial performance. They also help to avoid common roadblocks by taking crucial steps to set up your strategy.

Collecting Data Directly from the Site’s Source of Truth

Research sites will have the most success with metrics if they focus on data already within their grasp and recorded as part of their daily and natural workflow. For sites with a clinical trial management system (CTMS), this comes right from their operations data rather than surveys or manual entry into various sponsor and CRO systems.

A site CTMS makes collecting metrics an automatic process. For example, measuring the time it takes a site to open a study is easy when the site uses a CTMS to administer its portfolio of clinical trials. With a system in place, the site just needs to count the days between the date the protocol is sent for IRB review and the date the first patient is enrolled — these dates are already recorded within the CTMS. This approach not only ensures the metrics collected are meaningful but also an accurate representation of how the site performed in the past.

Utilizing actual operational data directly from the source, as opposed to each site submitting their own aggregate metrics, ensures data consistency for reporting analysis. Sites can easily retrieve and export this data and create snapshots of their performance to share with sponsors/CROs. This improves a site’s study conduct and results in more timely data for the sponsor and CRO.

How Multiple Stakeholders Benefit from Site-Based Metrics

Sites can give the sponsor some sense of their internal progress and projected timelines for completion. With visibility into a set of key milestones for the current trial and the site’s performance data from past trials for cycle times between these key milestones, it becomes much easier to predict when to expect certain activities to be completed (e.g., to receive the signed contract). Efficiencies are gained by increased transparency and eliminating the back and forth of repetitive phone calls.

Sites also reap the rewards of collecting metrics reflecting their business goals and daily operations to improve internal processes. By objectively measuring their performance, sites can better identify and target areas of weaknesses, as well as use metrics to promote their strengths. This self-awareness helps a site’s ability to select trials on which they will be successful, and ultimately prevent wasting both their time and the sponsor’s.

When sites bring data-driven rationale into conversations with leadership and sponsors, their requests are more likely to be understood and granted. Sponsors and CROs benefit when sites proactively promote their strong areas when being considered for study opportunities and have past performance data as an indication of future performance. The ability to complete site feasibility questionnaires with real data saves time for everyone and leads to more accurate expectations. Sponsors and CROs also build partnerships with the sites motivated to collect the desired data for measuring and improving clinical trial operations.

Some predictors of site success from the sponsor/CRO perspective that sites can support with their own metrics include:

Past performance: Tracking site performance over time and comparing performance to aggregate industry values.
Experience: Demonstrating experience and success using volumetrics such as the number of trials conducted, as well as cycle-time metrics.
Investigative site focus: Using performance metrics to identify areas for continuous improvement and strengthen the site’s clinical research infrastructure.
Historic speed to randomize the first study volunteer: Evaluating cycle time metrics to identify opportunities to improve processes and cycle times, including the time to get a trial to Open to Accrual status.

While metrics have long been associated with site-sponsor relationships, using metrics among sites to improve internal processes and strengthen relationships with sponsors is gaining traction. Site-centric performance metrics can be implemented using the tools already part of the site’s daily workflow to provide demonstrable results in a relatively short timeframe. These metrics can also show greater efficacy than the top-down approach currently employed by many sponsors and CROs. Using these tools to track site-centric metrics takes less effort to collect, is more actionable, and better motivates the right behaviors. An industry full of self-aware sites results in improved clinical research operations and a rich pool of metrics from which to draw.