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In late 2020, Advarra conducted an anonymous survey to collect site-specific study activation data. This data, reported in the full study activation report, covers a wide range of topics associated with clinical trial activation and startup. Topics included IRB/IBC, regulatory and compliance, and budgeting/finance, to name a few. For the purpose of this blog, we analyzed the information associated with Medicare coverage analysis (MCA).

An MCA identifies all items or services required in a clinical trial and describes what should be billed to Medicare. A proper coverage analysis (CA) outlines any applicable Medicare policy, while also addressing the potential costs which are not reimbursable by Medicare or private insurance. This may include costs the sponsor intends to cover, services bundled into the costs of other services, items provided free of charge without any monetary exchange, etc.

Advarra conducts CAs tailored specifically to your institution’s guidelines. Learn how to streamline the CA process through Advarra’s Coverage Analysis Service.

Demographics

Within the study activation survey, we asked how personnel identify the sites they work on behalf of academic medical centers/universities (AMCs), independent cancer centers, or health system-based sites. When compared to a question asking whether an MCA is required at a site, respondents answered the following:

100% of AMCs complete an MCA for clinical trials
51% of non-AMCs (health systems, private research sites) complete an MCA for clinical trials

With this result, it is reasonable to determine that AMCs are more prepared when billing Medicare for research assessments. However, looking at federal clinical trial billing-related lawsuits since 2005, nearly all settlements over one million dollars come from AMCs.

While this connection is surprising, several outside factors show this correlation does not imply causation. Our survey showed 21% of AMCs participated in more than 300 clinical trials per year, while only 6% of non-AMCs (health system-based sites and independent/private/dedicated investigative sites) participated in more than 300 clinical trials per year. AMCs also had a diverse portfolio, actively participating in clinical trials involving a wide range of disease settings.

Because of the high number of active clinical trials across a wide range of disease settings, AMCs appear to be more proactive in regard to billing compliance. This is due to the large portfolio of active studies and opportunity of billing-related oversights, emphasized by the number of federal clinical trial billing-related lawsuits.

Challenges

When asked about internal pain points associated with MCA development, the top response was the number of available staffing. The second most common result was staff expertise, and staff turnover was the third. Coverage analysis is a difficult topic to learn and perfect. This field of expertise often requires years of experience to ensure the quality of work. Each institution operates in its own specific way, making MCA development that much more of a challenge.

Turnarounds

Completing the CA in a timely manner is critical to study activation. The MCA is often required to confirm funding requirements are met, which trickles down to the turnaround times of budget/contract development. The site’s startup funding is then suspended, and more importantly, a patient’s treatment may potentially be delayed. In reference to turnaround times, sites said the following:

62% complete an MCA in 14 days or more
11% complete an MCA in 7 days or less

This survey also asked sites if they have an in-house team or an outsourced team completing MCA development. While several internal teams indicated they completed MCA turnaround in seven days or less, every respondent who indicated they completed MCA turnaround in 14 days or more did so via in-house operations. By comparison, outsourcing MCA to a professional service such as Advarra’s Coverage Analysis Service, institutions can expect MCA turnaround in 5-7 business days. When the CA is conducted efficiently, sites can move forward on their study activation process.

Cost Recovery

Performing an MCA is often a direct result of participating in research. We were curious as to whether the cost of performing an MCA was covered under clinical trial budgets and contracts. The survey results found:

49% of sites successfully recover the cost of MCA development

*Only 54% of sites request MCA cost recovery from sponsors

This shows that sponsors recognize the need for site MCAs and are willing to provide reimbursement for their efforts. Although half of our respondents stated their costs were not covered, the overwhelming majority of these sites did not request MCA cost recovery from their clinical trial sponsors. If you are curious as to whether the time and effort associated with MCA development may be reimbursed, talk to your sponsor. Again, many sponsors are aware of this billing compliance task and are willing to work with their sites to compensate for their costs.

Conclusion

Internal efficiencies are ever more important in clinical research. The need to complete MCAs in a timely manner is critical to the success of a clinical trial’s activation. Many sites face challenges in this area, regarding both internal staffing and MCA development timelines alike. However, this process is required in order to ensure billing compliance and to outline potential costs not covered by a patient’s insurance. This has been confirmed by sponsors, as many recognize the need for site-specific MCAs and are willing to provide reimbursement for their efforts.

Download the Study Activation Industry Report

To better understand study activation roadblocks, Advarra asked sites to weigh in on their study activation experiences. Our latest industry report outlines these findings, providing sponsors and sites suggestions and solutions, equipping them with information necessary to streamline and improve the overall study activation process. Access the Report

Diversity, equity, and inclusion (DEI) are critical pillars in the evolving landscape of cancer research. These values not only shape scientific inquiry but also directly impact the applicability and success of clinical trials, particularly among underrepresented populations. While DEI initiatives are gaining prominence, much work remains to integrate these principles into the fabric of clinical research.

The Importance of DEI in Cancer Research

Limited diversity in cancer research results in findings not fully reflecting the complexities of cancer as experienced by different populations. Without a diverse participant base, clinical trials may fail to provide comprehensive, generalized data to underserved groups, leaving a gap in treatment efficacy for minority populations.

Despite the growing awareness of DEI, many clinical trials still lack adequate representation from populations such as African American, Latinx, and other minority groups. Several factors contribute to this issue, including a long-standing mistrust of the medical system, logistical barriers, and financial constraints disproportionately affecting these communities.

Understanding the Distinction Between Diversity, Equity, and Inclusion

A nuanced understanding of DEI is crucial for successfully addressing gaps in clinical trial participation. Diversity refers to the presence of differences, such as race, gender, and socioeconomic status, within a given setting. However, diversity alone does not guarantee an inclusive or equitable environment. In other words, a diverse clinical trial team or participant pool does not automatically ensure everyone feels valued or included.

Equity goes a step further by ensuring equal access to opportunities and resources, recognizing individuals start from different places due to systemic barriers. For clinical trials, this means acknowledging and addressing the unique challenges faced by minority populations, such as health insurance coverage and the logistics of trial participation.

Building Trust With Minority Populations

A significant barrier to improving DEI in cancer research is the mistrust many minority populations feel toward the medical system. This mistrust is rooted in historical injustices, such as the Tuskegee Syphilis Study and unethical medical practices involving Black Americans. Recent studies continue to highlight this deep-seated mistrust, with 55% of Black Americans expressing distrust in the healthcare system.

To overcome this, building relationships through consistent presence and follow-up can help rebuild trust. Moreover, having diverse clinical research teams reflecting the communities they serve can go a long way in fostering trust and encouraging participation.

Strategies for Improving DEI in Clinical Trials

Improving diversity in clinical trials requires a multi-faceted approach, including the following strategies:

Community engagement: Establishing strong ties with the community through advisory boards and direct involvement in trial design.
Rethinking eligibility criteria: Many minority patients are excluded from trials due to comorbid conditions more prevalent in underserved populations. Revising inclusion and exclusion criteria to accommodate these conditions can increase minority participation.
Reducing participation barriers: Logistical challenges, such as transportation and time commitments, often deter participation. The FDA’s guidance on enhancing diversity in clinical trials suggests reducing the burden on participants by increasing visit windows, allowing for virtual communication, and decreasing visit frequency.
Policy changes: Recent legislation, such as the Clinical Treatment Act and the Henrietta Lacks Enhancing Cancer Research Act, aims to eliminate systemic barriers to trial participation. The Clinical Treatment Act, for instance, mandates Medicaid coverage of routine costs associated with clinical trials, removing a financial hurdle for many patients.

The Role of Cancer Centers in Advancing DEI

National Cancer Institute (NCI)-Designated Cancer Centers play a crucial role in advancing DEI within their catchment areas. These centers are expected to engage their local communities, particularly underrepresented groups, to reduce cancer burdens. Cancer centers can enhance minority recruitment by creating community advisory boards, involving community members in trial design, and maintaining a diverse research pipeline.

The Future of DEI in Clinical Research

As we look to the future, DEI efforts must be at the forefront of cancer research and clinical trials. Priorities include increased funding for research on structural barriers to participation, broader community engagement, and better representation in biorepositories to ensure comprehensive genetic research.

Additionally, policies supporting diversity in clinical trials must continue to evolve, including addressing the digital divide. As clinical trials increasingly rely on electronic communication, there is a risk of excluding those without access to digital resources, further exacerbating participation disparities.

Addressing DEI in cancer research is a multifaceted challenge requiring collaboration across research teams, community partners, policymakers, and healthcare institutions. By prioritizing trust-building, removing barriers, and rethinking traditional approaches to clinical trials, we can move closer to a more equitable and inclusive research landscape—one benefitting all populations.

At the core of daily regulatory operations are the documents required to facilitate, manage, and provide a record of the conduct of a research study. Historically reliant on paper binders, manual and redundant workflows, and burdensome monitor visits, many sites are seeking ways to streamline source document management. In the past few years, sites have increasingly turned to electronic systems to support remote workflows and keep their research moving. Facilitating remote monitoring across a site’s research portfolio is quickly becoming an expectation. To respond to these site needs, we have collaborated with our customer community to develop new workflows within our Advarra eRegulatory Management System. Continuing to transform the way essential protocol documents are routed and stored, we’ve introduced the capability to store and manage additional key study documents; subject binders and standard operating procedures (SOPs).

Store and Manage Subject Source Documents

Source documents associated with each study participant need to be stored by the research site and accessible to the sponsor for source document verification. These documents include signed consent forms, contact information, compensation records, and more. For every protocol binder, there are numerous additional subject binders to support each subject and their source documents related to the protocol, which dramatically increase your document storage needs. Ensuring proper storage of source documents is essential to the compliance and validity of your trial. Any source data captured on a paper document or in a system that does not allow controlled remote access, whether it is a signed consent form, patient diary, notes, and more can be scanned and uploaded into Advarra eReg for compliant storage and managed access for source document verification.

When you centralize your subject binders with Advarra eReg, the need to transport subject binders to multiple locations to be monitored is removed. Multiply that by the number of subjects you’re supporting across your research portfolio—the time, effort, and money you save grows exponentially.

Centralize and Retrieve SOP Documents

Not only are the processes outlined in your organization’s SOPs essential to execute in a consistent manner across your institution and participating sites, the controls in place that ensure appropriate study conduct and compliance also need to be communicated to external stakeholders. By centralizing your SOP management, you can quickly access SOP documents for internal staff and grant access to sponsor monitors, helping to bolster your organization’s audit readiness and enabling timely retrieval of any requested document.

Expand Remote Monitoring

It’s important to remember in this digital age, electronic workflows don’t automatically equate to remote capabilities. Unlike web-based systems such as SharePoint or Box, the intuitive, purpose-built workflows within Advarra eReg go beyond simply storing electronic versions of essential protocol documents, subject source documents, and SOP documents. Instead, eReg transforms the storage, upload, routing, signing, and verifying of your regulatory documents. Utilizing these workflows, your organization can efficiently and compliantly drive a complete remote monitoring process.

For example, Advarra eReg’s remote monitoring workflow supports easy access via a secure login link for the sponsor, as well full control over what the sponsor monitor can see and the timeframe for access. To increase transparency between your organization and the sponsor, you’ll also have the opportunity to view when the sponsor monitor logged into the application and what they downloaded for review.

Ensuring Scalability to Adapt to the Future of Research

Remote workflows and regulatory efficiencies will continue to be a priority and opportunity for research sites. Go beyond the binder and support your entire regulatory document management within a centralized, expanded eRegulatory system. To explore simple and efficient remote monitoring workflows, tour new storage capabilities and more, request an Advarra eReg Demo for your team.

Billing compliance is one of the most important and complicated processes researchers deal with on a day-to-day basis. The consequences of inaccurate billing can be severe, and ensuring workflows are being followed by all teams across an institution can be a difficult process.

More than a dozen individuals and groups can be involved in clinical research billing, and communication is key to ensuring billing procedures are being followed from start to finish. When communication breaks down or processes aren’t followed, it can leave the institution (as well as key individuals) at risk. For example, these breakdowns can include billing a trial participant’s insurance for items paid for by sponsors or accidentally billing for services that are promised free during the consent process. Other risks could include billing for services that only pertain to the research itself or billing for non-covered services during a non-qualifying trial.

Taking steps toward compliance

One way to overcome these challenges is to implement a clinical trial management system (CTMS) that centralizes billing information to help ensure accuracy. Combined with solid billing compliance processes, these systems help alleviate many of the concerns regarding communication and standardization across teams. Enterprise software like Advarra’s OnCore Enterprise Research System allow staff to build a coverage analysis, which is a protocol-specific billing list of items and services provided as part of the trial. The billing summaries (also called billing grids) mirror the protocol calendar and provide documentation of billing decisions, including an assessment of routine costs and why the study is believed to be qualifying. These are valuable tools, and an important step toward compliant billing.

In addition to ensuring charges are routed accurately, using a coverage analysis can bring further benefits to your research organization. For example, the ability to reference a clear list of what items are and aren’t billable early in the study startup process can be valuable when building your budget and negotiating with sponsors. The coverage analysis can also be used by compliance officers to monitor and audit the ongoing compliance of trials.

Increasing compliance with integrations

If you’ve already implemented a CTMS, another step towards billing compliance is integration with your electronic medical record (EMR) system. For example, OnCore is able to send complex study billing definitions to an EMR system through the IHE Clinical Research Process Content (CRPC) profile. This means all applicable team members involved in the research and/or billing process can leverage the same billing designations. If a patient is also a subject enrolled on a study, that status will be visible to the organization’s billing office, ensuring charges are routed properly and potential billing issues are avoided.

Want to learn more?

If you’d like to learn best practices for compliant billing and see how a clinical trial management system (CTMS) can help centralize your billing designation, register for our webinar Facilitating Compliant Billing Using the OnCore Enterprise Research System. We’ll demonstrate specific billing workflows within OnCore and discuss how integrating OnCore with your EMR can help your organization build a successful clinical research billing program.

Reporting and operations knowledge plays an important role in successful research conduct, from communicating with leadership and funding entities to informing decisions around study startup, protocol selection, and staff assignments. Having confident visibility into your research operations and resources has continued to grow as a priority for leadership across the country, evidenced by the increasing reliance on reporting and analytics teams.

However, the reporting landscape is wider than ever, ranging from ad hoc reporting off internal data warehouses to deployment of fully-fledged business intelligence solutions like Tableau or Power BI. Choosing the appropriate combination of methods, tools, and teams to derive meaningful, actionable information from your research data requires intentional planning for the highest return on investment. Here’s why thinking about reporting staff and tools as ‘either/or’ limits your organization’s potential.

The Shared Value of Standardization & Collaboration

Advarra Insights was created to address common challenges faced by research organizations across the industry. While operational hurdles and OnCore workflows may feel unique to your institution, our experience and collaboration with research teams revealed many common topics that could be addressed effectively through a standardized business intelligence solution. Advarra Insights contains turnkey dashboards that provide actionable insight into managing study activation, accruals, effort tracking, and more, which have been fine tuned to the shared reporting needs we see across the community.

Learn how UW Carbone Cancer Center benefited from Advarra Insights’ collaborative development to improve their site accrual

Maximize the Impact of In-House Reporting Teams

Consider this – when your reporting team is being inundated with requests and has limited bandwidth, what is the best use of their time? Comprehensive dashboards from Advarra Insights acts as your institution’s core suite of reports, providing teams with a collection of out-of-the-box analytics reports covering accrual, activation, and financials. By leveraging the effort already invested by our developers and community collaborators in Advarra Insights’ core reports, your custom reporting teams are unleashed and can refocus their effort on high value, high impact institutional reporting tailored to your unique datasets and inputs. This maximizes their time and expands the scope of work they can deliver.

For example, perhaps your institution has an initiative to improve and expand service to underserved populations. A way to maximize resource allocation is to leverage Insights’ Accrual Demographics dashboard to analyze and segment accruals by gender, race, and pediatric status. With those segments covered, in-house teams can focus on examining other accrual variables like rural vs urban that may rely on additional, institution-specific data sets available to your organization, like an EHR database. Leveraging both resources – the out-of-the-box reporting suite in Insights and in-house reporting teams – enables your institution to have a more robust, efficient view of underserved population accrual to then develop data-driven strategies for improvement.

Be Free of Behind-the-Scenes Burdens

When report writers use time to manage data gaps or fix errors on core reports, it detracts from the time spent on deeper, more institution-centric reporting. Advarra Insights ensures accurate, consistent, and up-to-date dashboards so you can efficiently and confidently provide insight to your organizational leadership and study teams. In addition, Advarra Insights aligns with OnCore’s security to more easily and securely share reports across your organization without worry of appropriate permissions or access. Rounded out with comprehensive documentation and secure hosting, you’ll be able to trust and quickly utilize the information available at your fingertips.

Leveraging standardization, maximizing your custom report capabilities, and removing behind-the-scenes burdens are all ways Advarra Insights can complement your current full-time reporting staff. Explore more about Advarra Insights to advance your research potential.

Finding new ways to more accurately and efficiently manage the regulatory compliance process is always a hot topic among researchers. Over the past four years, I’ve been working with Advarra customers to collaborate on the strategy and development of an eRegulatory system that addresses these needs. One thing has become clear: managing protocol documents using physical binders or an internal shared drive can put a research site in a difficult position, reducing productivity and regulatory compliance. Below are a few reasons to consider an eRegulatory system.

Centralizing your regulatory processes

Whether your regulatory department has a central body, or if you have separate regulatory offices per department, getting everyone to speak the same language and manage essential documents in the same system pays dividends in efficiency and compliance. As PI’s move from one protocol to another, or when staff change departments, having all regulatory information gathered in a standardized format will improve study start up and reduce the need for duplicate document management.

Ditching the paper and the manual document routing process

An eRegulatory system can help you avoid tracking down study staff members and PI’s by foot. It manages the legwork, notifying staff members when they need to sign and review essential documents. And by electronically signing documents and tracking them within the system, you save valuable staff time while maintaining 21 CFR Part 11 compliance.

Utilizing a single source of truth for staff credentials, training and more

An eRegulatory system eliminates the need to search the shared drive for the PI’s medical license or the protocol coordinator’s curriculum vitae across multiple protocols. The system can connect staff members to their protocols, and update credentials and training for staff members in one location and share them across all of the applicable protocols. You can also gain visibility of expiration dates for protocol documents. An eRegulatory system can run reports on expiration dates for 30/60/90 day intervals over multiple protocols, providing staff with valuable insight and allowing them to better manage their workload.

Easily preparing your site for monitor visits

Grant access to monitors to the essential documents they need to see on a site visit. You no longer need to find the binder and set it out for the monitor to ensure they are able to view the documents needed. An eRegulatory system ensures that all documentation is easily managed, all in the same user-friendly format.

What to expect from an eRegulatory system

eRegulatory systems are more than an electronic version of a paper binder. These systems go beyond the binder, strategically designed to improve cumbersome regulatory workflows, communicate with other electronic systems used by your organization, and increase compliance and remote capabilities. Did you know an eRegulatory system can:

not only store essential protocol documents but track owners, training, expiration dates and easily route for signatures?
manage multi-site trials, allowing a coordinating center to manage essential documents for participating sites?
integrate with other electronic systems like email, CTMS, or eIRBs?
manage delegation of authority workflows, including master delegation of authority?
securely allow remote access to sponsors and monitors?

By utilizing an eRegulatory system with purpose-built workflows to support your regulatory teams, you can reduce staff workload, increase regulatory oversight, and enhance compliance. If your organization is looking to improve regulatory efficiency, learn more about Advarra’s eRegulatory system or request a demo.

The promise of gene therapy treatments is upon us. In more than 20 years of experience in the clinical research space, I heard a lot of excitement over the years about genetically engineered treatments. In the last few years, that excitement has begun translating into reality. We see an accelerating gene therapy market, expected to grow globally by 16.6 percent between 2020-2027. Early phase research may be conducted in the halls of large academic medical centers who are equipped and experienced in working with genetically engineered treatments and biosafety requirements. However, all those new therapies must eventually go through larger scale clinical trials on their way to market approval. As gene therapies enter the pipeline at an exponentially-growing pace, how can private and hospital-based clinical trial sites prepare themselves to take advantage of the coming rush?

In this blog, we will explore how proactive clinical research sites, from small private clinics to large integrated health systems, are preparing for the accelerated trend of gene therapy research.

Understanding the Regulations

When treatments involve recombinant DNA, synthetic DNA, or messenger RNA, additional oversight is necessary. These treatments make permanent changes to the humans they are introduced into. Unlike typical drug treatments which are metabolized by the body; gene therapy treatments, in many cases, are making permanent changes to the human’s genetic profile and cannot be undone. Additional precautions and oversight by an institutional biosafety committee (IBC), are necessary in the handling and administration of these novel research compounds. The US National Institutes of Health, Office of Science Policy sets the guidelines for research involving recombinant or synthetic nucleic acid molecules. If you want to learn more about the additional rules and when IBC review is required, see our extensive IBC resources, blogs and webinars at Advarra.com.

Facility Preparation

Most clinical trial sites likely already have the basic facilities needed to conduct gene therapy research. Human gene therapy treatments typically fall into biosafety level 2 requirements, which are consistent with good laboratory and clinical practice precautions (e.g. sharps protocol, blood born pathogen protection, PPE, etc). For gene therapy treatments, some additional precautions need to be taken to protect the site staff and the surrounding community from inadvertent exposure to a compound which could permanently change their cells and genes. Some common items sites need to address:

Eye wash stations near where the gene therapy product will be administered
Non-porous surfaces (e.g. chairs, floors, etc) in all areas where the gene therapy product will be administered
No carpet or cloth chairs that cannot be sanitized
Designated rooms where the product will be administered
A fume hood if the product is prepared or mixed on-site
Hazardous waste disposal facilities and service

Preparing your site in advance, before a gene therapy clinical trial is at your doorstep, can save days or weeks off your study activation. The IBC will inspect your facility to determine if it is adequate. If you need help in making necessary preparations, the biosafety consulting team at Advarra can support your facility planning.

Standard Operating Procedures

In accordance with the NIH OSP Guidelines, the IBC is required to review the site’s standard operating procedures relating to safety precautions. The IBC is looking to ensure adequate plans are in place to keep the site staff and the surrounding community safe from inadvertent exposure to an investigational product which could make permanent changes to human cells and genes.

At a minimum, sites need to prepare the following procedures in advance of IBC review:

OSHA blood borne pathogen exposure control plan
Biohazardous waste/regulated medical waste disposal policy, procedures, or permits
Standard operating procedures (SOPs) for use and handling of the particular study agent, as well as spill and containment procedures

Clinical trial sites should carefully prepare these SOPs and combine with staff training for anyone who will be handling the gene therapy based investigational product.

Getting Registered With a Central IBC

Unless you are at a large academic medical center, likely your research site does not have its own institutional biosafety committee, so sites will need to register with an independent IBC. Sponsors conducting gene therapy trials pick their central IBC much in the same way they pick a central IRB; so you will want to partner with an experienced independent IBC who has plenty of experience conducting integrated IRB/IBC reviews. The registration process is reasonably straightforward and involves the independent IBC submitting paperwork to the National Institutes of Health, Office of Science Policy to register your site. Plan ahead since the OSP registration process can take upwards of eight weeks. If you plan to register with multiple independent IBCs, the OSP process must be repeated for each additional independent IBC provider you decide to work with.

Once your facility is ready, SOPs are written and implemented, and you have registered with an independent IBC, you are ready to start taking in gene therapy trials!

Get Noticed by Sponsors

Research sites actively seeking gene therapy trials, and more recently mRNA based COVID trials, can improve their overall portfolio of research and position their sites for an increased number of clinical trials. Here are some common things you can do to get yourself noticed:

Add cell and gene therapy capacity language on your research site’s website to let sponsors know you are ready and able to conduct gene therapy research
Proactively reach out to the cell and gene therapy centers of excellence at sponsors and CROs
Include documentation in your response to site feasibility questionnaires to let sponsors know you are registered with an IBC and ready to take on their next trial
Partner with an independent IBC who will actively promote your site to sponsors and CROs who are looking to place their gene therapy research at sites how are pre-registered and ready to get started quickly

Innovative treatments using gene therapy are growing and public perception of genetically engineered therapeutics is changing thanks to the mRNA COVID-19 vaccines now among us. Make sure your site and your participants can take advantage of these new, cutting-edge investigational products. Get ready for the rush!

At Advarra we know Gene Therapy Research. We offer the industry’s only truly integrated IBC and IRB service with optimized collaboration; and, with Advarra’s worldwide presence we have reviewed more protocols than any other integrated IRB and IBC. Our exclusive network of Gene Therapy Ready sites is standing by to rapidly start-up your gene therapy research. All backed by our amazing biosafety consulting team ready to help you from site selection through to market approval. Contact us today to learn why when you think Gene Therapy think Advarra!

Sites — Is your site part of the Advarra’s Gene Therapy Ready network? Get signed up today.

Sponsors/CROs — Looking to place your next Gene Therapy treatment or vaccine trial? Contact us to learn more about Advarra’s Gene Therapy Ready network and how we can support your next trial with integrated central IRB and IBC review.

More than ever, recent medical advancements encourage and allow hospitals and clinics to work together, adopting technology to streamline their operations. Finding the right software to fit an organization’s needs may require looking at multiple options available.

Recently, Advarra’s Staff Augmentation team worked with a customer’s associated hospital as it was faced with software termination. As the termination date loomed, a team of researchers needed to find new software to store their data; primarily, their financial data. Storing active data in a clinical trial management system (CTMS) is a lifeline for the research teams relying on it for reporting and billing. Losing a system can be devastating.

Collaborating with Advarra’s Staff Augmentation team, our customer’s goal was to move active data from their sunsetting system into a new CTMS, OnCore. As I stepped in, I knew I needed to provide the team with direction on what needed to be done and detail how I would help. I started by making and presenting a plan outlining the details into three major steps: analysis, migration, and training.

Analysis

First, I gathered the needs of the team, including their workflows and processes. Understanding what they had previously done would also help me understand how OnCore could streamline and improve their workflows. Once I had an understanding, I held demo sessions for their team to help them understand how to effectively use OnCore with their research studies. Not only did this help staff learn how to use OnCore, but it ensured their new CTMS met their data standards.

I next worked with the team to dig deeper into what data they stored in the old software. I wanted to understand what the purpose of the data was, and how it was used downstream to help me translate the data into OnCore for the customer. The team reconsidered what data they should keep and decided how they could expand their reporting capabilities. Throughout our conversations, I took note of the terminology they used so I could use the words that meant the most to them later on in training.

Migration

During our analysis, we finalized the primary data set containing protocol information, subject details, billable visits, vendor payables, and events. I identified that the data in their previous software was limited compared to the data that OnCore can capture. This was a chance for them to do even more in terms of their data and CTMS and I reviewed these opportunities with the customer.

I successfully moved all the data on time and on budget. During the migration process, I once again took note of the changes and opportunities so I could highlight them during training.

Training

Training staff to use OnCore was the last phase of the project and is key for adoption and the successful use of new software. Due to customer bandwidth, I worked out a schedule and scope of the training to match their needs and availability. As we went through end-user training, I created streamlined manuals for their specific workflows that they could reference after my time with them was complete. This also provided their support team with a better understanding of the workflows and how the software can help them in the future. Towards the end of the team’s training, I could tell they were still getting used to OnCore being centrally managed and supported. To provide guidance after I left, I gave them a tip sheet of functionalities they could change themselves and what requires central change.

My time with the customer effectively allowed them to migrate their data and workflows into OnCore without interrupting study activities. By contracting Advarra’s Staff Augmentation team to assist with short migration projects, study teams have the ability to move to OnCore without taxing their highly valuable and busy internal teams.

When thinking about clinical trial documentation compliance, 21 CFR Part 11 usually comes to mind. For those unfamiliar with the Code of Federal Regulations designation, 21 CFR Part 11 provides criteria for electronic records, electronic signatures and handwritten signatures applied to electronic records. However, the criteria covered in 21 CFR Part 11 are not the only requirements that should be considered for compliant document management associated with clinical trials. Multiple other regulations require maintenance of general and trial-specific documents in regards to human subjects protection (45 CFR 46, 21 CFR 56, and 21 CFR 50), privacy and security (HIPAA, 45 CFR 160 and 45 CFR 164), financial disclosure of clinical investigators (21 CFR 54), new drug development (21 CFR 312), and device development (21 CFR 812).

Regardless of whether you are a sponsor or an investigative site, it is imperative that you have a reliable system and associated policies for storage and upkeep of documents surrounding trial conduct.

Consider Document Management at an Organizational Level

When seeking approval for a new drug/biologic/vaccine/device, you’re required to provide documentation associated with the progressing development of that new treatment, including regulatory documents, protocols, agent documentation, contracts, source documents, case report forms and numerous other documents from pre-clinical and clinical trials. Together, these documents make up the Trial Master File (TMF), which is used by the approving agency (FDA in the U.S.) to ensure complete information is present during the review process.

Due to the extent of the TMFs, and to comply with the regulations listed above, it’s also necessary to document many different infrastructure items needed to conduct ethical and compliant research. Items like: IRB rosters, IRB review documents, financial disclosures, training of individuals involved in the conduct of research, signed informed consent forms, drug receipt/disposition records, policies and procedures, etc. Many of these items surpass the level of a single study, or even a single treatment pipeline. Thus, it is important to consider how such documents will be stored and managed at an organizational level. This is done in two ways: processes and systems.

Implement Effective Processes and Systems

Organizations should have centralized policies on how required documents are to be kept. These policies should discuss:

How documents should be stored and made accessible while they are still considered active
Designate the responsible party for records retention
How and when to archive documents (NIH, FDA, and HIPAA regulations all differ and may not be the only ones that must be considered)
How long to store documents once archived
Describe a process for dispersion of documents that have expired

The other aspect of the organizational maintenance of documents is the system. While it is possible to store paper copies of all necessary documents, this comes with considerable cost and effort to ensure they are kept in a safe and orderly fashion. This also requires duplication of documents to ensure all files have every required/necessary document. For example, let’s say that our investigator has five clinical trials. For each of those trials, we have several shared documents, including the investigator’s CV, training certificates (e.g. human subjects training, HIPAA, etc.), conflict of interest disclosures, and medical license. Anytime any of these documents are updated, all five trials must be updated. Depending on the system in place, if documents are not consistently maintained, this can be a source of a large number of regulatory deviations.

The Office of Human Research Protections (OHRP), the Office of Civil Rights (OCR), the FDA, as well as other regulatory authorities, have stated it is appropriate to store documents electronically with proper safeguards, such as security and encryption. Should you choose to electronically store and maintain these documents, it is imperative to consider several items, such as chain of custody, audit trails for changes, security to ensure that electronic signatures are from the intended signee, electronic storage, and backup requirements/options, and accessibility.

Choose the Right System to Increase Compliance and Productivity

Use of an electronic system does not automatically remove the issues associated with paper systems. Policy regarding scans of wet signatures and whether those scans can be considered “original” (i.e. can you throw away the paper copy) are necessary. Electronic systems can be created that are essentially a glorified Windows Explorer file system. If a system such as this is used, you must consider processes on how to update multiple copies of the same document in different locations (e.g. study “binders”/folders, with different departments/compliance units) in addition to the security concerns/access issues.

More sophisticated systems, such as Advarra’s eRegulatory Management System, help organizations manage documents in an easy and compliant manner. These systems have technical controls necessary to validate the system to be part 11 compliant along with an organization’s policies and processes; have access restrictions to allow only authorized personnel access to specific documents; and have methods in place to disseminate updated documents to different locations, ensuring compliance across multiple studies. Such an approach will ease the burden of the researcher, study staff, and compliance units across an entire organization. This will decrease deviations associated with documentation errors and improve efficiencies associated with study monitoring and compliance auditing.

Learn more about Advarra eReg

Advarra eReg boosts compliance and productivity with workflows designed specifically for organizations focused on regulatory compliance across their entire clinical research portfolio. The system was developed through collaboration with industry-leading academic centers, creating unique efficiencies enterprise-wide. With 21 CFR Part 11-compliant electronic signatures, master delegation of authority workflows, efficient remote monitoring and more, Advarra eReg provides a comprehensive solution to streamline your regulatory management.

To learn more, request a personalized eReg demo for your team.

While there are many important aspects of a clinical research trial, the trial itself wouldn’t happen without research participants. Running a successful trial depends on recruiting and retaining clinical research participants. In order for individuals to participate in a study, they must receive information about what their involvement would include and voluntarily agree to participate, known as the informed consent process. Aside from being a regulatory and ethical requirement, informed consent is a good way to ensure participant knowledge and start a relationship between researcher and participant based on communication and trust that continues throughout the trial.

Informed consent is defined as the process of providing participants important information pertaining to the clinical trial, including what procedures they will undergo and possible risks and benefits. The information is intended to help participants make an informed decision on whether or not they want to start or continue with a clinical trial.

When is Informed Consent Obtained?

The informed consent of the participant must be obtained before any research procedures start. This is documented by an informed consent form (ICF) signed by the participant. This document is kept on file for the duration of the clinical trial, as well as a specified time period afterwards for auditing purposes. Participants must know key aspects of the protocol and understand their involvement in the trial is voluntary. They can withdraw from the study at any given moment, without reason.

Informed consent is not a one-time process; it is the start of a relationship based on communication. Research staff should not only obtain informed consent before any trial-related procedures begin, but consistently throughout the trial. Oftentimes, new information arises and changes elements to the trial that may impact the participants’ decision to keep moving forward. While they might have agreed to the protocol the last time, it doesn’t guarantee they will agree to keep moving with the study if it is amended. It’s essential to maintain ongoing conversations with participants, and ensure they continue to understand the protocol, their responsibilities as well as have their questions answered and agree to continue.

Conversely, there are times when informed consent is not needed, although these cases are rare. Informed consent is typically waived during emergency situations when it’s unfeasible to obtain consent from the participant – such as a critically ill subject. It’s important during these situations for doctors to act in the subject’s best interest, even if it means ultimately deciding not to include them in the trial.

Why is Informed Consent Obtained?

There are many reasons why a participant decides to join a clinical trial – they might want to advance science, or they may see it as their best option for treatment. Regardless of their reasoning, participating is voluntary, and subjects can opt-out at any time without any given reason.

Since it’s voluntary, a research participant needs to go through the informed consent process on a consistent basis. Informed consent is obtained to assure the researcher that the participant knows every aspect of their participation in the trial – what the procedures or treatments are going to look like and the potential outcomes, including the benefits and the risks.

Obtaining informed consent also benefits the research staff. A good consent process means the participant understands what is being asked of them. An ongoing consent process means the participant stays up-to-date on what is happening next in the trial. If they are fully informed and truly understand what is being asked of them, they will be more likely to stick with the trial for its entirety. This improves data integrity, ensuring the trial meets its scientific objectives.

How is Informed Consent Documented?

There are two main ways consent is documented: on paper and in electronic format. Regardless of format, there are common elements to making sure the participant has the information needed and voluntary consent is obtained with their full understanding.

Paper consent is collected in person with a research professional and the participant, whereas electronic consent (eConsent) uses hyperlinks, videos, and assessment tools to assist with understanding the consent document. To ensure the consent is complete, information is reviewed by a physician or by other individuals (i.e., researchers) with appropriate scientific training and qualifications.

However, it’s important for the research team member facilitating the consent processer to break down the ICF in simple terms for their participants to understand. Oftentimes, participants do not have a scientific or medical background and have questions or need clarifications. Participants may also want to meet outside of the initial meeting so they can ask any questions they might have thought of after the fact or to address any concerns. They should be allowed to take the consent form home to think about their participation and talk to others, such as their primary care physician or family, about whether participating in the study is in their best interest.

Participants are a key stakeholder in clinical research. Ultimately, if the participant feels comfortable and educated during the trial, they will be more likely to stick through the trial. Knowing the basics of when, why, and how informed consent is obtained and documented provides a great foundation for ensuring participant satisfaction.

In a recent webinar, James Riddle, Shannon Roznoski, and Stuart Cotter of Advarra presented Regulatory Fine Points: Exploring 21 CFR Part 11 Validation. The trio reviewed how the partnerships between software vendors, research institutions, and other stakeholders work to support regulatory guidelines. They discussed in detail which parts each party is responsible for when building, implementing, and maintaining clinical trials software in a government-regulated process. Due to time constraints, they weren’t able to answer all audience questions during the Q&A period, so James, Shannon, and Stuart have responded to additional questions in this blog.

Q: What is the difference between electronic signatures and digital signatures and what are the Part 11 implications for each?
A: 21 CFR Part 11 part C covers this in some detail. A digital signature is typically used as a type of electronic signature, with digital implying some additional verification of the identity using a public key infrastructure. Digital implies a control on the electronic signature. However, you can also implement other controls around electronic signatures including biometrics. The implications for Part 11 are the same. If you are using an electronic signature instead of a physical wet ink signature for an FDA predicate rule requirement, Part 11 would apply.

Q: How can I tell if a system is compliant for electronically storing documents (whether DocuSign, network folders, or other systems)?
A: The best path is to first ask the vendor for their attestation showing the software was developed for Part 11 compliance. You can then contact your technology compliance team to verify the system is included in the organization’s overall computer software validation program.

Q: During the webinar, you discussed SOPs for the validation process. Are these SOPs created by the vendor or created by the site/sponsor who is implementing the software?
A: Both the vendor and consumer have responsibilities related to 21 CFR Part 11 compliance and validation, and the extent to which responsibilities lie with the vendor or consumer will depend on the type of software and how it is hosted. The sponsor or regulated entity is ultimately responsible for assessing the quality of the data used in support of clinical investigations.

At a minimum, an organization should have procedures in place that define a risk-based framework for evaluating the software you use and determining whether 21 CFR Part 11 applies (and to what extent). Your procedures should also define how vendors are assessed, how validation and change control are conducted, and how documentation is maintained. Training and user access are also generally managed by the organization and would need to be covered by policies or procedures. In this case, it is often possible to leverage procedures you already have in place.

For products that are offered in the Software as a Service (SAAS) model, where the vendor hosts and manages the product, the vendor takes on more responsibilities for compliance, and should have procedures in place related to physical and logical security, backups, disaster recovery, installation qualification, and some level of validation testing. It is still the responsibility of the consumer to audit the vendor to ensure they meet your requirements in these areas.

For products that are installed and maintained by your IT team on hardware managed by your organization, the responsibility for these activities would lie with your organization and would require the appropriate procedures to manage them.

Q: If 21 CFR Part 11 Compliance refers to systems used to store data/documents, what is the meaning of a Part 11-compliant signature?
A: 21 CFR Part 11 covers both electronic records and electronic signatures. Electronic records may be documents but may also be records in a database, such as subject eCRFs or lab data. Electronic signatures are applied electronically to an electronic record and must meet specific criteria outlined in the regulation in order to be considered Part 11-compliant.

Electronic signatures must be unique to the individual (usually a unique username and password combination), the identity of the individual must be verified by the organization, and the organization must certify to the FDA that they are adopting electronic signatures and that they are legally equivalent to hand-written signatures.

Within the system, the signature manifestations must be associated to the record being signed. The signature manifestation include:
• The printed name of the signer
• The date and time that the signature was applied
• The meaning of the signature

Q: Currently, some software is sold as 21 CFR Part 11-compliant, but offered alongside a version that is not FDA-compliant. These “non-compliant” systems may still have the ability to generate a report or certificate of completion with regard to validity of the signatures. If we can generate that audit trail, does it comply with Part 11?
A: Many organizations put themselves at risk by storing FDA-regulated documents (such as research regulatory binders) in electronic format on an un-validated shared file system or electronic records storage. Organizations can validate their shared file storage systems, but most don’t. It is better to rely on a known vendor who specializes in regulatory document management. Even when using a vendor, the organization responsible for the records must include the commercial software as part of their overall computer software validation program.

To learn more about how to stay compliant with your electronic systems, view our webinar Regulatory Fine Points: Exploring 21 CFR Part 11 Validation.

If you’d like to learn more about Advarra’s 21 CFR Part 11-compliant eRegulatory management system, sign up for a personalized demo.

Need guidance developing your organization’s overall computer software validation strategy? The Advarra consulting team can help.

The processes necessary to support regulatory compliance require valuable time and resources within a clinical research institution. Regulatory tasks in particular require frequent coordination between multiple roles and stakeholders to be efficient and successful. Those same workflows can be applied when referring to eRegulatory systems. Direct communication and integration between key operating systems like email, local and central IRBs, Clinical Trial Management Systems, and other eRegulatory instances all contribute to a more efficient and compliant trial.

Email Integration – Accelerate Study Start Up

Correspondence and supporting documents between sponsors, IRBs, and other stakeholders are essential to house in a protocol binder. However, manual workflows associated with downloading and uploading email messages and attached documents hinders efficiency, especially during study start up. By leveraging an email integration with your eRegulatory system, you can easily save correspondence (the emails themselves) as well as any attached documents to quickly review and associate them with the appropriate protocols in the system.

The industry’s most integrated eRegulatory system, Advarra eReg, allows you to seamlessly upload documents by utilizing unique email addresses for each protocol binder. For example, imagine a regulatory manager or coordinator receives a protocol update or important correspondence from the IRB or sponsor via email that was necessary to house in the protocol binder. Rather than having to download and then manually upload the information into the system, they’re now able to simply forward that email along or better yet, cc or bcc the eReg system to capture correspondence and attachments as you are working in your email. Once complete, your correspondence and attachments are stored in the protocol specific to your communication for easy long-term filing or additional routing. This not only eases the day-to-day file management burden for your staff but is especially impactful when applied to all studies across the organization.

IRB Integration – Increase Compliance while Reducing Effort

Documents shared between your IRB and organization are an essential component of your long-term binder storage and are often updated and routed throughout the lifecycle of a study. By utilizing integrations from both central and local eIRB systems to your eRegulatory system, you can reduce manual effort and increase compliance by syncing important documents via central intake processes.

Advarra eReg supports integration with Advarra’s Center for IRB Intelligence (CIRBI) Platform. In addition, Advarra eReg supports connections with your local eIRB system. With this IRB integration, all approved documents can be immediately accessible for your regulatory and clinical staff in eReg to take the necessary action. This also allows you to decrease time and effort needed to download documents from an external system and upload them into your regulatory binder across your institution’s research portfolio, maximizing time and effort saved.

Clinical Trial Management Systems Integration – Accelerate Study Start Up

An organization’s clinical trial management system (CTMS) is often the source of truth for all protocol and participant information. Minimize duplicate effort within regulatory workflows through integration with Advarra’s OnCore Research Enterprise System by pulling CTMS data related to protocols, contacts, and organizations, into a new protocol in eReg to support accurate and efficient binder building during study start up. This integration allows for organizations to level-up their technological workflows including streamlining the administration of staff training and delegation of authority. Connecting your CTMS and eReg systems through intentional, purpose-built workflows ensures your processes remain in sync across systems and match real-life workflows without the parameters of the applications.

eReg to eReg Integration – Efficiently Coordinate Multi-Site Trials

If you are the coordinating center for a multi-site trial, you can ease regulatory burden not only across your organization but across participating sites by leveraging the Advarra eReg-to-eReg integration. When coordinating multi-site trials using Advarra eReg, the sponsor or coordinating center can house not only their own documents related to studies, but also the site files of all participating sites, structured in a site-specific folder structure. Facilitated by a multi-site protocol connection, the coordinating site can request documents from the participating site, and the participating site can easily send the appropriate documents as requested.

While significant efficiencies occur through the eReg-to-eReg integration, for those participating sites operating on paper or not using an electronic system, the participating site can log into the coordinating site’s instance of eReg to upload their documents into the regulatory binder. With a simple review and routing workflow, the coordinating site can efficiently manage protocol documents across multiple sites to ensure study compliance, and effectively manage essential correspondence, amendments, and more.

Conclusion

Just as communication and coordination amongst regulatory staff, principal investigators, sponsors, and other stakeholders improves the efficiency of a trial, so does communication amongst your technology systems. As clinical research continues to move towards a remote environment, centralizing and integrating your regulatory management process and technology is vital to your institution’s success.