What are the differences between working with a local IRB and working with a central one? Since the National Institutes of Health (NIH) and the Common Rule agencies started requiring single institutional review board (IRB) review in multisite research, there have been conferences, workshops, blog posts, and other articles devoted to this topic.

Having worked in a local IRB at an academic medical center (AMC) for over 20 years, and now in my new role as Senior Vice President for IRB review at Advarra, I’m lucky to have gained perspectives on both types of IRBs. And when you come right down to it, I see the differences as minimal.

As IRBs, they both apply the same criteria for approval to the research, they both are responsible for the oversight of the research, and most obviously, and they both exist to protect participants. Thoughtful, dedicated IRB members exist in each and every IRB – local or central – and they both are audited regularly by federal agencies. Additionally, many have moved toward securing accreditation.

However, I do see one big difference: The effect of the single IRB (sIRB) mandate requires little to no real change in the way a central IRB operates, but it has had far more impact on local IRBs.

To examine why the sIRB impact is so great to local IRBs, I return to the 1998 OIG Report on IRBs, which tasked the Institute of Medicine to investigate and provide recommendations for the reform of IRBs. This activity coined the concept of human research protection programs (HRPPs) and lead to robust accreditation standards like those developed by the Association for the Accreditation of Human Research Protection Programs (AAHRPP).

As local IRBs began to build their programs to meet the accreditation standards, they took on many roles in addition to IRB review, such as:

  • Ancillary reviews (e.g., institutional biosafety committee [IBC] review, radiation for research review, and conflicts of interest [COI] reviews)
  • Gatekeeping activities (e.g., review of contract language for participant protections)

These additional responsibilities helped assure research was not initiated until all organizational requirements were met. This trend of expanded roles has resulted in HRPP/IRB offices that vary widely across medical centers, hospitals, and schools.

Today’s sIRB mandates require organizations to extract only the IRB review piece from a HRPP, leading to operational changes within a local IRB’s structure. To confound it further, study teams traditionally used to working with just their local IRB, or working with one central IRB, are now having to adopt processes for working with other local IRBs as well as with other central IRBs. Likewise, IRBs are having to learn to review and rely on other IRBs.

These paradigm shifts have left some local IRBs and their study teams under-resourced to manage working with multiple organizations for one multicenter research project. In this respect, established central IRBs have an advantage and have the resources to continue to review for the many organizations now subject to the single IRB mandate.

The significant shift for local IRBs does not change the actual review requirements or the considerations about how the risk-benefit ratio of the research is evaluated. It does bring to light the difference between IRB review and the many other responsibilities that local IRBs have taken on over the years. In the end, local and central IRBs are not that different – we really are much more the same.

For the past two years, the clinical research industry has seen an acceleration in staff shifting to a remote, work from home model. While this was initially in an effort to keep everyone safer from the COVID-19 pandemic, many organizations are permanently moving toward a remote or hybrid work model for their staff. How has this shaped current regulatory trends, and what is it going to suggest moving forward?

First, we need to understand why many organizations are shifting toward a new work environment. There are a couple of reasons for this move. The first, and perhaps most important, is staff-centricity. The ability to work remotely gives people more flexibility in their days. Whether your staff are parents with kids at home or have appointments to get to, working from home allows them to attend to these needs easier than if they were in an office setting.

From the site perspective, moving towards a remote or hybrid work model can attract talent to your institution as you work to fill the gaps in your staffing. Advertising a flexible work model is good for your organization as you try to recruit new team members. It can also expand the geographic area of potential candidates, as there will be less need to commute to a physical location.

For those working in clinical research operations, technology can provide tools to efficiently and compliantly support any type of model: onsite, hybrid, or remote. Working with eClinical solutions such as eRegulatory (eReg) or eSource eliminates the need for physical binders and centralizes management of regulatory documents and other information, ensuring it’s accessible anywhere.

Easing Staff Burden When Shifting to Remote Work

When moving towards a remote or hybrid work model, make sure you are equipping your staff to do so effectively. For example, a single organization often has staff members dispersed across a city. In the past, keeping your trials moving and being at the right place at the right time required a lot of coordination and making sure everything that was needed was in place. In the past, site staff would sometimes drive across town just to have an investigator sign a document. Switching to an eClinical suite eliminates the need for extensive coordination for all staff, as everything is accessible online, with no physical retrieval needed.

Additionally, an eClinical suite benefits more than just your staff. It also greatly reduces the need for onsite monitoring visits. Currently, many institutions have restrictions in place limiting who is on site. For sites without an eReg management system, this requires more planning and coordination to accommodate to this change. With Advarra eReg, sites are easily able to take their binders, designate which materials are available, set a timeframe, and see what the monitor sees. This enables a swift review for monitors, and less stress for research staff to make sure everything was in place.

Considerations When Adopting an eClinical Suite

One key benefit of going from paper to paperless data collection is eliminating some steps you take on paper that actually don’t provide any value. When moving from paper to digital, taking a step back to assess your current workflows will help you understand which steps need to stay in your digital workflow, and which ones can go. One example of this is evaluating your delegation of authority workflows. Moving from paper to digital is a great time to implement a master delegation of authority process, boosting efficiency within your teams and greatly reducing the “PI signature chasing” that’s prevalent during the delegation process.

However, when making the move from paper to digital, it’s important to understand it will take effort on behalf of your staff to get libraries built up and ready to use. Adopting technology to make your research more efficient for everyone is an investment – if you spend time now on building it up, your staff will continue to reap the benefits over and over. In the long run, your studies will become more scalable and efficient, enabling your staff to do more and serve more participants for each study.

Regulatory Trends to Watch in the Future

As we’ve seen the industry move toward adopting electronic technologies to keep their research moving forward, there are key trends to watch:

Patient Centricity

Utilizing an eClinical software such as eConsent enables research staff to find and enroll more participants in their studies, making it easier for them to actually participate once they are enrolled. The easier it is for someone to participate in a study, the more likely they are to continue on with the study, decreasing the dropout rate. In a time where increased trial complexity is making it more difficult to recruit and enroll participants, doing everything you can do to get participants in your funnel and keep them there is important. For this reason, if you’re looking to adopt technology, you also need to make sure your participants also find it easy to use.

Becoming More Site-friendly

Sponsors are seeing the way sites are becoming overburdened as they use multiple technology platforms to enter in data for studies, which causes significant challenges in staffing levels. As a result, it’s in a sponsor’s best interest to become more site-friendly. Part of doing so is letting sites use their own systems when conducting research, instead of sponsor-initiated technology. While there are a myriad of benefits to this, ultimately letting the sites use their own technology will enhance the overall research environment. This will help staff leave behind the one-off workflows that aren’t cohesive once placed in an electronic format, further streamlining their operational processes and making their research more efficient.

While deciding to convert to electronic processes is a lengthy process with many things to consider, it’s often worth the investment. As the clinical research industry continues to evolve to a hybrid or remote workforce, it’s important to consider the best option not only for your staff, but for any participants who they are working with on a trial.

For nearly 10 years, a growing biotech company worked to develop a nitric oxide and delivery device for babies in the newborn intensive care units (NICU). The organization also needed to file the appropriate documents for Food and Drug Administration (FDA) approval to bring this combination drug and device to market.

Confronted with the myriad of complexities of the 510K FDA filing process, this company also had to address the challenges of an unreliable internal infrastructure to advance the development of the product.

Essential Steps to Consider

Engage the right partner: Identify and engage a trusted strategic partner who brings a multi-dimensional perspective – strategic and tactical to your go-to-market plan. Your strategic partner should be able to provide insightful and comprehensive regulatory guidance for meeting the stringent FDA requirements for drug and device combination products.

Identify and assess: Critical to an effective and compliant manufacturing plan is developing and implementing current good manufacturing practice (cGMP) gaps in infrastructure.

For growing biotech companies, an analysis may reveal the need for:

  • FDA filing process assistance: Life cycle FDA regulatory support from experienced, FDA veterans through the FDA regulatory communication process
  • Experienced research and development (R&D) project management: Supplemental and scalable infrastructural support in project management with specific expertise in growing life-sciences companies
  • Quality management: Expert, ready-to-contribute manufacturing personnel to create and implement a quality control system in compliance with cGMP regulations
  • Strategic advisory support: Step-by-step plan for gaining FDA approval and advancing their drug/device combination to market
  • Clinical oversight management structure: The basis for a successful internal infrastructure within the organization
  • Comprehensive R&D expertise: Multidimensional perspectives from seasoned experts in regulatory affairs, clinical research operations, project management, and quality management experts ensured advancement through the entire 510K FDA filing process
  • Seamless implementation: Access to a scalable, flexible team of consultants with experience in implementing quality manufacturing experts; chemistry, manufacturing, and control (CMC); technical writers; and FDA communication practitioners to complete the new drug application (NDA) filing

What is Your Return on Investment?

Accelerate Time-to-FDA Approval and Market Commercialization

Eliminate the usual back and forth with the FDA and advance through a complicated filing process at a much quicker rate.

A growing biotech company obtained FDA approval for their combination drug and device within three years. Five months after approval, this company was able to launch its combination drug and device to the market.

Save Time and Money

Reallocate internal resources and save valuable time and resources through an accelerated timeline.

The days of using spreadsheets to painstakingly track patient enrollment and visits, financial metrics, regulatory documents, and other aspects of a clinical trial are thankfully over for most sites. From the largest research centers to the smallest, sites now recognize that a clinical trial management system (CTMS) can be configured to their needs and can bring powerful efficiencies insights, and compliance to their day-to-day operations.

What is a CTMS?

While other products exist to assist with specific trial activities like data capture, a CTMS centralizes and streamlines the way a trial is conducted, providing an end-to-end solution for managing all aspects of a clinical trial. A CTMS can assist with:

  • Managing protocols and tracking/reporting any amendments or deviations
  • Communicating with patients to remind them of upcoming visits or procedures
  • Managing staff scheduling so that effort is aligned with needs, and downtime/overbookings are minimized
  • Promote staff training and compliance with study protocols
  • Evaluating financial needs, tracking payments to vendors and participants, and providing billing summaries that identify which costs are routine and which are part of research operations
  • Tracking and analyzing patient outreach methods
  • Streamlining recruitment tasks and providing real-time updates on participant enrollment
  • Managing the supply chain for biospecimens, devices, or other products that will be used in the course of the trial
  • Supporting regulatory compliance

Almost all CTMS products include a comprehensive dashboard that enables sites to quickly and easily delve into any of these aspects of trial management, and promptly find the answers they need.

Who needs a CTMS?

As clinical trials become increasingly complex, any site, health system, or network can benefit from the capabilities a CTMS provides.

For example, Yale University’s Center for Clinical Investigation was already using an electronic medical record (EMR) to support daily patient care. When the team learned that their CTMS could strengthen billing and patient-safety compliance, while also streamlining research operations, they chose to leverage an integration between the two technologies. Now, when a medical center patient enrolls in a clinical trial, the CTMS flags that patient and sends information about the study to the EMR. If the participant visits the ER or is admitted to the hospital, the team is alerted. The integration also sends billing designations (routine vs. research) to the EMR, as well as a timeline of protocol procedures, tolerance windows for visits, and more. The research center staff report considerable time savings because now they only have to enter relevant data once; and managing billing compliance also has improved substantially.

Similarly, Velocity Clinical Research (formerly New Horizons), a site network based in Cincinnati, found that by implementing a CTMS, the team was better able to zero in on which recruitment efforts had the biggest payoff. In the end, they were able to recoup 50 percent of what they previously spent on TV advertising and funnel the savings into more efficient strategies. They have also found that the CTMS’s built-in communication tools have reduced patient no-shows by 10 percent.

Any site that is seeking to improve enrollment diversity, upgrade billing accuracy, increase profitability, improve budget forecasting, improve communication with patients or team members, or boost participant engagement can benefit from a CTMS. Not only can a CTMS simplify routine tasks and eliminate redundancy for teams, but all of these advantages can demonstrate to sponsors and CROs that your site is an efficient and organized research partner.

What to look for in a CTMS

Ideally, a CTMS should help your staff to visualize and optimize every aspect of your research portfolio. What are some other ways an efficient and effective CTMS should function? It should:

  • Include site-centric standardized workflows. These help streamline and simplify common tasks for staff — which in turn enables them to spend more time with patients and key trial activities. Such shared resources also allow sites to learn and benefit from each other’s experiences, and create a sense of community.
  • Integrate with other technology that sites already use, like EMRs, general ledger systems, and eIRBs, eRegulatory management systems, and more. This interoperability helps reduce duplication of tasks and maximizes data quality.
  • Release frequent software updates — at least three to four per year — to ensure that sites can nimbly adapt to changing industry requirements, and that PHI and other protected data remains secure
  • Employ robust customer support teams to empower sites to do their best work with a minimum of frustration or downtime.
  • Demonstrate a high customer retention rate. This indicates that sites are not just using the latest technology, but are realizing significant improvements in recruitment, operations, finances, and regulatory compliance over time.
  • Provide two-way communication tools that make it easy to schedule and remind patients of upcoming appointments, increasing their engagement, confidence, and retention.

Advarra has two CTMS systems to assist any type of site in centralizing and optimizing their research operations. OnCore Enterprise Research System best serves academic medical centers and cancer centers that support a large research volume. Clinical Conductor is best suited for health systems, research sites, and site networks.

As your site conducts clinical trials to develop safe and effective treatments, it’s important to operate in a way to maximize time and resources. With so many research studies becoming more complex, using a centralized system to improve clinical trial management is pivotal to your site’s success. Download our eBook to examine several challenges you may face as you conduct research, and how a clinical trial management system (CMTS) can address them.

In medical device research, the determination of “significant risk” or “nonsignificant risk” is sometimes confusing, especially for those new to device research. Unique to the device space, this risk determination is not the same as a “no more than minimal risk” determination often made for studies potentially eligible for expedited institutional review board (IRB) review.

Let’s take a closer look at what significant risk (SR) and nonsignificant risk (NSR) determinations mean for medical device clinical trials.

Definitions

Here’s a quick look at the definitions provided in the Food and Drug Administration’s (FDA’s) information sheet on SR and NSR medical device studies. If you’re not familiar with this document and work in this space, I strongly suggest you give it a read for more detailed information on these risk determinations and their implications.

Under 21 CFR 812.3(m), an SR device study involves an investigational device that:

  • Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a research subject;
  • Is meant to be used to support or sustain human life and presents a potential for serious risk to the health, safety, or welfare of a subject;
  • Plays an important role in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject;

OR

  • Otherwise presents a potential for serious risk to the health safety or welfare of a subject.

Conversely, an NSR device study is one that does not meet the above definition.

You’ll notice each option in the SR definition mentions “a potential for serious risk to the health, safety, or welfare of a subject.” If the investigational device meets one of these criteria and is deemed SR, the device will require an investigational device exemption (IDE) for the study to commence.

It’s possible a study can be determined SR even when the device under investigation was previously determined NSR. An approved laser may operate at more than one energy level or with various accessories according to the clinical setting and intended application, so the potential use may range from SR while others are NSR. Another example is a scope and/or another device used in a more invasive clinical setting than originally approved, which makes the device higher risk. The determination is based on how the device will be used in a particular study, not on the device alone.

SR/NSR Determinations are not Minimal Risk Determinations

Understandably, the SR/NSR risk determination is often confused with “no more than minimal risk” determinations. A “minimal risk” study means the research involves no greater than minimal risk to study subjects (i.e., the level of risk an average healthy person would expect to encounter during typical daily experiences), and it can be reviewed via expedited review, conducted by a designated IRB member rather than the fully convened IRB. SR/NSR and minimal risk determinations are separate and distinct. Just because a device study has been determined NSR does not mean the study would be considered minimal risk. In fact, it is possible and not uncommon to deem an NSR device study as greater than minimal risk, since its use in a study may represent more risk than described in the minimal risk categories, but clearly not significant in that it represents potential for serious risk to the health, safety, or welfare of a subject (not SR).

The Study is Determined “Significant Risk” — Now What?

The key differences between SR and NSR studies are found in the IDE approval process and in the sponsor’s reporting and record-keeping requirements.

More oversight and reporting are required for SR device studies since they are riskier by definition. The study sponsor must submit an IDE application and receive FDA approval of the study. An IRB may review an SR study while FDA is reviewing the IDE application, but the study cannot begin until the agency approves the IDE. The IDE brings with it additional responsibilities with which researchers must comply; for more information, check out FDA’s Device Advice section on IDE responsibilities (IDE responsibilities are outlined at 21 CFR 812.40 and subsequent parts of Subpart C).

Since NSR device studies are inherently less risky than SR studies, the agency imposes less stringent controls. The IRB serves as the surrogate for the FDA’s review, approval, and continuing review of NSR device studies. Therefore, an NSR study may begin with IRB approval and continue without prior FDA approval.

Making the Determination

The study’s sponsor is responsible for proposing the initial risk determination. The sponsor will submit a proposal based on the regulatory criteria to the IRB for consideration. FDA is also available to help make the determination, and in some cases, it’s possible the FDA has already made the risk determination before the study reaches the IRB. In these cases, the FDA’s determination is final.

If FDA hasn’t already made the risk determination, then it’s up to the IRB to decide whether it concurs with the sponsor’s risk assessment. The IRB may disagree with the sponsor’s assessment. Here are some key items the IRB will consider:

  • The basis for the risk determination
  • The type of harm resulting from device use
  • Any additional procedures a study subject may need to undergo as part of the study (the IRB must assess the potential harm of the procedure as well as of the device itself)

It is possible for the IRB to approve a SR device study with the condition that the study may not commence until the FDA provides an IDE.

Hot Spots

There are investigational devices that in themselves do not pose harm to subjects, but their use may impose significant risk. For example, an investigational diagnostic assay may detect a genetic variant present in tumor cells, making the tumor susceptible to treatment with a targeted chemotherapy. The device itself is never in contact with the study subject, but the sampling required to obtain tumor tissue (biopsy) may be invasive and pose significant risk. Additionally, as an investigational assay that has not been validated by another “gold standard” device, it poses risk related to false positive or false negative results. If results from the assay determine eligibility for study entry or direct the clinical care of the subject (e.g., treatment assignment, dosing), false positive results would impose risks related to the side effects of the drug with little likelihood of response and delay the subject from obtaining effective treatment. Conversely, false negative results would prohibit entry into a study which holds out the prospect of benefit.

In a similar vein, an investigational continuous blood glucose monitor may pose minimal physical risk from the device itself in the form of irritation or infection from the sampling pod. But the consequences of false readings from the device are significant and life-threatening if the subject receives false readings of their blood glucose levels.

Understanding the nuances of these determinations is critical for both the sponsor and IRB alike. The SR/NSR determinations are unique as they represent the delegation of duties from the FDA to the IRB to act as its surrogate in determining the regulatory status and pathway of an investigational device. If you’re ever unsure about a determination or want more information, your IRB is a great source to reach out to for any questions you may have.

Note: This article was originally published October 31, 2017, and has been updated to include new and clarifying information.

The most recent Cancer Center Support Grant (CCSG) guidelines released by the National Cancer Institute (NCI) include a new Core component called “Plan to Enhance Diversity (PED)”. Its purpose is to show both the membership and leadership of your NCI-designated cancer center reflect the population you serve. While there are no required data tables or metrics involved at the time, it is an opportunity for your center to show you are leading the efforts to enhance the diversity of your staff. Along with this new component, the NCI is dedicating a budget to enhancing diversity. You’ll be able to grow your diversity, equity, and inclusion programs with these CCSG funds.

More About the Plan to Enhance Diversity

The new narrative requirement asks you to share your center’s plan to enhance the participation of underrepresented populations in the research workforce and center leadership. Underrepresented populations are determined based on criteria set by the National Institute of Health (NIH). Under this plan, you must show your intentions to establish and support infrastructure and resources to support career-enhancing research opportunities for researchers from diverse backgrounds. This could be training or mentoring programs, or acquiring institutional resource commitments. Additionally, you must show how you will evaluate the success of your plan and the progress made.

Consider the Diversity of the Nation Versus Your Catchment Area

Diversity is no longer defined primarily by race and gender, but has broadened to include differences in cultural backgrounds, disabilities, age, sexual orientation, race, and gender. Dr. Henry Ciolino of the NCI indicated they are required to use the NIH definitions at this time, but centers can expand the definitions of underrepresented to discuss other gender categories, sexual orientation, and more distinct race and ethnic backgrounds.

The new guidelines request that you aim to have your membership represent the population of your catchment area and your leadership represent the population of the nation. The makeup of your catchment area and the United States could vastly differ from each other so to plan for both is undoubtedly a challenge. Here are some ways to prepare for this plan:

Leverage Your Institution’s Resources

Your center likely has a wide range of resources in place to help promote diversity, equity, and inclusion (DEI). Some strategies to make the most of these resources include:

  • Working with your university’s DEI office to develop new practices for the cancer center specifically and to show how you leverage institutional resources
  • Joining university-sponsored workshops and events for DEI education
  • Reaching out to learn about the benefits of hiring a DEI administrator specifically for your department
  • Discussing the pros and cons of cluster hiring, a method of hiring used to increase faculty diversity, and how you could potentially incorporate this practice into the cancer center to promote recruitment and retention
  • Requesting funding to support initiatives benefitting the cancer center and the university as a whole

Collaborate With Your Peers

NCI-designated cancer centers are a collaborative group. Institutions are willing to share what has been done well and what remains a challenge. For example:

  • University of Oregon offers the Presidential Undergraduate Research Scholars (PURS) program, emphasizing in engaging undergraduate students underrepresented in chemistry, physics, mathematics, and other subjects
  • University of California – San Francisco (UCSF) provides opportunities for underrepresented minorities through mentorship and training programs and a diversity steering committee. UCSF also works with its community to provide engagement opportunities for underrepresented and under resourced groups age 18 and under
  • Fred Hutchinson Cancer Research Center (Fred Hutch) is one of the first to practice cluster hiring at a cancer center

Members of Fred Hutch also created the Cancer Center DEI Network. Its goal is to “develop diversity, equity, and inclusion metrics, and share best practices on recruitment and diversity programs” in cancer centers.

Use Advarra EVAL to Track Your Efforts

Advarra’s Research Evaluation System (EVAL) offers ways for you to track and narrate your institution’s efforts to promote diversity in your membership and leadership. Whether it’s grants from individual donors or investments from your university, you can track how your dollars are spent to support research and publications, mentoring the future generation, community projects, and more. You will be evaluated based on your commitment to these efforts and the progress you make. Having a robust plan today is your opportunity to set and elevate the standards for future CCSG support.

 

As we step into 2022, the clinical research landscape is rapidly evolving, shaped by the lessons learned from the COVID-19 pandemic and the accelerated adoption of new technologies. This year promises to bring significant changes in study designs, participant engagement, and the integration of decentralized clinical trial (DCT) technologies. Below are key predictions and trends for the clinical research industry in 2022.

Decentralized Clinical Trials Take Center Stage

One of the most anticipated trends in clinical research for 2022 is the continued expansion of decentralized clinical trials (DCTs). These trials, which allow patients to participate remotely, have become a critical component of modern study designs. Rather than requiring participants to visit research sites for each interaction, DCTs offer flexibility, enabling them to participate from their homes or local communities using digital tools.

This year, the focus will likely be on consolidating various trial designs—such as adaptive and decentralized approaches—into more cohesive and participant-friendly formats. This shift is not just about convenience; it significantly broadens the pool of eligible participants, particularly those from rural or underserved areas. For instance, patients living far from major academic centers may only need to travel for initial screenings, with follow-up visits and data collection happening remotely. These technologies make participation easier for a diverse range of people, enhancing inclusivity and diversity in clinical trials.

Advances in Real-world Evidence

The use of real-world evidence (RWE) in clinical research is gaining momentum, with regulatory bodies like the FDA issuing guidance on how to effectively integrate RWE into clinical trials. RWE allows researchers to collect data from everyday settings, offering a more accurate reflection of how treatments perform outside the controlled environment of traditional trials.

This trend aligns with the broader goal of making clinical trials more representative of real-world populations. Remote data collection tools, such as wearable devices, enable researchers to capture real-time data, offering insights that were previously hard to obtain. These technologies allow researchers to measure evidence out in the real world rather than in controlled clinical settings. However, the increased reliance on remote data collection also introduces challenges, particularly in ensuring the validity and integrity of the data.

Innovation in mRNA and Gene Therapy

Building on the success of mRNA vaccines during the COVID-19 pandemic, 2022 is expected to see continued innovation in mRNA technology and gene therapy. These fields are pushing the boundaries of what’s possible in clinical research, offering new therapeutic options for a range of diseases.

As mRNA and gene therapy technologies become more advanced, clinical trials in these areas will likely incorporate more adaptive and decentralized designs. This approach will enable trials to be more flexible, faster, and inclusive. The focus will be on bringing together various biotech innovations and trial designs, helping to push clinical research forward.

The Role of Local Pharmacies and Community Clinics

Another exciting development is the increasing role of local pharmacies and community clinics in clinical research. With decentralized technologies enabling remote participation, there’s a growing need for professionals in the community to support participants. Local pharmacies and minute clinics are well-positioned to assist in this process, providing services such as sample collection and basic health checks.

This integration not only brings clinical research closer to participants but also diversifies the types of clinical research sites. decentralized trials could soon involve locations rather than just traditional research offices. This shift will further facilitate participant access to trials, improving recruitment and retention.

Streamlining Data Collection in Clinical Trials

While the explosion of data from wearable devices and remote monitoring offers significant benefits, it also poses a challenge. The sheer volume of data can be overwhelming, and it’s crucial for researchers to focus on collecting only the most relevant information. This more targeted approach to data collection will help streamline the trial process, allowing for quicker and more efficient studies.

Resurgence of Clinical Research in North America

In 2022, there is optimism in a resurgence of clinical research in North America. The COVID-19 pandemic has brought clinical trials into the public eye, raising awareness and interest in research participation. With decentralized technologies making trials more accessible, the potential for growth in the North American market is high.

Consolidation of Clinical Research Sites

Consolidation of clinical research sites is another trend expected to accelerate in 2022. Similar to the consolidation seen in hospital systems over the past decade, clinical research sites are beginning to merge into larger networks. This trend allows for more consistent operations and improved data quality, ultimately benefiting sponsors and participants alike. Additionally, these larger networks can tap into more resources, enabling them to support decentralized trials more effectively.

With diversity, equity, and inclusion efforts currently at the forefront of the research community’s collective mind, we’re also seeing increased interest in community-based participatory research (CBPR). Advarra’s institutional review board (IRB) members have had many conversations with researchers about how best to approach this type of research from a participant protections perspective. So what is CBPR? And what does it have to do with research diversity, equity, and inclusion? In this blog we define CBPR, explain common ways it is employed in research, and the benefits of conducting CBPR.

What is Community-based Participatory Research?

Also referred to as community-based research (CBR), CBPR is a partnership-based approach to research that takes place in community settings and involves community members in the project’s design and implementation.

Aimed to unite researchers and communities with shared goals, CBPR typically involves diverse community members, organizational representatives, and researchers in all aspects of the process from start to finish.

Dating back to the 1980s, CBPR’s basic principles of participatory research were introduced by:

  • Health Resources and Services Administration (HRSA)
  • Indian Health Service (IHS)
  • Substance Abuse and Mental Health Services Administration (SAMHSA)
  • Centers for Disease Control and Prevention (CDC)

In 1995, the National Institute of Environmental Health Sciences (NIEHS) became the first of the National Institutes of Health (NIH) to support CBPR when it funded 15 CBPR projects.

While CBPR is not confined to research in the area of health, it is most commonly employed in that arena. Typical topics for investigation include public health issues like HIV and violence prevention, mental health issues, and chronic conditions like diabetes and heart disease. In recent years, CBPR has especially been linked to an interest in studying and addressing health disparities and inequities and the conviction that communities that partner with researchers have a unique opportunity to improve their members’ health status. Oftentimes, CBPR is employed in research aimed to reduce or eliminate racial and ethnic health disparities in under-represented populations.

Why Engage in CBPR?

There are many reasons to engage in CBPR, including:

  • Improving research quality and validity by leveraging local knowledge and local theory based on the lived experience of the people involved
  • Strengthening the research and program development capacity of the partners
  • Overcoming the distrust of communities that have historically been the “subjects” of research
  • Working to bridge cultural gaps that may exist between the parties involved

What Does it Take to Succeed in CBPR?

Success with CBPR requires full cooperation between all stakeholders in the study’s design, implementation, and evaluation. Additional requirements include:

  • Open communication among all stakeholders
  • Full transparency and free sharing of ideas and experiences
  • Trust in and among all stakeholders
  • An equal sharing of power across all stakeholders
  • A shared commitment to the benefit for the community

Considerations for IRBs

Note that CBPR introduces a new set of considerations for institutional review boards (IRBs). As a result, it’s reasonable to ask your IRB what experience, if any, it has with CBPR, and what additional or unique considerations it will include in its review of a CBPR project. Some examples include:

  • Asking additional questions (in an application) from the principal investigator (PI) and study team or sponsor to help the IRB understand the roles of community partners
  • Assessing the adequacy of community engagement to ensure respect for the community affected
  • Assessing of adequate training for community partners
  • Gathering conflict of interest disclosures from the community partners, if applicable

Clinical trials are growing increasingly complex, more expensive, and demand patient diversity. Since 2013, trial objectives have increased by nearly 16% in Phase III trials, with data points collected increasing by more than 300%. In addition, sites are experiencing frustration and confusion caused by the multitude of technologies sponsors require, with an average of six sponsor-mandated systems per trial. Frequently faced with managing different technologies for each sponsor and trial, the administrative burden on sites is enormous.

Let me give you an example. We’ve heard from study coordinators at sites who once reported being able to perform six or seven participant visits a day who now report, it’s down to two or fewer. This stems from the multiple duplicative efforts required to enter data and documents into sponsor-imposed systems that sites often already have collected somewhere else.

At Advarra, we’re out to fix this challenge. Our goal is to create a standardized, seamless integration between sites and sponsors or contract research organizations (CROs) – ultimately creating a site-centric connected ecosystem of technology supporting clinical trials. Because, at the end of the day, sites and sponsors have the same goal: bringing treatments to market safely and efficiently.

Here are a few things to know when it comes to Advarra’s BYOT philosophy:

Ensuring Patient-centricity Starts with Being Site-centric

A recent survey led by Advarra and the Society for Clinical Research Sites showed that over 60% of sites report sponsor-provided platforms or portals have increased their operational burden significantly. This is a problem for both sites and participants. When sites are overburdened, they can’t provide clinical trial participants with the level of attention they need, resulting in a lack of overall patient-centricity and an increased risk of participant dropout.

Sites play a central and pivotal role in clinical trials, but their input is often overlooked. Sites must be able to use their own integrated technology to efficiently support both site and sponsor workflows. One of the places where we see delays in clinical trials is study startup. Miscommunication between sites and sponsors is often why these delays occur. This is unfortunate because study startup time is critical to participant well-being, especially those with life-threatening diseases. By seamlessly connecting site and sponsor systems and reducing duplicate workflows, BYOT decreases startup time, accelerates research, and allows stakeholders to bring treatments to market faster.

I’d love for participants to feel more engaged with the research team, because clinical research is, of course, not possible without willing participants. Enabling research coordinators to spend less time entering data and more time with participants will allow them to feel more engaged and a part of the wider team. This can also have downstream impacts to improve recruitment activities, patient consent workflows, and much more.

Sites and Sponsors Both Benefit from a Connected Technology Ecosystem

Technology must be connected and collaborative for sites and sponsors to be most effective. When sponsors prioritize their own needs, sites must take on new administrative tasks, distracting from their ability to focus on process improvement and participant well-being. Our survey with SRCRS also found that 28% of sites spend more than 15 hours a day interacting with multiple, disparate systems, issued to them by the sponsor or CRO; yet 86% of sites prefer to use at least some of their own technology solutions to manage and conduct industry trials. It’s also worth mentioning only 8% of sites prefer to use all sponsor-issued technology.

Sponsors, like sites, are doing the best they can. They have their own processes and vendors working to centralize information across growing global teams dealing with increasing workloads, variable regulatory and data security requirements. The current process isn’t ideal for anyone. That’s why at Advarra, our goal is to standardize and integrate actions, data, and documents between sites and sponsors to make their work more productive.

Sponsors will also benefit from the connected technology ecosystem: Enabling sites to use their own technology allows sponsors to connect with existing site technologies to exchange documents, conduct remote monitoring, track enrollment, and more. As an example, automated sponsor visibility into which documents a site has already uploaded can save a significant amount of time. Sites would only need to upload new documents as a result. This is only one example of how an intelligent, connected ecosystem can be a huge time saver.

BYOT will benefit all research stakeholders from sites to participants, making safer, smarter, and faster clinical trials a reality. We need to start challenging the existing norm for clinical trials because they’re growing more complex. This calls for a process solution, not a point solution.

At Advarra, we passionately desire to have more patients look at research as a viable care option and encourage more clinicians to recognize the value in clinical trials. The increasing momentum around patient-centricity and innovation in clinical research means the time is now to reform and strengthen the site-sponsor relationship.

The BYOT initiative feels like a natural extension of what we’re already working on at Advarra. We play a role in more than 60% of all industry clinical trials and see firsthand how impactful clinical research is. There’s an opportunity to make clinical research easier for those involved, and more effective for those who rely on it for life-saving treatments, and that’s what matters to me.

Training is an essential and often required, component of conducting clinical research. Effective training teaches researchers how to ethically and compliantly execute study activities, communicate with participants, manage regulatory requirements, interact with research tools and technology, and provide proper oversight of staff. Despite their potential impact on a study’s success, training programs are often outdated, unengaging, and redundant. Therefore, it is critical to select a vendor or program encompassing not only regulatory requirements but also your organization’s goals. When shopping for clinical research training programs, use the criteria below to ensure your training is engaging, efficient, and effective.

To print this checklist, right-click and select ‘Print’. You can then use this checklist offline as a PDF if desired.

Training Method and Delivery

How do you plan to deploy and implement your training program? Whether you’re planning to host training in-person, via online platforms, or leverage a hybrid approach, below are implementation considerations.

  • End-users can complete the training on their own time, at their own pace
  • Learning management system (LMS) is user-friendly and intuitive
  • Training is repeatable and consistent across the organization
  • Training completion is easily monitored and recorded
  • Training is accessible or easily referenced at any time throughout a trial or staff tenure
  • Training is available in multiple languages
  • Training is engaging (ex: clear visuals, quizzes, polls, interactive components)
  • Training offers test-out options of some or all of the content
  • Training is available to unlimited users
  • Training is positively received by trainees and teams, with proven results

Course Content

What should the training cover? Every training course should prove detailed enough to ensure your staff and investigators can conduct research but condensed enough to encourage comprehension and completion. That means creating educational and practical course content so your team can understand but execute. Below is a list of research topics for teams new to research. First, select the topics applicable to your team. Second, evaluate the program to understand and compare how much time is required to complete the programs you are considering.

  • Introduction to clinical research
  • Human Subjects Protection and HIPAA privacy protections​
  • ICH Good Clinical Practice​
  • Regulatory and financial startup
  • Diversity and inclusion in clinical trials
  • Clinical operations and launching the study
  • Investigational product management​
  • Participant recruitment and informed consent​
  • Executing study visits and clinical trial monitoring​
  • Assessing safety and AEs, deviations & non-compliance​
  • Regulatory and financial management​​
  • Readiness for FDA inspections​

Program Credibility and Experience

The best research training programs leverage experienced training teams with experienced researchers. There are two key factors to consider when evaluating program credibility:

  • Industry-specific: Does the training incorporate industry considerations, regulatory and ethical foundations, and address common challenges research staff feel?
  • Industry-backed: Is the program content created by those with real-world research experience?

CME/CEU Credit Options

To maximize a training program’s value, the content and credentials should apply beyond a single instance or event. Below are considerations for maximizing your training investment:

  • Recognized by TransCelerate SQT member organization
  • Training content qualifies for continuing education units (CEUs) at no additional cost
  • Training status or record is logged and accepted across studies, sponsors, or staff

More new-to-research sites are engaging in trials to reach patient populations, achieve enrollment, and startup objectives, and adapt to site staffing shortages and turnover. Unlike other offerings available in the market, Advarra’s Clinical Research Conduct Training integrates required research topics with an operational mindset to ensure researchers can quickly turn knowledge into practice while successfully and compliantly conduct a study, all within a third of the time required for traditional programs.

The amount of detail required in an audit may vary – ranging from an executive, high-level summary with detailed observations, to an exhaustive, all-inclusive report. A report may only include detailed observations, but it might also provide a list of all the documents reviewed, describing all processes reviewed in detail, along with any audit observations. While it’s critical for the auditor to understand the expectations of whom they are writing the report for, an impactful clinical audit report includes critical information to describe the status of the auditee in a factual way while excluding information that does not add value to the audience.

As defined in ICH E6 (R2), an audit is “a systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor’s standard operating procedures (SOPs), good clinical practice (GCP), and the applicable regulatory requirement(s).”

The audit’s output and report are written evaluations of the audit’s results. A typical audit report contains the following sections:

  • General information, including who was audited, what was audited, and where the audit occurred
  • Executive summary
  • Summary of observations (typically in table format)
  • What regulations and guidance the audit was conducted against
  • Audit scope
  • List of staff involved/interviewed in the audit
  • Documentation reviewed during the audit
  • Narrative section for describing topics covered and facilities reviewed during the audit
  • Detailed observations

Industry standards are shifting to focus on building quality into studies and determining critical-to-quality factors (ref. ICH E8 R1) and an appropriate risk management approach (ref. ICH E6 R2). The audit report should identify how quality and risk management are managed throughout the entirety of the study conduct.

Critical Steps: Executive Summary

The executive summary succinctly describes the audit’s key points. This gives the audience — especially senior management — the key information and audit outcome. It should include whether it is a routine or for-cause audit, site/vendor identification, dates of audit conduct, and if there were any significant concerns or major findings. Research teams need to include a summary of these findings and an overall statement of compliance and acceptability. They should also indicate if the audit was conducted as planned, and if not, it should state the reason for any deviations from the audit plan.

Critical Steps: Observations

Observations are graded relative to the level of non-compliance or deviation. An example of this is formatting observations as critical, major, minor, or recommendation. The definitions of these are usually described in an audit’s SOPs or detailed in the report template. The definitions are based on the impact or potential to subject safety, data integrity, and the protection of human subject rights.

Multiple major audit observations may result in a systemic critical audit observation, even though each of the major observations are not “critical” themselves. Similarly, the same can be said for multiple minor observations, which may result in a major observation. Potential critical observations must be escalated – usually within 24 hours – to a client, so they can take appropriate action right away. Ideally, reports should be reviewed to ensure consistent observation grading and categorization, providing an objective perspective to verify the report is complete and clear.

Observations should be structured clearly. Typically, they start with an overarching statement of the non-compliance, followed by a detailed description of the issue with examples, and references for non-compliance (e.g., applicable regulations, guidelines, SOPs, protocol, or other study-level plans). The details provided must be factual and not based on subjective information.

When describing the critical and major observations, it’s important to also provide an impact statement. This details how the observation potentially impacts patient safety, their rights, data integrity, etc. Critical and major observations require root cause investigation and corrective and preventive action (CAPA), as ICH E6 R2 addendum section 5.20 requires. Minor observations usually only require correction. Observations must stand alone as the auditee will likely receive them separately from the report. The details in the observation must allow for the auditee to understand the observation and enable them to take action to rectify it.

Critical Steps: Trending

In addition to grading observations, observations should also be categorized – and subcategorized if need be – so trending can be performed. Trending is important to understand the organization’s health, giving visibility to repeat or systemic issues. Instead of raising an observation for each individual discrepancy, similar issues should be grouped in one observation wherever possible, instead of surfacing an observation for each individual discrepancy. For example, instead of creating an observation for a missing ethics committee (EC) letter, and another observation for a missing protocol signature page, these can be grouped under investigator site file/essential documents.

Critical Steps: Narrative

The narrative section of the report is where there are differences in the level of detail required by each organization. A best practice is to evaluate what would be value-added for a particular audit and understand the audience who will read the report. Providing too much information may take away from the site’s or vendor’s status. Some examples include:

  • For a site audit, it would be relevant to detail the impact of COVID-19, as this could have resulted in missed patient visits or procedures. Facilities also may not have been available for routine patient visits, monitoring visits, or audits
  • For a site audit, a detailed description of the facilities and processes relevant to clinical trial’s conduct (e.g., pharmacy, investigational product administration or infusion of investigational product, laboratory sample, and processing) must be included
  • For a vendor audit, it may not be practical to describe company background/mergers in detail if the clinical or procurement team can be easily obtained from the internet
  • The clinical team may be familiar with the procedures necessary in the protocol; therefore, each step of a procedure does not need to be described in detail, but rather a high-level description would suffice. If any issues with the process or procedure are identified, the narrative references in the observation section rather than including that deviation detail in the narrative
  • Noting each reviewed narrative document can distract from the overall activity of the electronic trial master file (eTMF) or investigator site file (ISF) review activity. Staff can note their review for the eTMF and ISF and list any issues in the observation section or on a separate addendum to the report

Providing the correct level of information in an audit is a delicate balance. Critical to successful audit report writing is to understand the report’s audience, the essential information needed for the audience – site or vendor – to execute the plan, as well as sufficient detail allowing for a full understanding and a chance for observation correction.

Gene therapy studies are a relatively recent addition to the world of clinical research. As a result, the unique requirements for these trials are new to many of the sponsors and researchers undertaking the studies. One of these unique requirements is the institutional biosafety committee (IBC) review.

IBCs in clinical research focus on reviewing safety aspects of research involving engineered genetic material. They are responsible for assessing the risks associated with genetic modifications and experimental procedures, as well as occupational and environmental safety. While institutional review boards (IRBs) focus on protecting the rights and welfare of human beings participating in clinical research, IBCs, on the other hand, are tasked with protecting study personnel, the community, and the environment from exposure to engineered genetic material and other biohazards. An IBC may also advise the IRB in assessing potential risks to the study subjects.

IBC requirements can be challenging for sponsors in that many people have not had much, if any, experience with such committees. Another potential issue is IBCs at academic institutions often focus primarily on preclinical and non-clinical work; they may have less experience or expertise with clinical trials.

Gene therapy study sponsors are best served when their IBC and IRB reviews are aligned. There may be some overlap in the two committees’ responsibilities, and at some institutions, they may share the same personnel. However, a second review entity adds events and complexity to study startup timelines, potentially delaying the start of a clinical trial.

Fortunately, sponsors have the opportunity to streamline IRB and IBC reviews by coordinating the activities of these two committees via a vendor that offers both resources in-house.

Two Committees, One Vendor

Making use of dedicated, highly experienced review resources like those offered by an expert vendor can facilitate more streamlined processes, providing the opportunity for faster trial startup. Leveraging such resources to coordinate the activities of two separate review committees is an especially smart move for efficiency. Consider:

  • Relying on individual and locally administered IBCs and IRBs involves different submission deadlines, meeting schedules, policies, and procedures, increasing the likelihood of review outcome variability
    • On the other hand, working with a centralized expert allows for optimal coordination
  • A dedicated vendor offers the benefits of a dedicated team
    • Whereas the local committee staff members typically wear multiple hats and may be under-resourced
  • With coordinated IRB and IBC reviews, a single vendor can eliminate the duplicative reviews characteristic of unaffiliated IRBs and IBCs
  • With the key stakeholders on the same team and part of the same organization, aligned decision making is far more likely across the two committees

Together, IBC and IRB services offered by a single vendor are typically designed and built from the ground up to work well together. You can reasonably expect to work with a single point of contact for both committees, enjoy the benefits of state-of-the-art technology to help streamline submissions, and allow up-to-the-minute review of process status. And you will undoubtedly find fewer hurdles standing between you and your study’s startup goals.

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