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The discussion on decentralized clinical trials (DCTs) has been brought to the forefront in the wake of the COVID-19 pandemic. Most notably, almost all conferences I’ve attended recently have a session or track allocated to the topic. However, a few key issues are still missing from this discussion. Firstly, the conversation should pivot to how we can make clinical research participation as flexible as possible for people. Secondly, the technology underpinning a lot of decentralized trial aspects needs to be re-engineered from both a usability point of view so we instill confidence in those using it, and an integrated point of view so we don’t repeat the same administrative hurdles felt in today’s traditional trials. Finally, if sites are to evolve, their business must recognize the research direction and start implementing change now to facilitate a hybrid model between decentralized and brick-and-mortar solutions.

The Magic Word: Flexibility

Participants need to have flexibility and choice in their trial participation. Making clinical research 100% decentralized is not what participants want. According to data from non-profit, Fair Health, telehealth claims have steadily declined since the pandemic has eased and in-person services restarted. This suggests when it comes to health and clinical research, people still want physical options rather than solely relying on tech. The model likely to run in the long term is a hybrid between physical sites with in-person appointments and the use of decentralized tools. Telehealth is part of our future lives, but it won’t necessarily dominate. Having said that, telehealth usage is significantly higher now than before the pandemic. There is an opportunity for site businesses and tech companies to work together on solutions, paving the way for more merger and acquisition (M&A) activity in the space. This hasn’t happened yet because the valuations of these two types of businesses are not aligned. As we see the gap between the two sectors close, it will be easier for business opportunities like this to come to the fray and the site industry to consolidate along tech lines.

Improving Tech Will Improve Confidence

The technology used in decentralization tools is not at a level consumers feel comfortable with. When looking at the technological maturity of the health sector compared to other industries like energy, financial services, and consumer, the consulting firm BCG found it lags behind. Most devices feel like they are still in beta mode. As consumers, we are used to seamless user experiences with the tech options we interact with every day. For example, the likes of Amazon and Grubhub have set the bar very high. We must also consider the people using these tools. The age of people taking part in clinical research tends to skew older and from lower social-economic backgrounds. This makes it more difficult for them to access digital infrastructure. It also requires a higher standard for usability needs. Customers need to have confidence in the tech we’re asking them to use. In turn, they will have confidence in us as service providers. We need to re-engineer the user interface (UI) of health technology down to simple use cases like keeping an eDiary.

Changing Roles of Sites

The COVID-19 pandemic provided motivation to turn to more decentralized options in order to keep clinical research moving. Even though I recognize and agree with this trend, the question remains: How quickly will it accelerate in a post-COVID world? We must remember this industry works on evolution rather than revolution so my bet is it will be a slower burn than some people think. Nevertheless, sites have a responsibility to keep up with this shift. Site employees often act as a first line of support for participants—especially when tech goes wrong and participants need support. In fact, in some cases, I’ve seen instances where only site staff can contact tech providers’ helpdesks instead of participants. We need to ensure our employees feel comfortable with the technology we’re asking participants to use. In some larger sites, I predict entire roles dedicated to supporting coordinators with tech needs.

Improving access to clinical research is in everyone’s interest. The race to find a COVID-19 vaccine was an incredible awareness-raising moment for the industry. It raised awareness among tech providers who are solving age-old problems in the industry with new solutions. Equally, it raised awareness of taking part in clinical research among the general public. If we capitalize on this momentum and make a meaningful impact on the industry going forward, we should embrace a new flexible model. At site level, we have a unique advantage of direct interaction with trial participants and are a firsthand witness to their needs for a positive trial experience. We will always need physical sites when it comes to dedicated clinical research. Their role just might look slightly different. People working at sites need to show leadership now and embrace digital change, otherwise they will be left behind. How is your organization adapting and succeeding in a decentralized landscape? Hear from Dr. Paul Evans and other industry leaders on practical strategies to implement moving forward in our on-demand symposium, Adapting, Adopting, and Succeeding in a Decentralized Landscape. Watch now. [optin-monster slug=”swhbvwhsjfuiymifuhgb”]

One of the fastest growing areas in clinical research is clinical trials involving recombinant DNA, or gene therapy research. It’s an exciting space that is full of promise, but because of the risks involved, it’s also a highly regulated space. As many clinical research professionals are new to gene therapy research, confusion is common regarding the regulatory requirements.

When is IBC Oversight Needed?

While clinical research professionals are familiar with the role of the IRB to protect research subjects, most are unfamiliar with the added need for an Institutional Biosafety Committee (IBC) to review the risks associated with engineered genetic material in clinical trials. NIH Guidelines require IBC review for any genetic engineering research, including gene therapy research, that receives NIH funding or takes place at sites receiving NIH funding. This means any funding—even $1 of NIH funds for the site or the study means the study must be reviewed by an IBC.

Studies and sites completely independent of NIH funding may still require IBC review if the R&D that led to the investigational product was funded by the NIH. Even if there are truly zero NIH funds involved, IBC review is a best practice: NIH Guidelines state that “individuals, corporations, and institutions not otherwise covered by the NIH Guidelines are encouraged to adhere to the standards and procedures set forth” in the Guidelines (Section IV-D-1).

The rationale behind IBC review is to ensure a thorough risk assessment is performed regarding the risks associated with the genetically modified materials and a comprehensive risk mitigation plan is in place prior to conducting the research. Gene therapy research requires safety measures to ensure that research participants and study staff as well as the community and the environment surrounding the research site are not harmed by the modified genetic material or the infectious agents that may be utilized to deliver them. An IBC can help researchers utilize the appropriate safety measures to ensure research is conducted safely and responsibly.

Key Words for Determining Whether IBC Review is Needed

Certain key words can aid in determining if IBC review is likely required. The following is a list of common terms found in research protocols requiring IBC review:

Likely Needs IBC Review
Viral vector / Virus based gene delivery vector Common viruses include: • Adenovirus (Ad) • Adeno-Associated Virus (AAV) • Retrovirus • Lentivirus (e.g. HIV based vector) • Herpes virus (HSV) • Pox virus (e.g. vaccinia, canary pox or fowl pox)
Genetically modified or reprogrammed immune cells/white blood cells (e.g. CAR T cells)
DNA vaccines
Plasmid
Genetically modified
Recombinant DNA (rDNA)
Messenger RNA (mRNA)
Synthetic Nucleic Acids
Gene editing: CRISPR-Cas9, TALEN, Zinc Finger Nuclease (ZFN)
Gene silencing: Micro RNA (miRNA), RNA interference (RNAi), short hairpin RNA (shRNA), silencing RNA (siRNA)
Institutional biosafety committee (IBC)

The following list includes terms associated with types of clinical trials that increasingly utilize genetically modified materials and, in such cases, may require IBC review. The latter list includes terms that generally do not point to requiring IBC review.

Maybe Needs IBC Review (need more info about the design of the investigational product)
Vaccines, especially for cancer and infectious agents (e.g., Ebola, SARS, MERS, Zika, etc.)
Immunotherapy
Cellular therapy
Regenerative therapy

Not Likely to Need IBC Review
Genetic screening or testing (e.g., 23 and me)
Gene/genome sequencing
Monoclonal antibody based therapy (Anything with a name ending in “Mab”)
Tests that do not involve extraction and manipulation of genetic material (e.g., routine blood or urine tests)

Additional Help in Determining Whether IBC Review is Necessary

If you’re still unsure about whether your study requires IBC review, contact your IBC office for assistance. A quick call or email can likely resolve the question. If your site or institution lacks an IBC, or your IBC lacks the expertise to review a particular study, feel free to contact Advarra’s commercial IBC service. Our panel of experts is comfortable with the diverse challenges associated with genetic engineering research regardless of whether it is clinical, pre-clinical, non-clinical.

IBC review shouldn’t be an obstacle to conducting innovative research. Rather, consider the IBC your guide to understanding proper safety measures with gene therapy research. Gene therapy is inherently risky, and IBC review helps make sure those risks are minimized and properly managed.

Return on investment (ROI) is a critical metric for clinical research leadership. Determining how your organization is leveraging investments, from both outside sources and from within your institution, is key to securing future funding. Listed here are questions to ask as you evaluate your ROI and demonstrate the true value of your research.

1. How many publications did team members within a specific program produce last year?

Examining your program-wide research output shows how members, colleges and departments are collaborating to make the most of research investments. This data can be extremely useful for progress reports, sharing with your external advisory board, or within the program itself.

2. Who are my top-performing staff?

Identifying those who contribute to key accomplishments, such as high-impact publications or securing significant grant funds, is a great way to measure your research staff’s impact. By determining who appears at the top of the list in multiple categories, you can truly single out and reward your top performers.

3. What highlights or stories did we produce from grants in the past year?

Creating a process to document your successes is invaluable to your organization. Indicating the positive outcomes, such as honors your research organization earned or media coverage, can be a powerful tool to demonstrate your research’s impact on your community and the industry as a whole.

4. What research accomplishments were supported by which cores?

Shared resources within a research institution, or cores, play a big role in the research and may result in a publication. Determining which cores support the most publications can identify the most valuable cores within your organization. This information can be useful when making the case for additional resources.

Answering these questions can provide valuable insight into your organization’s research output. However, calculating these metrics can be a frustrating, time-consuming task for clinical research leadership. Since grants, publications, programs, and other research data are often scattered across the institution, it can take days, weeks, or even months to gather the necessary information. If your organization is struggling to gather this data, a research evaluation and reporting system can help.

Showcase your research ROI to the NCI, NIH, and internal leadership. Learn more about EVAL.

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

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

Components of Patient Centricity

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

Study Design

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

Retention

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

Communication

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

How eConsent Aligns with Patient Centricity

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

Enhancing the Participant Experience

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

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

Increasing Trial Success

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

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

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

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

I recently had the privilege of both presenting at and attending the 2021 Alliance for Regenerative Medicine (ARM) Annual Cell and Gene Meeting on The Mesa conference. This conference is the largest of its kind in the world, bringing together over 400 member organizations and other participants with a distinct focus on advancing innovative cell and gene-based treatments and cures. Advarra is the only independent institutional biosafety committee (IBC) represented in the ARM membership; we had the honor of receiving an invitation to present at the conference. Here are my takeaways from an amazing week of discussions.

Exponential Growth

At the conference, one thing was clear: Cell and gene therapies are growing and an increasingly important part of the overall healthcare system. No longer like science fiction movies, FDA-approved gene therapies are making real differences in people’s lives today. The number of investigational new drug (IND) applications for gene therapy-based treatments have grown exponentially prior to COVID and are holding steady at a high level despite COVID.

Source: “A Changing World in Gene Therapy Research: Exciting Opportunities for Medical Advancement and Biosafety Challenges,” Applied Biosafety.

A report released at the Cell and Gene conference indicated nearly 600 companies in North America and nearly 1,200 worldwide are developing innovative treatments and using cell and gene therapy rather than traditional drug- and device-based modalities. Advarra supports the majority of these companies through our independent institutional biosafety committee (IBC) review services, and we are looking forward to supporting more innovative sponsors in the months and years to come.

Manufacturing and Distribution is a Challenge

We have delivered traditional pharmaceuticals and devices for decades. Good manufacturing practice (GMP) is an established discipline, and we understand the mass production, packaging, and distribution of pills and vials. With complex gene therapies based on an individual’s unique genome, the old paradigms of a central manufacturing plant are out the window. Reagents, viral vectors, and complex chemistry, manufacturing, and controls (CMC) are needed on-site where the participant is located. Many gene therapies involve a technique where the participant’s own cells are altered and then re-infused back into them to generate the desired resulting outcome (e.g., immune cells now know how to attack cancer in the body). This presents a logistical challenge for the industry, as cell and gene therapies are increasingly reaching beyond the halls of large academic medical centers (AMCs). How do you get the manufacturing plant to the place where the participants are?

A good portion of the collaborative discussion at the conference surrounded how to solve these supply chain and manufacturing challenges. Several companies are in the process of developing mobile cell product manufacturing labs. These mobile labs (some the size of a small car) would enable small rural community health centers to offer the same innovative and life-altering treatments as large centers in urban areas. Other innovators are working on adapting participant-derived treatments by using pluripotent stem cells (PSCs) (the ones that can turn into any other kind of cell) from healthy donors and applying genetic manipulation to those healthy PSCs at a more central location, then rapidly ship the modified cells out to the patient for infusion.

For now, participants often must travel to the manufacturing facilities. However, the take home message from the conference is the cell and gene industry knows this paradigm must change and is working rapidly to prepare for the future.

Amazing Cures

Unlike a good number of traditional drug-based “therapies” treating symptoms over a long period of time, or working to suppress but not eliminate the underlying condition, cell and gene therapies offer the possibility of a one-time treatment and cure. There were multiple examples at the conference; I’ll share one for illustration. Orchard Therapeutics presented their work in metachromatic leukodystrophy (MLD). Kids with this condition, caused by a rare genetic mutation, experience debilitating neurological and muscular issues. This results in difficulty moving, eating, and eventually leads to paralysis. Nearly half of children diagnosed with the condition die within five years. There is currently no cure – only protracted, expensive, and invasive treatments.

Orchard’s gene therapy targets and corrects the gene mutation which causes MLD. Their research has preliminarily demonstrated an ability to deliver a permanent and lasting cure. Amazingly complex science with a truly heartwarming result: The ability for a child to live a normal life. And this was just one example of many. It makes me proud to represent Advarra, knowing we are playing a direct and important role in advancing life-giving science.

It is such an exciting time to be involved with clinical research. We are on the cusp of curing many of humanity’s most devastating diseases. As cell and gene passed therapies emerge to take on a larger portion of treatment options, Advarra will continue to play an active and engaged role in optimizing clinical research for the advancement of human health.

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

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

What is Quality?

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

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

The Challenge of Implementing a Clinical Trial Quality Management Plan

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

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

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

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

Conclusion

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

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

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

During the week of October 5-8, more than 1,700 Advarra technology customers gathered virtually for the Fall Onsemble Conference. A customer-exclusive conference, Onsemble is designed to bring together members from the research community to network, learn, and discuss strategies to keep research moving forward. With panels, sessions, keynotes, and virtual networking, members had numerous opportunities to draw inspiration for their respective institutions.

The main theme woven throughout the conference was site centricity and how attendees can go above and beyond while building connections to make research safer, smarter, and faster. New to this Fall’s conference was the CORE community, consisting of research professionals using Clinical Conductor CTMS. The CORE and Onsemble Community unification signifies a united community of research professionals with the mission to advance human health.

A Deep Dive into Advarra’s Products and Services

Jonathan Shough, President, Technology Solutions; James Wurdeman, Chief Product Officer; and Orla Mester, SVP Professional Services addressed the largest community of research professionals with a deep dive into updates on Advarra products and services. Stressing the importance of site centricity, a main theme throughout the presentation was building and enhancing end-to-end research site workflows. To make this a success, the industry needs to shift to a new model, leveraging enterprise site technology instead of burdensome systems provided by sponsors and CROs. Throughout the conference, Advarra leadership stressed the need for this shift, encouraging sites to adopt new technology.

Additionally, Mester stressed the importance of getting the most out of your technology investment with Advarra Professional Services. Industry-wide, sites are experiencing staff shortages, lack of skilled resources for study activation, and a changing operational landscape. As we move toward remote capabilities, Mester noted in the next year, 65% of contract research organizations (CROs) and 85% of sponsors will adopt eConsent, and 80% of all ongoing trials will have a remote element.

By leveraging Advarra products and services and outsourcing services, sites can bridge the workforce gap, improve activation timelines, and focus on the research at hand.

Creative Approaches to Accelerate Study Startup

Efficient study startup approaches continues to be a hot topic in the clinical research industry. In a panel discussion, led by Advarra’s Robann Cunningham; Neal Herman, Syneos Health; Clare Grace, Parexel; and Alison Lakin, University of Colorado Denver discussed methods to improve both study startup and industry collaboration.

The main point woven throughout the presentation included decentralized clinical trials (DCTs). Panelists noted if there were any silver linings to the COVID-19 pandemic, it was the industry getting serious about adopting decentralized modalities to efficiently conduct clinical research. Through DCTs, sites can free upreduce operational burdens and become more participant-centric. Paired with site technology and outsourcing startup activities, sites are well-positioned for streamlined study operations, allowing them to focus more on the participants in each trial and how they can benefit from the research at hand.

Tracking and Reporting Minority Clinical Trial Accruals

In his presentation Tracking and Reporting Minority Clinical Trial Accruals, Nick Fisher of Siteman Cancer Center outlined how to best track, calculate, report, and share minority clinical trial accrual rates. In the past, Fisher explained his site’s approach was to send a physical letter to principal investigators (PIs) noting their accrual goals compared to the targeted goal. However, there were no useful comparison tools or benchmarking tools in that approach.

Now, research staff at Siteman use OnCore to send out automated emails PIs, highlighting key information for accrual, including total accrual in the past 12 months and total minority accrual in the same timeframe. This helps PIs compare their work to minority accruals in other areas of the clinic, improving visibility and accountability throughout the organization.

Fisher outlined additional initiatives at Siteman, such as utilizing a community advisory board. This resource is designed to allow PIs to come in, present their studies to a board, and receive feedback on how their trial is or is not friendly to specific populations. Additionally, PIs receive feedback on what they can do to be more accessible and reach a broader population, helping more participants along the way. Through improved tracking efforts and resources such as this board, Fisher noted these opportunities create a culture to drive change within their organization.

These presentations were just a few of the more than 35 sessions at the four-day conference. Though virtual, the conference provided a plethora of valuable opportunities for sites to learn, network, and collaborate to truly move research forward.

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

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

Form a Strategic Plan

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

Ask the Right Questions

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

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

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

Involve Multiple Organizational Levels

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

Learn about the Advarra Insights reporting and analytics platform

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

Ask More Questions

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

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

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

Use Data to Drive Daily Work

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

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

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

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

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

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

What’s a DSMB’s Role in Research?

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

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

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

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

Why is DSMB Independence Important?

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

Eliminating the Perception of Bias

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

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

What is Charter Development?

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

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

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

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

A well-managed, participant-centric clinical trial has many moving parts, and easy access to the right technologies, services, and community of experts can make a significant difference. To meet this need, solutions providers have taken the approach of consolidating the knowledge, technology, and supporting services needed to efficiently conduct trials.

This approach eliminates the need for sites to perform ad hoc searches for technology and services, providing them with access to a comprehensive, technology-connected clinical research ecosystem. By addressing key challenges for research sites, this enables safer, more ethical, compliant, and efficient development of potentially life-changing therapies.

Choosing a Technology-Connected Research Ecosystem

When conducting a successful clinical trial, it takes a combination of staff, participants, and supporting technology. However, given the growing complexity and lower time to market expected of many current studies, sites and sponsors must find ways to conduct efficient and collaborative trials while meeting strict regulatory requirements. One way to do so is through adopting a connected clinical research ecosystem. There are many facets of a connected ecosystem, all aiding in a successful clinical trial.

Industry-Trusted IRB/IBC Review Services

The main purpose of the institutional review board (IRB) is to protect the participant’s rights and welfare. Meanwhile, the institutional biosafety committee (IBC) protects participants, study staff, and the community from risks associated with genetically engineered treatments and vaccines. While IRB oversight is required for most research involving human participants, IBC oversight is only required for research involving investigational products containing engineered genetic material.

While some sites may have a local IRB and/or IBC already onsite, it’s become increasingly important to also identify an independent review partner, particularly for industry-sponsored research. Specific to multisite studies, independent IRBs and IBCs provide more efficient review processes, which is appealing to industry sponsors.

So how do you find the right fit for your organization? Look for an independent IRB (and IBC as appropriate) with processes ensuring efficient quality documentation delivery while providing dedicated, attentive service and expertise to support your research. Additionally, choosing electronic systems will enable smarter and faster workflows while maintaining high transparency and quality standards.

Here are some basic criteria for evaluating the review services of an IRB or IBC:

Review the IRB or IBC meeting schedule to ensure it meets your researcher’s and stakeholder’s needs
Ensure use of electronic tools and dedicated staff for easy, efficient study administration. Their tools should be appropriate for your internal workflows
Request a demo and training, confirming there is an application programming interface (API) connection for added efficiency, if appropriate
Review the committee’s current roster to ensure there is appropriate expertise to review the types of research your institution conducts
Request a dedicated point of contact so you have a direct line of communication for any potential questions or issues

Finally, check if the Food and Drug Administration (FDA), Office for Human Research Protections (OHRP), or other regulatory authority has audited your IRB in the past. If so, it is a good sign if no FDA Form 483 was issued in the past 10 years or more. In addition, verify that they are registered with OHRP and FDA. It is also a good indicator of reliability if the IRB has full accreditation with the Association for the Accreditation of Human Research Protection Programs (AAHRPP) and a long history of compliance.

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Clinical Research Management Technologies

Clinical research technologies can enhance trial performance, empowering clinical sites to streamline workflows at each study stage. This results in time efficiency, less effort, and reduced costs. It is important to verify the potential clinical research technology and services provider includes a full suite of technologies to optimize study processes. At a minimum, make sure your vendor offers the following technologies.

Clinical Trial Management System (CTMS)

The CTMS platform is designed to enhance study startup, participant management, finance, compliance, oversight, reporting, and more. A CTMS configures study needs and is scalable to any organization’s size or decentralized complexity. Additionally, the CTMS should also enhance the trial management process, compliance assurance, and finance control. Such a trial management system should also allow oversight across multiple departments, sites, and networks.

Site-centric clinical trial management systems include remote workflow-enabling options for two-way texting, secure video, and instant payments. Not only is this easier for the participant, a comprehensive CTMS also simplifies recruiting, visits, and the stipend payment process. The CTMS must also be comprehensive and effective over a multitude of trials to ensure the solution is likely to support your organization’s needs.

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eClinical Solutions

eClinical solutions are participant-centric technologies designed to streamline source data collection, enhance regulatory management, and improve consent workflows. Adopting eClinical solutions such as eSource, eRegulatory management, and eConsent enables researchers to move away from costly paper processes, saving time and money in the process. These electronic systems help an organization become more efficient, compliant, and connected.

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Professional Services

Any services accessible within a trial ecosystem should cover process improvement, establish best practices, and increase research productivity. The right services enable your organization to streamline study activation, maximize technology investments, alleviate administrative burden, and add breakthrough efficiencies with technology-enabled professional services. Below are some examples of specific services and consulting to look for.

Coverage Analysis

Tailored to a specific organization’s needs, a coverage analysis is designed to prevent workflow bottlenecks, reduce administrative burden, and streamline the study activation process. A completed coverage analysis may be delivered into a CTMS environment, matching study calendars and eliminating the need for duplicate data entry.

Budget Negotiation Services

Budget negotiations are typically one of the most time-consuming startup activities. By enlisting a budget negotiation service for help, organizations can accelerate timelines, alleviate budget negotiation burdens, and meet funding goals.

Research Staffing Solutions

Engage research professionals to fill short- and long-term core team roles on-site and remotely, keeping your clinical operations on track in the wake of staff turnover or unforeseen project needs. Unlike other consultants or outsourcing firms, our unique product expertise and ability to fulfill multiple roles contribute strategic advice and follow-through skills to complete projects.

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Global Consulting

Partnering with a consulting team provides a proactive, comprehensive approach to navigating the research and development environment, ensures compliance, and mitigates risk throughout your trials.

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Expert Community

A major part of a healthy clinical research ecosystem is having a large community of clinical trial experts to network with, identify potential roadblocks, and celebrate successes in conducting efficient research. Just as important is the scope and quality of their connection to the larger clinical research ecosystem.

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Increasing Speed, Quality, and Revenue

The key to delivering a higher quality result faster, while increasing revenue to your organization, often involves combining technologies and services in the right way with your own study plans. Accessing the right choice of pre-vetted technology, supporting services, and seasoned experts provides a significant advantage. This is especially true with tailored technology and services for an organization’s specific needs. An organization with a wide range of pre-vetted technologies and services, paired with a knowledgeable team, provides much-needed guidance and assistance in a well-connected and resourceful ecosystem.

Are you using electronic source data capture?

According to ICH GCP 5.18 guidance, the purpose of trial monitoring is to verify each participant’s wellbeing is protected, data is accurate, and the trial is conducted in compliance with any regulatory requirements. Additionally, the Food & Drug Administration’s (FDA) Guidance for Industry establishes expectations for electronic source data capture, review, and retention. This guidance aims to help ensure source data’s reliability, quality, integrity, and traceability from electronic source to submission.

With today’s complex trials, the expectation of gathering faster results in an increasingly decentralized environment is only increasing, imploring investigators to implement electronic source data capture systems. How can researchers ensure this is done correctly? Leveraging the right technology to standardize a compliant process for source data capture is a proven way to reach these goals.

Why eSource is the ideal enabling technology

While electronic source data collection is not new, collecting source data in a variety of settings in a compliant manner is. With this in mind, how does one maintain data quality and integrity while ensuring participant safety and staying compliant?

The key is creating a truly decentralized process by incorporating electronic source data collection and management system into your workflow. Not to be confused with the more sponsor-centric process of an EDC, a comprehensive eSource system enables even the largest site networks and health systems to capture data from multiple locations immediately, automate quality checks across the enterprise, enable remote monitoring, and fast-track approvals from any location with a 21 CFR Part 11 compliant eSignature process. Beyond capturing screening and visit data effectively, a complete eSource system also helps team members, reviewers, and approvers to engage in 21 CFR part 11 compliant source data capture and management workflows with greater ease.

Compliant source data collection is essential to the validity and success of a clinical trial. Key contributors to a compliant decentralized process using a fully capable eSource system include:

Ability to easily build forms and establish a consistent process
Intuitive 21 CFR Part 11 compliant workflows for entering data into the eCRF from any location
Alerts and reminders focused on maintaining data capture quality and integrity
Fast assignment to a remote clinical investigator review and time stamped eSignature
Secure access for a remote monitor to conduct source data verification (SDV)
Process and status tracking across locations, with source document retention and full audit trail

The benefits are clear

Beyond the benefits of greater efficiency and savings over the cost of paper source documents, utilizing electronic source data capture also ensures a consistent ALCOA process. A key factor is the integrity of “contemporaneous” data entry with eSource during direct point of care/assessment of a human subjects. This decreases human error that often results from entering source data at a later date/time in a paper format. An eSource system actually enforces best practices by having researchers enter data in real time while assessments are being performed and collected, while the audit trail date/time stamps everything, better aligning the workflow for data integrity and ALCOA.

Introducing a comprehensive eSource system is key to keeping remote information organized and compliant. A consistent and compliant electronic process enables centralized oversight over many locations. Additionally, it enhances data integrity, encourages remote monitoring, enables timely eCRF completion, delivers faster payments, and promotes efficient remote procedures across your entire research organization.

A complete electronic 21 CFR Part 11 compliant source data system enables study workflows to capture source data in real-time, enhances data quality, allows remote monitoring, and optimizes site operations. This is important for ensuring a trial adheres to the Food & Drug Administration’s (FDA) guidance. Learn more about how Advarra eSource can support your remote workflows and compliance.

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

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

Regulatory Parameters and the Challenge of Inclusion

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

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

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

Access, Justice, and Scientific Value

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

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

Translation Processes

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

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

An Opportunity for the Research Community

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

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