Elevating our consulting capabilities to accelerate clinical research and bring therapies to market sooner.

YourEncore, a leading provider of drug development and commercialization advisory and consulting services to the biopharmaceutical industry, is becoming part of Advarra. YourEncore, combined with Advarra’s consulting services, provides unparalleled life-sciences consulting expertise worldwide to solve mission-critical challenges and bring life-changing therapies to market sooner. Through our integrated solutions that safeguard trial participants, empower clinical sites, ensure compliance, and optimize research performance, Advarra has the talent, tools, and technologies to accelerate the research and drug development journey for our clients.

Advarra Consulting serves biopharmaceutical companies, device manufacturers, academic medical centers, health systems, and institutions in nearly 60 countries. YourEncore exponentially increases the breadth and depth of expertise with industry practitioners who have extensive hands-on experience to provide effective solutions across the product development cycle. The combination of Advarra Consulting and YourEncore creates an agile life sciences advisory and consulting practice with the capability to swiftly mobilize resources and support client engagements worldwide.

Our combined deep bench of expert consultants offers something unique—they come from some of the most respected life sciences companies in the world with an average of over 25 years of industry experience. They’ve been there; they understand the need for innovative, sustainable solutions and they are distinguished in their capability to help clients deliver more valuable assets, implement more efficient organizations, and respond quickly to critical business challenges.

With an insightful knowledge base of more than 12,000 active and 30,000 historical research protocols through our IRB, IBC, and Longboat platforms, our expert teams are empowered with greater decision-making capabilities. What’s more, YourEncore’s center of excellence infrastructure, organized around practices in quality, regulatory and clinical; advances our capabilities to provide outcome-oriented solutions that accelerate innovation, reduce risk, enhance compliance, and drive operational effectiveness and efficiencies.

Quality

YourEncore’s quality and compliance subject matter experts help sponsor organizations successfully navigate complex compliance challenges with a broad range of phase-appropriate, fit-for-purpose solutions, including:

  • Regulatory inspection readiness and remediation
  • Quality management systems
  • Audit preparation, execution, and remediation

Regulatory

YourEncore’s seasoned regulatory experts provide the experience-based guidance required to help clients identify the right regulatory pathway, effectively navigate compliance with global regulatory agencies, and ensure a successful regulatory submission. Whether a client needs support across the development process or in preparation for a key milestone, YourEncore is uniquely positioned to provide support from strategic guidance to tactical hands-on execution. Our regulatory solutions and services include:

  • Regulatory strategy development
  • Regulatory submissions and operations support
  • Regulatory policy and intelligence

Clinical

YourEncore’s experts in clinical provide clients with access to the leading medical and scientific thinking required to advance the development of key assets, as well as the experience-based, strategic thinking essential to drive operational transformation. We help clients innovate how clinical trials are designed and managed with clinical solutions such as:

  • Drug and device development consulting
  • Clinical trial oversight and remediation
  • Pharmacovigilance planning and compliance
  • Organization design and optimization

Combining YourEncore with Advarra’s global consulting solutions, market-leading IRB and IBC review services, and technology solutions expands our capabilities toward advancing clinical research: safer, smarter, and faster™.

Read more about YourEncore becoming part of Advarra.

2020 changed everything, including training and learning.

Did you switch your training strategy to eLearning or web-based this year? With limited options, many organizations implemented virtual or on-demand training this year because of travel restrictions and limits on group events during the COVID-19 pandemic. Some organizations are still weighing the benefits or effectiveness of eLearning but haven’t taken the plunge yet, and a few organizations are just waiting until in-person training can resume.

Advarra went all-in on eLearning this year. With cases still growing near all Advarra offices, we have fully embraced our 100% virtual learning strategy to keep customers and staff safe. We started investing in our eLearning program in 2017, so Advarra’s Training Team was ready and equipped to convert all of our training to fully virtual learning this year when it became clear that COVID-19 was going to prevent us from conducting classroom training safely.

Why should you consider eLearning?

Some of the advantages of an eLearning program are clear – eLearning is accessible whenever it is convenient, staff can review it at any time, and it can (should!) include assessments or knowledge checks to make sure learners are really “getting it.” eLearning can be assigned to hundreds or thousands of staff at the same time – getting the message out about new processes or policy changes to everyone immediately. eLearning provides a consistent message and allows learners to work at their own pace. Have you ever been ten minutes from the end of a two-hour class with too much material left to cover? eLearning won’t ever have to cram, rush, or skip content due to time constraints.

There are other advantages to running an eLearning program. Consider a scenario where you have 300 staff to train on a new electronic software program, or who need to satisfy their requirement for annual human subjects protection training. What does it look like to train these 300 people? In the traditional manner of classroom training, it becomes a complex mathematical equation based on the number and size of your computer-equipped classrooms, the number of trainers on your team, the number of staff away from the clinics at one time, and the number of classes a trainer runs each week without collapsing from exhaustion. Sure, it might make sense to offer a morning, afternoon, and evening class so staff can choose a time to fit their schedule, but if one trainer is expected to teach all those classes, they’ll be running around from sunrise to sunset.

Now imagine your only computer training room seats 20 people. You’ll need to schedule at least 15 training sessions for 300 staff, which will require at least two to three weeks. What does that look like if you use eLearning instead? A series of eLearning modules provided in a learning management system (LMS) and completed by all impacted staff within a few days prior to go-live. No training room is needed.

Sounds great. What’s the catch?

Creating custom eLearning is a big project; creating the content, writing scripts and storyboards, designing the modules, incorporating feedback from subject matter experts (SMEs), and developing assessments require just as much time and effort as designing a classroom training program. You might choose to assign a project manager, one or more eLearning Developers, plus SMEs who know the content. An eLearning project might take 3-6 months or more. Calculate 6 months’ of an eLearning Developer’s salary, plus a Project Manager’s salary, appropriate software licenses, and time from subject matter experts – that will cost your organization $100,000 or more.

Sounds expensive. Are there any other options?

Advarra’s in-house team of eLearning developers can create custom eLearning for your organization for a fraction of the cost. We have internal experts on Advarra technologies and clinical research topics who can kickstart your eLearning projects, plus a team of full-time eLearning Developers with experience creating scripts, storyboards, interactive and engaging modules, and assessments. Using your workflow documents, standard operating procedures (SOPs), or existing training materials, we can start on your custom eLearning project today.

Is eLearning really worth it?

Someone is going to ask you about the return on investment (ROI) of eLearning. What is your department or organization’s ROI? Is it really wise to spend all this money on eLearning software, audio equipment, and new staff? If we hire eLearning Developers, how long will it take for them to onboard and learn your workflows and policies?

You will realize value from your eLearning program. On-demand training is more convenient; you won’t have to pay your staff to travel to and sit in a classroom. Knowledgeable staff will complete their tasks more efficiently with fewer errors.

eLearning provides the greatest ROI when it saves your organization time, so evaluate what training is required for many, several hours long, and offered frequently. You’ll see greater ROI if you reduce your costs – use Advarra’s custom eLearning services to launch your training program and realize value faster.

Don’t wait.

Organizations slow to adopt new training strategies will fall behind. Partnering with ACRP in spring 2019, we conducted a survey of over 1,500 clinical research staff. Our results found 1 in 3 respondents said they did not receive adequate initial training on the technologies they use regularly, and more than half said they didn’t receive any ongoing trainings for these technologies. Even more compelling, 80% of respondents found on-demand training (like eLearning) helpful. Your staff want on-demand training, and it can be just as effective as in-person training, so we encourage you to try it out.

Would you like to see some samples of our work? Learn more about our custom eLearning content.

The data gathered in a clinical trial is often collected by many different people, including investigators and coordinators, and interpreted by data managers and regulatory authorities. When the success of your research depends on controlling and understanding data collected during the trial, it is important to ensure every role who interacts with the data is reporting and interpreting the results in a consistent manner.

Why Use Medical Coding Dictionaries?

To conduct clinical trials, many sites and organizations rely on an electronic data capture (EDC) system to help them collect and store their data during a trial. During the trial timeline, these data are analyzed, and the results need to be shared with regulatory authorities. For example, the FDA requires detailed reporting for adverse events (AEs), which often require summarization by system organ class or body system. So how do you ensure that each role across a multi-site or global trial records information like AEs in a standardized way? To solve this problem, researchers use medical coding dictionaries, to standardize the language they use to report adverse events, medications and more.

Commonly Used Medical Dictionaries and Best Practices

Common medical dictionaries used in clinical research include MedDRA , used to classify adverse events, CTCAE, an NIH developed coding dictionary for coding and grading adverse events in Oncology, and WHODrug, used for coding concomitant medications. To maximize the benefits of coding dictionaries, it’s best practice to incorporate them into study start up and initial data collection so you can spend less time reviewing your data. Some EDC systems support this by allowing coding dictionaries to be imported into the system, so standard terms will auto populate into selections you can make.

Medical coding prevents common problems such as spelling errors, incorrect abbreviations, or non-standardized terms. Medical coding prevents common problems such as spelling errors, incorrect abbreviations, or non-standardized terms. For example, say a handful of participants mention they are feeling a potential side effect from the trial therapy. One participant may report suffering from head discomforts, while another reports experiencing dizziness. Standard coding dictionaries will help organize those otherwise scattered terms into a standard parent category, which can help identify important trends within the trial.

Not only does this form of standardization protect your clinical trial from misinterpretation of trial-related terms, it also increases the efficiency of the trial itself. When less revisions are necessary, less time is spent reviewing the trial data, and the study can come to conclusions faster so the next plan of action can be taken.

Implementing standard medical coding dictionaries into your trial workflows minimizes incorrect interpretations and can expedite your trial timeline. To learn more about incorporating efficient workflows into your research operations, sign up for a personal EDC demo.

In the clinical research industry, it’s no secret there are many moving parts, and sometimes, some aspects of research are part of outdated processes or new activities are put in place to meet current needs. If not updated, these outdated processes could hinder research sites, ultimately affecting the cadence of which they move a protocol through the phases.

To address current challenges and capitalize on these growth and improvement opportunities, clinical research organizations must be willing to evolve and change behaviors. The key to effective, productive change within a research institution lies at the nexus of people, process, and technology.

“People, process, and technology” isn’t a new concept. It’s a basic framework guiding change management across different businesses and industries for decades. However, in an industry as complex and ever-changing as clinical research, it’s easy to lose sight of this fundamental guiding principle when implementing change.

When planning and implementing improvements to your research operations – whether  hiring new people, creating new processes to support new activities, such as billing and collections, or adopting a new piece of technology – this list of considerations helps ensure you’re not forgetting the basic principles of change management. Refer to this list to make sure people, process, and technology are equally balanced considerations of your change management efforts.

People: Communication Is Key

Identify Key Stakeholders, Champions, and Possible Opposition

Before you implement a change, it’s critical to identify and empathize with the different audience segments impacted. Change can create uncertainty and resistance, so it’s important to keep your audience’s perceptions in mind throughout the change management process.

For example, perhaps you’ve uncovered an inefficiency in your current participant recruitment practices you think could be resolved by centralizing recruitment efforts under a single person or team of people. Before moving forward, think about how the staff currently involved in  recruitment might interpret the shift. Will they welcome the opportunity to focus on non-recruitment-related responsibilities, or will they feel threatened that a piece of their day-to-day job is being shifted elsewhere?

Conversely, consider how the staff member or team to whom this task is shifting will respond. Will they be excited to take on more recruitment-related tasks, or overwhelmed by adding these responsibilities to their already-full to-do list?

Clearly Communicate All Elements of the Change With Appropriate Audience Segments

Once you’ve identified the audience for your change and thought through how different segments of that audience might interpret and respond to your proposed change, establishing open communication lines with everyone involved and impacted is key. At the very minimum, your communication plan should answer the following questions:

  • What’s changing and why?
  • Who is responsible for executing the change you’ve proposed?
  • What are the desired outcomes of the change you’re implementing, and how will you measure progress towards those goals?
  • How should team members share feedback about the change, and how will that feedback be considered or acted on moving forward?

Process: Focus on Fixing What’s Broken

Understand Current State

It’s impossible to improve something you don’t understand. Prior to implementing a new process or changing a current procedure, take the time to understand current state.

For example, if you’ve identified sponsor invoicing as a challenge for your research organization, map out the current invoicing workflow. Who’s involved in each step of the current process, and what tools do those contributors rely on to complete each task? Where are there gaps, inefficiencies, or vulnerabilities?

Prioritize Quick Wins and High-Impact Process Improvements

Building on our above example, once you’ve mapped out your sponsor invoicing process, prioritize improvements based on changes with the fastest and greatest impact. If sponsor payment depends on data being entered into an electronic data capture tool (EDC), for instance, consider changes to ensure EDC data entry is completed in a more timely and consistent manner across all industry trials. Develop a standard operating procedure (SOP) and training materials enabling staff to complete the task efficiently and accurately.

Technology: Optimize Your Operations With Infrastructure Enabling Scale and Growth

Implement Technology to Complement and Elevate Your People and Processes

Technology is the final piece of the change management process. Once you have the right people and processes in place, making technology decisions to support those two pillars should be simpler. Try to view technology as an enabler of operational improvements, not a solution in and of itself.

When considering different research systems to implement at your organization, take into account how a system will impact and influence staff members’ day-to-day responsibilities. For example, when implementing a clinical trial management system (CTMS) at the enterprise level consider the variety of research staff who will utilize the tool, from clinical research assistants (CRAs) to institutional leadership. Include everyone in your technology discussion before purchasing, so you are positive the system you implement enhances workflows for all involved and addresses any bottlenecks in your current processes. When choosing technology for your research operations:

  • Identify tools that enable people to improve results
  • Implement solutions to automate tasks and streamline processes
  • Consider how adopted tools enable organizational scaling and growth

Learn More

People, process, and technology are fundamental to any successful operational change. Attention to all three is required to implement significant and lasting improvements to research operations.

Need help from change management experts with proven methodologies and worldwide capabilities? Contact Advarra for global virtual and on-site support.

There are many challenges involved in developing and negotiating a clinical trial budget that applies Medicare’s rules and regulations for device and drug clinical trials. In this blog, we’ll discuss these challenges, and suggest strategies to assist with this process.

Medicare and Clinical Trials

There are three regulations addressing Medicare coverage in clinical trials:

All three of the regulations allow Medicare beneficiaries to participate in clinical trials, as Medicare payment (coverage) is no longer precluded. However, rules must be followed to prevent triggering the False Claims Act and other fraud and abuse laws arising from noncompliance.

Medicare Claims Management

A Medicare Administrative Contractor (MAC) is a private healthcare insurer awarded a jurisdiction to process Medicare Part A and Medicare Part B claims. Currently, there are 12 A/B MACs. In addition to processing Medicare claims, MACs address coverage decisions, which includes developing local coverage determinations (LCDs) following specific guidelines.

Medicare Coverage Analysis

Early adopters of the NCD for Routine Costs in Clinical Trials set the stage with a process to work with the policy, which is called a Medicare Coverage Analysis (MCA) or Coverage Analysis (CA). While the three regulations addressing clinical trials have specific unique requirements, the MCA process works well with all three.

Sponsors and Clinical Trial Budgets

Sponsors have the daunting task of developing a study budget template. Typically, this is a line item budget with some pass-through costs; however, some budgets are a per-participant lump sum. Budget template considerations include the number of participants required, the number of sites, and whether the study is conducted within the US. The budget typically provides funding for items and services to conduct the clinical trial (to meet study objectives and ensure participant safety) and include time and effort, study startup fees, IRB fees, laboratory, and pharmacy costs. Other factors include the cost of healthcare within the US, standard of care (SOC) items and services billed to healthcare insurers, items/services required for research purposes only, and the concept of fair market value (FMV). A budget must be fair but not excessive; both too high and too low of a budget negatively impacts the clinical trial’s outcome.

Once completed, each site receives the budget template, along with the Clinical Trial Agreement, protocol, and informed consent. The site is expected to review the template and modify it based on the site’s charge master/research fee schedule and other specific terms/fees applicable to the site. All these costs vary by institution.

Site Budget Development

The site must consider FMV as well as the cost of providing healthcare at their site, resources needed to adequately conduct the study, pharmacy costs, laboratory costs, indirect costs, etc. If the site accepts governmental healthcare insurance funding (e.g., Medicare), they must also factor in the rules and regulations regarding drug and device clinical trials; for example, many items and services associated with clinical trial conduct (even if considered SOC) cannot be billed to Medicare.

With this in mind, payment of SOC items and services is often a big surprise for both sponsors and sites. The sponsor may assume the site will bill healthcare insurers for these items/services, so these are not line items on a study budget. For the site, if they are unable to bill Medicare for these items/services not covered by the sponsor, participation in the clinical trial can be cost prohibitive—the site may not be able to participate in the trial. Losing a participating study site affects accrual, which impacts the clinical trial meeting specific timelines/endpoints. If this occurs with many sites, and the sponsor is not equipped to address these issues, the study risks failing due to lack of accrual. This is a devastating scenario for all involved (sponsor, site, and participants).

The development of a good clinical trial budget is time-consuming and challenging for everyone involved. But it’s not an insurmountable challenge. Many sites and sponsors focus on potential participants to enroll in the study, but it’s important to also address budget needs and negotiations early. Through education and communication, sites and sponsors can address potential pitfalls early in the process before they become major issues.

In our next blog, we will address how to talk through clinical trial budget negotiations outlined in a case study scenario. Need assistance in developing or negotiating your next clinical budget? Contact Advarra for global virtual and on-site support.

When you work for a company that values collaboration, it puts you in a position to wear many different hats and provide a wealth of unique experiences. For 12 years I have helped Advarra customers with support, training, and advice, allowing me to speak frequently about technology adoption and best practices. Staff augmentation gives me the opportunity to take those experiences and put them in action, empowering our customers to make big changes.

During a recent project, I worked with a customer site on a financials roll-out, which included centralizing financial services. I worked with a team of intelligent, motivated, and dedicated staff determined to help their research teams find new cures while keeping trials financially successful.

Walking Through the Steps

Our first step was to accelerate the billing grid integration between their OnCore Enterprise Research System and their Epic electronic medical record (EMR). Since they were in the middle of an implementation, I worked with the team to rebuild their charge master. This helped minimize the risk of double billing errors and streamlined the overall process to reduce billing holds. These early steps gave me the opportunity clear up any confusions surrounding the charge master. When the connection to Epic went live, our customer viewed the project as a success.

While on site, I also noticed there were very few documented processes, and offered a Workflow Workshop to key stakeholders. The workshop is designed to evaluate the current state of processes in place and work to establish best practices in the organization. Hosting this workshop brought stakeholders together to analyze each process from beginning to end. We walked through processes involving protocols, budgets, and subjects. By the end of the workshop, everyone understood each process and the roles involved.

The next phase came with writing and updating current manuals and process documents to help staff understand OnCore best practices. My experience with the system enabled me to capture key workflows, and I helped create functional documents for each staff role, including updated software information, process details, and tip sheets.

After the manuals and process documents were updated, I then provided training and working sessions for the finance teams. Since the study team used OnCore and already understood the subject workflow, I tailored the training to focus solely on the financial workflows that were a priority for the customer. Each training included a demonstration of the financial workflow, the purpose behind it, and why it was necessary to implement. Additionally, I trained study teams in centralized sessions, helping teams move away from visit spreadsheets to documenting actual visit data in OnCore. We shared best practices and tips for making the requirements easier to follow with OnCore’s time-saving features. In the end, it was great to see these features work as expected in reducing staff time.

Next, we worked on adoption, an important (but often forgotten) step to all software roll-outs. We focused on in-person team visits, and found the benefits greatly outweighed the travel time. Face-to-face time with those who will use the system is invaluable, providing an ideal setting to address concerns and resistance to change. During adoption, there were a few skeptics and many great questions. Team leadership talked about the purpose and the importance of these changes, which go a long way to build trust and acceptance. There were also large group sessions with all research teams, giving us another great opportunity to reach people with information, process details, and expectations.

Finally, we went live with real trials and budgets. The start of a new project is a great time to demonstrate how this process works and to build even more trust through action. Our goal is to make a quality, consistent presentation to each study team and prove these workflow processes work. I also assisted with creating initial study calendars and budgets, and gave the budget team a checklist to QA, ensuring they worked properly. My last step was giving the team a list of future projects to consider once they were comfortable with the new workflows.

Through this process, we learned staff augmentation can help in many ways. Through the experience and best practices I brought to the customer team, we were able to optimize their use of OnCore, maximize the efficiency of study startup and financial processes, and put them on a path to success.

Advarra Staff Augmentation Services allows your organization to meet staffing needs, setting your team up for long-term success.

In a perfect world, all items or services performed as part of a patient’s standard of care (SOC) would be covered by Medicare, but that’s not always the case. Time and time again, we encounter labs, procedures, scans, and anything in between that Medicare or private insurance will not reimburse. This is especially critical within the scope of a clinical trial, where additional assessments outside the participant’s SOC is required. To address this concern, perform a coverage analysis, outlining what is and is not billable to Medicare.

A patient’s SOC refers to an item or service done as part of their routine care. For example, if someone is suspected to have a type of cancer, a physical exam would most likely be warranted as part of their SOC.

The primary purpose of Medicare is to provide basic health insurance. Many interpret this to mean all items or services done as part of the patient’s SOC are therefore covered by Medicare when performed. While this often true, there are frequent exceptions. Medicare has issued numerous documentations outlining these determinations, defining what Medicare intends to cover:

  • National Coverage Determinations (NCDs),
  • Local Coverage Determinations (LCDs),
  • Medicare Benefit Policy Manuals,
  • Appropriate Use Criteria Programs, and
  • Coverage with Evidence Development.

This process is long and complicated, usually involving a coverage analysis. Coverage analysis is a review to determine if a research study is eligible to receive Medicare coverage and outlines what items and services performed as part of the research study should be billed to Medicare. A proper coverage analysis outlines any applicable Medicare policy, while also addressing the potential costs which will not be reimbursable by Medicare or private insurance. This may include costs the sponsor intends to cover, services bundled into the costs of other services, items provided free of charge without any monetary exchange, etc.

When coverage analysis is overlooked, hospitals and research sites are subject to audits and lawsuits. In 2019 alone, the Department of Justice recovered over $3 billion in settlements and judgments under the False Claims Act. Individual sites commonly face multimillion-dollar settlements and are at risk of losing federal funding as a result.

Advarra conducts coverage analyses tailored specifically to your institution’s guidelines. Learn more about how to streamline the coverage analysis process through Advarra’s Coverage Analysis Service.

Research institutions performing clinical trials are often at an increased risk. Extended coverage is obtainable for clinical trials qualifying under Medicare’s National Coverage Determination for Routine Costs in Clinical Trials (310.1). This, however, does not overrule other forms of guidance issued by Medicare. In these cases, a coverage analysis is needed. A coverage analysis should not only document medical necessity, but also reference applicable guidance issued by Medicare.

Clinical staff provide excellent insights as to what is considered SOC. Nevertheless, without the proper training and experience in Medicare rules and regulations, organizations should not rely on clinical staff to perform a coverage analysis. This task should fall to specialized individuals who understand Medicare guidance, can interpret indications and limitations appropriately, and put the institution’s priorities first.

A specific example of coverage analysis is viral serology screening in the oncology setting. Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) serve a great purpose in determining whether a participant can safety receive chemotherapy treatment. Peer-reviewed and medically accepted treatment guidelines often recommend HBV, HCV, and HIV testing prior to chemotherapy. Some forms of chemotherapy even include a “black box warning”, FDA’s most stringent warning to call attention to serious side effects, outlining the need to perform these types of tests. However, Medicare released NCDs for each of these tests performed as part of a screening assessment. A proper coverage analysis calls attention to these applicable NCDs, clearly outlining why Medicare coverage is either indicated or limited.

Medicare may not always cover SOC items or services. Although, consider if Medicare indicates coverage of an item or service your institution does not view as SOC: is this item or service billable to Medicare?

The simple answer is no. Just because something can be billed to Medicare does not mean it should be billed to Medicare. If your research institution views an assessment as “non-covered” outside of the scope of a clinical trial, this practice should not change within a clinical trial. Billing practices should stay consistent and align not only with your institution’s priorities, but also the participant’s SOC.

A coverage analysis performed by specialized personnel should outline the topics listed above when applicable. At Advarra, our coverage analysis team emphasizes the need to document both medical necessity and Medicare guidance. This is done in a clear, logical manner that enables anyone from your institution to understand the billing determinations made. While it is important to note when items and services are performed as part of a participant’s standard of care, it is crucial to then confirm whether this is also covered by Medicare.

In a recent webinar, Advarra IRB and research compliance experts discussed key areas to consider as we look to ramp up research in the COVID-19 pandemic’s “new normal.” Presenters discussed challenges such as how to communicate with stakeholders, how to prioritize the research portfolio, and ways to ensure compliance and participant and staff safety. Due to time constraints we weren’t able to answer all audience questions during the Q&A period, so our experts have answered some of the most popular questions in this blog.

Note: IRB policies vary; please contact your IRB regarding any specific questions.

Q: How should participants be consented via phone or email?
A: There is no prohibition on consenting by phone or by email. If not consenting in person, you must be able to verify the identity of the individual with whom you are communicating, provide an opportunity to answer questions, and assure that the informed consent form (ICF) is signed and returned. For more information, see question 11 in FDA Guidance on Conduct of Clinical Trials of Medical Products During COVID-19 Public Health Emergency.

Q: Do you have any guidance on witness to signatures when consent is conducted over the phone or email?
A: When using a witness in the consent process, it is best practice to have an objective, unbiased individual serve as witness. The witness should attest that the prospective participant received the consent, that the individual had an opportunity to have questions answered, and that the individual stated he/she signed the document and would return it.

Q: Should research participants be notified—or consent be sought from them—if a sponsor requests all participants’ COVID-19 test results be provided as part of the study data/case report form (CRF) for a non-COVID-19 study?
A: Yes, if the data is going to be part of the research data set, then the protocol and ICF should be amended, and participants should be notified and sign the amended ICF.

Q: What are your thoughts about keeping studies open that can be conducted virtually?
A: From a site perspective, the program’s entire portfolio should be assessed and various factors considered. The purpose of research is to answer a scientific question, which requires quality and complete data collection. At the same time, the participant and staff safety must be considered. If safety cannot be maintained or the scientific question can no longer be answered, then the study likely needs to be paused or suspended. If the study is almost complete and procedures can be done virtually, then there is likely a compelling reason to keep it open.

Consider include the organization’s scientific priorities, the needs of the patient population(s) served, the ease of research conduct, the ability to move procedures virtually, and the study’s status. Additionally, the statistical analysis plan and possibly the data analysis plan will need to be amended to reflect changes in what data is collected and how it is collected.

Q: Do you have any suggestions for multisite study recruitment during this time?
A: Modes of recruitment can be specific to the research participant population and should be considered study by study. Take into account the participants’ age, socioeconomic status, technologic ability, and requested interaction with recruitment. Broadly speaking, different generations have different skills with technology tools. Depending on socioeconomic status and/or age, access to or use of cell phones (especially smartphones) may be limited. People may have the ability to answer phone calls or answer basic surveys online but may not interact well with uploading documents or pictures. Not all people are active on social media. The study may target minors which is a sensitive group to reach online. Security access on their devices may prevent them from being able to access sites or videos.

Q: Any suggestions for assessing participants’ technology access to be able to virtually participate in a study?
A: As discussed above, consider the participant population’s demographics. Certain populations may be more or less comfortable with electronic tools for virtual study conduct. Also consider geographic and socioeconomic factors for your site’s community and the target participant population; not everyone has regular, reliable high-speed internet access.

Q: Can IRBs require that sites/sponsors implement safety processes to decrease the risk of COVID-19?
A: An IRB has jurisdiction over the research. If the safety procedures are not specific to the research with data collected about those safety procedures, it is unlikely the IRB has authority to require general safety precautions.

Q: If patients must be screened for COVID-19 per hospital standards when coming for clinical trial-specific visits only, could this be reimbursed by sponsors?
A: This is worth discussing/negotiating with the sponsor, particularly if the person is only coming to the site for the clinical trial visit. If the participant is expected to cover the cost of the testing, then it should be disclosed in the ICF; that could impact people’s willingness to participate. Also consider to what extent the COVID-19 testing cost is covered by the local/regional health authority. If the jurisdictions provide testing at no cost (including coverage for facilities and practitioner time), it wouldn’t be appropriate to have the sponsor cover the cost.

Q: If the sponsor requires COVID-19 results be reported in an ongoing study, should participants be consented or reconsented?
A: Yes, if the data will be part of the research data set, and this is not part of the original protocol and ICF. The protocol and ICF should be amended, and participants should be notified and sign the amended ICF.

Q: Can you provide any budget-proof strategies around restarting research (e.g., adjusting costs for remote modalities vs the “old normal”)?
A: We suggest evaluating budgets as research resumes. Consider costs associated with additional technology, time, training, etc., and open conversations with the sponsor to help account for those costs. Also ask the organization’s/program’s administration and IT teams if existing technologies already exist that can be applied where possible, and find out whether multiple departments/units can combine efforts to spread the implementation impacts (and increase effectiveness). Think about organization/program-wide answers rather than study-specific answers.

Sponsors may recommend certain technologies, which may be the best solution—but if a technology is already in place that will speed transition to a remote/virtual environment, make sure it will meet study’s needs. Example: A sponsor may be able to provide “X” communication solution for conducting video visits. But if your organization already has solution “Y” in place (including IT vendor assessments, compliance assurances, policies, and processes), it may be better to tell the sponsor about that available technology so research can continue.

Q: Could confidentiality issues arise if participants being screened according to university-wide procedures answer COVID-19 screening questions that are reported to local public health authorities?
A: The screening procedure, which presumably is being conducted as part of research, should include information regarding privacy and confidentiality protections.

Q: Who should sites/sponsors consult with to determine if e-signature is legal in their setting?
A: Electronic systems used to generate electronic signatures on clinical trial records, including ICFs, during the COVID-19 public health emergency must comply with the requirements outlined in FDA regulations at 21 CFR part 11 (Part 11) when applicable. Compliance with Part 11 should be discussed with your technology team and potentially your legal department. Depending on the systems being used, your technology team will help identify if the necessary steps and documentation are in place. If you use a commercial off-the-shelf solution, the vendors may be able to provide sponsors and other regulated entities with information regarding Part 11 compliance. See FDA Guidance Use of Electronic Records and Electronic Signatures in Clinical Investigations Under 21 CFR Part 11 – Questions and Answers for more information.

The recent outbreak of the novel 2019 coronavirus (2019-nCov) in Wuhan, Hubei Province, China, has led to a surge of interest in coronavirus research and concern about the risks associated with coronaviruses. In this blog we’ll introduce coronaviruses and cover strategies for developing medical countermeasures to combat the recent outbreak. We’ll also review opportunities, risks, and risk mitigation strategies for coronavirus research.

Coronavirus (CoV) is a family of viruses that cause disease in mammals and birds. Most coronaviruses capable of infecting humans cause mild to moderate respiratory tract infections which are transmitted by respiratory droplets produced when an infected person coughs or sneezes. Certain notable coronavirus species can cause more virulent infections, including SARS, MERS, and 2019-nCov.

Over the last few days the nomenclature for this virus has changed: the World Health Organization (WHO) named the pneumonia associated with the infection “Covid-19 (coronavirus infectious disease 19),” and the International Committee on Taxonomy of Viruses named it “severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2)” due to the virus’ genetic similarity to the SARS associated coronavirus (SARS-CoV) responsible for the 2003 outbreak that caused 8098 infections and 774 deaths. For simplicity, in this article we’ll refer to the virus as 2019-nCoV and the pneumonia associated with the infection as Covid-19.

An important early victory in the fight against the 2019-nCoV is the sequencing of the viral genome, which has led to genetic tests/molecular diagnostics allowing for confirmation of infected individuals. The viral genome was originally made available by the Chinese government, and the CDC is making the sequences of confirmed US cases available online. The CDC has also made molecular diagnostic kits available to authorized labs so that a suspected case can be confirmed or ruled out within hours, rather than waiting days for samples to be shipped to the CDC for processing at a central lab.

Strategies for developing medical countermeasures

Antivirals and antibody-based treatments

Previously developed antivirals are actively being tested in the laboratory setting to evaluate if they can impede 2019-nCoV replication in cultured cells. Early tests show remdesivir and chloroquine may be effective, and the first US Covid-19 case was successfully treated utilizing remdesivir under a compassionate use protocol. Several clinical trials are currently being initiated to assess the safety and efficacy of various antiviral treatment regimens, including two Phase 3 trials testing remdesivir on Covid-19 patients in China.

Antibody-based treatments, which can bind to the virus in infected individuals and allow the immune system to destroy the bound virus particles, are also being investigated. Such passive immunization with neutralizing antibodies would confer transient protection to patients in a critical disease state—much like an anti-venom following a snake bite—allowing patients to recover from a critical disease state and for their immune system to clear the infection. Fortunately, the genetic similarity between SARS-CoV and 2019-nCoV suggests there is potential that antibodies developed against the earlier outbreak may be effective against the current one. One biotechnology firm claims to already possess two antibodies developed against SARS-CoV that bind to 2019-nCoV.

Vaccines

While antivirals and antibodies can be utilized to treat the disease, vaccines are the best way to prevent viral infection and control outbreaks. An effective vaccine can create an immune population no longer susceptible to infection and prevents the virus from spreading. A ring of vaccination around an outbreak can contain it and allow it to burn itself out without spreading to new hosts. Several groups are currently developing vaccines against 2019-nCoV, including pharmaceutical companies and the NIH.

Vaccines require two main components: a target antigen for the immune system to attack and an adjuvant to spur the immune response. The primary target for a vaccine is the spike protein on the virus surface, which the virus utilizes to bind to and infect host cells (see below). Antibodies binding to the spike protein prevent the virus from infecting host cells and label it for destruction by the immune system.

coronavirus image
Coronavirus

Various design strategies exist to achieve these objectives. Modern vaccines typically involve an inactive or attenuated form of the organism being vaccinated against (e.g., oral or inactivated polio vaccines, MMR vaccine) or a subunit vaccine containing only the antigenic parts of the organism (e.g., hepatitis B virus vaccine, gardasil human papillomavirus vaccine).

Currently available genetic engineering techniques and the 2019-nCoV genome sequence provide opportunities for research and development of new vaccines. Scientists can easily introduce single genes from the 2019-nCoV into expression systems to produce subunit vaccines. Introducing 2019-nCoV genes into weakened vaccine strains of existing viruses also serves as a means of delivering both the 2019-nCoV antigen and an adjuvant to spur the immune response.

Minimizing Risks Associated with Researching Genetically Engineered Vaccines

There are risks when utilizing genetic engineering technology. Introducing a coronavirus gene into another virus may have unintended consequences and pose occupational safety risks, as well as risks to the community and environment surrounding the research site. It is also important to mention that using the complete genetic sequence can enable creation of the virus in the laboratory setting. While a typical Biosafety Level 2 (BSL-2) laboratory provides adequate containment for expression of subunits, Biosafety Level 3 (BSL-3) containment is required for culturing and characterizing the virus as well as assaying vaccine efficacy in a challenge model utilizing laboratory animals.

BSL-3 laboratories are designed to contain aerosol transmissible pathogens. Lab design criteria include a double door entry system to provide security and an anteroom for donning and doffing personal protective equipment (PPE) including respiratory protection. The laboratory must have unidirectional, inward flowing, single pass air that is exhausted through a HEPA filter. All work must be performed within a negative pressured and HEPA filtered biosafety cabinet or another aerosol containment device. The facility must contain an autoclave for sterilizing infectious waste.

researcher on infectious disease
Dr. Terrence Tumpey working in BSL-3 enhanced laboratory conditions. This includes (but isn’t limited to) use of a powered air purifying respirator (PAPR), double gloves, suit, and working within a Class II biosafety cabinet (BSC). Photo credit: James Gathany – Public Health Image Library #7989.
Biosafety Level 3 diagram
A BSL-3 facility. Image source: WHO Laboratory Biosafety Manual, 3rd edition

The role of an institutional biosafety committee (IBC) is to conduct risk assessments for research involving engineered genetic material to ensure an appropriate risk mitigation plan is in place. IBC review is required when the research or the site/institution has ties to NIH funding. Even if there are no ties to NIH funding, IBC review is considered a best practice, and NIH recommends voluntary compliance.

Institutions embarking on coronavirus research should consult IBCs with adequate expertise to understand the science, risks, necessary safety practices, and regulatory requirements. There may be additional regulatory constraints depending on the coronavirus species: for example, since 2012 SARS coronavirus has been tightly regulated by the CDC as a select agent for its ability to pose a severe threat to public health and safety.

Time is of the essence in research involving an emergent infectious disease. IBCs at Institutions meet monthly or quarterly, and obtaining approval may take several review cycles. A centralized commercial IBC may be better equipped to conduct reviews efficiently: for example, in 2019 Advarra’s central IBC service has averaged turnaround times of about seven business days from submission to review.

Past research and current gene editing technology provide valuable tools for responding efficiently and effectively to this new coronavirus outbreak. In this kind of fast-paced environment, appropriately managing the risks associated with genetically engineered viruses is critical to developing treatments safely and responsibly.

Need support with your upcoming infectious disease study? Not sure where to start with biosafety measures? The experts at Advarra have worked in a variety of institutional and industry settings (including overseeing BSL-3 labs) and can help you address human subject protection, biosafety, and other research compliance needs. Contact us to get started.

After multiple delays, exceptions, and oh-so-many training sessions, on January 20, 2020, we reached the last remaining compliance milestone for the final revisions to the Federal Policy for the Protection of Human Subjects (“revised Common Rule”).

The Final Rule published in the Federal Register on January 19, 2017 (82 FR 7149), finalized the regulatory revisions, which seek to “modernize, simplify, and make more effective the current system of oversight” for clinical trials. Wondering what this all means for your research? Advarra’s got you covered with a variety of resources:

Still not sure what to do about the revised Common Rule? Advarra’s dedicated revised Common Rule experts have years of experience helping the research community understand and implement these changes to the way we conduct and oversee research. Contact us for customized support.

Our recent webinar on conducting planned emergency research had nearly 1,000 registrants, demonstrating the importance of this topic and the increasing number of trials using the exception from informed consent (EFIC) consent method outlined in FDA regulation 21 CFR 50.24. If you are not familiar with the regulatory requirements, we encourage you to listen to the webinar, which is now available on demand.

In this blog post we go beyond the regulatory requirements and examine three other key actions that research organizations may want to consider before conducting planned emergency research at their facilities.

A Quick Refresher on Planned Emergency Research

How do you conduct research on potentially life-saving treatments in trauma or emergency situations like a car crash, unexpected stroke, or similar catastrophic and unforeseen events? These patients are most likely incapacitated and either in emergency transport or presenting at the ER without their family or others who can make medical decisions, and time is of the essence to deliver life-saving care. The traditional prospective informed consent process, with time for the patient to carefully consider and discuss their options, doesn’t fit emergency situations where it is impossible to predict who will need treatment and be eligible for the research. Yet we must conduct this research to determine if innovative treatments for stroke, trauma, and other acute conditions are effective.

Found at 21 CFR 50.24, the FDA provides a regulatory pathway for conducting planned emergency research, including an EFIC. In a nutshell, FDA allows planned emergency research to occur only after first conducting community consultations and public disclosure to alert the local community that the research is occurring. The principal investigator (PI) must have a plan to get consent from family members or another authorized representative if possible, and to have the whole plan approved by the IRB. In the end, if there is no opportunity to get consent from family, and the patient is eligible for the experimental treatment, then under the EFIC regulations investigators may administer the experimental treatment without getting explicit prospective informed consent from the participant. Experimental treatments can be administered in the field, during transport, or at the ER even if the patient cannot consent.

This seems to go against all the tenets about research consent being voluntary. But without this exception to traditional informed consent processes, it would be nearly impossible to develop new treatments for use in emergency situations.

Before conducting this type of research, you should thoroughly understand the regulatory requirements, and any organization conducting planned emergency research should consider additional actions beyond simple compliance with 21 CFR 50.24. We focus here on three specific areas that should be carefully evaluated by an organization considering participating in planned emergency research.

1. Front-line Staff Communication Plan

Regulations require the IRB to approve plans for communicating with the community in advance of the research, as well as plans for telling the participant or their family about the research after the fact. The PI and study team are also trained in advance and know what is involved in the research. However, what about the front-line hospital staff or intensive care clinical staff who may not be part of the study directly, but will likely be the first folks confronted with questions from the participant or their family? Hearing “I don’t know, you need to talk with the investigator” is likely not what the participant or their family want to hear in the moment.

Facilities should have an education and communication plan that goes well beyond the study staff. A good internal communication plan should include:

  • A summary of the research, what type of participants might be involved, and a statement of why the hospital/organization feels it important to be involved.
  • A summary of how to provide basic responses to question so that at a minimum front-line staff have an idea about how to guide participants and family through initial questions such as, “What do you mean, what is this experiment you are talking about?”
  • Clear instructions on who staff should direct family or participants to for additional information.
  • Instructions to staff on how to identify in the medical record if a patient is part of a planned emergency research study.

Internal staff communication plans do not need to be elaborate, take a lot of time, or even be approved by the IRB (since they are not technically required). However, mapping out a plan prior to starting the research is a good idea and should be a requirement of the facility’s research administration.

2. Clinical Operations/Feasibility Evaluation

While the study protocol will likely outline many details on investigational treatment administration, during the feasibility review process it is imperative for research organizations to thoroughly and thoughtfully consider if their clinical operations units can really deliver quality research execution. Those considering conducting planned emergency research for the first time should take an extra look at their operations to ensure they are ready.

Some common areas to consider:

  • Investigational drug pharmacy – Does the pharmacy have capacity and training to respond with experimental drugs in the time frame needed with planned emergency research? Can research drug accountability be maintained?
  • Record keeping – Do your CTMS, EMR, and other systems have the operational capacity to rapidly identify patients in the ER and enroll them in an EFIC clinical trial? Since there is no “consent” event to trigger certain operations such as research billing codes, enrollment tracking, flags in the EMR, etc., will all these events work properly?

This of course is not an all-inclusive list; your organization may have other issues to consider. The key is to consider the operational issues in advance of starting the research, and perhaps even run simulations to demonstrate operational readiness. Remember, just because the IRB determines the research is approvable at your facility does not necessarily mean your facility has the operational capacity or integrated clinical operation organization necessary to successfully execute an EFIC study.

3. Plan for Media Inquiries

Perhaps it goes without saying, but when something goes wrong in an EFIC study, the potential for media attention is higher than in typical clinical trials. Most research organizations have some type of media policy or central group who handles media inquiries. Before conducting planned emergency research consider, two important points:

  1. Has your media department been briefed (or are they even aware) that EFIC research studies are being conducted at your organization (see “Front-line Staff Communication Plan” above)?
  2. Are you confident your media team is ready to respond to questions about EFIC research?
    • If there is a problem, how will you respond to potential questions about conducting research on patients without their consent?
    • Do you have a planned response to possible negative press?
    • Are you being proactive in anticipating issues and controlling the message?

Research is beneficial and necessary. Without it we would have no new treatments, advancements, or cures; however, that does not mean it always goes perfectly. It’s good to be prepared.

Summary

Planned emergency research with an EFIC is a vital and necessary avenue for testing potential new treatments in the challenging setting of emergency medicine. As with many aspects of clinical research, the regulations set a minimum floor that must be adhered to; but they are just the floor. To do this type of research well, organizations should look beyond the regulations. We’ve explored just three specific areas not covered in the regulation above; we are certain you can think of more!

Need help in determining if your organization is ready to conduct planned emergency research studies? Advarra’s IRB has a long history of reviewing EFIC studies, and the team at Advarra Consulting can support you with operating procedures, training, and other tools to ensure you are ready. Contact us to get started.

Forte, now a part of Advarra, provides the industry-renowned CMTS software OnCore. Read this case study to learn how OnCore can enroll and track a patient throughout an emergency research study.

 

 

As we near the end of 2019, let’s take a look back at the blogs that generated the most interest this year from readers like you.

Look back over 2019 with the top 5 most-read blogs of the year. Not surprisingly, hot topics like the revised Common Rule and perennially tricky topics like reporting to the IRB led the pack in 2019.

  1. Reporting to the IRB: What NOT to Report

We get it: reporting requirements are not always straightforward. That’s why in 2019 we got the facts from our IRB experts to demystify IRB reporting requirements, explaining what the regulations do and do not say and how Advarra addresses some of the undefined “gray areas.”

In addition to this popular blog, we also published pieces on investigator noncompliance and UADEs, and a late 2018 blog on SAEs kicked off the series.

  1. Quality Improvement Project vs Human Subject Research: What’s the Difference?

It’s not always easy to determine whether a project should be defined as quality improvement (QI) or if it truly is research involving human subjects. In this blog, we provide practical tools to help you appropriately categorize projects that don’t seem obviously one or the other at first glance.

  1. Informed Consent Changes in the Revised Common Rule

With most of the revised Common Rule taking effect in January 2019, we provided the research community with resources to assist with the transition. Read our recommendations on incorporating informed consent changes, including the new “key information” section and new consent elements related to identifiable private information and biospecimens.

  1. Can Ethics Review Catch Up to the CBD Craze?

Research on cannabidiol, or CBD, is complicated for a variety of reasons and remains largely inaccessible to most US researchers. However, the lack of IRB-reviewed research hasn’t stopped CBD consumers. Read our take on the current challenges surrounding CBD research.

  1. Six Key GDPR Questions to Review

While the General Data Protection Regulation (GDPR) took effect in May 2018, many international organizations remain uncertain about how it might apply to them. We outline key questions to help you determine where your organization fits within the GDPR framework.

Craving more great research compliance content? Visit Advarra’s Resource Library to access blogs, white papers, webinars, and more. Join our mailing list to receive the latest from Advarra right in your inbox.

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