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Implementing a clinical trial management system (CTMS) can generate significant improvements to the way your organization understands your research portfolio, manages the financial components of your trials, leverages reporting and analytics, and more. As with many enterprise technology solutions, interfacing with other technology used at your institution further enhances these efficiencies. Below are some key integrations — using systems your institution has likely implemented — your team can use to streamline research operations.

Integration 1: CRPC Billing Grid Interface

Integrated systems: CTMS and EMR
Key staff benefits: Billing team, clinical research staff

The Clinical Research Process Content (CRPC) profile facilitates the complex study billing definitions from a CTMS such as the OnCore Enterprise Research System to an electronic medical record (EMR) system. This integration allows all team members involved in the research and billing processes to leverage the same billing designations, which improves compliance and reduces duplicative processes in your CTMS and EMR systems.

Learn more about leveraging OnCore integrations to improve billing compliance

Integration 2: Subject/Protocol Information Interface (RPE)

Integrated systems: CTMS and EMR
Key staff benefits: Clinical research staff, research operations, billing team

You can also interface with your EMR to exchange subject enrollment status and protocol information, flagging research participants for clinical and billing workflows. This process, which uses the IHE Retrieve Process for Execution (RPE) profile, enhances participant safety and improves staff communication by centralizing vital information across your clinical, operational, and financial teams.

Learn how Atrium Health uses the RPE integration to help ensure patient safety

Integration 3: General Ledger System Interface

Integrated systems: CTMS and general ledger (GL) system (Workday, SAP and Oracle Peoplesoft)
Key staff benefits: Finance, research operations

Integrating a GL system such as the OnCore receivables interface automate two key components of the billing process: sending research activity-related invoices to the GL system and reconciling payment for those activities within the CTMS. This simple workflow eliminates the challenging and time-consuming manual process of managing invoices between the two systems. Your financial teams can see invoice and receipt information in real-time, allowing them to view the financial status of a protocol and act upon information quickly and efficiently.

Integration 4: Electronic Institutional Review Board (eIRB) Interface

Integrated systems: CTMS and eIRB system (ClickIRB, iMedRis, Homegrown Systems)
Key staff benefits: Regulatory staff, research operations

IRB approvals are a common trigger for a variety of tasks within the study activation process. With many institutions continually working to accelerate study activation, automation within this workflow can significantly improve efficiency. Interfacing an eIRB system with your CTMS ensures the IRB status is always up-to-date within both systems. This eliminates the need for regulatory coordinators to enter duplicate data entry, saving time and improving data quality.

Choosing the Right System for Your Organization

If system integrations are a key priority for your institution, you want to ensure you incorporate those needs into your search for an enterprise system. While many vendors may have technical processes in place for integrating with EMR, GL, and other systems, it’s important to understand what (if any) customers are leveraging those integrations across their research portfolio.

If you’d like to learn more about how you can leverage OnCore or Clinical Conductor (and the integrations mentioned above), contact us to schedule a demo today:

The Call to Action

Data is the most important asset for a pharmaceutical or biotechnology company to produce during clinical development. It is the foundation upon which everything else is built — without it, decisions cannot be made, and new treatments cannot be approved.

Therefore, efficiently acquiring high-quality data in a clinical trial should be a very high priority for the industry. The need to focus on a data strategy is increasing due to changes in the external environment as technology is constantly evolving. Electronic data capture (EDC) is now the normal way to way to capture case report form (CRF) data, and electronic patient reported outcomes (ePRO) is established as the approach to capturing patient-reported data. Additionally, automatic data capture through devices is expanding, and direct data capture from electronic health records is emerging.

In addition to technology, processes are changing with centralized monitoring, risk-based quality management, and, most recently, decentralized trials, all requiring re-evaluation processes. Trial designs are also evolving. Adaptive trial designs are now commonplace, requiring access to high-quality data throughout the study in order to decide rapidly on trial modifications. It also requires a very agile approach to study execution in order to implement study design changes on the fly. Recently, platform, umbrella, and basket trials were implemented, further stressing the infrastructure. With multiple trials conducted within one protocol, novel process development to handle the complexities became necessary.

There are multiple opportunities to capture data quickly, therefore accelerating drug development, but there is little evidence of clinical trial execution improving while cycle times are decreasing. Most companies lack an effective data strategy, as they do not build a solid foundation. An example of this is adopting an electronic data capture (EDC) technology. There is no evidence of reduced database lock times due to EDC. Many companies implemented an EDC without a comprehensive strategy. Data entry backlogs at the site did not decrease – in fact, in some cases, they increased. Not all checks were carried out in real-time as promised. Investigator signatures on case report forms (CRFs) are now on the critical path to database lock. These challenges are manageable, but there needs to be a well-thought-out strategy to do so, not a reliance on technology and assumptions.

When taking advantage of the multiple opportunities to improve efficiency and productivity through optimal data management, it is imperative for companies to develop a data strategy with mechanisms in place to maximize effectiveness once implemented.

The Scope of a Data Strategy

A successful data strategy needs to be comprehensive and detailed, covering every aspect of data management, from Phase I through Phase IV. It is not just about technology – a case in point is the poor initial implementation of EDC described above, which was often just about the technology, not about the impact on people and processes, all the way from the investigator’s site to database lock.

Our approach to developing the data strategy and ensuring compliance is to break it down into five equally important components: processes, resources, performance monitoring, tools, and information architecture.

Development Methodology

Developing a comprehensive data strategy is a major undertaking, requiring dedicated resources from multiple functions. This is especially important if strategy development is used as an opportunity to enhance existing components – for example, developing new data standards or introducing a master data repository. Best practices recommend implementing a strategy based on current processes and systems, updating it as gaps are filled and new solutions are implemented. Delaying its implementation while waiting for major changes means both momentum and short-term opportunities for increased efficiencies are lost.

The development organization’s strategic objectives should include developing a data strategy. As such, senior executives should fund and oversee these objectives at a high level. (buy generic modafinil) Additionally, create a cross-functional task force with various stakeholder memberships.

To expedite the development of the strategy and to bring in external expertise, select an outside vendor to manage the process and to assist in the document writing to minimize project continuity impacts.

Governance

Once the task force completes its work and the data strategy is implemented, set a governance structure in place through the data management group reporting up to the data strategy owner. Various governance bodies should also receive authority to enforce the data strategy. For example, if data standards aren’t adhered to, there’s no value to having these standards. The data strategy should describe the governance structure’s organization in depth.

Risk Management

The external environment can change unexpectedly and rapidly – an example of this is when a currently approved vendor must be replaced due to a failed audit or a business failure. Without a clear, comprehensive, data strategy, which describes the process for handling these situations, there will be lengthy delays, while the response is discussed and a process is developed ad hoc.

Conclusion

Every pharmaceutical, biotechnology, and contract research organization (CRO) should implement a data strategy if there isn’t one already in place. Those with a data strategy in place should consider potential enhancements. While both pose a major undertaking for an organization, if executed successfully, it will:

Increase efficiency through data standardization from set-up to reporting
Accelerate decision making driven by centralized policy access
Ensure a consistent approach to regulatory compliance
Introduce a standard and cost-effective approach to evaluating and implementing new processes and technologies
Measure data management process and system effectiveness through clear and relevant key performance indicators (KPIs)
Improve organizational discipline, enabling growth

Clinical development proceeds in phases, and each phase contains a set of clinical trials. These trials, including their sample size calculations, are typically designed independently. However, there are advantages to considering the program as a whole and designing it to optimize the study’s return on investment (ROI). Below are some examples where considering ROI benefits individual study designs and the program overall.

What is the Optimal Power for a Phase III Study?

Most Phase III clinical trials have a sample size providing between 80% and 90% power, or the probability of achieving a statistically significant result. But how should a sponsor choose between 80% and 90%? And are there ever situations where greater than 90% would make sense, or less than 80%? One way to address this question is to consider a Phase III trial as an investment and to maximize the return on that investment.

Assuming the treatment works by the exact prespecified amount, every additional percentage point in power provides a sponsor with the same benefit: an extra one percent chance of a significant result. But every additional percentage point in power does not entail the same cost – the higher the power, the greater the sample size increase required to add that one percent.

As shown below, increasing power from 90% to 91% takes about twice the sample size increment as increasing power from 80% to 81%. Increasing power from 95% to 96% takes about 3 ½ times the sample size increment. In fact, in the extreme, increasing power from 99% to 100% would require an infinite sample size increase. So, from an ROI’s perspective, there is an optimum point where increasing the sample size any further is not worth the gain in power.

How Big Should the Phase II Trials be?

Phase II trials can have multiple purposes, and one of them is to provide an estimate of the treatment effect’s magnitude to help design the Phase III program. Clearly, the larger the Phase II program, the more precise the estimate; and the more precise the estimate, the lower the chance of making one of two costly mistakes: launching a Phase III program with a treatment that doesn’t work or abandoning a treatment that does work. So, the bigger the Phase II program the better, right?

Again, interpret a Phase II program as an investment and understand the goal is to maximize its ROI. By making a set of assumptions, it’s possible to optimize either the size of the Phase II program, or the allocation of a fixed budget between Phase II and III.

Are the Phase II Results Promising Enough to Launch a Phase III Program?

When Phase II is complete, a sponsor faces a difficult and highly consequential decision for potential patients and to the business: to abandon the treatment, or to launch a Phase III program. The Phase II results are informative, but it is not at all intuitive to identify the point where the results are just barely promising enough to proceed.

In addition to the Phase II results, two key factors influence where that point lies: the prior belief in the treatment’s effect, and, if ultimately approved, the treatment’s expected profits. If the prior belief and/or expected profits are high enough, it might make sense to launch Phase III even with disappointing Phase II results.

Putting it all together, by defining a statistical model, it’s possible to optimize an entire clinical development program rather than designing a set of suboptimal individual trials. This includes the sample size allocation between Phase II and III as well as the threshold value defining whether or not the Phase II results are promising enough to proceed to Phase III. Of course, no sponsor would or should base their development program solely on such a model, but the model’s output can provide valuable information to guide the sponsor toward a program with an improved ROI.

Social media can be a valuable tool for researchers to connect with and recruit potential clinical trial participants. However, US regulations and regulatory guidance do not currently provide specific information on the use of social media clinical trial recruitment strategies. In this blog, we’ll explore how existing regulations might be applied to establish best practices in using social media for research participant recruitment and engagement.

Defining the Scope of Social Media

“Social media” can be defined as interactive platforms for electronic communications, used by groups of people to create, share, and exchange information. These platforms are typically internet-based and allow users to interact with other users through a website or mobile application.

Examples of social media usage in clinical trials include:

Facebook and Twitter advertising campaigns to recruit participants
A phone application (i.e., iPhone, iPad, or an Android platform-based phone) that users download on their phones and use as an electronic diary
A Pinterest board where a clinical trial site can “pin” news articles, blog postings, and enrolling clinical trials
A Facebook page for the study

Although the forums and types of social media are distinct, the review by the institutional review board (IRB) is based on the same fundamental principles and regulatory requirements that govern review of traditional recruitment materials.

Regulatory Basis

An IRB has “the authority to approve, require modifications in, or disapprove all research activities” covered by IRB regulations (21 CFR 56.109; 45 CFR 46.109). In addition, an IRB is required to ensure that appropriate safeguards exist to protect the rights and welfare of research participants (21 CFR 56.107(a); 21 CFR 56.111; 45 CFR 46.109).

To fulfill these responsibilities, FDA guidance indicates that the IRB is expected to review the methods and material that investigators propose to use to recruit participants, as recruitment is considered the beginning of the informed consent process for participants. The IRB must review advertising material to ensure that it is not unduly influencing and does not promise a certainty of cure beyond what is outlined in the informed consent form (ICF) and protocol.

These regulatory requirements and expectations may present a challenge to the IRB when asked to review campaigns where complex risk and/or benefit information is communicated to the potential participant. Applying current regulatory tenets to the realm of social media requires flexibility and sensitivity to the nuts and bolts of social media platforms and how they function.

Review Standards

As noted in the FDA information sheet Recruiting Study Subjects, the IRB should review the information contained in an advertisement and the mode of its communication. Generally, the following types of material should be reviewed:

Recruitment

Any direct advertising using social network ads, display ads, banner ads, rich media ads, paid search ads, and in-text ads
Any free-form listing of study-specific information including but not limited to a study description, contact information, and compensation designed to recruit participants
Any study-specific websites or posts designed to recruit participants
Any study results published or disseminated with an intent to create interest in new research opportunities

Communications

Any study- or site-specific websites or social media intended to serve as support for enrolled participants
Any communications intended for study retention or advertising for future studies

Interactions

Any study or site-specific websites or social media that allow for user-generated content
Any requests for the provision of identifiable private information (e.g., health) from potential or current participants
Any protocol study tools (applications or software) used to collect data for the research (e.g., an app that captures glucose or blood pressure readings, an app that interfaces with an implanted device, etc.)

IRBs may have varying policies regarding how this information should be submitted for review (e.g., final text and graphics). Researchers should consult with the IRB of record to ensure they understand IRB requirements.

Review should be undertaken in accordance with the guidelines set out in FDA guidance and the IRB’s written procedures. In addition to the standard guidelines, the IRB should account for any unique issues that may be unduly influential or raise privacy issues based on the proposed activity and the technology being used. For example, IRBs could legitimately raise concerns about using an open Facebook group to recruit, given that posts made to the page by interested parties could be viewed by others on the platform, resulting in potential inadvertent disclosures of sensitive health information.

Interactive Social Media Programs

One of the most difficult parts in a social media program is managing interaction with participants. Where an investigator, sponsor, or participant will interact with another participant (ge., through a Facebook page or an online message board), a written management/communication plan is advisable. The plan serves two prongs:

Sponsor/Site– Development of a plan allows a sponsor/site to define the nature, frequency, and scope of social media interactions, and ensure the rights and welfare of research participants are protected.
IRB– The IRB can use the plan to evaluate the social media program and ensure it is not unduly influential or coercive. Additionally, where social media will be used for the retention of participants, the IRB can ensure the information given to participants is in accordance with the regulations, and appropriate safeguards exist to protect the rights and welfare of research participants.

Conclusion

IRBs must consider a number of factors in developing review standards for social media and guidelines for social media plans. Existing guidance and regulations provide a good starting point for researchers and IRB to collaborate in ensuring social media recruitment strategies are ethical and appropriate.

While the pandemic’s long-lasting effects on clinical trials are not yet fully known, effective financial management is a critical component to inform the business adjustments your site is making in an ever-changing industry. Rethinking how your site’s fiscal priorities have shifted–and the possible effects of these shifts on operations, sponsors, and participants–can help ensure your financial management leads to long-term business success.

While the basics of tracking clinical trial financial activity have not changed, the tools used and the varying trial designs have significant ramifications on how clinical research sites comprehensively manage finances. Now more than ever, clinical research organizations need actionable business insights. Trial complexity, increasingly challenging recruitment, and shrinking study budgets all necessitate strong financial management.

Using clinical trial software empowers organizations to understand, monitor, and adjust financial operations as needed, especially over time and through changing industry dynamics. Clinical trial software is often equipped with business intelligence modules, allowing research organizations to get the answers they need with unparalleled access to real-time business data with the ability to create actionable reports almost instantaneously. The ability to visualize financial information at a granular level not only supports trial work but is necessary to satisfy sponsors and regulators.

Beyond day-to-day fiscal oversight and analytic evaluation, financial management supports clinical trial innovation, drives business growth, and increases revenue. Deploying a clinical trial management system (CTMS) and eClinical solutions enables sites to run distinct reports across all levels of the business. This helps visualize best (and worst) practices to enhance risk mitigation and leads to future growth opportunities. These reports help organizations make necessary business decisions regarding materials, personnel, space, and technology investments, all facilitating success.

It’s critical for CTMS and eClinical systems to support financial data collection, analytics, and reporting in order to maintain effective and efficient fiscal management. Leveraging a powerful and comprehensive suite of solutions can help a site manage the industry complexities at play today and for years to come.

In clinical research, utilizing your clinical trial management system (CTMS) to its fullest potential can allow for more streamlined financial management, visit management, compliance, patient recruitment, and more. But when looking for the right CTMS system or learning more about your organization’s current platform, what should you look for?

While it’s important to note not all CTMS are the same, understanding your organization’s operations, including its inefficiencies, can help you understand how to get the most from your system. This blog outlines what you should look for in a CTMS to maximize your organization’s return on investment (ROI).

Integration

Especially for large academic medical centers, cancer centers, and health systems, a key capability to streamline financial workflows and billing compliance is integration with your electronic medical record (EMR) system. For example, Advarra’s OnCore CTMS and Clinical Conductor CTMS are able to send complex study billing definitions to an EMR system through the Integrating the Healthcare Enterprise’s (IHE) clinical research process content (CRPC) profile. This means all applicable team members involved in the research and/or billing process can leverage the same billing designations. If a patient is also a participant enrolled in a study, this status is visible to the organization’s billing office, ensuring charges are routed properly, and potential billing issues are avoided.

Negotiate Contracts and Maintain Budgets

Regardless of the size of your site or your research volume, negotiating is necessary to ensure your team is receiving the maximum amount of money possible to conduct a study. However, in order to know how much money you should ask for, you need to know what your budgets currently look like and how your organization tracks expenses. If staff are just tracking numbers in spreadsheets, there’s still room for error.

A CTMS should help set up a comprehensive budget for each protocol. To get the most out of a budgeting tool, a CTMS can allow you to:

Gain visibility into financial needs per participant and per procedure
Maintain consistent costs for each procedure and protocol
Calculate the organization’s overhead
Help justify costs to the sponsor

For trials currently conducted, a CTMS enables you to track invoices and payments received from sponsors, helping to maintain a positive cash flow. Furthermore, these tools can allow you to see current transactions and identify which payments are outstanding.

Ensure Timely Payments to Participants and Vendors

As there are many moving parts in any given study, properly paying participants is no exception. It’s vital for staff to stay on top of it and promptly record visits so they can receive payment. If a visit isn’t recorded immediately, staff run the risk of delaying payment or forgetting to record it altogether. Additionally, vendors expect to be paid on time. Missing or delaying payments to them can potentially hinder any relationships built over time – or worse, jeopardize future opportunities.

As a central location for study-related information, a CTMS can make it easy to connect information between visits and financials. If a CTMS can automatically connect participant visits to financials, it greatly reduces the chance for errors to occur and further streamlines your workflows. When looking for an enterprise CTMS, understand it should enable you to:

Provide visit tracking to ensure participants receive fast, accurate reimbursements
Easily pay vendors
View payment statuses at a glance
Retrieve payment history quickly

Understand Time Spent on Protocols

In order to improve site productivity, you must understand the current protocol’s resource requirements and identify any potential inefficiencies. Compiling workload data is especially important in understanding time requirements in a protocol. Often tedious, it’s usually pushed to the side in order for staff to focus on more study-related tasks. However, if the time per task isn’t properly monitored, you may come up short when budgeting for time spent on a protocol. A CTMS’s effort tracking feature replaces spreadsheets and calculators, giving researchers a centralized location to store information critical to a study. Staff can benefit from an automated effort tracking system by:

Gaining insight into time spent on protocol tasks
Identifying inefficiencies
Justifying costs

Using a CTMS to its’ fullest potential allows you to improve financial workflows by centralizing information, automating communications, and ensure documentation is current. Over time, with the help of a CTMS, sites will have the ability to maximize their ROI, take on more protocols, and enhance their relationships with participants and vendors.

Clinical trials for gene therapy are booming, especially in the fields of oncology, infectious diseases, rare diseases, and regenerative medicine. In January of 2019, then-Food and Drug Administration (FDA) Commissioner Scott Gottlieb and Peter Marks, Director of the FDA Center for Biologics Evaluation and Research (CBER), announced new policies to advance gene therapy research and described the current state of gene therapy as “…similar to the period marking an acceleration in the development of antibody drugs in the late 1990s, and the mainstreaming of monoclonal antibodies as the backbone of modern treatment regimens.”

That prediction is already becoming reality. Consider: the FDA set records in subsequent years for Investigational New Drug (IND) applications for products containing engineered genetic material. Also, the three COVID-19 vaccines with FDA emergency use authorization (Pfizer, Moderna, and Janssen) all contain engineered genetic material.

Data adapted with permission from Peter Marks, Director, FDA Center for Biologics Evaluation and Research (CBER). Originally published in Applied Biosafety, 2019.

Current State of Gene Therapy Oversight at Institutions

Institutions receiving National Institutes of Health (NIH) support are required to have an institutional biosafety committee (IBC) review of research involving engineered genetic material (recombinant or synthetic nucleic acid molecules). Traditionally, IBCs at academic institutions meet monthly or sometimes quarterly, predominantly focusing on basic science research performed in laboratories and animal facilities rather than clinical trials. Given their charge, many IBCs may lack the expertise or experience to review clinical trials. To efficiently review gene therapy studies, the IBC should have expertise in human gene transfer as well as policies and procedures for the review of clinical trials.

Waiting until a gene therapy clinical trial is submitted to recruit an ad hoc reviewer or develop procedures for performing the review can introduce unnecessary and lengthy delays. Furthermore, some institutions’ institutional review boards (IRBs) will not accept a submission for a gene therapy study unless it is accompanied by the IBC review. Additionally, multisite studies can experience startup challenges on a greater scale, as sites with individual and locally administered IBCs involve different submission deadlines, meetings schedules, policies, and procedures and increased variability in review outcomes.

What Can Institutions Do to Prepare for a Surge in Gene Therapy Research?

The NIH allows institutions to utilize multiple IBCs, creating a situation where an institution can rely on an externally administered IBC with reviewer expertise in the clinical environment and human gene transfer research, while retaining their locally administered IBC for basic science research involving laboratories and animal models.

This approach provides similar benefits as central IRB review for clinical trials, such as increased review efficiency and consistent protections and oversight for multisite studies. The central IRB review concept was considered so beneficial that the NIH instituted a single IRB policy for NIH funded studies (effective January 25, 2018). The federal government followed suit with revisions to the Common Rule (45 CFR 46), the rule of ethics in the United States regarding biomedical and behavioral research involving human subjects, to require a single IRB (sIRB) of record for all federally funded research (effective January 20, 2020).

Institutions with externally administered central IBCs may position themselves as “gene therapy ready” to reflect the benefits of such a partnership and make them more attractive to sponsors and contract research organizations (CROs) during the site selection process.

In a 2021 interview with Advarra, Dr. Fred Locke, Director of the Moffitt Cancer Center’s Immune Cell Therapy program, stated, “If you can have a centralized IRB and IBC review, it simplifies the process.” Minimizing startup delays is of paramount importance, particularly in resistant or refractory disease cases.

As an example, the externally administered IBC review performed by Advarra has significantly streamlined study activation timelines. Advarra’s IBC averaged turnaround times of 3.3 business days (N = 118 reviews) from submission to review for National Cancer Institute (NCI) designated cancer centers. These centers previously experienced turnaround times of up to three to four months when working with their locally administered IBCs.

When the COVID-19 pandemic hit North America, Advarra’s IBC was able to prioritize review of COVID-19 research. Because Advarra has full-time resources dedicated to conducting and managing IBC review activities, Advarra’s IBC averaged 1.7 business day (N = 152 reviews) turnaround times on reviews for COVID-19 vaccine research. Advarra has also accelerated startup for the Meridian Clinical Research Network and IQVIA, the world’s largest CRO.

Where Should Institutions Start?

The best way an institution can prepare to participate in any gene therapy studies is to register an IBC with the NIH and become familiar with the basic requirements for IBC review. As the NIH Office of Science Policy (OSP) review of an institution’s IBC registration may take four to six weeks, institutions can compress timelines by registering their IBCs well in advance of having a new study ready for IBC review. This way institutions are ready to start the IBC review process immediately. There is no cost associated with registering an IBC with the NIH, and institutions may be registered with several IBCs.

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

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

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

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

The Considerations of IND Safety Reporting

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

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

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

Technology to Support IND Safety Reporting

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

While enrolling subjects is arguably the most crucial aspect of clinical research operations, this cannot be done without activating a study. Recently, Advarra conducted an anonymous survey to collect site-specific study activation data to help understand how sponsors can enable faster study activation at sites. This complex process must be done promptly to ensure resources are used appropriately and to reduce both site and sponsor costs.

However, as research continues to grow more complex, regulatory requirements evolve, and sites continue to take on more studies, the activation process continues to lengthen. With this in mind, how can sponsors best leverage their assets to ensure a seamless and efficient site activation process?

Leverage a Commercial IRB and IBC

An essential step in the study activation process is ethical protocol approval. Sponsors can set sites up for success by learning early if the site can work with a commercial, institutional review board (IRB), and institutional biosafety committee (IBC). By working commercially rather than locally, sites can experience a streamlined process through quicker access to information, enhanced communication, and easier record management. The more studies you send through a commercial IRB or IBC, the faster your relationship will build, ultimately making processes more seamless.

Additionally, working with an integrated IRB and IBC will benefit sponsors and sites alike. A way to encourage a site to use a commercial IRB (if they are able) is for sponsors to ask and understand what is needed in order to use one. This may help sites understand if a central IRB is available to them, it may be easier to use one. If the protocol is already approved by a central IRB for enrollment, the quicker researchers can move through the study activation process into the enrollment phase. The quicker enrollment occurs; the faster researchers can help sponsors meet their goals. More rapid activation and enrollment means less money is spent due to inaction.

When looking for an IRB or IBC to partner with, consider the following:

Speed
Flexibility
Accountability
Savings

Sponsors need to trust their protocol review will be of the utmost importance to an IRB or IBC, including efficient turnaround times and a dedicated point person to go to if any issues arise.

Understand Cost Recovery

A significant component of a site-sponsor relationship is understanding the cost for sites to run a research protocol. Sponsors should recognize how much it actually costs an individual site to conduct research. While many sponsors do understand these costs, it’s essential to acknowledge that, for example, a lot of sites are impacted by their institutional rules stating they cannot be compensated for a for-profit research program. Many state institutions paid with taxpayer money cannot subsidize industry clinical trials with taxpayer money; therefore, the cost of running a sponsored clinical trial is fully burdened on the site. As a sponsor, it is important to be cognizant of these types of implications when providing budgets to sites.

Survey results indicated sites want to ask sponsors to cover some infrastructure costs. In an effort to ensure research is conducted correctly, sponsors should be willing to engage in a dialogue to better understand the site’s costs at hand, and the sites should be able to provide specific information as to what those costs are. If sites are only providing a lump fee for activation to the sponsor, it is appropriate for the sponsor to ask to clarify that fee to better understand the infrastructure costs associated with running the study. Sponsors can use this information to make suggestions on how to better reduce costs to the site, which also helps sponsors understand the amount of time, effort, and resources dedicated from the site to the study.

Invest in Site Training and Engagement

Despite evidence of accelerated activation timelines and increased protocol compliance, efficient and comprehensive site training is often stuck in traditional investigator meeting formats not yet updated with best practices. Investing in site training and engagement technologies supports a quick and adequate understanding of study procedures, mechanism of action, and more to keep your research moving forward.

Training technology that stores, tracks, and facilitates training pieces like multi-media content, eLearning modules, virtual investigator meetings, training certificates, and amendment rollout also allows your study teams to monitor site training and activate sites in a timely and compliant manner. This investment not only supports site activation but maintains compliance as new site staff are brought on board and allows existing site staff the opportunity to refer to the training should questions arise.

Explore how a top-20 pharmaceutical company leveraged the Longboat Platform to expedite activation via study-specific training, decrease screen failures by 50%, increase enrollment by 20%, and achieve 21% fewer protocol deviations.

Communicate Effectively

As with anything else in research operations, clear and efficient communication between site personnel and sponsors is key to smoother study activation. As seen in survey responses, site operations teams reported delays in sponsor and researcher responses. Concisely identifying needs and requesting an appropriate response timeline will help everyone feel they are moving forward with all site activation activities instead of their communications feeling like they went into a black hole.

Additionally, sponsors can save time during the site activation process by working with sites to create master agreements with certain institutions. This may include using language in budgets, contracts, and commercial IRB/IBC documents. Having a templated master agreement in place with multiple institutions will lower startup effort across time, even though the effort is greater upfront. For sponsors, knowing who to talk to at a site level to get a template in place is an excellent place to start.

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

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

The Need to go Beyond Sponsor-Driven Metrics

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

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

Examples of Site-Driven Clinical Data Management Metrics

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

Some examples of key site metrics include:

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

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

Collecting Data Directly from the Site’s Source of Truth

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

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

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

How Multiple Stakeholders Benefit from Site-Based Metrics

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

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

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

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

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

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

In a remote clinical research landscape, a successful virtual investigator meeting can ensure a more cost-effective and compliant clinical trial. So, what makes a virtual investigator meeting more successful than others? Conducting a successful virtual investigator meeting relies on convenience, intentional engagement, and extended support. This blog will expand on those critical elements and provide examples of how to implement them in your next study.

Maximize Convenience

As a result of our new remote research landscape, principal investigators (PIs) and site staff will expect virtual options and accommodations. With busy schedules, tight budgets, and varying time zones depending on the study, it is easy to understand why site personnel are more inclined to train virtually. Maximize the convenience of your virtual investigator meeting even further by:

providing multiple virtual training events to accommodate schedules across your global footprint
considering a mix of mediums, with the deployment of training before an in-person Q&A web-meeting
offer training in the appropriate language for the location
and offer an on-demand option for those who were unable to attend or need a refresher to review on their own time.

Now that your virtual investigator meeting is as accessible and convenient as possible, utilize these strategies to make the most of your highly attended events.

Engage with Intention

Due to short attention spans, Zoom video conference fatigue, and minimized ability to gauge comprehension, implementing purposeful engagement strategies is essential to a stronger understanding and retention of training materials and can be even more effective than in-person meetings. Training tools such as multimedia, eLearning, quizzes, presentations, and more should be blended to keep audiences involved, engaged, and learning.

Multimedia: videos, animations, audio, etc.

Cater to both visual and auditory learners with videos designed to captivate and educate with clarity. Teach staff about protocol visits and procedures through short engaging videos. Use illustrated, 3D animations to ensure comprehension of the investigational product’s mechanism of action and complex treatments.

eLearning Modules: quizzes, reading materials, etc.

Utilize eLearning mechanisms to break down complex topics into understandable pieces and implement quizzes to test comprehension of base concepts before building further on them. eLearning can also support education before and after the virtual meeting. Online completion of training concepts spanning multiple studies, like GCP (good clinical practice) and HSP (human subject protection), reduces the duplicate effort for both the sponsor and staff members who have already completed standard training for other protocols.

PowerPoint Presentations

Not all PowerPoints are created equal and can be misinterpreted, varying widely between presenters and meetings. Make sure yours are intentionally designed, easy to read, and illustrated to increase effectiveness and consistency across presenters. Keep them short and integrate discussion questions or polls to touch base with your audience and gauge comprehension.

Extended Support & Access

Frequently disregarded, the key to executing a successful virtual investigator meeting is extending support and access to materials before as well as after the event itself. Frequent touch points with learning materials and access to training beyond the virtual event increase retention and engagement among users. Distribute eLearning materials before the event to prime information and lay a foundation for meeting discussion.

Time between the investigator meetings and a site’s first enrollment, as well as staff turnover and onboarding, can threaten an investigator’s adherence to the protocol and study efficiency. Virtual Investigator Meeting recordings, materials, and custom training content should be available on-demand for all necessary stakeholders.

Effectively extending support and training access to sites requires a solution to house meeting recordings and materials, as well as the ability to manage and store necessary training documents. Advarra’s experienced training staff helps successfully conduct virtual investigator meetings using the best practices above, and they are complemented by the Longboat Platform as the hub responsible for storing, managing, and tracking all training items.

Rooted in the strategies above, leverage Advarra’s 20 years of experience in site training and event management to conduct a successful virtual investigator meeting. Powered by the Longboat Platform, download the overview to learn what to expect from Virtual Investigator Meetings by Advarra.

While it may not have been common a few short years ago, cell and gene therapy’s popularity has grown exponentially in the past year, as researchers are rapidly expanding our understanding and potential uses of these innovative therapies.

The possibilities with this new technology are exciting. However, it’s important to understand how cell and gene therapy research is different from traditional drug development.

Cell and Gene Therapy vs Small Molecule Research: Understanding the Difference

From an institutional review board (IRB) perspective, the ethical and regulatory framework to review cell and gene therapy clinical trials and traditional drug trials are the same.

However, in many gene therapy trials, there’s an extra layer of review from an institutional biosafety committee (IBC). This isn’t always required, as it depends on federal support, but it’s considered best practice to include IBC review. This extra review is required because some gene therapies may make permanent, unchangeable impacts on the body, where traditional drug therapies eventually metabolizing out of the system. Since gene therapy has the ability to alter the human body at a cellular level, research staff preparing the products need to be educated and have appropriate procedures for safe handling.

As research and development of cell and gene therapies for cancer, Alzheimer’s, Huntington’s, a multitude of rare diseases, and other conditions move beyond academic medical centers (AMCs) and make their way into broader communities via Phase II and III trials, specific infrastructure is critical to ensure research sites are prepared to run a cell and gene therapy trial.

Building an Infrastructure

Many sites need guidance for conducting cell and gene therapy research safely and successfully. The extra work involved in these trials is sometimes surprising to stakeholders. These studies involve more regulatory logistics and preparation for executing the protocols, mainly through product handling. It’s important to account for shipping logistics, reviews, and other necessary startup requirements. Working with participants in different parts of the US may necessitate shipping biological materials with specific storage requirements, and not all sites are prepared for the specialized containment necessary. For more information on how to prepare your site, see our blog How Sites Can Win in the New Age of Genetically Engineered Treatments.

A Focus on Rare Diseases

Much of the promise of cell and gene therapies surrounds cures for genetically based rare diseases. When working in rare disease research, startup speed and first-patient-in timelines are of utmost importance. Oftentimes, when researchers are working with rare diseases, they are working with a very specific patient population – there may only be 1000 people in the world affected by this disease. Recruitment efforts need to be very precise to find the appropriate participants for these studies.

Because these studies can be very niche and selective, oftentimes, research staff and participants form a bond as they get to know one another. As the therapy is personalized, relationships become personal as well. Since the relationship is personal, the race to find a solution is more urgent. The mission of these studies has the ability to become very personalized since everyone is banded together.

Since this technology is still relatively new to the industry, study cadence and best practices are not yet identified or built into standard study designs. However, patient advocacy organizations may be willing to help and offer their expertise and support as researchers work to find a cure.

Current Cell and Gene Therapy Volume

Over the past year, Operation Warp Speed – the race to create a vaccine to combat the COVID-19 virus – elevated cell and gene therapy research into the spotlight via notable vaccines developed using mRNA and viral vector technology. While cell and gene therapy has been in the works for the past decade, the pandemic exposed the world to the promise of using genetically engineered materials in treatments. Recent FDA approval of a gene therapy with the ability to cure childhood blindness provided additional excitement for the cell and gene therapy space.