Clinical research is a vital driver of medical progress. Yet, many people are unaware of the essential role of institutional review boards (IRBs) in protecting clinical trial participants by ensuring compliance with human subject protection requirements. With more than three decades of experience, Advarra is dedicated to advancing clinical research by providing expert oversight. As a trusted partner in supporting the advancement of life-changing therapies, Advarra prioritizes transparency, compliance with regulatory requirements and guidance, integrity, and participant safety in every trial. The company’s rigorous review process, conducted by professionals—physicians, clinicians, therapeutic area experts, pharmacologists, and others—with deep expertise across various scientific disciplines, as well as non-scientists who provide ethical balance and participant advocacy, ensures that trials meet regulatory requirements and the highest ethical standards and minimize risks to study participants

What is Clinical Research? 

Clinical research tests new treatments and therapies to determine their safety, effectiveness, and potential to improve health outcomes. It is the foundation of medical innovation. Advancement in treatment of diseases—from cancer to diabetes to rare diseases—have all come about because of clinical trials.  Clinical trials progress through several phases:

  • In Phase I, the focus is on testing the safety, dosage, and side effects, rather than effectiveness of a new treatment in a small group of participants.
  • Phase II further assesses safety, investigates whether the new treatment is effective, and determines the optimal dose.
  • Phase III involves more significant groups of participants to confirm the new treatment’s effectiveness, monitoring long-term safety, and comparing it to existing therapies. 

Participants in clinical trials bravely volunteer to help test new treatments, contributing to scientific advances that ultimately stand to benefit society. This process ensures that new therapies meet the U.S. Food & Drug Administration’s standard for safety and efficacy. A critical part of clinical trials is to learn and confirm scientific assumptions, and to incorporate learnings to enhance the study protocols for the sake of safety, efficacy and efficiency to introduce products to patients in need.

The Vital Role of Institutional Review Boards (IRBs) 

As set forth in the federal regulations that govern the conduct of clinical trials, an IRB is an independent group of experts, including scientists and non-scientists, that reviews clinical trial proposals to ensure they meet ethical standards that are designed to protect participants’ rights. The role of the IRB is crucial in examining clinical trial designs to make sure the research complies with regulatory requirements and is ethically appropriate, informed consent procedures are thorough, clear, and transparent and that patient recruitment materials are accurate and not misleading. The IRB achieves its mission through a comprehensive and thoughtful review of study-related information/documentation (e.g., protocol, investigational product information, informed consent form(s), other participant facing materials).  This process better enables investigators and participants to engage in a discussion that empowers participants to fully understand the nature and potential risks and benefits of the trial, before agreeing to participate.  The role of the IRB is to review the study documentation and Investigator qualifications, collect safety reports, and evaluate requests for modifications to the study. The IRB does not monitor patients nor advise the sponsor on the design of the study.  Moreover, the IRB does not evaluate patients for inclusion or exclusion in a given clinical trial; such determinations are made by the investigators responsible for the conduct of each study. Advarra’s IRB is highly experienced and works diligently to provide expert oversight, ensuring that every clinical trial adheres to the highest ethical standards and is compliant with applicable regulations. 

The Impact of Clinical Research: Empowering Participants and Advancing Medicine

The existence of clinical trials is the reason why many life-saving treatment options are available today. For example, these trials may help to advance cancer treatments and chronic disease management medicines and potentially offer patients access to cutting-edge therapies that may not yet be available through conventional medical channels. 

The Future of Clinical Research

Advarra recognizes that clinical research is an essential component of medical progress, and we remain dedicated to upholding the highest standards of ethics, integrity, and regulatory compliance. 

Through expert oversight, Advarra works hand-in-glove with the most experienced researchers in the United States and Canada to advance new scientific discoveries. By remaining at the forefront of clinical research, Advarra is helping scientists and industry leaders bring new treatments to market and into the hands of patients who need them.

Institutional review boards (IRBs) play a crucial role in the ever-evolving field of clinical research. For more than 35 years, Advarra has been committed to protecting the rights and welfare of clinical trial participants while helping to improve healthcare outcomes, advancing medical knowledge, and bringing innovative, life-extending treatments to market that benefit millions of patients worldwide.

The Value of Clinical Research

Clinical research is the engine that drives medical innovation, leading to the discovery of new drugs, treatments and medical devices that enhance patients’ access to treatment options, improve patient care and outcomes, and transform the healthcare landscape. Innovations in fields such as immunotherapy, cancer and chronic diseases owe their existence to clinical trials, which judiciously test and evaluate safety and efficacy. Without clinical research, these medical breakthroughs would remain out of reach for patients. Over the years, Advarra has reviewed a wide range of clinical research studies and worked every day alongside leading pharmaceutical manufacturers, medical researchers, and healthcare institutions. Advarra ensures that clinical trials comply with the U.S. Food and Drug Administration’s (FDA)  regulations on good clinical practice, which are based on ethical standards outlined in frameworks such as the Belmont Report and the Declaration of Helsinki.

Protecting Trial Participants

Trial participants are courageous volunteers, and every step must be taken to ensure their rights and welfare are protected. That is not to say that they do not face potential risks. This is why IRBs are tasked with conducting an ethical review of clinical trial proposals to ensure participants are  informed of risks before and during their participation in any trial.

Advarra prides itself on not only providing ethical review services but also performing this critical work in a manner that fulfills regulatory requirements.  For example, Advarra’s IRB is composed of approximately 200 experts, including scientists with diverse and extensive therapeutic area expertise, allowing for specialized and highly knowledgeable reviews, as well as non-scientists such as legal experts, ethicists, and members with expertise in vulnerable populations offering a different perspective than members with scientific/medical backgrounds.   

Expertise and Experience

Advarra’s value to clinical research is driven by its team of dedicated professionals and collaborations with highly qualified research experts. Advarra draws members from leading academic institutions, government agencies, and clinical research organizations. This includes researchers, ethicists, and compliance professionals with decades of experience, many of whom have worked with prominent institutions and top academic medical centers. The team also receives ongoing training and professional development to stay at the top of current clinical research practices.  

Furthermore, Advarra’s IRB includes hundreds of expert members, many of whom bring expertise and experience in several therapeutic areas and disciplines, including oncology, bioethics, investigational pharmacy, internal medicine, psychology, physiology, radiology, public health, pediatrics, nursing, and social and behavioral science. Many individuals that belong to Advarra’s extended network of experts are active or recently retired clinicians from academic and large network clinical and hospital entities such as Harvard University, Mayo Clinic, Vanderbilt University, and several National Institutes of Health designated Comprehensive Care Centers.

This unique depth of expertise allows Advarra to maintain the highest standards in clinical trial reviews.

Industry-Leading Ethical Standards

Advarra is organized and operates in compliance with U.S. and Canadian regulations and policies governing research with human subjects, as applicable, and is fully accredited by the Association for the Accreditation of Human Research Protection Programs (AAHRPP).  Advarra’s commitment to quality and ethical conduct is apparent in our internal policies and operational procedures, which often exceed federal regulations and set a benchmark for the industry.  One such area that has always remained a focus for Advarra is our commitment to a robust set of policies that govern potential conflicts of interest.

Moreover, Advarra separates client services and IRB review teams to guarantee each clinical trial we review is unbiased.  This firewall ensures that clinical trial reviews focus solely on ethics and scientific integrity.  

Investing in Improvements

At Advarra, we understand that to maintain our position as a trusted partner to the clinical trials ecosystem, we need to invest in our people, processes, and technology.  While other companies in the clinical trial industry are reducing staff and investments in technology, Advarra is committed to fostering continued innovation. One significant investment in this area is the Center for IRB Intelligence (CIRBI) platform, which streamlines the review process, improving the speed and quality of clinical trial evaluations. Over $25 million has been invested in this platform to enhance the effectiveness of the IRB process without compromising its thoroughness. Advarra has continuously hired additional staff to manage the increasing workload, demonstrating our commitment to continuous improvement and ensuring our standards align with Advarra’s best-in-class practices.

Looking to the Future

Advarra’s work benefits clinical trial participants and the entire healthcare ecosystem. By ensuring clinical trials are ethical and are held to rigorous standards of scientific integrity, Advarra helps advance the development of new therapies and treatments. Advarra’s commitment to quality, transparency, and continuous improvement sets a high standard for clinical research, ultimately advancing medical science and improving patient outcomes worldwide.

2024 has been a year of growth and evolution in clinical research. The coming year is expected to be no different. As we look to 2025, Advarra thought leaders have compiled predictions and perspectives on key topics shaping the industry. These topics include perspectives on how artificial intelligence (AI) will be leveraged in clinical research, key regulatory trends shaping the industry, the movements of site consolidation, the continued challenges (and potential solutions) of study startup, and more.

2024 has been a year of growth and evolution in clinical research. The coming year is expected to be no different. As we look to 2025, Advarra thought leaders have compiled predictions and perspectives on key topics shaping the industry. These topics include perspectives on how artificial intelligence (AI) will be leveraged in clinical research, key regulatory trends shaping the industry, the movements of site consolidation, the continued challenges (and potential solutions) of study startup, and more.

Prediction Area: Artificial Intelligence

Advarra Thought Leader: Jeff Sidell, CTO

AI in clinical research is poised for significant evolution, driven by advances from organizations like OpenAI and Anthropic. These companies are laying the groundwork for more sophisticated AI applications designed to transform clinical operations, improving both efficiency and productivity. In addition to generative AI, there is promise in predictive analytics, which can leverage historical and real-time clinical operations data to forecast outcomes, optimize resource allocation, and streamline timelines.

AI can also automate labor-intensive tasks, such as extracting key information from protocol documents to populate downstream systems. For example, AI tools can pull data from protocols and automatically update clinical trial management systems (CTMS), reducing manual entry errors and increasing workflow speed. This same data could be used to auto-generate study calendars based on the schedule of assessments, streamlining trial planning.

Moreover, AI can enhance study design by analyzing past trials and recommending improvements based on data patterns. Site selection will also benefit from AI by identifying optimal sites with a high likelihood of recruitment success, considering factors like demographics, past performance, and patient availability. As AI continues to evolve, its ability to transform the efficiency, quality, and scalability of clinical research will grow exponentially.

Prediction Area: Study Startup

Advarra Thought Leader: Ashley Davidson, VP Product – Sponsor Technology

Clinical research study startup will continue to pose challenges for sponsors as the industry’s tendency to address individual process pain points with focused, siloed solutions persists. While these targeted technologies may offer immediate relief in specific areas – such as site identification, contract management, or regulatory document collection – they often fail to integrate seamlessly with other aspects of the startup process.

This fragmented approach results in inefficiencies and data silos, slowing down study initiation rather than accelerating it.

Sponsors, in pursuit of solving these isolated issues, may overlook the broader need for a more connected and streamlined workflow across the entire study startup process. To truly address the complexity of study startup, a more holistic strategy is needed – one prioritizing system integration and data connectivity. By linking key steps, such as site selection, regulatory submissions, and contract negotiations, sponsors could improve transparency and reduce redundancies.

The future of study startup will likely involve an increasing recognition of the value of connected systems enabling real-time data sharing and decision making. However, achieving this vision will require a shift from focusing solely on fixing individual pain points to building a unified, interoperable framework to bring together data and processes across the study startup ecosystem.

Prediction Area: Regulatory

Advarra Thought Leader: Julie Ozier, SVP Global Review Regulatory

Regulatory bodies, particularly the U.S. Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA), will continue to drive harmonization in the clinical research industry. Over the years, these agencies have made significant strides in aligning their rules and guidance, as seen with the harmonized definition of an institutional review board (IRB), informed consent, and the recent implementation of the single IRB (sIRB) model. This push for consistency aims to streamline regulatory processes and reduce administrative burdens for sponsors and researchers.

As the harmonization effort advances, the focus will likely shift toward refining guidelines and regulations for vulnerable populations, including children, pregnant women, and prisoners. These groups require special protections in clinical trials, and aligning regulations across agencies will simplify the ethical review and approval process for studies involving these populations. This consistency will enable more efficient trial oversight while ensuring the highest standards of protection for vulnerable participants.

Continued harmonization will not only ease the regulatory burden but also facilitate faster study initiation and improve compliance. It will foster a clearer, more unified regulatory framework, reducing confusion for sponsors and researchers, ultimately enhancing the inclusivity and efficiency of clinical research involving vulnerable groups.

Prediction Area: Increased Site Consolidation

Advarra Thought Leader: Christine Senn, SVP Site/Sponsor Innovation

After a year of site consolidation slowing down due to difficult times for most independent sites from Q3 2023 to present, 2025 will see an upsurge in consolidation.

There are varied opinions about site consolidation, but I would like to add some perspective: Pharmaceutical companies routinely buy up small pharmaceutical and biotech companies and add them to their portfolio. Contract research organizations (CROs) only came into existence in the 1980s and were, by default, all small when they started; consolidation brought us the large CROs we know of today and are used for global trials. Hospital systems built up smaller, independent hospitals and independent regional clinics, all in the hopes of improving profit margins by consolidating centralized operations – which has the goal of keeping these clinics and hospitals in business in order to reach more patients.

Site consolidation is much the same. It has its pros and cons, but I will speak to the positives of such consolidation. They are, of course, similar to the reasons all the businesses just mentioned aim to consolidate. First, in nearly any business in any industry, staying afloat financially is difficult. Consolidating resources and streamlining processes can improve profit margins, which can keep businesses afloat longer.

Second, there will always be some locations or business arms not doing well financially. In the case of clinical research sites, no sponsor wants to see a site close while they are in the middle of a trial. Being part of a larger network, the network is able to provide resources to stay afloat and continue doing research even while losing money. This is also true of academic medical centers, which often see their research activities losing money while the other business lines are able to keep this important endeavor afloat. It is often critical to conduct research without much, if any, profit.

Third is a related topic. As we approach a crisis of a lack of principal investigators and have become increasingly acutely aware of inadequate diversity and clinical trial enrollment, opening new sites is paramount to helping the industry as a whole. Again, a site network has the ability to help keep a new site bankrolled. In my experience, a new site is likely to lose money for up to a year.

Fourth, consolidation at a global level can improve trial enrollment and efficiency. There are many ways in which being a small biotech company, small CRO, or individual site is absolutely wonderful for this industry. At the same time, we know global sponsor companies and global CROs offer unique benefits in reach, understanding country-specific regulations, having staffing already onsite in various locations, etc. Global site networks offer a similar benefit.

Prediction Area: Industry Standards

Advarra Thought Leader: Elisa Cascade, Chief Product Officer

The increasing complexity of clinical research studies will continue to have far-reaching implications, particularly in terms of cost and efficiency. As protocols grow more complex, the associated cost to operate these studies rises at a time when sponsors are under pressure to manage expenses while also accelerating the pace of research. This tension between cost containment and speed to market highlights the need for innovative solutions to streamline processes and consolidate technology systems all without sacrificing quality.

One promising approach is the adoption of industry-wide standards which open the door towards greater connectivity and a digitized data flow. For example, use of a common protocol template can drive consistency and efficiency, reducing the time and effort needed for study design and technology setup. Standardization also simplifies integration between site and sponsor technology systems, enabling all users to operate in their system of choice and data and documents to flow throughout the connected ecosystem.

While the industry will continue to identify opportunities for standardization, implementing these standards will remain a challenge. Diverse stakeholders, competing priorities, the need for change management in large, conservative, process-driven organizations, and in some cases, older, monolithic technology can all slow down progress. To realize the full benefits of standardization, the industry must work collaboratively, overcoming hurdles in adoption and ensuring new standards are embraced and applied consistently across all phases of clinical research.

Selecting an electronic institutional review board (eIRB) system is a critical decision for institutions looking to streamline their research compliance processes. Navigating the eIRB landscape can be overwhelming for researchers, human research protection program (HRPP) team members, and institutions alike.

The responsibility to manage submissions, track approvals, and ensure compliance with increasingly complex regulatory standards is a top priority for the research community. Transitioning from a paper-based approach or an existing eIRB system can introduce both opportunities and challenges, making it essential for impacted teams to understand an eIRB system’s intricacies.

Research integrity is paramount, and selecting the best eIRB system for your institution is crucial. An effective eIRB system should streamline and enhance the review process while ensuring adherence to regulatory requirements.

Choosing a system that does not meet an institution’s expectations can lead to administrative burdens, inefficient workflows, delays in the review and approval of research proposals, and can lead to noncompliance with regulatory requirements.

Assess Your Needs

Each institution has unique policies (or local laws), workflows, and user expectations to consider when evaluating an eIRB system. Identifying your specific needs for an eIRB solution is crucial to ensuring the selected system effectively supports your institution’s research compliance requirements and goals. Some steps to take are:

  • Assess current processes: Begin by evaluating your current IRB processes and identifying pain points; as appropriate, this can also be completed for conflict of interest (COI), institutional animal care and use committee (IACUC), and institutional biosafety committee (IBC), especially if there are communication gaps between these offices. What are the major inefficiencies? Does the current process include burdensome workarounds and impacts your ability to efficiently complete reviews? What specific features are necessary for your institution? Would your institution benefit from a system with integration capabilities, the ability for customized reviews and process, or standardized templates and checklists?
  • Assess current eIRB system: Evaluate your current eIRB system and identify if it meets your institution’s expectations. Does the current system include upgrades, enhancing its features and functionality? Will the system upgrades impact research processes beneficial to the institution, such as increased efficiency and improved compliance?
  • Evaluate data migration: What historical protocol information will need to be transferred to a new eIRB system? Will the vendor assist with data migration efforts, or is the institution responsible for inputting historical data manually into the new system?
  • Review current research portfolio: What is the volume of your research portfolio and what type of research is conducted? What are the current turnaround times for the existing portfolio and what improvements need to be made to minimize future review delays?
  • Evaluate your ancillary review process: Does your research portfolio require ancillary reviews, such as radiation safety, COI, IBC, or scientific? Consider a system to help improve the efficiency and effectiveness of your institution’s ancillary reviews.
  • Analyze institutional research strategy: Is your institution looking to grow research? Will your institution be expanding support for the types of research conducted – i.e., sponsor-investigator research? Will the new eIRB system have the capability to support the institution’s research strategy?
  • Obtain stakeholder input: Engage with IRB members, researchers, and HRPP team members to gather insights into their needs and preferences. This will help in identifying must-have features and potential pitfalls. For example, what other systems (e.g., a clinical trial management system [CTMS], HR systems, learning management systems [LMS]) are stakeholders using? Is it beneficial to look for an eIRB system integrating with them?

Taking the time to identify and prioritize the needs of those who will utilize the eIRB system will not only facilitate a smoother implementation but will also contribute to a successful research program and goals.

Key Features to Look For

Each eIRB system has its own selling points; however, it’s important to focus on the system supporting the ethical oversight of research, the complexity of managing submissions, keeping track of approvals, and ensuring compliance with regulatory standards. Additionally, a system should enhance the overall user experience when submitting to the IRB. Some key features to consider include:

  • Compliance and regulatory oversight: If appropriate, ensure the system adheres to regulatory requirements such as 21 CFR Part 11 and is compliant with protocol and IRB policies. The system should also include the ability to capture regulations applied to a research project such as Common Rule, Food and Drug Administration (FDA) regulations, and expedited and exempt regulations.
  • User-friendly interface: A system should be intuitive. It is important for users to be comfortable using the system and complete tasks when needed.
  • Customizable workflows: Look for a system allowing you to create unique workflows to fit your institution’s specific needs. For example, if a study includes radiation, will the system allow for automatic routing to the radiation safety committee? Also, consider if the workflows include automation to help streamline processes and minimize “clicks” (or manual work by a user) required to complete a specific task in the system. For example, can the system be set up to send out continuing review reminder notifications for protocols with an upcoming expiration date or annual check-ins for minimal risk research?
  • Smart form creation: To help streamline the submission process, an eIRB system should include the ability to create and maintain smart forms. Smart forms are built with customizable digital elements or logic and are intended to capture protocol information. Creating customizable forms provides a standardized format for researchers to present their study protocols and supporting study documentation. In addition, this helps create consistency across various studies submitted to the IRB and drives higher quality applications.
  • Study documentation: The system should be able to store historical study information that is easy to access, view, and download.
  • Reporting: Metrics are essential for evaluating a system’s effectiveness, efficiency, and overall performance of the submission process. Look for a system with the ability to create and download customized reports on approval turnaround times, submission volume during a specific period, or types of studies submitted (e.g., studies involving children).
  • Passive education: To help with user experience, look for a system including the ability to build in frequently asked questions (FAQs); help text; and quick links to regulations, guidelines, and internal policies.
  • Integration capabilities: Check if the system integrates well with other institutional systems such as the COI program, grants management, research compliance, and ancillary reviews. Consider other areas outside of research such as reporting and analytics systems, as well as CTMS. An eIRB system with integration capabilities improves operational efficiencies, enhances compliance, and supports a more collaborative research environment.

Comparing eIRB Systems

Comparing the different eIRB systems available is a crucial, yet daunting, step. With so many different systems available, it’s challenging to pick a system best for your institution’s needs. With any new system, the intent is to have one to utilize over time, so finding a good fit will take time. Some key areas to consider when selecting a new system are:

  • Vendor research: Compile a list of potential vendors and evaluate them based on features, functionality, customer support, and cost. Each vendor will have unique offerings, so it is important to evaluate systems with one another and with your current needs.
  • Experience: Look for venders with a solid footprint in the eIRB space and consider their experience in working with institutions of your size. It is also important to know if a vendor can adapt to your growing research needs, such as the ability to accommodate an increase in research portfolio size.
  • eIRB system upgrades: As technology evolves and the research landscape changes, a system should update to stay relevant. It is important to inquire about future system updates and how they support the ever-changing research environment.
  • Demo requests: Schedule demonstrations with each potential vendor for a more hands-on experience. This will allow you to see the system in action and ask questions specific to your needs.

eIRB systems are not software solutions that will fix every broken process at your institution. Selecting an eIRB system requires deciding on which features you can and cannot live without.

Selecting an eIRB system is a significant investment for an institution’s research program. Seeking external expertise and guidance can be beneficial when looking into a new eIRB system. By following a structured approach and carefully considering the needs of your institution, you can ensure a successful transition to an efficient and compliant eIRB system.

In the complex landscape of clinical trials, the data monitoring committee (DMC) serves as the cornerstone at the intersection of participant safety and data integrity. A pivotal aspect of a DMC\’s effectiveness is its member composition, particularly key opinion leaders (KOLs).

The Role of KOLs in DMCs

KOLs are highly respected experts in their individual fields, often with extensive research experience and deep clinical insights into specific therapeutic areas and indications. Their involvement in DMCs brings several benefits:

  • Expertise and insight: KOLs provide advanced scientific and clinical insights crucial for interpreting complex data and making informed decisions
  • Credibility: The presence of recognized experts enhances the DMC\’s recommendations, fostering trust among stakeholders
  • Network influence: KOLs can leverage their professional networks to facilitate better communication and collaboration across the clinical trial ecosystem

The Importance of a Large KOL Network and Independent Third-party Support

A large KOL network greatly benefits DMCs and clinical trial sponsors. When leveraging such a network, it’s critical to have the right administration tools to support diverse reviewers.

Diverse Perspectives

A large network of KOLs is essential for comprehensive and balanced decision-making. Different experts bring varied viewpoints and experiences, which can lead to more thorough assessments of trial data and better strategies for addressing potential issues.

A geographically diverse membership also brings varied viewpoints on local treatments, access, and therapeutic questions. An experienced third party should have an extensive network of KOLs across numerous therapeutic areas. This vast network allows the company to match the right experts with a clinical trial’s specific needs, ensuring DMCs are composed of the most qualified and relevant professionals.

Access to Specialized Knowledge

A clinical trial can often span multiple disciplines and therapeutic areas. A broad network of KOLs provides access to specialized knowledge critical for evaluating the nuances of trial data. This is particularly important in complex global trials where it’s required to have expertise in multiple fields.

With a diverse DMC, it is important to have a rigorous selection process to ensure only the most qualified and independent KOLs serve on DMCs. This process includes thorough vetting for both financial and contractual conflicts of interest, ensuring the committee’s decisions are unbiased and focused solely on participant safety and data integrity.

Enhanced Problem Solving

With a larger pool of experts, DMCs can more effectively address unexpected challenges during clinical trials. The collective problem-solving capabilities of a diverse group of KOLs can lead to more innovative and effective solutions.

It’s necessary to provide comprehensive support and infrastructure with geographically diverse committees, since these are critical to a DMC functioning effectively. Considerations include logistical support, data analysis tools, and regulatory guidance, as well as ensuring KOLs can focus on their critical oversight responsibilities without administrative burdens.

Strengthened Regulatory Compliance

Global regulatory bodies highly value KOLs in DMCs due to what they bring to the oversight process. A large network of KOLs can help ensure trials meet international regulatory standards and any issues are promptly and appropriately addressed.

It’s crucial for a DMC administrator to provide global support. That administrator must be committed to continuous improvement and innovation, including regular updates to processes and tools to incorporate the latest advancements in clinical trial oversight. This commitment ensures DMCs benefit from cutting-edge methodologies and best practices, so members can focus on their review responsibilities with minimal administrative burden.

The Importance of Independent DMC Administration in Managing a Large KOL Network

A DMC’s effectiveness is undoubtedly hinged on having a large KOL network. Their expertise, diverse perspectives, and problem-solving capabilities are invaluable for maintaining clinical trial integrity and success. An independent third-party DMC administrator with an extensive KOL network, rigorous selection process, and robust support infrastructure is the ideal choice for leveraging the power of KOLs in DMCs.

For sponsors seeking to ensure the highest standards of safety and efficacy in their clinical trials, partnering with independent third-party DMC administrators offers unparalleled advantages. Having a large, independent, and diverse KOL network enhances the oversight process, ultimately contributing to the advancement of safe and effective medical therapies.

In an era where clinical trials are increasingly global, it’s more imperative than ever to leverage international expertise.

Data and safety monitoring boards (DSMBs), also known as data monitoring committees (DMCs), play a critical role in overseeing a clinical trial’s safety and efficacy. These independent committees are entrusted with the task of safeguarding study participant’s interests while ensuring the trial’s scientific integrity.

The February 2024 FDA draft guidance on DMCs highlights the necessity of incorporating diverse, global expertise into these critical oversight functions.

The Role of DSMBs in Clinical Trials

DSMBs are integral to clinical trial conduct, particularly those involving high-risk interventions or vulnerable populations. In a trial taking place in multiple countries, there is an increased need to understand any regional nuances. This may include differences in standard of care, acceptable practices, and the like.

The DSMB’s primary responsibilities include:

  • Monitoring patient safety: Ensuring participants are not exposed to undue risk and adverse events are promptly identified and addressed.
  • Evaluating interim data: Analyzing data at predefined intervals to determine if the study should continue, be modified, or be terminated early.
  • Ensuring study integrity: Protecting the trial’s integrity and credibility by preventing biases and maintaining confidentiality of interim results.

The 2024 FDA Draft Guidance: A Focus on Global Expertise

The latest FDA draft guidance emphasizes the importance of a diversified DMC composition, advocating for including key opinion leaders (KOLs) from around the world. The preamble makes clear the agency’s belief in the DMC’s role progressing alongside evolving trial conduct and design approaches.

The draft guidance highlights several key points pertinent to international trials:

  • Diversity of expertise: KOLs with varied backgrounds and expertise enhances the DMC\’s ability to address complex clinical and safety issues, and is crucial for interpreting data accurately and making informed decisions.
  • Global representation: Having DMC members who understand regional medical practices and regulatory environments is vital and ensures the DMC can provide culturally and contextually relevant oversight (e.g., local standards of care).
  • Enhanced objectivity: A DMC composed of diverse international experts can mitigate potential biases arising from local or regional perspectives. Consider the differences between supporting (concomitant) medications used in different countries or the differences generally in how a disease state is considered or treated. A multi-national DMC enhances the objectivity and credibility of the committee\’s recommendations.

These are important considerations no matter where a trial takes place; they are especially important when considering disparate cultural standards and other international differences.

Benefits of a DMC Leveraging a Worldwide Network of Key Opinion Leaders

Having a DMC whose members represent the regions included in a clinical trial allows for expertise and understanding both the culture and common medical practices. Consider the following:

  • Comprehensive expertise: A global network of KOLs brings together experts from diverse medical, scientific, and regulatory backgrounds. This allows DMCs to tackle complex issues from multiple angles – ensuring robust, well-rounded, and consistent decision-making processes.
  • Cultural competence and sensitivity: In multinational trials, cultural competence is critical. KOLs from different regions can provide insights into local healthcare practices, patient behaviors, and regulatory expectations. This cultural sensitivity enhances the DMC\’s ability to interpret data accurately and make decisions respectful of regional nuances.
  • Rapid access to specialized knowledge: In the event of an emerging safety concern or unexpected data trend, having KOLs with specific expertise readily available ensures timely and informed responses – thereby protecting participant safety and trial integrity.
  • Strengthened regulatory compliance: Different countries have varying regulatory requirements and expectations. A globally diverse DMC ensures the trial adheres to local regulations while maintaining high ethical standards. This compliance is crucial for the successful regulatory approval and dissemination of trial results.
  • Enhanced credibility and trust: Having respected KOLs enhances the credibility and trustworthiness of the DMC\’s recommendations. This is particularly important in high-stakes trials where public and stakeholder trust is paramount. For example, consider a global Phase III, double-blind study, in a novel new therapy. By having a trusted KOL on the DMC, physician investigators can feel confident their patient’s safety and welfare is independently supervised.
  • Fostering innovation and collaboration: Global collaboration fosters innovation by bringing together diverse perspectives and approaches. This collaborative spirit can lead to developing novel methodologies and strategies for monitoring and evaluating clinical trials, ultimately advancing the field of clinical research.

Global Perspectives Necessary for Clinical Trial Success

The FDA\’s February 2024 draft guidance on DMCs underscores the importance of incorporating global expertise and leveraging worldwide networks of KOLs. In an increasingly interconnected world, this approach is essential for ensuring a trial’s safety and efficacy.

By embracing diversity and fostering international collaboration, DMCs can enhance their oversight capabilities, protect participant safety, and uphold the highest standards of scientific integrity.

As we move forward, the integration of global expertise will continue to play a pivotal role in successful and credible clinical research endeavors.

Embracing the power of global expertise and fostering a worldwide network of KOLs not only aligns with regulatory expectations, it also represents a proactive approach to addressing modern clinical trial complexities. This strategy is indispensable for advancing the clinical research field and ultimately improving patient outcomes across the globe.

To grow your business, negotiate and collect fair payment for your work by understanding its true costs before budget discussions.

This includes all direct and indirect costs, and typically includes:

  • Personnel costs: salaries, overtime, training, and additional staffing if needed.
  • Facility costs: not only facility space, maintenance, utilities and equipment, but also any additional space or modifications needed for the study.
  • Procedure costs: electrocardiograms (ECGs), blood draws, IV infusions, radiology, ophthalmology, and other specialized assessments.
  • Supplies and materials: study-specific items like lab kits, diagnostic tools, medication storage, dry ice, and office supplies.
  • Participant costs: in-person recruitment practices, advertising, screening, travel reimbursements, stipends, and engagement.
  • Technology costs: fees for site-owned platforms such as a clinical trial management system (CTMS), eRegulatory management system, eSource platform, or any other specialized digital solution used during the trial.
  • Regulatory costs: fees for institutional review board (IRB) approvals, data privacy compliance, and audits.
  • Contingency costs: unexpected expenses such as protocol amendments, additional patient recruitment efforts, or other unanticipated expenses and delays.

In addition to covering your costs, here are several strategies to ensure you’re prepared for negotiation:

  • Ensure you fully understand the protocol, including all visits, procedures, tests, and specialized staff or equipment needed. Carefully outline the time and resources needed for each step. It is often helpful to bring in any staff with specialized skills during this step to make sure nothing is overlooked.
  • Leverage historical data and benchmarks to identify past challenges related to recruitment, timelines, and resources. The more you can learn from previous trials, the more confidently you can negotiate your next one.
  • Plan for the future by ensuring you are taking the overall study timeline into consideration. Longer trials typically incur higher costs due to increased staffing needs, extended participant engagement, ongoing data management, and sustained regulatory compliance efforts. In addition, make sure to account for inflation for salaries, procedure costs, and other material resources you need to conduct the trial.
  • Prepare a detailed justification for each cost in the budget. Be ready to explain why each cost is necessary and how it contributes to a successfully executed study. Sponsors are more likely to agree to a budget when they understand the rationale behind each expense.
  • Ensure the company is the signer, not the investigator. While a principal investigator (PI) as signer can work for a single site, as that site grows and potentially expands to include new sites, this can result in issues. Employing the company as the signer can improve timelines and establishes the company as the owner of the financial and ongoing business development relationship with the sponsor.

In addition to following the guidance above, you should be flexible in your negotiation. Find areas where you may be able to adjust, such as reducing or reallocating specific administrative costs. Understanding your bottom line and your ability to make concessions will help you negotiate a budget designed to cover your costs without compromising quality.

When negotiating terms, you should request 0% withholding or holdback to make sure you are quickly getting paid for your work. Especially in cases where a portion of the funds are dependent on closeout visits, holdbacks can result in waiting years to be reimbursed. In addition, you should request Net 30 payment terms. You are paying your team and incurring expenses for materials to conduct your research throughout the trial, and so you should be collecting funds from the sponsor as quickly as possible for the work you have performed.

Lastly, payment should be made upon “work complete” (e.g., visit data is entered into an electronic data capture [EDC] system, not reliant on a monitor review) to make sure you are in control of payment timelines, without the need to wait for action from the sponsor.

The International Council for Harmonisation (ICH) good clinical practice (GCP) guidelines are critical in ensuring the safety and rights of clinical trial participants. The guidelines also facilitated international harmonization of clinical research making it easier to conduct multi-national trials and bring new therapies to market more efficiently.

The Council was first formed in 1990 with the goal of harmonizing regulatory requirements across Europe, Japan, and the United States. The first guidelines published in 1996 and known as ICH GCP E6 provided guidance on the design, conduct, and reporting of clinical trials. ICH GCP R2 was subsequently published in 2016 and expanded on steps to ensure data integrity, encourage risk-based monitoring, and address the use of electronic records and signatures.

Updates to R3

Now, ICH GCP E6 R3 introduces quality by design, further refines risk management, and establishes clearer roles and responsibilities. The transition from R2 to R3 represents a significant evolution in the ICH guidelines – there are some key elements for sponsor organizations to focus on as they optimize clinical quality.

Quality by Design

R3 builds on the quality by design framework, introduced in ICH GCP R8. This framework encourages the implementation of quality assurance throughout the clinical trial lifecycle. Principle 6 of R3 expands on the identification and implementation of critical to quality (CtQ) factors – attributes vital to the protection of subjects and the integrity of the data collected. The guidelines encourage the strategic use of CtQ factors to detect and address deviations from GCP, as well as the protocol and regulatory requirements so that recurrence is prevented. Ultimately trial participant safety and data integrity is maintained.

Risk Proportionality

Risk management is further streamlined in R3, focusing on tailoring trial processes proportional to the risks they pose to subjects as well as critical data. Risks to CtQs factors should be proactively managed and risk language/monitoring adjusted according to new and changing information during the clinical trial. Furthermore, systems and processes capturing, managing, and analyzing data need to be fit for purpose, capturing data required by the protocol and should address key risks to subjects and data integrity.

Trial Design

The importance of robust and risk-based trial design is a key element of R3. Emphasis should be placed on creating operationally sound processes and avoiding unnecessary complexity, procedures, and data collection. This all starts with a well-designed clinical protocol, in addition to trial plans and documents aiding in protocol execution. Trial processes should also be optimized to focus on the key objectives and quality and risk management elements should be put in place. Sponsors should ensure a diverse multidisciplinary team of stakeholders supports the design of the study and the clinical development plan. Lastly, computerized systems used in the capture of data should be fit for purpose and support the CtQ factors.

As trial designs and clinical technologies become increasingly complex, sponsors must prioritize patient safety and data integrity more than ever. R3 acknowledges no clinical trial can be flawless, but it encourages organizations to adapt their processes and systems to address the most critical risks effectively. By embracing this proactive approach, organizations can continue to drive innovation while upholding the highest standards of clinical research and patient care and can more effectively bring world-class treatments to market.

Antibiotic resistance is an emerging problem. Some have argued bacteria are developing antibiotic resistance faster than we can research, develop, test and approve new antibiotics. The World Health Organization (WHO) has warned for several years that we are on the verge of a post-antibiotic world, noting in particular a post-antibiotic world may have already arrived, as there are too few antibiotics for an increasing number of antibiotic-resistant pathogens.

One possible solution to antibiotic resistance: bacteriophages (or phages), which are viruses that infect bacteria.

The Growing Problem of Antibiotic Resistance

Bacteria begin to exhibit resistance soon after the clinical deployment of a new antibiotic (Table 1). At a high level, defining antibiotic resistance may sound simple; it basically means bacteria devise a way to survive exposure to a substance that could previously stop their growth or kill them.

Table 1:

 

If someone fails to complete their prescribed course of antibiotics against a bacterial infection, the heartiest and most resistant of the initial population thrive and resistance spreads (see Figure 1 and Figure 2). It’s simple Darwinian evolution: the fittest survive and their descendants take over.

Another method of fostering antibiotic resistance is the prolonged low-level exposure to antibiotics, as is currently the case when people take prescribed antibiotics and excrete the unmetabolized drugs into the sewer. Sewage treatment plants are effective at treating biological waste, but chemicals like antibiotics are released into the environment with the treated water.

 

Also consider: Half the antibiotics produced in the U.S. are utilized in agriculture, further exacerbating the problem of antibiotic resistance developing in the environment.

While we can refer to antibiotic resistance as a single trait bacteria can develop, there are many different mechanisms for antibiotic resistance. Figure 3 illustrates some of these examples:

  • Bacteria can secrete enzymes that inactivate antibiotics (e.g., penicillinase inactivates penicillin)
  • Others pump the toxic drug out of the bacterial cell, much like some chemo-resistant cancers
  • Communities of bacteria can layer onto each other to form biofilms to make the collective more resistant to certain disinfectants and antibiotics
  • Some bacteria have anatomical structures like cell walls, capsules, and slime layers to protect the cell from external threats

Antibiotic resistance is encoded as a genetic trait and can be transmitted between bacteria by various means (see Figure 4).

These resistance genes are commonly found on small circles of DNA called plasmids. Bacteria can exchange plasmids through conjugation, a process where bacteria connect with a sex pilus and plasmids are shared.

When cells die, their plasmids can spill into the environment for other bacteria to pick up and use in a process called transformation.

Bacteriophages can also transfer genetic traits between bacterial host cells in a process called transduction.

What Are Bacteriophages?

Bacteriophages (phages for short) are viruses that infect bacteria.

Phages deliver their genetic material into the bacteria so, when the bacteria flourishes and reproduces, the bacteria also copies the viral genome and hands it down to bacterial progeny. As such, the virus reproduces with virtually no effort (see Figure 5).

However, when the host cell is under stress, the phages hijack the bacteria’s machinery to produce as many progeny viruses as quickly as possible while killing the host (see Figure 6). The progeny viruses are released into the environment to await another host to infect. These phages don’t just benefit from the bacteria when times are good. They often carry genes to help the bacteria succeed by giving it a selective advantage, such as bacterial toxins or antibiotic resistance genes.

Bacteriophages as a Potential Alternative to Antibiotics

Discovering a new class of antibiotics is difficult – we can go decades without a new class being identified. And in our global society where germs spread faster than ever before, we already have trouble keeping up with the spread of antibiotic resistance. Many argue we need a different approach.

As scientists look for new strategies to combat antibiotic resistance, the idea of taking advantage of bacteria’s natural pathogens has become resurgent.

Phages already exist as bacteria’s natural pathogen. While developing an entirely new class of antibiotic is challenging, making minor genetic modifications to a virus or phage is something fairly easily accomplished with modern technologies.

Current Research and Future Directions

Phages are currently under study as investigational products in clinical trials targeting different bacterial maladies. Here are just a few examples of how phage therapy could improve healthcare outcomes:

  • Cystic fibrosis poses a difficult challenge as a bacteria commonly found in the environment, Pseudomonas aeruginosa, forms biofilms in the lungs of patients and is a leading cause of death. Phages can be nebulized into the lungs and used to infect and kill the bacteria.
  • Antibiotic-resistant E. coli is capable of causing several conditions, including potentially lethal bloodborne infections and urinary tract infections which can form biofilms on urinary catheters. Intra-venous delivery of phages has potential as therapeutics for a broad range of conditions caused by antibiotic-resistant E. coli.
  • Naturally occurring phages are generally specific to a single species of bacteria. However, use of genetic engineering may allow drug companies to produce phages targeted to specific pathogenic bacteria while sparring the commensal (good) bacteria that contribute to human health (such as the bacteria found in the human intestines, vagina, and skin).

It is also important to consider environmental impacts of phage therapy. Researchers should avoid producing phages that could harm bacteria which contribute positively to the environment, agriculture, veterinary health, or human health.

Research use of any genetically modified microorganism should comply with biosafety guidelines issued by the National Institutes of Health and Centers for Disease Control. Review by an institutional biosafety committee (IBC) ensures the appropriate risk assessment has taken place and an adequate risk mitigation plan is implemented to protect researchers, the community, and the environment.

Bacteriophages aren’t necessarily the magic bullet to fix antibiotic resistance once and for all, but they certainly show promise in helping address the global problem. Research professionals interested in conducting research involving bacteriophages should first ensure their facilities have the appropriate biosafety protocols in place. It’s also important to be familiar with the risk profile associated with genetically modified bacteria and bacteriophages.

Managing clinical trial budgets efficiently is necessary for the success and sustainability of clinical research sites. Effective budget management not only ensures trials are financially viable but also maximizes return on investment (ROI). This enables sites to allocate resources strategically, attract more studies, and maintain long-term financial health.

Understanding ROI in Clinical Trials

Calculating ROI for clinical trials involves measuring the cost of collecting and analyzing data against the trial’s productivity (i.e., the impact and value of the data produced). The higher the ROI, the greater the financial return and the better use of resources.

It\’s difficult to calculate a clinical trial’s ROI if the potential research outcomes are unknown. However, a strong focus on cost-effective budget management can help research sites maximize their ROI.

Calculating the ROI of studies is essential for a research site’s success. It allows them to assess the financial viability of trials and ensure funding is allocated to the most profitable projects. By maximizing ROI, research sites can ensure sustainable growth and success in their research endeavors.

Strategies For Cost-effective Budget Allocation

Cost-effective budget allocation is the key to ensuring optimal use of resources in clinical trials. Prioritizing high-impact budget items, negotiating for better rates from vendors, making use of budget management technology, and using historical data to predict costs can all allow for more efficient use of funds.

Prioritizing Budget Items

High-impact items are those most likely to contribute to a trial’s overall success, efficiency, and quality. Identifying and prioritizing spending for these items is a central aspect of effective resource allocation, which is key to maximizing ROI. Examples of high-impact budget items include:

  • Patient recruitment and retention
  • Staff salaries
  • Patient care
  • Laboratory and medical procedures
  • Data management and analysis
  • Regulatory compliance
  • Staff training
  • Supplies and materials
  • Technology and equipment

Utilizing Technology

Budget management tools and software, like clinical trial management systems (CTMS), can streamline trial processes and reduce costs in several ways.

For example, these tools can automate the recording and tracking of financial data, reducing the risk of human error and ensuring greater data accuracy. It also records data on a centralized system available to both the research site and sponsor, so all parties have access to up-to-date information. In doing so, budget management tools allow for faster identification and mitigation of financial risks.

Software tools can also help to maintain a budget by accurately tracking expenses and keeping records of the budget list, budget summary, and any budget adjustments.

Leveraging Data

Historical data is very useful for accurately predicting costs in clinical trials and can help prevent overspending. It provides valuable insights into costs associated with:

  • Site payments
  • Vendor costs of supplies and services
  • Patient recruitment and retention
  • Effect of protocol complexity on costs
  • Staffing costs
  • Cost-effectiveness of research sites
  • Costs associated with different study durations
  • Cost of regulatory approval

The information gleaned from historical data analysis can allow for more effective optimization of a clinical trial budget and, therefore, resource allocation.

Detailed Cost Breakdown

When budgeting, consider all necessary activities and the costs associated with each activity. Research sites usually budget for staff salaries and training, but frequently overlook the costs of other essentials. Some examples of often-forgotten research costs include:

  • Costs associated with trial participants: These include the costs of recruiting participants, screen failures, and screening activities. They may also include costs relating to data entry, preparing institutional review board (IRB) documents, and scheduling assessments of participants.
  • Site costs: Charges for the study site include a start-up fee, payments for site personnel, and IRBs on site. Other potential costs include those for additional sites (or removal of sites), administrative fees, storage fees, and site closeout.
  • Safety costs: Safety costs include the cost of evaluating, addressing, and reporting adverse events. They may also include payments to safety oversight committees (e.g., for generating reports) and independent consultants.
  • Quality management costs: Quality management expenses are associated with clinical monitoring (including site monitoring and closeout visits), data management, and project management.
  • Regulatory costs: Regulatory costs may include submissions to regulatory authorities, such as applications for new investigational drug or device exemptions, annual reports, and final reports. They may also include the cost of registration to clinicaltrials.gov and those associated with posting results.
  • Other costs: Other costs commonly overlooked when budgeting for clinical trials are those of laboratory work, medical monitors, staff training, meeting, travel, translators, advertising, and shipping and storing investigational products.

Specific Cost Categories for Federally Funded Trials

The major cost categories for federally funded clinical trials are as follows:

  • Personnel costs: These include staff salaries and expenses and fringe benefits, such as health insurance and pension contributions.
  • Patient care costs: These are costs associated with the routine care covered by the trial.
  • Data management: Data management and monitoring in federally funded trials must meet federal standards. This often requires using specific electronic data capture systems and adhering to strict protocols.
  • Supplies and materials: These include costs for medical supplies (like drugs, medical devices, and other trial-related materials) and laboratory supplies (such as reagents, kits, and other materials for laboratory activities).
  • Patient reimbursement: Patients may be reimbursed for their time, travel, and other expenses.
  • Consultant fees: These are fees for medical or scientific experts providing consulting services to the clinical trial. In federally funded trials, these services must be justified and approved, and fees are capped according to federal guidelines.

Negotiating Better Contracts With Sponsors

Negotiating for a better contract with sponsors is a foundational aspect of cost-effective clinical trial budget management. Successful negotiation is a product of thorough preparation and effective communication, with careful consideration of factors such as:

  • Building relationships: A strong relationship with a sponsor can give you leverage in contract negotiations. Understanding your sponsor’s budget limitations can allow you to identify fair goals and requests. It is also helpful to identify your mutual goals so you can take a collaborative approach to negotiations.
  • Transparent communication: Open communication is at the heart of every successful professional relationship. When entering budget talks with a sponsor, clearly communicate the trial costs and maintain a firm-but-flexible attitude throughout negotiations. Clear itemization of costs can prevent misunderstandings and ensure coverage of all expenses.
  • Fair market value: Do some research prior to negotiations to establish the standard pricing for supplies and services, and make sure the budget reflects fair market value.
  • Redlining budgets: Identify which of your terms are non-negotiable (like site costs) and ensure your sponsor’s proposed budget aligns with these terms.
  • Avoiding double billing: Avoid duplicate charges for budget items by ensuring compliance with the research billing plan.
  • Gathering evidence: Leverage historical cost data from similar trials to support your budget requests, and gather well-documented evidence to support any requests for additional funding.
  • Escalation plans: Use internal and sponsor escalation plans to navigate any challenges arising during the negotiation process.
  • Long-term partnerships: Establishing a long-term, mutually beneficial partnership can help secure a more favorable budget from a sponsor.

Strong negotiation skills are central to the success and cost-efficiency of research institutions. Therefore, learning new strategies for budget negotiation can equip researchers with the tools to optimize their site’s use of resources and, therefore, the success of their research endeavors.

Identifying and Eliminating Budget Inefficiencies

Budget inefficiencies can bleed resources from a clinical trial, to the serious detriment of its overall ROI. Therefore, identifying and eliminating financial inefficiencies is vital for a research site’s success. Regular budget reviews and close budget monitoring, cost-benefit analysis, process improvement, budget management skills training, and strict regulatory compliance are vital for mitigating financial risks in clinical research.

Regular Budget Reviews

Conducting regular budget reviews can identify and address financial inefficiencies in a clinical trial. Unforeseen expenses can contribute to the failure of a clinical trial, and may include:

  • Inefficient use of research sites
  • Unnecessary protocol amendments
  • Unnecessary data collection and procedures
  • Inefficient monitoring strategies
  • Failure to leverage technology effectively
  • High participant dropout rates
  • Ineffective negotiation with vendors

Financial inefficiencies can be mitigated with careful planning and resource allocation, along with frequent budget reviews. Budget management tools, which allow for closely monitoring financial data, can make it easier to detect and address financial inefficiencies and improve a trial’s economic viability.

Cost-benefit Analysis

A cost-benefit analysis measures the financial costs of specific budget items against their potential benefits. This ensures each item adds value to the trial and each resource is used to its greatest benefit. It can also help researchers decide where to allocate resources to maximize a clinical trial’s ROI.

Process Improvement

Process improvements can enhance a trial’s speed, accuracy, and reliability while improving patient safety and clinical outcomes. This is essential for streamlining clinical trial processes to reduce waste and enhance cost efficiency. Examples of process improvements include:

  • Using adaptive trial designs allowing for real-time modifications and adjustments.
  • Optimizing patient recruitment and retention by utilizing data analytics to more effectively identify and target patient populations, more efficient screening processes, and patient-centric approaches to recruitment.
  • Leveraging technology like electronic data capture (EDC) systems and wearable medical devices to improve the speed and accuracy of data collection.
  • Optimizing data management and analysis using a centralized clinical data management system (CDMS) and standardizing data collection methods.
  • Reducing delays in obtaining regulatory approvals through standardization of contracts.

Training and Development

Training and development programs can improve the budget management skills of clinical staff and are, therefore, a solid investment in the long-term financial efficiency of a research site. These training programs can teach staff to:

  • Perform comprehensive budget planning and allocate resources effectively
  • Identify and plan for the costs of patient recruitment and retention
  • Consider effort costs associated with various recruitment strategies
  • Use budget management software tools to track and monitor a budget
  • Identify and mitigate financial risks
  • Negotiate effectively with vendors

Regulatory Considerations and Compliance

Clinical trial regulations are the laws and guidelines governing clinical research and ensuring participant safety, rights, and wellbeing. They include:

  • Good clinical practice (GCP)
  • Informed consent
  • Ethical approval from an IRB
  • Ongoing monitoring and reviews from the IRB
  • Regulatory authority approval (e.g., from the Food and Drug Administration [FDA])
  • Safety reporting (e.g., of adverse events)
  • Data management and privacy
  • Good manufacturing practice (GMP)

Compliance with these regulations is essential for protecting patient’s rights and safety, ensuring the integrity and validity of research, and securing regulatory approval for the marketing of new medical treatments. Therefore, researchers must carefully consider regulatory costs when budgeting for clinical trials, such as:

  • IRB approvals
  • Regulatory authority submissions
  • GCP compliance
  • Safety monitoring and reporting
  • Data management and privacy

Costs associated with regulatory compliance are divided into direct and indirect costs. Direct costs are those directly attributed to a particular aspect of regulatory compliance (such as GCP training costs). Indirect costs cannot be directly assigned to regulatory compliance, but are necessary for supporting regulatory activities. These may include staff salaries and infrastructure costs. The budget must factor in both direct and indirect costs, and resources must be allocated accordingly.

The budget must also account for both study-related and standard care costs. Study-related costs are expenses directly associated with the clinical trial, and may include:

  • Staff salary
  • Training
  • Fees for ethical or regulatory authorities
  • Data collection and monitoring costs
  • Laboratory costs
  • Insurance
  • Study-specific medical procedures
  • Participant reimbursements

Standard care costs are expenses that would be incurred regardless of whether a patient is participating in a clinical trial. These are routine medical care costs usually reimbursed by healthcare insurance providers, such as:

  • Diagnostic tests
  • Standard medications
  • Hospital treatment

Efficient budget management is essential for maximizing ROI in clinical trials. By prioritizing budget items, negotiating better contracts, leveraging technology, and conducting regular reviews, clinical research sites can optimize their financial resources and ensure sustainability. Implementing these strategies will not only improve financial outcomes, but also enhance operational efficiency and competitive positioning.

Achieving diversity, equity, and inclusion (DEI) in clinical trials is crucial for producing comprehensive and effective medical research benefitting all communities. DEI ensures clinical research encompasses diverse populations, considering variations in gender, race, ethnicity, socioeconomic status, and more. This helps to generate inclusive data essential for regulatory review and developing treatments effective for everyone.

Importance of DEI in Clinical Trials

Clinical trials are a cornerstone of medical research, contributing to the development of new drugs and treatments. However, historical underrepresentation of marginalized communities has often led to incomplete or biased data. For example, treatments working well for one group may not be effective or could even be harmful to another group due to differences in genetics, lifestyle, or environment. This highlights the need for diverse participation in clinical trials to ensure all populations benefit from medical advancements.

The U.S. Food and Drug Administration (FDA) emphasizes the need for equal representation in clinical trials to generate useful and inclusive data. The agency’s draft guidance calls for Diversity Action Plans to ensure diverse participants are enrolled, which is critical for developing safe and effective drugs and medical devices for everyone.

The National Institute on Minority Health and Health Disparities emphasizes DEI in research goes beyond race and ethnicity, but should also face for the diverse lived experiences of different populations considering factors such as:

  • Socioeconomic status
  • Age
  • Biological status
  • Pregnancy status
  • Unhealthy behaviors (such as substance use)
  • Environmental conditions (such as pollution)
  • Underlying medical conditions or comorbidities

Challenges to Achieving DEI in Clinical Research

Achieving DEI in clinical research is not without challenges. Some common barriers to diverse clinical trial enrollment include:

  • Mistrust: Historical mistreatment by medical professionals, such as the Tuskegee Syphilis Study and the mishandling of genetic information from the Havasupai Tribe, has led to a deep mistrust of clinical trials among certain communities. Overcoming this requires significant education and outreach to build trust and inform people about the safety and importance of participating in clinical trials.
  • Lack of awareness and education: Many potential participants may not understand what clinical trials entail, their purpose, or the protections in place to ensure safety. More educational efforts are needed to demystify important clinical research and encourage participation.
  • Environmental barriers: Physical barriers such as distance from research sites, lack of transportation, and time constraints can prevent potential participants from enrolling in clinical trials. To address this, creating research sites within underserved communities or employing decentralized clinical trial models can help improve accessibility and encourage diverse participation.
  • Community engagement: Building relationships with communities is crucial for understanding their unique needs and concerns. Engaging community leaders and providing transparency throughout the trial process can help foster trust and encourage participation.

Strategies for Promoting DEI in Clinical Trials

To address these challenges, several strategies can be employed:

  • Community outreach and education: Building relationships with community leaders and organizations can help promote understanding and trust. This involves going beyond traditional healthcare settings and engaging in places like community centers, faith-based organizations, and local health fairs.
  • Culturally competent communication: Effective communication tailored to different cultural and linguistic groups is essential for encouraging diverse participation. Ensuring clinical trial information is accessible and understandable can help break down enrollment barriers.
  • Diverse research staff and investigators: Having a diverse team of researchers and investigators who reflect the communities they serve can help foster trust and increase enrollment from underrepresented groups. Potential participants are more likely to trust and engage with study staff who share similar backgrounds or experiences.
  • Decentralized clinical trials: By employing decentralized models, which can include home visits, remote monitoring, or using local healthcare facilities, clinical trials can become more accessible to participants who may face geographic or logistical barriers.

Regulatory and Ethical Considerations

To ensure ethical standards are upheld, regulatory frameworks such as the Belmont Report and the Declaration of Helsinki guide the ethical conduct of clinical research. These guidelines stress the importance of informed consent, respect for persons, and equitable participant selection. Regulatory bodies like institutional review boards (IRBs) are crucial for reviewing and approving research studies, ensuring they meet ethical standards and protect participant rights.

Other guidelines include:

21 CFR 56.111 and 45 CFR 46.111 Criteria for IRB approval of research including assessing equitable selection of participants. \”In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted.\”
21 CFR 56.107 and 45 CFR 46.107 Regulations describe the need for diverse IRB membership, “including consideration of race, gender, cultural backgrounds, and sensitivity to such issues as community attitudes.” If the IRB regularly reviews research involving vulnerable populations, the IRB should include in its review one or more people knowledgeable about and experienced in working with such populations.
21 CFR 50 Subpart B and 45 CFR 46.116 Based on “respect for persons” from the Belmont report, this regulation outlines general requirements for informed consent, including basic and additional elements of that should be included in an informed consent document. Also advises against exculpatory language and requires minimized possibility of coercion and undue influence. Provides instruction on providing consent materials in a language understandable to the participant.

Promoting diversity, equity, and inclusion in clinical research is essential for developing safe, effective, and equitable treatments. Overcoming historical mistrust, improving accessibility, and engaging communities are key steps toward achieving this goal. By prioritizing DEI, clinical trials can provide more comprehensive and relevant data designed to benefits all individuals, ensuring the medical advancements of tomorrow are built on a foundation of inclusivity and fairness.

At institutional research programs around the U.S., there exists a pervasive myth: internal institutional review board (IRB) reviews are free. Years of relying on local IRB reviews have led many in research to mistakenly believe there is no cost associated with local IRB review.

This misconception can lead to significant budgeting oversights, impacting both the institution and its research strategy – especially in the current era of single IRB (sIRB) mandates.

In this blog, we hope to debunk this myth while also providing practical strategies for assessing and establishing IRB review costs.

Internal IRBs serving as single IRBs for multicenter trials can use this flexible approach, originally developed by Kelley O’Donoghue for an R1 research university. The model also supports other local human research protection program (HRPP) functions, ensuring these research-related resource expenditures are appropriately valued and funded.

Challenges Arising from IRB Cost Misconceptions

The misconception of free internal IRB reviews overlooks the various resources—personnel, processes, technology, and time—required for IRB reviews. This can lead to inadequate budgeting and unforeseen financial strains.

Many investigators, as well as grants and contracts offices, are not fully aware of the costs associated with IRB reviews. This can result in incomplete budget planning for federal grants, potentially resulting in resource shortfalls (and scrambling for additional funds) as the research proceeds.

Additionally, when IRB resourcing is not properly accounted for, institutions serving as single IRBs for multisite research studies may not be able to adequately provide sIRB services.

Investigators may also face uncertainty regarding whether their local institution will charge for sIRB reviews or if they will need to seek external IRB partnerships.

Implementing a Costing Model for IRB Reviews

A practical approach to managing IRB review costs is to implement a costing model. Let’s explore one possible framework for this purpose.

The approach we present here assigns weights to each HRPP activity based on workload and operating budget, calculates a dollar value per work unit, and assigns costs for each IRB activity. These activities may include initial reviews, continuing reviews, modifications, and consent forms.

This model offers flexibility and adaptability, allowing institutions to tailor it to their specific needs and circumstances. By assigning a value to each activity, institutions can better understand the financial implications of their IRB reviews and plan accordingly.

As a best practice, periodically review and adjust these templates to reflect changes to the actual work and costs. This helps the institution maintain a balance between accurate costing and supporting its investigators.

How to Build a Costing Model for IRB Reviews

If organizations have not yet determined the actual cost of their IRB’s work, HRPP experts suggest the following steps.

Note: In this model, the generic term “work unit” is used to mean “the value assigned to the IRB work based on the operating budget.”

  1. Examine IRB review data from the most recently completed fiscal year to identify the items approved and number of reviews performed in that year.
    • Weight each activity based on the work required as a percentage comparison to other HRPP activities.
      • For example, an HRPP may decide full board review should be weighted 100%. Comparatively, they may then weight expedited review at 85%, since it does not require as many resources as full board.
    • Using the activity totals from the most recent fiscal year, calculate how many work units were used in total.
  2. Next, determine the cost per work unit.
    • Multiply the number of activities by the weighted percentage, then divide the overall operating budget by the total of weighted activities for that fiscal year. This is your cost per work unit.
    • See Figure 1 for an example of these calculations.

 

    •  

3. Assign a cost for each IRB activity: Start by rounding your work unit costs so they’re easier to work with. Then assign the “work” required for each IRB activity, and calculate the cost per activity.

      • The cost per activity will serve as the budget template’s building blocks.
      • Figure 2 provides an example of these calculations for an organization serving as single IRB, with costs broken down by protocol-level and site-level activities.

Creating a Budget Template 

With the true costs of IRB review established, you can develop a budget template to help ensure grant budgets and other financial projections account for all potential costs.  

When building your template, be sure to identify the factors potentially impacting costs. These may include the number of participating sites, the study’s duration, expected number of amendments or modifications, and other variables.  

Figure 3 provides an example of a single IRB budget template based in this model. 

For realistic budget planning, be sure not to underestimate costs. Consider all potential expenses to prevent budget shortfalls during the project. This includes administrative and expert time, technology expenses, and any other relevant costs the organization incurs.   

Best Practices for Internal and Single IRB Communications 

Understanding and communicating the true costs of IRB reviews is essential for effective financial planning for an HRPP. Developing clear policies and procedures, maintaining ongoing communication, and utilizing flexible financial models are key for success. 

Effective communication within the institution about IRB processes and costs helps ensure all stakeholders, including researchers, grants and contracts offices, and other stakeholders (including vice presidents for research), understand the true cost of IRB reviews. 

By understanding the financial realities of IRB reviews and implementing effective communication and financial planning strategies, HRPP leadership can better support their research programs.  

Recognizing no IRB review is truly free is the first step towards creating a sustainable and transparent financial model benefitting both the institution and its researchers. 

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