Clinical Data Strategies for Navigating Complex Trials

Clinical

Data Strategies for Navigating Complex Trials

We have all felt it. Clinical trials are becoming more complex, seemingly every day.

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CHAPTER 1

What to Know about Clinical Trial Complexity

CHAPTER 2

Transforming Technology for Data Complexity

CHAPTER 3

Handling Complex and Innovative Designs

CHAPTER 4

Addressing Complex External Data Workflows

CHAPTER 5

Complex Trial Success Depends on an Innovative, Flexible Mindset

What to Know about Clinical Trial Complexity

We have all felt it. Clinical trials are becoming more complex, seemingly every day. But what do we mean by complexity? In considering this question, it can be helpful to consider the different dimensions of complexity that clinical professionals face- encompassing trial complexity, data complexity, and operational complexity. Addressing these interconnected areas is vital to assure data quality, successful trial outcomes and overcome R&D (Research and Development) productivity challenges.

Understanding Trial Design Complexity

To better target interventions, and enhance patient benefit, innovative trials such as adaptive designs and master protocols are becoming more common especially in oncology and rare diseases. While efficient, these trials require sophisticated statistical methodologies and expertise to navigate them successfully. In turn, these kinds of trial designs often encompass related data complexities due to the type of external data sources used, and the requirement for multiple interim analyses.

Understanding Data Complexity

The integration of numerous and diverse data sources demands a lot of study teams. Researchers must move beyond traditional data management and monitoring to overseeing complex external data workflows incorporating patient-reported outcomes, genomics, and biomarker data, among others. This proliferation of data increases the need for advanced analytics and real-time processing capabilities to ensure data integrity, inform timely decision-making, and accelerate timelines.

Understanding Operational Complexity

Factors including trial globalization, complex trial designs, and an extensive ecosystem of vendors and stakeholders, are contributing to growing operational complexity. This sense of operational complexity is further heightened by the pressure for teams to do more with less. Operational and organizational complexity means that experience matters more than ever – to effectively manage intricate communications and ensure the smooth running of projects with multiple time-sensitive deliverables.

Consequences of Complexity

In a presentation at the eClinical Solutions elluminate ENGAGE conference, Ken Getz, Executive Director of the Tufts Center for the Study of Drug Development, touched on how the increasing complexity of studies correlates to slower cycle times and reduced productivity. The more complex the trial design and operational requirements, according to Getz, the greater the resource allocation needed for management, thereby increasing the overall time and cost of trial completion.

Strategic Approaches to Managing Complexity

Holistic Transformation

While technology advances hold great promise, technology alone cannot address this mounting challenge. A holistic approach to managing clinical trial complexity involves synchronizing people and processes, in combination with technology. An end-to-end data strategy focuses on creating a seamless workflow that enhances efficiency and reduces bottlenecks caused by complex trial designs.

Leveraging Expertise and Technology

Expert handling of complex trial designs is essential. This includes involving personnel (either on your in-house team or through collaborating with experienced partners) skilled in complex data capture and management, and advanced statistical methodologies, such as Bayesian approaches, to navigate through sophisticated trial protocols and analyze data effectively.

Technology Alignment and Real-Time Data

Adopting technology solutions plays a critical role in operationalizing a data strategy. Effective technology integration provides real-time data access, crucial for making faster decisions especially in trials with adaptive components and interim analyses. Such technology solutions also support the aggregation and analysis of data from various sources, ensuring comprehensive data oversight.

Partnering with an Eye on Future Needs

Partnering with technology and service providers can help trial sponsors develop efficiencies and scale their operations to match growing trial complexity. These partnerships are vital for ‘future-proofing’ operations and preparing organizations to work efficiently regardless of how processes, technologies, and the clinical trial landscape evolve.

The following chapters feature a series of examples of how a variety of different clinical research sponsors worked with the team at eClinical Solutions to address their complex study challenges through both technology and outsourcing solutions.

CHAPTER 2

Transforming Technology for Data Complexity

A robust clinical data infrastructure is especially essential in complex clinical trials to manage data quality and enable real-time analysis and integration of diverse data sources. In tandem with data infrastructure initiatives, companies are turning to risk-based methodologies, supported by technology solutions to enhance efficiency and enable focus on the critical data that matters most. This focus on critical data is especially important within the complex trial landscape. Reflecting these priorities, a leading, midsized global biopharmaceutical company implemented the elluminate Clinical Data Cloud - a platform for all clinical and operational data- to revolutionize clinical data strategy. By extending the implementation to include Risk-Based Quality Management (RBQM) and enhanced platform integration, the company was able to avoid data migration to a disparate system. Additionally, existing workflows were integrated, and best practices established to guide future studies.

Efficiently Integrating RBQM Saves Time and Money THE CHALLENGE

Facing the need to further evolve their clinical data infrastructure after successfully implementing elluminate, the company aimed to incorporate an RBQM and risk-assessment categorization tool (RACT) within a defined timeline. They required a solution that not only melded well with existing workflows but was also adaptable to future changes. The alternative—integrating a standalone RBQM system—would involve data migration and reformatting and additional resource allocation.

THE SOLUTION

The team chose to implement elluminate RBQM and avoid a slow, painful data migration to a disparate RBQM point solution. With elluminate, the data infrastructure was already in place, enabling RBQM to be implemented quickly. By selecting elluminate RBQM potential risks could be assessed, identified, and mitigated faster.

Case Study

Modernizing Data Infrastructure

In response to rapid growth, the biopharma company needed to evolve its clinical data infrastructure. The company’s growth and the increasing complexity of its studies necessitated a departure from outdated, resource-intensive processes to a more modern, efficient, and scalable approach.

THE CHALLENGE

As the company expanded, it became crucial to adopt a clinical data strategy that not only maximized the value of their data, but would also be adaptable to future demands. The primary requirements were: Enhanced data insight and flexibility for future needs.

• Greater data visualization and analysis.

• On-demand access to data from CROs and other sources and visibility into metrics and performance.

• Increased efficiency and cost reduction through automated processes.

THE SOLUTION

In 2020, the company implemented the elluminate Clinical Data Cloud, and leveraged Mapper, Clinical Analytics, and Data Central. The platform centralized various data types from multiple sources into one platform, allowing real-time data access and eliminating interoperability issues. This consolidation has led to significant process improvements across functions, fostering better resource management and cost-efficiencies.

THE RESULTS

Since its implementation for 40 studies:

• There has been a noticeable reduction in the time required for data quality monitoring, which in turn, shortened clinical trial cycles.

• Internal resource utilization improved as data standardization tasks decreased.

• The platform enabled quicker identification of potential issues through enhanced dashboards and metrics, optimizing resource allocation.

THE RESULTS

Study closeout times were reduced by 3-4 weeks per study due to proactive data review and issue management capabilities.

The platform contributed to achieving a 7-day database lock goal.

Streamlined workflows and advanced data review features reduced the resource burden.

Post-implementation, the company swiftly realized multiple benefits, notably:

• The successful standardization of RACT and RBQM across 25 clinical studies, resulting in considerable cost reductions both upfront and per study.

A complete elimination of the need for costly data migrations to external RBQM systems.

• Continued expansion of elluminate platform capabilities, leveraging the robust data infrastructure for ongoing growth and innovation in their data management strategies.

The successful deployment of elluminate RBQM not only met critical business objectives but also positioned the biopharma company to further explore and adopt additional data functionalities, supporting their vision of a modernized data culture against a backdrop of complexity.

Handling Complex and Innovative Designs

Adaptive, and other complex and innovative trial designs trials have the potential to increase overall trial efficiency and flexibility, and are growing in popularity particularly within oncology and rare disease indications. However, in turn, this flexibility increases complexity, requiring advanced statistical methods and robust data management to maintain data integrity and comply with regulatory standards.

A subset of innovative studies are master protocol trials, that research multiple therapies and/or patient subpopulations under the same protocol. The following case studies detail successful efforts resolving key client data challenges with innovative electronic data capture (EDC) approaches, and statistical partnerships tailored to complex oncology trials. A U.S.-based biopharmaceutical company and a leading research institution both confront the intricacies of such trials, emphasizing the need for an innovative mindset, strategic approach to data, and advanced statistical capabilities to efficiently manage and adapt to dynamic research demands.

The Impact of Innovative EDC Approaches for Complex Oncology Trials

Master protocols are increasingly common in oncology development. They can test multiple hypotheses simultaneously and need a flexible approach to data capture.

THE CHALLENGE

The company needed an effective electronic data capture (EDC) system for early phase trials with complex designs, including up to 12 study arms and over 15 patient cohorts. Traditional EDC build approaches were inefficient and costly due to the need for separate casebooks for each study part and frequent protocol amendments.

THE SOLUTION

The company collaborated with eClinical Solutions, leveraging their 15+ years of experience in clinical data acquisition, and Medidata Rave expertise to develop a streamlined, flexible and highly innovative EDC implementation for their master protocol. A lead programmer was assigned to ensure efficient communication and swift resolution of issues. The proposed adaptive database design allowed for a single database to support multiple study arms and adjustments post-production without disrupting ongoing studies.

Case Study

THE RESULTS

The new EDC system facilitated rapid study setup and easy customization to meet specific trial requirements, reducing downstream issues, and significantly reducing software pass-through costs involved in more traditional database design approaches. This approach has since been successfully applied to other master protocol trials. Factors that contributed to this success included• There has been a noticeable reduction in the time required for data quality monitoring, which in turn, shortened clinical trial cycles.

• Innovation-focused team culture capable of creating sophisticated solutions for complex data challenges

The eClinical Solutions team’s extensive experience with the Medidata platform enabled enhanced EDC flexibility and customization.

• A deep understanding of clinical protocols enabled effective data capture solutions.

• Consistent assignment of a lead programmer helped maintain continuity and excellent communication with the client.

Strategic Partnerships Provide Foundation for Effective Master Protocol Studies

A leading research institution, needing to address a significant unmet patient need, sought to coordinate a trial under a master protocol. This would require deep external data and biostatistics expertise and technology flexible enough to facilitate efficient data handling and fast decision-making.

THE CHALLENGE

The research team’s master protocol entailed complex operational, data, and statistical challenges. These challenges required continuous adaptations such as modifying treatment arms or sample sizes based on interim results, demanding real-time data access and extensive collaboration across multiple stakeholders. The dynamic nature of this kind of trial necessitates advanced statistical techniques and robust communication channels to manage the complexities effectively.

THE SOLUTION

eClinical Solutions leveraged its extensive experience to support this complex trial which incorporated sophisticated statistical approaches, including Bayesian methods. The integration of elluminate into the solution enhanced transparency and eased the quick decision-making essential for the adaptive components. With elluminate, the team could unify data collection across varied data types, supporting the trial’s multiple treatment arms efficiently.

THE RESULTS

eClinical Solutions leveraged its extensive experience to support this complex trial which incorporated sophisticated statistical approaches, including Bayesian methods. The integration of elluminate into the solution enhanced transparency and eased the quick decision-making essential for the adaptive components. With elluminate, the team could unify data collection across varied data types, supporting the trial’s multiple treatment arms efficiently.

• Streamlined decision-making with real-time data access, and flexible support in response to adaptations.

• Rigorous data standards and use of standardized analytical frameworks, ensuring data integrity.

• A strong foundation for collaboration, efficient cross-organizational decision-making, and partnerships.

Case Study

Addressing Complex External Data Workflows

A key characteristic of growing trial complexity is the increasing variety and volume of data collected outside traditional electronic data capture (EDC) solutions, from diverse sources such as labs, imaging, biomarker and genomic data. Streamlining the management of this external data through both processes and technology is essential to ensure its quality, consistency, and realization of its full value.

Through strategic integration of technology and a collaborative approach, the following case studies explore how eClinical Solutions helped two pharmaceutical companies to overcome challenges related to their management of non-EDC data.

Optimizing External Data Management in Rare Disease Trials

A biotechnology firm needed a comprehensive end to end data strategy to help them manage a large volume and variety of external data sources from multiple vendors across a portfolio of studies.

THE CHALLENGE

Modern trials feature multiple data types and data sources captured outside of traditional EDC. For the biotech company, this necessitated improved handling to prevent process delays related to data standardization and vendor management for studies with up to 20 external data sources. Key issues included:

Multiple data transfer agreements and related vendor coordination.

The need to standardize data such as biomarkers and genetic information.

• Broad variability around how external data was collected and managed based on data type and source.

THE SOLUTION

eClinical Solutions delivered end-to-end biometrics services using elluminate, and incorporating experts from the dedicated Center of Excellence for External Data to promote best practices and effective management of all data types. An external data management lead coordinated with the biotechnology client’s team, enhancing control over vendor activities and data transfers. External data-specific kick-off meetings and comprehensive tracking systems (including a detailed tracker of vendors, timelines, and data transfer statuses) were set up to streamline workflows and improve oversight. Standardized Data Transfer Agreement (DTA) templates facilitated compliance and uniformity in data handling.

Case Study

THE RESULTS

The strategic approach taken by the combined biotechnology and eClinical Solutions team enabled timely interim analyses while leading to several improvements in trial efficiency. These measures not only streamlined data processes but also ensured that critical data was effectively prioritized. Benefits included:

• One of the more complex studies achieved a 30% faster end-to-end process from Last Patient Last Visit (LPLV) to database lock compared to industry norms.

• Cross-study efficiencies were realized in managing data transfer agreements (DTAs), reconciliations, and communications, which are expected to benefit future trials as well.

Effective eSource Data Management in Phase 1 Trials

A leading pharmaceutical company in Europe collaborated with eClinical Solutions to manage data in a Phase 1 double-blind, placebo-controlled rare disease and oncology study.

THE CHALLENGE

The study’s goal was to determine the Maximum Tolerated Dose safely, involving rigorous data review across 50+ patients and multiple data sources. The study’s ambitious project timeline necessitated data review meetings every three weeks. Rather than deploying a traditional electronic data capture system, the sponsor’s clinical CRO (Contract Research Organization) was using an eSource tool to collect data directly from the sites, and the sponsor sought a data workflow that could accommodate this approach.

THE SOLUTION

eClinical Solutions crafted a strategy allowing for the integration and continuous cleaning of data from eSource and external sources within the elluminate platform. This required meticulous mapping to standardize data formats and involved both automated and manual coding processes to ensure data integrity and readiness. To adapt to the non-EDC systems involved in the study, a hybrid workflow was implemented.

To meet the sponsor’s timing objectives, the project was managed through “micro timelines” that tracked and coordinated all activities, supported by a dedicated lead and regular updates to maintain momentum.

THE RESULTS

The collaborative approach allowed the team to meet the tight deadlines and efficiently manage extensive data from over 50 patients. Highlights include:

Continuous data cleaning and integration enabled rapid decision-making and an accelerated final data lock, paving the way for future automation enhancements in query resolutions.

The project not only adhered to timelines but also achieved cost savings, demonstrating the efficacy of the integrated eSource data management strategy.

The project’s success to date is underpinned by eClinical Solutions’ expertise in biometrics and their ability to foster strong collaborations with all stakeholders, ensuring that innovative and decentralized workflows were effectively utilized.

Case Study

Complex Trial Success Depends on an Innovative, Flexible Mindset

As clinical trials continue to become more complex, a proactive, innovative, and flexible mindset is essential. Trials are not going to become simpler, so the future of successfully navigating trials hinges upon a transformative and integrated approach.

This holistic transformation involves not just adopting new technologies but also rethinking existing processes and workflows to enhance efficiency and data integrity. Leveraging advanced analytics and real-time data access capabilities, as showcased in the case studies featured in this eBook, can be extremely helpful. These technologies facilitate faster decisionmaking and more robust data oversight, essential in trials featuring complex protocols or multiple interim analyses. Moreover, embracing a culture of continuous innovation and flexibility—

able to adapt to new challenges swiftly— is vital for sustaining efficiency and responsiveness in our rapidly evolving field.

Predictions for handling future complexities suggest that trials will increasingly rely on sophisticated data science techniques and growing application of emerging technologies. This shift will necessitate a comprehensive reskilling of the workforce to align with emerging data science roles and responsibilities, ensuring that teams are not only prepared to handle current data complexities but are also equipped for future advancements. The adoption of artificial intelligence (AI) and machine learning (ML), integrated with a flexible Clinical Data Lakehouse architecture, are fundamental steps toward aligning with future technological landscapes, enabling sponsors to manage data more effectively and scale operations seamlessly.

Further, the strategic use of partnerships reflects the importance of collaboration in this dynamic environment. By aligning with experienced technology and service providers, trial sponsors can enhance their operational capabilities and better manage the complexities introduced by new trial designs, technologies, and data sources. These partnerships are essential for futureproofing operations in the context of an increasingly complex future, preparing organizations to thrive irrespective of evolving clinical trial paradigms.

In conclusion, managing the complexity of modern clinical trials effectively requires a concerted effort towards innovation, strategic flexibility, and holistic transformation. By integrating advanced technologies, fostering a flexible and innovative culture, and enhancing skills across teams, organizations can not only navigate current complexities but also position themselves successfully for future challenges in the realm of clinical research.

Click here to learn more about best practices in the ever-changing world of complex trials.

About eClinical Solutions

eClinical Solutions’ industry-leading data & analytics platform, elluminate®, and biometrics services experts help biopharma researchers at large, mid-size, and emerging life sciences organizations manage trial complexity in less time and with fewer resources. Clients get accurate and timely data insights for better decision-making – enabling them to reduce cycle times, improve productivity, easily scale, and develop tomorrow’s breakthroughs with today’s resources.

For more information about how eClinical Solutions Biometrics Services experts and the elluminate Clinical Data Cloud can help you address the challenges of your complex clinical trials, contact your eClinical Solutions Representative or visit www.eclinicalsol.com.