Case Study #1: Clinical Data Management

Comprehensive Research Solutions, LLC (CRS) has been working successfully with AstraZeneca over the past 3+ years in the area of clinical data management (CDM), focused on the delivery of clean quality clinical trial data prior to submission to FDA.

Outsourcing clinical data management to CRS led to increase in efficiency of clinical trial data management and added an extra layer of objective quality control.

The case study below outlines a specific example of how CRS has helped AstraZeneca with preparation of data submission to FDA for study drug Kocelugo (Selumetinib), which resulted in FDA approval of the first drug for treatment of pediatric patients with NF1 in April 2020.

The Challenge

  • The Sponsor’s (CTEP) requirements to data management had standards which were different from AstraZeneca’s standards on the clinical trial “A Phase I/II Study of the Mitogen Activated Protein Kinase Kinase (MEK) 1 Inhibitor Selumetinib (AZD6244; Hydrogen Sulfate) in Children with Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas” in application of Selumetinib for new indication for pediatric patients. This difference is rooted in the fact that the goal of gov research is “to advance scientific knowledge and help all people” and pharma’s – putting a drug on the market.
  • AstraZeneca Project team experienced substantial demand for additional data management resources familiar with the CTEP requirements, tools and systems utilized at NCI, the NCI/POB coordination site, and other sites participating in the clinical trial.
  • Difficulties in managing capacity and ensuring quick turnaround times due to discovering unanticipated tasks which had to be completed while preparing data for submission to FDA.

Our Solution

  • CRS took a lead in working with multiple stake holders including AstraZeneca project team, NCI Office of Clinical Director, Pediatric Oncology Team, vendors associated with AstraZeneca and NCI, as well as multiple participating study sites. Deep institutional knowledge, understanding of applicable federal regulations, and experience with numerous CTEP sponsored clinical trials enabled CRS to proactively anticipate and manage challenges associated with preparation of data for submission to FDA.
  • CRS took measures to perform extensive data QC, guided sites in data collection, and streamlined data cleaning activities. CRS developed and implemented Project Plan, appropriate standard operating procedures (SOPs) and Data Management metrics and manuals that were suitable for the project strategy. CRS staff focused on the following activities:
    • establishing and coordination of communication between AstraZeneca’s team and NCI/POB study team
    • assessment of the data query process and improvement recommendations
    • assessment of database readiness for blind data review, database lock, and archival
    • data quality reviews (assessment of data completeness and data extraction accuracy) in each data capture system, data cleaning coordination
    • development of data entry manuals for study databases
    • data transfer specifications
    • validation of new data checks
    • development of tools to keep track of the monitoring queries resolution and responses progress
    • development of processes for data reconciliation
    • creating data narratives for FDA submissions
    • data management closure and archival
  • Established a dedicated Clinical Data Management team led by an experienced Study Manager on NCI site. This included scaling up the project team quickly to accommodate an increase in workload, establishing ongoing evaluation of adequacy of existing data cleaning and making recommendations for improvements.
  • CRS was uniquely positioned to overcome the challenges due CRS’ institutional knowledge of NCI and availability of qualified on-site staff with knowledge of and access to NCI systems. CRS developed a tailored solution to deliver a flexible and cost-efficient service that effectively met our client’s needs. This included:
    • Creation of our own extensive training documentation to help with the on-boarding of new team members. This included ‘super users’, who were experts in the client systems and served as the primary point of contact for questions and support.
    • CRS resources and services were aligned to client objectives, systems and measurements leading to efficient work and ability to meet tight timelines.

Outcome

CRS successfully bridged the difference in practices between NCI, a government institute, and AsraZeneca, and facilitated application of AsraZeneca SOPs and standards for preparation of FDA submission.  CRS’ advanced understanding of both, NCI processes and AstraZeneca requirements, enabled to achieve data submission for priority FDA review which resulted in the recent drug approval on the market. Outsourcing CDM work to CRS enabled specific outcomes to AsrtaZeneca:

  • Resource flexibility including the availability of trained staff at the client site on a short notice
  • Improved communication and relationships with NCI stakeholders which CRS brought to the project
  • Improved timelines on client’s deliverables
  • Improved ‘Quality and on-time deliveries’ metrics
  • Optimal cost locations such as having CRS staff working from NCI the coordinating site location
  • Reduction in training requirements for the client as they were able to utilize the CRS team and their expertise
  • Reduction in client project management of studies and client oversight as this was provided by CRS on the NCI coordination site, which supported an improvement in overall efficiencies as the client was able to allocate their own resources to other projects.

The ultimate outcome of the work supported by CRS’ services was successful submission to FDA and following approval of Koselugo (Selumetinib) for pediatric patients with NF1 in April 2020. This is the first drug available for children with this condition.

Case Study #2: Biostatistics and statistical programming (BSP) service

During clinical trials it is essential that biostatistics and statistical programming teams operate efficiently to ensure a quality data output in the shortest time possible. Having a number of clinical trials running at any one time can put even the most skilled internal teams under pressure, leading more and more companies to turn to experienced outsourcing partners to keep up the pace.

Outsourcing BSP services to a clinical research organization (CRO), such as CRS can help to increase the efficiency, reduce overall trial costs and add an extra layer of objective quality control.

The case study below outlines a specific example of how CRS has helped AstraZeneca with preparation of data submission to FDA for Kocelugo (Selumetinib), which resulted in FDA approval of the first drug for treatment of pediatric patients with NF1 in April 2020. 

The Challenge

  • Difference in the purpose and practices in clinical trials data review and analysis between a government institute and commercial pharmaceutical company. This difference is rooted in the fact that the goal of government research is “to advance scientific knowledge and help all people” and pharma’s – achieving FDA approval and bringing drugs to the market
  • AstraZeneca was collaborating with National Cancer Institute, Pediatric Oncology Branch for conducting PhaseI/II clinical trial for application of Selumetinib for new indication, treatment of pediatric patients with NF1
  • AstraZeneca Project team experienced a substantial demand for additional statistical programming resources and an unpredictable requirement for statistical analysis expertise and medical writing capabilities
  • Difficulties in managing capacity and ensuring quick turnaround times due to unanticipated peaks and troughs in the workload
  • Lack of adequate internal resourcing with knowledge of and access to NCI systems, understanding of specifics of NCI process.

Our Solution

CRS was uniquely positioned to overcome the challenges due CRS’ institutional knowledge of NCI and availability of qualified on-site staff with knowledge of and access to NCI systems. CRS developed a tailored solution to deliver a flexible and cost-efficient service that effectively met our client’s needs. This included:

  • Establishing a dedicated team on NCI site. This team was overseen and coordinated by a dedicated CRS program manager and provided prompter support. This included scaling up the project team quickly to accommodate an increase in workload
  • Establishing robust communication lines and schedule with all stakeholders, including AsrtaZeneca points of contact, NCI Pediatric Oncology Branch, and multiple vendors working on the clinical trial data. This created a greater sense of collaboration and working as part of the same team and not as an independent service provider
  • Developed appropriate standard operating procedures (SOPs) that were suitable for the project strategy. This was supported by the creation and implementation of a requirement-specific training program delivered by the client to ensure the CRS team could operate as an extension of its internal team
  • Creation of our own extensive training documentation to help with the on-boarding of new team members This included experts in the client systems, who were the primary point of contact for questions and support. CRS staff analyzed data and worked on preparation of complex data reports in order to structure data in the manner required for submission to FDA.

CRS resources and services were aligned to client objectives, systems and measurements leading to efficient work and ability to meet tight timelines.

Outcomes

The ultimate outcome of the work supported by CRS services was successful submission to FDA and following approval of Koselugo (Selumetinib) for pediatric patients with NF1 in April 2020. This is the first drug available for children with this condition.

  • Resource flexibility including the availability of trained staff at the client site at short notice
  • Improved communication and relationships with NCI stakeholders, which CRS brought to the project
  • Improved timelines on client deliverables
  • ‘Quality and on-time deliveries’ metrics improvements
  • Ability to use optimal cost locations such as having CRS staff working from NCI , the coordinating site location
  • Reduction in training requirements for the client as they were able to utilize the CRS team and their expertise
  • Reduction in client project management of studies and client oversight as this was provided by CRS on the NCI coordination site, which supported an improvement in overall efficiencies as the client was able to allocate their own resources to other projects

CRS successfully bridged the difference in practices between NCI, a government institute, and AsraZeneca and facilitated application of AsraZeneca SOPs and standards for preparation of FDA submission.  CRS’ great understanding of both, NCI processes and AstraZeneca requirements enabled to achieve data submission for priority FDA review and, the recent drug approval on the market.