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Since the 1990s, BIOS CTCC has coordinated international, federally funded, and industry-sponsored trials across a range of conditions for investigators at Johns Hopkins University and other medical centers. Its focus is to provide multicenter coordinating infrastructure to a variety of clinical trials evaluating therapeutic, preventive, and diagnostic interventions.

Study Design

The study design of a clinical trial is essential to the validity, scientific integrity, data credibility, and success of the trial. The selection of the clinical trial design is dependent upon factors such as the disease class, the phase of the trial or stage of drug development, and the expected outcome. A well-designed study follows established aims and objectives and informs elements such as eligibility criteria, selection and randomization of participants, blinding/masking, selection of end points, and the analytic method best suited to analyzing this unique dataset. BIOS CTCC experts work in an active collaboration with every investigator and their team to design a feasible study that meets their scientific hypothesis, tailoring each design to ensure a solid foundation for the trial.

Project Management

BIOS CTCC has managed projects at more than 200 international clinical centers. With activation and recruitment accountability systems developed over multiple FDA- and NIH-sponsored trials, enrolling centers have consistently had an outstanding record of participant and site personnel retention. The project management process includes:

  • Methodologies training
  • Protocol practices training
  • User-friendly processes for regulatory approvals and contract negotiations
  • Grant preparation
  • Quarterly and annual reporting
  • Submission organization for local, regional, and international review boards, ethics committees, regulatory authorities, and community consultations

Project managers have available a library of study handbooks, SOPs, operation manuals, and management tools. They can implement and validate central image collection and analysis, as well as validate paper and customized web-based data collection systems with onsite monitoring and external review. 

Electronic Platforms

BIOS CTCC is a pioneer in all aspects of managing clinical trials, including the electronic domain. Electronic platforms empower investigators and trialists to simultaneously access regulatory, contractual, and primary trial data for validation cross-checking and early quality monitoring of data timeliness and accuracy. The audit capability of these electronic processes provides economies in staffing, monitoring simplification, and straightforward reporting of project management accomplishments and problems. It is a virtual environment for workgroups to more rapidly review safety and protocol problems, adjudicate endpoints, and provide complete and up-to-date site performance assessments. These innovations also translate into greater site communication and investigator education. Electronic innovations include:

  • Remote monitoring of medical record repositories
  • Fully electronic image reading center
  • Real-time adjudication of trial eligibility
  • Site-specific quality assessments
Compliance and Partners

BIOS CTCC trials follow the Code of Federal Regulations 21 CFR 312 and are registered with clinicaltrials.gov. BIOS CTCC is approved for clinical trial project management by the Johns Hopkins Medicine IRB and is recognized as a coordinating center by the Western IRB (WIRB) and other IRBs. Partners include university and industry core centers, device and pharmaceutical companies, international drug distributors and contract research organizations, and software developers. A cadre of support services includes:

  • Investigational drug pharmacists
  • Regulatory specialists
  • Monitors
  • Long-standing relationships with the Johns Hopkins (JH) Office of Research Administration and Institute for Clinical and Translational Research

Clinical Coordinating Center (CCC)

When serving as the Clinical Coordinating Center, BIOS CTCC provides study planning, risk assessment, project management, development of study materials, training websites, and site management including identification, start-up and training, recruitment, retention, engagement strategies, customizable eTMF systems, sIRB coordination and training, and IDE/IND management.

Operational Tools
  • Accelerated Start-up Program (ASU): organizes trials into monthly, time-sensitive objectives to decrease start-up time and to activate sites earlier 
  • Global Electronic Management System (GEMS): an electronic dashboard that drives and tracks the start-up cycle 
  • Site Assessment Survey Instrument (SASI): a web-based screening tool that assesses site readiness and feasibility to assist study PIs in site selection
  • Risk Assessment Tool: identifies, qualifies, and ranks risks to proactively assess and manage risks before they occur 
Gaming

BIOS CTCC also embeds competitive gaming into trial operations to enhance site engagement, establish rapport between sites and the CCC, and improve performance before start-up, during start-up, and after site activation. These operational tools and processes can decrease the number of site start-up days. 

Data Coordinating Center (DCC)

When serving as the Data Coordinating Center, BIOS CTCC can provide data management, data analysis, and statistical design services. The data management and biostatistics teams specialize in eCRF development; EDC system builds; data quality control; data extraction, transforming, and loading (ETL); data reporting; visualization; and statistical analyses. The staff provides essential recommendations and support to the design and methodologies in all aspects, including trial development, execution, and close-out, while ensuring quality, validity, and reliability of the final product. Team members are involved in all phases of a trial from protocol development to final analysis.

Trial Support
  • Production of clean analytic datasets
  • Reports: data and safety monitoring, safety surveillance, study-specific ad-hoc reports
  • Prep work for interim and final analyses and close-out of study databases

Clinical Monitoring

BIOS CTCC has demonstrated effective clinical site monitoring by ensuring the protection of patients’ well-being and privacy; the alignment of all study materials with the approved GCP, protocol, and other materials; and the quality and integrity of the study’s data. 

Good Clinical Practice

Clinical trials are conducted by our organization under Good Clinical Practice (GCP) standards (e.g., the FDA IND/IDE regulations, E6, and similar U.S. and international regulations and guidance). Additionally, BIOS CTCC has forged strong working relationships with NIH/NINDS, the FDA Office of Orphan Products Development, and PCORI and CDER personnel that facilitate IND, grant, and contract approvals.

Trial Management

BIOS CTCC has standard operational procedures to manage quality control, imaging, safety reporting, data entry and security, training and certification, and records maintenance, filing, and storage. We employ a risk-based Clinical Quality Management System (QMS) that generally follows the model promulgated by TransCelerate BioPharma, an industry consortium, to develop a quality management and monitoring plan. This plan utilizes an integrated risk-based approach, encompassing risk management, monitoring, and patient-safety activities across multiple acute disease processes to ensure human subject protection, regulatory compliance, and the reliability of the trial results. 

Role Flexibility and Training

With staffing capable of “role flexibility,” we have identified and mitigated recruitment problems, improved protocol compliance, and diminished novel unanticipated safety issues. We have demonstrated the ability to standardize protocols across enrollment centers by educating sites unfamiliar with a protocol to perform quality, detailed collection of study data, parallel clinical course, and “standard of care” concurrent therapy data.

Data Management

BIOS CTCC has experience designing and maintaining EDC systems, collaborating with investigators, project managers, and related trial team members, and making recommendations as needed so the data can be collected efficiently. The BIOS CTCC data core has established standardized CRF libraries for different EDC platforms. These libraries help to build study EDCs efficiently and with high quality. Other responsibilities include quality control and quality assurance procedures from a statistical data analysis perspective. Standard processes for these activities were also established. 

Data Databases

The data management team is able to manage data from multiple sources, in multiple formats, and move it to one or more data repositories. We have developed sophisticated and scalable pipelines that can extract, process, store, analyze, and present data from various data sources efficiently from start to finish. Using modern tools, such as Python, R, and SAS, we created applications that enable us to process and load data in various formats into our central data warehouse. Data sources we have handled in the past include relational databases, XML files, flat data files, JSON files, and calls to application APIs. The BIOS CTCC data warehouse is hosted at the Johns Hopkins Data Center. The server is HIPAA-compliant and provides 24/7 operation.

Statistical Support

BIOS CTCC’s team of experienced faculty and staff-level biostatisticians provide support to studies through all phases of the trial, beginning with protocol and statistical analysis plan (SAP) development through study closeout and final analysis. The team provides input on study design using appropriate statistical methodologies, as well as sampling, power size calculations, randomization, and blinding. The team also creates and validates analytic datasets used for interim DSMB safety analyses, as well as primary and secondary endpoint, subgroup, and/or exploratory analyses.

Programming Languages

The team has experience using multiple programming languages including SAS, R, STATA, and Python to perform statistical analyses and further utilize R Markdown and Tableau to provide data tabulations and visualizations for various audiences.

Training

BIOS CTCC offers a comprehensive training venue that capitalizes on its ability to disseminate multilevel training for research personnel managing mRCTs. Available curricula maximize existing knowledge and procedures, lessening learning curves at leadership and middle management levels, as well as more traditional trial- and role-specific task training for clinical centers per established delegation of responsibility. Task training covers the trial life cycle for entry-level and recertification before and throughout the course of each study. 

Training Website

The training program utilizes a WordPress-based platform developed by the data management team. The training website features include:

  • Password-protected login
  • Training materials
  • Quizzes
  • Attestations
  • Certificates study-related documents
  • Online seminar recordings
  • Meeting minutes
  • Trial information (when designated as accessible by the public for recruitment purposes)
  • Google Analytics (track visitors and site performance)
Available Resources and Training

Our web-based training includes site training, retraining, and testing/validation of the training status of each investigative team. Study personnel can access study-related documents (i.e., protocol and standard operating procedures) and provide training and proficiency in topics, including:

  • Integrated quality risk management training
  • Trial planning and execution training
  • IT (Information Technology) security training
  • Electronic Data Capture (EDC) training

At the end of training, post-testing, and certificates of completion, together with an eTMF system, can establish timelines that trigger retraining at appropriate intervals. We correlate training activity with protocol deviations frequency within and across sites to foster clinical trial integrity. 

Data and Safety Monitoring Board Unit (DSMB Unit)

The Data and Safety Monitoring Board (DSMB) oversees and monitors the conduct of clinical trials to ensure the safety of participants and the validity and integrity of study data. To facilitate the work of DSMBs, the JHU-Tufts TIC established a DSMB unit composed of a DSMB unit director, a DSMB manager, and three research assistants. The National Institutes of Health (NIH) requires formal DSMBs for all phase 3 clinical trials. For phase 1 and phase 2 clinical trials, a DSMB may be established if the principal investigator, their institution, or the clinical trial funding agency deems it necessary.

DSMB Organization

The DSMB unit is an independent entity supporting the investigator, the DSMB members, and the funding agency. The unit collects documentation of the DSMB members’ qualifications for nomination and conflicts of interest, communicates with the sponsors/funding institutes/centers (ICs), and navigates issues related to the appointment of board members. Depending on trial-specific needs, the DSMB unit organizes and manages DSMB meetings in person or via web conferencing. This includes pre-specified DSMB meetings, DSMB-convened meetings in response to a safety event, and ad hoc meetings requested by the DSMB chair, study team, or sponsor.

Guiding Documents

The DSMB unit also works with each study team to ensure appropriate guiding documents such as the DSMB charter, the data and safety monitoring plan, the statistical analysis plan, the data management plan, conflict of interest forms, and the quality monitoring plan provide a framework for each study’s DSMB. These guiding documents establish the overall framework for each study’s data and safety monitoring. They include the following topics:

  • Monitoring entity
  • Participant safety plans (adverse event and reporting guidelines)
  • Data accuracy plans
  • Monitoring plans
  • Interim analysis plans

To ensure interconnection and consistency in these documents, the DSMB unit liaises between study teams, safety teams, statistician teams, data and clinical coordinating centers, and DSMB members. The DSMB unit is also in constant communication with the funding IC representatives to ensure compliance with its policies. Additionally, the DSMB unit prepares the open session meeting minutes and captures any recommendations the DSMB may have for the study team. To date, the DSMB unit has successfully managed or is currently managing DSMB meetings for 16 clinical trials.

BIONIC Image Lab and Reading Center

The Brain Injury Outcomes NeuroImaging Center (BIONIC) core image lab and reading center has developed innovative, accurate methods for the qualitative and quantitative volumetric analysis of brain lesions, as well as general image acquisition, harmonization, de-identification, archiving, and management protocols across a spectrum of imaging modalities. Specific imaging modalities that BIONIC has experience with include: CT, CTA, MRI, fMRI, PET, echocardiogram, ultrasound, and others. BIONIC also utilizes machine learning (ML) and artificial intelligence (AI) to help optimize workflows and productivity. It has successfully combined image and data management systems to produce meaningfully designed reports of outcomes, surgical performance, drug delivery, infection tracking, new events, and adverse event (AE) tracking across multiple clinical trials targeting a range of therapeutic areas.