GOOD CLINICAL PRACTICE
BIOS has GCP processes in place in the form of standard operational procedures (SOPs) and PWGs (Protocol Working Guidelines) to manage workflow and issues related to quality control, imaging, safety reporting, data entry, training and certification, financial planning, and the operational requirements for records maintenance, data security, filing and storage of study records. This experience demonstrates the center’s ability to develop solid outcomes-based approaches across multiple acute disease processes employing functional outcomes and quality of life measures. BIOS has developed study handbooks, SOPs, and manuals of operations and procedures, as well as evaluation tools for neuropsychological outcome, brain hemorrhage outcome, stroke outcome, and cardiac arrest outcome. It has implemented, tested and validated, via internal and external monitoring, multicenter brain CT and MRI data collection, storage and central reading efforts in numerous multicenter trials. The center has validated paper and customized web-based data collection systems with onsite monitoring and external review and has substantial experience with FDA CDER, FDA (IND) new drug application, FDA orphan products processes and approvals. BIOS has managed multicenter IRB approval processes, including additional regulatory experience with European Union regulatory and ethical requirements and has practical experience in augmenting study activities with additional sites for NIAID, NINDS and FDA-sponsored studies. BIOS staff are also experienced in EFIC (Exception from Informed Consent) studies, which are used for emergency research trials. Two such studies, RAMPART, a seizure trial, and ProTECT, a traumatic brain injury trial, are part of the NIH funded NETT (Neurologic Emergency Treatment Trials). The start-up work for these trials included collaborating with the IRB, to conduct community consultation and public disclosures regarding the purpose and scope of the trials.
BIOS utilizes public-private partnerships including inter-university center collaborations, materials agreements with pharmaceutical companies, international drug distributors, CROs, software developers, foundations, and device companies. Since organizing as a research center in the late 1990’s, the team has developed a consortium of nearly 100 international, clinical sites, many of which, for more than a decade, has participated in multiple trials. With recruitment accountability learned from FDA and NINDS sponsored trials, BIOS has built outstanding capabilities to assess, measure, and meet recruitment requirements. BIOS has provided consistent training for methodologies and protocol practices and user-friendly processes for regulatory approvals and contract negotiations. BIOS and its enrolling centers have had an outstanding track record of center and site personnel retention. Likewise, it has a cadre of familiar support services across trials, such as investigational drug pharmacists, site regulatory specialists, monitors, drug distributors, and a long-standing relationship with the JHU Office of Research Administration and the JHU CTSA.
MODEL TRAINING PROGRAMS
BIOS is a recognized leader in training medical and non-medical personnel in emergency neurological protocols, critical care protocols, ICU protocols, and functional outcomes. BIOS demands a rigorous, ongoing training program for all clinical site participants throughout the lifespan of each trial managed. It has a substantial up-to-date library of targeted training tools for acute and chronic status assessments required by clinical trials including but not limited to: surgical techniques, drug administration, imaging-dosing decision-making, the NIH Stroke Scale, Glasgow Coma Score, Glasgow Outcome Scale (GOS), extended GOS, Stroke Impact Scale, and neuropsychological testing, as well as a training library of data forms for capture of physiologic and interventional data.
The use of wide-ranging web capabilities enables BIOS to connect to consortia sites, which has exponentially improved the utilization of trial-specific web-based training. The BIOS experience is that web utilization has become a front-and-center feature of our trial management style—in discussions with coordinators and investigators about protocol, protocol variances, performance, goals, and burdens. Every opportunity is a training opportunity, and every training opportunity is a sequence reinforced through a repetitious FAQ-newsletter-live broadcast-website posting-self test. Presently, our web-based training includes site training, retraining and testing/validation of the training status of each investigative team. Our training utilizes both mandatory group training sessions and individual site team-building education. Key elements of training are always followed by a test to demonstrate competency and protocol mastery. A repository of trial instruction modules, hosted by our CRO partner, allows individualized or multisite coordinator and investigator training and training of new personnel (Emissary.com). New training modules are broadcast multiple times each month and then posted to each trial’s website for future reference and training
All trials follow regulations published in the Code of Federal Regulations 21 CFR 312 defining the procedures and requirements governing the use of investigational new drugs and the monitoring of serious and unanticipated adverse events and are registered with Clinicaltrials.gov. BIOS is approved for multi-trial, multisite management by the JHU IRB and is likewise recognized as a coordinating center by the Western IRB (WIRB) and other IRBs. In collaboration with one of three satellite Surgical Centers (University of Chicago, I. Awad; U. Cincinnati, M. Zuccarello; and UCLA, P. Vespa) BIOS performs standardized treatment and performance metrics, depending on trial assignments. The Center for Drug Evaluation and Research (CDER, FDA) monitors many treatment protocols under IND 8523. Experience includes grant preparation, quarterly and annual reports, and activities for local and regional IRBs, Health Canada, MRA and other European agencies, FDA, NIH, CDER and pharmaceutical ISTs.
ELECTRONIC TRIAL MANAGEMENT
BIOS is a paperless management group that has pioneered the conduct of all aspects of a trial in the electronic domain. This allows all team members simultaneous access to regulatory, contract and primary medical trial data for validation cross-check, timely data collection, and early quality monitoring. The audit capability of these electronic processes allows for economies in staffing, simplification of monitoring, straightforward dissemination of project management accomplishments and problems, and the development of virtual workgroups to more rapidly review safety and protocol problems, adjudicate endpoints, and provide complete and up-to-date site performance assessments. As described above, in each area, these economies translate into greater site communication and investigator education. Specific electronic innovations include remote monitoring using electronic medical record repositories, development of a fully electronic CT and MRI image reading center for multisite trials (including the training and support of study coordinator based DICOM image transfer), real-time image and surgical procedure adjudication of trial eligibility, and site-specific electronic quality assessments.
ON-CALL ENROLLMENT CENTER
BIOS functions 24/7 for site randomizations and enrollment decision-making. Central enrollment monitoring is critical when subjects are infrequent, as in rare disorders and new consortia. When performance processes are based on unique patient, image, and diagnostic data, correct screening decisions, enrollment by strata/group assignments should be based on the technical reading of clinical history, images, and diagnostic testing. BIOS has minimized this variable and increased enrollment by developing a study enrollment and protocol compliance monitoring capability that works in real time with digitally transmitted data to assure compliance and quality at this most critical study stage.
CENTRALIZED DATA EVALUATIONS
The BIOS CT/MRI reading center has developed innovative, accurate methods for the qualitative and quantitative volumetric analysis of brain lesions. It has successfully combined image and data management systems to produce meaningfully designed reports of neurological outcomes, neurosurgical performance, drug delivery, infection tracking, new brain bleeding events, and neurological adverse event (AE) tracking.
BIOS personnel have significant experience collaborating with NIH staff, meeting on multiple occasions to discuss grant program development and completion specifics. BIOS has forged strong working relationships with NIH/NINDS, the FDA Office of Orphan Products Development, and CDER personnel that facilitate IND, grant, and contract approvals.
BIOS has demonstrated its capacity to complete project goals and recruitment, as well as safety and dose-finding tasks. 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 and parallel clinical course and “standard of care” concurrent therapy data. This process is made possible with the use of innovative data collection and clinical care “standard operating procedures.”