Overview of CDE Project
Internal discussion about developing CDEs began at NINDS in 2006 and the CDE Project goals were first formalized on the Internet in 2007. The CDE Project is intended to develop data standards in clinical research to harmonize data collection across clinical studies. There are four primary goals of the CDE Project.
- Disseminate standards for the collection of data from participants enrolled in studies of neurological diseases.
- Create easily accessible tools for investigators that are needed to collect study data.
- Encourage focused and simplified data collection to reduce burden on investigators and practice-based clinicians to increase clinical research participation.
- Improve quality control without increasing cost by providing uniform data descriptions and tools across NINDS-funded clinical studies of treatment for neurological diseases.
There are also 4 primary CDE benefits:
- Facilitate study start-up by allowing investigators access to appropriate data elements, definitions, and range and logic checks for forms, thereby reducing the time for study development.
- Facilitate development of specifications for common report templates than can be submitted to oversight committees such as a Data and Safety Monitoring Boards (DSMBs) or Observational Safety Monitoring Boards (OSMBs).
- Facilitate data sharing and data aggregation by employing standard definitions and common forms.
- Encourage common outcome measures (e.g., functional, cognitive) that may be relevant across the neurological diseases
The process of developing CDEs across neurological diseases included the NINDS CDE Team, consisting of NINDS Program Directors and KAI Research Inc. (KAI), which was retained by NINDS as a contractor to facilitate CDE development and implementation. The CDE team identified NINDS-funded clinical trials and epidemiological studies, and study investigators were asked to provide the CRFs and MOPs used in those protocols. In addition to NINDS-funded research, the literature was examined to identify clinical reports with enrollments of at least 300 subjects. Following initial review, a “critical” core of data content areas across neurologic diseases was developed and included: (1) Demographics, (2) Inclusion/Exclusion criteria, (3) Medical history, (4) Physical exam, (5) Concomitant medications, (6) Treatment log, (7) Outcome measures or study endpoints, (8) Study discontinuation/Completion, and (9) Genetic elements.
Although several CDE measures were identified, the critical core primarily represents content areas rather than specific CDE recommendations. For example, demographics are important across clinical studies, although specific demographic characterization may differ across neurologic diseases or patient age. Inclusion/exclusion criteria will vary by disease, and may also differ according to specific research questions being addressed. Treatment logs will reflect specific treatment interventions being investigated. Definitions of “good outcomes” differ by disease. Not all clinical research studies have a genetic component. Nevertheless, the initial CDE initiative framed important areas to address and identified initial content to be evaluated during the development of disease-specific CDEs.
The final CDE products were to include:
- Generic data elements and items in a structure that facilitates data independence
- Data Dictionary with definitions and variable name tags
- Template study forms in Microsoft WORD and PDF format
- Logic and range checks
- Manuals of Procedures (MOPs)
- Web site that facilitates access to the CDE data elements, data dictionary, forms, and MOPS (http://www.commondataelements.ninds.nih.gov)
Development of Epilepsy CDEs
After identifying elements spanning neurological diseases, the next step in the CDE process was to develop disease-specific CDEs for epilepsy, traumatic brain injury (TBI), stroke, Parkinson disease, and spinal cord injury. The development of epilepsy-specific CDEs began in 2008 with the NINDS CDE Team drafting a list of potential Epilepsy CDE Working Group members. The Working Group included epilepsy specialists across disciplines and research backgrounds, as well as biostatisticians experienced in epilepsy research.
The Epilepsy CDE Working Group met initially at the 2008 annual meeting of the American Epilepsy Society (AES) in Seattle. During the discussion of NINDS’s goal in developing CDEs for clinical studies, concern emerged that although the CDEs were intended to be guidelines, they would evolve into requirements to be included in all epilepsy studies (clinical trials and clinical research projects). An additional concern was whether all CDEs would be expected to be included in all NINDS funded projects, regardless of the specific epilepsy research question. Consequently, two tiers of CDEs were proposed since certain CDEs would not be applicable to all studies. The primary CDE tier was established for all clinical epilepsy studies (e.g., seizures and syndromes), and a secondary CDE tier was developed for selected epilepsy research (e.g., pediatric, surgical, cognitive).
The CDE areas spanning neurologic disease were used to facilitate discussion, and nine epilepsy-specific CDEs areas were subsequently identified. These include: (1) Antiepileptic Drugs (AEDs) and Other Antiepileptic Therapies (AETs), (2) Comorbidities, (3) Electrophysiology, (4) Imaging, (5). Neurological Exam, (6) Neuropsychology, (7) Quality of Life, (8) Seizures and Syndromes, and (9) Surgery and Pathology. Most content areas are indeed epilepsy-specific and are not readily applicable to other neurological conditions. Working Group members volunteered to serve on specific subcommittees, and subgroup chairs were identified by the Working Group CoChairs in consultation with the NINDS CDE Team. Subcommittee composition is shown in .
Membership in Epilepsy CDE Working Group Subcommittees
Each CDE subcommittee, with members of the NINDS CDE team, met by teleconference during the first year on a schedule determined by the group’s chair. Subgroup conference calls began in April 2009 and continued every 4–6 weeks through the spring of 2010. Drafts from each subcommittee were presented when the Working Group reconvened at the 2009 AES annual meeting in Boston. CDEs were modified at this meeting based upon group feedback, and a final Working Group teleconference was conducted in February 2010. Additional modifications of the CDEs were made based upon this teleconference, with a plan of posting the final product on the Web for public commentary by July 2010. The initial work product of each group took one of two forms. Some groups created template CRFs while others recommended existing, validated instruments for specific domains of epilepsy research, along with the rationale for specific recommendations.