On behalf of my colleague Angela Ribble, and myself, I thank the Standard and Security Subcommittee of the NCVHS for the opportunity to provide comment on PRMI terminology issues. Angela Ribble is a Project Manager with the Southwest Oncology Group (SWOG), one of the Clinical Trials Cooperative Groups sponsored by the National Cancer Institute. Angela's duties include oversight of the SWOG database, development of case report forms (CRFs), Clinical Research Associates (CRA) Workbench website, and intergroup interactions. She also serves as the HIPAA Privacy Officer. My name is Beverly Meadows and I am a Nurse Consultant, Clinical Trials Development and Informatics, with the Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis (DCTD), of the National Cancer Institute (NCI). I am the coordinator of the Common Data Elements (CDE) Project for CTEP and Assistant Project Officer for the Cancer Trials Support Unit (CTSU). We work with PMRI terminology in the context of cancer clinical trial data collection and management. Prior to proceeding with my testimony, I would like to present a brief overview of CTEP and the Cooperative Group Program as background for my presentation.
The mission of CTEP is to improve the lives of cancer patients by finding better ways to treat, control and cure cancer. CTEP accomplishes this mission by funding an extensive national program of cancer research, which includes the Clinical Trials Cooperative Group Program. In addition, CTEP attempts to forge broad collaborations within the research community and works extensively with the pharmaceutical/biotechnology industry to effectively develop new cancer treatments.
The Clinical Trials Cooperative Group Program, which was established 1955, was originally funded under research grants from the NCI to test new anticancer agents provided by the NCI drug development program. Over the intervening years the focus of the Program has evolved to address definitive studies of combined modality approaches for the treatment of cancer. The efforts of thousands of individual investigators who participate in the Cooperative Group protocols were instrumental in accruing over 27,000 patients to Group treatment studies in 2002.
Section 1 - PMRI Terminology Users "Terminology Specific"
1. Check those applications or clinical process that you use this terminology for, include strengths and weaknesses and address mapping to other terminologies:
The PMRI terminology being reviewed for this testimony is the NCI Thesaurus, which was developed by the National Cancer Institute to provide a centralized reference terminology based on the working vocabularies used by the NCI and collaborative groups. One of the vocabulary endeavors recently created to address suggestions from an independent review committee for restructuring cancer clinical trials is the Common Data Elements (CDEs). In 1997, a collaborative effort was initiated between the Cooperative Groups and the NCI to develop a dictionary of terms that would both address the needs of the end-users, while providing a usable format for system designers to incorporate terms into Group legacy databases. The vocabulary services at NCI were consulted to discover any similar efforts in current databases that might contribute to the CDE effort. Since this effort standardizes actual questions rather than terminology systems, no matches existed in the NCI Thesaurus due to the unique focus of the CDEs. However, the goal of the CDE project is to standardize responses to questions which often entail a list of valid values that are drawn from NCI Thesaurus controlled terminology. In some instances, several terminologies are needed to accommodate the requirements of reporting mandates or the needs of the clinical community. An example of the latter would be the use of both the World Health Organization (WHO) and French American British (FAB) naming conventions for hematological diseases such as leukemia.
One category of data that must be collected is laboratory results to establish the patient's eligibility for inclusion on the trial, and to track the response of various body systems to the treatment regimen. Prior to initiating the trial, the history and physical examination of the patient provides baseline information as to the status of the patient's disease and overall level of health. One or several modalities are specifically chosen for inclusion in the treatment regimen based on findings from prior research. Modalities include the administration of agents, or intervention using surgical or radiological techniques. NCI Thesaurus is utilized as the controlled terminology to provide valid values for these various clinical content domains.
Alterations in health status may be precipitated by the treatment regimen, which may cause an adverse event of varying intensity. Adverse events are evaluated using the Common Toxicity Criteria (CTC), which is mapped to terminology from the Medical Dictionary for Regulatory Affairs (MedDRA) mandated for reporting to the FDA. In addition to the correct term, the clinician must also grade the intensity of the adverse event and objectively assess the temporal relationship or attribution of the event to the intervention. NCI Metathesaurus provides complete MedDRA terminology and mappings. Adverse event terms created by experts such as SWOG trialists in the field, as represented in the CDEs and NCI Thesaurus, can then be mapped to MedDRA preferred terms. In addition, NCI Thesaurus staff maintain updates of adverse event mappings to comply with reporting mandates using the most recent available version of MedDRA.
Strengths and Weaknesses
The CDE project was initiated to incorporate regulatory vocabularies, and to facilitate electronic communication among diverse applications. However, a more important aspect of the CDE project is to create data elements that are meaningful to end-users such as clinical research associates (CRAs), data managers and research nurses who are essential to initiating and maintaining data integrity, a process which begins with the abstraction of clinical data from patient source documents.
There are several concerns when structuring a vocabulary to facilitate clinical research. A primary concern is flexibility to respond to the dynamics of the science. Since clinical trials must reflect current science, it is essential to offer timely inclusion of new terms into the vocabulary without creating obstacles for the research process. Domain experts are consulted to provide basic categories or metadata, such as definitions and suggested valid values, for newly submitted vocabulary elements. The NCI Thesaurus is utilized to assure the correct representation of these values with a dual purpose of enriching not only the CDE Dictionary but also for updating the NCI Thesaurus to reflect current practice in the clinical arena.
Section II - PMRI Terminology Users "General"
Implementation and Usage of the CDEs in a Clinical Setting
Although terminology systems are often stored as remote repositories distant from the actual practice setting, the CDE project addresses the applied use of a controlled vocabulary in a companion NCI pilot project, the Cancer Trials Support Unit (CTSU). One of the goals of the CTSU is to create a remote data capture (RDC) system for the collection and management of clinical trial data for Phase III treatments trials lead by the Cooperative Groups. To accommodate the adoption of CDEs as a standard for data exchange, the laborious task of mapping is necessary to link terms in the database reference libraries unique to each Cooperative Group to comparable CDEs. The standardized vocabulary provided by the NCI Thesaurus facilitates this mapping process to produce a common terminology for exchange of data across disparate systems.
With the growth of the CDE Dictionary, a robust infrastructure was needed to accommodate the needs of the scientific community and also to address the technological aspects of adapting terminology as a data exchange standard. Prior to building the infrastructure, a standard was needed to universally represent the metadata that defines each CDE. A decision was made to use the ISO1179 metadata standard to provide a stable and more robust infrastructure as the Cancer Data Standards Repository or caDSR. An electronic application was also developed to facilitate CDE development using the NCI Thesaurus as a basis for identifying data element concepts and valid value domains.
Although the actual use of the remote data capture (RDC) system is just beginning, the CDEs and data standards have been incorporated to meet the challenge of data transfer to not only consider the development of new systems, but also to accommodate the legacy systems where data from other studies are stored. When terminologies are chosen as standards, the selection criteria should strongly consider the actual use potential to bridge the gap between vocabulary repositories and the implementation of these vocabularies in clinical settings. The actual utility of a standardized vocabulary can only be tested when implemented in an end-user application.