Approaches and informatics tools to assist in the integration of similar clinical research questionnaires.

OBJECTIVE: The integration of similar clinical research questionnaires is a complex process that can benefit from informatics approaches and tools that provide a systematic structure for performing mapping and integration. This systematic approach is necessary to address complex issues in integration such as data heterogeneity, differing levels of granularity of questions and responses, and other issues involving semantic differences. Informatics tools and approaches have been successfully applied to various standard clinical vocabulary integration processes but not for questionnaire integration or mapping. METHODS: A systematic approach to questionnaire integration was developed in the context of a collaboration of researchers using Trial/DB, a database designed to support clinical research. This approach was applied to the integration of questionnaires involving breast cancer risk factors from each of three research sites. RESULTS: From 375 questions on the three original questionnaires, we identified 65 concepts that were measured by two or three of the sites. An algorithm was developed and used to formalize the process of mapping questions and answers across the questionnaires. The approach was applied to previously collected data and prospective data in disparate data-base systems to import and merge the data from these three sites into Trial/DB. CONCLUSION: Informatics tools that support a systematic approach to mapping questionnaires can be used throughout the research process from questionnaire integration and creation, legacy data integration to data library maintenance and curation.

ALFRED: the ALelle FREquency Database. Update.

Elaboration of ALFRED (http://alfred.med.yale.edu) is being continued in two directions. One of which is developing tools for efficiently annotating the entries and checking the integrity of the data already in the database while the other is to increase the quantity and accessibility of data. Information contained in ALFRED such as, polymorphic sites, number of populations and frequency tables (one sample typed for one site) has significantly increased.

TrialDB: A web-based Clinical Study Data Management System.

Clinical Study Data Management Systems (CSDMSs) are a class of software that support centralized management of data generated during the conduct of clinical studies. Commercial CSDMSs include Oracle Clinical, ClinTrial and MetaTrial. Such systems, which are typically deployed at an institutional or organizational level, must accommodate diverse types of data from different clinical domains that is generated by different groups of clinical investigators. Large-scale CSDMSs typically employ a high-end database engine that is usually accessed over an intranet or the Internet using Web-based technologies. CSDMSs in institution-wide use for a variety of clinical domains are best served by entity-attribute-value (EAV) modeling for the clinical data: all the commercial CSDMSs that we are aware of use EAV design. However, de novo development of EAV databases for data management is a challenging task. A large body of generic metadata-driven code must be developed before a basic EAV application can be written. Clearly, the availability of pre-existing software with the requisite functionality would be very valuable. We will discuss the benefits of such software being in open-source form.

Issues in computer-based decision support in public health illustrated using projects involving childhood immunization.

The article discusses issues that arise in implementing computer-based decision support using childhood immunization as a source of examples. The examples include (1) IMM/Serve, a program that provides patient-specific recommendations, (2) informatics tools developed to help validate IMM/Serve's knowledge and functionality, and (3) tools developed to explore how computers can help ensure immunization data quality. Issues discussed include the complexity of creating computer-based decision support, the need for a continuing process of revision and testing as the health field evolves over time, and the potential value of computer-based tools to assist in this process.

Maintaining and incrementally revalidating a computer-based clinical guideline: a case study.

The paper explores the issues involved in maintaining the logic within a complex computer-based clinical guideline, using as a case study IMM/Serve, an operational guideline whose domain is childhood immunization. For a period of more than a year and a half, we have maintained a log of (1) the national changes to the immunization recommendations, (2) the local customizations of IMM/Serve's logic, and (3) certain logic problems that arose in the process of accommodating these changes and customizations. We describe the nature of these changes, customizations, and problems. We also discuss how different types of domain knowledge might assist in the automated process of validating successive versions of the logic. The paper's goal is to use the immunization domain to provide specific examples of the issues and problems that arise in maintaining a computer-based clinical guideline.

Exploring the utility of demographic data and vaccination history data in the deduplication of immunization registry patient records.

Duplicate patient records pose a major problem for many immunization registries, as well as for many electronic patient record systems. This paper reports two complementary studies exploring the deduplication of immunization registry records. One study explores the utility of different demographic data elements, singly and in combination, to assist in the deduplication process. The second study explores how clinical patient data (vaccination history data) might assist in this process. To assess the utility of demographic data elements, data were used from three registries after duplicates had been identified. A computer program, IMM/Scan, was written to count the number of true-positive (TP) matches and false-positive (FP) matches found when using different Boolean combinations of demographic data elements. In this study, a strategy of "ORing high value ANDed pairs of data elements" appeared to be most powerful. To assess the utility of vaccination history data, record pairs were drawn from 440,000 patient records. Two metrics on patient history were tested: (1) the number of identical doses shared by two records, and (2) the number of "extra" doses in the combined history of two records. In this study, sample findings include: (1) for pairs of nonduplicate records, 93% had no identical doses and 90.6% had "extra" doses, and (2) for pairs of duplicate records, 83.8% had one or more identical doses and 82% contained no "extra" doses. These studies demonstrate potentially useful approaches to using demographic data and patient history data to assist the automated deduplication of immunization patient records.

Domain-constrained generation of clinical condition sets to help test computer-based clinical guidelines.

The paper describes T/Gen, a prototype computer-based tool designed to help maintain the knowledge in a computer-based clinical practice guideline that provides patient-specific recommendations. T/Gen takes as input a set of clinical conditions to which a guideline must react, and allows the user to specify domain-specific constraints as to which combinations of conditions do not make sense or do not need to be exhaustively tested against one another. T/Gen automatically generates constrained sets of combinations of clinical conditions, each corresponding to a clinical case (or to several closely related clinical cases) that can be used to help test the computer-based guideline. The combinations can be used to test the guideline logic using T/Gen's built-in logic interpreter, or to generate a set of test cases for use in testing an operational guideline system. T/Gen has been developed and tested with five pilot guidelines, for two childhood immunization series, for influenza vaccination, for primary thyroid screening, and for embryo transplantation. The paper describes how T/Gen's approach is implemented for the five pilot guidelines, outlines the current status and future directions of the project, and discusses the design issues that arose in the course of carrying out the work.

Integration of multidisciplinary sensory data: a pilot model of the human brain project approach.

The paper provides an overview of neuroinformatics research at Yale University being performed as part of the national Human Brain Project. This research is exploring the integration of multidisciplinary sensory data, using the olfactory system as a model domain. The neuroinformatics activities fall into three main areas: 1) building databases and related tools that support experimental olfactory research at Yale and can also serve as resources for the field as a whole, 2) using computer models (molecular models and neuronal models) to help understand data being collected experimentally and to help guide further laboratory experiments, 3) performing basic neuroinformatics research to develop new informatics technologies, including a flexible data model (EAV/CR, entity-attribute-value with classes and relationships) designed to facilitate the integration of diverse heterogeneous data within a single unifying framework.

ALFRED: an allele frequency database for diverse populations and DNA polymorphisms--an update.

ALFRED (the ALelle FREquency Database) is designed to store and disseminate frequencies of alleles at human polymorphic sites for multiple populations, primarily for the population genetics and molecular anthropology communities. Currently ALFRED has information on over 180 polymorphic sites for more than 70 populations. Since our initial release of the database we have focussed on increasing the quantity and quality of data, making reciprocal links between ALFRED and other related databases, and providing useful tools to make the data more comprehensible to the end user. ALFRED is accessible from the Kidd Lab home page (http://info.med.yale. edu/genetics/kkidd/) or from ALFRED directly (http://alfred.med.yale. edu/alfred/index.asp).

Informatics issues in the national dissemination of a computer-based clinical guideline: a case study in childhood immunization.

IMM/Serve is a computer-based guideline that provides patient-specific recommendations regarding childhood immunization. IMM/Serve is currently installed at an estimated 75 sites within the US Indian Health Service (IHS), with plans to extend its use to roughly 150 additional sites nationwide by the end of the year 2000. The dissemination of IMM/Serve within the IHS provides a case study with concrete examples that illustrate the diverse informatics issues that arise in the widespread dissemination of a computer-based clinical guideline.

Application of a model to guide ethical decision making in burn treatment.

Ethical considerations in the decision to resuscitate and continue treatment of a massive burn injury are complex. As survival improves, the parameters we use in deciding to resuscitate are less clear. The point at which further treatment is futile is often difficult to recognize, and the decision-making process of whether to withhold or withdraw care can cause great anxiety for the family, as well as for the burn team. The identification of the operative ethical principles in this decision-making process helps clarify issues and values. Although there is no simple algorithm for decision making with ethical dilemmas, the systematic application of the decision-making model presented here that consists of 4 prioritized questions that address medical indications, patient preferences, quality-of-life issues, and contextual factors can focus the problem and define options. In addition, early use of a hospital bioethics committee is advocated to resolve conflict and to provide an acceptable forum for discussion.

Reengineering a database for clinical trials management: lessons for system architects.

This paper describes the process of enhancing Trial/DB, a database system for clinical studies management. The system's enhancements have been driven by the need to maximize the effectiveness of developer personnel in supporting numerous and diverse users, of study designers in setting up new studies, and of administrators in managing ongoing studies. Trial/DB was originally designed to work over a local area network within a single institution, and basic architectural changes were necessary to make it work over the Internet efficiently as well as securely. Further, as its use spread to diverse communities of users, changes were made to let the processes of study design and project management adapt to the working styles of the principal investigators and administrators for each study. The lessons learned in the process should prove instructive for system architects as well as managers of electronic patient record systems.

Opportunities at the intersection of bioinformatics and health informatics: a case study.

This paper provides a "viewpoint discussion" based on a presentation made to the 2000 Symposium of the American College of Medical Informatics. It discusses potential opportunities for researchers in health informatics to become involved in the rapidly growing field of bioinformatics, using the activities of the Yale Center for Medical Informatics as a case study. One set of opportunities occurs where bioinformatics research itself intersects with the clinical world. Examples include the correlations between individual genetic variation with clinical risk factors, disease presentation, and differential response to treatment; and the implications of including genetic test results in the patient record, which raises clinical decision support issues as well as legal and ethical issues. A second set of opportunities occurs where bioinformatics research can benefit from the technologic expertise and approaches that informaticians have used extensively in the clinical arena. Examples include database organization and knowledge representation, data mining, and modeling and simulation. Microarray technology is discussed as a specific potential area for collaboration. Related questions concern how best to establish collaborations with bioscientists so that the interests and needs of both sets of researchers can be met in a synergistic fashion, and the most appropriate home for bioinformatics in an academic medical center.

Exploring performance issues for a clinical database organized using an entity-attribute-value representation.

BACKGROUND: The entity-attribute-value representation with classes and relationships (EAV/CR) provides a flexible and simple database schema to store heterogeneous biomedical data. In certain circumstances, however, the EAV/CR model is known to retrieve data less efficiently than conventionally based database schemas. OBJECTIVE: To perform a pilot study that systematically quantifies performance differences for database queries directed at real-world microbiology data modeled with EAV/CR and conventional representations, and to explore the relative merits of different EAV/CR query implementation strategies. METHODS: Clinical microbiology data obtained over a ten-year period were stored using both database models. Query execution times were compared for four clinically oriented attribute-centered and entity-centered queries operating under varying conditions of database size and system memory. The performance characteristics of three different EAV/CR query strategies were also examined. RESULTS: Performance was similar for entity-centered queries in the two database models. Performance in the EAV/CR model was approximately three to five times less efficient than its conventional counterpart for attribute-centered queries. The differences in query efficiency became slightly greater as database size increased, although they were reduced with the addition of system memory. The authors found that EAV/CR queries formulated using multiple, simple SQL statements executed in batch were more efficient than single, large SQL statements. CONCLUSION: This paper describes a pilot project to explore issues in and compare query performance for EAV/CR and conventional database representations. Although attribute-centered queries were less efficient in the EAV/CR model, these inefficiencies may be addressable, at least in part, by the use of more powerful hardware or more memory, or both.

A cost-benefit analysis of initial burn cultures in the management of acute burns.

It is common practice to obtain cultures in the first 24 hours after burn injuries. However, little evidence exists that these tests change clinical practice or clinical outcome. We conducted a retrospective chart review to determine how often the results of wound and other cultures lead to changes in the clinical treatment of patients. A total of 598 charts were reviewed. Four hundred forty-seven patients had a length of stay in the hospital of 1 day or less and were primarily treated in the emergency department and then discharged from the hospital. Wound cultures were obtained for 42 (10%) of these patients. Thirty cultures (71%) had no significant growth. Twelve cultures (29%) grew mixed common skin flora. No patients in this group were "pan-cultured." No patients in this group required antibiotic treatment on the basis of culture results. A total of 151 patients were admitted to the burn center, with an average length of stay of 3.9 days (range, 2-125 days). In this group, 45 patients (30%) had wound cultures and 24 patients (16%) were pan-cultured in the first 24 hours after admission to the hospital. Enterococcus species grew in the initial wound culture of 1 patient, and the patient was treated with antibiotics. Antibiotics were not ordered for any other patients on the basis of cultures. The collection of routine cultures during the first 24 hours after admission to the hospital is not cost-effective and rarely alters or provides therapeutic direction. An estimated $14,000 per year decrease in charges could be achieved by the elimination of cultures taken during the first 24 hours of admission to the hospital.

ALFRED: a Web-accessible allele frequency database.

We present a Web-accessible database (ALFRED) that allows public access to gene frequency data for a diverse set of population samples and genetic systems. The data in ALFRED are modeled based on the experience and needs of a single laboratory, but with the expectation that the database will meet the needs of a much broader scientific community that needs population-specific gene frequency estimates. Our database currently contains data on more than 40 populations representing most major regions of the world and data on more than 150 genetic systems including SNPs, STRPs, and insertion-deletion polymorphisms. While data are not available for all population-genetic system combinations, over 2000 allele frequency tables already exist. In this paper, we enumerate the broad needs in the scientific domain, describe their significance, and describe how we have designed the database to meet those needs. We compare our database with dbSNP, the NCBI database that has a broader but overlapping purpose.

PathMaster: content-based cell image retrieval using automated feature extraction.

OBJECTIVE: Currently, when cytopathology images are archived, they are typically stored with a limited text-based description of their content. Such a description inherently fails to quantify the properties of an image and refers to an extremely small fraction of its information content. This paper describes a method for automatically indexing images of individual cells and their associated diagnoses by computationally derived cell descriptors. This methodology may serve to better index data contained in digital image databases, thereby enabling cytologists and pathologists to cross-reference cells of unknown etiology or nature. DESIGN: The indexing method, implemented in a program called PathMaster, uses a series of computer-based feature extraction routines. Descriptors of individual cell characteristics generated by these routines are employed as indexes of cell morphology, texture, color, and spatial orientation. MEASUREMENTS: The indexing fidelity of the program was tested after populating its database with images of 152 lymphocytes/lymphoma cells captured from lymph node touch preparations stained with hematoxylin and eosin. Images of "unknown" lymphoid cells, previously unprocessed, were then submitted for feature extraction and diagnostic cross-referencing analysis. RESULTS: PathMaster listed the correct diagnosis as its first differential in 94 percent of recognition trials. In the remaining 6 percent of trials, PathMaster listed the correct diagnosis within the first three "differentials." CONCLUSION: PathMaster is a pilot cell image indexing program/search engine that creates an indexed reference of images. Use of such a reference may provide assistance in the diagnostic/prognostic process by furnishing a prioritized list of possible identifications for a cell of uncertain etiology.

IMM/Scrub: a domain-specific tool for the deduplication of vaccination history records in childhood immunization registries.

IMM/Scrub is a pilot tool developed to assist in the deduplication of vaccination history records in childhood immunization registries. This problem is complicated by a number of factors including that fact that: (1) some doses are numbered and some are not, (2) doses may have different dose numbers, (3) doses may specify different preparations within a vaccine series, (4) one dose may indicate a combination vaccine and the other dose may specify one component of that combination, (5) two doses may have slightly different dates, and (6) combinations of any of these problems may occur together. IMM/Scrub is designed to help detect 10 different types of vaccination dose duplicates and also allows the user to specify flexibly the conditions in which a duplicate dose might be automatically eliminated. In addition, IMM/Scrub is linked to the IMM/Serve immunization forecasting program, which can provide additional assistance in the data cleaning process. The paper describes (1) the design of the current pilot implementation of IMM/Scrub, (2) the lessons learned during its implementation, and (3) our preliminary experience applying it to data from three immunization databases, from a state, a metropolitan area, and an academic medical center.

Using a computer database to monitor compliance with pharmacotherapeutic guidelines for schizophrenia.

OBJECTIVE: The study examined whether prescription data from a computerized database could be used to measure conformance with treatment recommendations of the Schizophrenia Patient Outcomes Research Team (PORT). METHODS: Records of an academically affiliated Veterans Affairs medical center were reviewed to identify patients who were hospitalized for schizophrenia and later seen for at least two outpatient visits in the six months after discharge (N=353). RESULTS: Conformance with only three of the 18 PORT pharmacotherapeutic recommendations could be measured with the available data. In regard to the recommendation to use antipsychotics other than clozapine as first-line treatments in acute episodes, 77 percent of the sample filled a prescription for an antipsychotic during the acute episode. Of these, only 6 percent received an antipsychotic regimen that included clozapine. In regard to the PORT recommendation on dosage during acute symptom episodes, 42 percent of the patients on conventional antipsychotics received dosages below the recommended range, 5 percent were above the range, and 53 percent were within it. In contrast, of the 53 patients who received clozapine or risperidone, 87 percent received prescriptions within the recommended dosage range. As for the recommendation to offer a trial of clozapine to patients who do not respond to adequate trials of two different classes of conventional drugs, 10 percent of patients who were switched from conventional regimens to clozapine were receiving dosages of conventional medications below the recommended range. CONCLUSIONS: Patient prescription data can provide preliminary measures to cost-effectively assess conformance with treatment. However, the approach has several limitations, and complementary analyses would enhance its usefulness.