Computable Phenotype of a Crohn's Disease Natural History Model.

BACKGROUND: Analytic tools to study important clinical issues in complex, chronic diseases such as Crohn's disease (CD) include randomized trials, claims database studies, or small longitudinal epidemiologic cohorts. Using natural language processing (NLP), we sought to define the computable phenotype health state of pediatric and adult CD and develop patient-level longitudinal histories for health outcomes. METHODS: We defined 6 health states for CD using a subjective symptom-based assessment (symptomatic/asymptomatic) and an objective disease state assessment (active/inactive/no testing). Gold standard for the 6 health states was derived using an iterative process during review by our CD experts. We calculated the transition probabilities to estimate the time to transitions between the various health states using nonparametric Kaplan-Meier estimation and a Markov model. Finally, we determined a standard utility measure from clinical patients assigned to different health states. RESULTS: The NLP computable phenotype health state model correctly ascertained the objective test results and symptoms 96% and 85% of the time, respectively, based on a blinded chart evaluation. In our model, >25% of patients who begin as asymptomatic/active transition to symptomatic/active over the following year. For both adult and pediatric CD health states, the utility assessments of a symptomatic/inactive health state closely resembled a symptomatic/active health state. CONCLUSIONS: Our methodology for a computable phenotype health state demonstrates the application of real-world data to define progression and optimal management of a chronic disease such as CD. The application of the model has the potential to lead to a better understanding of the true impact of a therapeutic intervention and can provide long-term cost-effectiveness analyses for a new therapy. HIGHLIGHTS: Using natural language processing, we defined the computable phenotype health state of Crohn's disease and developed patient-level longitudinal histories for health outcomes.Our methodology demonstrates the application of real-world data to define the progression of a chronic disease.The application of the model has the potential to provide better understanding of the true impact of a new therapy.

Assessment of reliability and validity of IBD phenotyping within the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium (IBDGC).

BACKGROUND: The NIDDK IBD Genetics Consortium (IBDGC) collects DNA and phenotypic data from inflammatory bowel disease (IBD) subjects to provide a resource for genetic studies. No previous studies have been performed on the reliability and validity of phenotypic determinations in either Crohn's disease (CD) or ulcerative colitis (UC) using primary records. Our aim was to determine the reliability and validity of these phenotypic assessments. METHODS: The de-identified records of 30 IBD patients were reviewed by 2 phenotypers per center using a standard protocol for phenotypic assessment. Each phenotyper evaluated 10 charts on 2 occasions 5 months apart. Reliability was expressed as the kappa (kappa) statistic. Performance characteristics were determined by comparison to a consensus-derived "gold standard" and by generation of receiver operating characteristic (ROC) curves. RESULTS: Agreement for diagnosis was excellent (kappa = 0.82; 95% confidence interval [CI]: 0.71-0.92). Agreement for CD location was good for jejunal, ileal, colorectal, and perianal disease with kappa between 0.60 and 0.74 but was fair for esophagogastroduodenal (kappa = 0.36). Agreement for UC extent (kappa = 0.67; 95% CI: 0.48-0.85), and CD behavior (kappa = 0.67; 95% CI: 0.49-0.83) were very good. Area under the ROC curves was greater than 0.84 for diagnosis, CD behavior, UC extent, and ileal and colonic CD location. CONCLUSIONS: IBD phenotype classification using a standard protocol exhibited very good to excellent inter- and intrarater agreement and validity. This study highlights the importance of standard protocols in generating reliable and valid phenotypic assessments. The data will facilitate estimates of phenotyping misclassification rates that should be considered when making inferences from IBD genotype-phenotype studies.

A cost-effectiveness analysis of diagnostic strategies for symptomatic patients with ileal pouch-anal anastomosis.

OBJECTIVE: Pouchitis is often diagnosed based on symptoms and empirically treated with antibiotics (treat-first strategy). However, symptom assessment alone is not reliable for diagnosis, and an initial evaluation with pouch endoscopy (test-first strategy) has been shown to be more accurate. Cost-effectiveness of these strategies has not been compared. The aim of this study was to compare cost-effectiveness of different clinical approaches for patients with symptoms suggestive of pouchitis. METHODS: Pouchitis was defined as pouchitis disease activity index scores > or =7. The frequency of pouchitis in symptomatic patients with ileal pouch was estimated to be 51%; the efficacy for initial therapy with metronidazole (MTZ) and ciprofloxacin (CIP) was 75% and 85%, respectively. Cost estimates were obtained from Medicare reimbursement data. RESULTS: Six competing strategies (MTZ trial, CIP trial, MTZ-then-CIP trial, CIP-then-MTZ trial, pouch endoscopy with biopsy, and pouch endoscopy without biopsy) were modeled in a decision tree. Costs per correct diagnosis with appropriate treatment were $194 for MTZ trial, $279 for CIP trial, $208 for MTZ-then-CIP trial, $261 for CIP-then-MTZ trial, $352 for pouch endoscopy with biopsy, and $243 for pouch endoscopy without biopsy. Of the two strategies with the lowest cost, the pouch endoscopy without biopsy strategy costs $50 more per patient than the MTZ trial strategy but results in an additional 15 days for early diagnosis and thus initiation of appropriate treatment (incremental cost-effectiveness ratio $3 per additional day gained). The results of base-case analysis were robust in sensitivity analyses. CONCLUSIONS: Although the MTZ-trial strategy had the lowest cost, the pouch endoscopy without biopsy strategy was most cost-effective. Therefore, based on its relatively low cost and the avoidance of both diagnostic delay and adverse effects associated with unnecessary antibiotics, pouch endoscopy without biopsy is the recommended strategy among those tested for the diagnosis of pouchitis.