Objective disease activity assessment and therapeutic drug monitoring prior to biologic therapy changes in routine inflammatory bowel disease clinical practice: TARGET-IBD.

BACKGROUND: Inflammatory bowel disease (IBD) treatment paradigms recommend objective disease activity assessment and reactive therapeutic drug monitoring (TDM) prior to changes in biologic therapy. We aimed to describe objective marker and TDM assessment in routine clinical practice prior to biologic therapeutic changes in adult IBD patients. METHODS: TARGET-IBD is a prospective longitudinal cohort of over 2100 IBD patients receiving usual care at 34 US academic or community centers enrolled between June 2017 and October 2019 who received biologic therapy and had a dose change or biologic discontinuation for lack of efficacy. Objective markers of disease activity within 12 weeks prior included fecal calprotectin, C-reactive protein (CRP), endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). TDM data for infliximab or adalimumab was obtained. RESULTS: 525 patients (71.4% Crohn's disease [CD], 28.6% ulcerative colitis [UC]) receiving biologic therapy underwent dose change (55.6%) or discontinuation (44.4%) for lack of efficacy. The majority were Caucasian (85.7%), 18-39 years old (52.2%), privately insured (81.5%), and at academic centers (73.7%). For dose changes, 67.5% had at least one objective disease activity assessment or TDM in the 12 weeks prior (CD 67.9%, UC 66.2%; P = 0.79). The most common objective marker was CRP in both CD (39.1%) and UC (54.5%). CRP and calprotectin were used significantly more in UC (P = 0.02 and P = 0.03). TDM was obtained in 30.7% (28.8% UC, 31.4% CD; P = 0.72) prior to dose change. For biologic discontinuation, 79.4% patients underwent objective assessment or TDM prior. In CD, CRP (46.3%) was most common, and CT (P = 0.03) and MRI (P < 0.001) were significantly more frequent than in UC. TDM was performed in 40.1% of patients (43.5% UC, 38.0% CD, P = 0.49) prior to discontinuation. Among all participants with dose change or discontinuation, endoscopy was performed in 29.3% with CD and 31.3% with UC. Academic care setting was associated with objective assessment before therapy change (OR 1.59, 95% CI 1.01-2.50). CONCLUSION: Nearly one-third of patients undergoing a biologic dose change or discontinuation do not undergo objective disease activity assessment or TDM. Assessment choice differs by disease. Future studies assessing the impact of such practices on long-term outcomes are needed.

Recommendations for Standardizing Clinical Trial Design and Endoscopic Assessment in Postoperative Crohn's Disease.

BACKGROUND: The lack of standardized methods for clinical trial design and disease activity assessment has contributed to an absence of approved medical therapies for the prevention of postoperative Crohn's disease (CD). We developed recommendations for regulatory trial design for this indication and for endoscopic assessment of postoperative CD activity. METHODS: An international panel of 19 gastroenterologists was assembled. Modified Research and Development/University of California Los Angeles methodology was used to rate the appropriateness of 196 statements using a 9-point Likert scale in 2 rounds of voting. Results were reviewed and discussed between rounds. RESULTS: Inclusion of patients with a history of completely resected ileocolonic CD in regulatory clinical trials for the prevention of postoperative recurrence was appropriate. Given the absence of approved medical therapies, a placebo-controlled design with a primary end point of endoscopic remission at 52 weeks was appropriate for drug development for this indication; however, there was uncertainty regarding the appropriateness of a coprimary end point of symptomatic and endoscopic remission and the use of currently available patient-reported outcome measures. The modified Rutgeerts Score, endoscopic assessment of the anastomosis, and a minimum of 5cm of neoterminal ileum were also appropriate; although the appropriateness of other indices including the Simple Endoscopic Score for CD for endoscopic assessment of postoperative CD activity was uncertain. CONCLUSIONS: A framework for regulatory trial design for the prevention of postoperative CD recurrence and endoscopic assessment of disease activity has been developed. Research to empirically validate end points for these trials is needed.

Development of Entrustable Professional Activities for Advanced Inflammatory Bowel Disease Fellowship Training in the United States.

BACKGROUND: The level of inflammatory bowel disease (IBD) training in general gastroenterology fellowship is often insufficient to prepare trainees to deliver advanced IBD care in practice. Advanced IBD fellowships have been developed to fill this training gap, but there is no established curriculum, and significant variability exists across programs. Entrustable professional activities (EPAs) are practical and realistic objectives that define essential tasks of a specialty that physicians should master to be competent during independent practice. The American College of Gastroenterology (ACG) and Crohn's & Colitis Foundation (Foundation) established a task force to develop and appraise EPAs for advanced IBD fellowship. METHODS: Entrustable professional activities were developed using a multistep approach in a similar manner to other specialties. Initial EPAs identified via focus groups were evaluated, critiqued, and changed using an iterative model of feedback. The final EPAs were selected after the task force conducted a 3-phase modified Delphi method consisting of 2 sequential rounds of web-based voting and an in-person consensus meeting. RESULTS: Ten EPAs for advanced IBD fellowship were established including detailed descriptions with the associated knowledge, skills, and attitudes for each that can serve as curricular milestones. CONCLUSION: Ten EPAs describing the core work of an advanced IBD fellowship-trained physician have been established by a multisociety task force. Creating EPAs for an advanced curriculum comes with unique challenges, particularly the need to prevent duplication of prior training competencies while demonstrating the potential for unique milestones.

Shifting Cost-drivers of Health Care Expenditures in Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel diseases (IBD) are costly, chronic illnesses. Key cost-drivers of IBD health care expenditures include pharmaceuticals and unplanned care, but evolving treatment approaches have shifted these factors. We aimed to assess changes in cost of care, determine shifts in IBD cost-drivers, and examine differences by socioeconomic and insurance status over time. METHODS: The Medical Expenditure Panel Survey (MEPS), a nationally representative database that collects data on health care utilization and expenditures from a nationally representative sample since 1998, was utilized. Adult subjects with IBD were identified by ICD-9 codes. To determine changes in per-patient costs or cost-drivers unique to IBD, a control population of rheumatoid arthritis (RA) subjects was generated and matched in 1:1 case to control. Total annual health care expenditures were obtained and categorized as outpatient, inpatient, emergency, or pharmacy related. Temporal cohorts from 1998 to 2015 were created to assess change over time. Per-patient expenditures were compared by disease state and temporal cohort using weighted generalized linear models. RESULTS: A total of 641 IBD subjects were identified and matched to 641 RA individuals. From 1998 to 2015, median total annual health care expenditures nearly doubled (adjusted estimate 2.20; 95% CI, 1.6-3.0) and were 36% higher in IBD compared with RA. In IBD, pharmacy expenses increased 7% to become the largest cost-driver (44% total expenditures). Concurrently, inpatient spending in IBD decreased by 40%. There were no significant differences in the rate of change of cost-drivers in IBD compared with RA. CONCLUSIONS: Per-patient health care costs for chronic inflammatory conditions have nearly doubled over the last 20 years. Increases in pharmaceutical spending in IBD may be accompanied by reduction in inpatient care. Additional studies are needed to explore patient-, disease-, system-, and industry-level cost mitigation strategies.

The Cost of Inflammatory Bowel Disease: An Initiative From the Crohn's & Colitis Foundation.

BACKGROUND: The Crohn's & Colitis Foundation's Cost of Inflammatory Bowel Disease (IBD) Care Initiative seeks to quantify the wide-ranging health care costs affecting patients living with IBD. We aimed to (1) describe the annualized direct and indirect costs of care for patients with Crohn's disease (CD) or ulcerative colitis (UC), (2) determine the longitudinal drivers of these costs, and (3) characterize the cost of care for newly diagnosed patients. METHODS: We analyzed the Optum Research Database from the years 2007 to 2016, representing commercially insured and Medicare Advantage-insured patients in the United States. Inclusion for the study was limited to those who had continuous enrollment with medical and pharmacy benefit coverage for at least 24 months (12 months before through 12 months after the index date of diagnosis). The value of patient time spent on health care was calculated as number of workplace hours lost due to health care encounters multiplied by the patients' estimated average wage derived from the Bureau of Labor Statistics. Comparisons between IBD patients and non-IBD patients were analyzed based on demographics, health plan type, and length of follow-up. We used generalized linear models to estimate the association between total annual costs and various patient variables. RESULTS: There were 52,782 IBD patients (29,062 UC; 23,720 CD) included in the analysis (54.1% females). On a per-annual basis, patients with IBD incurred a greater than 3-fold higher direct cost of care compared with non-IBD controls ($22,987 vs $6956 per-member per-year paid claims) and more than twice the out-of-pocket costs ($2213 vs $979 per-year reported costs), with all-cause IBD costs rising after 2013. Patients with IBD also experienced significantly higher costs associated with time spent on health care as compared with controls. The burden of costs was most notable in the first year after initial IBD diagnosis (mean = $26,555). The study identified several key drivers of cost for IBD patients: treatment with specific therapeutics (biologics, opioids, or steroids); ED use; and health care services associated with relapsing disease, anemia, or mental health comorbidity. CONCLUSION: The costs of care for IBD have increased in the last 5 years and are driven by specific therapeutics and disease features. In addition, compared with non-IBD controls, IBD patients are increasingly incurring higher costs associated with health care utilization, out-of-pocket expenditures, and workplace productivity losses. There is a pressing need for cost-effective strategies to address these burdens on patients and families affected by IBD.

Extraintestinal Manifestations of Inflammatory Bowel Disease: Epidemiology, Etiopathogenesis, and Management.

PURPOSE OF REVIEW: Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) represent a complex array of disease processes with variable epidemiologic penetrance, genetic antecedents, and phenotypic presentations. The purpose of this review is to provide an overview of primary and secondary EIMs as well as salient treatment strategies utilized. RECENT FINDINGS: While the genetic antecedents remain incompletely understood, the treatment armamentarium for EIMs has expanded with new pharmaceutical drug classes that effectively treat IBD. EIMs are an increasingly recognized complication of IBD that require prompt recognition, multidisciplinary management, and a multifaceted therapeutic approach. This review highlights the complexities and ramifications of EIM management and offers therapeutic guidance.

Value-Based Health Care in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with significant resource utilization and health care burden. It is emerging as a global disease affecting an increasing proportion of the population. Along with evolving epidemiological trends, the paradigm of managing IBD has also changed. With a burgeoning repertoire of therapeutic options, improved use of health informatics, and emphasis on health care value, the treatment paradigm for IBD has experienced seismic shifts. In this review, we focused on value-based health care (VBHC)-a health care model that emphasizes monitoring outcomes to emphasize patient-centered, cost-effective IBD patient care. Several quality initiatives have been developed worldwide, and successful models of care were created for proper implementation of these initiatives. Although there are significant challenges to scale these models to a national level, it is still possible to successfully implement VBHC models within health systems to improve the quality of care provided to patients with IBD.

A Randomized Controlled Trial of TELEmedicine for Patients with Inflammatory Bowel Disease (TELE-IBD).

INTRODUCTION: Telemedicine has shown promise in inflammatory bowel disease (IBD). The objective of this study was to compare disease activity and quality of life (QoL) in a 1-year randomized trial of IBD patients receiving telemedicine vs. standard care. METHODS: Patients with worsening symptoms in the prior 2 years were eligible for randomization to telemedicine (monitoring via texts EOW or weekly) or standard care. The primary outcomes were the differences in change in disease activity and QoL between the groups; change in healthcare utilization among groups was a secondary aim. RESULTS: 348 participants were enrolled (117 control group, 115 TELE-IBD EOW, and 116 TELE-IBD weekly). 259 (74.4%) completed the study. Age was 38.9 ± 12.3 years, 56.6% were women, 91.9% were Caucasian, 67.9% had Crohn's disease (CD) and 42.5% had active disease at baseline. In CD, all groups experienced a decrease in disease activity (control -5.2 ± 5.0 to 3.7 ± 3.6, TELE-IBD EOW 4.7 ± 4.1 to 4.2 ± 3.9, and TELE-IBD weekly 4.2 ± 4.2 to 3.2 ± 3.4, p < 0.0001 for each of the groups) In UC, only controls had a significant decrease in disease activity (control 2.9 ± 3.1 to 1.4 ± 1.4, p = 0.01, TELE-IBD EOW 2.7 ± 3.1 to 1.7 ± 1.9, p = 0.35, and TELE-IBD Weekly 2.5 ± 2.5 to 2.0 ± 1.8, p = 0.31). QoL increased in all groups; the increase was significant only in TELE-IBD EOW (control 168.1 ± 34.0 to 179.3 ± 28.2, p = 0.06, TELE-IBD EOW 172.3 ± 33.1 to 181.5 ± 28.2, p = 0.03, and TELE-IBD Weekly 172.3 ± 34.5 to 179.2 ± 32.8, p = 0.10). Unadjusted and adjusted changes in disease activity and QoL were not significantly different among groups. Healthcare utilization increased in all groups. TELE-IBD weekly were less likely to have IBD-related hospitalizations and more likely to have non-invasive diagnostic tests and electronic encounters compared to controls; both TELE-IBD groups had decreased non-IBD related hospitalizations and increased telephone calls compared to controls. DISCUSSION: Disease activity and QoL, although improved in all participants, were not improved further through use of the TELE-IBD system. TELE-IBD participants experienced a decrease in hospitalizations with an associated increase in non-invasive diagnostic tests, telephone calls and electronic encounters. Research is needed to determine if TELE-IBD can be improved through patient engagement and whether it can decrease healthcare utilization by replacing standard care.

The Association Between Sustained Poor Quality of Life and Future Opioid Use in Inflammatory Bowel Disease.

Background: Inflammatory bowel disease (IBD) is associated with poor quality of life and disability. The short inflammatory bowel disease questionnaire (SIBDQ) is validated to determine patients quality of life at single time points, or improvement over time. Few studies have evaluated if sustained poor quality of life is associated with future healthcare utilization patterns. Methods: We analyzed patients from a prospective IBD natural history registry with 4 consecutive years of follow-up. SIBDQ was measured at outpatient visits. Healthcare utilization data were temporally organized into a 2-year observation period, and 2-year follow-up period. Mean SIBDQ score <50 during the first 2 years was categorized as having "poor quality of life". Primary outcomes of interest were measures of unplanned healthcare utilization and opioid use. Results: From a total of 447 participants (56.1% female, 66.1% Crohn's disease, 34.9% ulcerative colitis), 215 (48.1%) were classified as having poor quality of life. Poor quality of life was significantly associated with Crohn's disease (P < 0.01), history of IBD related surgery, and tobacco use (all P < 0.01). In the follow-up period, the same patients with poor quality of life were more likely to have abnormal biomarkers of inflammation, more telephone calls and office visits, experience unplanned care, and be exposed to opiates (all P < 0.05). After multivariable analysis, poor quality of life remained an independent predictor of future opiate use (odds ratio: 2.2, P = 0.003) and decreased time to first opiate prescription (hazard ratio: 1.67, P = 0.019) in the follow-up period. Conclusions: IBD patients with sustained poor quality of life are at an increased risk of opiate use and decreased time to opiate exposure. Routine measurement of quality of life in the outpatient setting may provide insight into those at risk for narcotic use and healthcare utilization. 10.1093/ibd/izy040_video1izy040.video25791709872001.

Telephone Encounters Predict Future High Financial Expenditures in Inflammatory Bowel Disease Patients: A 3-Year Prospective Observational Study.

BACKGROUND: Telephone activity is essential in management of complex chronic diseases including inflammatory bowel disease (IBD). Telephone encounters logged in the electronic medical record have recently been proposed as a surrogate marker of disease activity and impending health care utilization; however, the association between telephone calls and financial expenditures has not been evaluated. STUDY: We performed a 3-year prospective observational study of telephone encounters logged at a tertiary referral IBD center. We analyzed patient demographics, disease characteristics, comorbidities, clinical activity, and health care financial charges by telephone encounter frequency. RESULTS: Eight hundred one patients met inclusion criteria (52.3% female; mean age, 44.1 y), accounted for 12,669 telephone encounters, and accrued $70,513,449 in charges over 3 years. High telephone encounter frequency was associated with female gender (P=0.003), anxiety/depression (P<0.001), and prior IBD surgery (P<0.001). High telephone encounter categories had significantly more hospitalizations (P<0.001), IBD surgery (P<0.001), worse quality of life (P<0.001), more corticosteroid (P<0.001), biological (P<0.001), and opiate prescriptions (P<0.001). High telephone encounter frequency patients amassed higher total available charges in each year (P<0.001) and over the 3 years (P<0.001). Telephone encounters in 2009 (P=0.02) and 2010 (P<0.001) were significantly associated with financial charges the following year after controlling for demographic, utilization, and medication covariates. CONCLUSIONS: Increased telephone encounters are associated with significantly higher health care utilization and financial expenditures. Increased call frequency is predictive of future health care spending. Telephone encounters are a useful tool to identify patients at risk of clinical deterioration and large financial expense.

The Cost of Crohn's Disease: Varied Health Care Expenditure Patterns Across Distinct Disease Trajectories.

BACKGROUND: Patients with Crohn's disease (CD) encompass a heterogeneous disease spectrum, with variable health care utilization and expenditure patterns. Lémann Index (LI) is a metric that quantifies cumulative bowel damage and has shown utility in delineating distinct disease phenotypes. We aimed to characterize the financial burden from all medical care in CD cohort in relation to the variations in LI-based disease phenotypes. METHODS: CD patients with 5-year (y) follow-up from a prospective registry were included. LI was calculated from first (LI1) and last (LI2) clinical encounters. Change in score (LI2-LI1) or Delta LI (DLI) was used for association analysis with health care expenditures. RESULTS: A total of 243 patients with CD formed the study population (median age, 44 years; 58% women; median disease duration 12 years). DLI was used to define disease trajectories: DLI <0 (indicating improving bowel damage); DLI = 0 (stable); DLI >0 (worsening); which comprised 15.6%, 30.9%, and 53.5% of the cohort, respectively. Patients with DLI >0 had significantly higher CD-related surgeries, health care utilization, medication (steroids and biologics) use as well as higher median 5 years total and stratified charges compared with the other groups. Total 5-year expenditure was $56 million; 67% of which was related to hospitalization. Total expense showed independent positive correlation with LI2 (P = 0.001) and DLI (P = 0.001), and negative correlation with age (P = 0.029) and 5-year quality of life score (P = 0.024). CONCLUSIONS: The financial burden of CD is significantly associated with worsening bowel damage. Further research should focus on the prediction and management of the costliest/sickest patients with CD.

Group-Based Trajectory Modeling of Healthcare Financial Charges in Inflammatory Bowel Disease: A Comprehensive Phenotype.

OBJECTIVES: Inflammatory bowel disease (IBD) is a heterogeneous group of chronic inflammatory gastrointestinal conditions with variable disease courses often requiring significant healthcare expenditures. We aimed to identify disease trajectory patterns based on longitudinal financial expenditures and to assess the association of classic disease activity parameters with financial charges. METHODS: This was an analysis of a consented, prospective, natural history IBD registry (2009-2013) from a tertiary IBD center of 2,203 patients and their associated medical charges excluding pharmacy expenses. We applied group-based trajectory modeling to longitudinal healthcare financial charges to determine patterns of charges. We assessed the association between charge patterns and disease activity, quality of life, healthcare utilization, and medication requirement. RESULTS: The final model included 1,600 IBD patients with 5-year charges. We identified six distinct trajectories over the study period. Consistently High charges were associated with Crohn's disease (66.0% Consistently High patients, P<0.01), perianal involvement (22.6%, P<0.01), ulcerative colitis extent (89.7% extensive, P=0.01), prior IBD surgery (52.5%, P<0.01), and depression/anxiety (36.2%, P<0.01). Compared with other trajectories, Consistently High charges had higher 5-year disease activity indices (Harvey-Bradshaw P<0.01; ulcerative colitis activity index P<0.01), elevated C-reactive protein rates (72.3%, P<0.01), IBD surgery (64.5%, P<0.01), hospitalization (97.2%, P<0.01), corticosteroid (70.9%, P<0.01) and antitumor necrosis factor requirement (50.4%, P<0.01), and worse quality of life (P<0.01). Annual trends in parameters were reflected in temporal changes in financial charges. The majority of financial burden stemmed from inpatient care. CONCLUSIONS: Healthcare financial charges represent a novel phenotype in IBD that reflect trends in classic disease activity parameters and allow for subgroup identification of temporal disease trajectories.

The Inflammatory Bowel Disease Specialty Medical Home: A New Model of Patient-centered Care.

New models of health care have emerged over the past decade. Accountable care organizations and patient-centered medical homes are designed to improve the patient experience, enhance health care quality, and decrease cost. These models have been developed in the primary care domain and have yet to be tested in specialty care. Certain chronic diseases require principal care by a specialist or health care team. The specialty medical home would provide patient-centered care for specific populations of patients whose health care derives from a single chronic disease. This article defines the parameters for a specialty medical home and provides a specific payer-provider experience for the comprehensive care of an inflammatory bowel disease population.

Demographic and Clinical Predictors of High Healthcare Use in Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory condition requiring significant healthcare expenditure. Subgroups of individuals contribute disproportionately to spending. We aimed to determine demographic and clinical factors predictive of high healthcare expenditures for IBD patients followed over a multiyear period. METHODS: This was a registry analysis using a prospective observational, consented, natural history registry from a tertiary IBD center and associated medical charges, not including pharmacy expenses. The 100 patients with the highest medical charges (top 5%) were compared with the median 300 patients. Logistic regression determined demographic and clinical factors associated with high charge patients. RESULTS: IBD patients in the high charge group had significantly more unemployment (P < 0.0001), were of black race (P = 0.013), comorbid psychiatric illness (P = 0.002), hypertension (P = 0.01), diabetes (P = 0.004), opiate use (P < 0.0001), perianal involvement (P = 0.002), penetrating disease (P < 0.0001), and extensive colitis (P = 0.01). In multivariate analysis, unemployment (Crohn's disease [CD]: odds ratio [OR], 3.04; 95% confidence interval [CI], 1.32-7.02; ulcerative colitis [UC]: OR, 2.68; 95% CI, 1.20-5.99), psychiatric illness (UC: OR, 2.08; 95% CI, 1.03-4.19), opiates (CD: OR, 5.61; 95% CI, 2.67-11.82; UC: OR, 5.14; 95% CI, 2.52-10.48), prior surgery (CD: OR, 3.29; 95% CI, 1.59-6.82; UC: OR, 2.72; 95% CI, 1.39-5.32), penetrating CD (OR, 3.29; 95% CI, 1.02-10.62), and corticosteroid requirement (CD: OR, 3.78; 95% CI, 1.86-7.65; UC: OR, 2.98; 95% CI, 1.51-5.90) remained independently associated with high charges. CONCLUSIONS: High expenditure IBD patients were affected by more severe disease. The high prevalence of depression, anxiety, and chronic pain in these patients suggests the need for focused treatment of these comorbidities ultimately to reduce financial burden.

TELEmedicine for Patients with Inflammatory Bowel Disease (TELE-IBD): Design and implementation of randomized clinical trial.

BACKGROUND: Inflammatory bowel diseases (IBD), comprised of ulcerative colitis and Crohn's disease, are chronic disorders characterized by worsening of symptoms followed by symptom-free periods. Symptoms have a profound negative impact on quality of life and are associated with increased health care utilization. Despite effective treatments, outcomes are suboptimal secondary to nonadherence, medication intolerance, inconsistent monitoring, poor patient knowledge and limited access to care. OBJECTIVES: Compare disease activity and quality of life over 1 year in a randomized trial of IBD patients receiving standard care versus telemedicine. METHODS: Patients evaluated at 3 IBD referral centers with worsening symptoms within the last 2 years are eligible for randomization to one of two interventions or standard care. The interventions consist of either every other week or weekly assessment of symptoms, side effects, weight and delivery of medication prompts and education via texts to the participant's mobile phone. Individualized alerts and action plans are created on a secure portal. Participants in the standard care group undergo routine and urgent follow-up visits and telephone calls. The primary outcomes group comparisons of changes in disease activity and quality of life scores from baseline to 6 and 12 months. CONCLUSIONS: Methods such as telemedicine are needed to improve monitoring, adherence, self-efficacy, and patient knowledge in IBD. If effective, telemedicine should decrease symptoms, improve quality of life, and decrease health care utilization. The burden associated with use of telemedicine for patients and providers needs to be assessed. The trial is ongoing and will be completed in July 2016.

Physician assessment of ulcerative colitis activity correlates poorly with endoscopic disease activity.

BACKGROUND: Subjective physician assessment is the cornerstone of routine ulcerative colitis (UC) management. Endoscopic and histologic assessment of UC provides objective measures of inflammatory disease activity. The level of agreement between physician impression of UC activity and endoscopic disease activity has not been evaluated. The aim was to assess the level of agreement between physician's clinical impression of UC disease activity and endoscopic and histologic findings of inflammation. METHODS: Using the Medical Archival Retrieval System at the University of Pittsburgh Medical Center, we reviewed clinical information on all UC patients between 1995 and 2008 who had clinic visits recorded prior to colonoscopy. Clinical UC disease activity was defined by the physician's clinical impression and the endoscopic and histologic activity by colonoscopy with biopsy. The level of agreement between colonoscopy assessment of UC with histologic and clinical assessment was determined by sensitivity, specificity, positive and negative predictive values, and the kappa coefficient. RESULTS: There were 369 UC patients who had a clinic visit proximate to a colonoscopy. The mean age of patients was 46 ± 16 years (50% female). The performance of clinical impression in recognizing disease activity, as determined by endoscopy, was relatively poor: sensitivity = 56.0%, predictive value negative = 56.8%, kappa coefficient = 0.35. In contrast, the performance of histological evaluation in recognizing disease activity was markedly better: sensitivity = 93.5%, predictive value negative = 89.1%, kappa coefficient = 0.70. CONCLUSIONS: The physician's clinical impression of UC activity shows poor agreement with endoscopy and histology, with over one-third of patients with chronic inflammation underrecognized by clinical impression. The consequences of underestimated UC activity by clinical assessment may include undertreatment of active disease and uncontrolled chronic inflammation.

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.