Best practices for detection, assessment and management of suspected immune-mediated liver injury caused by immune checkpoint inhibitors during drug development.

Immune checkpoint inhibitors (ICIs) have shown significant efficacy in patients with various malignancies, however, they are associated with a wide range of immune-related toxicities affecting many organs, including the liver. Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) is a distinctive form of drug induced liver injury (DILI), that differs from most DILI types in presumed underlying mechanism, incidence, and response to therapeutic interventions. Despite increased awareness of ILICI and other immune-related adverse effects of ICIs reflected by recent guidelines for their management in post marketing clinical practice, there is lack of uniform best practices to address ILICI risk during drug development. As efforts to develop safer and more effective ICIs for additional indications grow, and as combination therapies including ICIs are increasingly investigated, there is a growing need for consistent practices for ILICI in drug development. This publication summarizes current best practices to optimize the monitoring, diagnosis, assessment, and management of suspected ILICI in clinical trials using ICI as a single agent and in combination with other ICIs or other oncological agents. It is one of several publications developed by the IQ DILI Initiative in collaboration with DILI experts from academia and regulatory agencies. Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, ILICI detection, approach to a suspected ILICI signal, causality assessment, hepatic discontinuation rules and additional medical treatment.

Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis.

UNLABELLED: GIFT-I is a phase 3 trial evaluating the efficacy and safety of a 12-week regimen of coformulated ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) for treatment of Japanese hepatitis C virus genotype 1b-infected patients. It consists of a double-blind, placebo-controlled substudy of patients without cirrhosis and an open-label substudy of patients with compensated cirrhosis. Patients without cirrhosis were randomized 2:1 to once-daily OBV/PTV/r (25 mg/150 mg/100 mg; group A) or placebo (group B). Patients with cirrhosis received open-label OBV/PTV/r (group C). The primary efficacy endpoint was the rate of sustained virological response 12 weeks posttreatment in interferon-eligible, treatment-naive patients without cirrhosis and hepatitis C virus RNA ≥100,000 IU/mL in group A. A total of 321 patients without cirrhosis were randomized and dosed with double-blind study drug (106 received double-blind placebo and later received open-label OBV/PTV/r), and 42 patients with cirrhosis were enrolled and dosed with open-label OBV/PTV/r. In the primary efficacy population, the rate of sustained virological response 12 weeks posttreatment was 94.6% (106/112, 95% confidence interval 90.5-98.8). Sustained virological response 12 weeks posttreatment rates were 94.9% (204/215) in group A, 98.1% (104/106) in group B (open-label), and 90.5% (38/42) in group C. Overall, virological failure occurred in 3.0% (11/363) of patients who received OBV/PTV/r. The rate of discontinuation due to adverse events was 0%-2.4% in the three patient groups receiving OBV/PTV/r. The most frequent adverse event in patients in any group was nasopharyngitis. CONCLUSION: In this broad hepatitis C virus genotype 1b-infected Japanese patient population with or without cirrhosis, treatment with OBV/PTV/r for 12 weeks was highly effective and demonstrated a favorable safety profile.

A Pilot, Predictive Surveillance Model in Pharmacovigilance Using Machine Learning Approaches.

INTRODUCTION: The identification of a new adverse event (AE) caused by a drug product is one of the key activities in the pharmaceutical industry to ensure the safety profile of a drug product. Machine learning (ML) has the potential to assist with signal detection and supplement traditional pharmacovigilance (PV) surveillance methods. This pilot ML modeling study was designed to detect potential safety signals for two AbbVie products and test the model's capability of detecting safety signals earlier than humans. METHODS: Drug X, a mature product with post-marketing data, and Drug Y, a recently approved drug in another therapeutic area, were selected. Gradient boosting-based ML approaches (e.g., XGBoost) were applied as the main modeling strategy. RESULTS: For Drug X, eight true signals were present in the test set. Among 12 potential new signals generated, four were true signals with a 50.0% sensitivity rate and a 33.3% positive predictive value (PPV) rate. Among the remaining eight potential new signals, one was confirmed as a signal and detected six months earlier than humans. For Drug Y, nine true signals were present in the test set. Among 13 potential new signals generated, five were true signals with a 55.6% sensitivity rate and a 38.5% PPV rate. Among the remaining eight potential new signals, none were confirmed as true signals upon human review. CONCLUSION: This model demonstrated acceptable accuracy for safety signal detection and potential for earlier detection when compared to humans. Expert judgment, flexibility, and critical thinking are essential human skills required for the final, accurate assessment of adverse event cases.

Drug-Induced Liver Injury in the Elderly: Consensus Statements and Recommendations from the IQ-DILI Initiative.

The elderly demographic is the fastest-growing segment of the world's population and is projected to exceed 1.5 billion people by 2050. With multimorbidity, polypharmacy, susceptibility to drug-drug interactions, and frailty as distinct risk factors, elderly patients are especially vulnerable to developing potentially life-threatening safety events such as serious forms of drug-induced liver injury (DILI). It has been a longstanding shortcoming that elderly individuals are often a vulnerable population underrepresented in clinical trials. As such, an improved understanding of DILI in the elderly is a high-priority, unmet need. This challenge is underscored by recent documents put forward by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) that encourage data collection in the elderly and recommend improved practices that will facilitate a more inclusive approach. To establish what is already known about DILI in the elderly and pinpoint key gaps of knowledge in this arena, a working definition of "elderly" is required that accounts for both chronologic and biologic ages and varying states of frailty. In addition, it is critical to characterize the biological role of aging on liver function, as well as the different epidemiological factors such as polypharmacy and inappropriate prescribing that are common practices. While data may not show that elderly people are more susceptible to DILI, DILI due to specific drugs might be more common in this population. Improved characterization of DILI in the elderly may enhance diagnostic and prognostic capabilities and improve the way in which liver safety is monitored during clinical trials. This summary of the published literature provides a framework to understand and evaluate the risk of DILI in the elderly. Consensus statements and recommendations can help to optimize medical care and catalyze collaborations between academic clinicians, drug manufacturers, and regulatory scientists to enable the generation of high-quality research data relevant to the elderly population.

Evaluation of myocardial infarction and coronary artery disease in subjects taking lopinavir/ritonavir: a study using clinical trial and pharmacovigilance databases.

OBJECTIVE: There is growing interest in studying age-related diseases, such as coronary artery disease (CAD) and resulting myocardial infarction (MI) in HIV-infected patients. While some cohort studies indicate that several antiretrovirals (ARVs), including the protease inhibitor lopinavir/ ritonavir (LPV/r), are associated with an increased relative risk (RR) of MI, other studies show a reduction of MI and CAD in subjects taking ARVs when compared with HIV+ patients not taking ARV therapy. This manuscript reviews data from Abbott-sponsored clinical trials and pharmacovigilance reporting system. METHODS: A systematic search was performed to retrieve cases of MI and CAD in Abbott's clinical trial and pharmacovigilance safety databases. The rates of MI and CAD, and risk factors for the events were reviewed in detail. RESULTS: The rate of MI and CAD per 1,000 patient treatment years (PTY) was 1.24 (95% CI = 0.40 - 2.90) and 2.74 (95% CI = 1.37 - 4.90), respectively, for subjects taking LPV/r during clinical trials. The frequency of pharmacovigilance reports of MI and CAD were 2.9 per 100,000 PTY and 3.6 per 100,000 PTY, respectively. Most subjects who had MI and CAD events had multiple baseline risk factors. CONCLUSIONS: Relatively few subjects experienced MI or CAD during Abbott-sponsored clinical trials of LPV/r. Analysis of clinical trial and pharmacovigilance data did not indicate an increased risk of MI or CAD associated with LPV/r compared with the general population. In general, the subjects that experienced MI or CAD had known traditional risk factors suggesting that addressing modifiable risk factors could decrease the risk of MI or CAD. ARVs have not been thoroughly studied in subjects at high risk for MI and CAD, and further studies of this population could identify whether starting ARVs affects the incidences of cardic events in subjects with many traditional risk factors

Overview of Causality Assessment for Drug-Induced Liver Injury (DILI) in Clinical Trials.

Causality assessment for suspected drug-induced liver injury (DILI) during drug development and following approval is challenging. The IQ DILI Causality Working Group (CWG), in collaboration with academic and regulatory subject matter experts (SMEs), developed this manuscript with the following objectives: (1) understand and describe current practices; (2) evaluate the utility of new tools/methods/practice guidelines; (3) propose a minimal data set needed to assess causality; (4) define best practices; and (5) promote a more structured and universal approach to DILI causality assessment for clinical development. To better understand current practices, the CWG performed a literature review, took a survey of member companies, and collaborated with SMEs. Areas of focus included best practices for causality assessment during clinical development, utility of adjudication committees, and proposals for potential new avenues to improve causality assessment. The survey and literature review provided renewed understanding of the complexity and challenges of DILI causality assessment as well as the use of non-standardized approaches. Potential areas identified for consistency and standardization included role and membership of adjudication committees, standardized minimum dataset, updated assessment tools, and best practices for liver biopsy and rechallenge in the setting of DILI. Adjudication committees comprised of SMEs (i.e., utilizing expert opinion) remain the standard for DILI causality assessment. A variety of working groups continue to make progress in pursuing new tools to assist with DILI causality assessment. The minimum dataset deemed adequate for causality assessment provides a path forward for standardization of data collection in the setting of DILI. Continued progress is necessary to optimize and advance innovative tools necessary for the scientific, pharmaceutical, and regulatory community.

Consensus Guidelines: Best Practices for Detection, Assessment and Management of Suspected Acute Drug-Induced Liver Injury During Clinical Trials in Adults with Chronic Viral Hepatitis and Adults with Cirrhosis Secondary to Hepatitis B, C and Nonalcoholic Steatohepatitis.

With the widespread development of new drugs to treat chronic liver diseases (CLDs), including viral hepatitis and nonalcoholic steatohepatitis (NASH), more patients are entering trials with abnormal baseline liver tests and with advanced liver injury, including cirrhosis. The current regulatory guidelines addressing the monitoring, diagnosis, and management of suspected drug-induced liver injury (DILI) during clinical trials primarily address individuals entering with normal baseline liver tests. Using the same laboratory criteria cited as signals of potential DILI in studies involving patients with no underlying liver disease and normal baseline liver tests may result in premature and unnecessary cessation of a study drug in a clinical trial population whose abnormal and fluctuating liver tests are actually due to their underlying CLD. This position paper focuses on defining best practices for the detection, monitoring, diagnosis, and management of suspected acute DILI during clinical trials in patients with CLD, including hepatitis C virus (HCV) and hepatitis B virus (HBV), both with and without cirrhosis and NASH with cirrhosis. This is one of several position papers developed by the IQ DILI Initiative, comprising members from 16 pharmaceutical companies in collaboration with DILI experts from academia and regulatory agencies. It is based on an extensive literature review and discussions between industry members and experts from outside industry to achieve consensus regarding the recommendations. Key conclusions and recommendations include (1) the importance of establishing laboratory criteria that signal potential DILI events and that fit the disease indication being studied in the clinical trial based on knowledge of the natural history of test fluctuations in that disease; (2) establishing a pretreatment value that is based on more than one screening determination, and revising that baseline during the trial if a new nadir is achieved during treatment; (3) basing rules for increased monitoring and for stopping drug for potential DILI on multiples of baseline liver test values and/or a threshold value rather than multiples of the upper limit of normal (ULN) for that test; (4) making use of more sensitive tests of liver function, including direct bilirubin (DB) or combined parameters such as aspartate transaminase:alanine transaminase (AST:ALT) ratio or model for end-stage liver disease (MELD) to signal potential DILI, especially in studies of patients with cirrhosis; and (5) being aware of potential confounders related to complications of the disease being studied that may masquerade as DILI events.

Use of tablet personal computers for sensitive patient-reported information.

Notebook-style computers (e/Tablets) are increasingly replacing paper methods for collecting patient-reported information. Discrepancies in data between these methods have been found in oncology for sexuality-related questions. A study was performed to formulate hypotheses regarding causes for discrepant responses and to analyze whether electronic data collection adds value over paper-based methods when collecting data on sensitive topics. A total of 56 breast cancer patients visiting Duke Breast Clinic (North Carolina) participated by responding to 12 subscales of 5 survey instruments in electronic (e/Tablet) format and to a paper version of 1 of these surveys, at each visit. Twenty-one participants (38%) provided dissimilar responses on paper and electronic surveys to one item of the Functional Assessment of Cancer Therapy-General (FACT-G) Social Well-Being scale that asked patients to rate their satisfaction with their current sex life. Among these 21 patients were 8 patients who answered the question in the electronic environment, and 13 patients who answered both paper and electronic versions but with different responses. Eleven patients (29%) did not respond to the item on either e/Tablet or paper; 45 patients (80%) answered it on e/Tablet; and 37 patients (66%) responded on the paper version. The e/Tablet electronic system may provide a "safer" environment than paper questionnaires for cancer patients to answer private or highly personal questions on sensitive topics such as sexuality.

Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension.

BACKGROUND: The relative effectiveness of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) for lowering blood pressure is unknown. PURPOSE: To compare the benefits and harms of ACE inhibitors versus ARBs for treating essential hypertension in adults. DATA SOURCES: MEDLINE (1966 to May 2006), the Cochrane Central Register of Controlled Trials (Issue 2, 2006), and selected reference lists were searched for relevant English-language trials. The MEDLINE search was updated to August 2007 to identify head-to-head trials that reported blood pressure outcomes and major cardiovascular events. STUDY SELECTION: 61 clinical studies that directly compared ACE inhibitors versus ARBs in adult patients with essential hypertension, reported an outcome of interest, lasted at least 12 weeks, and included at least 20 patients. DATA EXTRACTION: A standardized protocol with predefined criteria was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality and applicability; and assess the strength of the body of evidence for key outcomes. DATA SYNTHESIS: ACE inhibitors and ARBs had similar long-term effects on blood pressure (50 studies; strength of evidence, high). No consistent differential effects were observed for other outcomes (few studies reported long-term outcomes), including death, cardiovascular events, quality of life, rate of single antihypertensive agent use, lipid levels, progression to diabetes, left ventricular mass or function, and kidney disease. Consistent fair- to good-quality evidence showed that ACE inhibitors were associated with a greater risk for cough. There were fewer withdrawals due to adverse events and greater persistence with therapy for ARBs than for ACE inhibitors, although this evidence was not definitive. Patient subgroups for whom ACE inhibitors or ARBs were more effective, associated with fewer adverse events, or better tolerated were not identified. LIMITATIONS: Few studies involved a representative sample treated in a typical clinical setting over a long duration, treatment protocols had marked heterogeneity, and substantive amounts of data about important outcomes and patient subgroups were missing. CONCLUSION: Available evidence shows that ACE inhibitors and ARBs have similar effects on blood pressure control, and that ACE inhibitors have higher rates of cough than ARBs. Data regarding other outcomes are limited.

Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems.

BACKGROUND: Stage at diagnosis plays a significant role in colorectal cancer (CRC) survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis. METHODS: Two distinct healthcare populations in the United States (US) were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA) hospitals from 2003-2007. We assessed metastatic CRC patients treated from 2003-2006 at 10 non-VA, fee-for-service (FFS) practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic). Race was dichotomized (white, non-white). Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression. RESULTS: 342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77%) reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD) age 67 (11), Charlson index 2.0 (1.0), and were 63% white. FFS patients were mean age 61 (13), Charlson index 1.6 (1.0), and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.58-1.00; p = 0.045); no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82-1.44; p = 0.57). In both cohorts, no association was found between stage at diagnosis and either age or race. CONCLUSION: Higher comorbidity may lead to earlier stage of CRC diagnosis. Multiple factors, perhaps including increased interactions with the healthcare system due to comorbidity, might contribute to this finding. Such increased interactions are seen among patients within a healthcare system like the VA system in the US versus sporadic interactions which may be seen with FFS healthcare.

Utility of the advanced chronic kidney disease patient management tools: case studies.

Appropriate management of advanced chronic kidney disease (CKD) delays or limits its progression. The Advanced CKD Patient Management Toolkit was developed using a process-improvement technique to assist patient management and address CKD-specific management issues. We pilot tested the toolkit in 2 community nephrology practices, assessed the utility of individual tools, and evaluated the impact on conformance to an advanced CKD guideline through patient chart abstraction. Tool use was distinct in the 2 sites and depended on the site champion's involvement, the extent of process reconfiguration demanded by a tool, and its perceived value. Baseline conformance varied across guideline recommendations (averaged 54%). Posttrial conformance increased in all clinical areas (averaged 59%). Valuable features of the toolkit in real-world settings were its ability to: facilitate tool selection, direct implementation efforts in response to a baseline performance audit, and allow selection of tool versions and customizing them. Our results suggest that systematically created, multifaceted, and customizable tools can promote guideline conformance.

Opportunities for improving management of advanced chronic kidney disease.

Evidence suggests that management of advanced chronic kidney disease affects patient outcomes. To identify clinical areas that demand attention from a quality improvement perspective, we sought to examine the extent of conformance to an advanced chronic kidney disease guideline in a range of practices. A total of 237 patient medical records were abstracted from 4 primary care providers and 4 nephrology private practices across the country. In the practices studied, management of advanced chronic kidney disease patients was suboptimal for patients managed by primary care providers as well as those managed by nephrologists (overall conformance 27% and 42%, respectively), specifically for anemia, bone disease, and timing for renal replacement therapy. The current exercise (in conjunction with a literature search and focused and individual interviews with providers and patients) offered valuable information that was used to develop a toolkit for optimizing management of advanced chronic kidney disease.

Assessing the quality of colorectal cancer care: do we have appropriate quality measures? (A systematic review of literature).

RATIONALE, AIMS AND OBJECTIVES: The burden of illness from colorectal cancer (CRC) can be reduced by improving the quality of care. Identifying appropriate quality measures is the first step in this direction. We identified process measures currently available to assess the quality of diagnosis and management of CRC. We also evaluated the extent to which these measures are ready to be implemented in clinical practice, and identified areas for future research. METHODS: We searched MEDLINE, Cochrane Database of Systematic Reviews, and relevant grey literature. We identified 3771 abstracts and reviewed 74 articles that included quality measures for diagnosis or management of CRC. Measures from traditional quality improvement literature, and from epidemiological and other studies that included quality measures as part of their research agenda, were considered. In addition, we devised a summary rating scale (IST) to appraise the extent of a measure's importance and usability, scientific acceptability and extent of testing. RESULTS: The coverage of general process measures in CRC is extensive. Most measures are important, but need to be developed and field-tested. The best available measures relate to pathology and chemotherapy. No measures are available for assessing quality of management of stage IV rectal cancer and hepatic metastasis; chemotherapy for stage II colon cancer; and procedure notes. CONCLUSIONS: There is an urgent need to refine existing measures and to develop scientifically accurate quality measures for a comprehensive assessment of the quality of CRC care. The role of the federal government and professional societies is critical in pursuing this goal.

Facilitated process improvement: an approach to the seamless linkage between evidence and practice in CKD.

BACKGROUND: Two common strategies for guideline implementation are preformed practice improvement tools, such as flowcharts, and process reengineering by total quality management (TQM) teams. Prespecified tools fail to accommodate local circumstances, TQM requires an unrealistic level of local commitment, and neither has a proven track record for success. METHODS: We describe an alternative approach termed facilitated process improvement (FPI), a systematic exploration of potential modifications to systems of care, and its application to the implementation of an evidence-based chronic kidney disease (CKD) guideline, focusing on individuals not yet requiring renal replacement therapy. The FPI steps followed by the implementation work group to develop a set of implementation tools for the Renal Physicians Association Advanced CKD Guideline included: (1) developing functional specifications of processes, including actions and prerequisites required; (2) investigating processes of care in a variety of site types to understand processes and reasons for failures; (3) developing practical tools corresponding to root causes of failures of processes and subprocesses; and (4) developing a meta-tool to tailor local selection of tools. RESULTS: Formal needs assessment identified processes of care related to 3 major tasks: identify patients, develop and communicate patient-specific management plan, and implement plan. Subtasks were identified to address root causes of failures, and, for each, tools were modified from existing or developed de novo by the work group, which further developed an organized management approach that uses 4 categories of tools: (1) assessment tools identify opportunities for improvements; (2) tailoring tools, a unique feature of this approach, determine which tools are applicable; (3) implementation tools identify patients and communicate and implement management plan; and (4) evaluation tools assess the impact of implementation. CONCLUSION: The work group, in collaboration with community clinicians, patients, and CKD and tool experts, developed and used FPI to provide a range of tools in a fashion that supports and simplifies local assessment, tailoring, implementation, and evaluation. With the formative work completed, practitioners whose practice improvement experience level and other resources may be limited will find it more feasible and practical to provide optimal advanced CKD management without the demands of conventional TQM or continuous quality improvement.

Dissemination of Evidence-based Practice Center reports.

The Evidence-based Practice Center (EPC) program within the Agency for Healthcare Research and Quality (AHRQ) provides detailed evidence reports for partner organizations that they can translate into activities that improve patient care. A review of these dissemination activities provides a rich opportunity to understand how to create more successful linkages between best evidence and best practice. On the basis of interviews with EPC directors, AHRQ staff, and representatives of public and private users of EPC reports, we summarize the variety of efforts to disseminate the work of the EPCs. We also identify a case example of a successful dissemination of an EPC report. Experience to date reinforces the importance of creating close ties between researchers and the policymakers, clinicians, and other decision makers who use EPC evidence reports; developing a conceptual framework to guide the process; and establishing the resource foundation for the entire effort.

Poor documentation prevents adequate assessment of quality metrics in colorectal cancer.

To standardize oncology clinical practice and improve patient outcomes, multiple organizations have developed cancer-specific metrics on the basis of a systematic background review, expert guidance, and fundamental elements of cancer care-staging and treatment.

Recommendations for a clinical decision support for the management of individuals with chronic kidney disease.

BACKGROUND AND OBJECTIVES: Care for advanced CKD patients is suboptimal. CKD practice guidelines aim to close gaps in care, but making providers aware of guidelines is an ineffective implementation strategy. The Institute of Medicine has endorsed the use of clinical decision support (CDS) for implementing guidelines. The authors' objective was to identify the requirements of an optimal CDS system for CKD management. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The aims of this study expanded on those of previous work that used the facilitated process improvement (FPI) methodology. In FPI, an expert workgroup develops a set of quality improvement tools that can subsequently be utilized by practicing physicians. The authors conducted a discussion with a group of multidisciplinary experts to identify requirements for an optimal CDS system. RESULTS: The panel considered the process of patient identification and management, associated barriers, and elements by which CDS could address these barriers. The panel also discussed specific knowledge needs in the context of a typical scenario in which CDS would be used. Finally, the group developed a set of core requirements that will likely facilitate the implementation of a CDS system aimed at improving the management of any chronic medical condition. CONCLUSIONS: Considering the growing burden of CKD and the potential healthcare and resource impact of guideline implementation through CDS, the relevance of this systematic process, consistent with Institute of Medicine recommendations, cannot be understated. The requirements described in this report could serve as a basis for the design of a CKD-specific CDS.

Feasibility and acceptability to patients of a longitudinal system for evaluating cancer-related symptoms and quality of life: pilot study of an e/Tablet data-collection system in academic oncology.

Programmed, notebook-style, personal computers ("e/Tablets") can collect symptom and quality-of-life (QOL) data at the point of care. Patients use an e/Tablet in the clinic waiting area to complete electronic surveys. Information then travels wirelessly to a server, which generates a real-time report for use during the clinical visit. The objective of this study was to determine whether academic oncology patients find e/Tablets logistically acceptable and a satisfactory means of communicating symptoms to providers during repeated clinic visits. Sixty-six metastatic breast cancer patients at Duke Breast Cancer Clinic participated. E/Tablets were customized to electronically administer a satisfaction/acceptability survey, several validated questionnaires, and the Patient Care Monitor (PCM) review of symptoms survey. At each of the four visits within six months, participants completed the patient satisfaction/acceptability survey, which furnished data for the current analysis. Participant demographics were: mean age of 54 years, 77% Caucasian, and 47% with less than a college education. Participants reported that e/Tablets were easy to read (94%), easy to navigate (99%), and had a comfortable weight (90%); they found it easy to respond to questions using the e/Tablet (98%). Seventy-five percent initially indicated satisfaction with PCM for reporting symptoms; this proportion increased over time. By the last visit, 88% of participants indicated that they would recommend the PCM to other patients; 74% felt that the e/Tablet helped them remember symptoms to report to their clinician. E/Tablets offered a feasible and acceptable method for collecting longitudinal patient-reported symptom and QOL data within an academic, tertiary care, breast cancer clinic.