Martha S. Bayliss

The effects of interferon alpha-2b in combination with ribavirin on health related quality of life and work productivity

BACKGROUND/AIMS Interferon plus ribavirin is the most effective therapy for chronic hepatitis C. The aim of this study was to evaluate the effect of chronic hepatitis C and therapy on health-related quality of life and work functioning. METHODS Nine hundred and twelve patients with hepatitis C infection were randomized in a controlled trial of Interferon alpha 2b 3 MU tiw for 24 or 48 weeks plus ribavirin 1000-1200 mg or placebo. Questionnaire-based assessments of health-related quality of life and work functioning were performed before, during, and after treatment. Outcome measures included the SF-36 Health Survey and additional generic and specific scales. Work functioning was assessed as missed days, shorter hours or less productivity at work. RESULTS Pre-treatment, patients had significant impairment in five of eight SF-36 concepts compared to matched population norms. Sustained responders had a return to normal for four of these five concepts. Quality of life did not improve in non-responders. Improvements in histology, viral load or ALT values predicted improvements in quality of life. Sustained responders also had improvements in work functioning and productivity. CONCLUSIONS Hepatitis C patients had impaired quality of life. After combination therapy, sustained virologic responders achieved benefits in their quality of life and work functioning.

PRO development: rigorous qualitative research as the crucial foundation

Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity.

A questionnaire to assess the generic and disease-specific health outcomes of patients with chronic hepatitis C

A 69-item questionnaire measuring generic functioning and well-being and disease-specific health outcomes was developed and tested using the pre-treatment data from patients with chronic hepatitis C (CHC) participating in two randomized trials of interferon α-2b (n = 157). The questionnaire included all eight scales from the SF-36 and measures of nine other generic and disease-specific health concepts. Psychometric tests confirmed the assumptions underlying the construction and scoring of all generic and disease-specific scales. Cross-sectional tests of ‘known groups’ validity showed that CHC patients scored worse on the generic scales than patients with other chronic conditions and worse than a healthy general population. The generic and disease-specific scale scores were lower in the presence of physical findings of CHC, as hypothesized, but only the physical functioning and bodily pain scales were linked to cirrhosis or extreme alanine aminotransferase (ALT) ratios. This instrument will be useful in studies of health outcome among patients with CHC, a condition whose health burden appears to have been underestimated in studies to date.

Predicting declines in physical function in persons with multiple chronic medical conditions: what we can learn from the medical problem list

BackgroundPrimary care physicians are caring for increasing numbers of persons with comorbid chronic illness. Longitudinal information on health outcomes associated with specific chronic conditions may be particularly relevant in caring for these populations. Our objective was to assess the effect of certain comorbid conditions on physical well being over time in a population of persons with chronic medical conditions; and to compare these effects to that of hypertension alone.MethodsWe conducted a secondary analysis of 4-year longitudinal data from the Medical Outcomes Study. A heterogeneous population of 1574 patients with either hypertension alone (referent) or one or more of the following conditions: diabetes, coronary artery disease, congestive heart failure, respiratory illness, musculoskeletal conditions and/or depression were recruited from primary and specialty (endocrinology, cardiology or mental health) practices within HMO and fee-for-service settings in three U.S. cities. We measured categorical change (worse vs. same/better) in the SF-36® Health Survey physical component summary score (PCS) over 4 years. We used logistic regression analysis to determine significant differences in longitudinal change in PCS between patients with hypertension alone and those with other comorbid conditions and linear regression analysis to assess the contribution of the explanatory variables.ResultsSpecific diagnoses of CHF, diabetes and/or chronic respiratory disease; or 4 or more chronic conditions, were predictive of a clinically significant decline in PCS.ConclusionsClinical recognition of these specific chronic conditions or 4 or more of a list of chronic conditions may provide an opportunity for proactive clinical decision making to maximize physical functioning in these populations.

A new tool for monitoring asthma outcomes: the ITG Asthma Short Form

Background: Asthma treatment has broadened from managing clinical markers to incorporate factors that are most meaningful to patients, collectively called health-related quality of life (HQL). Objective: To develop an asthma-specific HQL tool, meeting demands for brevity, usefulness and measurement precision. Methods: The 20-item Sydney Asthma Quality of Life Questionnaire (AQLQ) and six additional items were studied using factor analysis, reliability and validity tests among asthma patients 14 and older. Results: The 15-item Integrated Therapeutics Group Asthma Short Form (ITG-ASF) retains the validity of the AQLQ with improved scaling properties and interpretability. The ITG-ASF yields 6 scores: Symptom-Free Index, Functioning with Asthma, Psychosocial Impact of Asthma, Asthma Energy and Asthma-Confidence in Health and a Total. All items correlated 0.40 or higher with their hypothesized scales and passed discriminant validity tests, with scaling success rates from 75 to 100%. Reliability exceeded the minimum of 0.70 for group comparisons. Ceiling and floor effects were acceptable. Scales were valid in relation to changes in asthma severity and lung function. The best predictor of asthma severity (National Asthma Education and Prevention Program (NAEPP) staging) was the Symptom-Free Index. A Spanish translation is available, Chinese-American is forthcoming. The reading grade level is 4.8. Conclusions: Development of the ITG-ASF was a data-driven process maximizing measurement precision and breadth while minimizing burden. The ITG-ASF is a brief, comprehensive and empirically valid tool that complements traditional markers of the outcomes of asthma care.

Health-related quality of life (HRQL) for individuals with self-reported chronic physical and/or mental health conditions: panel survey of an adult sample in the United States.

BackgroundIn the US, approximately 53% of adults have at least one chronic condition. Comorbid physical and mental health conditions often have an incremental negative impact on health-related quality of life (HRQL). Primary study objectives were to quantify the impact on HRQL of a) ≥ 1 physical condition , b) ≥ 1 comorbid mental health conditions added to a physical one, c) ≥ 1 mental health condition, and d) ≥ 1 comorbid physical conditions added to at least one related to mental health. Decrements were based on a “Healthy” reference group reporting no chronic conditions.MethodsParticipants were sampled (n = 3877) from the US adult population as part of a 2009 normative survey. Demographics, number/ type of chronic conditions, and HRQL data were self-reported. HRQL was defined through SF-36v2® Physical Component Summary (PCS) scores and Mental Component Summary (MCS) scores. Participant “morbidity” groupings included Healthy; Physical Health Condition only, Mental Health Condition only, and Physical and Mental Health (Comorbid). PCS and MCS scores were also analyzed by physical disease clusters (e.g., cardiovascular, gastrointestinal). Multivariate regression models were used for all analyses.Results81% of participants were Caucasian; 9% African American. Males and females were about equally represented; 63% were ≥ 45 years old. The average number of reported chronic conditions was 2.4 (SD = 2.4). Relative to the Healthy group, the Physical Condition group scored 6.4 (males) and 7.5 (females) points lower on PCS. The addition of a comorbid mental health condition resulted in a total reduction of 11 points in PCS and 15 points in MCS. Compared to the Healthy group, ≥ 1 mental health conditions was associated with MCS decrements of 11–12 points. A physical comorbidity led to additional decrements of 3–4 points for MCS, with a total of 15 points. Incremental HRQL burden defined by both MCS and PCS scores was relatively similar across the 5 defined physical disease clusters.ConclusionResults provide quantitative information for US adults on specific PCS and MCS score decrements associated with a comorbid condition related to mental health, as well as a comorbid condition related to physical health.

Impact of changes in asthma severity on health-related quality of life in pediatric and adult asthma patients: results from the asthma outcomes monitoring system

The goals of asthma treatment have broadened beyond managing traditional clinical markers of disease severity, and now include a focus on benefits of treatment in terms that are most meaningful to patients. Measurement of both generic and disease-specific health-related quality of life (HQL) is advocated because each provides complementary information about how the condition affects everyday functioning and well-being and whether treatments have their intended effects. The purpose of this study was to determine the impact of changes in asthma severity (defined using NHLBI/NAEPP severity staging) on patient-assessed HQL. Two hundred and thirty-three pediatric asthma patients and 269 adult asthma patients were evaluated in a one-year observational study. Analyses were performed to compare the generic and asthma-specific scores for patients whose asthma severity improved, stayed the same, or worsened over one year. The asthma-specific scales are sensitive to changes in disease severity. Of the generic scales, those tapping areas of physical health are more affected than the mental/emotional scales. This confirms that HQL measures are responsive to changes in asthma severity. They complement traditional clinical markers used to evaluate changes in a patients disease state and thus give the physician another useful tool in following the clinical progress of the child with asthma.

The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI): Revision for Clinical Use, Content Validation, and Inter-rater Reliability

PurposeThe Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) is a method for assessing the likelihood that a patient’s muscle symptoms (e.g., myalgia or myopathy) were caused or worsened by statin use. The objectives of this study were to prepare the SAMS-CI for clinical use, estimate its inter-rater reliability, and collect feedback from physicians on its practical application.MethodsFor content validity, we conducted structured in-depth interviews with its original authors as well as with a panel of independent physicians. Estimation of inter-rater reliability involved an analysis of 30 written clinical cases which were scored by a sample of physicians. A separate group of physicians provided feedback on the clinical use of the SAMS-CI and its potential utility in practice.ResultsQualitative interviews with providers supported the content validity of the SAMS-CI. Feedback on the clinical use of the SAMS-CI included several perceived benefits (such as brevity, clear wording, and simple scoring process) and some possible concerns (workflow issues and applicability in primary care). The inter-rater reliability of the SAMS-CI was estimated to be 0.77 (confidence interval 0.66–0.85), indicating high concordance between raters. With additional provider feedback, a revised SAMS-CI instrument was created suitable for further testing, both in the clinical setting and in prospective validation studies.ConclusionsWith standardized questions, vetted language, easily interpreted scores, and demonstrated reliability, the SAMS aims to estimate the likelihood that a patient’s muscle symptoms were attributable to statins. The SAMS-CI may support better detection of statin-associated muscle symptoms in clinical practice, optimize treatment for patients experiencing muscle symptoms, and provide a useful tool for further clinical research.

Psychometric Evaluation of a Novel Instrument Assessing the Impact of Migraine on Physical Functioning: The Migraine Physical Function Impact Diary

The objective of this study was to evaluate the measurement properties of the Migraine Physical Function Impact Diary (MPFID), a novel patient‐reported outcome (PRO) measure for assessing the impact of migraine on physical functioning.

Measuring the effect of therapy in rheumatoid arthritis clinical trials from the patient’s perspective

Abstract Objective: Health measurements used to evaluate the effectiveness of rheumatoid arthritis (RA) therapies often fail to reflect patients’ priorities, despite recommendations towards more patient-centered assessments. The goals of the current review are: (1) to present guidelines, tools, and required steps for successful implementation of patient-reported outcome (PRO) measurement in RA clinical trials; and (2) to identify gaps between recommendations and current practices. Methods: The first objective was addressed by reviewing existing frameworks for assessment of health-related quality of life among patients with RA and guidelines on the evaluation of PRO instruments, with a focus on evidence required to demonstrate the adequacy of PRO-based labeling claims. The second goal was addressed by conducting an empirical investigation of the overlap between patients’ perspectives and current practices regarding PROs in RA studies, elaborated from systematic literature searches. The first search identified qualitative studies that reported direct input from patients with RA, while the second identified the main health outcomes measured in RA trials, with a focus on biologic therapy. Results: Our review revealed a set of outcomes that have thus far not been widely used to assess treatment benefit in RA, despite evidence of their importance to patients. The psychometric properties of PRO instruments used to evaluate commonly assessed domains are presented, as are recommendations for PRO tools that assess domains less often measured in RA studies. Conclusions: Although the validity of some PRO tools among patients with RA is well established, further work needs to be done in several health domains which have traditionally received insufficient attention.