Asha Hareendran

Proposing a standardized method for evaluating patient report of the intensity of dyspnea during exercise testing in COPD

Background Measuring dyspnea intensity associated with exercise provides insights into dyspnea-limited exercise capacity, and has been used to evaluate treatment outcomes for chronic obstructive pulmonary disease (COPD). Three patient-reported outcome scales commonly cited for rating dyspnea during exercise are the modified Borg scale (MBS), numerical rating scale for dyspnea (NRS-D), and visual analogue scale for dyspnea (VAS-D). Various versions of each scale were found. Our objective was to evaluate the content validity of scales commonly used in COPD studies, to explore their ability to capture patients’ experiences of dyspnea during exercise, and to evaluate a standardized version of the MBS. Methods A two-stage procedure was used, with each stage involving one-on-one interviews with COPD patients who had recently completed a clinic-based exercise event on a treadmill or cycle ergometer. An open-ended elicitation interview technique was used to understand patients’ experiences of exercise-induced dyspnea, followed by patients completing the three scales. The cognitive interviewing component of the study involved specific questions to evaluate the patients’ perspectives of the content and format of the scales. Results from Stage 1 were used to develop a standardized version of the MBS, which was then subjected to further content validity assessment during Stage 2. Results Thirteen patients participated in the two-stage process (n = 6; n = 7). Mean forced expiratory volume in 1 second (FEV1) percent predicted was 40%, mean age 57 years, and 54% were male. Participants used a variety of terms to describe the intensity and variability of exercise-induced dyspnea. Subjects understood the instructions and format of the standardized MBS, and were able to easily select a response to report the level of dyspnea associated with their recent standardized exercise. Conclusion This study provides initial evidence in support of using a standardized version of the MBS version for quantifying dyspnea intensity associated with exercise in patients with COPD.

The development of a patient-reported outcome measure for assessing nighttime symptoms of chronic obstructive pulmonary disease.

BackgroundThe assessment of symptoms of chronic obstructive pulmonary disease (COPD) is important for monitoring and managing the disease and for evaluating outcomes of interventions. COPD patients experience symptoms during the day and night, and symptoms experienced at night often disturb sleep. The aim of this paper is to describe methods used to develop a patient-reported outcome (PRO) instrument for evaluating nighttime symptoms of COPD, and to document evidence for the content validity of the instrument.MethodsLiterature review and clinician interviews were conducted to inform discussion guides to explore patients’ nighttime COPD symptom experience. Data from focus groups with COPD patients was used to develop a conceptual framework and the content of a new PRO instrument. Patient understanding of the new instrument was assessed via cognitive interviews with COPD patients.ResultsThe literature review confirmed that there is no instrument with evidence of content validity currently available to assess nighttime symptoms of COPD. Additionally, the literature review and clinician interviews suggested the need to understand patients’ experience of specific symptoms in order to evaluate nighttime symptoms of COPD. Analyses of patient focus group data (N = 27) supported saturation of concepts and aided in development of a conceptual framework. Items were generated using patients’ terminology to collect data on concepts in the framework including the occurrence and severity of COPD symptoms, use of rescue medication at night, and nocturnal awakening. Response options were chosen to reflect concepts that were salient to patients. Subsequent cognitive interviewing with ten COPD patients demonstrated that the items, response options, recall period, and instructions were understandable, relevant, and interpreted as intended.ConclusionsA new PRO instrument, the Nighttime Symptoms of COPD Instrument (NiSCI), was developed with documented evidence of content validity. The NiSCI is ready for empirical testing, including item reduction and evaluation of psychometric properties.

Evaluation of the psychometric properties of the Nighttime Symptoms of COPD Instrument

Background Nighttime symptoms can negatively impact the quality of life of patients with chronic obstructive pulmonary disease (COPD). The Nighttime Symptoms of COPD Instrument (NiSCI) was designed to measure the occurrence and severity of nighttime symptoms in patients with COPD, the impact of symptoms on nighttime awakenings, and rescue medication use. The objective of this study was to explore item reduction, inform scoring recommendations, and evaluate the psychometric properties of the NiSCI. Methods COPD patients participating in a Phase III clinical trial completed the NiSCI daily. Item analyses were conducted using weekly mean and single day scores. Descriptive statistics (including percentage of respondents at floor/ceiling and inter-item correlations), factor analyses, and Rasch model analyses were conducted to examine item performance and scoring. Test–retest reliability was assessed for the final instrument using the intraclass correlation coefficient (ICC). Correlations with assessments conducted during study visits were used to evaluate convergent and known-groups validity. Results Data from 1,663 COPD patients aged 40–93 years were analyzed. Item analyses supported the generation of four scores. A one-factor structure was confirmed with factor analysis and Rasch analysis for the symptom severity score. Test–retest reliability was confirmed for the six-item symptom severity (ICC, 0.85), number of nighttime awakenings (ICC, 0.82), and rescue medication (ICC, 0.68) scores. Convergent validity was supported by significant correlations between the NiSCI, St George’s Respiratory Questionnaire, and Exacerbations of Chronic Obstructive Pulmonary Disease Tool-Respiratory Symptoms scores. Conclusion The results suggest that the NiSCI can be used to determine the severity of nighttime COPD symptoms, the number of nighttime awakenings due to COPD symptoms, and the nighttime use of rescue medication. The NiSCI is a reliable and valid instrument to evaluate these concepts in COPD patients in clinical trials and clinical practice. Scoring recommendations and steps for further research are discussed.

Impaired Health Status and the Effect of Pain and Fatigue on Functioning in Clinical Trial Patients with Systemic Lupus Erythematosus

Objective. Our study evaluated the impaired health status of clinical trial patients with systemic lupus erythematosus (SLE) and explored the relationship between changes in fatigue and pain and their effect on overall health status. Methods. Pooled treatment and placebo data from a phase Ib clinical trial of adults with moderate/severe SLE were analyzed. Measures included patient-reported Medical Outcome Study Short Form-36 Survey, Version 2 (SF-36v2), Fatigue Severity Scale, and numeric rating scales (NRS) for pain and global health assessment and clinician-reported global assessment of disease activity (MDGA). Disease burden was compared to the US general population. Health status of responders and nonresponders on pain or fatigue were compared. Results. The sample included 161 patients with SLE, predominantly female (96%) and white (72%), with average age of 43 ± 11 years. Mean SF-36v2 component summary scores reflected overall problems with physical [physical component summary (PCS); 35.2 ± 9.7] and mental health (mental component summary; 40.9 ± 12.9). Patients with SLE had worse health status on all SF-36v2 subscales than the US general population and comparable age and sex norms (effect size −0.51 to −2.15). Pain and fatigue responders had greater improvements on SF-36v2 scores (bodily pain, physical functioning, social functioning, PCS), patient global health assessment NRS, and MDGA than nonresponders. There was moderate agreement in responder status, based on global assessments by patients and clinicians (68.1%), with some discrepancy between patients who were MDGA responders but patient assessment nonresponders (27.7%). Conclusion. Improvements in patient-reported pain or fatigue correlated with improvements in overall health. Patient assessments offer a unique perspective on treatment outcomes. Patient-reported outcomes add value in understanding clinical trial treatment benefits.

Measuring the impact of migraine for evaluating outcomes of preventive treatments for migraine headaches

BackgroundMigraine is characterized by headache with symptoms such as intense pain, nausea, vomiting, photophobia, and phonophobia that significantly impact individuals’ lives. The objective of this study was to develop a strategy to measure outcomes from the patients’ perspectives for use in evaluating preventive treatments for migraine.MethodsThis study used a multi-stage process. The first stage included concept identification research through literature review, patient-reported outcome (PRO) instrument content review, and clinician interviews, and resulted in a list of concepts relevant to understand the migraine experience. These results informed the design of the subsequent concept elicitation stage that involved qualitative interviews of adults with migraine to understand their experiences. Information from these two stages was used to develop a conceptual disease model (CDM) of the migraine experience. This CDM was used to identify concepts of interest (COI) to evaluate patient-relevant outcomes for assessing treatment benefit of migraine prophylactics. In the final stage, existing PRO instruments were reviewed to assess coverage of concepts related to the selected COI.ResultsNine articles from 563 screened abstracts underwent full review to identify migraine-relevant concepts. This concept identification and subsequent concept elicitation interviews (Nu2009=u200932; 21 episodic migraine; 11 chronic migraine) indicated that people with migraine experience difficulties during and between migraine attacks with considerable day-to-day variability in the impact on movement, ability to perform every day and social activities, and emotion. The CDM organized concepts as proximal to and more distal from disease-defining migraine symptoms, and was used to identify impact on physical function as the key COI. The item level review of PRO instruments revealed that none of the existing PRO instruments were suitable to collect data on impact of migraine on physical functioning, to evaluate treatment benefit.ConclusionsThe impact of migraine includes impairments in functioning during and between migraine attacks that vary considerably on a daily basis. There is a need for novel PRO instruments that reflect patients’ migraine experience to assess treatment benefit of migraine prophylactics. These instruments must evaluate the concepts identified and be able to capture the variability of patients’ experience.

Capturing patients' perspectives of treatment in clinical trials/drug development

The patients perspective of treatment outcomes is increasingly important to consumers and providers of healthcare. Recent studies have shown that traditional clinical endpoints may not accurately reflect the patient experience with treatment. Often patients experience of their disease and associated treatment differs from the perspective of their physicians. When implemented with a clear and effective assessment strategy, patient-reported outcome (PRO) measures can be used to collect data directly from patients in the clinical setting. These data can be applied to a range of outcomes, such as treatment efficacy, safety, and patient satisfaction. Such information is valuable at various stages of drug development and can be used to understand the patients perspective of the treatment for evaluating the treatment benefit of new products and to engage patients to make decisions about treatment options and ultimately to support commercialization of pharmaceutical products. Recognizing the value of these data, various regulatory agencies have recently released guidelines on how to best implement these measures in clinical trials to support label claims. The purpose of this paper is to discuss the benefits of collecting PRO data for evaluating the outcomes of treatments in clinical trials, through the product life cycle.

EQ-5D™-derived utility values for different levels of migraine severity from a UK sample of migraineurs

BackgroundTo estimate utility values for different levels of migraine pain severity from a United Kingdom (UK) sample of migraineurs.MethodsOne hundred and six migraineurs completed the EQ-5D to evaluate their health status for mild, moderate and severe levels of migraine pain severity for a recent migraine attack, and for current health defined as health status within seven days post-migraine attack. Statistical tests were used to evaluate differences in mean utility scores by migraine severity.ResultsUtility scores for each health state were significantly different from 1.0 (no problems on any EQ-5D dimension) (pu2009<u20090.0001) and one another (pu2009<u20090.0001). The lowest mean utility, − 0.20 (95% confidence interval [CI]: -0.27 – -0.13), was for severe migraine pain. The smallest difference in mean utility was between mild and moderate migraine pain (0.13) and the largest difference in mean utility was between current health (without migraine) and severe migraine pain (1.07).ConclusionsResults indicate that all levels of migraine pain are associated with significantly reduced utility values. As severity worsened, utility decreased and severe migraine pain was considered a health state worse than death. Results can be used in cost-utility models examining the relative economic value of therapeutic strategies for migraine in the UK.

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.

The effect of aclidinium bromide on daily respiratory symptoms of COPD, measured using the Evaluating Respiratory Symptoms in COPD (E-RS: COPD) diary: pooled analysis of two 6-month Phase III studies

BackgroundReducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD). We evaluated the effect of aclidinium bromide 400xa0μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS™: COPD) scale (formerly EXACT-RS).MethodsData were pooled from the aclidinium 400xa0μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction. Patients were stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) Groups A–D. Change from baseline in E-RS scores, proportion of responders (patients achieving pre-defined improvements in E-RS scores), and net benefit (patients who improved minus patients who worsened) were analyzed.ResultsOf 1210 patients, 1167 had data available for GOLD classification. Mean (standard deviation) age was 63.2 (8.6) years, 60.7xa0% were male, and mean post-bronchodilator forced expiratory volume in 1xa0s was 54.4xa0% predicted. Compared with placebo, aclidinium 400xa0μg BID significantly improved RS-Total (2.38 units vs 0.79 units, pu2009<u20090.001) and domain scores (all pu2009<u20090.001) at Week 24, and doubled the likelihood of being an RS-Total score responder (pu2009<u20090.05), irrespective of GOLD group. The net benefit for RS-Total (Overall: 56.9xa0% vs 19.4xa0%; Au2009+u2009C: 65.7xa0% vs 6.3xa0%; Bu2009+u2009D: 56.0xa0% vs 20.8xa0%, for aclidinium 400xa0μg BID and placebo respectively; all pu2009<u20090.05) and domain scores (all pu2009<u20090.05) was significantly greater with aclidinium compared with placebo, in both GOLD Groups Au2009+u2009C and Bu2009+u2009D.ConclusionsAclidinium 400xa0μg BID significantly improved respiratory symptoms regardless of the patients’ level of symptoms at baseline. Net treatment benefit was similar in patients with low or high levels of symptoms.Trial registrationATTAIN (ClinicalTrials.gov identifier: NCT01001494) and AUGMENT COPD I (ClinicalTrials.gov identifier: NCT01437397).

Development and exploration of the content validity of a patient-reported outcome measure to evaluate the impact of migraine- the migraine physical function impact diary (MPFID)

BackgroundAdults with migraine experience substantial reductions in quality of life during and in-between migraine attacks. Clinical and regulatory guidelines encourage the inclusion of patient reported outcomes for the evaluation of benefits of interventions for migraine.MethodsThe conceptual framework and items for a new patient-reported outcome (PRO) instrument, the Migraine Physical Function Impact Diary (MPFID), were developed using scientific methods recommended to ensure content validity of PRO instruments. The MPFID was developed to measure the impact of migraine on physical functioning based on themes raised in concept elicitation (CE) interviews (conducted previously) with adults with migraine. Cognitive interviews were conducted with adults with migraine to further explore content validity. The instrument was modified following an interim analysis of a first round of cognitive interviews, to assess comprehensiveness and clarity of items, instructions, and response options. Refinements were subsequently tested in additional cognitive interviews.ResultsThe conceptual framework included impacts on physical functioning experienced by most adults with migraine and deemed clinically relevant for measuring the outcome of an intervention for migraine. Concepts in the framework included the impact of migraine on physical impairments (acts) and ability to complete day-to-day activities and perform everyday activities (tasks). MPFID items were generated to evaluate functioning over the past 24xa0h and to collect data daily, to capture experiences on days with migraine as well as the days in-between migraines. Items asked about needing to rest or lie down; ability to get out of bed, stand up, bend over, walk, perform household chores, do tasks outside the home, keep routines or schedules, get ready for the day, do activities that require concentration or clear thinking; difficulty moving head and body, doing activities requiring physical effort; avoiding interacting with others. Initial modifications based on the first round of cognitive interviews (nu2009=u20098) included clarifying instructions, updating three items to enhance specificity and clarity, and revising one item to include gender-neutral language. The second round of interviews (nu2009=u20099) confirmed acceptability of revisions and supported content validity.ConclusionsThe results provide qualitative evidence supporting the content validity of the MPFID for evaluating outcomes of interventions for migraine.