Outcome measures for migraine: Measuring the impact of migraine and results of migraine treatment.

The experience of migraine symptoms and the impacts of migraine on quality of life (QOL) are best reported by the person experiencing them. Therefore, patient-reported outcome (PRO) measures are often used to collect data about the experience and impact of migraine, and value of migraine treatments. PRO concepts that are assessed for the evaluation of migraine treatment outcomes are myriad and diverse (e.g., symptoms, impacts, satisfaction). The first step toward developing a precise strategy to evaluate the outcomes of a treatment is identifying WHAT to measure. This is followed by considerations around HOW to measure the concept. "Selecting What to Measure" section of this chapter discusses the important PRO concepts (WHAT) to measure the impact of migraine and to evaluate interventions for migraine. "Selecting How to Measure" section of this chapter focuses on HOW to collect data about these outcomes in the context of research to evaluate migraine treatments. PRO endpoints recommended in international migraine guidelines and examples of PRO measures that can be used for collecting data to support these endpoints are discussed. The final section of this chapter suggests considerations for selecting PRO measures for evaluating the impact of migraine and migraine treatments and for using these measures to collect data in clinical research.

Reducing the physical, social, and emotional impact of episodic migraine: Results from erenumab STRIVE and ARISE phase III randomized trials.

OBJECTIVE: The purpose of this study was to examine changes in the functional impact of migraine following treatment with erenumab, as measured by the Migraine Functional Impact Questionnaire (MFIQ). BACKGROUND: The MFIQ, a novel patient-reported outcome (PRO) measuring the impact of migraine on four domains (physical function, social function, and emotional function [PF, SF, and EF]; usual activities [UAs]) and a single item assessing overall impact on UA, was included in phase III trials evaluating erenumab 70 and 140 mg monthly for migraine prevention among people with episodic migraine (EM). METHODS: In the ARISE study, 577 patients with EM were randomized to erenumab 70 mg or placebo. In the STRIVE study, 955 patients with EM were randomized to erenumab, 70 mg or 140 mg or placebo. Pairwise comparisons of least-squares mean (LSM) change from baseline in MFIQ scores (with associated 95% confidence interval [CI]) were assessed for each active treatment versus placebo. RESULTS: In ARISE, greater reductions from baseline to month 3 were observed for 70 mg versus placebo for PF (LSM [95% CI]: -3.2 [-6.4 to -0.1]; p = 0.046) and EF (-4.0 [-7.3 to -0.7]; p = 0.019) domain scores. In STRIVE, between-group differences also reflected reductions from baseline to the average of months 4-6 that favored erenumab on all four MFIQ domain scores. Reductions in impact for 70 mg compared to placebo were -4.3 (95% CI: -6.8 to -1.7; p < 0.001) for PF, -4.0 (-6.3 to -1.7; p < 0.001) for UA, -3.7 (-6.1 to -1.2; p = 0.003) for SF, and -5.3 (-7.9 to -2.6; p < 0.001) for EF domain scores. Improvements were also observed for 140 mg versus placebo with between-group differences of -5.7 (95% CI: -8.2 to -3.2; p < 0.001) in PF, -5.1 (-7.5 to -2.8; p < 0.001) in UA, -5.0 (-7.4 to -2.6; p < 0.001) in SF, and -7.2 (-9.9 to -4.5; p < 0.001) in EF domain scores. There were also greater improvements in the overall impact on UA score for 70 mg (LSM [95% CI]: -4.3 [-7.0 to -1.7]; p = 0.001) and 140 mg (-5.3 [-8.5 to -3.2]; p < 0.001) versus placebo. CONCLUSIONS: The MFIQ measures the frequency of impacts and level of difficulty on multiple functional domains that provide a more complete picture of the effects of migraine. MFIQ scores showed that in comparison with placebo, patients treated with erenumab had greater reductions in the functional impact of migraine, providing insight into treatment benefits that extend beyond improvements in clinical status and health-related quality of life previously reported based on clinical end points and other PROs.

The experience of itch in children with psoriasis: A qualitative exploration of the Itch Numeric Rating Scale.

BACKGROUND/OBJECTIVES: Psoriasis is a chronic, immune-mediated dermatologic disorder with a prevalence among children estimated at 0.1%-0.45%, and a median age of onset at approximately 7-10 years. Pediatric psoriasis is known to have negative impacts on health-related quality of life. Among the most bothersome symptoms, itch has been measured using the Itch Numeric Rating Scale (NRS). This study explored the symptom and impacts of itch with pediatric psoriasis patients and evaluated the content validity of the Itch NRS in children. METHODS: Semi-structured qualitative interviews were conducted among a sample of pediatric patients diagnosed with plaque psoriasis. RESULTS: Concept elicitation interviews were completed with 22 children (ages 7-17 years). When asked about most frequent symptoms, 61% reported itching (n = 14) and 65% reported flaking (n = 15). The majority reported itching as bothersome; about half described impacts on their regular activities. Cognitive interviews were completed with 25 children (ages 8-17 years). Most reported that independently completing the Itch NRS would be easy, and all described the meaning of the response options similar to the intended value. Overall, the Itch NRS was received favorably, with comments that the scale was easy or relevant to their experience with psoriasis. CONCLUSIONS: This qualitative study supports the content validity of the Itch NRS for use in a pediatric psoriasis population aged 8-17. Given the established importance of itch to pediatric psoriasis patients, future research exploring the impact of itch on the lives of pediatric psoriasis patients may provide a valuable contribution to the field.

Use of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) in X-Linked Myotubular Myopathy: Content Validity and Psychometric Performance.

X-linked myotubular myopathy (XLMTM) is a life-threatening, congenital myopathy characterized by extreme hypotonia, weakness, delayed motor milestones, and respiratory failure, often resulting in pediatric mortality. This study evaluated the content validity and psychometric performance of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders as a measure of neuromuscular functioning in children with X-linked myotubular myopathy. This study was conducted in two phases. Phase I assessed the content validity of the measure for use in an XLMTM pediatric population through: literature review, clinical expert interviews, caregiver interviews, and a modified-Delphi panel among clinicians. Phase II assessed psychometric performance based on the INCEPTUS observational clinical study and the ASPIRO interventional gene therapy study, including tests of reliability (internal consistency, test-retest, and interrater), validity (construct and criterion), and responsiveness based on observational and interventional clinical trial data analyses. Data established construct validity and reliability of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders among XLMTM patients before administration of resamirigene bilparvovec, and sensitivity to study drug administration as evidenced by the significant post-administration response in ASPIRO. Findings support the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders as an appropriate neuromuscular functioning assessment in a pediatric X-linked myotubular myopathy patient population.

Evaluating the Psychometric Properties of the Migraine Functional Impact Questionnaire (MFIQ).

BACKGROUND: Migraine is a chronic neurologic disease that can be associated with significant migraine-related impact, disability, and burden. Patient-reported outcome measures (PRO) are included in clinical trials of migraine interventions to capture treatment effects from a patient perspective. Clinical and regulatory guidelines also encourage use of PROs in trials. The Migraine Functional Impact Questionnaire (MFIQ) is a novel PRO measure, assessing the impact of migraine on Physical Function (PF), Usual Activities (UA), Social Function (SF), and Emotional Function (EF), in the past 7 days. Scientific methods recommended to meet the requirements of the U.S. Food and Drug Administration were followed, to ensure that the MFIQ content included outcomes that were relevant to adults with migraine and were clinically relevant, specifically to evaluate preventive treatments for migraine. OBJECTIVE: The objective of this study was to conduct item analyses informing item reduction and scoring, and to evaluate the psychometric properties of the MFIQ. METHODS: In a prospective, observational study, adults with migraine completed the MFIQ as well as additional clinical and PRO instruments, including the Headache Impact Test (HIT-6TM ), Patient-Reported Outcomes Measurement Information System Physical Function Short Form 10a (PROMIS-PF), Migraine-Specific Quality-of-Life Questionnaire (MSQ), and Patient Global Rating of Change (PGIC). Item-level evaluation, item response theory (IRT), and factor analysis were used to select final MFIQ items, identify domains, and inform scoring. Psychometric properties of the MFIQ were evaluated to assess reliability (internal consistency and test-retest), validity (construct and known-groups), and responsiveness. RESULTS: The study enrolled 569 adults with migraine. Subjects had an average age of 39.9 years (SD 12.0), 87.2% were female, and 80.8% were white. Five items were dropped from the draft version based on results of item-level analyses reviewed in the context of previous qualitative research to produce the final 26-item MFIQ (v.2). Four domain scores (PF, UA, SF, and EF) and a global item score for impact on UA were identified. Higher scores on a 0-100 scale represent greater impact. All scores exhibited high internal consistency (α ≥ 0.89) and moderate test-retest reliability among stable subjects (ICCs ≥ 0.47). Construct validity was demonstrated by significant correlations (all P < .0001) between MFIQ domain scores, related PRO scores, and the frequency of migraine days and headache days. All domain scores differentiated between subgroups ("known groups") defined based on established levels of clinical severity: number of monthly migraine and headache days, migraine interference levels and scores on other PRO instruments (P < .05). Improvements in MFIQ scores corresponded with clinical improvement (percent reduction in monthly migraine days), improvement in migraine interference with daily activities, and related improvements in PRO scores (P < .05), demonstrating that the MFIQ was responsive to changes in migraine impact. CONCLUSIONS: The MFIQ is a reliable and valid measure that can be used to collect data about migraine impact. The MFIQ is being used to evaluate outcomes of migraine interventions in clinical trials and observational studies. It could potentially also be used in clinical practice both for initial and ongoing assessments for monitoring outcomes and to enhance communication between patients and healthcare professionals for the management of migraine.

Development of a New Tool for Evaluating the Benefit of Preventive Treatments for Migraine on Functional Outcomes - The Migraine Functional Impact Questionnaire (MFIQ).

OBJECTIVE: The objective of this study was to develop a method for evaluating patient-relevant outcomes of interventions for preventing migraine attacks, followed by an assessment of the content validity of a new patient-reported outcome (PRO) instrument: the Migraine Functional Impact Questionnaire (MFIQ). BACKGROUND: The aim of preventive treatments for migraine is not only to reduce migraine frequency, but also to restore patients' ability to function and improve quality of life. METHODS: A multi-stage process based on best practice methods and regulatory guidelines for ensuring content validity of PRO instruments for evaluating treatment benefit was followed. Qualitative concept elicitation interviews conducted to understand the experiences of adults with migraine underpinned the development of the instrument. The initial stage included the development of a conceptual disease model (CDM) based on information from these interviews. This CDM was used to identify the concepts of interests (COI) to evaluate outcomes of preventive treatments. The results of the interviews were also used in stage 2, to develop a measurement framework for collecting data about these COI. In the third stage, existing instruments were reviewed for coverage of the concepts in the framework and evidence of concept elicitation to the point of saturation, to support content validity. In the fourth stage, an instrument was drafted to evaluate concepts in the framework, based on the qualitative data collected from the interviews. Following a review by clinical and translation experts, the new instrument was tested in adults with migraine in the fifth stage using 2 rounds of cognitive interviews, and was modified based on interview feedback. In the last stage, the instrument was linguistically adapted, using methods recommended for PRO instruments, to ensure conceptual equivalence of language versions for use in international studies. Each language version was tested in at least 5 native speakers using cognitive interviews. RESULTS: Results from the concept elicitation interviews suggested that migraine had an impact on various aspects of functioning. A conceptual framework for evaluating functional outcomes was developed for the concept selected based on a review of the CDM - physical and emotional functioning, every day activities, and social/leisure activities. Existing PROs lacked coverage of some concepts in the conceptual framework, had recall periods that were inappropriate for capturing the experience of COI or did not have evidence of content validity. A novel PRO instrument, the MFIQ, was developed to address these gaps. Cognitive interviews with 9 adults with migraine resulted in minor changes to the items of the MFIQ, and a final round of 8 interviews confirmed the changes were acceptable and supported its validity. The interviews conducted to test linguistic adaptations confirmed conceptual equivalence in the 25 countries evaluated. CONCLUSIONS: Development of the MFIQ followed best measurement practices to ensure content validity and followed regulatory guidelines for PRO instruments to evaluate benefits of treatments. The MFIQ was developed for use in clinical trials or clinical practice settings to track outcomes of preventive treatments that are most relevant to adults with migraine.

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).

BACKGROUND: Adults 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. METHODS: The 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. RESULTS: The 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 24 h 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 (n = 8) 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 (n = 9) confirmed acceptability of revisions and supported content validity. CONCLUSIONS: The results provide qualitative evidence supporting the content validity of the MPFID for evaluating outcomes of interventions for migraine.

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

BACKGROUND: Migraine 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. METHODS: This 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. RESULTS: Nine articles from 563 screened abstracts underwent full review to identify migraine-relevant concepts. This concept identification and subsequent concept elicitation interviews (N = 32; 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. CONCLUSIONS: The 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.

Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification.

INTRODUCTION: The Short Opiate Withdrawal Scale (SOWS)-Gossop is a 10-item questionnaire developed to evaluate opioid withdrawal symptom severity. The scale was derived from the original 32-item Opiate Withdrawal Scale in order to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The objective of this study was to examine the psychometric properties and provide score interpretation guidelines for the SOWS-Gossop 10-item version. METHODS: Blinded, pooled data from two trials assessing the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid detoxification were used to evaluate the quantitative psychometric properties and score interpretation of the SOWS-Gossop. RESULTS: Five hundred fifty-five (N=555) observations were available at baseline with numbers decreasing to n=213 at day 7. Mean (standard deviation) SOWS-Gossop scores were 10.4 (6.86) at baseline, 8.7 (6.49) on day 1, 10.5 (7.21) on day 2, and 3.1 (3.95) on day 7. Confirmatory factor analysis indicated that the SOWS-Gossop items loaded on a single factor consistent with a single total score. Intra-class correlations (95% confidence interval) were 0.78 (0.70-0.85) between baseline and day 1, 0.84 (0.79-0.89) between days 4 and 5, and 0.88 (0.83-0.91) between days 6 and 7, demonstrating good test-retest reliability. Mean SOWS-Gossop scores varied significantly (p<0.0001) by Modified Clinical Global Impression severity groups supporting known-groups validity. Most correlations with conceptually similar instruments were over 0.4, providing evidence of construct validity. Results suggest that a change score of approximately 2-4 points is likely a small but meaningful improvement on the SOWS-Gossop Total Score. CONCLUSIONS: The findings of this study indicate that the SOWS-Gossop includes concepts that are relevant to patients' experiences with opioid withdrawal and has excellent psychometric properties. The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings.

Assessing the Reliability and Validity of the Sheehan Irritability Scale in Patients With Major Depressive Disorder.

OBJECTIVE: Irritability is a significant component in the clinical manifestation of major depressive disorder (MDD). The Sheehan Irritability Scale (SIS) was developed to assess irritability-related symptoms in patients with psychiatric disorders. Data from a phase 2 clinical trial (June 2008-July 2009) was utilized to evaluate the psychometric properties of the SIS. The trial population included patients diagnosed with MDD, according to DSM-IV and confirmed via the MINI diagnostic scale, who had inadequate response to citalopram. METHOD: The secondary analyses included 586 patients from the United States and India. Data from the SIS, depression severity measures (17-item Hamilton Depression Rating Scale [HDRS-17], Montgomery-Asberg Depression Rating Scale [MADRS], Quick Inventory of Depressive Symptomatology-Self-Report [QIDS-SR]), and other measures (Sheehan Disability Scale [SDS], Clinical Global Impressions-Severity of Illness scale [CGI-S]) were used in the psychometric evaluation. All statistical tests used a significance level of .05 unless otherwise noted. RESULTS: Internal consistency (0.92-0.99) and test-retest reliability (0.83 to 0.98) were excellent. Concurrent validity was demonstrated through strong correlations between the SIS total score and HDRS-17, QIDS-SR, SDS, CGI-S, and MADRS scores. SIS total scores were significantly different by clinical severity level (P < .001). Minimally important difference estimates suggest that a 7- to 8-point change in the SIS total score may be clinically meaningful. CONCLUSIONS: The SIS has excellent reliability, acceptable validity, and good responsiveness, making the SIS appropriate for use in clinical research and practice. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00692445.

Content validity of the Sheehan Irritability Scale in patients with major depressive disorder.

The Sheehan Irritability Scale (SIS) measures the frequency, severity, and impairment associated with irritability in psychiatric patients. The content validity of the SIS in patients with major depressive disorder (MDD) has not been evaluated. A cross-sectional, qualitative research study was conducted to assess the content validity of the SIS among patients with MDD. One-on-one interviews were conducted, starting with open-ended questions to evaluate the consistency of the SIS content with patient experiences of irritability. Participants then completed the SIS and cognitive interviews around the comprehension of the SIS content (instructions, items, response options). Participants included 24 patients diagnosed with MDD who had an inadequate response to an antidepressant treatment. The sample was: 50.4 mean years, 66.7% female, and 91.7% white racial background. All concepts on the SIS were spontaneously mentioned by at least one participant, and when probed about the symptoms, the majority of participants (66.7-100%) reported the concepts being part of their experience. The majority of participants (70.8-100%) understood the SIS instructions, items, and response scales. This study provides evidence of content validity of the SIS in patients diagnosed with MDD, supporting the use as a measure of irritability in patients with depression.

Assessment of Parkinson's disease levodopa-induced dyskinesia: a qualitative research study.

BACKGROUND AND OBJECTIVES: The 26-item Parkinson disease dyskinesia scale (PDYS-26) was developed to assess the impact of Parkinson's disease levodopa-induced dyskinesias (PD-LID). The purpose of this qualitative research study was to assess the content validity of the PDYS-26 in an independent sample and to use the findings to suggest a conceptual framework around the impact of PD-LID. METHODS: PD patients experiencing LID and their caregivers were recruited from four US clinical sites. Stage I involved 22 qualitative concept elicitation interviews with patients and caregivers, and 11 qualitative cognitive interviews (CI) with patients about the PDYS-26. The PDYS-26 was modified based on Stage I findings. Stage II consisted of 13 CI on the Modified PDYS. RESULTS: Forty-six participants were interviewed across both stages of the study. Patient mean age was 67.3 (SD ± 9.55) years; 19 (54.3 %) female; 34 (97.1 %) white. The content validity of the PDYS-26 was generally supported. A revised conceptual framework with three hypothesized domains (body control, activities of daily living, social consequences) was developed. Modifications were made to the PDYS-26 (i.e., emphasizing LID in the instructions; response scale modification; deleting or modifying items), which resulted in the 22-item Modified PDYS. CONCLUSIONS: Stage I and II findings suggested a number of modifications to the scale in order to improve the content validity. Psychometric testing of the revised scale with a larger patient sample is suggested to evaluate item performance, establish scoring, and provide quantitative support for the conceptual framework.

The impact of medication on health-related quality of life in patients with generalized anxiety disorder.

BACKGROUND AND OBJECTIVE: Generalized anxiety disorder (GAD) is a psychiatric disorder characterized by excess worry and anxiety. GAD impacts overall health-related quality of life (HRQL), level of functioning, and disability. This literature review was conducted to understand the impact of pharmacological treatments on HRQL and functional outcomes. METHODS: A literature review was conducted to identify randomized controlled trials (RCTs) comparing GAD pharmacological treatments with one or more patient-reported outcome (PRO) measure assessing HRQL, disability, functioning, or work productivity. Four databases were searched (PubMed, EMBASE, Cochrane Reviews, PsycInfo). Limits included English-language publications from 2004-2014. Abstracts and articles were reviewed to select articles reporting results of RCTs of pharmacological treatments for GAD that included one or more PRO measure. Article abstraction and summarization focused on key elements of the study design and PRO results. RESULTS: One hundred sixty-three abstracts were reviewed; 44 articles were requested; 12 articles, representing 19 studies, were deemed relevant. The Sheehan Disability Scale (SDS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) were the most frequently utilized PRO measures. In clinical trials with significant anxiety symptom reductions, the SDS and Q-LES-Q also improved with treatment and differentiated from placebo. Two trials included a measure of work productivity; both demonstrated significant improvements with short-term treatment. CONCLUSION: Treatments that reduce anxiety symptoms are also associated with improvements in patient-reported HRQL, function, and disability. In addition to evaluation of treatment impacts on anxiety symptoms, clinical trials should include PRO measures of HRQL, disability, and functioning.

Assessment of sleep in patients with fibromyalgia: qualitative development of the fibromyalgia sleep diary.

OBJECTIVES: Sleep disturbance is a common experience in fibromyalgia (FM). The field lacks a sleep specific patient reported outcome (PRO) measure developed and validated in a FM population. The study objective is to gain an in-depth understanding of sleep in FM and to develop a PRO measure of it. METHODS: Research involved the following stages: 1) A literature review conducted to identify key concepts associated with FM patient experience of sleep and PRO measures that have been used to assess this; 2) Qualitative interviews with therapeutic area experts; 3) Focus groups with FM patients who experienced sleep disturbance; 4) Development of a conceptual framework and the Fibromyalgia Sleep Diary (FMSD); and 5) Cognitive interviews with patients to explore content validity of the FMSD. RESULTS: The literature review and expert interviews supported sleep disturbance being an important aspect of the FM patient experience, and underscored the need for a new FM specific sleep PRO measure. Results from the focus groups demonstrated that FM patients experience sleep disturbances that they attribute to their FM symptoms, such as pain and stiffness, confirming the importance of understanding more about sleep changes. Aspects of sleep raised by FM patients included poor sleep quality and insufficient quantity including difficulty with falling asleep, getting comfortable, and staying asleep; restlessness; light sleep; not feeling rested upon awakening; and difficulty starting the day. Cognitive interview results showed that the 8-item FMSD, developed to reflect the concepts identified above, was relevant to FM patients with content that was interpreted as intended. CONCLUSIONS: The FMSD was developed in line with the recommendations of the FDA PRO guidance and ISPOR PRO Task Force. The qualitative evidence generated thus far strongly supports the content validity of the FMSD as a PRO measure of sleep disturbance in FM populations. Psychometric evaluation of the FMSD to demonstrate reliability, validity and sensitivity to change is recommended as a next step.

Review of patient-reported outcome measures in chronic hepatitis C.

BACKGROUND: Chronic hepatitis C (CHC) and its treatment are associated with a variety of patient-reported symptoms and impacts. Some CHC symptoms and impacts may be difficult to evaluate through objective clinical testing, and more easily measured through patient self-report. This literature review identified concepts raised by CHC patients related to symptoms, impacts, and treatment effects, and evaluated integration of these concepts within patient-reported outcome (PRO) measures. The goal of this work was to provide recommendations for incorporation of PRO measurement of concepts that are relevant to the CHC experience into CHC clinical trial design. METHODS: A three-tiered literature search was conducted. This included searches on concepts of importance, PRO measures used in clinical trials, and existing PRO measures. The PRO Concept Search focused on reviewing issues raised by CHC patients about CHC symptoms, disease impact, and treatment effects. The CHC Trials with PRO Endpoints Search reviewed clinical trials with PRO endpoints to assess differences between treatments over time. The PRO Measure Search reviewed existing PRO measures associated with the concepts of interest. RESULTS: This multi-tiered approach identified five key concepts of interest: depression/anxiety, fatigue, flu-like symptoms, cognitive function, insomnia. Comparing these five concepts of interest to the PRO measures in published CHC clinical trials showed that, while treatment of CHC may decrease health-related quality of life in a number of mental and physical domains, the PRO measures that were utilized in published clinical trials inadequately covered the concepts of interest. Further review of 18 existing PRO measures of the concepts of interest showed only four of the 18 were validated in CHC populations. CONCLUSIONS: This review identified several gaps in the literature regarding assessment of symptoms and outcomes reported as important by CHC patients. Further research is needed to ensure that CHC clinical trials evaluate concepts that are important to patients and include measures that have evidence supporting content validity, reliability, construct validity, and responsiveness.

A qualitative assessment of the concept of dependence in Alzheimer's disease.

BACKGROUND: The Dependence Scale (DS) was designed to assess levels of patient need for care due to deficits typical of Alzheimer's disease (AD). This study examined content validity of the DS based on input from patients, caregivers, and clinicians. METHODS: Qualitative interviews with experts, patients, and caregivers were used to collect information on the concept of dependence and to assess content validity. RESULTS: Nine clinicians rated item relevance ''high'' with consensus on the primacy of functional abilities and dependence in the measurement of AD progression. Twenty-two US, 11 UK, and 14 informal caregivers from Spain participated in focus groups; 18 patients participated in 3 separate focus groups. Discussion supported DS hierarchy of dependence, capture of mild-to-severe dependence, suitability of response options, and short recall time frame. CONCLUSIONS: Clinicians, caregivers, and patients support content validity of the DS in mild-to-moderate AD. The DS may be valuable to capture dependence within future clinical dementia trials.

Psychometric evaluation of the Medication Satisfaction Questionnaire (MSQ) to assess satisfaction with antipsychotic medication among schizophrenia patients.

The Medication Satisfaction Questionnaire (MSQ) is a single-item questionnaire which evaluates satisfaction with antipsychotic medication in schizophrenia patients. This study evaluated the reliability and validity for its use in research and clinical settings. Data pooled across treatment groups (control vs. Paliperidone ER) from a randomized 6-week study were used to conduct four psychometric assessments of the MSQ: (1) test-retest reliability, (2) convergent validity, (3) known-groups validity, and (4) minimally important difference (MID). This analysis included 191 randomized subjects. Test-retest reliability was evaluated for patients with no change in satisfaction from weeks 2 to 4 and weeks 4 to 6 (ICC=0.80; 0.83, respectively). Convergent validity was demonstrated through large correlations with Treatment Satisfaction Questionnaire for Medication (TSQM) global score (r=0.72-0.77), and through small correlations with variables measuring clinical symptoms and functioning (e.g., Positive and Negative Syndrome Scale (PANSS) total score [r=-0.30 to -0.17], CGI-S [r=-0.35 to -0.27], SF-36 Physical Functioning Score [r=0.18] and side effects and extrapiramidal measures (including UKU, ESRS-A, SAS). Mean MSQ scores were significantly different between those who completed and discontinued the study, and between different satisfaction groups based on TSQM, demonstrating good known-groups validity. MID estimates for the MSQ ranged from 0.47 (standard error of measurement) to 0.58 (anchor-based method). Results suggest that the MSQ has acceptable reliability and validity, making this single-item questionnaire appropriate and easy to use in clinical research and potentially in clinical practice. A 1-point change on the MSQ may be considered clinically meaningful.

Characterizing the burden of premature ejaculation from a patient and partner perspective: a multi-country qualitative analysis.

BACKGROUND: Premature ejaculation (PE) is a common sexual dysfunction among men which affects men and their partners. Little qualitative data are available to characterize the impact of PE on men and their partners about ejaculatory control, sexual satisfaction, emotional distress and relationships. The objective of this study was to assess the impact of PE from the perspective of men with PE and the female partners of men with PE on their sexual experience, distress and relationships. METHODS: Qualitative data were collected through 14 focus groups in the US and through one-on-one interviews in the US, UK, Italy, France, Germany, and Poland. Study participants included heterosexual men with PE and female partners of males with PE. All participants were asked about how PE affects their daily life, including emotional impacts. One-on-one interviews also included obtaining feedback on the male and female versions of 4-single item measures of PE focusing on ejaculatory control, satisfaction with intercourse, interpersonal distress, and relationship difficulty. RESULTS: Participants included 172 males with PE and 67 female partners of men with PE. Lack of control over ejaculation and dissatisfaction with intercourse emerged as central themes of PE. Lack of ejaculatory control resulted in greater dissatisfaction and greater emotional distress, including feelings of inadequacy, disappointment, and anxiety. Continued PE ultimately leads to greater problems with partners and often disrupts partner relationships. Participants indicated that PE was keeping them from attaining complete intimacy in their relationships even when their partners were generally satisfied with sexual intercourse. Impacts of PE on sexual satisfaction, emotional distress and partner relationships were consistent across countries. Feedback on the single-item PE measures confirmed relevance of the item content and further confirmed major themes identified from the qualitative data. CONCLUSION: This qualitative study provides valuable insights on the substantial psychosocial burden of PE in the US and the Europe. Lack of control over ejaculation resulted in dissatisfaction with intercourse and increased emotional distress, and wide-ranging impact for both men with PE and their partners of men with PE. Data collected in this study may help inform the content of new patient reported measures for use in PE research.

Does epoetin alfa improve health-related quality of life in chronically ill patients with anemia? Summary of trials of cancer, HIV/AIDS, and chronic kidney disease.

OBJECTIVES: Anemia, defined as having low levels of hemoglobin (HGB), is caused by disease-related (e.g., bone marrow suppression, nutritional deficiency) or treatment-related (e.g., chemotherapy, antiretroviral therapy) factors. Although epoetin alfa has been shown to improve HGB outcomes in cancer, HIV/AIDS, and chronic kidney disease (CKD), these results have been viewed in isolation, rather than across populations. The purpose of this article is to review findings from trials that evaluated the impact of epoetin alfa on HGB and health-related quality of life (HRQL) across various populations with different underlying causes of anemia. METHODS: A review of clinical trials published in English between January 1993 and September 2005. Searches were conducted using MEDLINE and EMBASE. Between- and within-group changes in HGB and HRQL were examined. RESULTS: One hundred ten articles were retrieved and 18 were reviewed. Statistically significant improvements in HGB were generally seen (1) between groups for cancer patients receiving epoetin alfa compared with those receiving placebo or standard of care (SOC) (between-group differences in changes from baseline to end point ranging from 1.2 to 1.9 g/dl); and (2) within groups for HIV/AIDS and CKD patients receiving epoetin alfa (changes from baseline to end point of 2.5 and 2.9 g/dl and 2.7 g/dl, respectively). Statistically and clinically significant improvements in HRQL, particularly with regard to fatigue, were seen across chronic conditions based on the Linear Analog Scale Assessment energy scale; where improvements of at least 8 mm-considered clinically relevant-were generally seen (1) between groups for cancer patients receiving epoetin alfa compared with those receiving placebo or SOC (differences in changes from baseline to end point from 0.8 to 19.8 mm); and (2) within groups for HIV/AIDS and CKD patients receiving epoetin alfa (changes from baseline to end point of 23 and 25 mm and 28 mm, respectively). CONCLUSIONS: Results of published clinical trials suggest that treatment of anemia associated with cancer, HIV/AIDS and CKD can have a significant impact on HRQL, particularly fatigue, and that this impact is both statistically and clinically significant.

The patient experience of depression and remission: focus group results.

Few depression measures were developed with the patient perspective. To obtain patient views on depression and early symptom resolution, 4 focus groups (N=31) were conducted. Patients also completed the Quick Inventory of Depressive Symptomology (Self-Report), SF-36, and a rating of the bothersomeness and significance of 12 symptoms of depression. Transcripts were reviewed for major themes. Irritability was a key symptom and it remitted earlier than others. Important to participants were low mood, low energy, lack of motivation, lack of focus/concentration, feelings of guilt, self-critical thoughts, feeling overwhelmed, lack of enjoyment, hypersomnia, restlessness, anger, and irritability. Gender differences emerged; most men reported irritability as one of the first symptoms to remit; for women, motivation level and energy commonly remitted first. Results suggest that new measures of treatment outcome should encompass irritability, anger, and ability to cope with life stressors.