Meaningful Within-Patient Change in Subjective Total Sleep Time in Patients with Insomnia Disorder: An Analysis of the Sleep Diary Questionnaire Using Data from Open-Label and Phase III Clinical Trials.

BACKGROUND: The Sleep Diary Questionnaire (SDQ), a modified version of the Consensus Sleep Diary, is a 17-item sleep diary for assessing subjective total sleep time (sTST: total time spent asleep at night) and other sleep parameters in insomnia trials. sTST is a key parameter of efficacy in insomnia trials; however, the magnitude of improvement in this parameter that people with insomnia disorder consider clinically meaningful is unclear. OBJECTIVE: The aim of this study was to estimate meaningful within-patient change for sTST using clinical trial data. METHODS: Data were from an open-label trial of zolpidem and pooled data from a phase III placebo-controlled trial of daridorexant. In both trials, adults with moderate to severe insomnia completed the SDQ daily. Meaningful change in sTST was estimated in an anchor-based analysis using outcome measures that were correlated with change in weekly average sTST (Spearman correlation coefficient ≥ 0.30): the Insomnia Severity Index, patient global assessments and impressions of severity and change in daytime and night-time symptoms (PGA-S, PGI-S, PGI-C), and clinician global impressions of severity and change in patients' daytime symptoms (CGI-S, CGI-C). Meaningful within-patient change estimates were 'triangulated' to identify a value where they converged. RESULTS: In the open-label trial (N = 114), subjects with a 1-point or 1-step improvement on the anchors had mean increases in sTST of 60.1-83.2 min at day 8 and 55.5-68.2 min at day 15. For subjects with a 2-point or 2-step improvement on the anchors, mean increases in sTST were 79.6-81.4 min at day 8 and 80.1-93.5 min at day 15. In the phase III trial (N = 930), weekly average increases in sTST for subjects with a 1-point or 1-step improvement on the anchors were 39.3-46.7 min at month 1 and 47.3-58.3 min at month 3. For subjects with a 2-point or 2-step improvement on the anchors, mean increases in sTST were 60.7-76.2 min at month 1 and 70.1-87.7 min at month 3. Triangulation of these values supported a meaningful within-patient change threshold starting at 55 min. CONCLUSION: Increasing sTST is an important treatment outcome for people with insomnia. An increase in sleep time of approximately 55 min is meaningful to patients. CLINICAL TRIALS REGISTRATION: NCT03056053 (17 February 2017) and NCT03545191 (4 June 2018).

Meaningful Within-Patient Change on the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ): Analysis of Phase III Clinical Trial Data of Daridorexant.

BACKGROUND: The Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) is a new validated 14-item patient-reported outcome (PRO) instrument for evaluating daytime functioning in people with insomnia. It comprises three domains: Alert/Cognition, Mood, and Sleepiness. OBJECTIVE: The aim of this analysis was to estimate the minimum within-patient change for IDSIQ scores that an adult patient with insomnia would consider meaningful. METHODS: Data were from a randomized, double-blind, placebo-controlled, phase III clinical trial of daridorexant in adults with insomnia. Subjects completed the IDSIQ daily in the evening, with a recall period of 'today', throughout the 3-month double-blind treatment period. Scores were calculated as a weekly average. Each IDSIQ item was scored on an 11-point numeric rating scale ranging from 0 (not at all/none at all) to 10 (very/a lot), with a higher score indicating a greater severity or impact. PRO measures with correlation coefficients ≥0.30 were included in a subsequent anchor-based analysis. For the IDSIQ total score and each IDSIQ domain, meaningful within-patient change was estimated as the minimum score change patients would consider meaningful in an anchor-based analysis using data from PRO instruments capturing daytime and night-time insomnia symptoms (the Insomnia Severity Index [four items, each scored 0-4, with a higher score indicating greater symptom severity; assessed at screening, baseline, month 1 and month 3], Patient Global Assessment of Disease Severity [6-point scale from 'none' to 'very severe'; assessed weekly], Patient Global Impression of Severity [4-point scale from 'none' to 'severe'; assessed weekly], and Patient Global Impression of Change [7-point scale from 'very much better' to 'very much worse'; assessed weekly for night-time and daytime symptoms separately]). A supplemental distribution-based analysis was also conducted to support the anchor-based analysis. RESULTS: The analysis included 930 subjects aged 18-88 years. Spearman correlation coefficients for the relationships between score changes/ratings for anchors and the IDSIQ (0.36-0.44 at month 1, 0.45-0.57 at month 3) were all above the prespecified threshold of 0.30. Mean IDSIQ score changes at months 1 and 3 based on the different anchors supported meaningful within-patient change estimates starting at 17 points for the IDSIQ total score, 9 points for the Alert/Cognition domain, and 4 points for the Mood and Sleepiness domains. CONCLUSION: This analysis demonstrates the meaningful within-patient change for the IDSIQ total score and domain scores, that the instrument is sensitive to changes in the patient experience of insomnia, and that it can be used in clinical trials to evaluate changes in daytime functioning. CLINICAL TRIALS REGISTRATION: NCT03545191 (4 June 2018).

Symptoms, impacts, and suitability of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT™) questionnaire in patients with sarcoidosis-associated pulmonary hypertension (SAPH): a qualitative interview study.

BACKGROUND: Sarcoidosis-associated pulmonary hypertension (SAPH) is a prevalent and serious complication of sarcoidosis. No SAPH-specific self-report instruments for assessing SAPH symptoms and their impact on patients are available to date. This study sought to determine whether the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT™) questionnaire is suitable for use in patients with SAPH. METHODS: Patients diagnosed with SAPH participated in qualitative one-on-one telephone interviews to better understand SAPH symptoms and their impacts on patients' lives and to determine the appropriateness of the PAH-SYMPACT™ for use in patients with SAPH. The interviews comprised concept elicitation, completion of the PAH-SYMPACT™, and cognitive debriefing. Interview transcripts were analyzed by content analysis. RESULTS: Eleven patients with SAPH were interviewed between August 2019 and June 2020. In the concept elicitation, all 11 participants endorsed shortness of breath and nine participants (82%) rated it as their "most bothersome or severe" symptom. Impacts endorsed by all 11 participants were difficulty walking uphill or up stairs and difficulty in performing daily activities. Cognitive debriefing indicated that the PAH-SYMPACT™ items were relevant and understandable to most participants and reflected their experiences of SAPH. Participants indicated that no key symptoms or impacts of SAPH were missing. They also reported that the PAH-SYMPACT™ instructions and response options were clear, and that it would be feasible to complete the 11 symptom items and one oxygen use item as part of their daily schedule. CONCLUSIONS: This study suggests the PAH-SYMPACT™ is suitable for assessing symptoms and their impact in patients with SAPH. However, larger longitudinal studies are needed to confirm that it is fit for use in this patient population and that it can be used to reliably detect temporal changes in patients' symptom status. Trial registration Not applicable.

Validation and clinical value of the MANAGE-PD tool: A clinician-reported tool to identify Parkinson's disease patients inadequately controlled on oral medications.

INTRODUCTION: Making Informed Decisions to Aid Timely Management of Parkinson's Disease (MANAGE-PD) is a clinician-reported tool designed to facilitate timely identification and management of patients with advancing Parkinson's disease (PD) with suboptimal symptom control while on standard therapy. The objective of this study was to evaluate the validity and clinical value of the tool. METHODS: Driven by structured inputs from a steering committee and panel of PD experts, the tool was developed to classify patients into 3 categories. Validity and clinical value were elucidated using a two-pronged approach: (i) hypothetical patient vignettes (n = 10) developed based on the MANAGE-PD tool and rated by 17 PD specialists and 400 general neurologists (GN) and (ii) patients with PD (n = 2546) managed in real-world clinical settings. Vignette validity was based on concordance between PD experts' clinical judgement and MANAGE-PD vignette categorization. Patient-level data was used for known-group comparisons (validity) and discordant pair analysis (clinical value). RESULTS: The tool demonstrated strong validity and clinical value among PD specialists (intraclass coefficient [ICC] 0.843; Fleiss weighted kappa [ƙweighted] 0.79) and GN (ICC 0.690; ƙweighted 0.65) using patient vignettes. MANAGE-PD also demonstrated real-world validity and clinical value based on ability to identify patients with incrementally higher clinical, economic, and humanistic PD burden across categories of the tool (p < 0.01). CONCLUSIONS: MANAGE-PD demonstrated robust validity and clinical value in identifying patients with suboptimal PD symptom control. Clinical use of MANAGE-PD may complement treatment decision-making and facilitate timely and comprehensive management of patients with advancing PD.

Symptoms, impacts, and suitability of the Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT™) questionnaire in patients with chronic thromboembolic pulmonary hypertension (CTEPH): a qualitative interview study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension caused by blood clots and scar tissue in the blood vessels of the lungs. Health-related quality of life is often significantly impaired in patients with CTEPH. However, a better understanding of how CTEPH symptoms affect patients' lives is needed to optimally assess the impact of the disease and treatment. OBJECTIVES: This qualitative study aimed to better understand the symptoms of CTEPH and how they affect patients' lives, as well as to determine the appropriateness of the Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT™) questionnaire for use in this patient population. METHODS: Adults diagnosed with CTEPH, recruited from two clinical sites in the US, participated in one-to-one qualitative telephone interviews. They described their experience of CTEPH symptoms and the impact these symptoms have on their lives. They also provided feedback on the comprehensibility and relevance of the PAH-SYMPACT™'s instructions, items, and response options. RESULTS: Participants (N = 12) had a mean age of 62.5 years. Two thirds were female and most (83%) had undergone pulmonary endarterectomy and/or balloon pulmonary angioplasty. The most frequently endorsed symptoms were shortness of breath (endorsed by all 12 participants), fatigue (11 participants), and lightheadedness (10 participants). All participants identified shortness of breath as an "extremely important" symptom, and seven participants rated fatigue as "extremely important." The most frequent impacts of CTEPH were on ability to walk quickly (endorsed by all 12 participants), ability to walk up inclines or stairs (11 participants), and ability to carry things (11 participants). The PAH-SYMPACT™ items were relevant to most participants and reflected their experience of CTEPH. All participants indicated that no important CTEPH symptoms were missing from the PAH-SYMPACT™. Overall, the instructions, items, and response options of the PAH-SYMPACT™ were clear and easy to understand. CONCLUSIONS: The symptoms and impacts experienced by patients with CTEPH align with items included in the PAH-SYMPACT™. The PAH-SYMPACT™ appears to be fit for purpose for assessing disease status in patients with CTEPH.

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.

Clostridium difficile Infection-Daily Symptoms (CDI-DaySyms™) questionnaire: psychometric characteristics and responder thresholds.

BACKGROUND: The purpose of the current study was to determine the final content validation, psychometric characteristics, clinically meaningful improvement, and responder thresholds of the Clostridium difficile infection (CDI)-Daily Symptoms (CDI-DaySyms™) patient-reported outcome (PRO) questionnaire. METHODS: This validation study was part of two phase III studies (NCT01987895 and NCT01983683) conducted in patients with mild-to-moderate or severe CDI who completed the CDI-DaySyms™ daily throughout the treatment period. The questionnaire was evaluated in three stages: final PRO item content validation (Stage I); psychometric evaluation of reliability and construct validity (Stage II); and determination of clinically meaningful improvement and responder thresholds using distribution-based methods (Stage III). RESULTS: The analysis included 168 patients. Most patients were female and Caucasian with mild-to-moderate CDI. The mean age was 57.1 years. Initial item analysis supported by confirmatory factor analysis demonstrated the relevance of 10 items grouped into three distinct domains (Diarrhea Symptoms, Abdominal Symptoms, and Systemic/Other Symptoms). Domain scores demonstrated acceptable internal consistency and test-retest reliability, were sensitive to change, and correlated in expected directions with other relevant symptom and disease-severity measures. Responder thresholds were defined as score changes of - 1.00, - 0.80, and - 0.70 in the Diarrhea Symptoms, Abdominal Symptoms, and Systemic/Other Symptoms domains, respectively. CONCLUSIONS: The CDI-DaySyms™ is a valid measure of patient-reported CDI symptoms, with good measurement properties, which supports its utility as an endpoint in clinical studies. Further studies confirming responder thresholds based on anchor-based methods are required. TRIAL REGISTRATION: NCT01987895 , registered November 20, 2013; NCT01983683 , registered November 14, 2013.

Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson's disease: a multi-country Delphi-panel approach.

BACKGROUND: Lack of a global consensus on the definition of advanced Parkinson's disease (APD) and considerations for timing of device-aided therapies may result in heterogeneity in care. OBJECTIVES: To reach consensus among movement disorder specialists regarding key patient characteristics indicating transition to APD and guiding appropriate use of device-aided therapies in the management of PD symptoms. METHODS: A Delphi-panel approach was utilized to synthesize opinions of movement disorder specialists and build consensus. RESULTS: A panel was comprised of movement disorder specialists from 10 European countries with extensive experience of treating PD patients (mean =24.8 ± 7.2 years). Consensus on indicators of suspected APD and eligibility for device-aided therapies were based on motor symptoms, non-motor symptoms, and functional impairments. Key indicators of APD included: (i) motor-moderate troublesome motor fluctuations, ≥1 h of troublesome dyskinesia/day, ≥2 h "off" symptoms/day, and ≥5-times oral levodopa doses/day; (ii) non-motor-mild dementia, and non-transitory troublesome hallucinations; (iii) functional impairment-repeated falls despite optimal treatment, and difficulty with activities of daily living. Patients with good levodopa response, good cognition, and <70 years of age were deemed as good candidates for all three device-aided therapies. Patients with troublesome dyskinesia were considered good candidates for both levodopa-carbidopa intestinal gel and Deep Brain Stimulation (DBS). PD patients with levodopa-resistant tremor were considered good candidates for DBS. CONCLUSION: Identifying patients progressing to APD and suitable for device-aided therapies will enable general neurologists to assess the need for referral to movement disorder specialists and improve the quality of care and patient outcomes.

The CDI-DaySyms: Content Development of a New Patient-Reported Outcome Questionnaire for Symptoms of Clostridium difficile Infection.

OBJECTIVES: To develop a patient-reported outcome (PRO) questionnaire for symptoms of Clostridium difficile infection (CDI) following the US Food and Drug Administration PRO guidelines. METHODS: Patients' experiences of CDI symptoms were elicited in open-ended discussions with patients and nurses at five US sites (stage 1). A draft PRO measure was developed after demonstration of concept saturation. Two rounds of cognitive interviews were conducted with patients at three US sites (stage 2), with revision of the draft measure after each round. All patients were 18 years or older, with confirmed CDI. The study was conducted with input from a panel of five CDI experts in Europe and North America. RESULTS: Stage 1 included interviews with 18 patients and supplementary interviews with 6 nurses; 16 additional patients were interviewed in stage 2. Patients were representative of the general CDI population and were diverse in age, sex, and disease severity. Concept saturation was reached in stage 1. Items were organized in a draft conceptual framework with five hypothesized domains: diarrhea, abdominal discomfort, tiredness, lightheadedness, and other symptoms. Stage 2 demonstrated initial content validity of the 13-item draft daily diary (CDI-DaySyms). Participants reported that the questions were clear, relevant, and comprehensive. They were able to use the instructions to complete the diary correctly and considered the 24-hour recall period appropriate. CONCLUSIONS: The CDI-DaySyms captures symptoms relevant to patients undergoing CDI, demonstrating initial content validity. Final content and psychometric validity are being evaluated in a substudy comprising patients from two ongoing international clinical trials (ClinicalTrials.gov identifiers NCT01987895 and NCT01983683).

Psychometric Validation of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire: Results of the SYMPHONY Trial.

BACKGROUND: Disease-specific patient-reported outcome (PRO) instruments are important in assessing the impact of disease and treatment. The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire is the first instrument for quantifying pulmonary arterial hypertension (PAH) symptoms and impacts developed according to the 2009 US Food and Drug Administration PRO guidance; previous qualitative research in patients with PAH supported its initial content validity. METHODS: Content finalization and psychometric validation were conducted by using data from A Study of Macitentan in Pulmonary Arterial Hypertension to Validate the PAH-SYMPACT (SYMPHONY), a single-arm, 16-week trial with macitentan 10 mg in US patients with PAH. Item performance, Rasch analysis, and factor analyses were used to select the final item content of the PRO and to define its domain structure. Internal consistency, test-retest reliability, known-group and construct validity, sensitivity to change, and influence of oxygen on item performance were evaluated. RESULTS: Data from 278 patients (79% female; mean age: 60 years) were analyzed. Following removal of redundant/misfitting items, the final questionnaire has 11 symptom items across two domains (cardiopulmonary and cardiovascular symptoms) and 11 impact items across two domains (physical and cognitive/emotional impacts). Differential item function analysis confirmed that PRO scoring is unaffected by oxygen use. For all four domains, internal consistency reliability was high (Cronbach's alpha > 0.80), and scores were highly reproducible in stable patients (intraclass correlation coefficient: 0.84-0.94). Correlations with the Cambridge Pulmonary Hypertension Outcome Review questionnaire and the 36-item Medical Outcomes Study Short Form Survey were moderate to high ([r] = 0.34-0.80). The questionnaire differentiated well between patients with varying disease severity levels and was sensitive to improvements in clinician- and patient-reported disease severity. CONCLUSIONS: The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire is a brief, disease-specific PRO instrument possessing good psychometric properties that can be administered in clinical practice and clinical studies. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01841762; URL: www.clinicaltrials.gov.

Patient preferences for important attributes of bipolar depression treatments: a discrete choice experiment.

PURPOSE: The purpose of this study was to assess patient preferences regarding pharmacological treatment attributes for bipolar depression using a discrete choice experiment (DCE). METHODS: Adult members of an Internet survey panel with a self-reported diagnosis of bipolar depression were invited via e-mail to participate in a web-based DCE survey. Participants were asked to choose between hypothetical medication alternatives defined by attributes and levels that were varied systematically. The six treatment attributes included in the DCE were time to improvement, risk of becoming manic, weight gain, risk of sedation, increased blood sugar, and increased cholesterol. Attributes were supported by literature review, expert input, and results of focus groups with patients. Sawtooth CBC System for Choice-Based Conjoint Analysis was used to estimate the part-worth utilities for the DCE analyses. RESULTS: The analytical sample included 185 participants (50.8% females) from a total of 200 participants. The DCE analyses found weight gain to be the most important treatment attribute (relative importance =49.6%), followed by risk of sedation (20.2%), risk of mania (13.0%), increased blood sugar (8.3%), increased cholesterol (5.2%), and time to improvement (3.7%). CONCLUSION: Results from this DCE suggest that adults with bipolar depression considered risks of weight gain and sedation associated with pharmacotherapy as the most important attributes for the treatment of bipolar depression. Incorporating patient preferences in the treatment decision-making process may potentially have an impact on treatment adherence and satisfaction and, ultimately, patient outcomes.

Development and validation of a primary sclerosing cholangitis-specific patient-reported outcomes instrument: The PSC PRO.

Primary sclerosing cholangitis (PSC) is a chronic liver disease associated with inflammation and biliary fibrosis that leads to cholangitis, cirrhosis, and impaired quality of life. Our objective was to develop and validate a PSC-specific patient-reported outcome (PRO) instrument. We developed a 42-item PSC PRO instrument that contains two modules (Symptoms and Impact of Symptoms) and conducted an external validation. Reliability and validity were evaluated using clinical data and a battery of other validated instruments. Test-retest reliability was assessed in a subgroup of patients who repeated the PSC PRO after the first administration. One hundred two PSC subjects (44 ± 13 years; 32% male, 74% employed, 39% with cirrhosis, 14% with a history of decompensated cirrhosis, 38% history of depression, and 68% with inflammatory bowel disease [IBD]) completed PSC PRO and other PRO instruments (Short Form 36 V2 [SF-36], Chronic Liver Disease Questionnaire [CLDQ], Primary Biliary Cholangitis - 40 [PBC-40], and five dimensions [5-D Itch]). PSC PRO demonstrated excellent internal consistency (Cronbach alphas, 0.84-0.94) and discriminant validity (41 of 42 items had the highest correlations with their own domains). There were good correlations between PSC PRO domains and relevant domains of SF-36, CLDQ, and PBC-40 (R = 0.69-0.90; all P < 0.0001), but lower (R = 0.31-0.60; P < 0.001) with 5-D Itch. Construct validity showed that PSC PRO can differentiate patients according to the presence and severity of cirrhosis and history of depression (P < 0.05), but not by IBD (P > 0.05). Test-retest reliability was assessed in 53 subjects who repeated PSC PRO within a median (interquartile range) of 37 (27-47) days. There was excellent reliability for most domains with intraclass correlations (0.71-0.88; all P < 0.001). CONCLUSION: PSC PRO is a self-administered disease-specific instrument developed according to U.S. Food and Drug Administration guidelines. This preliminary validation study suggests good psychometric properties. Further validation of the instrument in a larger and more diverse sample of PSC patients is needed. (Hepatology 2018;68:155-165).

A history of health-related quality of life outcomes in psychiatry.

Health-related quality of life (HRQoL) is a multidimensional concept that includes subjective reports of symptoms, side effects, functioning in multiple life domains, and general perceptions of life satisfaction and quality. Rather than estimating it from external observations, interview, or clinical assessment, it is best measured by direct query. Due to a perception that respondents may not be reliable or credible, there has been some reluctance to use self-report outcomes in psychiatry. More recently, and increasingly, HRQoL assessment through direct patient query has become common when evaluating a range of psychiatric, psychological, and social therapies. With few exceptions, psychiatric patients are credible and reliable reporters of this information. This article summarizes studies that highlight the development, validation, and application of HRQoL measures in psychiatry. Thoughtful application of these tools in psychiatric research can provide a much-needed patient perspective in the future of comparative effectiveness research, patient-centered outcomes research, and clinical care.

La calidad de vida relacionada con la salud (CdVRS) es un concepto multidimensional que incluye la percepcíon subjetiva de los síntomas, los efectos secundarios, el funcíonamiento en múltiples aspectos de la vida y la percepción general de satisfacción y calidad de vida. Más que estimarla a partir de observaciones externas, la entrevista o la evaluación clínica, es mejor cuantificarla mediante preguntas directas. Ya que se ha considerado que los encuestados pueden no ser confiables o creíbles, en psiquiatría ha habido cierta reticencia a los resultados de auto-reporte. Más recientemente y en forma crecíente la determinación de la CdVRS mediante preguntas directas al paciente se ha hecho común en la evaluación de una serie de terapias psiquiátricas, psicológicas y sociales. Los pacientes psiquiátricos excepcionalmente son creíbles y confiables al entregar esta información. Este artículo resume estudios psiquiátricos que destacan el desarrollo, validación y aplicación de las mediciones de la CdVRS. La aplicación cuidadosa de estas herramientas en la investigación psiquiátrica puede proporcionar una perspectiva muy necesaria del paciente para el futuro de la investigación sobre comparación de eficacia, de la investigación acerca de los resultados centrados en el paciente y de los cuidados clínicos.

La qualité de vie liée à la santé (QdVLS), concept multi-dimensionnel, prend en compte des éléments subjectifs des symptômes, des effets secondaires, du fonctionnement dans différents domaines de la vie et de la perception générale de la satisfaction et de la qualité de vie. Son estimation par questions directes est préférable à celle d'observations externes, d'entretien ou d'évaluation clinique. En psychiatrie, l'utilisation de résultats auto déclarés a fait l'objet d'une certaine réticence en raison du sentiment d'un manque de fiabilité ou de crédibilité des personnes interrogées. L'évaluation de la QdVLS par interrogation directe du patient est de plus en plus utilisée ces derniers temps, pour évaluer une série de thérapies psychiatriques, psychologiques et sociales. À de rares exceptions près, les patients psychiatriques sont crédibles et fiables dans leurs réponses à ces évaluations. Cet article résume des études qui soulignent le développement, la validation et la mise en œuvre des mesures de la QdVLS en psychiatrie. Dans l'avenir, l'emploi judicieux de ces outils en recherche psychiatrique nous donnera le point de vue essentiel du patient en ce qui concerne la recherche d'efficacité comparative, la recherche des résultats centrés sur le patient et les soins cliniques.

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.

Evaluation of patient preference and willingness to pay for attributes of maintenance medication for chronic obstructive pulmonary disease (COPD).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD is characterized by poor treatment adherence, and patient medication preferences may contribute to adherence. METHODS: A discrete choice experiment with an internet panel drawn from the USA was used to evaluate preference and willingness to pay (WTP) of COPD patients for long-acting maintenance medications. Key attributes derived from earlier qualitative research (brief literature review and focus groups) with COPD patients on maintenance therapy included symptom relief, speed of feeling medication start to work, inhaler ease of use, rescue medication use, side effects, and monthly out-of-pocket co-pay. Patients were presented with hypothetical medications with different profiles and asked which they preferred. Utilities and marginal WTP in monthly co-pay dollars were estimated for all patients and by severity. RESULTS: Utilities for 515 participants were in the expected direction and highest for the most favorable attribute levels. Each attribute evaluated was important, and participants were willing to pay a premium to obtain each benefit. On average, WTP was as high as $US64 for complete symptom relief, $US59 for no side effects, $US32 to rarely use rescue medication, $US16 for a quick and easy to use inhaler, and $US13 for feeling medication work quickly (within 5 min; average WTP $US18/month for patients with severe/very severe COPD). CONCLUSION: As expected, efficacy and safety were most valued by patients; however, this study showed that other COPD medication attributes, such as rescue medication, ease of use, and feeling medication work quickly, are also important in patient preferences.

Patient-reported outcomes in insomnia: development of a conceptual framework and endpoint model.

This article describes qualitative research conducted with patients with clinical diagnoses of insomnia and focuses on the development of a conceptual framework and endpoint model that identifies a hierarchy and interrelationships of potential outcomes in insomnia research. Focus groups were convened to discuss how patients experience insomnia and to generate items for patient-reported questionnaires on insomnia and associated daytime consequences. Results for the focus group produced two conceptual frameworks: one for sleep and one for daytime impairment. Each conceptual framework consists of hypothesized domains and items in each domain based on patient language taken from the focus group. These item pools may ultimately serve as a basis to develop new questionnaires to assess insomnia.

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.

The anemia impact measure (AIM): development and content validation of a patient-reported outcome measure of anemia symptoms and symptom impacts in cancer patients receiving chemotherapy.

PURPOSE: To develop a patient-reported outcome instrument for measuring anemia symptoms and their impact in patients with chemotherapy-induced anemia (CIA). METHODS: Qualitative research was conducted using six focus groups and 24 interviews with 46 CIA patients, eight interviews in patients receiving chemotherapy with no CIA history and two interviews in patients successfully treated for CIA. Atlas.ti 5.0 was used to organize key concepts. Cognitive interviews with 16 CIA patients and assessment of relevance of each item to CIA by 10 clinicians were also conducted to evaluate content validity. RESULTS: Most CIA patients were white (76%) and female (83%), and the average age was 60 years. The most common cancer types were breast cancer (54%) and lung cancer (17%). Tiredness was the most prevalent symptom and rated as the most important by 83% of CIA patients; weakness, shortness of breath, lightheadedness, and dizziness were ranked next in importance. The final anemia impact measure (AIM) contains: (1) daily CIA symptom diary (9 items), and (2) impact of CIA-related tiredness (29 items covering daily living activities, social activities, cognitive function, and emotions). Cognitive interviews found that the AIM was relevant and easy to understand. CONCLUSIONS: The AIM assesses important patient-perceived CIA symptoms and their impact and was developed using extensive patient qualitative data.

Development and psychometric evaluation of 2 age-stratified versions of the Pediatric GERD Symptom and Quality of Life Questionnaire.

OBJECTIVES: The Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire (PGSQ) represents 2 related age-stratified tools developed to assess pediatric gastroesophageal reflux disease (GERD). These include the PGSQ-Cp (for children ages 2 to 8 years, parent/caregiver report) and the PGSQ-A (for adolescents ages 9-17 years). The objective of the present study was to develop and evaluate PGSQ measurement properties. MATERIALS AND METHODS: The PGSQ items were generated based on information from focus groups, expert clinician review, and cognitive debriefing interviews. The symptoms of pediatric GERD and the effect of these symptoms were addressed. The tools were evaluated in a 3-week psychometric evaluation with participants from 11 clinical sites in the United States. The study included other measures such as the Pediatric Quality of Life questionnaire (PedsQL) and clinician-rated GERD severity. After item reduction, internal consistency, reproducibility, construct validity, known-group validity, and responsiveness were assessed. RESULTS: The 231 participants included 75 parents of children ages 2 to 8 years and 75 children ages 9 to 17 years with GERD and 41 parents of children and 40 children ages 9 to 17 years without GERD. Exploratory factor analysis demonstrated 4 symptom subscales for the PGSQ-Cp and 3 symptom subscales for the PGSQ-A. Both had subscales for total impact and school impact. High to moderate internal consistency was observed, ranging from 0.76 to 0.96 for the PGSQ-Cp and from 0.67 to 0.94 for the PGSQ-A. The PGSQ significantly differentiated between patients with GERD and controls (P < 0.0001, PGSQ-Cp; P < 0.0022-0.0001, PGSQ-A) and demonstrated responsiveness. CONCLUSIONS: These results support the reliability, validity, and responsiveness of both versions of the PGSQ. The instruments should be useful for clinical studies.

Psychometric evaluation of a Patient-Rated Most Troubling Symptom Scale for Depression: findings from a secondary analysis of a clinical trial.

The objective of this study was to assess the reliability and validity of the presence and severity of eight symptoms rated on the Patient-Rated Troubling Symptoms for Depression (PaRTS-D) instrument used in a risperidone augmentation trial. PaRTS-D total score (sum of four most severe symptoms) and global total score (sum of all eight symptoms) were determined weekly. Clinician-rated and patient-rated instruments were completed at selected time points. Statistical tests of reliability and validity were performed. The frequency of symptoms rated as one of the four most troubling were sadness, 73.5%; trouble concentrating, 70.9%; reduced involvement, 61.9%; tense/uptight, 56.0%; reduced sleep, 52.2%; negative thoughts, 42.9%; inability to feel emotion, 26.5%; and reduced appetite, 13.1%. Evidence of two factors (somatic-related and depression-related) was observed in the exploratory factor analysis. Baseline PaRTS-D total score correlated with the Quality of Life Enjoyment and Satisfaction Questionnaire and the Sheehan Disability Scale. PaRTS-D global total score showed high internal consistency reliability. PaRTS-D total score and global total score distinguished between patients with high and low-Hamilton Rating Scale for Depression Scores and were responsive to Patient Global Improvement Scale changes. The PaRTS-D total score minimal important difference was 4-5 points. In conclusion, PaRTS-D may be useful in symptom presence and severity assessments from the patient's perspective and as an adjunctive to other instruments in major depressive disorder diagnosis and response to treatment.