Antipsychotic treatment experiences of people with bipolar I disorder: patient perspectives from an online survey.

BACKGROUND: Oral antipsychotic (AP) medications are frequently prescribed to people with bipolar I disorder (BD-I). A cross-sectional online survey examined the experiences of people living with BD-I with a history of recent AP use. METHODS: Adults with self-reported physician-diagnosed BD-I (N = 200) who received oral APs during the prior year completed a survey on AP-related experiences, including side effects and their perceived burden on social functioning, adherence, and work. Items also assessed preferences for trade-offs (balancing symptom management and side effects) when considering a hypothetical new AP. The perceived impact of specific, prevalent side effects on adherence, work, and preferences for a hypothetical AP were also examined. Analyses were descriptive. RESULTS: The survey sample had a mean age of 43.2 (SD = 12.4) years, was 60% female, and 31% nonwhite. Almost all participants (98%) had experienced AP side effects. Common self-reported side effects were feeling drowsy or tired (83%), lack of emotion (79%), anxiety (79%), dry mouth (76%), and weight gain (76%). Weight gain was cited as the most bothersome side effect, rated by most participants (68%) as "very" or "extremely bothersome." Nearly half of participants (49%) reported that AP side effects negatively impacted their job performance; almost all (92%) reported that side effects - most commonly anxiety and lack of emotion - negatively impacted social relationships (e.g., family or romantic partners). The most commonly-reported reason for stopping AP use was dislike of side effects (48%). Side effects most likely to lead to stopping or taking less of AP treatment included "feeling like a 'zombie'" (29%), feeling drowsy or tired (25%), and weight gain (24%). When considering a hypothetical new AP, the most common side effects participants wanted to avoid included AP-induced anxiety (50%), weight gain (48%), and "feeling like a 'zombie'" (47%). CONCLUSIONS: Side effects of APs were both common and bothersome, and impacted social functioning, adherence, and work. Findings highlight the prevailing unmet need for new APs with more favorable benefit-risk profiles.

The Inflammatory Bowel Disease Questionnaire in Randomized Controlled Trials of Treatment for Ulcerative Colitis: Systematic Review and Meta-Analysis.

PURPOSE: The 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32) is the most frequently used instrument to capture disease-specific quality of life in randomized clinical trials for ulcerative colitis. This review and meta-analysis provides the first synthesis of evidence regarding the sensitivity of IBDQ-32 total and domain scores to treatment efficacy. METHODS: A systematic literature search and risk-of-bias assessment yielded 14 articles that were included in the primary analysis. Treatments were categorized as efficacious if they met the primary efficacy endpoint (which was not the IBDQ-32); otherwise they were categorized as non-efficacious. A continuous measure of treatment efficacy was calculated for each primary efficacy endpoint. Meta-analysis using random-effects models compared standardized mean differences in IBDQ-32 total and domain change scores between target dose and control arms. Meta-regression compared the association between treatment efficacy and these outcomes. RESULTS: Studies with efficacious treatments showed larger mean improvements relative to controls in IBDQ-32 total scores and all 4 domains (Hedges' g range: 0.49 to 0.67; P<0.001 for all). At the same time, patients in studies with non-efficacious treatments showed small and nonsignificant improvements in these outcomes relative to controls (Hedges' g range: 0.05 to 0.23; P>0.09 for all). Meta-regression models showed that the magnitude of treatment efficacy was a positive predictor of these same IBDQ-32 outcomes. CONCLUSIONS: These analyses found that IBDQ-32 scores are sensitive to treatment. The results provided here support the use of the IBDQ-32 to capture treatment benefits on quality of life for patients with ulcerative colitis.

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.

Associations between Health-Related Quality of Life and Self-Reported Emergency Room Department Visits and Inpatient Hospitalizations: Insights from a Secondary Data Analysis of Patients with Light-Chain (AL) Amyloidosis.

INTRODUCTION: Light-chain (AL) amyloidosis is a rare, progressive, and typically fatal disease. Health-related quality of life (HRQoL) has been shown to be a significant prognostic factor associated with clinical outcomes such as survival and response to treatment. A better understanding of how patterns of HRQoL may be prospectively associated with costly healthcare resource utilization, such as emergency department (ED) visits and inpatient hospitalizations, is warranted. METHODS: A secondary data analysis of a non-interventional, longitudinal online study of patients with AL amyloidosis (n = 224) was conducted. Negative binomial regression models were used to examine whether initial HRQoL scores (as measured by the SF-36v2® Health Survey [SF-36v2], where higher scores reflect better HRQoL) and changes in HRQoL were associated with the number of ED visits and inpatient hospitalizations during a 12-month period. Incidence rate ratios were interpreted by 5-point decrements in initial HRQoL scores and minimally important changes in HRQoL change scores. RESULTS: There were significant inverse associations between initial SF-36v2 scores and subsequent rates of ED visits and inpatient hospitalizations across all domains and summary components (p < 0.05 for all). In contrast, changes in physical, but not mental, functioning were associated with rates of ED visits and inpatient hospitalizations during a 12-month period of observation. CONCLUSION: Scores from patient-reported HRQoL surveys may be helpful in identifying patients at risk of future ED visits and hospital admissions, and may serve as a proxy for disease severity. Such information can provide stakeholders with insight into the humanistic and societal cost associated with AL amyloidosis.

Patient-reported treatment-related symptom burden for patients with advanced melanoma in Canada.

BACKGROUND: Little is known on the impact of emerging treatments for advanced melanoma (stages III and IV) on patients' functioning and well-being. The objective of this study was to describe the patient-reported treatment-related symptom (TRS) burden in advanced melanoma. METHOD: Twenty-nine in-depth, qualitative interviews were conducted among adult patients with advanced melanoma in Canada using a semi-structured interview method. Interviews were transcribed verbatim, and key concepts were identified using a grounded theory analytic approach. RESULTS: The 29 patients reported 13 unique treatment journeys involving the following drug therapy categories: cytotoxic chemotherapies, CTLA-4 inhibitors, BRAF or MEK inhibitors, and PD-1 inhibitors. Patients typically underwent multiple treatment episodes over time. Common TRSs included nausea, fatigue, diarrhea or constipation, and skin rashes. Patients described these as impacting their physical functioning, ability to perform activities of daily living, social functioning, and overall quality of life. CONCLUSION: Our findings provide a description of the patient's experience with treatment for advanced melanoma. Our sample included patients typically diagnosed in mid-life, facing an urgent sequence of medical procedures and a pharmacological treatment journey that was burdensome. There is a need for less toxic and more efficacious treatments earlier in the patient journey to alleviate the impact of advanced melanoma treatment on patients' health-related quality of life.

Psychometric validation of the work productivity and activity impairment questionnaire in ulcerative colitis: results from a systematic literature review.

Patients with ulcerative colitis, a type of inflammatory bowel disease, report negative impacts of disease symptoms on work-related outcomes, including absenteeism and presenteeism. As a way to better understand the impact of this disease and its treatment on work-related outcomes, the current review examines the use of the Work Productivity and Activity Impairment Questionnaire (WPAI), a patient-reported outcomes measure of absenteeism, presenteeism, and impairment in other activities, in studies of patients with ulcerative colitis. This review assesses the measurement properties of the WPAI in this patient population: its reliability, construct validity, ability to detect change, and responsiveness to effective treatments. Relevant data were extracted from 13 sources (journal articles and conference posters) identified following a systematic review of the published and gray literature. The evidence supports the WPAI as having test-retest reliability (reproducibility) over time; convergent validity, as indicated by moderate correlations with measures of quality of life and moderate-to-strong correlations with measures of disease activity; known-groups validity, as indicated by differences in WPAI scores between patients with active and inactive disease; ability (sensitivity) to detect change, as indicated by substantial improvement in scores for patients who achieve remission, accompanied by substantial worsening of scores for patients who relapse; and, responsiveness to treatment, with improvements in scores following treatments that reduce disease activity. Limitations included a lack of available evidence from randomized-controlled trials that could speak more directly to the WPAI's responsiveness to treatment. In conclusion, we recommend the use of the WPAI for measuring work outcomes in both observational studies and interventional trials that include patients with ulcerative colitis.

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.

Improving Medical Communication in Migraine Management: A Modified Delphi Study to Develop a Digital Migraine Tracker.

OBJECTIVE: This study aimed to identify the essential content and amount of information to be collected from people with migraine via a patient-facing smartphone-based migraine tracker for them to share with clinicians during live discussions to assist in optimizing migraine management. The proposed tracker is intended for use in non-interventional research to evaluate disease burden in episodic migraine and chronic migraine patients as assessed by demographic and clinical characteristics and health resource utilization in an integrated delivery network setting. The proposed tracker is not intended for commercial purposes. BACKGROUND: Epidemiological studies suggest migraine is underdiagnosed and undertreated. Studies of patient-clinician interactions suggest that effective medical communication may help address these issues. METHODS: Four migraine practice leaders, an epidemiologist with extensive migraine experience, and a measurement expert took part in a modified Delphi panel process to identify data elements that could be collected from people with migraine through a smartphone-based migraine tracker. Importantly, the proposed tracker would not be intended to replace the patient-clinician encounter but to support the encounter through enabling the patient to document migraine symptoms and experiences in a timely and accurate manner for sharing with a clinician as part of a broader face-to-face discussion. The panel reviewed questions derived from the existing migraine diaries in the public domain, those used in clinical trials, and patient-centric surveys assessing the impact of migraine on physical function and other related concepts. Key considerations included identification of the most clinically useful data elements for a shared communication tool for people with migraine under the care of a clinician. The panel also identified numerous functionality requirements for such a tool and provided recommendations on the most effective way to present results to a clinician. RESULTS: The expert panel opined that people with migraine may value the ability to capture a relatively broad range of information for their own migraine-tracking purposes, while clinicians will likely find greater value in a small set of data relevant to the management of migraine. The panel identified the 3 most essential concepts in categories of data for a clinician, for which they coined the term "The 3 Fs": Frequency of days with headache; Frequency of acute medication usage; and Functional impairment. Information on the frequency of days with headache was felt to combine with the information on the frequency of acute medication usage to provide essential insights into current migraine management strategy and its outcomes, and to assist considerations of preventive measures. Functional impairment was treated as an effective surrogate for headache severity and was assessed based on the following: degree of difficulty in performing activities of daily living, impact on absenteeism (taking leave from work or cancelling/avoiding other activities) and presenteeism (performing work or other daily activities, with reduced productivity/capability), and amount of rest required as a result of a migraine attack. The modified Delphi panel process resulted in the selection of 13 questions in 8 categories to elicit sufficient and meaningful data comprising headache occurrence, symptoms, daily/preventive and as-needed/acute medication usage, triggers, ability to concentrate, and functional impairment. The panel also agreed that the tracker should generate 2 distinct reports: one for people with migraine that would include a wider range of data about symptoms and perceived triggers, and a targeted report for the clinician that would place prime emphasis on the 3 Fs for aggregating the results of each headache occurrence and the trend over time. CONCLUSIONS: A system that easily captures critical data elements about migraine, with specific feedback displays for patients to share with clinicians during live discussions, may offer some benefit to people with migraine and their clinicians by facilitating more objective communication and optimizing management. The tracker's output may enable people with migraine to track a wide range of data for their own purposes, allowing them to better understand their condition, while a synthesized view of the selected data may support more informed clinical decision-making for the clinician and individualized, evidence-based discussion with the patient. As a result, this shared decision-making tool may enable patients to more accurately convey essential migraine information during live patient-clinician discussions to drive improved management and patient outcomes.

Burden of Ulcerative Colitis on Functioning and Well-being: A Systematic Literature Review of the SF-36® Health Survey.

BACKGROUND AND AIMS: This review is the first to evaluate the burden of ulcerative colitis [UC] on patients' quality of life by synthesizing data from studies comparing scores from the SF-36® Health Survey, a generic measure assessing eight quality-of-life domains, between UC patients and matched reference samples. METHODS: A systematic review of the published literature identified articles reporting SF-36 domains or physical and mental component summary scores [PCS, MCS] from UC and reference samples. Burden of disease for each SF-36 domain was then summarized across studies by comparing weighted mean differences in scores between patient and reference samples with minimally important difference thresholds. RESULTS: Thirty articles met pre-specified inclusion criteria. SF-36 scores were extracted from five samples of patients with active disease, 11 samples with a mixture of disease activity, five samples of patients in clinical remission, and 13 samples of patients following proctocolectomy with ileostomy or ileal pouch-anal anastomosis, along with respective reference samples. Clinically meaningful burden was observed in samples with active or mixed disease activity [deficits: PCS = 5.6, MCS = 5.5] on all SF-36 domains except Physical Functioning. No burden was observed in samples in remission or post-surgical patients [deficits: PCS = 0.8, MCS = 0.4] except for the General Health perception domain. CONCLUSIONS: Patients with active UC experience a clinically meaningful burden of disease across most aspects of quality of life. Patients with inactive UC exhibit negligible disease burden and are comparable to the general population on most quality-of-life outcomes. Thus, treatments which effectively induce and maintain remission may restore physical and mental health status.

Humanistic burden of disease for patients with advanced melanoma in Canada.

BACKGROUND: Metastatic melanoma is a highly aggressive cancer, often striking in the prime of life. This study provides new information directly from advanced melanoma (stage III and IV) patients on how their disease impacts their health-related quality of life (HRQL). METHODS: Twenty-nine in-depth, qualitative interviews were conducted with adult patients with advanced melanoma in Canada. A semi-structured interview guide was used. Interviews were transcribed verbatim and key concepts were identified using a grounded theory analytic approach. RESULTS: Many patients' journeys began with the startling diagnosis of an invasive disease and a vastly shortened life expectancy. By the time they reached an advanced stage of melanoma, these patients' overall functioning and quality of life had been greatly diminished by this quickly progressing cancer. The impact was described in terms of physical pain and disability, emotional distress, diminished interactions with friends and family, and burden on caregivers. CONCLUSION: Our findings provide evidence of signs, symptoms, and functional impacts of advanced melanoma. Signs and symptoms reported (physical, mental, and social) confirm and expand on those reported in the existing clinical literature. Primary care physicians should be better trained to identify melanomas early. Oncology care teams can improve on their current approaches for helping patients navigate treatment options, with information about ancillary services to mitigate disease impacts on HRQL, such as mental health and social supports, as well as employment or financial support services.

Psychometric validation of the SF-36® Health Survey in ulcerative colitis: results from a systematic literature review.

PURPOSE: To conduct a systematic literature review of the reliability, construct validity, and responsiveness of the SF-36® Health Survey (SF-36) in patients with ulcerative colitis (UC). METHODS: We performed a systematic search of electronic medical databases to identify published peer-reviewed studies which reported scores from the eight scales and/or two summary measures of the SF-36 collected from adult patients with UC. Study findings relevant to reliability, construct validity, and responsiveness were reviewed. RESULTS: Data were extracted and summarized from 43 articles meeting inclusion criteria. Convergent validity was supported by findings that 83% (197/236) of correlations between SF-36 scales and measures of disease symptoms, disease activity, and functioning exceeded the prespecified threshold (r ≥ |0.40|). Known-groups validity was supported by findings of clinically meaningful differences in SF-36 scores between subgroups of patients when classified by disease activity (i.e., active versus inactive), symptom status, and comorbidity status. Responsiveness was supported by findings of clinically meaningful changes in SF-36 scores following treatment in non-comparative trials, and by meaningfully larger improvements in SF-36 scores in treatment arms relative to controls in randomized controlled trials. The sole study of SF-36 reliability found evidence supporting internal consistency (Cronbach's α ≥ 0.70) for all SF-36 scales and test-retest reliability (intraclass correlation coefficient ≥0.70) for six of eight scales. CONCLUSIONS: Evidence from this systematic literature review indicates that the SF-36 is reliable, valid, and responsive when used with UC patients, supporting the inclusion of the SF-36 as an endpoint in clinical trials for this patient population.

Light Chain (AL) Amyloidosis: The Journey to Diagnosis.

BACKGROUND: Light chain (AL) amyloidosis is a rare, complex disease associated with significant morbidity and mortality. Delays in diagnosis are common and may have detrimental consequences on patients' prognosis. Too little is known regarding the patient journey to diagnosis. OBJECTIVE: The objective of this study was to describe the patient-reported journey to a correct diagnosis for AL amyloidosis. METHODS: Using a mixed-methods approach, data were collected from clinician (n = 4) and patient (n = 10) interviews and a survey of community-based patients with AL amyloidosis (n = 341). Data were used to document the patient experience between the onset of symptoms and the receipt of a diagnosis. RESULTS: Delays in diagnosis were common. Qualitative and quantitative data indicated that initial symptoms were varied and similar to other more prevalent diseases. Two themes regarding the journey to diagnosis emerged: (1) barriers to an early diagnosis; and (2) the emotional toll of the journey. Time to diagnosis was heavily influenced by how patients interpreted their initial symptoms, whether they sought early medical help, and challenges associated with making differential diagnoses. Survey results indicate that patients with primary cardiac involvement were more likely to receive a delayed diagnosis than those with primary kidney involvement. Patients described mixed emotions associated with the eventual diagnosis of AL amyloidosis. CONCLUSIONS: These data support a need for better early identification and support for patients seeking a diagnosis. Increasing clinician awareness may reduce the time to diagnosis. Additional research is needed to identify optimal diagnostic testing to reduce delays in treatment initiation and subsequent severe impacts on health.

Tofacitinib in Patients with Ulcerative Colitis: Health-Related Quality of Life in Phase 3 Randomised Controlled Induction and Maintenance Studies.

BACKGROUND AND AIMS: Tofacitinib is an oral, small molecule Janus kinase [JAK] inhibitor that is being investigated for ulcerative colitis [UC]. We evaluated health-related quality of life [HRQoL] in tofacitinib UC Phase 3 studies. METHODS: Patients ≥ 18 years old in OCTAVE Induction 1 [N = 598] and 2 [N = 541] with moderately to severely active UC were randomised [1:4] to placebo or tofacitinib 10 mg twice daily [BID] for 8 weeks. Subsequently, OCTAVE Sustain re-randomised [1:1:1] clinical responders [N = 593] from induction studies to placebo, tofacitinib 5 mg BID, or 10 mg BID, for 52 weeks. Inflammatory Bowel Disease Questionnaire [IBDQ] and SF-36v2® Health Survey [SF-36v2] assessed HRQoL. RESULTS: In OCTAVE Induction 1 and 2, mean changes from baseline IBDQ were greater with tofacitinib 10 mg BID at Week 8 [28.9 and 31.5] versus placebo [15.4 and 17.2; p < 0.0001]; mean changes from baseline SF-36v2 Physical and Mental Component Summaries [PCS/MCS] were also greater with 10 mg BID [PCS: 6.8 and 6.8; MCS: 6.8 and 7.6] versus placebo [PCS: 2.5 and 4.6; MCS: 3.5 and 4.4; p < 0.01]. In OCTAVE Sustain atWeek 52, changes in IBDQ were maintained with tofacitinib 5 mg [-1.3] and 10 mg BID [0.6], and larger with placebo [-20.2; p < 0.0001]. Changes in SF-36v2 PCS/MCS were also maintained with 5 mg [PCS: 0.0; MCS: -1.0] and 10 mg BID [PCS: 0.3; MCS: 0.1] versus placebo [PCS: -5.2; MCS: -6.7; p < 0.0001] at Week 52 in OCTAVE Sustain. CONCLUSIONS: Tofacitinib 10 mg BID induction therapy significantly improved HRQoL versus placebo at Week 8. Improvements were maintained through 52 weeks' maintenance therapy with tofacitinib 5 mg and 10 mg BID. CLINICALTRIALS.GOV REGISTRATION NUMBERS: NCT01465763, NCT01458951 and NCT01458574.

Treatment Tolerability in Patients with Immunoglobulin Light-Chain Amyloidosis.

BACKGROUND: Immunoglobulin light-chain amyloidosis (AL amyloidosis) is a rare and often fatal disease for which there is currently no treatment approved by the US Food and Drug Administration or the European Medicines Agency. Treatment options, which are typically based on therapies for multiple myeloma and are used off-label, are associated with substantial adverse events (AEs). Because the severity of AEs is often determined by clinicians, evaluations of treatment tolerability may not fully consider patients' own experience with treatment. OBJECTIVES: To explore the prevalence of AEs and treatment tolerability problems as reported by patients who received therapies for AL amyloidosis, and to examine the effects of AEs on treatment continuation and on health-related quality of life (HRQOL). METHODS: Patients with AL amyloidosis were recruited for this noninterventional, longitudinal, online survey. The patients responded to survey items regarding demographics, disease characteristics, most recent AL amyloidosis treatment, and HRQOL. The study analyses are based on data collected during the 6-month follow-up survey and are restricted to patients who completed the baseline and 6-month surveys and received treatment for AL amyloidosis within 6 months before the follow-up survey. RESULTS: A total of 100 patients met the inclusion criteria and were included in the study. The patients self-reported having a variety of AEs, which ranged in severity. Overall, 69.4% of patients had problems tolerating their treatment in the past 6 months, of whom 22% discontinued at least 1 therapy. In addition, approximately 33% of patients reduced their AL amyloidosis treatment because of AEs. Most often reported AEs included fatigue (83%), shortness of breath (53%), nausea (52%), and diarrhea (51%). Overall, 50% of the patients reported that their treatment was moderately well-tolerated and 41% said it was very well-tolerated. Those whose treatment was not well-tolerated had significantly worse HRQOL than patients whose treatment was well-tolerated. CONCLUSIONS: Patient-reported experiences should be considered by clinicians when making treatment-related decisions. More research is needed to explore additional factors that may contribute to treatment discontinuation in patients with AL amyloidosis.

Psychometric validation of the SF-36 Health Survey in light chain amyloidosis: results from community-based and clinic-based samples.

BACKGROUND: Light chain (AL) amyloidosis, a rare and life-threatening protein misfolding disorder, causes organ damage and severely impacts health-related quality of life (HRQoL). No patient-reported outcome (PRO) HRQoL measure has been validated for use in an AL amyloidosis patient population, leaving a gap for researchers conducting observational studies and clinical trials for drug development. The SF-36 Health Survey (SF-36) has been the most frequently used PRO in AL amyloidosis studies to date, and early qualitative validation studies support its use in this population. The aim of this study was to assess the psychometric properties of the SF-36 among patients with AL amyloidosis. METHODS: Data from community-based (n=341) and clinic-based (n=1,438) observational studies were used to document the psychometric properties of the SF-36 in this disease population. Reliability was estimated using internal consistency (Cronbach's alpha) and test-retest reliability (intraclass correlation). Convergent validity, known-groups validity, and the ability to detect change were assessed with available criterion variables. RESULTS: Scale reliability (Cronbach's alpha ≥0.780 for all scores) and test-retest reliability (intraclass correlation coefficients ≥0.731 for all) were acceptable. Scale convergent validity was supported by strong correlations with conceptually related measures. Mean SF-36 scores varied by response to treatment (P<0.05 for all scores) and a self-reported measure of disease severity (P<0.001 for all scores). Data indicate that the SF-36 is sensitive to changes in other measures over time. CONCLUSION: This study provided clear and consistent evidence of the psychometric properties of the SF-36 in both community-based and clinic-based samples of patients with AL amyloidosis.

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.

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

OBJECTIVE: 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. METHODS: In a prospective, observational study, adults with episodic migraine (EM) or chronic migraine (CM) used an eDiary to complete the MPFID (assessing daily impacts of migraine on physical function) and a headache diary (capturing migraine days, migraine pain intensity, and migraine interference) each day, and other PRO instruments related to migraine. Item-level evaluation, item response theory (IRT), and exploratory factor analysis (EFA) methods were applied to identify domains, select final MPFID items, and develop scoring procedures. Psychometric properties of the final 13-item MPFID were evaluated using confirmatory factor analysis and tests of reliability (Cronbach's α for internal consistency and intra-class correlation [ICC] for test-retest) and validity (convergent and known-groups). RESULTS: The study enrolled 569 adults with chronic or episodic migraine, mean (SD) age 39.9 (12.0) years and 87.2% female. Item-level analyses based on interim data informed selection of a set of 13 items for the MPFID, through evaluation of floor/ceiling effects, item-to-item correlations, factor loadings, and IRT-based fit/misfit statistics. Two domain scores (EA: Impact on Everyday Activities; PI: Physical Impairment) and a global item score for impact on everyday activities were identified. EA and PI domains exhibited high internal consistency (α = 0.97; α = 0.93) and good test-retest reliability among stable subjects (ICCs = 0.74 and 0.77). Convergent validity was demonstrated by moderate correlations (r = ±0.50-0.68; P < .0001) between MPFID domain scores and number of migraine days, headache days, bed days, and other migraine-related PRO instruments. EA and PI scores differentiated between groups who varied by number of migraine days, migraine interference levels, migraine pain intensity, and median split groups of scores based on other PROs instruments (P < .05). CONCLUSIONS: The MPFID has robust psychometric properties (ie, reliability and validity). Findings supported two distinct domains about the impact of migraine on physical functioning: Impact on Everyday Activities and Physical Impairment. Both domain scores showed evidence of excellent reliability and construct validity in assessing the impacts of migraine on physical functioning.

A longitudinal evaluation of health-related quality of life in patients with AL amyloidosis: associations with health outcomes over time.

Light chain (AL) amyloidosis is a rare disease associated with significant, irreversible organ dysfunction and high case fatality. An observational study was conducted to assess health-related quality of life (HRQoL) in patients treated for AL amyloidosis between 1994 and 2014 with both high dose melphalan and stem cell transplantation (HDM/SCT) or non-SCT chemotherapy regimens. The SF-36v1® Health Survey (SF-36) was administered to assess HRQoL during clinic visits. Analysis of variance was used to compare pre- and post-treatment HRQoL within each treatment group to an age- and gender-adjusted general population (GP) normative sample. Cox proportional hazard models were fit to examine associations between pre-treatment levels of HRQoL and mortality within 1 and 5 years after initiating specific treatment regimens (HDM/SCT: n = 402; non-SCT chemotherapy regimens: n = 172). Among patients who received HDM/SCT, there were significant improvements following treatment in vitality, social functioning, role-emotional and mental health. Worse pre-treatment SF-36 physical component scores were associated with a greater risk of mortality in both treatment groups and follow-up periods (P ≤ 0·005 for both). [Correction added on 20 October 2017, after first online publication: This P value has been corrected]. Using HRQoL assessments in every physician visit or treatment may provide valuable insights for treating rare conditions like AL amyloidosis.