Correction: The Patient Experience of Acute Lymphoblastic Leukemia and Its Treatment: Social Media Review.

[This corrects the article DOI: 10.2196/39852.].

Validation of NASH-CHECK: a novel patient-reported outcome measure for nonalcoholic steatohepatitis.

BACKGROUND: Standardized measures for evaluating patients' experiences with nonalcoholic steatohepatitis (NASH) and their perceived changes with treatment in clinical trials have been limited. To meet this need, a patient-reported outcome (PRO) measure, NASH-CHECK, was developed to evaluate symptoms and health-related quality of life for patients with NASH. The objective of this study was to conduct a quantitative evaluation of the psychometric properties of NASH-CHECK. METHODS: The study used data from a phase 2, randomized controlled trial of adult patients with NASH (NCT02855164). Analyses were conducted to determine the optimal scoring of NASH-CHECK and to evaluate reliability, construct validity, and ability to detect change in NASH-CHECK scale scores. RESULTS: Data were available for 253 patients with NASH (61% female; mean [standard deviation] age = 53 [12] years). Following initial item-level analyses, including correlations and exploratory factor analysis, three items were removed from the measure. Confirmatory factor analysis supported the formation of four multi-item scales (Cognitive Symptoms, Activity Limitations, Social Impact, and Emotional Impact) and five single-item scales (Abdominal Pain, Abdominal Bloating, Fatigue, Sleep, and Itchy Skin). Psychometric analyses of the final NASH-CHECK scales provided support for their internal reliability, test-retest reliability, construct validity, and ability to detect change. CONCLUSION: The results support NASH-CHECK as a reliable, valid, and responsive measure to assess patients' perspectives of symptoms and the health-related quality of life impact of NASH in clinical trials and in routine practice.

The Patient Experience of Acute Lymphoblastic Leukemia and Its Treatment: Social Media Review.

BACKGROUND: Adult patients with acute lymphoblastic leukemia (ALL) report substantial disease- and treatment-related impacts on their health-related quality of life (HRQOL). Patient-reported information (PRI) shared on social media may provide a distinct opportunity to understand the patient experience outside of formal research contexts and help inform the development of novel therapies. OBJECTIVE: This qualitative social media review aimed to assess PRI shared on social media websites to gain a better understanding of the symptom, HRQOL, and treatment impacts on individuals with ALL. METHODS: We identified English-language posts on 3 patient advocacy websites (Patient Power, The Patient Story, and Leukaemia Care) and YouTube that included PRI about experiences with ALL or ALL treatments shared by adults (aged ≥18 years) with a self-reported ALL diagnosis. Patients' demographic and disease characteristics were extracted from posts (where available), and the posts were analyzed thematically. A network analysis was conducted to delineate possible associations among ALL symptoms, HRQOL impacts, and treatment-related symptoms and impacts. RESULTS: Of the 935 social media posts identified, 63 (7%) met the review criteria, including 40 (63%) videos, 5 (8%) comments posted in response to videos, and 18 (29%) blog posts. The 63 posts were contributed by 41 patients comprised of 21 (51%) males, 18 females (44%), and 2 (5%) whose gender was not reported. Among the patients, 13 (32%) contributed >1 source of data. Fatigue (n=20, 49%), shortness of breath (n=13, 32%), and bruising (n=12, 29%) were the symptoms prior to treatment most frequently discussed by patients. Patients also reported impacts on personal relationships (n=26, 63%), psychological and emotional well-being (n=25, 61%), and work (n=16, 39%). Although inpatient treatment reportedly restricted patients' independence and social functioning, it also provided a few patients with a sense of safety. Patients frequently relied on their doctors to drive their treatment decisions but were also influenced by family members. The network analysis indicated that disease-related symptoms were primarily associated with patients' physical functioning, activities of daily living, and ability to work, while treatment-related symptoms were primarily associated with emotional well-being. CONCLUSIONS: This social media review explored PRI through a thematic analysis of patient-contributed content on patient advocacy websites and YouTube to identify and contextualize emergent themes in patient experiences with ALL and its treatments. To our knowledge, this is the first study to leverage this novel tool to generate new insights into patients' experiences with ALL. Patients' social media posts suggest that inpatient care for ALL is associated with restricted independence and social functioning. However, inpatient care also provided a sense of safety for some patients. Studies such as this one that capture patients' experiences in their own words are valuable tools to further our knowledge of patient outcomes with ALL.

A Review of Labeling Based on Patient-Reported Outcome Endpoints for New Oncology Drugs Approved by the European Medicines Agency (2017-2021).

OBJECTIVE: A review of new oncology indications approved by the European Medicines Agency (EMA) for 2012-2016 showed that 33% of new drugs had labeling based on patient-reported outcomes (PROs). We reviewed labeling text based on PRO endpoints for new oncology indications approved during 2017-2021. METHODS: New oncology drugs approved by EMA to treat indications of cancers during 2017-2021 were identified from the EMA website. PRO-related language reported in EMA summaries of product characteristics (SmPCs) were summarized and compared with similar findings reported for oncology indications approved during 2012-2016. RESULTS: Review documents by the EMA during 2017-2021 were available for 49 new oncology drugs for 70 cancer indications. Submissions for 52 (74.3%) of the 70 indications included PRO data for EMA review. Of all submissions, 14 (20.0%) approvals contained PRO-related language in the SmPC. Broad concepts such as health-related quality of life were most common and found in 8 of 14 (57.1%) PRO-related labels. CONCLUSION: PRO-related language appeared in SmPCs for 20% of all indications of new oncology drugs approved by EMA during 2017-2021 compared with approximately 33% of EMA approvals during 2012-2016. PRO-related labeling during the same periods showed a greater decline (from 47% to 27%) for indications of new oncology drugs that also included PRO data. One possible reason for this decline may be the increase in open-label studies from 62% between 2012 and 2016 to approximately 79% between 2017 and 2021.

Patient Perceptions Regarding Ciltacabtagene Autoleucel Treatment: Qualitative Evidence From Interviews With Patients With Relapsed/Refractory Multiple Myeloma in the CARTITUDE-1 Study.

INTRODUCTION: Ciltacabtagene autoleucel (cilta-cel), a novel chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated early, deep, and durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), and improvements in health-related quality of life (HRQoL) in CARTITUDE-1 (NCT03548207). Patient perspectives on treatment provide context to efficacy outcomes and are an important aspect of therapeutic evaluation. METHODS: Qualitative interviews were conducted in a subset of CARTITUDE-1 patients (n = 36) at screening, Day 100, and Day 184 post cilta-cel on living with MM, therapy expectations, and treatment experiences during the study. RESULTS: Patients most wanted to see change in symptoms with the greatest impact on HRQoL: pain (85.2%) and fatigue (74.1%). The primary treatment expectation was achieving remission (40.7%), followed by extended life expectancy (14.8%). Patients most often defined meaningful change as improvement in symptoms (70.4%) and return to normalcy (40.7%). The percentage of patients reporting symptoms (pain, fatigue, bone fracture, gastrointestinal, neuropathy, and weakness) decreased from 85.2% to 22.2% across symptom types at baseline to 29.2% to 0% on Day 184 after cilta-cel. Improved symptoms and positive sentiments corresponded with improved perception of overall health status and reduced pain level, respectively. Most patients reported that their expectations of cilta-cel treatment had been met (70.8%) or exceeded (20.8%) at Day 184, and 70.8% of patients considered cilta-cel therapy better than their previous treatments. CONCLUSION: Overall HRQoL improvements and qualitative interviews showed cilta-cel met patient expectations of treatment and suggest the long treatment-free period also contributed to positive sentiments.

Is IQWiG's 15% Threshold Universally Applicable in Assessing the Clinical Relevance of Patient-Reported Outcomes Changes? An ISPOR Special Interest Group Report.

This article discusses a recent methodological change to assess the additional benefit of drug intervention by the German Federal Joint Committee (Gemeinsamer Bundesausschuss), a key stakeholder in EUnetHTA21 (European Network for Health Technology Assessment joint consortium for future EU HTA regulation), methodological workstream. The German Federal Joint Committee (Gemeinsamer Bundesausschuss) set a universal individual response threshold at ≥ 15% of the scale range of the measurement instrument, for all patient-reported outcomes, to achieve an additional benefit rating for a given pharmaceutical intervention. This approach is originally based on a corresponding recommendation from the Institute for Quality and Efficiency in Health Care. The merits of this approach are reviewed from various perspectives, including the evidence basis, statistical and psychometric considerations, and regulatory perspectives by the ISPOR Clinical Outcomes Assessment Special Interest Group's multistakeholder group of authors (academia, contract research organizations, and industry). Particular focus is placed on the patient perspective within the Institute for Quality and Efficiency in Health Care approach. The article development incorporated feedback from ISPOR members during well-attended ISPOR US and European conference presentations and 2 formal rounds of written review. The authors concluded that the ≥ 15% response threshold is incongruent with previously defined and scientifically established thresholds and is not well-suited for universal implementation. Further scientific evidence and discussion among all stakeholders are needed, especially should this universal rule be considered in the context of future joint clinical assessments of health technologies in the European Union scheduled from 2025 onward.

The patient experience of relapsed refractory multiple myeloma and perspectives on emerging therapies.

BACKGROUND: Relapsed refractory multiple myeloma (RRMM) is a disease that is nonresponsive or progressive on therapy, and although patients can achieve remission, relapse is common. As more treatment options become available for multiple myeloma (MM), it is important to understand patients' experiences of current and emerging therapies. AIMS: This study aimed to better understand patient experiences with treatment and therapies for MM using qualitative interviews and patient-reported information (PRI) shared on social media. METHODS: Semistructured qualitative interviews were conducted with adults with RRMM who resided in the United States. In addition to the interviews, PRI was collected from YouTube and a patient advocacy website. Key themes from the interviews and PRI were summarized, and illustrative quotes were extracted. RESULTS: Twenty participants were interviewed; 11 were female, and mean (standard deviation) age was 60 (7.0) years. The PRI included 14 posts and 19 unique contributors (10 were female). Similar treatment-related symptoms were reported in the interviews and PRI. Fatigue and pain were the most frequently reported symptoms while receiving treatment in both the interviews and PRI. These symptoms had a meaningful impact on health-related quality of life (HRQOL); being off treatment and returning to normal living was described as an ideal treatment outcome. Nearly all interview participants (n = 18) preferred a treatment that would allow for a treatment-free interval, if it had the same efficacy and safety profile as a continuous treatment. CONCLUSION: The symptom experience reported in this study is consistent with known RRMM symptoms and HRQOL impacts. Additionally, this study highlighted that patients' treatment expectations are changing relative to their past treatment experience. Individuals living with RRMM strongly desire therapies with a treatment-free interval and minimal impact on their HRQOL.

Development of the Pulmonary Hypertension Functional Classification Self-Report: a patient version adapted from the World Health Organization Functional Classification measure.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by progressive limitations on physical activity, right heart failure, and premature death. The World Health Organization functional classification (WHO-FC) is a clinician-rated assessment used widely to assess PAH severity and functioning, but no equivalent patient-reported version of PAH symptoms and activity limitations exists. We developed a version of the WHO-FC for self-completion by patients: the Pulmonary Hypertension Functional Classification Self-Report (PH-FC-SR). METHODS: Semistructured interviews were conducted with three health care providers (HCPs) via telephone to inform development of the draft PH-FC-SR. Two rounds of semi-structured interviews were conducted with 14 US patients with a self-reported PAH diagnosis via telephone/online to elicit concepts and iteratively refine the PH-FC-SR. RESULTS: HCPs reported that the WHO-FC was a useful tool for evaluating patients' PAH severity over time and for making treatment decisions but acknowledged that use of the measure is subjective. Patients in round 1 interviews (n = 6) reported PAH symptoms, including shortness of breath (n = 6), fatigue (n = 5), syncope (n = 5), chest pains (n = 3), and dizziness (n = 3). Round 1 patients identified challenges with the original WHO-FC, including comprehensibility of clinical terms and overlapping descriptions of class II and III, and preferred the Draft 1 PH-FC-SR over the original WHO-FC. After minor changes were made to Draft 2, round 2 interviews (n = 8) confirmed patients understood the PH-FC-SR class descriptions, interpreting them consistently. CONCLUSIONS: The HCP and patient interviews identified and confirmed certain limitations inherent within the clinician-rated WHO-FC, including subjective assessment and overlapping definitions for class II and III. The PH-FC-SR includes patient-appropriate language, symptoms, and physical activity impacts relevant to patients with PAH. Future research is recommended to validate the PH-FC-SR and explore its correlation with the physician-assessed WHO-FC and other outcomes.

Qualitative study: burden of menopause-associated vasomotor symptoms (VMS) and validation of PROMIS Sleep Disturbance and Sleep-Related Impairment measures for assessment of VMS impact on sleep.

PURPOSE: We evaluated the impact of menopause-associated vasomotor symptoms (VMS) on sleep. We also sought to establish the content validity of Patient-Reported Outcomes Measurement Information System (PROMIS) short form Sleep-Related Impairment and Sleep Disturbance measures in postmenopausal women with moderate to severe VMS. METHODS: Cross-sectional, in-person, qualitative interviews were conducted in the United States (Texas, Illinois) and European Union (UK, France) with women aged 40-64 years experiencing moderate to severe VMS (≥35/wk). Main outcomes were impact of VMS on sleep based on concept elicitation and content validity of PROMIS Sleep-Related Impairment and Sleep Disturbance short forms via cognitive debriefing. RESULTS: Thirty-two women (US: n = 16; EU: n = 16) participated. A majority (US: 93.8%; EU: 93.8%) said VMS affected sleep; specifically, they had sleep interrupted by sweating or overheating and had difficulty returning to sleep. Sleep disturbance was the most bothersome aspect of VMS (US: 75%; EU: 50%). VMS-associated sleep disturbance affected next-day work productivity, mood, relationships, daily activities, concentration, social activities, and physical health. Participants found both PROMIS sleep measures relevant and easy to answer; the Sleep Disturbance measure was considered the most relevant. Participants had no difficulty remembering their experiences over the 7-day recall period and found the response options to be distinct. CONCLUSION: VMS associated with menopause significantly interferes with sleep and next-day functioning (e.g., work productivity), supporting assessment of sleep outcomes in studies evaluating treatment of VMS. Women with moderate to severe VMS found that the PROMIS Sleep-Related Impairment and Sleep Disturbance short forms assessed constructs important to understanding sleep in the context of menopause-associated VMS.

Development of a Patient-Reported Outcome Measure for Non-Alcoholic Steatohepatitis (NASH-CHECK): Results of a Qualitative Study.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease characterized by excessive liver fat accumulation, inflammation, cell injury, and fibrosis. It is viewed as largely asymptomatic in its earlier (non-cirrhotic) stages, and information on the patient-perceived impact of NASH is scarce. OBJECTIVE: This study aimed to develop a NASH-specific patient-reported outcome (PRO) measure (NASH-CHECK) for use as a trial endpoint, using methods compliant with regulatory expectations. METHODS: A NASH conceptual model was developed based on the literature and clinical/patient expert review. The model guided concept elicitation (CE) interviews in patients with non-cirrhotic NASH recruited via a US tertiary care center. NASH-CHECK content was generated via thematic analysis of CE data and review by clinical/patient experts. Cognitive debriefing (CD) interviews with US patients evaluated content validity. RESULTS: The literature review confirmed that NASH impacts on functioning and health-related quality of life (HRQoL). Overall, 23 CE and 20 CD interviews were conducted. Key symptoms reported in CE interviews included pain in the upper-right abdomen (n = 14), fatigue (n = 18), poor sleep quality (n = 12), impaired memory (n = 13), and reduced focus (n = 11); key HRQoL impacts included impaired physical functioning, reduced ability to conduct daily living tasks, reduced quality of relationships, low mood, anxiety, and self-consciousness. The 52-item first-draft NASH-CHECK was reduced to 31 items based on patient feedback on item relevance, acceptability, and comprehension. CONCLUSIONS: The interviews revealed key symptoms and broad HRQoL impacts of NASH. As a disease-specific PRO measure assessing symptoms and HRQoL, the NASH-CHECK is relevant, comprehensive, and acceptable to patients and clinicians.

Patient and healthcare professional experiences of the Salford Lung Studies: qualitative insights for future effectiveness trials.

BACKGROUND: Randomized controlled trials (RCTs) conducted in the routine care setting provide the opportunity to better understand the effectiveness of new medicines but can present recruitment difficulties. An improved understanding of the challenges/opportunities for patient and healthcare professional (HCP) engagement in clinical research is needed to enhance participation and trial experience. In this study, we explored patient and HCP drivers for, and experiences of, participation in the Salford Lung Studies (SLS), and their views on future trial participation and the overall value of such trials. METHODS: This was a qualitative study set in Salford, UK, comprising patient telephone interviews (N = 10) and HCP advisory boards (one with general practitioners [GPs], one with practice managers [PMs]); all individuals had participated in the SLS. Semi-structured telephone interviews were recorded, transcribed and analysed thematically. Advisory board meetings were analysed based on transcriptions of audio recordings and field notes. RESULTS: For patients, key positive aspects of the SLS were the ease/convenience of study assessments and excellent relationships with study nurses. GPs and PMs considered the SLS to be well-organized and highlighted the value of research nurse support; they also described minor challenges relating to trial systems, initial financial strain on practices and staff turnover. All participants indicated that they were very likely to participate in future trials, citing a design closely aligned with routine care practice as essential. Several strategies to encourage trial participation were suggested, such as clearly communicating benefits to patients and ensuring flexible study assessments. CONCLUSIONS: Patients and HCPs had positive experiences of the SLS. The study design, closely aligned with routine care, was considered important to their high likelihood of participating in future trials. The experiences of patients and HCPs in the SLS provide valuable insights that will help inform future best practice in the design and conduct of future real-world effectiveness RCTs in primary care. The detailed first-hand experiences of HCPs will be of significant value to others considering engaging in clinical research and participating in effectiveness RCTs.

Exploring the Impact of Fatigue in Progressive Multiple Sclerosis: A Mixed-Methods Analysis.

BACKGROUND: Patient-focused literature on fatigue in progressive forms of multiple sclerosis (MS) is sparse. This study aimed to explore progressive MS patients' experiences of fatigue. METHODS: Adult patients in the United States with primary progressive MS (n=21) and secondary progressive MS (n=23), recruited from research panels, completed the following PRO measures: Patient Global Impression of Severity (Fatigue) (PGI-F); Fatigue Scale of Motor and Cognitive Functions (FSMC); Modified Fatigue Impact Scale (MFIS); Patient Health Questionnaire, two-item version (PHQ-2); and Patient Determined Disease Steps (PDDS). Patients subsequently participated in a 45-minute semistructured telephone interview and were asked to describe their MS symptoms and to comment on how MS affected their day-to-day lives. More detailed questions followed on the nature of their fatigue, including symptoms, impacts, frequency, and bothersomeness. RESULTS: Patients' mean age was 52.5 years, mean time since diagnosis was 14.7 years, and 81.8% were female. 79.5% of patients were unemployed and/or receiving disability benefits. Of all spontaneously reported MS symptoms, fatigue was the most common (n=38, 86.4%), followed by ambulation problems (n=31, 70.5%) and muscle weakness (n=25, 56.8%). Patients used the words "tired," "exhausted," "wiped out," and having "little or no energy" to describe their fatigue. More patients rated fatigue as their "most troubling symptom" (n=17, 38.6%) compared with other MS-related symptoms. Half of patients reported feeling constantly fatigued, and more than 90% reported experiencing fatigue at least daily. The top three most frequently reported negative impacts of fatigue were social functioning, emotional well-being, and cognitive functioning (all >80%). Patients described themselves as "homebodies," as fatigue limited their social interactions with friends and family and impacted the types of activities they could participate in. Patients attributed their inability to think clearly or focus for long periods of time to their fatigue. Patients also reported experiencing depression and anxiety because of their fatigue, which would often have further negative effects on their relationships with friends and family. On the fatigue PRO measures, mean (standard deviation) scores were 75.2 (14.7) on the FSMC and 55.0 (15.2) on the MFIS. Most participants scored in the "high" fatigue category on the FSMC (84.1%) and above the clinically significant fatigue threshold (86.4%). MFIS and FSMC total scores correlated with PGI-F (polyserial correlations r=0.74 and r=0.62, both p<0.01) and PHQ-2 (r=0.56 and r=0.57, both p<0.01), but not with PDDS (r=0.09 and r=0.02, both p>0.05). CONCLUSIONS: Fatigue is a common, troublesome, and disabling symptom which has a profound impact on patients' daily lives, as evidenced by qualitative analyses and high scores on established fatigue measures observed in this sample. These findings provide insights into the burden of fatigue and can inform its measurement in both clinical and research settings. Treatments that improve the symptoms of fatigue or prevent exacerbations are needed for patients with progressive MS.

Health-related quality of life and patient-reported outcome measures in NASH-related cirrhosis.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is known to have a negative impact on patients' health-related quality of life (HRQoL), even before progression to cirrhosis has occurred. The burden of NASH-related cirrhosis from the patient perspective remains poorly understood. Herein, we aimed to identify the burden of disease and HRQoL impairment among patients with NASH-related compensated cirrhosis. METHODS: This targeted literature review sought first to identify the humanistic burden of disease from the perspective of patients with diagnosed NASH-cirrhosis and, secondly, to identify generic or disease-specific patient-reported outcome measures (PROMs) used to assess the impact of NASH-cirrhosis. Searches were conducted in bibliographical databases, grey or unpublished literature, liver disease websites, support group websites and online blogs. A quality assessment of specific PROMs was conducted. RESULTS: Patients with NASH-cirrhosis are reported to suffer from lower HRQoL than patients with non-cirrhotic NASH and the general population with respect to physical health/functioning, emotional health and worry, and mental health. Thirteen PROMs were identified, of which 4 were liver-disease specific: CLDQ, CLDQ-NAFLD, LDQoL and LDSI. The most commonly used measures do not comply with current industry or regulatory standards for PROMs and/or are not validated for use in a cirrhotic NASH population. CONCLUSIONS: Patients with NASH-cirrhosis have lower HRQoL and poorer physical health than patients with non-cirrhotic NASH. However, the literature lacked detail of the everyday impact on patients' lives. Currently, a number of PROMs are available to measure the impact of the disease in patients with chronic liver conditions. The lack of studies that include qualitative insights in this population mandates further exploration and research. LAY SUMMARY: It is not well understood how having non-alcoholic fatty liver disease (NAFLD)-related cirrhosis affects a person's everyday wellbeing and quality of life. Some research has been done with patients who have early stages of liver disease but not people with cirrhosis. We found that patients with NAFLD-related cirrhosis tended to have poorer health than patients without cirrhosis. But there was not very much information from patients themselves and there were no tools or questionnaires just for this group of patients.

Patient-Centered Insights on Treatment Decision Making and Living with Acute Myeloid Leukemia and Other Hematologic Cancers.

Expectations relating to treatment and survival, and factors influencing treatment decisions are not well understood in adult patients with acute myeloid leukemia. This study analyzed combined findings from a targeted literature review with patient-reported information shared on YouTube to further understand patient perspectives in hematologic cancers and, in particular, acute myeloid leukemia. The targeted literature review included articles concerning patient (aged ≥ 18 years) experiences or perspectives in acute myeloid leukemia or other hematologic cancers. YouTube video selection criteria included patients (aged ≥ 60 years) with self-reported acute myeloid leukemia. In total, 26 articles (13 acute myeloid leukemia-specific and 14 other hematologic cancers, with one relevant to both populations) and 28 videos pertaining to ten unique patients/caregivers were identified. Key concepts reported by patients included the perceived value of survival for achieving personal and/or life milestones, the emotional/psychological distress of their diagnosis, and the uncertainties about life expectancy/prognosis. Effective therapies that could potentially delay progression and extend life were of great importance to patients; however, these were considered in terms of quality-of-life impact and disruption to daily life. Many patients expressed concerns regarding the lack of treatment options, the possibility of side effects, and how their diagnosis and treatment would affect relationships, daily lives, and ability to complete certain tasks. Both data sources yielded valuable and rich information on the patient experience and perceptions of hematologic cancers, in particular for acute myeloid leukemia, and its treatments. Further understanding of these insights could aid discussions between clinicians, patients, and their caregivers regarding treatment decisions, highlight outcomes of importance to patients in clinical studies, and ultimately, inform patient-focused drug development and evaluation.

A descriptive follow-up interview study assessing patient-centred outcomes: Salford Lung Study in Asthma (SLS Asthma).

The Salford Lung Study in Asthma (SLS Asthma) was a multicentre, randomised, controlled, open-label trial that assessed initiating once-daily, single-inhaler fluticasone furoate/vilanterol (FF/VI) 100 µg/25 µg or 200 µg/25 µg versus continuing usual care. A subgroup (n = 400) from SLS Asthma was enrolled in this exploratory, interview-based follow-up study. Quantitative and qualitative data were collected via questionnaires. The primary objective was to capture patient-centred outcomes (symptom experience, quality of life [QoL], disease management behaviours) and patient experience. Secondary objectives were to assess the correlation of patient-reported outcomes with pre-defined variables from SLS Asthma (Asthma Control Test [ACT] score). The follow-up sample was representative of the SLS Asthma population; half reported asthma improvement during the study. Breathlessness was the most likely symptom to improve (47.8% of patients reported improvement). Most patients reported 'no change' in overall QoL (57.5%) and daily life domains (functioning 66.3%, activities 68.3%, relationships 86.8%, psychological 68.5%). Functioning was reported as the most frequently improved domain (29.8% of patients). Perceived improvement in asthma control (42.5%) and confidence (37.3%) was frequent. ACT responders (defined as patients achieving an ACT score ≥20 and/or an increase of ≥3 in ACT score from baseline at Week 52) were more likely to report asthma improvement (88.7% of patients reporting 'a lot' of improvement) than non-responders. Patients' asthma experiences generally improved during SLS Asthma. Clinical improvements were often associated with perceived improvement by patients, particularly among ACT responders.

Follow-up interviews from The Salford Lung Study (COPD) and analyses per treatment and exacerbations.

The Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD) was a 12-month, Phase III, open-label, randomised study comparing the effectiveness and safety of initiating once-daily fluticasone furoate 100 µg/vilanterol 25 µg (FF/VI) with continuing usual care (UC). Follow-up interviews were conducted among a subset of 400 patients who completed SLS COPD to further understand patients' experiences with treatment outcomes and the impact of COPD, and potential risk factors associated with higher rates of exacerbations during SLS COPD. Another objective was to explore how such patient-centred outcomes differed by randomised treatment. Patients' perceived control over COPD and effects on quality of life (QoL) were similar between treatment groups at the time of the follow-up interview, but more patients in the FF/VI group compared with UC reported perceived improvements in COPD control and QoL during the study. Of patients who experienced ≥2 exacerbations during SLS COPD, a greater percentage were women, were unemployed or homemakers, or were on long-term sick leave. Having ≥2 exacerbations also appeared to be associated with smoking, seeing a hospital specialist, a feeling of having no/little control over COPD, perceived worsening of feelings of control and reduced overall QoL since the start of the study, being aware of impending exacerbation occurrence and a more severe last exacerbation. Initiation of FF/VI was associated with a greater perceived improvement in patients' control of their COPD and QoL throughout SLS COPD than continuation of UC. Suggestions that smoking status and feelings of control are potentially related to exacerbation require further investigation.

Is the EQ-5D fit for purpose in asthma? Acceptability and content validity from the patient perspective.

BACKGROUND: The increasing emphasis on patient-reported outcomes in health care decision making has prompted greater rigor in the evidence to support the instruments used. Acceptability and content validity are important properties of any measure to ensure it assesses the relevant aspects of the target concept. The purpose of this study was to evaluate the acceptability and content validity of the EQ-5D 5-Level (EQ-5D-5L) to assess the impact of asthma on patients' lives. METHODS: Qualitative interviews were conducted with 40 adults with asthma in the United Kingdom. The first 25 interviews used cognitive-debriefing methods to assess the relevance and acceptability of the EQ-5D-5L and two asthma-specific measures for comparison: an asthma-specific, preference-based measure (the Asthma Quality of Life Utility Index-5 Dimensions) and an Asthma Symptom Diary. The final 15 interviews combined concept elicitation to identify patient-perceived asthma impact, and cognitive debriefing to assess relevance and acceptability of the EQ-5D-5L and the Asthma Symptom Diary. Cognitive-debriefing feedback on the content of the measures was collated and summarized descriptively. The concept-elicitation data were analyzed thematically. RESULTS: Participants were aged 20 to 57 years and 62.5% were female. Although some participants expressed positive opinions on aspects of the EQ-5D-5L, only the usual activities dimension was consistently considered relevant to participants' asthma experiences. The mobility and self-care dimensions prompted strong negative reactions from some participants. Variations in interpretation of the mobility dimension and difficulties with multiple concepts in the pain/discomfort and anxiety/depression dimensions also were noted. Concepts reported by participants as missing included environmental triggers, asthma symptoms, emotions, and sleep. The EQ-5D-5L was the least preferred measure to describe the impact of asthma on participants' lives. Participants reported shortness of breath and impact on activities as especially salient issues. CONCLUSIONS: The content of the EQ-5D-5L was poorly aligned with the patient-perceived impact of asthma, and the measure failed to meet basic standards for acceptability and content validity as a measure to assess the impact of asthma from the patient perspective. The shortcomings identified raise concerns regarding the appropriateness of the EQ-5D in asthma and further evaluation is warranted.

Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD): follow-up interviews on patient-centred outcomes.

This study investigated patient perceptions, experiences and management of COPD throughout the SLS COPD study. Follow-up interviews were conducted with 400 patients who completed SLS COPD; a mixed-methods approach was used to collect quantitative and qualitative information. Structured interviews using closed-ended questions were conducted with 360 patients, detailing aspects of background/lifestyle information and COPD. Extended interviews containing open-ended questions on perceptions of COPD and quality of life (QoL) in addition to the closed-ended questions were completed by 40 further patients. Participants also completed the Adherence Starts with Knowledge-12 (ASK-12) and the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire. Quantitative data were analysed descriptively; qualitative data were analysed using qualitative description. The participants (n = 400) were reasonably representative of the SLS COPD population; mean age was 66.2 years. Breathlessness was the most commonly recalled symptom of/associated with COPD (88.5% of patients) and was the symptom that changed the most (improved, 26.8%/worsened, 20.9%) throughout the study. Participants' daily functioning and activities were most affected by symptoms of/associated with COPD, followed by relationships and psychological issues. 66.5% of participants experienced exacerbations, 60.5% of whom reported self-management as their first treatment strategy (taking antibiotics, resting and/or corticosteroids). Qualitative analysis revealed COPD symptoms, breathlessness in particular, to have a significant impact on mobility and in turn QoL. In conclusion, breathlessness was cited in these interviews as the COPD symptom with the greatest impact on participants' daily functioning, activities and self-care. The findings provided significant additional knowledge to the SLS COPD study findings.

A Review of Patient-Reported Outcome Labeling in the United States (2011-2015).

BACKGROUND: A review of new drug approvals (NDAs) by the Food and Drug Administration (FDA) for 2006 to 2010 showed that 24.1% of new drugs had patient-reported outcome (PRO) labeling. OBJECTIVES: To review PRO labeling for NDAs for 2011 to 2015 and to compare key findings reported previously. METHODS: A review of the FDA drug approval reports for NDAs was conducted using the FDA Web site to determine the number of NDAs for the period 2011 to 2015. For all identified NDAs, drug approval package and product labeling were reviewed to identify PRO end-point status and PRO labeling. NDAs for the period 2006 to 2015 were grouped by disease category as per the International Classification of Diseases, Tenth Revision. Data were summarized for all NDAs and for approvals in diseases that traditionally rely on PROs for evaluating treatment benefit (PRO-dependent). Results were compared with NDAs for the period 2006 to 2010. RESULTS: In the period 2011 to 2015, 16.5% of the 182 NDAs had PRO labeling. For PRO-dependent NDAs, this figure was 46.9% and 46.0% for the period 2006 to 1010 and the period 2011 to 2015, respectively. Most of the PRO labeling for the period 2011 to 2015 was based on primary end points (76.7%). Almost all PRO labeling was for concepts proximal to the disease. CONCLUSIONS: There is potential for increased PRO labeling, especially for drug approvals in diseases that traditionally rely on PROs for evaluating treatment benefit to satisfy regulatory needs. Less PRO labeling based on secondary end points may be indicative of drug manufacturers' reluctance to aid and enhance the value propositions of their products to all stakeholders, including patients.