Development and Content Validation of Novel Patient-Reported Outcome Measures to Assess Disease Severity and Change in Patients with Erythropoietic Protoporphyria: The EPP Impact Questionnaire (EPIQ).

Purpose: Erythropoietic protoporphyria (EPP), a rare inherited disorder, presents in early childhood with severe, painful phototoxicity, with significant impacts on health-related quality of life (HRQoL). Previous studies have not captured all concepts important to patients. Therefore, this study sought to develop a novel, comprehensive, and content valid patient-reported outcome (PRO) measure to assess the efficacy of new therapies. Patients and Methods: Qualitative interviews were conducted with EPP participants and clinical experts to obtain views on concepts relevant to patients. Results informed the development of novel PROs, which were debriefed during subsequent combined concept elicitation and cognitive debriefing interviews. Results: Twenty-three interviews were conducted with 17 adults and 6 adolescents with EPP. Concept elicitation revealed that participants experienced many symptoms with significant variability. The most common were burning, pain, swelling, and tingling. Tingling was the most common prodromal symptom, while burning was the most bothersome, and pain was the worst full reaction symptom. Participants reported being negatively impacted in their ability to do daily activities, and social and emotional functioning. Many reported impacted ability to work and be productive at their job. Participants reviewed and completed the newly developed PRO measures assessing full reactions and ability to do activities, as well as items to assess severity and change in severity of prodromal symptoms, full reactions, and EPP overall. All measures were found to be comprehensive, clear, and relevant. Conclusion: PRO measures are needed to assess important aspects of HRQoL and evaluate therapeutic response. These PRO measures are unique in assessing overall severity and change in EPP.

Qualitative and psychometric evaluation of the PROMIS®-Fatigue SF-7a scale to assess fatigue in patients with moderately to severely active inflammatory bowel disease.

BACKGROUND: This study evaluated the content validity and psychometric properties of the Patient-Reported Outcomes Measurement Information System® (PROMIS)-Fatigue Short Form 7a (SF-7a) v1.0 scale to determine its suitability in clinical trials to assess fatigue in patients with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A qualitative interview assessed patients' experience living with CD (N = 20) and UC (N = 19). The contents of the SF-7a scale were cognitively debriefed to evaluate content validity. A psychometric evaluation was performed using data from clinical trials of patients with CD (N = 360) and UC (N = 214). Correlations with Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Activity Index (CDAI; CD only), and Mayo score (UC only) determined validity. The Patient Global Impression of Change (PGIC) was used to evaluate reliability and responsiveness to change. Using PGIC as an anchor, a preliminary threshold for clinically meaningful change was identified to define fatigue response in both CD and UC patients. RESULTS: All patients reported fatigue as a common symptom. Patients confirmed SF-7a items were relevant to assessing fatigue, instructions and response options were clear, and its 7-day recall period was appropriate. Higher SF-7a scores were associated with higher disease activity (CDAI and Mayo score) and lower health-related quality of life (IBDQ), confirming known groups validity. The correlation of the SF-7a scale was higher with fatigue-related items. (rs ≥ -0.70) than with items not directly associated with fatigue. Test-retest reliability was moderate to good (0.54-0.89) among patients with stable disease, and responsiveness to change in disease severity was demonstrated from baseline to Week 12. A ≥7point decrease was identified as a reasonable threshold to define clinically meaningful improvement. CONCLUSION: The SF-7a scale is a valid, reliable, and sensitive measure of fatigue in patients with moderately to severely active IBD and can be used to evaluate treatment response.

Development and content validation of a sunlight exposure diary in patients with erythropoietic protoporphyria.

BACKGROUND: Erythropoietic protoporphyria is a rare, inherited disorder presenting in early childhood with severe, painful phototoxicity. EPP has significant impacts on health-related quality of life, though there is variable disease severity. Accurately capturing how much time individuals with EPP can spend outdoors before they develop symptoms is critical to understanding HRQoL and measuring therapeutic response. Therefore, the goal of this study was to develop a comprehensive and content valid sun exposure diary to assess the efficacy of new therapies in individuals with EPP. METHODS: Qualitative interviews were conducted with adult and adolescent EPP participants, as well as five clinical experts, to obtain their input on the content of an existing sun exposure diary. Revisions to the diary were made based on evidence generated in cognitive debriefing interviews analyzed in eight consecutive groups of EPP participant. RESULTS: Interviews were conducted with 17 adults and 6 adolescents with EPP. The average age of adults was 40 years and of adolescents was 14 years. Clinical experts thought the original diary needed clarification on the description of symptoms, how time outdoors was captured, and the distinction between direct vs. indirect sunlight. Participants with EPP also noted these items needed revision, and that the distinction between prodromal symptoms and full reaction symptoms should be clarified. In the final diary version, participants with EPP found most items to be clear and easy to complete/think about. Seventy-six percent of participants (13/17) asked thought the diary was easy to complete. The remainder thought the majority of the diary was easy to complete with the exception of select questions. CONCLUSIONS: Evaluating a new treatment for EPP requires accurately capturing time in sunlight and symptoms in this unique disorder. The newly developed sun exposure diary is content valid and can be used to assess important aspects of symptoms and daily life and therefore evaluate clinically meaningful therapeutic response.

Perceptions of patient disease burden and management approaches in systemic mastocytosis: Results of the TouchStone Healthcare Provider Survey.

BACKGROUND: Systemic mastocytosis (SM) is a rare clonal neoplasm driven by the KIT D816V mutation and has a broad range of debilitating symptoms. In this study, the authors evaluated SM disease perceptions and management strategies among US health care providers (HCPs). METHODS: Hematologist/oncologist (H/O) HCPs and allergist/immunologist (A/I) HCPs who were treating four or more patients with SM completed an online, 51-item TouchStone HCP Survey, which queried provider characteristics, perceptions of disease burden, and current management. Descriptive analyses by specialty and SM subtype were performed. RESULTS: Of 304 HCPs contacted, 111 (37%) met eligibility criteria, including 51% A/I specialists and 49% H/O specialists. On average, the HCPs had 14 years of practice experience and cared for 20 patients with SM. A/I HCPs saw more patients with nonadvanced SM (78%) compared with H/O HCPs, who saw similar proportions of patients with nonadvanced SM (54%) and advanced SM (46%). HCPs reported testing 75% of patients for the KIT D816V mutation and found an estimated prevalence of 47%. On average, HCPs estimated 8 months between symptom onset and SM diagnosis. HCPs reported that 62% of patients with indolent SM felt depressed or discouraged because of symptoms. In terms of treatment goals for SM, both types of specialists prioritized symptom improvement for nonadvanced SM and improved survival for advanced SM while also prioritizing improving patient quality of life. CONCLUSIONS: Both A/I and H/O specialists highlighted unmet needs for patients with SM. The HCPs surveyed reported a lower rate of KIT D816V mutations and a perceived shorter time between symptom onset and SM diagnosis compared with published estimates. LAY SUMMARY: Specialists treating systemic mastocytosis (SM) completed a 51-item questionnaire about their clinical practices and perceptions of disease impact. The study included 111 hematology, oncology, allergy, and immunology physicians. Physicians reported that most patients had nonadvanced disease, yet SM symptoms significantly disrupted their patients' lives. Physicians estimated that SM is diagnosed within months of symptom onset, in contrast with published reports of years' long delays reported by patients with SM. This study identified unmet needs that can inform educational and patient management priorities in this rare disease.

Patient-reported outcomes among patients with systemic mastocytosis in routine clinical practice: Results of the TouchStone SM Patient Survey.

BACKGROUND: Systemic mastocytosis (SM) is a rare clonal neoplasm driven by KIT D816V and other mutations. Data were collected from the patient perspective on disease burden and included an SM-specific symptom assessment tool. METHODS: US adults aged 18 years and older with a self-reported SM diagnosis completed an online TouchStone SM Patient Survey of 100 items, including the 12-item Short-Form Health Survey, the Indolent Systemic Mastocytosis Symptom Assessment Form, and the Work Productivity and Activity Impairment Questionnaire, as well as questions about SM diagnosis, the impact of SM on daily activities, work impairment, and health care use. The results were analyzed using descriptive statistics. RESULTS: Fifty-six individuals completed the survey (89% women; median age, 48 years; mean time since diagnosis, 6.7 years), reporting indolent SM (66%), aggressive SM (9%), smoldering SM (5%), and unknown SM subtype (18%). Over a 1-year recall, respondents reported seeking emergency care for anaphylaxis (30%) and taking three or more prescription medications (52%) for SM. Over one half of patients (54%) reduced their work hours because of SM, and 64% avoided leaving home because of symptoms. A majority of respondents (93%) had experienced ≥10 SM-related symptoms, noting that the most bothersome were anaphylactic episodes (18%), abdominal/stomach pain (16%), diarrhea/loose stools (13%), and fatigue (11%). Whereas an Indolent Systemic Mastocytosis Symptom Assessment Form-derived total symptom score of 28 is used to indicate moderate-to-severe symptoms, the mean total symptom score was 52.7. Mental and physical component summary scores from the 12-item Short-Form Health Survey were below population norms. CONCLUSIONS: Patients who were surveyed reported substantial symptom burden and unmet needs because of SM, as evidenced by seeking emergency care and reporting bothersome symptoms, poor quality of life, and reduced work hours and productivity. LAY SUMMARY: The objective of this research was to understand the burden and unmet needs in the rare disease of systemic mastocytosis (SM) to guide future care. Fifty-six patients completed an online survey containing questions about their diagnosis, medications, health care use, quality of life, and SM symptoms. The results demonstrated that SM is associated with severe and burdensome symptoms, anaphylactic events, emergency department visits, use of multiple medications, reduced ability to work, and poor physical and psychological quality of life. These findings suggest the need for future advances to address unmet needs in patients affected by SM.

Evaluating the Content Validity, Clarity, and Relevance of Two Patient-Reported Outcomes for Use With Adults With EGFR-Mutated NSCLC.

INTRODUCTION: NSCLCs account for most lung cancers; approximately 30% involve a mutation in the EGFR gene. This study sought to identify one or more patient-reported outcome (PRO) measures relevant for use in clinical trials to assess symptoms and health-related quality of life in this population. METHODS: Patients with NSCLC from the United States, Europe, and Asia and including those with an exon 20 insertion mutation and other EGFR mutations participated in a combination of concept elicitation and cognitive debriefing interviews to report symptoms and impacts of their NSCLC and provide feedback on the clarity and relevance of several PRO measures. RESULTS: A total of 30 individuals participated (mean age = 57 years, 87% female, 80% white). The most often reported symptoms included fatigue, shortness of breath, cough, and weight loss. Individuals with the exon 20 insertion mutation (n = 21) more frequently reported negative impacts on daily life, physical functioning, and social functioning but less frequently reported negative impacts to emotional functioning. The PROMIS Short-Form version 2.0-Physical Function 8c and the NSCLC Symptom Assessment Questionnaire were deemed clear, relevant, and easy to complete. The concepts identified during the concept elicitation portion of the interviews were mapped to the content of each PRO, and all items within both PROs were endorsed by at least 20% of the participants. CONCLUSIONS: These results support the content validity, clarity, and relevance of the PROMIS Short-Form version 2.0-Physical Function 8c and the NSCLC Symptom Assessment Questionnaire in a population with EGFR-mutated NSCLC. Both would be appropriate for inclusion in future studies.

Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study.

BACKGROUND: Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies. METHODS: IMAGE was a multinational, prospective, observational study assessing adult patients with advanced melanoma treated with ipilimumab or non-ipilimumab systemic therapies between June 2012 and March 2015 with ≥3 years of follow-up. Adjusted OS curves based on multivariate Cox regression models included covariate effects. Safety and patient-reported outcomes were assessed. RESULTS: Among 1356 patients, 1094 (81%) received ipilimumab and 262 (19%) received non-ipilimumab index therapy (systemic therapy [chemotherapy, anti-programmed death 1 antibodies, or BRAF ± MEK inhibitors], radiotherapy, and radiosurgery). In the overall population, median age was 64 years, 60% were male, 78% were from Europe, and 78% had received previous treatment for advanced melanoma. In the ipilimumab-treated cohort, 780 (71%) patients did not receive subsequent therapy (IPI-noOther) and 314 (29%) received subsequent non-ipilimumab therapy (IPI-Other) on study. In the non-ipilimumab-treated cohort, 205 (78%) patients remained on or received other subsequent non-ipilimumab therapy (Other-Other) and 57 (22%) received subsequent ipilimumab therapy (Other-IPI) on study. Among 1151 patients who received ipilimumab at any time during the study (IPI-noOther, IPI-Other, and Other-IPI), 296 (26%) reported CTCAE grade ≥ 3 treatment-related adverse events, most occurring in year 1. Ipilimumab-treated and non-ipilimumab-treated patients who switched therapy (IPI-Other and Other-IPI) had longer OS than those who did not switch (IPI-noOther and Other-Other). Patients with prior therapy who did not switch therapy (IPI-noOther and Other-Other) showed similar OS. In treatment-naive patients, those in the IPI-noOther group tended to have longer OS than those in the Other-Other group. Patient-reported outcomes were similar between treatment cohorts. CONCLUSIONS: With long-term follow-up (≥ 3 years), safety and OS in this real-world population of patients treated with ipilimumab 3 mg/kg were consistent with those reported in clinical trials. Patient-reported quality of life was maintained over the study period. OS analysis across both pretreated and treatment-naive patients suggested a beneficial role of ipilimumab early in treatment. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01511913. Registered January 19, 2012 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01511913.

Disease and Treatment-Related Burden in Patients With Acromegaly Who Are Biochemically Controlled on Injectable Somatostatin Receptor Ligands.

Medical treatment for acromegaly commonly involves receiving intramuscular or deep subcutaneous injections of somatostatin receptor ligands (SRLs) in most patients. In addition to side effects of treatment, acromegaly patients often still experience disease symptoms even when therapy is successful in controlling GH and IGF-1 levels. Symptoms and side effects can negatively impact patients' health-related quality of life. In this study, we examine the disease- and treatment-related burden associated with SRL injections as reported through the use of the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ ©) and clinician-reported symptom severity through the Acromegaly Index of Severity (AIS). Patients included in this analysis were enrolled in a randomized phase 3 study, were biochemically-controlled (an IGF-1 < 1.3 × the upper limit of normal [ULN] and average GH < 2.5 ng/ml) and receiving SRL injections for ≥6 months with a stable dose of either long-acting octreotide or lanreotide monotherapy for ≥4 months. The sample (N = 91) was 65% female, 91% Caucasian, with a mean [standard deviation (SD)] age of 53 (1) years. Two-thirds of patients reported that they still experience acromegaly symptoms; 82% of these said they experience symptoms all of the time. Three-fourths experienced gastrointestinal (GI) side effects after injections, and 77% experienced treatment-related injection site reactions (ISRs). Patients commonly reported that these interfered with their daily life, leisure, and work activities. Those with higher symptom severity, as measured by the AIS, scored significantly worse on several Acro-TSQ domains: Symptom Interference, GI Interference, Treatment Satisfaction, and Emotional Reaction. Despite being biochemically controlled with injectable SRLs, most patients reported experiencing acromegaly symptoms that interfere with daily life, leisure, and work. GI side effects and ISRs were also common. This study highlights the significant disease burden that still persists for patients with acromegaly that have achieved biochemical control with the use of injectable SRLs.

Determination of thresholds for minimally important difference and clinically important response on the functional outcomes of sleep questionnaire short version in adults with narcolepsy or obstructive sleep apnea.

PURPOSE: This study estimated thresholds for clinically important responses and minimally important differences for two indicators of improvement for the 10-item version of the functional outcomes of sleep questionnaire (FOSQ-10). METHODS: Participants with excessive daytime sleepiness with narcolepsy or obstructive sleep apnea received 12 weeks of solriamfetol treatment. Participants completed the FOSQ-10 and other patient-reported outcome measures, including the single-item patient global impression of change (PGI-C) assessment. Clinicians completed the single-item clinician global impression of change (CGI-C) for each participant. Data from the two studies were analyzed separately, both without regard to treatment assignment. In total, 690 participants (47% female, mean age 48 years, 77% Caucasian, 91% from North America) were enrolled. Two clinically important changes, defined as a minimally important difference and a clinically important response, were determined using distribution and anchor-based analyses. A receiver operating characteristic analysis was used to determine the optimal FOSQ-10 change threshold. RESULTS: Spearman correlations between change in FOSQ-10 scores and PGI-C and CGI-C were - 0.57 and - 0.49 for participants with narcolepsy and - 0.42 and - 0.37 for participants with obstructive sleep apnea. Receiver operating characteristic analysis suggested minimally important difference and clinically important response estimates of 1.7 and 2.5 and 1.8 and 2.2 points in narcolepsy and obstructive sleep apnea, respectively. CONCLUSIONS: Minimally important difference and clinically important response estimates for the FOSQ-10 for adults with excessive daytime sleepiness in narcolepsy or obstructive sleep apnea will be helpful for interpreting changes over time and defining a clinical responder. CLINICALTRIALS. GOV IDENTIFIERS: NCT02348593 (first submitted January 15, 2015) and NCT02348606 (first submitted January 15, 2015).

Relationship between sleep efficacy endpoints and measures of functional status and health-related quality of life in participants with narcolepsy or obstructive sleep apnea treated for excessive daytime sleepiness.

This study examined the correlation between improvements in excessive daytime sleepiness in participants with obstructive sleep apnea or narcolepsy and changes in functional status, work productivity and health-related quality of life. Data from two 12-week randomized controlled trials of solriamfetol were analyzed. Participants completed the Epworth Sleepiness Scale, 10-item Functional Outcomes of Sleep Questionnaire, Work Productivity and Activity Impairment questionnaire and 36-Item Short Form Health Survey and performed the Maintenance of Wakefulness Test at baseline and weeks 4, 8 and 12. Patient Global Impression of Change was assessed at weeks 4, 8 and 12. Pearson correlations were calculated for change in scores from baseline to week 12. For both studies, changes in the 10-item Functional Outcomes of Sleep Questionnaire were highly correlated (absolute value >0.5) with changes in Epworth Sleepiness Scale scores; changes in multiple domain scores of the 36-Item Short Form Health Survey and Work Productivity and Activity Impairment questionnaire were moderately correlated (0.3-0.5) with changes in Epworth Sleepiness Scale scores in both studies and highly correlated for participants with narcolepsy. Changes in Maintenance of Wakefulness Test scores correlated moderately with changes in Epworth Sleepiness Scale scores in both studies. At week 12, Patient Global Impression of Change ratings correlated highly with Epworth Sleepiness Scale and 10-item Functional Outcomes of Sleep Questionnaire scores for both disorders. Other correlations were low. Self-reported assessments of sleepiness and global improvement appear to be more strongly correlated with measures of functioning and health-related quality of life than objectively assessed sleepiness.

Patient reported outcome data from acromegaly patients treated with injectable somatostatin receptor ligands (SRLs) in routine clinical practice.

BACKGROUND: Acromegaly patients managed on Somatostatin receptor ligands (SRLs), the most common first-line pharmacotherapy for acromegaly, may still experience acromegaly symptoms such as headache, sweating, fatigue, soft tissue swelling, and joint pain, even those with normal IGF-1. Additionally, treatment with SRLs may cause injection site reactions and other side effects such as gastro-intestinal (GI) symptoms. This study utilized patient-reported outcome measures to examine the burden associated with acromegaly and its treatment for patients receiving a stable dose of long-acting SRLs in routine clinical practice. METHODS: US acromegaly patients on a stable dose of SRL seen by their treating healthcare provider in the past 12 months completed a one-time online survey including the Acro-TSQ, an acromegaly-specific tool for assessing symptom burden and treatment satisfaction and convenience. RESULTS: One hundred five patients were enrolled (mean age 49.9 years, 79.1% female). Patients experienced numerous symptoms, including > 80% who experienced joint pain, acro-fog, swelling of soft tissue, and fatigue/weakness. Many symptoms occurred constantly, while some occurred at the end of the injection cycle, even among those with IGF-1 < = 1.0 ULN. Injection site reactions were common. Patients were moderately satisfied with their current treatment; symptoms and side effects often affected daily activities. On average, patients reported > 3 acromegaly provider visits/year. CONCLUSIONS: Despite receiving a stable dose of SRL and regular visits with an acromegaly healthcare provider, US acromegaly patients in routine clinical practice, and even the subgroup with normal IGF-1, report significant burden of disease and treatment.

Symptoms and impacts in anemia of chronic kidney disease.

BACKGROUND: Anemia is a frequent complication of chronic kidney disease (CKD) that negatively affects patients' health-related quality of life. METHODS: We conducted qualitative concept elicitation (CE) and cognitive debriefing (CD) interviews to assess the frequency, duration, and severity of symptoms and impacts associated with anemia of CKD and to facilitate the development of a new patient-reported outcome (PRO) measure. We interviewed 36 patients with CKD and hemoglobin levels ≥8.0 to <12.0 g/dL using a semi-structured interview guide developed specifically for this study until saturation was reached. We used MAXQDA to perform qualitative analysis of interview transcripts to determine the most relevant symptoms and impacts (based on the frequency of concept mentions) experienced by participants. RESULTS: Most participants had stage 4/5 CKD (81%) and were being treated with an erythropoietin stimulating agent (69%). Spontaneously reported symptoms included feeling tired (79%), shortness of breath (39%), and weak/lacking strength (36%). We developed the Chronic Kidney Disease and Anemia Questionnaire (CKD-AQ), which includes 23 items assessing frequency and severity of the most relevant symptoms and impacts identified by patients with anemia of CKD. The CD interviews confirmed the clarity and relevance of the concepts identified in the CE phase. CONCLUSION: The CKD-AQ is a novel PRO measure that captures the frequency and severity of the most relevant symptoms and impacts associated with anemia of CKD. Future studies will evaluate its psychometric properties and its potential utility in anemia management.

An evaluation of the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ) in adult patients with acromegaly, including correlations with other patient-reported outcome measures: data from two large multicenter international studies.

PURPOSE: The Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ) is a new patient-reported outcome (PRO) measure for patients with acromegaly receiving injectable somatostatin analogs (SSAs) to assess clinical symptoms and adverse drug reaction interference, treatment satisfaction, and convenience. We evaluated its scale structure, reliability, validity, responsiveness, and what constitutes clinically meaningful change. METHODS: Data from two longitudinal studies (N = 79 and 82) of patients receiving a stable injectable SSA dose for ≥ 6 months who completed the Acro-TSQ and other collateral measures (e.g., AcroQoL, AIS, WPAI:SHP, EQ-5D-5L) were analyzed. RESULTS: The first study demonstrated internal consistency of the Acro-TSQ. However, several items had high ceiling effects, responsiveness could not be established, and the minimally important difference (MID) was not estimable. In the second study, factor analysis revealed six scales: Symptom Interference, Treatment Convenience, Injection Site Interference, GI Interference, Treatment Satisfaction, and Emotional Reaction. Internal consistency and test-retest reliability were confirmed; most scales demonstrated significant differences in mean scores by disease severity. Correlations between Acro-TSQ scales and other collateral measures exceeded 0.30 in absolute value, confirming convergent validity. Responsiveness in Acro-TSQ scale scores reflected improved disease control. The MID was estimated for Symptom Interference (10-12 points), Treatment Convenience (9-11) and GI Interference (8-10). CONCLUSIONS: The Acro-TSQ is a brief, yet comprehensive tool to monitor important outcomes associated with injectable acromegaly SSA treatments. Its content reflects both disease and treatment burden as well as patient satisfaction, and its relevant for use in clinical studies.

Observed discordance between outcomes reported by acromegaly patients and their treating endocrinology medical provider.

BACKGROUND: Acromegaly patients, even those with IGF-1 values within the normal range receiving somatostatin receptor ligands (SRLs), often suffer from significant symptoms. It is not known to what extent patients' medical providers are aware of the frequency and severity of acromegaly symptoms or level of treatment satisfaction with SRLs. This study sought to examine the concordance between outcomes reported by acromegaly patients treated with long-acting SRLs and those perceived by their medical provider. METHODS: US acromegaly patients on a stable dose of SRL and seen by their medical provider in the past year completed an online survey which included the Acro-TSQ. Their medical providers were interviewed about the perception of their patient's symptoms, level of control, and general health, and completed relevant portions of the Acro-TSQ. Concordance between patient and medical provider reported data was examined. RESULTS: Medical providers reported that their patients experienced acromegaly symptoms on a regular basis, however, there was poor agreement between patients and medical providers on the frequency, severity, and pattern of symptoms, as well as on the severity of injection site reactions and multiple domains of the Acro-TSQ, with patients generally reporting symptoms and injection site reactions more often and with higher severity than medical providers. CONCLUSIONS: Medical providers were aware that their patients who were receiving a stable dose of SRL regularly experienced acromegaly symptoms. Addressing discordance in patient- and medical provider-reported frequency and severity of acromegaly symptoms and injection site reactions by facilitating better communication may improve care of acromegaly patients.

Development of a novel patient-reported measure for acromegaly: the Acro-TSQ.

PURPOSE: Somatostatin analogs (SSAs) represent a mainstay of medical treatment for acromegaly, currently available as either intramuscular or deep subcutaneous injections. Patient-reported outcomes (PROs) are increasingly common as relevant outcomes in studies of acromegaly and its treatment, but there are no validated PRO measures available that focus on the disease burden and the impact of treatment, specifically designed for use in patients with acromegaly. We sought to develop a new and unique PRO measure, the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ). METHODS: Concept elicitation (CE) interviews were conducted with acromegaly patients in the United States receiving SSA injections at a stable dose for ≥ 6 months. A questionnaire was drafted based on these interviews; combined CE and cognitive debriefing (CE/CD) interviews were then conducted to confirm the content, clarity, and relevance of the questionnaire. RESULTS: Nineteen subjects completed interviews [n = 9 CE, n = 10 CE/CD; n = 15 Lanreotide Depot/Autogel (Somatuline), n = 4 Octreotide LAR (Sandostatin LAR)]. Most subjects responded positively when asked about the effectiveness of their current treatment; however, breakthrough symptoms, injection site reactions, and side effects were commonly reported and had negative impacts on social and emotional well-being and daily activities. All 10 subjects involved in debriefing interviews found the questionnaire to be relevant, easy to complete, and found the response options to be clear. The resulting 26-item Acro-TSQ covers symptoms and symptom control, gastrointestinal side effects and their impact on daily activities, the emotional impact of treatment, convenience and ease of use, and overall satisfaction. CONCLUSIONS: The Acro-TSQ is a novel PRO, focused on both disease burden and impact of treatment; it was found to be comprehensive, clear, and relevant for patients with acromegaly receiving injectable SSA treatment.

Validity and responsiveness of the Urticaria Activity and Impact Measure: A new patient-reported tool.

BACKGROUND: Chronic spontaneous urticaria (CSU), also known as chronic idiopathic urticaria, may produce hives, itch, and angioedema. The Urticaria Activity and Impact Measure (U-AIM) is a newly developed 9-item patient-reported measure designed for use in routine clinical practice to assess CSU activity and impact during the previous 7 days. OBJECTIVE: To evaluate validity, responsiveness, and clinically meaningful change of the U-AIM. METHODS: Data from a 24-week, open-label, single-arm period of a randomized, placebo-controlled study of omalizumab were used to assess the psychometric properties of U-AIM items for itch, hives, and angioedema. RESULTS: A total of 206 patients (75% female; mean age, 44.6 years) were enrolled. At baseline, U-AIM results included prevalent severe itch (55%) and more than 12 hives (67%), angioedema (15%), and bother by itch (84%), hives (84%), and angioedema (49%). The Urticaria Patient Daily Diary (UPDD) mean weekly scores were 15.4 (itch severity), 16.8 (number of hives), and 32.2 (Urticaria Activity Score [UAS7]). At baseline, week 12, and week 24, U-AIM itch and hives items and UAS7 proxy scores (the sum of itch severity and number of hives during 7 days) demonstrated strong correlation coefficients with their corresponding measures from the UPDD (itch severity: 0.634-0.806; hives number: 0.735-0.843; UAS7 proxy: 0.724-0.852). Changes in U-AIM scores differentiated patients by their perspective of symptom improvement. Meaningful change thresholds were established for itch severity and number of hives scores (range, 0.8-1.0 for both) and the UAS7 proxy score (range, 10.5-12.5). CONCLUSION: The U-AIM is valid and responsive to change and may help clinicians monitor CSU activity and track treatment effectiveness.

Development of Focal Segmental Glomerulosclerosis Patient-Reported Outcome Measures: Symptom Diary and Symptom Impact Questionnaire.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a kidney disease that affects patients' functioning and well-being. This study aimed to develop patient-reported outcome questionnaires to measure patient experiences related to FSGS. STUDY DESIGN: Qualitative patient interviews to identify important symptoms and concepts (concept elicitation) formed the basis for the development of 2 questionnaires, one on symptoms and one on their impact. Additional qualitative interviews were implemented to evaluate/refine the questionnaires (cognitive debriefing). Transcripts of concept elicitation and cognitive debriefing interviews, conducted by telephone, were analyzed for concepts of interest using qualitative text analysis. SETTING & PARTICIPANTS: Patients with FSGS (aged 18-65 years with estimated glomerular filtration rates ≥ 40mL/min/1.73m2) whose disease remained inadequately controlled after 2 or fewer courses of treatment. METHODOLOGY: Qualitative concept elicitation and cognitive debriefing interviews. ANALYTICAL APPROACH: Interview transcripts were analyzed using qualitative software, MAXQDA. RESULTS: 30 patients completed concept elicitation interviews; 9 patients completed cognitive debriefing interviews. Frequently mentioned symptoms included swelling from the waist down/legs/knees/feet/ankles (67%), fatigue (57%), stomach/abdomen swelling (43%), body pain/pressure (30%), and shortness of breath (20%), as well as impacts on physical (52%), emotional (68%), and social functioning (89%). Based on analyses of interview transcripts and clinical input, 2 questionnaires, one on symptoms and one on the impact of the symptom, were drafted. The 23-item FSGS Symptom Diary (assessing the frequency and severity of FSGS symptoms during the past 24 hours) and the FSGS Symptom Impact Questionnaire (17 items assessing interference with activities and emotions during the past 7 days) were iteratively revised based on cognitive debriefing interviews. LIMITATIONS: The study was restricted to English-speaking adults located in the United States, and the concept elicitation interview group had a low number of African Americans. CONCLUSIONS: The FSGS Symptom Diary and FSGS Symptom Impact Questionnaire are new FSGS-specific patient-reported outcomes measures designed to support a comprehensive assessment of symptoms and symptom impact in adults with FSGS. Future research is needed to evaluate their quantitative measurement properties.

Development of the Systemic Lupus Erythematosus Steroid Questionnaire (SSQ): a novel patient-reported outcome tool to assess the impact of oral steroid treatment.

BACKGROUND: Oral glucocorticoids (steroids) are the mainstay of treatment for systemic lupus erythematosus (SLE), but their use is often associated with short- and long-term side effects. Following a literature review and discussions with patients with SLE, clinicians, and payers, a need was identified for a comprehensive SLE-specific tool that can be used to evaluate the side effects and benefits of steroids over time from a patient perspective. The objective of this study was to develop a patient-reported outcome (PRO) measure to assess general impact (baseline burden), benefits, side effects, and impacts associated with the use of oral steroids in patients with SLE. METHODS: A qualitative research protocol was developed in which adults with SLE currently receiving or who had received steroids in the past year were recruited from six US rheumatology practices to participate in concept elicitation (CE) interviews. The SLE Steroid Questionnaire (SSQ) was developed based on CE interview results and clinical input. Cognitive debriefing interviews with a second group of patients with SLE evaluated the content, clarity, and relevance of the items. The SSQ was refined using patient feedback, clinician review, and a translatability assessment. The protocol received central independent review board approval. RESULTS: Thirty-three patients (52% moderate disease severity; 58% currently receiving steroids, mean dose 8.7 mg/day) completed CE interviews. Patients reported benefits, side effects, and impacts from steroids. The refined SSQ contains 50 items assessing steroid dose/duration (4 items), general impact (baseline burden; 19 items), benefits (7 items), work/productivity (3 items), side effects (10 items), emotions (6 items), and overall satisfaction (1 item). CONCLUSION: The SSQ is a unique PRO, developed using robust scientific methodology in accordance with the Food and Drug Administration PRO Guidance. It was designed to comprehensively assess the patient experience with steroid therapy and better understand the benefits and burden of steroids for patients with SLE.