Development of the Cold Agglutinin Disease Symptoms and Impact Questionnaire (CAD-SIQ).

OBJECTIVES: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia. This study aimed to identify disease-related symptoms and impacts important to patients with CAD, and to develop a novel CAD-specific patient-reported outcome measure. METHODS: Adults with CAD were randomly selected from a United States patient panel to participate in concept elicitation (CE) interviews to identify important symptoms and impacts or cognitive debriefing (CD) interviews to assess the comprehension and relevance of the draft item set. RESULTS: Overall, 37 adults were included (mean [range] age 67.2 [35-87] years). In CE interviews (n = 16), the most frequently reported CAD-related symptoms were reactions to cold environments and fatigue (both 93.8%). CAD had negative impacts on enjoyable activities (81.3%) and daily activities (75.0%). Following CE, standard survey methodological principles were used to develop a draft item pool of 14 concepts. Items were refined through three iterative rounds of CD interviews (n = 21), yielding 11 final items: fatigue; cold sensitivity; dyspnea; wearing extra clothing; limited physical, social, and enjoyable activities; difficulty with usual activities; mood; frustration; and anxiety/stress. CONCLUSIONS: The novel 11-item CAD-Symptoms and Impact Questionnaire provides a measure of the symptoms and impacts of CAD that are important to patients.

Experiences, attitudes, and perceptions of caregivers of individuals with treatment-resistant schizophrenia: a qualitative study.

BACKGROUND: Treatment-resistant schizophrenia (TRS) affects about one-third of individuals with schizophrenia. People with TRS do not experience sustained symptom relief and at the same time have the most severe disease-related disability and associated costs among individuals with severe mental disorders. Like caregivers of people with treatment-responsive schizophrenia, caregivers of individuals with TRS experience the disease burden along with their care recipients; however, for those providing care for individuals with TRS, the stress of the burden is unrelenting due to uncontrolled symptoms and a lack of effective treatment options. The objective of this study is to better understand the burden of TRS from the caregiver perspective and to explore their perception of available treatments. METHODS: Eight focus groups with non-professional, informal caregivers of individuals with TRS were conducted in 5 US locations. TRS was defined as failure of ≥2 antipsychotics and persistent moderate-to-severe positive symptoms of schizophrenia, per caregiver report. RESULTS: The 27 caregivers reported an average of 37 h/week providing direct care, and 21 reported being on call "24/7." Caregivers commonly reported that their care recipients exhibited symptoms of auditory hallucinations (89%), agitation/irritability/hostility (81%), suspiciousness (78%), tangentiality (74%), and cognitive impairment (74%); 70% of caregivers ranked suspiciousness/persecution as the most challenging symptom category. Caring for an individual with TRS impacted many caregivers' finances, career prospects, social relationships, and sense of freedom. Additionally, multiple medication failures led to a sense of hopelessness for many caregivers. CONCLUSIONS: Persistent positive symptoms caused significant perceived burden, feelings of being overwhelmed and having no relief, and substantial negative impacts on caregivers' emotional and physical health. To address these substantial unmet needs, policy makers should be aware of the need for practical, social, and emotional support for these caregivers and their families. Additionally, new treatment options for TRS should be developed.

Screening and treatment for short cervical length in pregnancy: a physician survey in the United States.

PURPOSE: To evaluate how physicians in the United States (US) screen for, define, and treat a short cervix to prevent preterm birth. METHODS: This was a cross-sectional, web-based survey of 500 physicians treating pregnant patients with a short cervix in the US. Respondents' geographic region was monitored to ensure balance across the nine US Census divisions. RESULTS: Respondents were predominantly obstetrician/gynecologists (86%, 429/500; mean age 49 years). Physicians reported that a median of 90% of their pregnant patients undergo cervical length screening; 81% (407/500) use transvaginal ultrasound. Physicians consult multiple evidence sources to inform their patient care, most commonly clinical guidelines (83%; 413/500) and published research (70%; 349/500). Most physicians (98%; 490/500) reported treating pregnant patients with a short cervix; 95% (474/500) use synthetic and/or natural progestogen, alone or in combination with other treatment modalities. If reimbursement was not a concern, 47% of physicians (230/500) would choose vaginal progesterone as their preferred treatment to prevent preterm birth in all patients with a short cervix, and 45% (218/500) would choose a synthetic progestogen. CONCLUSION: US guidelines recommend transvaginal ultrasound for cervical length screening; 81% of physicians in this study reported using this method. Most physicians surveyed use progestogens to treat a short cervix, with approximately half choosing a synthetic progestin (45%) and half choosing natural progesterone (47%) as their preferred treatment, despite national guidelines recommending only vaginal natural progesterone for this indication. Additional physician education is required to implement current and best practices.

Assessing the burden of treatment-emergent adverse events associated with atypical antipsychotic medications.

BACKGROUND: Treatment of schizophrenia and major depressive disorder (MDD) with atypical antipsychotics (AAPs) show improved efficacy and reduced side effect burden compared with older antipsychotic medications. However, a risk of treatment-emergent adverse events (TEAEs) remains. TEAEs are hard to quantify and perspectives on the importance of TEAEs differ across patients and between patients and physicians. The current study is a qualitative assessment that investigates TEAEs of AAPs from both patient and physician perspectives to provide better understanding of the occurrence and burden of TEAEs associated with these medications. METHODS: Focus groups comprised of patients with MDD and interviews with patients with schizophrenia were conducted at two qualitative research facilities, along with a physician focus group at one of the facilities. Information collected from patients included an exhaustive list of TEAEs experienced, and the frequency and level of bother of each TEAE; from psychiatrists, information included an exhaustive list of TEAEs based on personal observations and patient report, frequency of TEAEs, clinically important TEAEs, and levels of patient-perceived bother. Standard qualitative analysis methods were used to identify, quantify, characterize, and summarize patterns found in the data collected. RESULTS: A total of 42 patients (25 with MDD and 17 with schizophrenia) and 4 psychiatrists participated in the study. TEAEs reported as bothersome across both patients groups included cognitive issues, weight gain and/or increased appetite, low energy, extrapyramidal symptoms (EPS), and need to sleep/excessive sleep/excessive sleepiness. TEAEs considered more bothersome by patients with schizophrenia were weight gain, low energy, EPS, mental anxiety, and increased positive symptoms; those considered more bothersome by patients with MDD were cognitive issues, somnolence/sedation, and flat/restricted affect. TEAEs considered most clinically important by psychiatrists included metabolic syndrome, weight gain, neutropenia, hyperglycemia, and QT prolongation; those TEAEs considered most bothersome to patients from physicians' perspectives included weight gain, reduced sexual desire or performance, EPS, akathisia, and hormonal issues. CONCLUSIONS: The wide range of TEAEs that are both frequent and bothersome and the variation in perceived burden according to diagnosis highlight the need for a tailored TEAE-awareness approach when choosing an AAP.

Patient-completed or symptom-based screening tools for endometriosis: a scoping review.

PURPOSE: The objective of this review was to evaluate existing patient-completed screening questionnaires and/or symptom-based predictive models with respect to their potential for use as screening tools for endometriosis in adult women. Validated instruments were of particular interest. METHODS: We conducted structured searches of PubMed and targeted searches of the gray literature to identify studies reporting on screening instruments used in endometriosis. Studies were screened according to inclusion and exclusion criteria that followed the PICOS (population, intervention, comparison, outcomes, study design) framework. RESULTS: A total of 16 studies were identified, of which 10 described measures for endometriosis in general, 2 described measures for endometriosis at specific sites, and 4 described measures for deep-infiltrating endometriosis. Only 1 study evaluated a questionnaire that was solely patient-completed. Most measures required physician, imaging, or laboratory assessments in addition to patient-completed questionnaires, and several measures relied on complex scoring. Validation for use as a screening tool in adult women with potential endometriosis was lacking in all studies, as most studies focused on diagnosis versus screening. CONCLUSIONS: This literature review did not identify any fully validated, symptom-based, patient-reported questionnaires for endometriosis screening in adult women.

Patient-centered assessment of cognitive symptoms of depression.

OBJECTIVE: To identify and explore concepts important to patients with cognitive symptoms of major depressive disorder (MDD) and adapt an existing patient-reported outcome (PRO) measure to assess these symptoms. METHODS: Four focus groups were conducted with MDD patients (n = 33) to elicit relevant concepts and determine whether one of several PRO scales could be used to assess cognitive symptoms of depression. Following selection and minor modification of the Perceived Deficits Questionnaire (PDQ), cognitive debriefing interviews were conducted with additional patients (n = 17) to further refine and adapt this measure for use in MDD. Minor revisions based on patient input yielded the PDQ for Depression (PDQ-D). RESULTS: Focus group participants reported a variety of cognitive symptoms that were classified into 7 general categories: lack of focus and clear thought, memory problems, difficulty with lexical access, difficulty with divided attention, difficulty with decision making, difficulty thinking quickly, and difficulty learning new things. Limitations in work productivity were the most commonly reported impacts of cognitive symptoms. While suggesting a few modifications, focus group participants reacted positively to the PDQ based on the breadth, specificity, and relevance of the items. Cognitive debriefing participants indicated that the modified PDQ items were generally easy to understand and relevant to their experiences with MDD. CONCLUSION: Because cognitive symptoms are burdensome to patients with MDD, their assessment is important to optimize treatment outcomes. The PDQ-D has the potential to supplement existing assessment methods, providing unique information important for both comprehensive evaluation of individuals with MDD and evaluation of new treatments.

Evaluating Elements of the Care Partner Experience in Individuals Who Care for People with Alzheimer's Disease Across the Severity Spectrum.

INTRODUCTION: Non-professional care partners play an important and often evolving role in the care of persons living with Alzheimer's disease (PLWAD). We investigated two elements of the care partner experience, namely time and strain incurred by care partners providing care to PLWAD across the severity spectrum. METHODS: Data gathered from the Alzheimer's Disease Patient and Caregiver Engagement (AD PACE) What Matters Most (WMM) study series were analyzed to determine how much time care partners spent providing care to PLWAD based on where the care recipients lived. Additionally, quantitative assessments of weekly hours providing care and the strain experienced by care partners were conducted using the UsAgainstAlzheimer's A-LIST Insights Series survey, which included the Modified Caregiver Strain Index (MCSI). Finally, a targeted literature review was conducted to contextualize findings and characterize the existing literature landscape. RESULTS: Care partners in the AD PACE WMM studies (n = 139) spent significantly more hours providing care for recipients who lived with someone (mean ± standard deviation [SD], 57.3 ± 44.3 h/week) than for recipients who lived alone (26.0 ± 12.0 h/week) (P = 0.0096) or lived in assisted living/nursing home (23.6 ± 14.4 h/week) (P = 0.0002). In the A-LIST Insights Series survey, care partners provided an overall mean (± SD) 58.1 ± 53.0 h of direct care each week, with caregiving hours increasing with increasing severity of AD/AD-related dementias (AD/ADRD). Additionally, care partners for recipients with mild (n = 14), moderate (n = 111), and severe AD/ADRD (n = 91) had overall mean MCSI scores of 9.0 ± 3.8 (range 2-14), 13.3 ± 4.8 (range 4-23), and 17.5 ± 5.3 (range 4-26), respectively, with higher scores suggesting greater care partner strain. CONCLUSIONS: Persons living with AD require increasing levels of care along the spectrum of disease, and even individuals with early disease need care from partners. Early interventions that slow progression of AD and programs that improve family function may have beneficial impact on the experiences of care partners for recipients with mild, moderate, or severe AD.

Understanding Patients' Experiences with Borderline Personality Disorder: Qualitative Interviews.

Background: Patient perspectives of living with borderline personality disorder (BPD) are not traditionally captured in the literature. To overcome this gap, we explored participants' experiences with BPD to gain a better understanding of symptoms and impacts related to the condition. Methods: Two experienced researchers conducted semistructured interviews with a subset of participants from a randomized controlled trial evaluating a BPD treatment. The interview study was independent from the trial. Interviews focused on participants' experiences with BPD prior to the trial, including the symptoms and impacts of BPD. Interview transcripts were analyzed to identify dominant trends and generate patterns in the way participants described their experiences with BPD. Results: A total of 50 adults with BPD participated in the interview study. The mean age of the participants was 28.5 years (range, 18-53 years) and 72.0% were female. All participants described having difficulties with extreme emotional responses and interpersonal relationships, and most participants reported experiencing issues with self-image, impulsivity, suspiciousness/distrust, feelings of emptiness, and anger. The symptoms that were most bothersome to participants were extreme moods or emotional responses and a pattern of unstable personal relationships. All participants remarked that their BPD-related symptoms negatively impacted their interpersonal relationships, and nearly two-thirds of the sample reported that the impact of BPD on their relationships was the most bothersome. Additionally, more than half of the participants discussed impacts on work or school, memory or thinking, self-care, and financial and legal issues. Conclusion: Participants reported that the most bothersome symptoms of BPD were those related to extreme moods or emotional responses and interpersonal relationships. Participants similarly described the impact of BPD on their interpersonal relationships as the most bothersome. Overall, participant perspectives from this study indicate that the burden of BPD is significant and new treatments tailored to patients' real-world needs are warranted.

Practice patterns and perspectives regarding treatment for symptoms of menopause: qualitative interviews with US health care providers.

OBJECTIVE: To document health care providers' views regarding treatments for symptoms associated with menopause and discussions with patients about symptoms and treatment decisions. Results informed development of a data collection form for a retrospective medical record review (reported separately). METHODS: Registered US gynecologists or primary care providers from all US regions were identified from local association directories and an in-house database and were invited to participate in a qualitative interview if they consulted with three or more patients per week presenting with menopausal symptoms. Participants provided demographic data, information about patients' symptoms, and health care provider and patient views on prescription and nonprescription therapies. Key concepts/themes from interviews were identified. RESULTS: Participating health care providers (10 gynecologists, 10 primary care providers) agreed there are effective treatment options for menopausal symptoms, particularly vasomotor symptoms and vaginal dryness and/or atrophy. Health care providers reported that treatment was generally dictated by symptoms that interfered with quality of life and/or daily activities, although patients often had symptoms for months before presentation. All health care providers said they prescribe hormone and/or nonhormone therapies for treatment of menopausal symptoms; half stated that they typically inquire about patients' nonprescription therapy use, and 45% recommend specific nonprescription therapies. The most commonly cited barriers to initiation of any therapy for menopausal symptoms were patient concerns about risks and financial considerations (ie, insurance or cost). CONCLUSIONS: US health care providers reported prescribing therapies for menopausal symptoms and noted that these therapies were perceived as generally effective; however, barriers to initiation of prescription therapy exist, and new treatment options are needed.

Technical Review of Clinical Outcomes Assessments Across the Continuum of Alzheimer's Disease.

INTRODUCTION: Insight into the relationship between concepts that matter to the people affected by Alzheimer's disease (AD) and the clinical outcome assessments (COAs) commonly used in AD clinical studies is limited. Phases 1 and 2 of the What Matters Most (WMM) study series identified and quantitatively confirmed 42 treatment-related outcomes that are important to people affected by AD. METHODS: We compared WMM concepts rated as "very important" or higher to items included in COAs used commonly in AD studies. RESULTS: Twenty COAs designed to assess signs, symptoms, and impacts across the spectrum of AD were selected for review. Among these 20 COAs, only 5 reflected 12 or more WMM concepts [Integrated Alzheimer's Disease Rating Scale (iADRS), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory-Mild Cognitive Impairment (ADCS-ADL-MCI), Alzheimer's Disease Composite Scores (ADCOMS), and Clinical Dementia Rating; Clinical Dementia Rating-Sum of Boxes (CDR/CDR-SB)]. Multiple symptoms and impacts of AD identified as important and meaningful in the WMM studies map only indirectly at best to 7 of the 20 most widely used COAs. CONCLUSION: While many frequently used COAs in AD capture some concepts identified as important to AD populations and their care partners, overlap between any single measure and the concepts that matter to people affected by AD is limited. The highest singly matched COA reflects fewer than half (45%) of WMM concepts. Use of multiple COAs expands coverage of meaningful concepts. Future research should explore the content validity of AD COAs planned for AD trials based on further confirmation of the ecological validity of the WMM items. This research should inform development and use of core outcome sets that capture WMM items and selection or development of new companion tools to fully demonstrate clinically meaningful outcomes spanning WMM.

Assessing What Matters to People Affected by Alzheimer's Disease: A Quantitative Analysis.

INTRODUCTION: In this phase of the ongoing What Matters Most study series, designed to evaluate concepts that are meaningful to people affected by Alzheimer's disease (AD), we quantified the importance of symptoms, impacts, and outcomes of AD to people at risk for or with AD and care partners of people with AD. METHODS: We administered a web-based survey to individuals at risk for or with AD (Group 1: unimpaired cognition with evidence of AD pathology; Group 2: AD risk factors and subjective cognitive complaints/mild cognitive impairment; Group 3: mild AD) and to care partners of individuals with moderate AD (Group 4) or severe AD (Group 5). Respondents rated the importance of 42 symptoms, impacts, and outcomes on a scale ranging from 1 ("not at all important") to 5 ("extremely important"). RESULTS: Among the 274 respondents (70.4% female; 63.1% white), over half of patient respondents rated all 42 items as "very important" or "extremely important," while care partners rated fewer items as "very important" or "extremely important." Among the three patient groups, the minimum (maximum) mean importance rating for any item was 3.4 (4.6), indicating that all items were at least moderately to very important. Among care partners of people with moderate or severe AD, the minimum (maximum) mean importance rating was 2.1 (4.4), indicating that most items were rated as at least moderately important. Overall, taking medications correctly, not feeling down or depressed, and staying safe had the highest importance ratings among both patients and care partners, regardless of AD phase. CONCLUSION: Concepts of importance to individuals affected by AD go beyond the common understanding of "cognition" or "function" alone, reflecting a desire to maintain independence, overall physical and mental health, emotional well-being, and safety. Preservation of these attributes may be key to understanding whether interventions deliver clinically meaningful outcomes.

The Patient Voice: Exploring Treatment Preferences in Participants with Mild Cognitive Concerns to Inform Regulatory Decision Making.

OBJECTIVE: We aimed to assess the feasibility of developing a discrete-choice experiment survey to elicit preferences for a treatment to delay cognitive decline among people with a clinical syndrome consistent with early Alzheimer's disease, including the development of self-reported screening criteria to recruit the sample. METHODS: Using input from qualitative interviews, we developed a discrete-choice experiment survey containing a multifaceted beneficial treatment attribute related to slowing cognitive decline for respondents with self-reported cognitive concerns. In two rounds of in-person pretest interviews, we tested and revised the survey text and discrete-choice experiment questions, including examples, language, and levels associated with the Alzheimer's Disease Assessment Scale-Cognitive Subscale, along with a set of de novo self-reported questions for identifying respondents who had neither too mild nor too advanced cognitive decline. Self-reported memory and thinking problems were compared with symptoms from studies of patients with early Alzheimer's disease (e.g., mild cognitive impairment, mild Alzheimer's disease) to determine whether those studies' recruited patients were similar to our anticipated target population. Round 1 pretest interviews resulted in significant simplifications in the survey instrument, revisions to the inclusion and exclusion criteria, and revisions to the screening process. In round 2 of the pretest interviews, the ability of participants to provide consistent responses to the self-reported screening questions was further assessed. In addition, to evaluate participants' ability to understand and independently complete the discrete-choice experiment survey, two interviewers independently evaluated each participant's ability to make trade-offs in the discrete-choice experiment questions and to understand the content of the survey. RESULTS: Round 1 (15 pretest interviews) identified challenges with the survey instrument related to the complexity of the choice questions. The screening process did not screen out seven respondents with more advanced cognitive decline, as determined qualitatively by the interviewers and by these participants' inability to complete the survey. The survey instrument and screening criteria were revised, and an initial online screener was added to the screening process before round 2 pretests. In round 2 pretests, 12 participants reported cognitive problems similar to the target population for the survey but were judged able to understand and independently complete the discrete-choice experiment survey. CONCLUSIONS: We developed self-reported screening criteria that identified a sample of individuals with memory and thinking concerns who were similar to individuals with clinical symptoms of early Alzheimer's disease and who were able to independently complete a simplified discrete-choice experiment survey. Quantitative patient preference studies provide important information on patients' willingness to trade off treatment benefits/risks. Adapting the technique for patients with cognitive decline requires careful testing and adjustments to survey instruments. This work suggests it is the severity of cognitive impairment, rather than its presence, that determines the ability to complete a simplified discrete-choice experiment survey.

Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis.

INTRODUCTION: Itch associated with atopic dermatitis (AD) has a profoundly negative effect on patients of all ages. Therefore, itch is a main target for AD therapeutic approaches, and treatments are perceived as beneficial when they achieve an itch reduction. In the absence of a validated scale for children aged 6-11 years that is suitable for assessing itch intensity in clinical trial settings, the Worst Itch Scale was developed. METHODS: Qualitative interviews, comprising concept elicitation and cognitive debriefing, were conducted to develop and evaluate the content validity of the Worst Itch Scale. Psychometric assessments used data from the LIBERTY AD PEDS phase 3 trial of dupilumab in patients aged 6-11 years with severe AD. These included test-retest reliability, construct validity, known-groups validity and responsiveness. Thresholds for clinically meaningful change were defined using anchor- and distribution-based methods. RESULTS: The Worst Itch Scale consisted of two items asking about 'worst itching' experienced 'last night' and 'today'. Worst Itch Scale scores showed large, positive correlations with existing patient-reported outcome (PRO) measures of itch, and weaker correlations with clinician-reported outcome (ClinRO) measures assessing objective signs of AD. Improvements in Worst Itch Scale scores were highly correlated with improvements in other itch PROs and moderately correlated with improvements in ClinROs. The responder definition based on the primary anchor, a 1-point improvement in the Patient Global Impression of Disease, was 2.84. Supportive anchors produced response estimates ranging from 2.43 to 4.80 points. CONCLUSIONS: The Worst Itch Scale is a fit-for-purpose (e.g. well-defined, reliable, responsive and valid) scale for evaluating worst itch intensity in children aged 6-11 years with severe AD. The within-patient threshold for defining a clinically meaningful response was a ≥ 3-4-point change in the Worst Itch Scale score. TRIAL REGISTRATION: NCT03345914. Video: How can we reliably assess itch intensity in children 6-11 years with severe atopic dermatitis in clinical trial settings?

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.

The development and validation of the daily electronic Endometriosis Pain and Bleeding Diary.

BACKGROUND: The objective of this study was to develop and validate a daily electronic Endometriosis Pain and Bleeding Diary (EPBD) for assessing treatment-related changes in endometriosis symptoms from the patient's perspective in a clinical trial setting. METHODS: The EPBD items were developed based on clinician input and the results of 5 focus groups (N = 38) and 3 iterative sets of cognitive interviews (N = 22). The psychometric properties were evaluated using data collected in a usual-practice, non-intervention study conducted at 4 sites in the United States. Existing questionnaires were also administered to explore the construct validity of the EPBD. The development and validation processes were consistent with the recommendations in the 2009 FDA Patient Reported Outcomes Guidance to Industry. RESULTS: Focus group participants described 2 distinct types of pain (intermittent and continuous), which they felt were relevant and important to monitor. Participants also indicated that pain and bleeding/spotting associated with intercourse were important symptoms related to endometriosis. Cognitive interviews with additional endometriosis patients served to optimize item content, wording, and response options. Psychometric analyses found the EPBD items to behave as expected, for example, item-level means for subjects with severe endometriosis symptoms were higher (i.e., worse) compared with subjects with mild symptoms. Item-total correlations for the EPBD pain items (range 0.40-0.89) indicated that the items were related but not redundant. EPBD pain ratings correlated highly with the modified Brief Pain Inventory-Short Form Pain Intensity score (range 0.46-0.61). Women with severe endometriosis symptoms reported significantly higher intermittent and continuous dysmenorrhea and intermittent and continuous pelvic pain ratings and greater interference with daily activities compared with women with mild symptoms (all p < 0.01). CONCLUSIONS: The results of this study show that the 17-item EPBD reliably and validly characterizes the types of pain that endometriosis patients identified as being important. As a daily patient-reported assessment, it overcomes the significant potential for intra- and inter-rater variability and rater and recall bias that is inherent in the Biberoglu and Behrman Scale. Additional studies are required to confirm the dimensionality and optimal scoring of the EPBD, to corroborate the present results, and to assess other important measurement properties, such as responsiveness.

Development and psychometric evaluation of the Endometriosis Treatment Satisfaction Questionnaire.

PURPOSE: To develop and psychometrically evaluate the Endometriosis Treatment Satisfaction Questionnaire, a patient-reported assessment of satisfaction with endometriosis treatment. METHODS: The Endometriosis Treatment Satisfaction Questionnaire was developed based on the results of five focus groups and three iterative sets of cognitive interviews along with expert opinion and a review of the literature. The psychometric properties were assessed using data collected during a multicenter, randomized, proof-of-concept trial. The development and validation processes followed the guidance recommended by the United States FDA for patient-reported outcome instruments. RESULTS: The Endometriosis Treatment Satisfaction Questionnaire's reliability, validity, and utility as a measure of patient satisfaction with their endometriosis treatment were supported. The results of the item-level analyses showed no evidence of distributional anomalies or response scale biases. The Endometriosis Treatment Satisfaction Questionnaire is unidimensional, has excellent internal consistency reliability, and discriminates well between known groups. Scores correlated well with other patient-reported outcome measures of endometriosis without being redundant. CONCLUSIONS: The Endometriosis Treatment Satisfaction Questionnaire has utility for assessing patient satisfaction with endometriosis treatment and may be useful in clinical trials that are assessing new treatments for endometriosis, especially when deciding between competing treatments or regimens that are found to have similar tolerability and efficacy.

Patients' perspectives of endometriosis-related fatigue: qualitative interviews.

BACKGROUND: Endometriosis-related fatigue is common and negatively impacts multiple areas of many women's lives, particularly in day-to-day activities, social activities, physical activities, mood and emotions, relationships with family or partners, and work or school. Multiple studies have documented fatigue as a significant symptom of endometriosis. Additional research is needed to better understand endometriosis-related fatigue and its impacts on patients. METHODS: This qualitative study consisted of individual in-person semistructured interviews conducted with 22 adult females reporting moderate to severe endometriosis-related pain. Women with self-reported, surgically confirmed endometriosis and moderate to severe endometriosis-related pain were recruited from qualitative research firms in two locations in the United States. Qualified subjects participated in semistructured interviews that lasted approximately 45 min each. Interviews were audio recorded and transcribed for qualitative analysis. RESULTS: All 22 participants reported experiencing fatigue related to their endometriosis. While the degree of severity of their endometriosis-related fatigue varied, 21 of the 22 participants stated that it was at least "somewhat bothersome." Most participants noted an impact from endometriosis-related fatigue on day-to-day activities, social activities, physical activities, mood and emotions, relationships with family or partner, and work or school. CONCLUSIONS: The data presented here indicate that endometriosis-related fatigue has a pervasive impact on the functioning of women living with this condition. Future studies should measure any changes in fatigue that may be associated with treatment for endometriosis.

Assessing what matters most to patients with or at risk for Alzheimer's and care partners: a qualitative study evaluating symptoms, impacts, and outcomes.

BACKGROUND: The What Matters Most (WMM) study was initiated to evaluate symptoms, AD-related impacts, treatment-related needs, preferences, and priorities among individuals with or at risk for Alzheimer's disease (AD) and their care partners. The objective of this qualitative study phase was to identify a comprehensive set of concepts of interest that are meaningful to individuals across the AD continuum. METHODS: Interviews were conducted with 60 clinically referred individuals and care partners across 5 AD stages (n = 12 each): group 1 (non-clinically impaired individuals with AD pathology), group 2 (individuals with mild cognitive impairment and AD pathology), group 3 (individuals with mild AD), group 4 (individuals with moderate AD and their care partners), and group 5 (care partners of individuals with severe AD). Interviews were conducted by experienced interviewers, audio-recorded, and transcribed. Dominant trends were identified in each interview and compared across subsequent interviews to generate themes or patterns in descriptions of AD symptoms, impacts, and desired treatment outcomes. RESULTS: All participants endorsed current issues related to memory; nearly all participants (n = 55; 92%) across the five groups endorsed symptoms related to communication and language. Groups 1-3 reported an impact on mood/emotions (n = 23; 64%) and a decrease in social activities or outgoingness (n = 17; 47%). Current and future concerns reported by the overall sample included memory (n = 48; 80%), dependence (n = 40; 67%), and "other" concerns (n = 33; 55.0%) (e.g., uncertainty about the future, burdening others). The most desired AD treatment outcomes were improvement or restoration of memory (n = 40; 67%) and stopping AD progression (n = 35; 58.3%). Group-level differences were observed in the symptoms, impacts, and desired treatment outcomes among patients and care partners across the AD continuum. CONCLUSIONS: Cognitive functioning issues-particularly in memory and communication-are present even in preclinical and early-stage AD, including among those without a formal AD diagnosis. While the impacts of AD vary across the disease-severity spectrum, improved memory and disease modification were treatment outcomes considered most important to participants across all 5 AD stages. Neuropsychological assessments traditionally used in AD clinical trials may not evaluate the often-subtle concepts that are important to patients and care partners. Results from this study will inform the second phase of the WMM project-a quantitative study to elicit the relative importance of these concepts of interest to people at risk for and living with AD and their care partners.

Development and psychometric evaluation of the Diabetic Gastroparesis Symptom Severity Diary.

BACKGROUND: Diabetic gastroparesis (DG) is defined as delayed gastric emptying with associated gastrointestinal symptoms, without mechanical obstruction. Patient-reported symptoms are critical for diagnosis and evaluation of treatment benefit in DG. The Diabetic Gastroparesis Symptom Severity Diary (DGSSD), a new patient-reported outcome measure, was developed for use in clinical trials to support product approval and labeling claims for DG treatments. MATERIALS AND METHODS: Initial DGSSD development was based on a review of the existing instruments and qualitative research (focus groups and cognitive debriefing interviews) in 41 patients with DG. Psychometric evaluations (individual items and composite scores) were conducted using data from Phase IIa and IIb relamorelin clinical trials. RESULTS: Qualitative research in patients with DG resulted in a six-item DGSSD, included in the Phase IIa trial, addressing symptom severity for nausea, vomiting, abdominal pain, early satiety, and bloating, as well as vomiting frequency. An item addressing severity of postprandial fullness (PPF) was subsequently added based on regulatory advice and included in the Phase IIb trial. Measurement properties were generally strong for weekly averages of daily item and composite scores. Item-level intraclass correlation coefficients ranged from 0.79 to 0.97 and correlations with other measures matched hypothesized patterns; the discriminating ability and responsiveness of the DGSSD were also supported. Multiple methods supported the computation of a composite score based on items addressing nausea, abdominal pain, bloating, and PPF severity. CONCLUSION: Qualitative and quantitative evidence support use of the DGSSD as a reliable and valid measure from which to derive endpoints to evaluate treatment benefit in future DG interventional trials.