The impacts of migraine on functioning: Results from two qualitative studies of people living with migraine.

OBJECTIVE: To describe the impact of migraine on functioning based on comprehensive data collection, analysis, and reporting of patients' experiences. BACKGROUND: Qualitative research conducted to understand patients' perspectives on living with migraine has often focused on narrow topics or specific groups of patients or has been selectively reported. METHODS: Qualitative interviews with 71 participants were conducted during two concept elicitation studies as part of the Migraine Clinical Outcome Assessment System (MiCOAS) project, an FDA grant-funded program designed to develop a core set of patient-centered outcome measures for migraine clinical trials. Participants self-reported being diagnosed with migraine by a healthcare professional and participated in semi-structured qualitative interviews about their experiences with the symptoms and impacts of migraine. Interview transcripts were coded to identify and define concepts, which were then grouped into broad domains based on conceptual similarities. RESULTS: A total of 66 concepts were identified: 12 for physical functioning, 16 for cognitive functioning, 10 for social role functioning, 19 for emotional and psychological functioning, and 9 related to migraine management. Participants described a complex and varied relationship between migraine attack symptoms and impacts on functioning. Impacts from migraine were further influenced by numerous contextual factors, such as people's individual social environments and the level of day-to-day demand for functioning they face. CONCLUSION: Findings showed that migraine impacted individual functioning in multiple ways and the nature of these impacts was dependent on social-contextual factors. The results are being used in the development of core measures designed to improve our understanding of the burden of migraine and the efficacy of migraine therapies. The results also offer new insights and raise new questions about migraine experience that can be used to guide future research.

Priority acute and preventive migraine treatment benefits: Results of the Migraine Clinical Outcome Assessment System (MiCOAS) qualitative study of people living with migraine.

BACKGROUND: There is renewed emphasis on including patients in determining, defining, and prioritizing outcomes for migraine treatment. OBJECTIVES: To obtain insights directly from people living with migraine on their priorities for treatment. METHODS: A total of 40 qualitative interviews were conducted as part of the Migraine Clinical Outcome Assessment System project, a United States Food and Drug Administration grant-funded program to develop a core set of patient-centered outcome measures for migraine clinical trials. Interviews included a structured exercise in which participants rank-ordered pre-defined lists of potential benefits for acute and preventive migraine therapy. The 40 study participants who reported being diagnosed with migraine by a clinician ranked the benefits and explained their rationale. RESULTS: Study participants consistently ranked either pain relief or absence of pain as their top priority for acute treatment. Relief/absence of other migraine symptoms and improved functioning were also prioritized. For preventive treatment, participants prioritized reductions in migraine frequency, symptom severity, and attack duration. Few differences were found between participants with episodic migraine and those with chronic migraine. However, participants with chronic migraine ranked "increased predictability of attacks" much higher than those with episodic migraine. Participants' rankings were influenced by prior expectations and experiences of migraine treatments, which caused many participants to deprioritize desired benefits as unrealistic. Participants also identified several additional priorities, including limited side-effects and reliable treatment efficacy in both acute and preventive treatments. CONCLUSION: The results showed the participants prioritized treatment benefits aligned with existing core clinical outcomes used in migraine research, but also valued benefits that are not typically assessed, such as predictability. Participants also deprioritized important benefits when they believed treatment was unlikely to deliver those outcomes.

Patient-reported experiences with migraine-related cognitive symptoms: Results of the MiCOAS qualitative study.

OBJECTIVES: To capture patients' perspectives on migraine-related cognitive symptoms during pre-headache, headache, post-headache, and interictal periods. BACKGROUND: Migraine-related cognitive symptoms are reported by people with migraine both during and between attacks. Associated with disability, they are increasingly viewed as a priority target for treatment. The Migraine Clinical Outcome Assessment System (MiCOAS) project is focused on developing a patient-centered core set of outcome measures for the evaluation of migraine treatments. The project focuses on incorporating the experience of people living with migraine and the outcomes most meaningful to them. This includes an examination of the presence and functional impact of migraine-related cognitive symptoms and their perceived impact on quality of life and disability. METHODS: Forty individuals with self-reported medically diagnosed migraine were recruited via iterative purposeful sampling for semi-structured qualitative interviews conducted using audio-only web conferencing. Thematic content analysis was performed to identify key concepts around migraine-related cognitive symptoms. Recruitment continued until concept saturation was achieved. RESULTS: Participants described symptoms consistent with migraine-related deficits in language/speech, sustained attention, executive function, and memory that manifest during pre-headache (36/40 [90%] reported ≥1 cognitive feature), headache (35/40 [88%] reported ≥1 cognitive feature), post-headache (27/40 [68%] reported ≥1 cognitive feature), and interictal periods (13/40 [33%] reported ≥1 cognitive feature). Among participants reporting cognitive symptoms during pre-headache, 32/40 (81%) endorsed 2-5 cognitive symptoms. Findings were similar during the headache phase. Participants reported language/speech problems consistent with, for example, impairments in receptive language, expressive language, and articulation. Issues with sustained attention included fogginess, confusion/disorientation, and trouble with concentration/focus. Deficits in executive function included difficulty processing information and reduced capacity for planning and decision-making. Memory issues were reported across all phases of the migraine attack. CONCLUSIONS: This patient-level qualitative study suggests that cognitive symptoms are common for persons with migraine, particularly in the pre-headache and headache phases. These findings highlight the importance of assessing and ameliorating these cognitive problems.

Impact of the COVID-19 pandemic on people living with migraine: Results of the MiCOAS qualitative study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health crisis that has had a range of impacts on people living with migraine. METHODS: Qualitative interviews performed as part of the Migraine Clinical Outcome Assessment System project, a multi-stage Food and Drug Administration-grant funded program to develop a patient-centered core set of outcome measures for use in migraine clinical trials, offered an opportunity to explore the experience of living with migraine during the pandemic as well as to examine whether migraine treatment priorities, symptoms, and associated disability changed due to the pandemic. Semi-structured interviews were conducted in the United States between the summer and fall of 2020 with 40 individuals with self-reported, medically diagnosed migraine who self-reported that they had not tested positive for or been diagnosed with COVID-19. RESULTS: Seventy percent (n = 28) of the sample reported ≥1 pandemic-related impact on their life with migraine. Fourteen participants reported both positive and negative impacts, twelve reported negative impacts only, and two reported positive impacts only. Among those reporting ≥1 pandemic-related impact, nine participants (32%) reported more frequent and five (17%) reported less frequent migraine attacks. Other negative impacts included interrupted medical care (n = 9; 32%), and greater stress (n = 13; 46%). The most frequent positive impact reported was greater access to health care (n = 8; 29%). Ictal and interictal symptoms were not noted to change due to the pandemic, but some respondents reported less disability due to increased flexibility of schedules and reduced expectations. Treatment priorities did not change due to the pandemic. CONCLUSION: The global COVID-19 pandemic has resulted in both negative and positive impacts for people living with migraine. Lessons to be considered when moving into a post-pandemic world include benefits of and satisfaction with telehealth and the benefits and importance of healthy lifestyle habits and flexibility such as improved sleep, reduced stress, and fewer social expectations.

Patient perspectives on symptoms, health-related quality of life, and treatment experience associated with relapsed/refractory multiple myeloma.

PURPOSE: This study aimed to better understand the patient perspective and treatment experience of relapsed and/or refractory multiple myeloma (RRMM). METHODS: This qualitative study enrolled adult RRMM patients from 6 US clinics who had ≥ 3 months of life expectancy, ≤ 6 prior lines of therapy, and ≥ 1 treatment regimen with a proteasome inhibitor and immunomodulator, or a CD38 monoclonal antibody or an alkylating agent, and a steroid. In-person semi-structured qualitative interviews were conducted to capture concepts that were relevant and important to patients. Topics included RRMM symptoms and impacts and the mode of administration, frequency, duration, convenience, side effects, and overall experience with RRMM treatment. RESULTS: A total of 22 patients completed interviews. At enrollment, 59.1% of participants were using regimens containing dexamethasone, 36.4% daratumumab, 27.3% carfilzomib, and 18.2% lenalidomide. More participants had experience using intravenous or injectable therapy alone (40.9%) than oral therapy alone (18.2%). Back pain and fatigue were the most frequently reported symptoms (40.9% each); 27.3% reported no symptoms. Most participants reported physical function limitations (86.4%), emotional impacts (77.3%), MM-related activity limitations (72.7%), and sleep disturbances (63.6%). Most participants perceived treatment effectiveness based on physician-explained clinical signs (68.2%) and symptom relief (40.9%). Participants experienced gastrointestinal adverse events (59.1%), fatigue (59.1%), sleep disturbances (31.8%), and allergic reactions (31.8%) with treatment. Key elements of treatment burden included the duration of a typical treatment day (68.2%), treatment interfering with daily activities (54.5%), and infusion duration (50.0%). CONCLUSIONS: These results provide treatment experience-related data to further understand RRMM treatment burden and better inform treatment decision-making.

A qualitative study to understand the experience of somatostatin analog treatments from the perspective of patients with neuroendocrine tumors.

PURPOSE: Neuroendocrine tumors (NETs) negatively impact patients' quality of life. Octreotide long-acting release (LAR) and lanreotide depot are somatostatin analogs (SSAs) approved to treat NETs. The study objective was to explore SSA treatment experiences and preferences of patients with NETs. METHODS: Qualitative interviews were conducted in US adults (≥ 21 years) with NETs who had ≥ 6 months' treatment with each SSA and transitioned from octreotide LAR to lanreotide depot within the previous year. Participants were asked open-ended questions about their experiences with octreotide LAR and lanreotide depot, treatment preferences, and SSA treatment attributes. RESULTS: Twenty participants (mean age: 58 years; 90% female; 85% white) completed interviews. The most common reasons for treatment transition were doctor recommendation (70%), treatment not working as expected (55%), and injection type preference (45%). Participants reported 34 unique favorable attributes of SSA treatment and 82 unique unfavorable attributes. Symptom control was the most frequently reported favorable attribute (associated with octreotide LAR by 60% of participants and lanreotide depot by 65%). Painful injection (65%) was most frequently cited unfavorable attribute for octreotide LAR and injection experience dependent on administrator (35%) for lanreotide depot. The three SSA treatment attributes rated as most important were side effects, symptom control, and ability to stabilize tumor. CONCLUSION: Our qualitative data provide valuable insight into the treatment attributes that patients with NETs consider important when making SSA treatment decisions. Factors related to injection administration, side effects, and symptom control are important to patients and should be included in patient-provider communications in clinical contexts.

Non-Small Cell Lung Cancer Symptom Assessment Questionnaire: Psychometric Performance and Regulatory Qualification of a Novel Patient-Reported Symptom Measure.

BACKGROUND: The Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) was developed to incorporate the patient's perspective into evaluation of clinical benefit in advanced non-small cell lung cancer trials and meet regulatory expectations for doing so. Qualitative evidence supported 7 items covering 5 symptom concepts. OBJECTIVE: This study evaluated measurement properties of the NSCLC-SAQ's items, overall scale, and total score. METHODS: In this observational cross-sectional study, a purposive sample of patients with clinician-diagnosed advanced non-small cell lung cancer, initiating or undergoing treatment, provided sociodemographic information and completed the NSCLC-SAQ, National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lung Symptom Index (FLSI-17), and a Patient Global Impression of Severity item. Rasch analyses, factor analyses, and assessments of construct validity and reliability were completed. RESULTS: The 152 participants had a mean age of 64 years, 57% were women, and 87% where White. The majority were Stage IV (83%), 51% had an Eastern Cooperative Oncology Group performance status of 1 (32% performance status 0 and 17% performance status 2), and 33% were treatment naïve. Rasch analyses showed ordered thresholds for response options. Factor analyses demonstrated that items could be combined for a total score. Internal consistency (Cronbach  α = 0.78) and test-retest reliability (intraclass correlation coefficient = 0.87) were quite satisfactory. NSCLC-SAQ total score correlation was 0.83 with the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lung Symptom Index-17. The NSCLC-SAQ was able to differentiate between symptom severity levels and performance status (both P values < .001). CONCLUSIONS: The NSCLC-SAQ generated highly reliable scores with substantial evidence of construct validity. The Food and Drug Administration's qualification supports the NSCLC-SAQ as a measure of symptoms in drug development. Further evaluation is needed on its longitudinal measurement properties and interepretation of meaningful within-patient score change. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

Symptoms of Major Depressive Disorder Scale: Performance of a Novel Patient-Reported Symptom Measure.

BACKGROUND: The Symptoms of Major Depressive Disorder Scale (SMDDS) was expressly developed on the basis of qualitative data to directly incorporate patients' voices into evaluation of treatment benefit in major depressive disorder (MDD) clinical trials. OBJECTIVES: To collect quantitative data necessary to refine/optimize the SMDDS and document its psychometric properties. METHODS: In this multicenter, observational study, participants with clinically diagnosed MDD completed questionnaires in 2 waves. Wave 1 was designed to refine the SMDDS using Rasch measurement evaluations and item reduction analyses. On a subset of wave 1 subjects, 7 to 12 months later, wave 2 further examined item performance and measurement properties. Exploratory factor analyses and assessments of construct validity and reliability (internal consistency and reproducibility) were completed. RESULTS: Using wave 1 data (N = 315; females = 71%, white = 81%, mean age = 44 years), the SMDDS was revised from 36 to 16 items. The Rasch item threshold map indicated that all but 1 item (suicidal ideation) were appropriately ordered. The 207 wave 2 participants were 74% females, 82% white, with a mean age of 45 years. The exploratory factor analyses resulted in a single component (all standardized factor loadings >0.46). Cronbach α was 0.93 and the 7-day test-retest intraclass correlation coefficient (n = 93) was 0.84 (95% confidence interval 0.77-0.89). SMDDS scores discriminated between MDD severity levels. CONCLUSIONS: The 16-item SMDDS generated highly reliable scores with substantial evidence of construct validity. On the basis of the evidence of appropriate content validity and sound psychometric performance, the Food and Drug Administration qualified the SMDDS as an outcome measure to support exploratory efficacy endpoints in MDD clinical trials.

Physicians' Perspectives on Cost, Safety, and Perceived Efficacy Determine Aminosalicylate Use in Crohn's Disease.

BACKGROUND: Aminosalicylates are the most commonly prescribed therapy in Crohn's disease (CD), despite uncertainty in the evidence to support their efficacy. AIMS: To examine physicians' perspectives on aminosalicylate use for CD and explore the discordance between clinical practice and the evidence base. METHODS: A qualitative interview study was performed amongst physicians with at least 4 years of independent experience in managing CD patients. Semi-structured telephone interviews were conducted using an exploratory interview guide. Interview transcripts were thematically analyzed to elucidate concepts pertaining to treatment strategies for CD, motivations for prescribing aminosalicylates, perceived benefits and harms of aminosalicylate use, and the relationship between the evidence and real-world prescribing practices. RESULTS: A representative sample of thirty physicians from four different countries and multiple practice environments (university/teaching hospitals, public practice, private/community practice, and subspecialty gastroenterology clinics) participated. Nearly all physicians (93.3%, 28/30) reported prescribing aminosalicylates for CD. Aminosalicylates were endorsed as first-line therapy for mild CD by nearly half of participants (13/30, 43.3%). A favorable safety profile, possible efficacy in mild colonic CD, and patient reluctance to step-up to other therapies were primary motivators for aminosalicylate use. Almost half of respondents (46.7%) expressed that the evidence informing aminosalicylate efficacy in CD differed substantially from their own clinical experience. CONCLUSIONS: Physicians' beliefs about efficacy in subgroups of CD patients, safety, and patient preferences primarily motivate aminosalicylate prescription in CD. There is a lack of confidence in published clinical trials, and a desire for more robust evidence to inform 5-ASA use in CD.

Assessment of Patient-Reported Outcome Instruments to Assess Chronic Low Back Pain.

Objective: To identify patient-reported outcome (PRO) instruments that assess chronic low back pain (cLBP) symptoms (specifically pain qualities) and/or impacts for potential use in cLBP clinical trials to demonstrate treatment benefit and support labeling claims. Design: Literature review of existing PRO measures. Methods: Publications detailing existing PRO measures for cLBP were identified, reviewed, and summarized. As recommended by the US Food & Drug Administration (FDA) PRO development guidance, standard measurement characteristics were reviewed, including development history, psychometric properties (validity and reliability), ability to detect change, and interpretation of observed changes. Results: Thirteen instruments were selected and reviewed: Low Back Pain Bothersomeness Scale, Neuropathic Pain Symptom Inventory, PainDETECT, Pain Quality Assessment Scale Revised, Revised Short Form McGill Pain Questionnaire, Low Back Pain Impact Questionnaire, Oswestry Disability Index, Pain Disability Index, Roland-Morris Disability Questionnaire, Brief Pain Inventory and Brief Pain Inventory Short Form, Musculoskeletal Outcomes Data Evaluation and Management System Spine Module, Orebro Musculoskeletal Pain Questionnaire, and the West Haven-Yale Multidimensional Pain Inventory Interference Scale. The instruments varied in the aspects of pain and/or impacts that they assessed, and none of the instruments fulfilled all criteria for use in clinical trials to support labeling claims based on recommendations outlined in the FDA PRO guidance. Conclusions: There is an unmet need for a validated PRO instrument to evaluate cLBP-related symptoms and impacts for use in clinical trials.

Concept Elicitation Within Patient-Powered Research Networks: A Feasibility Study in Chronic Lymphocytic Leukemia.

OBJECTIVES: To explore the feasibility of using social media-based patient networks to gather qualitative data on patient-reported outcome (PRO) concepts relevant to chronic lymphocytic leukemia (CLL). METHODS: Between August and November 2013, US-residing members of the PatientsLikeMe online CLL patient community completed open-ended web-based surveys designed to elicit descriptions of CLL symptoms, impacts, and treatment-related perceptions. Qualitative telephone follow-up interviews were conducted with a subsample of respondents. Survey responses and interview transcripts were coded for qualitative analysis using Atlas.ti. RESULTS: Fifty survey responses were included in the analyses. Participants were age 60.5 ± 6.9 years, 54% female, and 96% white. When surveyed, 20% were receiving current treatment, 16% were in remission, and 64% were treatment-naïve. Among respondents, 369 descriptions of CLL symptoms were coded. Fatigue-related symptoms were expressed most frequently, with 54% reporting "fatigue," "tiredness," or both in their responses. These concepts were followed by night sweats (38%), swollen lymph nodes (32%), and frequent infections (28%). Among impacts of CLL, worry and fear (66% of respondents), depressed feelings (52%), and work limitations (50%) were noted most frequently. CONCLUSIONS: Survey results identified constitutional symptoms of CLL included in existing PRO instruments and the literature. Although the findings suggest that qualitative data obtained through social media applications can be potentially useful in supporting concept identification for newly developed PRO instruments, they also indicate that online approaches alone may not be sufficient to achieve efficient and exhaustive concept elicitation. Further research is needed to identify whether the results can support content validity in the same way as established qualitative research methods.

Qualitative Interviews Exploring Adverse Event Mitigation Strategies in Adults Receiving Amikacin Liposome Inhalation Suspension.

INTRODUCTION: This study aimed to gain insight from patients with refractory Mycobacterium avium complex lung disease (MAC-LD) into strategies used to manage adverse events (AEs) associated with amikacin liposome inhalation suspension (ALIS). METHODS: We conducted semi-structured interviews with US patients with refractory MAC-LD prescribed ALIS in a real-world setting. Interview transcripts were analyzed and coded to identify patterns in participants' descriptions of their ALIS treatment experiences, including AEs and their disruptiveness, and AE mitigation strategies, including participants' ratings of strategies' effectiveness. Concept saturation was also assessed. RESULTS: Twenty participants (mean age 48.7 years; 80% women; mean ALIS duration 5.45 months) were interviewed. At the time of the interview, 15 participants (75%) had received ALIS for > 1 month and 13 (65%) were currently receiving ALIS. Participants described 44 unique AE mitigation strategies, which can be categorized into three groups: prepare for treatment; prevent increased emergence of AEs; and persist on treatment by mitigating AEs. Common strategies (reported by ≥ 50% of participants) included use of educational materials from the patient support program, localized management of throat irritation, and symptom management to reduce fatigue. Evidence of concept saturation was observed: no new strategies were identified in the last five interviews, which suggests the sample was robust enough to identify all mitigation strategies likely to be used by the broader patient population. CONCLUSIONS: This real-world study identified a diverse set of potential AE mitigation strategies intended to help individual patients prepare for ALIS treatment, prevent the increased emergence of certain AEs, and mitigate the impact of AEs on treatment persistence. Developing a comprehensive accounting of the types of mitigation strategies in use among patients in real-world settings can inform future investigation of the effectiveness of such strategies, and support evidence-based recommendations for treatment management.

Development and Validation of a Visual Symptom-Specific Patient-Reported Outcomes Instrument for Adults With Cataract Intraocular Lens Implants.

PURPOSE: To develop a patient-reported outcome measure for capturing visual and ocular symptoms before and after implantation of intraocular lenses (IOLs) for treatment of cataracts. DESIGN: Questionnaire development and validation study. METHODS: The Questionnaire for Visual Disturbances (QUVID) was developed based on a literature and instrument review; 13 clinician interviews among ophthalmologists in the United States and Europe; and 67 hybrid qualitative patient interviews among adult patients in the United States and Australia before and/or after monofocal, traditional multifocal, or trifocal IOL implantation. Assessment of the QUVID's psychometric properties was conducted via a noninterventional cross-sectional study of previously treated cataract patients in the United States, Canada, and Australia (n = 150), and assessment of ability to detect meaningful change via 2 pivotal US clinical trials among patients with trifocal or extended vision IOL compared with monofocal IOL controls (n = 457). RESULTS: The QUVID includes subitems about the bothersomeness of 7 visual symptoms: starburst, halo, glare, hazy vision, blurred vision, double vision, and dark areas. The postoperative version contains 1 item asking the respondents whether their symptoms bothered them enough to want another surgery, if the IOL was the cause. CONCLUSIONS: The QUVID was reviewed by the US Food and Drug Administration and found appropriate as a fit-for-purpose measure, demonstrating requisite evidence for content validity, construct validity, reliability, and ability to detect change.

Associations between minimum wage policy and access to health care: evidence from the Behavioral Risk Factor Surveillance System, 1996-2007.

OBJECTIVES: We examined whether minimum wage policy is associated with access to medical care among low-skilled workers in the United States. METHODS: We used multilevel logistic regression to analyze a data set consisting of individual-level indicators of uninsurance and unmet medical need from the Behavioral Risk Factor Surveillance System and state-level ecological controls from the US Census, Bureau of Labor Statistics, and several other sources in all 50 states and the District of Columbia between 1996 and 2007. RESULTS: Higher state-level minimum wage rates were associated with significantly reduced odds of reporting unmet medical need after control for the ecological covariates, substate region fixed effects, and individual demographic and health characteristics (odds ratio = 0.853; 95% confidence interval = 0.750, 0.971). Minimum wage rates were not significantly associated with being uninsured. CONCLUSIONS: Higher minimum wages may be associated with a reduced likelihood of experiencing unmet medical need among low-skilled workers, and do not appear to be associated with uninsurance. These findings appear to refute the suggestion that minimum wage laws have detrimental effects on access to health care, as opponents of the policies have suggested.

The Cystic Fibrosis Impact Questionnaire: qualitative development and cognitive evaluation of a new patient-reported outcome instrument to assess the life impacts of cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) experience significant disease burden, including progressive pulmonary decline and reduced survival. This multicenter qualitative study was conducted to develop a new patient-reported outcome (PRO) measure to assess the impact of CF on patients' quality of life: the Cystic Fibrosis Impact Questionnaire (CF-IQ). Semi-structured qualitative concept elicitation (CE) interviews with patients and caregivers documented CF-related symptoms, impacts, and treatment experiences. Coded interview data were considered alongside existing PROs, published literature, and expert opinion to develop an initial scale. Three rounds of cognitive interviews evaluated respondent comprehension and facilitated refinement of the CF-IQ. RESULTS: Adult (N = 20) and pediatric (N = 22) patients with CF and their parents/caregivers (N = 22) completed CE interviews at 7 US clinics. The sample included patients aged 6-58 years, 57% females, and represented a broad range of disease severity (forced expiratory volume in 1 s range: 22%-127% predicted). Interviews identified 59 unique CF-related impact concepts in domains, including activity limitations (physical, social, leisure), functional limitations (school, work), vulnerability/lack of control, emotional impact, treatment burden, and future outlook. Concept saturation was achieved, and a draft questionnaire was developed. Findings from the cognitive interviews (n = 18) confirmed that instructions, items, and response scales were relevant and clear, and interpreted as intended by patients. CONCLUSION: The CF-IQ is a 40-item novel PRO scale assessing a comprehensive set of patient-relevant concepts to characterize the multifaceted nature of CF. Qualitative interview data support the content validity of the CF-IQ, which is currently undergoing additional psychometric evaluation in patients with CF.

Development of the symptoms and impacts questionnaire for Crohn's disease and ulcerative colitis.

BACKGROUND: Patient-reported outcome (PRO) measures historically used in inflammatory bowel disease have been considered inadequate to support future drug labelling claims by regulatory agencies. AIMS: To develop PRO tools for use in Crohn's disease (CD) and ulcerative colitis (UC) following guidance issued by the US FDA and the ISPOR (International Society for Pharmacoeconomics and Outcomes Research). METHODS: Concept elicitation and cognitive interviews were conducted in adult patients (≥18 years) across the United States and Canada. Semi-structured interview guides were used to collect data, and interview transcripts were coded and analysed. Concept elicitation results were considered alongside existing literature and clinical expert opinion to identify candidate PRO items. Cognitive interviews evaluated concept relevance, interpretability and structure, and facilitated instrument refinement. Concept elicitation participants, except those with an ostomy, underwent centrally read endoscopy to assess inflammatory status. RESULTS: In all, 54 participants (mean age: 46.2 years; 66.7% female) were included in the CD concept elicitation interviews. In total, 80 symptom concepts and 61 impact concepts were identified. After three waves of cognitive interviews, the 31-item Symptoms and Impacts Questionnaire for CD (SIQ-CD) was developed. In the UC concept elicitation phase, 53 participants were interviewed (mean age: 41.4 years; 49.1% female). In total, 79 symptoms concepts and 49 impact concepts were identified. Following two waves of cognitive interviews, the 29-item Symptoms and Impacts Questionnaire for UC (SIQ-UC) was developed. Both instruments include four symptom and six impact domains. CONCLUSIONS: We developed PROs to support CD and UC drug labelling claims. Psychometric validation studies to evaluate instrument reliability and responsiveness are ongoing.

Web-based collaborative care for type 1 diabetes: a pilot randomized trial.

BACKGROUND: To determine whether a Web-based diabetes case management program based in an electronic medical record can improve glycemic control (primary outcome) and diabetes-specific self-efficacy (secondary outcome) in adults with type 1 diabetes, a pilot randomized controlled trial was conducted. METHODS: A 12-month randomized trial tested a Web-based case management program in a diabetes specialty clinic. Patients 21-49 years old with type 1 diabetes receiving multiple daily injections with insulin glargine and rapid-acting analogs who had a recent A1C >7.0% were eligible for inclusion. Participants were randomized to receive either (1) usual care plus the nurse-practitioner-aided Web-based case management program (intervention) or (2) usual clinic care alone (control). We compared patients in the two study arms for changes in A1C and self-efficacy measured with the Diabetes Empowerment Scale. RESULTS: A total of 77 patients were recruited from the diabetes clinic and enrolled in the trial. The mean baseline A1C among study participants was 8.0%. We observed a nonsignificant decrease in average A1C (-0.48; 95% confidence interval -1.22 to 0.27; P = 0.160) in the intervention group compared to the usual care group. The intervention group had a significant increase in diabetes-related self-efficacy compared to usual care (group difference of 0.30; 95% confidence interval 0.01 to 0.59; P = 0.04). CONCLUSIONS: Use of a Web-based case management program was associated with a beneficial treatment effect on self-efficacy, but change in glycemic control did not reach statistical significance in this trial of patients with moderately poorly controlled type 1 diabetes. Larger studies may be necessary to further clarify the intervention's impact on health outcomes.

Frames of Reference in Self-Reports of Health, Well-being, Fatigue, and Pain: A Qualitative Examination.

OBJECTIVES: Self-reports in survey research can be affected by internal comparison standards, or Frames of Reference (FoRs), that people apply when making their ratings. The goal of this study was to determine which FoRs people naturally use when rating their health, subjective well-being, fatigue, and pain. We further examined whether FoRs varied by content domain and age group. METHODS: One hundred adults from a community sample of the US general population participated in individual semi-structured qualitative interviews. Participants provided self-report ratings on two of the four content domains and were then systematically queried about FoRs. Interview responses were summarized and coded into broad FoR categories. RESULTS: Four broad FoR categories emerged: References to (1) Other People, (2) an Earlier Time in Life, (3) an Important Event in the Past, and (4) a Hypothetical Situation. FoRs were reported in the majority (80.5%) of responses and multiple FoRs were reported in 34% of responses. The reporting of FoRs was evident for all domains, but was more prevalent for well-being compared to pain. References to a Hypothetical Situation were only mentioned in the well-being and health domains. For health, references to Other People were more frequently reported at older compared to younger ages. DISCUSSION: Our results extend prior work by demonstrating that participants' reporting of FoRs is evident in ratings of various content domains. They further suggest that a limited number of FoRs are used and that their identification holds promise for understanding and controlling systematic group differences in FoRs.

Mixed-methods development of a new patient-reported outcome instrument for chronic low back pain: part 1-the Patient Assessment for Low Back Pain - Symptoms (PAL-S).

We describe the mixed-methods (qualitative and quantitative) development and preliminary validation of the Patient Assessment for Low Back Pain-Symptoms (PAL-S), a patient-reported outcome measure for use in chronic low back pain (cLBP) clinical trials. Qualitative methods (concept elicitation and cognitive interviews) were used to identify and refine symptom concepts and quantitative methods (classical test theory and Rasch measurement theory) were used to evaluate item- and scale-level performance of the measure using an iterative approach. Patients with cLBP participated in concept elicitation interviews (N = 43), cognitive interviews (N = 38), and interview-based assessment of paper-to-electronic mode equivalence (N = 8). A web-based sample of patients with self-reported cLBP participated in quantitative studies to evaluate preliminary (N = 598) and revised (n = 401) drafts and a physician-diagnosed cohort of patients with cLBP (N = 45) participated in preliminary validation of the measure. The PAL-S contained 14 items describing symptoms (overall pain, sharp, prickling, sensitive, tender, radiating, shocking, shooting, burning, squeezing, muscle spasms, throbbing, aching, and stiffness). Item-level performance, scale structure, and scoring seemed to be appropriate. One-week test-retest reproducibility was acceptable (intraclass correlation coefficient 0.81 [95% confidence interval, 0.61-0.91]). Convergent validity was demonstrated with total score and MOS-36 Bodily Pain (Pearson correlation -0.79), Neuropathic Pain Symptom Inventory (0.73), Roland-Morris Disability Questionnaire (0.67), and MOS-36 Physical Functioning (-0.65). Individual item scores and total score discriminated between numeric rating scale tertile groups and painDETECT categories. Respondent interpretation of paper and electronic administration modes was equivalent. The PAL-S has demonstrated content validity and is potentially useful to assess treatment benefit in cLBP clinical trials.

Patient-Centered Research to Support the Development of the Symptoms of Major Depressive Disorder Scale (SMDDS): Initial Qualitative Research.

BACKGROUND: Content valid, patient-reported outcome (PRO) measures of major depressive disorder (MDD) symptoms are needed to assess MDD treatment benefit. While a range of questionnaires are currently available to evaluate aspects of depression from the patient's perspective, their comprehensiveness and qualitative development histories are unclear. OBJECTIVE: The objective of this study was to describe the process and results of the preliminary qualitative development of a new symptom-based PRO measure intended to assess treatment benefit in MDD clinical trials. METHODS: Qualitative interviews were conducted with adult MDD patients in the USA who recently experienced a major depressive episode. Experienced interviewers conducted concept elicitation (CE) and cognitive interviews using semi-structured interview guides. The CE interview guide was used to elicit spontaneous reports of symptom experiences along with probing to further explore and confirm concepts. The cognitive interview guide was developed to evaluate concept relevance, understandability, and structure of the draft items, and to facilitate further instrument refinement. RESULTS: Forty patients participated in the CE interviews. A total of 3022 symptom codes, representing 84 different concepts were derived from the transcripts. Data from the CE interviews were considered alongside existing literature and clinical expert opinion during an item-generation process, leading to development of a preliminary version of the Symptoms of Major Depressive Disorder Scale (SMDDS). Fifteen patients participated in three waves of cognitive interviews, during which the SMDDS was further refined. CONCLUSIONS: The SMDDS is a 35-item PRO measure intended for use as an endpoint in MDD clinical trials to support medical product labeling. The SMDDS uses a 7-day recall period and verbal rating scales. It was developed in accordance with the US Food and Drug Administration (FDA)'s PRO Guidance and best practices. Qualitative interviews have provided evidence for content validity. Future quantitative studies will confirm the SMDDS's measurement properties and support FDA qualification.