The value of co-creating a clinical outcome assessment strategy for clinical trial research: process and lessons learnt.

BACKGROUND: In support of UCB pharmaceutical research programs, the aim of this research was to implement a novel process for patient involvement in a multidisciplinary research group to co-create a clinical outcome assessment strategy to accurately reflect the experience of people living with early-stage Parkinson's. Patient experts were an integral part of the decision-making process for patient-reported outcome (PRO) research and instrument development. METHODS: In partnership with two patient organizations (Parkinson's UK and the Parkinson's Foundation), 6 patient experts were recruited into a multidisciplinary research group alongside clinical, patient engagement and involvement, regulatory science, and outcome measurement experts. The group was involved across two phases of research; the first phase identified what symptoms are cardinal to the experience of living with early-stage Parkinson's and the second phase involved the development of PRO instruments to better assess the symptoms that are important to people living with early-stage Parkinson's. Patient experts were important in performing a variety of roles, in particular, qualitative study protocol design, conceptual model development, and subsequent co-creation of two PRO instruments. RESULTS: Involving people with Parkinson's in PRO research ensured that the expertise of these representatives from the Parkinson's community shaped and drove the research; as such, PRO instruments were being developed with the patient at the forefront. Working with patient experts required considerable resource and time allocation for planning, communication, document development, and organizing meetings; however, their input enriched the development of PRO instruments and was vital in developing PRO instruments that are more meaningful for people with Parkinson's and clinicians. CONCLUSIONS: Conducting PRO research, in the context of clinical development involving pharmaceutical companies, requires balancing regulatory and scientific rigor with tight time constraints. Incorporating a multi-stakeholder perspective, which included patient experts as joint investigators, had a strong positive impact on our research, despite the logistical complexities of their involvement. Due to the input of patient experts, the innovative clinical outcome assessment strategy and the co-created novel PRO instruments were more relevant and holistic to the patient experience of early-stage Parkinson's.

Patient-reported outcome (PRO) instruments allow people living with a disease and participating in a clinical study to describe the symptoms and experiences that they consider meaningful. PRO instruments use tools such as questionnaires and scales to capture patient perspectives on a treatment that might not be captured by a clinical measurement. It is recommended that the patient community and patient experts are included in the development of PRO instruments to accurately capture information that is important to them. Building on the experience of a recent PRO research project in support of UCB pharmaceutical programs, this article provides recommendations on how pharmaceutical companies can partner with patient organizations and involve patient experts as joint investigators in the co creation of PRO instruments. Despite the additional resource and time required, involving patient experts and patient organizations into the research collaboration had a strong positive impact and ensured that the PROs were meaningful to patients (in this instance, people living with early-stage Parkinson's). Patient organizations facilitated patient engagement and recruitment in research activities, maintained communication with the pharmaceutical company's research team, and built trust between collaborators by implementing patient engagement tools and best practices. Patient experts contributed to several parts of the PRO instrument development process: study design, identifying key symptoms and experiences, and developing individual PRO questions. Co-creation between the pharmaceutical company, patient experts, and patient organizations resulted in considerable improvements to typical PRO instrument development for use in clinical trials and is thus recommended.

A Mixed-method Approach to Develop an Ambulatory Module of the SMA Independence Scale.

BACKGROUND: Limited qualitative data exist on the symptoms and impacts of spinal muscular atrophy (SMA) experienced by ambulant individuals. An ambulant module of the SMA Independence Scale (SMAIS) was developed to quantify the assistance required to perform everyday mobility-related activities. OBJECTIVE: The objective of this study was to develop a patient-centered module that provides key insights into what constitutes independence for ambulant and near-ambulant individuals with SMA. METHODS: A stepwise, mixed-method approach was used. Semi-structured interviews were conducted in three waves with individuals with SMA and caregivers of children with SMA who were ambulant or near-ambulant (can walk ≥5 steps with support). Wave 1 interviews (n = 20) focused on concept elicitation. Wave 2 and 3 interviews (n = 15, both) involved completion and cognitive debriefing of items generated based on Wave 1 interviews. Therapeutic area experts were consulted throughout all key steps of the study. In particular, feedback was provided for item refinement and response option decisions. A macro-level preliminary, exploratory analysis, using Rasch Measurement Theory (RMT), provided insight on measurement properties. RESULTS: Wave 1 resulted in 42 mobility and 11 instrumental activity of daily living (iADL) items. During Wave 2, participants defined independence as completing a task with supportive aids but without help from another person, leading to item refinement and modifications to the response scale. Lack of conceptual relevance and ceiling effects led to the removal of all iADL items after Wave 2, and 41 mobility items were tested in Wave 3. Final exploratory RMT and item refinement to reduce overlap led to a 27-item set related to mobility tasks. CONCLUSIONS: Our study provides preliminary support for using the 27-item SMAIS-Ambulatory Module for ambulant or near-ambulant individuals with SMA. Larger-scale analyses to further assess the psychometric properties of the scale are warranted.

Development and early qualitative evidence of two novel patient-reported outcome instruments to assess daily functioning in people with early-stage Parkinson's.

BACKGROUND: Previous research on concepts that are important to people living with early-stage Parkinson's indicated that 'functional' slowness, fine motor skills, and subtle gait abnormalities are cardinal concepts that are not comprehensively captured by existing patient-reported outcome (PRO) instruments that are used in clinical practice and research to assess symptoms and daily functioning within this patient population. We sought to develop novel PRO instruments to address this unmet need. METHODS: PRO instrument development was led by a multidisciplinary research group, including people living with Parkinson's (termed 'patient experts'), as well as patient engagement and involvement, regulatory science, clinical, and outcome measurement experts. A first set of PRO instruments, termed Early Parkinson's Function Slowness (42 items) and Early Parkinson's Mobility (26 items), were drafted to capture 'functional' slowness, fine motor skills, and subtle gait abnormalities. These PRO instruments were used in cognitive debriefing interviews with people living with early-stage Parkinson's (who were not involved with the multidisciplinary research group) to identify issues with relevance, clarity, ease of completion, conceptual overlap, or missing concepts. RESULTS: Sixty people living with early-stage Parkinson's were interviewed, which led to refining the items to 45 for the Early Parkinson's Functional Slowness and 23 for the Early Parkinson's Mobility PRO instruments. Refinement included rewording items to address clarity issues, merging or splitting items to address overlap issues, and adding new items to address missing concepts. The Early Parkinson's Function Slowness PRO instrument resulted in a multidimensional instrument covering upper limb, complex/whole body, general activity, and cognitive functional slowness. The Early Parkinson's Mobility PRO instrument resulted in comprehensive coverage of everyday mobility tasks, with a focus on gait concepts, plus complex/whole body, balance, and lower limb mobility. CONCLUSIONS: The Early Parkinson's Function Slowness and Early Parkinson's Mobility PRO instruments aim to address gaps in existing PRO instruments to measure meaningful symptoms and daily functioning in people living with early-stage Parkinson's. Utilizing a meticulous study design led by a multidisciplinary research group that included patient experts helped to ensure that the PRO instruments were patient-centric, content valid, and meaningful from a clinical and measurement perspective.

Patient Experience in Early-Stage Parkinson's Disease: Using a Mixed Methods Analysis to Identify Which Concepts Are Cardinal for Clinical Trial Outcome Assessment.

INTRODUCTION: Qualitative research on patient experiences in early-stage Parkinson's disease (PD) is limited. It is increasingly acknowledged that clinical outcome assessments used in trials do not fully capture the range of symptoms/impacts that are meaningful to people with early-stage PD. We aimed to conceptualize the patient experience in early-stage PD and identify, from the patient perspective, those cardinal symptoms/impacts which might be more useful to measure in clinical trials. METHODS: In a mixed-methods analysis, 50 people with early-stage PD and nine relatives were interviewed. Study design and results interpretation were led by a multidisciplinary group of patient, clinical, regulatory, and outcome measurements experts, and patient organization representatives. Identification of the cardinal concepts was informed by the relative frequency of reported concepts combined with insights from patient experts and movement disorder specialists. RESULTS: A conceptual model of the patient experience of early-stage PD was developed. Concept elicitation generated 145 unique concepts mapped across motor and non-motor symptoms, function, and impacts. Bradykinesia/slowness (notably in the form of "functional slowness"), tremor, rigidity/stiffness, mobility (particularly fine motor dexterity and subtle gait abnormalities), fatigue, depression, sleep/dreams, and pain were identified as cardinal in early-stage PD. "Functional slowness" (related to discrete tasks involving the upper limbs, complex mobility tasks, and general activities) was deemed to be more relevant than "difficulty" to patients with early-stage PD, who report being slower at completing tasks rather than encountering significant impairment with task completion. CONCLUSION: Patient experiences in early-stage PD are complex and wide-ranging, and the currently available patient-reported outcome (PRO) instruments do not evaluate many early-stage PD concepts such as functional slowness, fine motor skills, and subtle gait abnormalities. The development of a new PRO instrument, created in conjunction with people with PD, that fully assesses symptoms and the experience of living with early-stage PD, is required.

We conducted research to find out about the experiences and symptoms that have the greatest impact on everyday living for people with early-stage Parkinson's disease. This research also looked at which symptoms patients think are important to be tracked in clinical trials. The research team running this study included people living with Parkinson's disease (called "patient experts"). The team also included technical experts and representatives of patient organizations. To begin with, people living with early-stage Parkinson's disease and relatives were interviewed. The interviews collected their thoughts on the impact of early-stage Parkinson's disease on their daily lives. These insights revealed which experiences and symptoms were most important. The research team analyzed ideas and quotes from the interviews to create a picture of early-stage Parkinson's disease. The symptoms that mattered the most to people living with early-stage Parkinson's disease were tremor, rigidity/stiffness, fatigue, depression, sleep/dreams, and pain. Another important symptom was slowness of movement (which is called "bradykinesia/slowness"), and in particular "functional slowness," which included tasks involving the upper limbs, complicated movement tasks, and general activities. Effects on mobility were also important, particularly fine motor skills and subtle walking abnormalities. This research shows the wide-ranging effects that early-stage Parkinson's disease has on patients from their perspective. It also shows which effects are important to capture in trials of therapies aimed at this patient group.

The FATIGUE-PRO: a new patient-reported outcome instrument to quantify fatigue in patients affected by systemic lupus erythematosus.

OBJECTIVES: This study aimed to implement a patient-centred and evidence-based approach to develop a novel patient-reported outcome (PRO) instrument to measure fatigue in patients with SLE. METHODS: A three-step mixed methods psychometric (MMP) approach was followed. Steps comprised first draft item generation and review using interview data; evaluation and refinement of second draft items using mixed methods data, including interview and quantitative data from a phase 2 clinical study in SLE analysed using Rasch Measurement Theory (RMT) analysis; and evaluation of the final FATIGUE-PRO items using RMT and complementary Classical Test Theory (CTT) analyses. Guided by MMP criteria, a team of clinicians and outcome-measurement experts assessed evidence to inform instrument development. RESULTS: Step 1 culminated in 55 items (n = 39 patients interviewed). Their refinement in step 2 using mixed methods evidence led to the final FATIGUE-PRO instrument comprising 31 items across three scales of fatigue: physical fatigue (9 items), mental and cognitive fatigue (11 items) and susceptibility to fatigue (11 items). Qualitative (n = 43 patients) and quantitative (n = 106 patients) evidence strongly supported the scales' content comprehensiveness and targeting, item quality and fit, conceptual uniqueness and appropriateness of the response scale. The FATIGUE-PRO further benefited from excellent reliability (RMT: 0.92-0.94 and CTT: 0.95-0.96) and supportive evidence of construct validity from assessments against other PROs. CONCLUSION: The conceptual advances, comprehensive coverage and strong psychometric properties of the FATIGUE-PRO will significantly advance the measurement and management of fatigue in SLE, both in clinical trials and routine practice. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov), NCT02804763.

The Patient Experience of Fatigue in Systemic Lupus Erythematosus: A Conceptual Model.

INTRODUCTION: Fatigue is frequently experienced in systemic lupus erythematosus (SLE) and is a key outcome in clinical research trials. However, SLE fatigue is complex and poorly understood, and challenging to measure. We aimed to characterise fatigue from the patients' perspective and develop a conceptual model of fatigue based on qualitative interviews. METHODS: We conducted semi-structured qualitative interviews exploring fatigue in patients with SLE recruited from a social network (n = 29) and a phase 2 clinical study (n = 43). Transcripts were coded thematically, and codes were inductively categorised into a conceptual model. RESULTS: Fatigue was the most commonly reported symptom in the interviews and generated a wide range of codes. From these, our concept-driven approach revealed three overarching domains of the fatigue experienced in SLE: (i) physical manifestation of physical and bodily symptoms (including physical energy, stamina and impact on movement); (ii) mental and cognitive manifestation (including mental energy, motivation, and cognitive functioning symptoms); and (iii) susceptibility to fatigue or how easily 'fatigable' patients are, meaning how easily they become fatigued and how easily their fatigue is alleviated (including the rapid, disproportionate, and/or unpredictable onset of fatigue, non-restorative sleep, and need for more sleep/rest breaks). Within each of these, participants described the severity, variation and impact of fatigue on everyday life. Participants also described how the SLE fatigue experience differed from 'everyday tiredness'. CONCLUSIONS: The findings of this research indicate that comprehensive measurement of fatigue in SLE will require consideration and quantification of the three domains described in our conceptual model. Future research will explore whether this conceptual model can form the basis of a valid and reliable measurement of fatigue in SLE.

Development of the Myasthenia Gravis (MG) Symptoms PRO: a case study of a patient-centred outcome measure in rare disease.

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease, characterised by fluctuating muscle weakness which makes it challenging to assess symptom severity. Mixed methods psychometrics (MMP), which combines evidence from qualitative research and modern psychometrics, is a versatile approach to the development of patient-centred outcome measures (PCOM) in the context of rare disease. Our objective was to develop the MG Symptom patient-reported outcome (PRO) to assess key aspects of MG severity from the patient perspective. METHODS: We used MMP to develop a novel PRO instrument in a multi-step process. An initial conceptual model for MG patient experience was developed and expanded based on preliminary literature review and two waves of concept elicitation interviews with people with MG (Step 1). Based on this, the novel PRO instrument, the MG Symptoms PRO, was drafted. The draft instrument was refined by combining qualitative and quantitative data collected in a Phase 2 clinical study (Step 2). RESULTS: Findings from the literature review and concept elicitation interviews (n = 96) indicated that patient experience in MG includes proximal muscle weakness symptoms related to several body parts, along with muscle weakness fatigability and general fatigue. Then, a set of 42 items across five scales (ocular-, bulbar-, and respiratory muscle weakness, physical fatigue, and muscle weakness fatigability) was developed. Qualitative evidence endorsed its relevance, clarity, and ease of completion; quantitative analysis with Rasch measurement theory methods demonstrated strong measurement properties, including good targeting and high reliability. Classical test theory analyses showed adequate reliability of the instrument and mild to moderate correlations with other widely used MG-specific outcome measures. CONCLUSIONS: The MG Symptoms PRO has potential to be used both to measure treatment benefit in clinical trials and monitor symptom severity in clinical practice. Its component scales were purposefully designed to stand alone, enhancing interpretability of scores given the heterogeneity of MG, and enabling modular use. Compared with existing MG PROs, it contains more detailed assessments of muscle weakness and muscle weakness fatigability symptoms, which are of key importance to people with MG. The MMP approach used may serve as a case study for developing PCOMs across rare disease indications.

Psychometric Analysis from EMBODY1 and 2 Clinical Trials to Help Select Suitable Fatigue PRO Scales for Future Systemic Lupus Erythematosus Studies.

INTRODUCTION: Fatigue is one of the most important symptoms reported by patients with systemic lupus erythematosus (SLE) and a key concept of interest in SLE clinical trials. Despite this, fatigue remains poorly understood and sub-optimally measured by existing patient-reported outcome (PRO) instruments and scales. Here, we psychometrically evaluated the measurement properties of three PRO scales that purport to measure fatigue, using data from two SLE clinical trials. METHODS: Data were pooled from two completed phase 3 SLE trials: EMBODY1 (NCT01262365) and EMBODY2 (NCT01261793). FACIT-F, SF-36 Vitality and LupusQoL Fatigue data were selected for post hoc Rasch Measurement Theory psychometric analysis in two stages: (1) scale-to-sample targeting, thresholds for item response options, item fit statistics, and reliability; and (2) proposal and evaluation of pooled fatigue items based on the best-performing items. Responsiveness analyses on group-level (two effect size [ES] calculations and relative efficiency) and individual level (within person statistically significant difference), were conducted to compare original scales and pooled item sets. RESULTS: Scale-to-sample targeting was good for FACIT-F, but suboptimal for SF-36 Vitality and LupusQoL Fatigue. Thresholds for item response options were ordered for all three scales. Item misfit was found in all three scales (FACIT-F 10/13; SF-36 Vitality 4/4; LupusQoL Fatigue 1/4). Reliability statistics were good for FACIT-F (0.93) and LupusQoL Fatigue (0.80) but low for SF-36 Vitality (0.53). The pooled fatigue items improved some psychometric properties despite persisting misfit issues (2/10) and were more sensitive in detecting change at week 24 compared with un-pooled data (ES 0.41 vs. 0.26-0.25). CONCLUSIONS: FACIT-F, SF-36 Vitality, and LupusQoL Fatigue were found to have important limitations in the EMBODY1 and EMBODY2 SLE clinical trials. Findings from pooled fatigue items support the need for further research to improve conceptual underpinnings of fatigue PROs and make them fit for purpose for drug development.

Development and psychometric evaluation of the assessment of self-injection questionnaire: an adaptation of the self-injection assessment questionnaire.

BACKGROUND: Patient-reported outcome (PRO) instruments provide robust and effective means of evaluating patients' treatment experience; however, none adequately cover experience using self-injection devices with enhanced features, such as an electromechanical autoinjector (e-Device). The aim of this study was to develop a PRO instrument that accurately assesses patient experience of using an e-Device and to evaluate its psychometric properties. METHODS: A mixed-methods approach was taken; two parallel, targeted literature reviews were conducted to identify relevant concepts and existing self-injection PRO instruments that could be adapted. Patient feedback obtained from two focus groups was used to inform initial instrument development. The pilot instrument was then administered in a multicenter, open-label, phase 3 clinical study in which patients self-injected certolizumab pegol using an e-Device, to gather evidence of its psychometric qualities. Exit interviews were conducted with a sub-sample of patients enrolled in the study to confirm the appropriateness and clarity of the items included and cognitively debrief the instrument. Confirmatory factor analysis (CFA) was conducted on all items, and each domain's internal consistency was measured using Cronbach's ɑ. RESULTS: The literature searches identified several e-Device-specific concepts related to device features, device function, side effects/reactions/pain, confidence, and interference/convenience in daily life. Seven existing PRO instruments were identified. The Self-Injection Assessment Questionnaire (SIAQ), containing pre- and post-injection questionnaire modules, was selected as most suitable and adapted using feedback from 19 patients in the two focus groups to form the pilot Assessment of Self-Injection (ASI) questionnaire. CFA resulted in some changes to the grouping of items in the post-injection module domains following psychometric evaluation of the ASI. Internal consistency was satisfactory for all pre- and post-injection domains (ɑ > 0.8). Cognitive debriefing results from 12 patient exit interviews confirmed the ASI's appropriateness and clarity. CONCLUSIONS: The ASI was developed iteratively with patient input and was evaluated in its intended clinical context of use. Psychometric analyses indicated promising cross-sectional results; the ASI was well understood and considered relevant by patients self-injecting using the e-Device, suggesting that it could be used in real-world settings to aid with clinical decision making. TRIAL REGISTRATION: NCT03357471.

Psychometric performance of the PROMIS® depression item bank: a comparison of the 28- and 51-item versions using Rasch measurement theory.

PURPOSE: The aim of this study is to illustrate an example application of Rach Measurement Theory (RMT) in the evaluation of patient-reported outcome (PRO) measures. RMT diagnostic methods were applied to evaluate the PROMIS® Depression items as part of a series of papers applying different psychometric paradigms in parallel to the same data. METHODS: RMT was used to examine scale-to-sample targeting, scale performance and sample measurement of two PROMIS depression item pools including respectively 28 and 51- items. RESULTS: Sub-optimal but improved targeting was displayed in the 51-item pool which covered 27% of the range of depression measured in the sample compared to only 15% in the 28-item bank, further reducing the sample percentage with lower depression not covered by the scale (28% Vs 34%). Satisfactory scale performance was observed by the 28-item bank with marginal item misfit. However, deviations from the RMT criteria in the 51-itempool were observed including: 9 reversed thresholds; 12 misfitting items and 12 item-pairs displaying dependency. Overall reliability was good for sets of items (Person Separation Index = 0.93 and 0.95), but sub-optimal sample measurement (17% Vs 19% fit residuals outside of the recommended range). CONCLUSIONS: The RMT approach in this exercise provided evidence that compared to the 28-item bank, the extended 51-item version of the PROMIS depression, improved sample-to-scale targeting. However, targeting in the lower end of the concept of interest remained sub-optimal and scale performance deteriorated. There may be a need to improve the conceptual breadth of the construct under investigation to ensure the inclusion of items that capture the full range of the concept of interest for this context of use.

Red cell distribution width correlates with fatigue levels in a diverse group of patients with systemic lupus erythematosus irrespective of anaemia status.

OBJECTIVES: Fatigue remains a debilitating feature of systemic lupus erythematosus (SLE). Although in some cases this may be the result of intercurrent fibromyalgia, mood disorder or untreated metabolic syndrome, in many cases the cause is unclear. The aim of this study was to investigate the relationship between fatigue and red cell distribution width (RDW), a measure of variability in erythrocyte size and volume. METHODS: A total of 225 patients were recruited from three clinics in England and Australia. Patients completed the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score or 12-item Short Form survey (SF-12) to measure fatigue, which was compared with RDW and haemoglobin. In a subgroup of 72 patients, markers of disease activity were also assessed for correlation with fatigue using univariate and multivariate analysis with fatigue as the dependent variable. RESULTS: In all three groups, significant correlations between fatigue and RDW were observed (p<0.001; p=0.02; p<0.001 respectively) and this was preserved in multivariate analysis. There was no correlation between fatigue and haemoglobin in two groups (with the correlation between RDW and fatigue remaining significant in non-anaemic patients in the third group). In subgroup analysis, fatigue was not associated with any measures of disease activity. CONCLUSIONS: We report a reproducible, statistically significant association between RDW and fatigue levels in a diverse population of patients with SLE. The findings of this study raise the possibility of a potential novel biological basis for fatigue in those in whom there is a lack of an alternate explanation.

Development of a gait module to complement the 12-item Multiple Sclerosis Walking Scale: a mixed methods study.

BACKGROUND AND OBJECTIVE: The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported outcome instrument that quantifies the progressive loss of walking ability from the patient perspective. However, previous psychometric analyses indicated floor and ceiling effects across the multiple sclerosis severity spectrum. This study aimed to address floor effects by creating a gait module that can be used in conjunction with the MSWS-12 for better measurement of treatment benefit in the higher functioning multiple sclerosis population. METHODS: We used a step-wise mixed methods study design, with relapsing-remitting multiple sclerosis patients (wave 1, n=88; wave 2, n=30), combining qualitative (concept elicitation and cognitive debriefing interviews) and quantitative (Rasch Measurement Theory) data collection and analytical techniques and consultation interviews with three neurologists specializing in multiple sclerosis. RESULTS: Thirty-seven walking ability concepts were identified, and a five-domain conceptual framework was created. Draft items were generated and refined with patient and neurologist input. Draft items covered gait-related concepts such as dragging, shuffling, limping, tripping and falling. Rasch measurement theory psychometric analysis indicated administering MSWS-12 plus gait items improved measurement precision in targeted populations with better walking ability. CONCLUSION: Study findings indicate that new gait items could improve sensitivity to detect clinical change in walking ability for higher functioning multiple sclerosis patients.

Addressing the targeting range of the ABILHAND-56 in relapsing-remitting multiple sclerosis: A mixed methods psychometric study.

BACKGROUND: ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients. OBJECTIVE: The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients. METHODS: A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) analytic techniques, and consultation interviews with three clinical neurologists specializing in multiple sclerosis. RESULTS: Original ABILHAND was well understood in this context of use. Eighty-two new manual ability concepts were identified. Draft supplementary items were generated and refined with patient and neurologist input. Rasch measurement theory psychometric analysis indicated supplementary items improved targeting to higher-functioning multiple sclerosis patients and measurement precision. The final pool of Early Multiple Sclerosis Manual Ability items comprises 20 items. CONCLUSION: The synthesis of qualitative and quantitative methods used in this study improves the ABILHAND content validity to more effectively identify manual ability changes in early multiple sclerosis and potentially help determine treatment effect in higher-functioning patients in clinical trials.

Measuring the impact of multiple sclerosis: Enhancing the measurement performance of the Multiple Sclerosis Impact Scale (MSIS-29) using Rasch Measurement Theory (RMT).

BACKGROUND: Study objectives were to evaluate the Multiple Sclerosis Impact Scale (MSIS-29) and explore an optimized scoring structure based on empirical post-hoc analyses of data from the Phase III ADVANCE clinical trial. METHODS: ADVANCE MSIS-29 data from six time-points were analyzed in a sample of patients with relapsing-remitting multiple sclerosis (RRMS). Rasch Measurement Theory (RMT) analysis was undertaken to examine three broad areas: sample-to-scale targeting, measurement scale properties, and sample measurement validity. Interpretation of results led to an alternative MSIS-29 scoring structure, further evaluated alongside responsiveness of the original and revised scales at Week 48. RESULTS: RMT analysis provided mixed evidence for Physical and Psychological Impact scales that were sub-optimally targeted at the lower functioning end of the scales. Their conceptual basis could also stand to improve based on item fit results. The revised MSIS-29 rescored scales improved but did not resolve the measurement scale properties and targeting of the MSIS-29. In two out of three revised scales, responsiveness analysis indicated strengthened ability to detect change. CONCLUSION: The revised MSIS-29 provides an initial evidence-based improved patient-reported outcome (PRO) instrument for evaluating the impact of MS. Revised scoring improves conceptual clarity and interpretation of scores by refining scale structure to include Symptoms, Psychological Impact, and General Limitations. CLINICAL TRIAL: ADVANCE (ClinicalTrials.gov identifier NCT00906399).

Further explorations of illness uncertainty: carers' experiences of Parkinson's disease.

OBJECTIVE: Dominant models of illness uncertainty define uncertainty as 'an inability to determine the meaning of illness-related events'. Recent research has shown patient uncertainty to be multidimensional encompassing personal issues indirectly affected by illness. The nature of carer uncertainty has yet to be fully explored. The present study aimed to investigate the nature of illness uncertainty in the carers of patients with Parkinson's disease (PD). DESIGN: Eighteen carers of a spouse with PD participated in semistructured interviews. Transcripts were thematically analysed, statements were coded as uncertain if they reflected 'a lack of certainty, or a state of limited knowledge, understanding or worry regarding an existing or future outcome'. RESULTS: The domains of uncertainty expressed by carers closely fitted the five domain framework of patient uncertainty: symptoms and prognosis, medical management, self-management, social functioning and impact. An additional 'carer-role' domain was identified. CONCLUSIONS: Carer uncertainty about PD went beyond issues directly related to the illness. The findings have implications for research into uncertainty suggesting that widely used measures may not be accurately capturing the nature of carer uncertainty about chronic illness. The breadth of uncertainty reported has implications for the provision of appropriate support to improve caregiver well-being.

Quantifying beliefs regarding telehealth: Development of the Whole Systems Demonstrator Service User Technology Acceptability Questionnaire.

Introduction Telehealth (TH) is a potential solution to the increased incidence of chronic illness in an ageing population. The extent to which older people and users with chronic conditions accept and adhere to using assistive technologies is a potential barrier to mainstreaming the service. This study reports the development and validation of the Whole Systems Demonstrator (WSD) Service User Technology Acceptability Questionnaire (SUTAQ). Methods Questionnaires measuring the acceptability of TH, quality of life, well-being and psychological processes were completed by 478 users of TH. The 22 acceptability items were subject to principal components analysis (PCA) to determine sub-scales. Scale scores, relationships between scales and other patient-reported outcome measures (PROMs), and group differences on scales were utilised to check the reliability and validity of the measure. Results PCAs of SUTAQ items produced six TH acceptability scales: enhanced care, increased accessibility, privacy and discomfort, care personnel concerns, kit as substitution and satisfaction. Significant correlations within these beliefs and between these scales and additional PROMs were coherent, and the SUTAQ sub-scales were able to predict those more likely to refuse TH. Discussion The SUTAQ is an instrument that can be used to measure user beliefs about the acceptability of TH, and has the ability to discriminate between groups and predict individual differences in beliefs and behaviour. Measuring acceptability beliefs of TH users can provide valuable information to direct and target provision of services to increase uptake and maintain use of TH.

Patient Uncertainty Questionnaire-Rheumatology (PUQ-R): development and validation of a new patient-reported outcome instrument for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a mixed methods study.

BACKGROUND: An in-depth qualitative exploration of uncertainty in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) led to the development of a five-domain conceptual framework of patient uncertainty in these two conditions. The purpose of this study was to develop and evaluate a new patient-reported outcome (PRO) instrument for patient uncertainty in SLE and RA on the basis of this empirically developed conceptual framework. METHODS: Cognitive debriefing interviews were conducted to pre-test the initial items generated on the basis of the preliminary qualitative exploration of patient uncertainty in SLE and RA. Two separate field tests were conducted in five hospital sites to evaluate the measurement properties of the new instrument; the first to identify and form scales, and the second to assess measurement properties of the final version in an independent sample. Psychometric evaluation was conducted in line with the Rasch Measurement Theory (RMT), examining the extent to which sample to scale targeting was satisfactory, measurement scales were constructed effectively and the sample was measured successfully. Traditional psychometric techniques were also used to provide complementary analyses best understood by clinicians. RESULTS: Pre-testing supported the relevance, acceptability and comprehensibility of the initial items. Findings indicated that the Patient Uncertainty Questionnaire for Rheumatology PUQ-R instrument fulfilled the expectations of RMT to a large extent (including person separation index 0.73 - 0.91). The PUQ-R comprises 49 items across five scales; symptoms and flares (14 items), medication (11 items), trust in doctor (8 items), self-management (6 items) and impact (10 items) which further displayed excellent measurement properties as assessed against the traditional psychometric criteria (including Cronbach's alpha 0.82 - 0.93). CONCLUSION: The PUQ-R has been developed and evaluated specifically for patients with SLE and RA. By quantifying uncertainty, the PUQ-R has the potential to support evidence-based management programmes and research.

Osteoarthritis: Patient Expectations about Future Pain, Stiffness and Function.

OBJECTIVES: The aim of the present study was to examine the difference between osteoarthritis patients' self-reported assessments of current pain, stiffness and physical function and their expectations of these symptoms in one and five years' time, and to determine the significant predictors of positive expectations. METHODS: Eighty patients completed ratings of baseline assessments and one- and five-year expectations of pain, stiffness and physical function using the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Measures of illness perceptions, coping styles, health values, satisfaction, quality of life, optimism, self-esteem and moods were also collected at baseline. Agreement between patients' current assessment and expectations were calculated using intra-class correlations (ICCs). Paired-sample t-tests were conducted to look at differences between assessments. Univariate logistic regressions were then performed to identify the variables significantly associated with positive expectations of pain, stiffness and function. Significant variables (p < 0.05) were entered into a forward stepwise multivariate logistic regression to identify unique independent predictors of positive expectations for each of the WOMAC subscales. RESULTS: Differences were found between current assessments and expectations, with the majority of patients being positive about future symptoms. There were some differences between the predictors for one- and five-year expectations, with current assessments of health status only affecting five-year expectations. CONCLUSIONS: It is necessary to investigate further the variables that may contribute to positive expectations in osteoarthritis patients in order to manage the condition more effectively.