Validation of a new glucocorticoid-specific Patient-Reported Outcome Questionnaire (the Steroid PRO).

OBJECTIVES: Glucocorticoids used in the treatment of inflammatory rheumatic conditions can impact on health-related quality of life. An underpinning qualitative study developed a long-list of candidate items for a treatment-specific patient-reported outcome (PRO) measure. The objective of this paper is to determine scale structure and psychometric properties of the Steroid PRO. METHODS: A cross-sectional survey of adults from the UK, USA, Australia and New Zealand, taking glucocorticoids for a rheumatic disease. Initial survey collected demographics, clinical information, 40 Steroid PRO candidate items and EuroQol-5 Dimensions- 5 levels (EQ-5D-5L). Follow-up, 3-5 days later, collected Steroid PRO candidate items and a condition-change ('transition') question. Analysis included Rasch measurement model, exploratory factor analysis (EFA), and hypothesis testing for discriminative validity, convergence validity and test-retest reliability. RESULTS: Total responses 946: UK n=743 (79%); USA n=139 (15%); Australia/New Zealand n=64 (7%); mean age 57.6 (SD=13.6); 833 (88%) women. Participants with inflammatory arthritis n=197 (21%), connective tissue disease and/or vasculitis n=402 (42%), giant cell arteritis and/or polymyalgia rheumatica n=347 (37%). Twenty-five items were removed due to lack of fit to Rasch model. Of the remaining items, EFA suggested four subscales: Social impact (4 items); Impact on appearance (3 items); Psychological impact (5 items); Treatment concerns (3 items). Rasch modelling supported a four-subscale structure and total score, confirming construct validity and reliability. Hypothesis testing confirmed discriminant and convergence validity. Intraclass correlation coefficient (total score) was 0.809 demonstrating excellent (test-retest) reliability. CONCLUSIONS: The Steroid PRO is a 15-item, valid and reliable scale for measuring the impact of glucocorticoid therapy in people with rheumatic diseases.

Validation of a patient-reported outcome measure for giant cell arteritis.

OBJECTIVES: GCA is systemic vasculitis manifesting as cranial, ocular or large vessel vasculitis. A prior qualitative study developed 40 candidate items to assess the impact of GCA on health-related quality of life (HRQoL). This study aimed to determine final scale structure and measurement properties of the GCA patient reported outcome (GCA-PRO) measure. METHODS: Cross-sectional study included UK patients with clinician-confirmed GCA. They completed 40 candidate items for the GCA-PRO at times 1 and 2 (3 days apart), EQ-5D-5L, ICECAP-A, CAT-PROM5 and self-report of disease activity. Rasch and exploratory factor analyses informed item reduction and established structural validity, reliability and unidimensionality of the final GCA-PRO. Evidence of validity was also established with hypothesis testing (GCA-PRO vs other PRO scores, and between participants with 'active disease' vs those 'in remission') and test-retest reliability. RESULTS: The study population consisted of 428 patients: mean (s.d.) age 74.2 (7.2), 285 (67%) female; 327 (76%) cranial GCA, 114 (26.6%) large vessel vasculitis and 142 (33.2%) ocular involvement. Rasch analysis eliminated 10 candidate GCA items and informed restructuring of response categories into four-point Likert scales. Factor analysis confirmed four domains: acute symptoms (eight items), activities of daily living (seven items), psychological (seven items) and participation (eight items). The overall scale had adequate Rasch model fit (χ2 = 25.219, degrees of freedom = 24, P = 0.394). Convergent validity with EQ5D-5L, ICECAP-A and Cat-PROM5 was confirmed through hypothesis testing. Internal consistency and test-retest reliability were excellent. CONCLUSION: The final GCA-PRO is a 30-item, four-domain scale with robust evidence of validity and reliability in measuring HRQoL in people with GCA.

Outcomes in Ankle Replacement Study (OARS).

Aims: The aim of this study was to capture 12-month outcomes from a representative multicentre cohort of patients undergoing total ankle arthroplasty (TAA), describe the pattern of patient-reported outcome measures (PROMs) at 12 months, and identify predictors of these outcome measures. Methods: Patients listed for a primary TAA at 19 NHS hospitals between February 2016 and October 2017 were eligible. PROMs data were collected preoperatively and at six and 12 months including: Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ (foot and ankle)) and the EuroQol five-dimension five-level questionnaire (EQ-5D-5L). Radiological pre- and postoperative data included Kellgren-Lawrence score and implant position measurement. This was supplemented by data from the National Joint Registry through record linkage to determine: American Society of Anesthesiologists (ASA) grade at index procedure; indication for surgery, index ankle previous fracture; tibial hind foot alignment; additional surgery at the time of TAA; and implant type. Multivariate regression models assessed outcomes, and the relationship between MOXFQ and EQ-5D-5L outcomes, with patient characteristics. Results: Data from 238 patients were analyzed. There were significant improvements in MOXFQ and EQ-5D-5L among people who underwent TAA at six- and 12-month assessments compared with preoperative scores (p < 0.001). Most improvement occurred between preoperative and six months, with little further improvement at 12 months. A greater improvement in MOXFQ outcome postoperatively was associated with older age and more advanced radiological signs of ankle osteoarthritis at baseline. Conclusion: TAA significantly benefits patients with end-stage ankle disease. The lack of substantial further overall change between six and 12 months suggests that capturing PROMs at six months is sufficient to assess the success of the procedure. Older patients and those with advanced radiological disease had the greater gains. These outcome predictors can be used to counsel younger patients and those with earlier ankle disease on the expectations of TAA.

Measuring the impact of steroid therapy on health-related quality of life in patients with rheumatic diseases: international development of a glucocorticoid treatment-specific patient-reported outcome measure.

OBJECTIVES: Glucocorticoids (GCs) ('steroids') are used to treat rheumatic diseases but adverse effects are common. We aimed to explore the impact of GC therapy on health-related quality of life (HRQoL), to inform the development of a treatment-specific patient-reported outcome measure (PROM) for use in clinical trials and practice. METHODS: Semi-structured qualitative interviews were conducted with patients from the UK, USA and Australia, treated for a rheumatic condition with GCs in the last 2 years. Purposive sampling was used to select participants with a range of demographic and disease features. An initial conceptual framework informed interview prompts and cues. Interviews elicited GC-related physical and psychological symptoms and salient aspects of HRQoL in relation to GC therapy. Interview data were analysed inductively to develop initial individual themes and domains. Candidate questionnaire items were developed and refined. RESULTS: Sixty semi-structured qualitative interviews were conducted (UK n = 34, USA n = 10, Australia n = 16). The mean age was 58 years; 39/60 were female; and 18 rheumatic diseases were represented. Some 126 individual themes were identified and organized into six domains: physical symptoms; psychological symptoms; psychological impact of steroids; impact of steroids on participation; impact of steroids on relationships; and benefits of steroids. Candidate questionnaire items were tested and refined by piloting with patient research partners, iterative rounds of cognitive interviews and linguistic translatability assessment, informing a draft questionnaire. CONCLUSION: We describe an international qualitative study to develop candidate items for a treatment-specific PROM for patients with rheumatic diseases. A future survey will enable the validation of a final version of the PROM.

Computerized adaptive testing for the Oxford Hip, Knee, Shoulder, and Elbow scores : accurate measurement from fewer, and more patient-focused, questions.

AIMS: The aim of this study was to develop and evaluate machine-learning-based computerized adaptive tests (CATs) for the Oxford Hip Score (OHS), Oxford Knee Score (OKS), Oxford Shoulder Score (OSS), and the Oxford Elbow Score (OES) and its subscales. METHODS: We developed CAT algorithms for the OHS, OKS, OSS, overall OES, and each of the OES subscales, using responses to the full-length questionnaires and a machine-learning technique called regression tree learning. The algorithms were evaluated through a series of simulation studies, in which they aimed to predict respondents' full-length questionnaire scores from only a selection of their item responses. In each case, the total number of items used by the CAT algorithm was recorded and CAT scores were compared to full-length questionnaire scores by mean, SD, score distribution plots, Pearson's correlation coefficient, intraclass correlation (ICC), and the Bland-Altman method. Differences between CAT scores and full-length questionnaire scores were contextualized through comparison to the instruments' minimal clinically important difference (MCID). RESULTS: The CAT algorithms accurately estimated 12-item questionnaire scores from between four and nine items. Scores followed a very similar distribution between CAT and full-length assessments, with the mean score difference ranging from 0.03 to 0.26 out of 48 points. Pearson's correlation coefficient and ICC were 0.98 for each 12-item scale and 0.95 or higher for the OES subscales. In over 95% of cases, a patient's CAT score was within five points of the full-length questionnaire score for each 12-item questionnaire. CONCLUSION: Oxford Hip Score, Oxford Knee Score, Oxford Shoulder Score, and Oxford Elbow Score (including separate subscale scores) CATs all markedly reduce the burden of items to be completed without sacrificing score accuracy.Cite this article: Bone Jt Open 2022;3(10):786-794.

Patient perceptions of health-related quality of life in giant cell arteritis: international development of a disease-specific patient-reported outcome measure.

OBJECTIVES: GCA is a large vessel vasculitis (LVV) presenting with headache, jaw claudication, musculoskeletal and visual involvement. Current treatment is glucocorticoids and anti-IL-6 tocilizumab in refractory disease. The objective of this study was to explore the impact of GCA and its treatment on people's health-related quality of life (HRQoL), to inform the development of a disease-specific patient-reported outcome measure (PROM) for use in clinical trials and practice. METHODS: Participants from the UK and Australia, with biopsy- or imaging-confirmed GCA, were interviewed to identify salient aspects of HRQoL in relation to GCA and its treatment. Purposive sampling included a range of demographic and disease features (cranial, LVV-GCA and visual involvement). Inductive analysis identified individual themes of importance, then domains. Candidate questionnaire items were developed from the individual themes, refined by piloting, cognitive interviews and a linguistic translatability assessment. RESULTS: Thirty-six interviews were conducted to saturation with participants with GCA from the UK (25) and Australia (11). Mean age was 74 years, 23 (63.9%) were female, 13 (36.1%) had visual loss and 5 (13.9%) had LVV-GCA. Thirty-nine individual themes within five domains were identified: physical symptoms; activity of daily living and function; participation; psychological impact; and impact on sense of self and perception of health. Sixty-nine candidate items were developed from individual themes; piloting and refinement resulted in a 40-item draft questionnaire. CONCLUSION: This international qualitative study underpins the development of candidate items for a disease-specific PROM for GCA. The draft questionnaire is now ready for psychometric testing.

Accelerating Rare Disease Drug Development: Lessons Learned from Muscular Dystrophy Patient Advocacy Groups.

With scientific and molecular advancements related to disease pathogenesis, advances in gene and stem cell therapies, and the promise of lucrative markets for biopharmaceutical companies, there has been a rapid expansion in the number of potential new muscular dystrophy (MD) treatments. The first champion for a newly diagnosed MD patient and their caregivers is typically an MD-specific patient advocacy group (PAG). Muscular dystrophy PAGs have been among the most active in the rare disease drug development space. Notable achievements in the last decade include promulgating the first U.S. clinical research guidance, setting up registries and natural history studies, and investing in companies-some of which have brought potentially disease-modifying products to the market. This paper will discuss five key strategies that have been successfully employed by MD PAGs to advance treatments: (1) creating a national registry, (2) understanding the barriers to identifying patients with certain subtypes of muscular dystrophy to participate in clinical trials, (3) partnering with the biopharmaceutical industry, (4) collaborating with the regulators, and (5) incorporating market access and use insights early in clinical development. While clearly helpful within the MD community, these tactics could also be employed by PAGs representing other types of rare diseases.

Use of Big Data to Aid Patient Recruitment for Clinical Trials Involving Biosimilars and Rare Diseases.

Patient recruitment and retention are arguably the greatest challenges to the timely execution of clinical trials. This is particularly true in the case of trials involving biosimilars and those focused on rare diseases. For biosimilars, recruitment success typically hinges on difficulty of access to reimbursement for the originator product and may be hindered by competition from studies with other biosimilars and those with new chemical entities. For rare diseases, recruitment success depends not only on finding enough patients but also on retaining them for the duration of the trial. Historical success with patient recruitment-in addition to site qualifications-needs to be considered in parallel with current market competition and results in an ever-changing patient recruitment environment. Multiple companies supporting the biopharmaceutical industry, such as Contract Research Organizations, have begun to leverage sophisticated data modeling tools and techniques to find additional patients for biosimilar and rare disease trials and/or to find patients more quickly. In addition, these companies seek to better understand the population of interest and refine their statistical assumptions when conducting clinical trials or real-world analyses. The largest and most well-established companies that support the biopharmaceutical industry now have unparalleled access to big data from clinical trials, electronic health records, medical claims, laboratory tests, and prescriptions. This paper will discuss how big data can be harnessed to aid patient recruitment with a focus on clinical trials for biosimilars and orphan rare diseases.

Updating the Clinical Picture of Facioscapulohumeral Muscular Dystrophy: Ramifications for Drug Development With Potential Solutions.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a complex, inheritable, and rare muscle disease that affects the entire body. The major symptom of FSHD is progressive weakening and loss of skeletal muscles. The usual location of these weaknesses at onset is the origin of the name: face (facio), shoulder girdle (scapulo), and upper arms (humeral). FSHD appears to have varying molecular and genetic determinants with commensurate differences in disease progression. METHODS: Facioscapulohumeral muscular dystrophy (MD) is probably the most prevalent form of MD but has neither disease-modifying treatments nor a cure. As the mechanism of action becomes further elucidated, more biopharmaceutical companies are investing capital into finding treatments for patients with FSHD. Sponsors of treatments for FSHD patients should be aware of some of the common misconceptions associated with FSHD drug development with the goal of optimizing the chance to prove safety and efficacy for each potential treatment for FSHD in the clinical trial setting. RESULTS: Four major topics with potential clinical manifestations for patients with FSHD will be discussed related to muscle weakness, respiratory issues, animal models and prevalence. CONCLUSION: The authors offer multiple solutions to help counteract misconceptions with each scenario during clinical trial drug development.

The Arthroplasty Candidacy Help Engine tool to select candidates for hip and knee replacement surgery: development and economic modelling.

BACKGROUND: There is no good evidence to support the use of patient-reported outcome measures (PROMs) in setting preoperative thresholds for referral for hip and knee replacement surgery. Despite this, the practice is widespread in the NHS. OBJECTIVES/RESEARCH QUESTIONS: Can clinical outcome tools be used to set thresholds for hip or knee replacement? What is the relationship between the choice of threshold and the cost-effectiveness of surgery? METHODS: A systematic review identified PROMs used to assess patients undergoing hip/knee replacement. Their measurement properties were compared and supplemented by analysis of existing data sets. For each candidate score, we calculated the absolute threshold (a preoperative level above which there is no potential for improvement) and relative thresholds (preoperative levels above which individuals are less likely to improve than others). Owing to their measurement properties and the availability of data from their current widespread use in the NHS, the Oxford Knee Score (OKS) and Oxford Hip Score (OHS) were selected as the most appropriate scores to use in developing the Arthroplasty Candidacy Help Engine (ACHE) tool. The change in score and the probability of an improvement were then calculated and modelled using preoperative and postoperative OKS/OHSs and PROM scores, thereby creating the ACHE tool. Markov models were used to assess the cost-effectiveness of total hip/knee arthroplasty in the NHS for different preoperative values of OKS/OHSs over a 10-year period. The threshold values were used to model how the ACHE tool may change the number of referrals in a single UK musculoskeletal hub. A user group was established that included patients, members of the public and health-care representatives, to provide stakeholder feedback throughout the research process. RESULTS: From a shortlist of four scores, the OHS and OKS were selected for the ACHE tool based on their measurement properties, calculated preoperative thresholds and cost-effectiveness data. The absolute threshold was 40 for the OHS and 41 for the OKS using the preferred improvement criterion. A range of relative thresholds were calculated based on the relationship between a patient's preoperative score and their probability of improving after surgery. For example, a preoperative OHS of 35 or an OKS of 30 translates to a 75% probability of achieving a good outcome from surgical intervention. The economic evaluation demonstrated that hip and knee arthroplasty cost of < £20,000 per quality-adjusted life-year for patients with any preoperative score below the absolute thresholds (40 for the OHS and 41 for the OKS). Arthroplasty was most cost-effective for patients with lower preoperative scores. LIMITATIONS: The ACHE tool supports but does not replace the shared decision-making process required before an individual decides whether or not to undergo surgery. CONCLUSION: The OHS and OKS can be used in the ACHE tool to assess an individual patient's suitability for hip/knee replacement surgery. The system enables evidence-based and informed threshold setting in accordance with local resources and policies. At a population level, both hip and knee arthroplasty are highly cost-effective right up to the absolute threshold for intervention. Our stakeholder user group felt that the ACHE tool was a useful evidence-based clinical tool to aid referrals and that it should be trialled in NHS clinical practice to establish its feasibility. FUTURE WORK: Future work could include (1) a real-world study of the ACHE tool to determine its acceptability to patients and general practitioners and (2) a study of the role of the ACHE tool in supporting referral decisions. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Patients with severe hip and knee arthritis may require joint replacement. General practitioners make the decision to refer patients to hospital based on an assessment of their symptoms. Pain and function can be measured using patient questionnaires and the questionnaire scores can indicate whether or not the severity of disease warrants referral (i.e. whether or not the patient is a candidate for joint replacement based on their 'capacity to benefit'). However, we do not know whether or not basing treatment decisions on such scores is correct, nor do we know what exact pain score thresholds should be used for referral. After a thorough search, we found that the Oxford Hip and Knee Scores were the best instruments. A high score (i.e. a maximum score of 48) indicates less pain and better function. The threshold values for referral for surgery were scores of 40 for hips and 41 for knees. The process of evaluating scoring systems, the choice of scoring systems and the threshold values were discussed and agreed by a panel of patients and by doctors throughout the study. Most patients with severe joint pain benefit from joint replacement, and these operations are cost-effective. However, above a certain level (a score of 40 for hips and 41 for knees), patients are not thought to typically benefit from surgery. Below these values, lower presurgery scores indicate a steadily increasing likelihood of benefit in terms of reduced pain and better function. This information provides the basis for a tool to help doctors decide who to refer for joint replacement: the Arthroplasty Candidacy Help Engine (ACHE). Use of the ACHE tool prevents patients who are unlikely to benefit from joint replacement being referred unnecessarily and allows the NHS to concentrate resources on those who will benefit most from arthroplasty treatment.

Feasibility and Construct Validation of the Patient Reported Outcomes Measurement Information System in Systemic Vasculitis.

OBJECTIVE: The Patient Reported Outcome Measurement Information System (PROMIS) is a collection of item banks of self-reported health. This study assessed the feasibility and construct validity of using PROMIS instruments in vasculitis. METHODS: Data from a multicenter longitudinal cohort of subjects with systemic vasculitis were used. Instruments from 10 PROMIS item banks were selected with direct involvement of patients. Subjects completed PROMIS instruments using computer adaptive testing (CAT). The Medical Outcomes Study Short Form-36 (SF-36) was also administered. Cross-sectional construct validity was assessed by calculating correlations of PROMIS scores with SF-36 measures and physician and patient global scores for disease activity. Longitudinal construct validity was assessed by correlations of between-visit differences in PROMIS scores with differences in other measures. RESULTS: During the study period, 973 subjects came for 2306 study visits and the PROMIS collection was completed at 2276 (99%) of visits. The median time needed to complete each PROMIS instrument ranged from 40 to 55 s. PROMIS instruments correlated cross-sectionally with individual scales of the SF-36, most strongly with subscales of the SF-36 addressing the same domain as the PROMIS instrument. For example, PROMIS fatigue correlated with both the physical component score (PCS; r = -0.65) and with the mental component score (MCS; r = -0.54). PROMIS physical function correlated strongly with PCS (r = 0.81) but weakly with MCS (r = 0.29). Weaker correlations were observed longitudinally between change in PROMIS scores with change in PCS and MCS. CONCLUSION: Collection of data using CAT PROMIS instruments is feasible among patients with vasculitis and has some cross-sectional and longitudinal construct validity.

Updating OMERACT Core Set of Domains for ANCA-associated Vasculitis: Patient Perspective Using the International Classification of Function, Disability, and Health.

OBJECTIVE: Aspects of antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) prioritized by patients with AAV were described using the International Classification of Function, Disability, and Health (ICF). METHODS: Items identified during 14 individual interviews were incorporated into an ICF-based questionnaire administered to participants of 2 vasculitis patient symposia: 36 in the United Kingdom and 63 in the United States. RESULTS: Categories identified as at least "moderately relevant" by ≥ 5% of subjects included 44 body functions, 14 body structures, 35 activities and participation, 31 environmental factors, and 38 personal factors. CONCLUSION: Identified categories differ from those identified by the current Outcome Measures in Rheumatology (OMERACT) core set and those prioritized by vasculitis experts.

Systemic vasculitis and patient-reported outcomes: how the assessment of patient preferences and perspectives could improve outcomes.

The systemic vasculitides are a group of multisystem diseases, which can be life and organ threatening. High-dose immunosuppressants are required to control inflammation in vital organs, such as the kidneys, lungs, skin, joints, and eyes. Patients report a range of impacts on their health-related quality of life due to symptoms, irreversible damage, and the adverse effects of medications. The measurement of patient perspectives within clinical studies in vasculitis is essential to capture outcomes of greatest importance to patients. Validated generic, disease-specific and symptom-specific patient-reported outcomes available for use in patients with systemic vasculitis are reviewed here.

Validation of the ANCA-associated vasculitis patient-reported outcomes (AAV-PRO) questionnaire.

OBJECTIVES: To finalise and validate a disease-specific patient-reported outcome (PRO) measure: the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire. Using a 35-item candidate questionnaire developed following 50 qualitative interviews in the UK, USA and Canada, a longitudinal survey was conducted to determine the final scale structure and validate the AAV-PRO. METHODS: Participants were recruited via Vasculitis UK and the Vasculitis Patient-Powered Research Network. The 35-item candidate questionnaire was completed at baseline and 3 months; UK participants completed the EuroQol-5D-5L (EQ-5D-5L), while US participants completed a test-retest exercise, 3-5 days after baseline. Scale structure was defined using exploratory factor analysis (EFA) and Rasch analysis. Convergent and known groups validity, test-retest reliability and longitudinal construct validity were assessed. RESULTS: There were 626 participants with AAV; >25% reporting 'active disease'. EFA and Rasch analysis supported a 29-item profile measure comprising six domains: 'organ-specific symptoms', 'systemic symptoms', 'treatment side effects', 'social and emotional impact', 'concerns about the future' and 'physical function'. Mean domain scores were higher for participants with 'active disease' versus 'remission' (p<0.001). Construct validity was demonstrated by correlations between domain scores and the EQ-5D-5L (range r=-0.55 to 0.78), all p<0.0001. In participants reporting 'no change' (n=97) during the test-retest, intraclass correlation coefficient values were high (range 0.89-0.96) for each domain. CONCLUSIONS: The AAV-PRO, a new disease-specific PRO measure for AAV, has good face and construct validity, is reliable, feasible and discriminates among disease states.

Health-related quality of life in ANCA-associated vasculitis and item generation for a disease-specific patient-reported outcome measure.

OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are multisystem diseases of the small blood vessels. Patients experience irreversible damage and psychological effects from AAV and its treatment. An international collaboration was created to investigate the impact of AAV on health-related quality of life (HRQoL), and develop a disease-specific patient-reported outcome measure to assess outcomes of importance to patients. METHODS: Patients with AAV from the UK, USA, and Canada were interviewed to identify salient aspects of HRQoL affected by AAV. The study was overseen by a steering committee including four patient research partners. Purposive sampling of interviewees ensured representation of a range of disease manifestations and demographics. Inductive analysis was used to identify themes of importance to patients; these were further confirmed by a free-listing exercise in the US. Individual themes were recast into candidate items, which were scrutinized by patients, piloted through cognitive interviews and received a linguistic and translatability evaluation. RESULTS: Fifty interviews, conducted to saturation, with patients from the UK, USA, and Canada, identified 55 individual themes of interest within seven broad domains: general health perceptions, impact on function, psychological perceptions, social perceptions, social contact, social role, and symptoms. Individual themes were constructed into >100 candidate questionnaire items, which were then reduced and refined to 35 candidate items. CONCLUSION: This is the largest international qualitative analysis of HRQoL in AAV to date, and the results have underpinned the development of 35 candidate items for a disease-specific, patient-reported outcome questionnaire.

Patient perceptions of glucocorticoids in anti-neutrophil cytoplasmic antibody-associated vasculitis.

Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) are multisystem diseases of small blood vessels, collectively known as the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). This study explores the patient's perspective on the use of glucocorticoids, which are still a mainstay of treatment in AAV. Patients with AAV from the UK, USA, and Canada were interviewed, using purposive sampling to include a range of disease manifestations and demographics. The project steering committee, including patient partners, designed the interview prompts and cues about AAV, its treatment, and impact on health-related quality of life. Interviews were transcribed and analysed to establish themes grounded in the data. A treatment-related code was used to focus analysis of salient themes related to glucocorticoid therapy. Fifty interviews were conducted. Individual themes related to therapy with glucocorticoids emerged from the data and were analysed. Three overarching themes emerged: (1) Glucocorticoids are effective at the time of diagnosis and during relapse, and withdrawal can potentiate a flare, (2) glucocorticoids are associated with salient emotional, physical, and social effects (depression, anxiety, irritation, weight gain and change in appearance, diabetes mellitus, effect on family and work); and (3) patient perceptions of balancing the risks and benefits of glucocorticoids. Patients identified the positive aspects of treatment with glucocorticoids; they are fast-acting and effective, but, they voiced concerns about adverse effects and the uncertainty of the dose-reduction process. These results may be informative in the development of novel glucocorticoid-sparing regimens.

OMERACT Endorsement of Patient-reported Outcome Instruments in Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

OBJECTIVE: The antineutrophil cytoplasmic antibody-associated vasculitides (AAV) are multiorgan diseases. Patients with AAV report impairment in their health-related quality of life (HRQOL) and have different priorities regarding disease assessment compared with physicians. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group previously received endorsement for a core set of domains in AAV. Two approaches to measure patient-reported outcomes (PRO) were presented at OMERACT 2016. METHODS: A novel 5-step tool was used to facilitate assessment of the instruments by delegates: the OMERACT Filter 2.0 Instrument Selection Algorithm, with a red-amber-green checklist of questions, including (1) good match with domain (face and content validity), (2) feasibility, (3) do numeric scores make sense (construct validity)?, (4) overall ratings of discrimination, and (5) can individual thresholds of meaning be defined? Delegates gave an overall endorsement. Three generic Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (fatigue, physical functioning, and pain interference) and a disease-specific PRO, the AAV-PRO (6 domains related to symptoms and HRQOL), were presented. RESULTS: OMERACT delegates endorsed the use of the PROMIS instruments for fatigue, physical functioning, and pain interference (87.6% overall endorsement) and the disease-specific AAV-PRO instrument (89.4% overall endorsement). CONCLUSION: The OMERACT Vasculitis Working Group gained endorsement by OMERACT for use of the PROMIS and the AAV-PRO in clinical trials of vasculitis. These instruments are complementary to each other. The PROMIS and the AAV-PRO need further work to assess their utility in longitudinal settings, including their ability to discriminate between treatments of varying efficacy in the setting of a randomized controlled trial.

A unified multi-level model approach to assessing patient responsiveness including; return to normal, minimally important differences and minimal clinically important improvement for patient reported outcome measures.

OBJECTIVE: This article reviews and compares four commonly used approaches to assess patient responsiveness with a treatment or therapy (return to normal (RTN), minimal important difference (MID), minimal clinically important improvement (MCII), OMERACT-OARSI [Outcome Measures in Rheumatology-Osteoarthris Reseach Society International] (OO)) and demonstrates how each of the methods can be formulated in a multilevel modelling (MLM) framework. DESIGN: Cohort study. SETTING: A cohort of patients undergoing total hip and knee replacement were recruited from a single UK National Health Service hospital. POPULATION: 400 patients from the Arthroplasty Pain Experience cohort study undergoing total hip (n=210) and knee (n=190) replacement who completed the Intermittent and Constant Osteoarthritis Pain questionnaire prior to surgery and then at 3, 6 and 12 months after surgery. PRIMARY OUTCOMES: The primary outcome was defined as a response to treatment following total hip or knee replacement. We compared baseline scores, change scores and proportion of individuals defined as 'responders' using traditional and MLM approaches with patient responsiveness. RESULTS: Using existing approaches, baseline and change scores are underestimated, and the variance of baseline and change scores overestimated in comparison with MLM approaches. MLM increases the proportion of individuals defined as responding in RTN, MID and OO criteria compared with existing approaches. Using MLM with the MCII criteria reduces the number of individuals identified as responders. CONCLUSION: MLM improves the estimation of the SD of baseline and change scores by explicitly incorporating measurement error into the model and avoiding regression to the mean when making individual predictions. Using refined definitions of responsiveness may lead to a reduction in misclassification when attempting to predict who does and does not respond to an intervention and clarifies the similarities between existing methods.

The Oxford knee score and its subscales do not exhibit a ceiling or a floor effect in knee arthroplasty patients: an analysis of the National Health Service PROMs data set.

PURPOSE: In this study, we examined whether the OKS demonstrated a floor or a ceiling effect when used to measure the outcome of knee replacement surgery in a large national cohort. METHODS: NHS PROMs database, containing pre- to 6 month post-operative OKS on 72,154 patients, mean age 69 (SD 9.4), undergoing knee replacement surgery, was examined to establish the proportion of patients achieving top or bottom OKS values pre- and post-operatively. RESULTS: Pre-operatively, none of patients achieved the maximum/'best' (48) and minimum (0) scores. Post-operatively, no patients (0 %) achieved the minimum/'worst' score, but the percentage achieving the maximum score increased to 2.7 %. Subgroup analyses demonstrated that the highest post-operative overall ceiling percentage was 3 %, in a subgroup of patients between 60 and 79 years of age and 13.7 % in a group of patients who had a pre-operative OKS above 41. Furthermore, 10.8 % of patients achieved the top post-operative OKS-PCS and 4.7 % top post-operative OKS-FCS. CONCLUSION: Based on NHS PROMs data, the OKS does not exhibit a ceiling or floor effect overall, or for both its pain and function subscales, and remains a valid measure of outcomes for patients undergoing TKA. LEVEL OF EVIDENCE: Large-scale retrospective observations study, Level II.