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.

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.

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.

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.

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.

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.

Patient-reported outcome measures in arthroplasty registries.

The International Society of Arthroplasty Registries (ISAR) Steering Committee established the Patient-Reported Outcome Measures (PROMs) Working Group to convene, evaluate, and advise on best practices in the selection, administration, and interpretation of PROMs and to support the adoption and use of PROMs for hip and knee arthroplasty in registries worldwide. The 2 main types of PROMs include generic (general health) PROMs, which provide a measure of general health for any health state, and specific PROMs, which focus on specific symptoms, diseases, organs, body regions, or body functions. The establishment of a PROM instrument requires the fulfillment of methodological standards and rigorous testing to ensure that it is valid, reliable, responsive, and acceptable to the intended population. A survey of the 41 ISAR member registries showed that 8 registries administered a PROMs program that covered all elective hip or knee arthroplasty patients and 6 registries collected PROMs for sample populations; 1 other registry had planned but had not started collection of PROMs. The most common generic instruments used were the EuroQol 5 dimension health outcome survey (EQ-5D) and the Short Form 12 health survey (SF-12) or the similar Veterans RAND 12-item health survey (VR-12). The most common specific PROMs were the Hip disability and Osteoarthritis Outcome Score (HOOS), the Knee injury and Osteoarthritis Outcome Score (KOOS), the Oxford Hip Score (OHS), the Oxford Knee Score (OKS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC), and the University of California at Los Angeles Activity Score (UCLA).

Patient-reported outcome measures in arthroplasty registries Report of the Patient-Reported Outcome Measures Working Group of the International Society of Arthroplasty Registries Part II. Recommendations for selection, administration, and analysis.

- The International Society of Arthroplasty Registries (ISAR) Patient-Reported Outcome Measures (PROMs) Working Group have evaluated and recommended best practices in the selection, administration, and interpretation of PROMs for hip and knee arthroplasty registries. The 2 generic PROMs in common use are the Short Form health surveys (SF-36 or SF-12) and EuroQol 5-dimension (EQ-5D). The Working Group recommends that registries should choose specific PROMs that have been appropriately developed with good measurement properties for arthroplasty patients. The Working Group recommend the use of a 1-item pain question ("During the past 4 weeks, how would you describe the pain you usually have in your [right/left] [hip/knee]?"; response: none, very mild, mild, moderate, or severe) and a single-item satisfaction outcome ("How satisfied are you with your [right/left] [hip/knee] replacement?"; response: very unsatisfied, dissatisfied, neutral, satisfied, or very satisfied). Survey logistics include patient instructions, paper- and electronic-based data collection, reminders for follow-up, centralized as opposed to hospital-based follow-up, sample size, patient- or joint-specific evaluation, collection intervals, frequency of response, missing values, and factors in establishing a PROMs registry program. The Working Group recommends including age, sex, diagnosis at joint, general health status preoperatively, and joint pain and function score in case-mix adjustment models. Interpretation and statistical analysis should consider the absolute level of pain, function, and general health status as well as improvement, missing data, approaches to analysis and case-mix adjustment, minimal clinically important difference, and minimal detectable change. The Working Group recommends data collection immediately before and 1 year after surgery, a threshold of 60% for acceptable frequency of response, documentation of non-responders, and documentation of incomplete or missing data.

Evaluating the psychometric properties of an e-based version of the 39-item Parkinson's Disease Questionnaire.

BACKGROUND: The 39-item Parkinson's Disease Questionnaire (PDQ-39) is the most thoroughly validated and extensively used self-report measure for the assessment of health-related quality of life in people with Parkinson's (PwP). Given the extent of its use and increasing emphasis on electronic data capture, an e-based version of the PDQ-39, the ePDQ, has recently been developed. The aim of this short report is to present some key reliability and validity data that confirm the psychometric quality of the ePDQ. FINDINGS: Participants were emailed a unique link to an online survey incorporating the ePDQ and demographic questions. A total of 118 PwP fully completed the survey. Floor and ceiling effects were calculated to ensure responses were not biased to extreme values. Consequently, score reliability was assessed by item-total correlations with a range from 0.34 to 0.90. Cronbach's alpha was calculated at between 0.64 and 0.95 for the eight domains of the ePDQ. Construct validity was assessed by comparing domain scores in relation to disease duration and gender, with hypothesised differences being largely confirmed. Construct validity was further assessed following a higher order factor analysis which confirmed the appropriateness of calculating a summary index score. Subsequently, significant, but moderate correlations were calculated between the ePDQ summary index score and disease duration and age at diagnosis. CONCLUSIONS: Results indicate that the ePDQ largely mirrors the properties of its parent instrument, the PDQ-39, in terms of reliability and validity. Potential users can therefore incorporate the ePDQ into computer-based data capture systems with confidence.

What is the optimal time point to assess patient-reported recovery after hip and knee replacement? A systematic review and analysis of routinely reported outcome data from the English patient-reported outcome measures programme.

BACKGROUND: It is unclear if there is a clinically important improvement in the six to 12-month recovery period after hip and knee replacement. This is an obvious gap in the evidence required by patients undergoing these procedures. It is also an issue for the English PROMs (Patient-Reported Outcome Measures) Programme which uses 6-month outcome data to compare the results of hospitals that perform hip and knee replacements. METHODS: A systematic review of studies reporting the Oxford Hip Score (OHS) or Oxford Knee Score (OKS) at 12 months after surgery was performed. This was compared with six-month outcome data collected for 60, 160 patients within the English PROMs programme. A minimally important difference of one standard error of the measurement, equivalent to 2.7 for the OHS and 2.1 for the OKS, was adopted. RESULTS AND DISCUSSION: Six studies reported OHS data for 10 different groups containing 8,308 patients in total. In eight groups the change scores reported were at least 2.7 points higher than the six-month change observed in the PROMs programme (20.2 points). Nine studies reported OKS data for 13 different groups containing 4,369 patients in total. In eight groups the change scores reported were at least 2.1 points higher than the six-month change observed in the PROMs programme (15.0 points). CONCLUSIONS: There is some evidence from this systematic review that clinically important improvement in the Oxford hip and knee scores occurs in the six to 12 month recovery period. This trend is more apparent for hip than knee replacement. Therefore we recommend that the English Department of Health study the impact on hospital comparisons of using 12- rather than six-month outcome data.

Can pain and function be distinguished in the Oxford Knee Score in a meaningful way? An exploratory and confirmatory factor analysis.

PURPOSE: The purpose of this paper was to examine if pain and functioning can be distinguished in the Oxford Knee Score (OKS) in a meaningful way. This was done by (1) conducting exploratory factor analysis to explore the factorial structure of the OKS and (2) conducting confirmatory factor analysis to examine whether a two-factor solution is superior to a one-factor solution. METHODS: Secondary data analysis of four independent datasets containing OKS scores on 161,973 patients was performed. Four independent datasets contained data on: (1) 156, 788 patients from the NHS HES/PROMS dataset, (2) 2,405 consecutive patients from the South West London Elective Operating Centre, (3) 2,353 patients enrolled in the Knee Arthroplasty Trial and (4) 427 consecutive patients listed for knee replacement surgery at the Nuffield Orthopaedic Centre in Oxford. RESULTS: Factor extraction methods suggested that, depending on the method employed, both one- and two-factor solutions are meaningful. Overall and in each data set some cross-loading occurred and item loadings were consistent across two factors. On confirmatory factor analysis, both one- and two-factor models had acceptable fit indices. This allowed the creation of the 'OKS pain component' and the 'OKS functional component' subscales. CONCLUSIONS: Factor analysis confirmed the original conceptual basis of the OKS but offered an option to perform additional analyses using pain and functional subscales. Further research should focus on providing further evidence on construct validity and responsiveness of the newly derived subscales.

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.

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.

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.

Factors associated with satisfaction in patients undergoing elbow surgery: a prospective study.

HYPOTHESIS: Evidence on factors associated with patient satisfaction with elbow surgery is sparse; outcomes of surgery are not necessarily related to patient satisfaction. This study explored the hypothesis that condition-specific outcome measures would more closely reflect patient satisfaction than generic measures. MATERIALS AND METHODS: The prospective cohort comprised 104 consecutive patients/elbows undergoing elbow surgery. Preoperative and 6 month postoperative outcome questionnaires included the Oxford Elbow Score (OES), Disabilities of the Arm, Shoulder and Hand (DASH), and Short Form (SF)-36 general health survey. Clinical assessments used the standard Mayo Elbow Performance Score (MEPS). Patients who were "very pleased" with surgery were compared with others regarding which factors were associated with being "very pleased" at 6 months after surgery. RESULTS: By 6 months, 54% of patients were very pleased with their surgery. Preoperative scores were generally not associated with subsequent patient satisfaction. Postoperative scores and change scores for the OES Pain and Social-Psychological scales and the DASH were moderately to highly correlated with patient satisfaction (r(s), -0.43 to -0.72; all P < .001), whereas SF-36 and MEPS change scores were only correlated to a small extent (r < or = 0.34; all P < .05). A multivariable analysis revealed that patients' age, postoperative elbow pain, and change in elbow function each independently influenced the odds of patients being very pleased with surgery. DISCUSSION: Associations between outcome measures and patient satisfaction revealed likely differences between patients' and clinicians' perceptions of which aspects of outcome rated as important. CONCLUSIONS: Patient-reported results are more likely than clinically assessed outcome measures, and condition-specific are more likely than generic measures, to reflect patient-rated satisfaction with elbow surgery.

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.

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.

The Oxford shoulder score revisited.

The validated, patient-reported Oxford shoulder score (OSS) was introduced around 10 years ago, primarily for the assessment of outcomes of shoulder surgery (excluding shoulder stabilisation) in randomised trials. Its uptake has steadily increased in a number of countries and its use has also been extended. Recently a number of issues have been raised in relation to other related patient-reported outcome measures which were devised around the same time as the OSS. This included recommendations to change the scoring system. This paper reviews issues concerning patient-reported outcome measures that apply to the OSS and makes some recommendations (including changes to the scoring system) as to how it should be used.

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.