Impact of osteoarthritis disease severity on treatment patterns and healthcare resource use: analysis of real-world data.

OBJECTIVE: To understand treatment patterns and healthcare resource utilization (HCRU) related to osteoarthritis (OA) disease severity in patients in five European countries. METHOD: Data were drawn from the Adelphi OA Disease Specific Programme™ (2017-18). Physicians classified their patients as having mild, moderate, or severe OA, and provided details on their current prescribed therapy and HCRU, including healthcare professional (HCP) consultations, diagnostics and testing, and hospitalizations. Comparisons between disease severity groups were made using analysis of variance and chi-squared tests. RESULTS: The study included 489 physicians (primary care physicians, rheumatologists, orthopaedic surgeons) reporting on 3596 OA patients: 24% mild, 53% moderate, and 23% severe disease. Both physicians and patients reported decreasing satisfaction with treatment with greater disease severity, despite the number of classes of prescribed drugs and increased use of opioids, which were used in almost half of patients with severe OA. For patients whose treatment was not effective, physicians prescribed the same therapeutic options, which were cycled in subsequent treatment lines, with multiple treatment regimens being commonly used. Patients with greater symptom severity also had more physician consultations, while the numbers of tests/imaging, predominantly X-rays, conducted to diagnose or monitor OA increased significantly with disease severity. The type of HCP involvement in patient management also varied by OA severity. CONCLUSIONS: Across five European countries, the use of both non-pharmacological and pharmacological treatments increases with greater disease severity. Those with more severe disease place a greater demand on healthcare resources, with HCP consultations, tests, and hospital visits increasing with severity.

Time to first and sustained improvement in WOMAC domains among patients with osteoarthritis receiving tanezumab.

Objective: To assess onset of effect in three placebo- or nonsteroidal anti-inflammatory drug (NSAID)-controlled trials of tanezumab in patients with moderate-to-severe osteoarthritis. Methods: Post-hoc nonparametric Kaplan-Meier analyses were used to estimate median time to first improvement and to sustained improvement in Western Ontario and McMaster Universities Osteoarthritis Index domain (Pain, Physical Function, Stiffness) scores across a range of improvement thresholds (0-100%, in 5% increments). Time to first improvement was defined as the first week scores met the pre-specified threshold. Time to sustained improvement was defined as the first week scores met the pre-specified threshold and were sustained (on average) for the remainder of the treatment period. Results: Across all domains, tanezumab-treated patients had shorter median times to first improvement (at most thresholds) and reached higher levels of improvement than placebo-treated patients. No substantial differences were observed between tanezumab doses (2.5 and 5 â€‹mg), or between tanezumab and NSAIDs. Most patients experiencing an event of first improvement went on to experience a sustained event. At low thresholds, sustained improvement occurred simultaneously with, or shortly after, first improvement. At higher thresholds, median time to sustained improvement was longer than median time to first improvement. Conclusions: Following initiation of tanezumab treatment, first improvement of osteoarthritis symptoms of 30% was evident within 2-4 weeks and sustained improvement was evident within 2-8 weeks. Time to improvement of 50% was more variable, with first and sustained events expected within 4-16 and 8-24 weeks, respectively. ClinicalTrialsgov identifiers: NCT02697773; NCT02709486; NCT02528188.

Physician and patient perceptions of surgical procedures for osteoarthritis of the knee in the United States, Europe, and Japan: results of a real-world study.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis, with the knee being the joint most frequently affected, and symptomatic knee OA affecting around one quarter of the general population. For patients who do not respond to non-pharmacologic or pharmacologic treatment, surgery is a recommended option. The objectives of this study were to compare the willingness of patients with knee OA to undergo surgery, together with reasons for delaying surgery, and factors affecting successful outcomes. METHODS: A point-in-time survey was conducted in 729 primary care physicians, rheumatologists, orthopedic surgeons, and 2,316 patients with knee OA across three geographical regions: Japan, the United States (US), and Europe (EUR: France, Spain, Italy, Germany, and the United Kingdom), in order to garner their perceptions of knee surgery. Regression models were used to identify factors that might affect patients' and physicians' perceptions of surgery, including severity of OA (mild/moderate/severe), number of affected joints, surgery status, and willingness to undergo or delay surgery. RESULTS: Baseline demographics were similar between US and EUR, although patients in Japan were more likely to be female, older, and only 7% in fulltime employment. We found that few patients with end-stage knee OA, across all regions, but particularly Japan, were willing to undergo surgery (Japan 17%, US 32%, EUR 38%), either through fear, or the lack of awareness of the risk/benefits. Moreover, surgeons are prepared to delay surgery in elderly or unwilling patients, due to their dissatisfaction with the outcome, and may defer surgery in younger patients due to the need for future revision. We also identified a disconnect between physicians, of whom over 80% consider improved functioning to be the most important outcome of surgery, and patients, who seek pain relief (Japan 60%, US 35%, EUR 14%). Since physicians across all regions considered pain reduction to be an indication of surgery success (Japan 27%, US 47%, EUR 43%), this may indicate a need for improved communication to patients on the potential benefits of surgery. CONCLUSION: Managing the expectations of patients undergoing surgery remains an important goal in the treatment of knee OA and may help guide physician choice.

Care pathways in atopic dermatitis: a retrospective population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) is a complex disease with variations in severity and healthcare utilization. Examining patient pathways through analyses of longitudinal patient data provides an opportunity to describe real-world clinical patient care and evaluate healthcare access and treatment. OBJECTIVE: To describe longitudinal care pathways including health care management, treatment patterns and disease progression (by proxy measures) in patients with AD. MATERIALS AND METHODS: This was a longitudinal observational study, which used linked data from national and regional healthcare registers in Sweden. Patients with AD were identified through diagnosis in primary or secondary care or by dispensed medications. Descriptive statistics for number of healthcare visits, type of dispensed drug class, rate of - and time to - referral to secondary care and treatment escalation were calculated. RESULTS: A total of 341 866 patients with AD distributed as 197 959 paediatric (age < 12), 36 133 adolescent (age ≥ 12- < 18) and 107 774 adult (age ≥ 18) patients were included in this study. Healthcare visits to primary and secondary care and dispensation of AD-indicated treatments were more common during the year in which managed AD care was initiated. Topical corticosteroids (TCSs) and emollients were the most frequently used treatments across all age cohorts while systemic treatment was uncommon in all age cohorts. Among patients who initiated treatment with TCSs, 18.2% escalated to TCSs with higher potency following the start of managed AD care. CONCLUSIONS: We found that healthcare contacts and use of AD-indicated treatments were concentrated in the year during which managed AD care was initiated and decreased significantly thereafter. Since a significant proportion of patients with AD have flares and persistent AD, our results suggest that patients with AD may be monitored infrequently and are undertreated. There is a need to inform practitioners about adequate treatment options to provide individualized care, in particular for patients with persistent severe AD.

Cost-Effectiveness of Bosutinib for the Treatment of Adult Patients with Chronic Phase Chronic Myeloid Leukemia in the Second-Line Setting.

BACKGROUND: A recently conducted matching-adjusted indirect comparison demonstrated that bosutinib improved progression-free survival, and delayed progression to advanced disease compared with dasatinib and nilotinib in patients with second line (2L) chronic-phase chronic myeloid leukemia (CP-CML). However, the long-term clinical and economic impact of using bosutinib versus dasatinib and nilotinib has not been evaluated. The objective was to determine the cost-effectiveness of bosutinib compared with dasatinib and bosutinib compared with nilotinib from a US payer perspective. METHODS: A cost-effectiveness model was developed using partition survival methods and three health states: progression-free, progression, and death. Trial data (individual patient-level and aggregate-level data) informed the progression-free and overall survival estimates. Costs included drugs and medical resource use. Utility values were obtained from literature. Sensitivity analyses (SAs) included one-way and probabilistic sensitivity analyses (PSAs). RESULTS: Comparing bosutinib versus dasatinib resulted in a gain of 0.4 discounted life years, 1.5 quality-adjusted life years (QALYs), and incremental costs of $28,459 (values in 2020 US dollars), for an incremental cost-effectiveness ratio (ICER) of $19,811/QALY gained. Comparing bosutinib versus nilotinib resulted in a gain of 0.8 discounted life-years, 1.8 QALYs, and incremental costs of $76,563, for an ICER of $41,932/QALY gained. Drug costs and extrapolation distribution type were the main drivers of the model in the one-way SAs. In the PSAs, bosutinib had >90% and >80% probabilities of being cost-effective at a willingness-to-pay threshold of $100,000/QALY versus dasatinib and nilotinib, respectively. CONCLUSIONS: Our results suggest that compared with dasatinib and nilotinib, bosutinib may represent good value for money for treating 2L CP-CML patients.

Investigating diagnosis, treatment, and burden of disease in patients with ankylosing spondylitis in Central Eastern Europe and the United States: a real-world study.

INTRODUCTION/OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory immune-mediated condition. We compared AS diagnosis, treatment, and burden in Central Eastern European countries (CEE), where this has been less researched, and the United States (US) from a real-world perspective. METHODS: Point-in-time survey of rheumatologists and their AS patients was conducted in the US (Apr-Oct 2018) and CEE (Aug-Nov 2019) via physician- and patient-completed record forms, including clinical and patient-reported outcomes. Statistical analysis included descriptive statistics, t-tests, Fisher's exact tests, and generalized linear models. RESULTS: In total, 487 patients were recruited from 88 rheumatologists in the US and 922 patients from 126 rheumatologists in CEE. Time from onset of symptoms to final AS diagnosis was longer in CEE than the US (4.2 vs 2.7 years, p < 0.05). At diagnosis, a greater use of conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and injected steroids was reported in CEE vs the US (43.7% vs 27.6%, p < 0.05; 19.3% vs 8.7%, p < 0.05). 22.9% of US patients received a biologic DMARD at diagnosis vs 10% of CEE patients (p < 0.05). At current consultation, biologic DMARD use in CEE was lower vs the US (27.9% vs 71.0%, p < 0.05). CEE vs US patients had greater disease activity (mean Bath Ankylosing Spondylitis Disease Activity Index 4.2 vs 3.1, p < 0.05) and worse quality of life (QoL; mean Ankylosing Spondylitis Quality of Life Questionnaire score 6.2 vs 8.4, p < 0.05). CONCLUSIONS: AS patients in CEE vs the US faced slower diagnosis and worse access to biologics, disease activity, and QoL. Whether early access to biologics can improve symptoms, QoL, and daily activities in AS patients in CEE remains to be seen. Key Points • The study provided evidence on the real-world approach to the diagnosis, treatment, and burden of axSpA (axial spondyloarthritis) in CEE compared with the US. • The study reported patients in CEE experienced longer delays in diagnosis and poorer access to biologics than in the US. • This may have resulted in higher disease activity, greater levels of pain, and poorer outcomes, as reported by patients with axSpA in CEE.

Comparative efficacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis.

Given the lack of head-to-head studies of systemic therapies in moderate-to-severe atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data to inform clinical decision-making. In this NMA, eligible randomized controlled trials (RCTs) published before 24 October 2019 were identified by a systematic literature review. Short-term (12-16 weeks) efficacy (Investigator's Global Assessment [IGA] and Eczema Area and Severity Index [EASI] responses), patient-reported outcomes (PROs) and safety data from each trial were abstracted and analysed separately for monotherapy and combination therapy (systemic plus topical anti-inflammatory therapy). RCTs were analysed in fixed-effects and random-effects Bayesian NMA models. Overall, 19 phase 2 and phase 3 RCTs of abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab and upadacitinib were included. In monotherapy RCTs, upadacitinib 30 mg once daily (QD) had the numerically highest efficacy (83.6% achieved ≥50% improvement in EASI [EASI-50 response]), followed by abrocitinib 200 mg QD (74.6%), upadacitinib 15 mg QD (70.5%), dupilumab 300 mg every 2 weeks (Q2W) (63.4%) and abrocitinib 100 mg QD (56.7%). Similar trends in EASI-75 and EASI-90 response were observed. In combination therapy RCTs, abrocitinib 200 mg QD had the highest EASI-50 (86.6%), followed by dupilumab 300 mg Q2W (82.4%) and abrocitinib 100 mg QD (79.7%). Similar findings were observed for IGA response and PROs. In monotherapy and combination therapy RCTs, the probability of treatment-emergent adverse events (TEAEs) was higher among all active treatments than with placebo (except for dupilumab 300 mg Q2W [odds ratio (OR), 0.96; 95% credible interval (CrI), 0.45-2.18] and abrocitinib 100 mg QD [OR, 0.95; 95% CrI, 0.35-2.66] in combination therapy RCTs), although active treatments did not significantly differ from one another. Abrocitinib, dupilumab and upadacitinib were consistently the most effective systemic therapies in adult and adolescent patients with AD, with no significant TEAE differences in short-term RCTs.

Patient preferences for osteoarthritis pain and chronic low back pain treatments in the United States: a discrete-choice experiment.

OBJECTIVE: To quantify preferences for attributes of potential analgesic treatments for moderate-to-severe pain associated with osteoarthritis (OA) and/or chronic low back pain (CLBP) as relevant to injectable nerve growth factor (NGF)-inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. METHODS: We used a discrete-choice experiment (DCE) to elicit preferences for attributes of OA and CLBP pharmaceutical treatments, and a best-worst scaling (BWS) exercise to further characterize the relative importance of treatment-related side-effect risks. The survey was completed online by 602 US residents with self-reported chronic, moderate-to-severe OA pain and/or CLBP who had tried, had contraindications for, or were unwilling to take currently available pharmaceutical therapies. In the DCE, respondents repeatedly chose between two hypothetical treatments defined by six attributes (symptom control; treatment-related risks of (1) severe joint problems, (2) heart attack, and (3) physical dependence; mode/frequency of administration; and cost). In the BWS exercise, respondents evaluated ten side-effect risks. Random-parameters logit models were estimated; conditional relative attribute importance, maximum acceptable risks, and willingness to pay were calculated. RESULTS: The most important DCE attributes were improving symptom control (scaled conditional relative importance, 10.00) and reducing risk of physical dependence (6.99). The three most important BWS attributes were, in rank order, risks of stroke, physical dependence, and heart attack. Respondents were willing to accept a > 4% treatment-related risk of severe joint problems for even modest symptom improvement. CONCLUSION: A pharmaceutical treatment with a risk of severe joint problems was viewed as an acceptable alternative to other treatments with comparable efficacy but risks associated with NSAIDs or opioids.

Results of a global, patient-based survey assessing the impact of psoriatic arthritis discussed in the context of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory musculoskeletal disease, manifesting as peripheral arthritis, enthesitis, dactylitis, spondylitis, and skin and nail psoriasis. A core set of domains for measuring the impact of PsA has been developed, including pain, patient global assessment, physical function, health-related quality of life (HRQoL), and fatigue. To understand the impact of PsA on health domains from a patient's perspective, a global survey was developed and results reported in the context of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire. METHODS: An online patient-based global survey was conducted by The Harris Poll in Australia, Brazil, Canada, France, Spain, Taiwan, the UK, and the US between November 2, 2017 and March 12, 2018. Eligible patients were ≥ 18 years old with a diagnosis of PsA for > 1 year, had visited a rheumatologist/dermatologist in the past 12 months and reported using ≥ 1 synthetic/biologic disease-modifying antirheumatic drug for PsA. Patients reported on PsA severity and symptoms, and the impact of PsA on HRQoL. After survey completion, responses were aligned with PsAID health domains. Descriptive statistics and chi-square tests were conducted. RESULTS: This analysis included 1286 patients from eight countries. Most patients (97%) reported musculoskeletal symptoms relating to PsA in the past year. Common moderate/major impacts of PsA were on physical activity (78%), ability to perform certain activities (76%), work productivity (62%), and career path (57%). Skin/nail symptoms occurred in 80% of patients. Overall, 69% of patients reported that PsA had a moderate/major impact on emotional/mental wellbeing, 56% on romantic relationships/intimacy, and 44% on relationships with family and friends. Social impacts included emotional distress (58%), social shame or disapproval (32%), and ceased participation in social activities (45%). Over half of all patients experienced unusual fatigue over the past 12 months (52%). The health domains that patients reported as being impacted by PsA aligned with life impact domains of the patient-derived PsAID health domains. CONCLUSION: These results highlight the impact of PsA on multiple health domains from a patient perspective that should be considered during shared decision-making processes between healthcare providers and patients.

Considerations for development of an evidence dossier to support the use of mobile sensor technology for clinical outcome assessments in clinical trials.

BACKGROUND: Mobile sensors offer enormous potential for the collection of informative clinical endpoints in clinical trials to support regulatory decision making and product labelling. There are currently no specific guidelines on the information needed to enable regulators to review and accept proposed endpoints derived from mobile sensors for use in drug development trials. OBJECTIVE: The purpose of this working group report is to recommend the structure and content of an evidence dossier intended to support whether a clinical endpoint derived from mobile sensor data is fit-for-purpose for use in regulatory submissions for drug approvals. EVIDENCE DOSSIER: The structure and content of a dossier to provide evidence supporting the use of a sensor-derived clinical endpoint is described. Sections include clinical endpoint definition and positioning, the concept of interest, the context of use, clinical validation and interpretation, study implementation, and analytical validity with sensor performance verification in support of the selected sensor. CONCLUSIONS: In the absence of definitive regulatory guidance, this report provides a considered approach to compiling a comprehensive body of evidence to justify acceptance of mobile sensors for support of new drug applications.

Examining the association between pruritus and quality of life in patients with atopic dermatitis treated with crisaborole.

BACKGROUND: Pruritus is a leading cause of reduced health-related quality of life (QoL) in atopic dermatitis (AD). Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. In identical Phase 3 studies (NCT02118766, NCT02118792), crisaborole reduced disease and pruritus severity versus vehicle. OBJECTIVE: Quantify the relationship between pruritus and QoL using data from these studies. METHODS: Patients aged ≥2 years were randomly assigned 2 : 1 to receive crisaborole:vehicle twice daily for 28 days. QoL was measured at baseline and day 29 using the Dermatology Life Quality Index (DLQI; patients aged ≥16 years), the Children's Dermatology Life Quality Index (CDLQI; patients aged 2-15 years) and the Dermatitis Family Impact (DFI; caregivers of patients aged 2-17 years). Pruritus was measured using the Severity of Pruritus Scale (SPS), a 4-point scale from 0 ('no itching') to 3 ('bothersome itching/scratching that disturbs sleep'), and captured morning and evening via electronic diary. Data from crisaborole and vehicle arms were pooled for this analysis. A repeated-measures longitudinal model was used to estimate relationships between pruritus (SPS) and QoL (DLQI, CDLQI and DFI in separate analyses). RESULTS: One thousand five hundred and twenty two patients received crisaborole or vehicle. A linearity assumption for the relationship between SPS and DLQI (n = 294), CDLQI (n = 1200), and DFI (n = 1293) was appropriate. For DLQI, SPS score of 0 was associated with 'no negative effect on patient QoL'; SPS score of 1 was associated with 'small effect on patient QoL'; SPS score of 2 was associated with 'moderate effect on patient QoL'; and SPS score of 3 was associated with 'very large effect on patient QoL'. The pattern of relationships between SPS and CDLQI and DFI was similar. CONCLUSIONS: The relationships between SPS and DLQI, CDLQI and DFI substantiate the significant link between pruritus and patient/caregiver QoL in AD.

HaemoPREF: Further evaluation of patient perception and preference for treatment in a real world setting.

INTRODUCTION: Adherence to haemophilia A (HA) treatment may be influenced by patients' beliefs about their condition and treatment. Furthermore, difficulties administering treatment may lead to poor adherence. New treatment strategies aim to reduce the burden associated with administration and to improve patient perception of treatment, which, in turn, increase adherence levels. AIMS: This study aimed to examine patient perception of HA treatment and related factors using patient-reported outcome (PRO) questionnaires and to confirm the psychometric properties of a recently developed questionnaire, the HaemoPREF. METHODS: A non-interventional, cross-sectional, questionnaire study was conducted with adult HA patients in Spain (n=31), Germany (n=10) and Italy (n=48), who were using ReFacto AF with the FuseNGo administration device. Patients completed the HaemoPREF and other questionnaires measuring related constructs: treatment adherence, satisfaction and well-being, online at two time points. Correlational, regression and psychometric analyses were conducted. RESULTS: PRO scores indicated that patients are satisfied with and adherent to their treatment. Multivariate regression of the HaemoPREF global score identified a number of significant predictors (P≤.05). The HaemoPREF Global Score had a moderate relationship with subscales on the related questionnaires (mean correlation=0.43; range=0.39-0.48). The HaemoPREF demonstrated good test-retest reliability (intraclass correlation coefficient=0.82), internal consistency reliability (Cronbach's alpha range=0.69-0.82) and convergent validity with measures of treatment satisfaction (Spearman correlation coefficient, r=.48) and well-being (r=.41). CONCLUSION: The findings suggest that patients using ReFacto AF with FuseNGo were satisfied with and adherent to their treatment. The HaemoPREF can identify important concepts relating to patient treatment experience in HA.

Treatment patterns with topicals, traditional systemics and biologics in psoriasis - a Swedish database analysis.

BACKGROUND: Little data exist on real-world treatment patterns in psoriasis, especially from European settings. OBJECTIVE: To estimate, for topicals, systemics and biologics, the time to non-persistency, switching, augmentation and insufficient treatment result (only for biologics), as well as to estimate the time to restart, in patients treated with each treatment class in Sweden based on registry data. METHODS: This database analysis utilized data from patients with psoriasis from several Swedish administrative registers. Patients were identified through combinations of diagnoses from two regional registers and filled prescriptions for relevant treatments from the Swedish Prescribed Drug Register. Kaplan-Meier time-to-event ('survival') functions were estimated with relevant treatment events as failure and the proportions of patients having experienced an event at specific time-points were derived from the failure rates. RESULTS: For topicals, systemics and biologics the number of indexed treatment episodes were 25,396, 2963, and 628 respectively. One year after treatment initiation, the proportion of patients who were classed as non-persistent with topicals, systemics and biologics were estimated at 88.3%, 47.9% and 43.2% respectively. Among patients who remained persistent, within 1 year of treatment start the proportions of treatment episodes in which patients were augmented were estimated at 56.0% for topicals, 45.3% for systemics and 58.9% for biologics. In addition, within 1 year of non-persistence, 49.0% of topicals, 60.8% of systemics and 80.2% of biologics treatment episodes were re-initiated, with 35.4-52.5% re-initiated on the non-persistent treatment depending on treatment class. In addition, among patients on biologics, 29.2% of treatment episodes had an insufficient treatment result within 1 year of treatment start. CONCLUSION: Persistency to psoriasis treatments may be sub-optimal and patients who remain persistent relatively frequently receive augmentation therapy or switch to another therapy. Therefore, current treatment options in psoriasis may be insufficient.

Systematic review and meta-analysis of pharmacological therapies for pain associated with postherpetic neuralgia and less common neuropathic conditions.

OBJECTIVE: To estimate the relative efficacy of pharmacological therapies for the treatment of postherpetic neuralgia (PHN), multiple sclerosis (MS)-related pain, posttraumatic pain, central poststroke pain (CPSP) and human immunodeficiency virus (HIV)-related neuropathic pain (NeP). METHODS: This systematic review (through June 2011) identified randomised, controlled trials of treatments for these conditions. Bayesian mixed treatment comparison (MTC) methods were used to determine the relative efficacy and safety among the treatments within each pain condition. RESULTS: Fifty studies were identified: 33 PHN, 2 MS-related pain, 3 CPSP, 3 posttraumatic pain and 9 HIV-related NeP. Data from 28 PHN studies including 21 interventions and 4317 patients were included into the PHN MTC. Of treatments studied in ≥ 50 patients, opioids had the greatest mean pain reduction of -1.70 vs. placebo on an 11-point numeric rating scale. Pregabalin ≥ 300 mg/day was most effective for ≥ 30% and ≥ 50% pain reduction [relative risk (RR) vs. placebo = 2.44 and 2.13, respectively]. Data identified for MS-related pain, CPSP, posttraumatic pain and HIV-related NeP were sparse; only 7 of 17 studies had ≥ 50 patients. Adverse events (AEs) and discontinuations for most treatments were not significantly greater than placebo except in PHN, where 8 of 12 treatments had higher risks of AEs compared with placebo and tricyclic antidepressants and opioids had higher risk of discontinuation compared with placebo. CONCLUSIONS: Guideline-recommended treatments for PHN were more effective than placebo on the pain NRS and for ≥ 30% and ≥ 50% pain reduction. Although guidelines exist for the management of less common NeP conditions, little published evidence supports them. These results highlight the need for additional evaluations and more complete reporting of outcomes to help guide physicians' treatment selections.

Development and psychometric evaluation of a novel tool for assessing patient perception and preference for haemophilia treatment (HaemoPREF).

Prophylactic use of treatment is important for good outcomes in haemophilia, yet adherence can be suboptimal. To better understand the relationship between treatment adherence and patients' beliefs about treatment there is a need to quantify patients' treatment attitudes. The aim of this study was to develop a brief, clinically relevant, patient-reported outcome (PRO) to measure ease of use and patients' preference for haemophilia treatment. A 40-item questionnaire was completed by male adults with haemophilia A from Austria, Germany, Italy, Spain and the UK. Robust statistical methods for item evaluation including item-level statistics, dimensionality analyses and input from clinical and outcomes experts were used to inform item reduction. Retained items were subjected to psychometric evaluation including exploratory factor analysis (EFA), known-groups validity and internal consistency reliability. 273 patients completed the questionnaire. Of the 40 items, 28 items were flagged for possible deletion based on item-level statistics, three of which were retained due to clinical relevance. Two items had acceptable statistical performance but were deleted based on low clinical relevance. A total of 13 items were retained. EFA produced a conceptually defined 5-factor solution. The survey had acceptable known-groups validity and internal consistency. Refinements were made to wording and scoring, and one new item was added to assess general ease of use, resulting in a 14-item questionnaire - the HaemoPREF. Preliminary measurement properties of the HaemoPREF support the instrument to evaluate patient perception and preference for haemophilia treatment. Further psychometric evaluation is required to examine and confirm the measurement properties of the scale.

Assessment of progression-free survival as a surrogate end-point for overall survival in patients with metastatic renal cell carcinoma.

BACKGROUND: To determine suitability of progression-free survival (PFS) as a surrogate end-point for overall survival (OS), we evaluated the relationship between PFS and OS in 750 treatment-naïve metastatic renal cell carcinoma (mRCC) patients who received sunitinib or interferon-alpha (IFN-α) in a phase III study. METHODS: The relationship between PFS and post-progression survival (PPS; the difference between PFS and OS) was studied, which correctly removes inherent dependencies between PFS and OS, to properly estimate whether and to what extent PFS can serve as a surrogate for OS. A Weibull parametric model to failure time data was fit to determine whether longer PFS was significantly and meaningfully predictive of longer PPS. In a sensitivity analysis by Kaplan-Meier non-parametric method, PPS curves for three approximately equal numbered groups of patients categorised by PFS were compared by log-rank test. RESULTS: In the Weibull parametric model, longer PFS was significantly predictive of longer PPS (P<0.001). The model also allowed prediction of estimated median PPS duration from actual PFS times. In the Kaplan-Meier (non-parametric) analysis, incrementally longer PFS was also associated with longer PPS, and the PPS curves for the three PFS groups were significantly different (P<0.0001). CONCLUSIONS: A positive relationship was found between PFS and PPS duration in individual mRCC patients randomised to first-line treatment with sunitinib or IFN-α. These results indicate that PFS can act as a surrogate end-point for OS in the first-line mRCC setting and provide clinical researchers with a potentially useful approach to estimate median PPS based on PFS.

Impact of physician specialty on classification of physician-perceived patient severity for patients with osteoarthritis.

BACKGROUND: Physicians often classify patients' osteoarthritis (OA) severity subjectively. As treatment decisions are influenced by severity classifications, it is important to understand the factors that influence physicians' OA severity ratings. This research sought to empirically identify physician and patient characteristics that lead to a patient being perceived as having more severe OA. METHODS: Data were analyzed from the OA IX Disease Specific Program, a large cross-sectional survey of OA physicians and patients in Germany, the UK, and USA between September 2011 and January 2012. Eligible, consenting physicians completed a Patient Record Form (PRF) for 10 consecutive OA patients. The PRF asked physicians to report the patient's demographics [age, gender, body mass index (BMI), ethnicity], their assessment of the patients' symptom severity, treatment, probability for surgery, to rate their overall OA severity (mild, moderate or severe) and the factors that had influenced the rating. Chi-squared tests and analysis of variance were used to identify patient characteristics that significantly impacted physicians' OA severity ratings. Controlling for the significant patient characteristics, we then examined the impact of physician specialty on physician's OA severity ratings. Finally, we investigated the differences in physician-reported factors that influenced the physicians' rating of patients' severity between physician specialties. RESULTS: Three hundred and sixty-three physicians [220 primary care physicians (PCPs), 48 rheumatologists, 95 orthopedic surgeons] recruited 3561 patients. Patients with greater age and BMI, worse symptoms and greater health care use were given higher OA severity ratings. Controlling for these factors, orthopedic surgeons rated their OA patients as more severe than PCPs and rheumatologists [adjusted odds ratio (OR) 1.8, 95% confidence interval (CI) 1.4-2.4]. Specialists (rheumatologists and orthopedic surgeons) were more likely than PCPs to use joint spaced narrowing based on X-ray and severity of joint deterioration radiographic severity to assess patients' OA severity (joint space narrowing: 79% and 78% vs 55%, P < 0.0001). CONCLUSIONS: Patient age, BMI, presence and severity of symptoms and health care use significantly impacted physicians' OA severity ratings, but radiographic changes appeared to be given greater weight among orthopedic surgeons and rheumatologists than PCPs when assessing patient severity. Whether these differences translate into different treatment recommendations for similar patients is unknown, and warrants study.