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OBJECTIVE This study assessed associations between severity of, and prescription medication use for, chronic low back pain (CLBP) and health-related quality of life, health status, work productivity, and healthcare resource utilization. METHODS This cross-sectional study utilized SF-12, EQ-5D-5L, and work productivity and activity impairment (WPAI) questionnaires, and visits to healthcare providers among adults with self-reported CLBP participating in the National Health and Wellness Survey in Germany, France, UK, Italy, and Spain. Respondents were stratified into four groups according to pain severity (mild or moderate/severe) and prescription medication use (Rx-treated or Rx-untreated). Differences between groups were estimated using generalized linear models controlling for sociodemographics and health characteristics. RESULTS Of 2086 respondents with CLBP, 683 had mild pain (276 Rx-untreated, 407 Rx-treated) and 1403 had moderate/severe pain (781 Rx-untreated, 622 Rx-treated). Respondents with moderate/severe pain had significantly worse health-related quality of life (SF-12v2 physical component summary), health status (EQ-5D-5L), and both absenteeism and presenteeism compared with those with mild pain, including Rx-untreated (moderate/severe pain Rx-untreated vs. mild pain Rx-untreated, p ≤ 0.05) and Rx-treated (moderate/severe pain Rx-treated vs. mild pain Rx-treated, p ≤ 0.05) groups. Significantly more visits to healthcare providers in the last 6 months were reported for moderate/severe pain compared with mild pain for Rx-treated (least squares mean 13.01 vs. 10.93, p = 0.012) but not Rx-untreated (8.72 vs. 7.61, p = 0.072) groups. Health-related quality of life (SF-12v2 physical component summary) and health status (EQ-5D-5L), as well as absenteeism and presenteeism, were significantly worse, and healthcare utilization was significantly higher, in the moderate/severe pain Rx-treated group compared with all other groups (all p ≤ 0.05). CONCLUSION Greater severity of CLBP was associated with worse health-related quality of life, health status, and absenteeism and presenteeism, irrespective of prescription medication use. Greater severity of CLBP was associated with increased healthcare utilization in prescription medication users.

To evaluate healthcare resource utilization (HCRU) by osteoarthritis (OA) pain severity.Cross-sectional surveys of US physicians and their patients were conducted between February and May 2017. Using the Numeric Rating Scale, patients were classified by self-reported pain intensity in the last week into mild (0-3), moderate (4-6), and severe (7-10) cohorts. Parameters assessed included clinical characteristics, HCRU, and current caregiver support. Descriptive statistics were obtained, and analysis of variance and chi-square tests were performed.Patients (n = 841) were mostly female (60.9%) and white (77.8%), with mean age of 64.6 years. Patients reported mild (45.4%), moderate (35.9%), and severe (18.7%) OA pain. Mean number of affected joints varied by pain severity (range mild: 2.7 to severe: 3.6;Greater current pain was associated with more prior HCRU including imaging for monitoring progression, HCP visits including more specialty care, hospitalizations, surgery/planned surgery, and loss of independence due to functional disability. Yet rates of hospitalizations and X-ray use were still sizable even among patients with mild pain. These cross-sectional findings warrant longitudinal assessment to further elucidate the impact of pain on HCRU.

Background Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We examined the effect of tofacitinib induction treatment on Inflammatory Bowel Disease Questionnaire (IBDQ) items in adults with moderate to severe UC. Methods Data were pooled from the randomized, 8‑week, double-blind, phase 3 OCTAVE Induction 1 and 2 studies. The IBDQ was self-administered by patients at baseline, week 4, and week 8, with higher scores indicating better health-related quality of life (HRQoL). Change from baseline in IBDQ items was analyzed for 10 mg of tofacitinib twice daily (BID) vs placebo using a linear mixed-effects model, with no multiplicity adjustment performed. Effect sizes were calculated. Subgroup analyses by tumor necrosis factor inhibitor (TNFi) experience were performed. Results Significant improvements (nominal P < 0.05) were observed in all IBDQ items with 10 mg of tofacitinib BID vs placebo at weeks 4 and 8. For the overall population, the largest treatment differences across all items were reported for “bowel movements been loose” at weeks 4 and 8, and “problem with rectal bleeding” at week 8 (mean treatment differences all 1.1; both in bowel symptoms domain). These items also showed the largest effect sizes. Treatment benefits were generally slightly numerically higher in TNFi-experienced vs TNFi-naïve patients. Conclusions Tofacitinib induction therapy improved all IBDQ items vs placebo in patients with UC, reflecting improvements in HRQoL, with greatest benefits reported in bowel symptoms domain items (Funded by Pfizer Inc; OCTAVE Induction 1 and OCTAVE Induction 2; ClinicalTrials.gov, NCT01465763 and NCT01458951, respectively).

Objectives Evaluate relationships between changes in dermatologic assessments and quality of life (QoL) measures; quantify dermatologic symptom severity impacts on QoL in patients with psoriatic arthritis (PsA) treated with tofacitinib. Methods Data were from two phase III studies; patients received tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg every other week, or placebo advancing to tofacitinib 5 or 10 mg BID at Month 3. Repeated measures longitudinal models assessed relationships between dermatologic assessments (predictors) Itch Severity Item (ISI), Physician’s Global Assessment of Psoriasis (PGA-PsO), and Patient’s Global Joint and Skin Assessment-Visual Analog Scale-Psoriasis question (PGJS-VAS-PsO), and QoL measures (outcomes) Dermatology Life Quality Index (DLQI) and Short Form-36 Health Survey Version 2 (SF-36v2). Models included one predictor and one outcome. Results Direct, approximately linear relationships existed between predictors and outcomes. ISI/PGA-PsO/PGJS-VAS-PsO improvements from baseline of ≥3/≥2/≥40-mm VAS corresponded with clinically meaningful DLQI improvements; improvements from baseline of ≥4/≥3/≥40-mm VAS generally corresponded with clinically meaningful improvements across component scores and all SF-36v2 domains. Conclusions Substantial links exist between dermatologic symptoms and QoL in patients with PsA, potentially informing patient-centered care and research. Rheumatologists should be aware of dermatologic manifestations and QoL impacts in patients with PsA. ClinicalTrials.gov NCT01877668; NCT01882439

Patients with psoriatic arthritis (PsA) experience impaired health-related quality of life (HRQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA, which has been associated with improvements in dermatologic endpoints in patients with PsA. To assess the extent to which tofacitinib affects patient HRQoL via improvements in dermatologic symptoms, including itch, data were pooled from patients with PsA who received tofacitinib in phase III studies (NCT01866668 and NCT01882439). Mediation modeling assessed the indirect effects (via Itch Severity Item [ISI] and Physician’s Global Assessment of Psoriasis [PGA-PsO]) and direct effects (via all other factors) of tofacitinib treatment on dermatology-specific HRQoL (measured by Dermatology Life Quality Index [DLQI]). In the initial model, the treatment effect on DLQI was largely mediated by itch (ISI, p &lt, 0.0001) and PGA-PsO (p &lt, 0.01). The model was re-specified to assess the indirect effects only of itch and PGA-PsO on DLQI. Here, 17.7% of the treatment effect on DLQI was attributable to PGA-PsO (p = 0.0006), and 82.3% to itch (p &lt, 0.0001). Tofacitinib-dependent improvements in DLQI were primarily mediated by itch relief, in addition to improvements in PGA-PsO.

Background Several different Physician Global Assessment (PGA) versions have been used in clinical studies as a co-primary end point to evaluate psoriasis severity. Tofacitinib is an oral Janus kinase inhibitor. We performed an analysis of the PGA using data from studies of tofacitinib in moderate to severe chronic plaque psoriasis. Methods Data from 3641 patients with moderate to severe chronic plaque psoriasis, enrolled in one of four phase III tofacitinib studies (OPT Pivotal 1 and 2, OPT Compare and OPT Retreatment), were used to evaluate a three-item PGA scale. Results Confirmatory Factor Analyses showed that equal weighting of the three items (erythema, induration and scaling) was appropriate. The PGA demonstrated acceptable test–retest reliability (Intraclass Correlation Coefficient, 0.7) and internal consistency (Cronbach’s Coefficient Alpha ≥ 0.9 at primary time points). The Clinically Important Difference was estimated as 0.55 (95% confidence interval: 0.546–0.563). Known-group validity was shown by demonstrating that PGA scores could discriminate between different degrees of disease severity. The PGA was significantly correlated with other clinical end points in the studies (Psoriasis Area and Severity Index, r = 0.75–0.79; Dermatology Life Quality Index, r = 0.44–0.57; Patient Global Assessment, r = 0.66–0.72). Conclusions Consistent with previous findings from a phase II study, these results indicate that this PGA is a valid, reliable instrument for evaluating disease severity in clinical studies of psoriasis. Electronic supplementary material The online version of this article (10.1186/s12895-019-0088-2) contains supplementary material, which is available to authorized users.

Crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis. Using pooled data from two phase 3 studies (NCT02118766/NCT02118792), mediation modeling determined the interrelationship among pruritus, quality of life (QoL), and treatment. Patients aged ≥ 2 years received crisaborole ointment 2% or vehicle twice daily for 28 days. QoL measures were Dermatology Life Quality Index (DLQI) (≥ 16 years) and Children’s Dermatology Life Quality Index (CDLQI) (2–15 years). Pruritus was assessed by the Severity of Pruritus Scale (4-point scale from 0 to 3). The indirect effect of crisaborole on QoL mediated through its effect on pruritus was 51% (DLQI model, p 0.05). Mediation modeling shows that crisaborole affects QoL mostly indirectly through pruritus severity reduction.

Purpose To evaluate the relationship between self-reported concerns about becoming addicted to a medication and health-related quality of life (HRQoL) in patients with osteoarthritis (OA). Methods This real-world study used patient-level cross-sectional survey data collected from the US Adelphi Disease Specific Programme (DSP). The DSP for OA selected 153 physicians who collected de-identified data on their next nine adult patients with OA. Each patient completed a disease-relevant survey, which included the Likert-scale question, “I am concerned about becoming addicted to my medicine,” (CAA) with responses ranging from “completely disagree” [1] to “completely agree” [5]. HRQoL was measured by the EQ-5D-5L index value and the EQ Visual Analogue Scale (VAS). A set of ordinary least squares regressions using HRQoL measures as outcomes and CAA as a continuous predictor were estimated. Standardized effect size (ES) was used to gauge the magnitude of effects. Results A total of 866 patients with OA completed the survey (female, 61.2%; White, 77.7%; mean age, 64.2 years). Of the 775 patients who completed the CAA question, almost one-third responded that they “agree” (18%) or “completely agree” (11%), while 27% responded “completely disagree” and 20% “disagree.” Regression analyses found that patients who have concerns about medication addiction have significantly different EQ-5D-5L index values and EQ VAS scores compared with patients who do not have this concern (p Conclusion Our findings suggest that concern about medication addiction in patients with OA may have an impact on patient HRQoL, with more concerned patients reporting poorer HRQoL outcomes.

Background In psoriatic arthritis (PsA), further understanding of the relationships between clinical measures and patient-reported outcomes (PROs) is needed. This post hoc analysis evaluated associations between minimal disease activity (MDA) as a continuous outcome (termed ScoreMDA) or Psoriatic Arthritis Disease Activity Score (PASDAS) with selected PROs not included in the composite measures. Methods Data from two phase 3 studies of tofacitinib in PsA (OPAL Broaden [NCT01877668; N = 422]; OPAL Beyond [NCT01882439; N = 394]) were included. MDA (binary outcome) was defined as meeting ≥5/7 criteria. For ScoreMDA, each criterion was assigned a value (1 = true; 0 = false; score range, 0–7; scores ≥5 indicated MDA). For PASDAS (score range, 0–10), higher scores indicated worse disease activity. PROs analyzed included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Patient’s Assessment of Arthritis Pain visual analog scale (Pain VAS), and EuroQoL-Five Dimensions-Three Level Health Questionnaire visual analog scale (EQ-5D-3L VAS) and utility index. Relationships were evaluated using repeated measures regression models. Results Similar, approximately linear relationships were confirmed between PASDAS or ScoreMDA and PROs in both studies. In OPAL Broaden and OPAL Beyond, a one-point difference in PASDAS was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (− 6.7 mm, − 6.9 mm), Pain VAS (9.9 mm, 10.7 mm), and FACIT-F (− 2.8, − 3.3). A one-point difference in ScoreMDA was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (5.0 mm, 5.5 mm) and FACIT-F (1.9, 2.7) in OPAL Broaden and OPAL Beyond, respectively. Conclusions Linear associations between PASDAS or ScoreMDA and PROs provide interpretable and quantifiable metrics between composite clinical measures and PROs, highlighting the importance of these measures in understanding the relevance of treat-to-target goals in PsA. Trial registration ClinicalTrials.gov, NCT01877668. Registered on June 12, 2013. ClinicalTrials.gov, NCT01882439. Registered on June 18, 2013

Introduction The Investigator’s Static Global Assessment (ISGA) is a 5-point rating scale that is recommended by the US Food and Drug Administration for assessing the severity of atopic dermatitis (AD), and ISGA success is a widely used endpoint in AD clinical studies. In this study, we seek to interpret the relationship of ISGA with treatment, pruritus, and quality of life (QoL) by conducting post hoc analyses of pooled data from two phase 3 crisaborole studies. Methods Patients aged ≥ 2 years with baseline ISGA of 2 (mild) or 3 (moderate) were randomly assigned 2:1 to receive crisaborole or vehicle for 28 days. Disease severity, pruritus severity, and QoL were assessed with the ISGA, Severity of Pruritus Scale (SPS), and Dermatology Life Quality Index (DLQI; patients aged ≥ 16 years), or Children’s Dermatology Life Quality Index (CDLQI; patients aged 2–15 years), respectively. The effect of treatment on ISGA and the relationship between ISGA and QoL were analyzed using a longitudinal repeated-measures model. The interrelationship between treatment, disease severity, pruritus, and QoL was analyzed with a mediation model. Results Overall, 1522 patients (crisaborole, n = 1016; vehicle, n = 506) were included. Estimated longitudinal profiles indicated changes in ISGA by day 8 were large for crisaborole (effect size [ES]: − 0.68) and small for vehicle (ES: − 0.34). There was a direct relationship between ISGA and DLQI and CDLQI severity bands in the longitudinal repeated-measures model. For both QoL mediation models, treatment effects on QoL were mediated indirectly by reduction in pruritus (DLQI, 42.4%; CDLQI, 58.1%) and disease severity (DLQI, 12.2%; CDLQI, 33.1%). Conclusions These post hoc analyses suggest that ISGA success is a clinically meaningful endpoint associated with reduction in the severity of pruritus and improvement in QoL. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00506-y.

Purpose: The 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32) is the most frequently used instrument to capture disease-specific quality of life in randomized clinical trials for ulcerative colitis. This review and meta-analysis provides the first synthesis of evidence regarding the sensitivity of IBDQ-32 total and domain scores to treatment efficacy. Methods: A systematic literature search and risk-of-bias assessment yielded 14 articles that were included in the primary analysis. Treatments were categorized as efficacious if they met the primary efficacy endpoint (which was not the IBDQ-32); otherwise they were categorized as non-efficacious. A continuous measure of treatment efficacy was calculated for each primary efficacy endpoint. Meta-analysis using random-effects models compared standardized mean differences in IBDQ-32 total and domain change scores between target dose and control arms. Meta-regression compared the association between treatment efficacy and these outcomes. Results: Studies with efficacious treatments showed larger mean improvements relative to controls in IBDQ-32 total scores and all 4 domains (Hedges’ g range: 0.49 to 0.67; P < 0.001 for all). At the same time, patients in studies with non-efficacious treatments showed small and nonsignificant improvements in these outcomes relative to controls (Hedges’ g range: 0.05 to 0.23; P > 0.09 for all). Meta-regression models showed that the magnitude of treatment efficacy was a positive predictor of these same IBDQ-32 outcomes. Conclusions: These analyses found that IBDQ-32 scores are sensitive to treatment. The results provided here support the use of the IBDQ-32 to capture treatment benefits on quality of life for patients with ulcerative colitis.

Although the osteoarthritis (OA) burden is well-recognised, the benefit of currently available OA pharmacological therapy is not clear. This study aimed to assess whether the impact of OA pain on health-related quality of life (HRQoL), work, and healthcare resource utilisation (HRU) differed by both pain severity and prescription medication status.This cross-sectional study used pooled data from the 2016/2017 European National Health and Wellness Survey. Respondents with self-reported physician-diagnosed OA and pain were included. Outcomes examined included HRQoL, health utility, health status, work productivity and activity impairment, and HRU. Groups derived from self-reported pain severity and prescription medication use were compared using chi-square tests, analysis of variance, and generalised linear models controlling for socio-demographics, health behaviours, and health status.Respondents with OA (n=2417) reported mild (40.4%, of which 44.9% prescription-treated) and moderate to severe pain (59.6%, of which 54.0% prescription-treated). HRQoL, health utility, health status, and work and activity impairment were substantially worse among the moderate/severe pain prescription-treated group compared to the rest (e.g. SF-12v2 physical component score [PCS] for moderate/severe pain prescription-treated=34.5 versus mild pain prescription-treated =39.3, moderate/severe pain prescription-untreated=40.6, and mild pain prescription-untreated=45.6; p0.01). HRU such as the mean number of emergency room visits for6 months was higher in the prescription-treated groups (0.51-0.52, 95% CI 0.437-0.71) than the prescription-untreated groups (0.30-0.34, 95% CI 0.21-0.46; p0.05).Persons with moderate to severe OA pain treated with available prescription medications have poor health status and HRQoL and increased HRU compared to those not receiving prescription medications.

Postmenopausal women (PMW) can experience side-effects (breast pain/tenderness and vaginal spotting/bleeding) associated with estrogen plus progestin therapies (EPTs). To assess these outcomes, the Breast Pain and Tenderness Daily Diary (BPT-DD) and the Vaginal Bleeding and Spotting Daily Diary (VBS-DD) were developed for electronic completion (eDiaries). This study evaluated the psychometric properties of the eDiaries.The eDiaries were completed daily for 28 days by 202 PMW experiencing breast pain/tenderness and/or vaginal spotting/bleeding while on EPTs. Confirmatory factor analysis (CFA) investigated the BPT-DD structure. Response distributions, test-retest reliability (intraclass correlation coefficient [ICC]), internal consistency (BPT-DD only), and construct validity (via known groups and convergent validity analyses) were assessed.Completion rates were high: over 90% of women missed3 daily entries. CFA supported the BPT-DD unidimensional structure (Bentler's Comparative Fit Index0.98). BPT-DD inter-item correlations (r = 0.77-0.89) and internal consistency (Cronbach's alpha = 0.95-0.97) were high and good test-retest reliability was demonstrated (ICC ≥ 0.70). The eDiaries correlated moderately (0.40), in a logical pattern with other instruments, supporting convergent validity. Known-groups analyses indicated both measures demonstrated significant differences between patients of differing severity (p 0.001).The study provides evidence of strong psychometric properties for the BPT-DD and VBS-DD to assess breast pain/tenderness and spotting/bleeding in PMW.

Background and aims This review is the first to evaluate the burden of ulcerative colitis [UC] on patients' quality of life by synthesizing data from studies comparing scores from the SF-36® Health Survey, a generic measure assessing eight quality-of-life domains, between UC patients and matched reference samples. Methods A systematic review of the published literature identified articles reporting SF-36 domains or physical and mental component summary scores [PCS, MCS] from UC and reference samples. Burden of disease for each SF-36 domain was then summarized across studies by comparing weighted mean differences in scores between patient and reference samples with minimally important difference thresholds. Results Thirty articles met pre-specified inclusion criteria. SF-36 scores were extracted from five samples of patients with active disease, 11 samples with a mixture of disease activity, five samples of patients in clinical remission, and 13 samples of patients following proctocolectomy with ileostomy or ileal pouch-anal anastomosis, along with respective reference samples. Clinically meaningful burden was observed in samples with active or mixed disease activity [deficits: PCS = 5.6, MCS = 5.5] on all SF-36 domains except Physical Functioning. No burden was observed in samples in remission or post-surgical patients [deficits: PCS = 0.8, MCS = 0.4] except for the General Health perception domain. Conclusions Patients with active UC experience a clinically meaningful burden of disease across most aspects of quality of life. Patients with inactive UC exhibit negligible disease burden and are comparable to the general population on most quality-of-life outcomes. Thus, treatments which effectively induce and maintain remission may restore physical and mental health status.

Background:Due to its impact on their health-related quality of life (QoL), fatigue is considered a core domain of disease assessment in patients (pts) with ankylosing spondylitis (AS). Psychometric data analyses in pts with rheumatoid and psoriatic arthritis have previously demonstrated that the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is a reliable and valid measure in these pt populations,1,2 but there are limited data supporting the psychometric validity and reliability of the FACIT-F scale in adult pts with active AS.Objectives:To further evaluate the psychometric properties of the FACIT-F scale in adult pts with active AS.Methods:This post hoc analysis used data from the Phase (P)2 (NCT01786668, Study 1) and P3 (NCT03502616, Study 2) studies of tofacitinib in pts with active AS. Second-order confirmatory analysis (CFA) evaluated the measurement model of FACIT-F with two domains (Experience and Impact) and the total score at baseline (BL) and the studies’ respective primary analysis time points, Week (W)12 (Study 1) or W16 (Study 2). At the same time points, internal consistency reliability was examined by Cronbach’s Coefficient alpha (α), and convergent validity was assessed through correlations of FACIT-F domain and total scores with a set of pt-reported outcomes (PROs): Pt Global Assessment of Disease Activity (PtGA), total back pain/nocturnal spinal pain due to AS, Short Form-36 Health Survey (SF-36v2), Bath AS Functional Index, Bath AS Disease Activity Index and ASQoL. Test-retest reliability was assessed by calculating Intraclass Correlation Coefficients (ICCs). The known-groups validity assessment was derived from an anchor-based repeated measures longitudinal model, with PtGA scores as the anchor (PtGA represented pt state from ‘no disease activity’ to ‘very active disease’ [PtGA=0 and 10, respectively]), and FACIT-F domain/total scores as the outcome. Estimations of ability to detect change and meaningful within-pt change (MWPC) were derived from anchor-based repeated measures longitudinal models, with change from BL in PtGA scores as the anchor and change from BL in FACIT-F domain/total scores as the outcome.Results:The CFA model fit the data well (Bentler’s Comparative Index ≥0.92 at BL, W12 [Study 1] and W16 [Study 2]), supporting the measurement model of the FACIT-F scale in pts with AS. Across time points in each study, the FACIT-F domain and total scores demonstrated excellent internal consistency (Cronbach’s Coefficient α ≥0.88), and correlations between FACIT-F domain/total scores, and all PROs assessed generally exceeded 0.40. Generally, in both studies, the largest correlations (0.62–0.85) were between FACIT-F domain/total scores and the SF-36v2 vitality domain score and ASQoL. Test-retest reliability was acceptable for all FACIT-F domain/total scores (ICC ranged from 0.75–0.89 in both studies). An approximately linear relationship was observed between FACIT-F total scores and PtGA scores in both studies (Figure), as well as for Experience and Impact domain scores. The differences in FACIT-F domain/total scores were large and statistically significant between ‘no disease activity’ and ‘very active disease’ pt groups (standardised effect size ≥1.17), supporting known-groups validity. Ability to detect change was evidenced by an approximately linear relationship between changes in PtGA and FACIT-F domain/total scores in both studies; when pts experienced a change in PtGA, values for FACIT-F domain/total scores changed accordingly. Conservatively, MWPC was estimated as 6.3 for FACIT-F total score, and 2.8 and 3.6 for FACIT-F Experience and Impact domain scores, respectively.Conclusion:This quantitative analysis of data from two clinical studies of tofacitinib demonstrates the validity and reliability of the FACIT-F scale in adult pts with active AS. Therefore, these findings support the use of FACIT-F in AS studies.References:[1]Cella et al. J Rheumatol 2005; 32: 811-819.[2]Cella et al. J Patient Rep Outcomes 2019; 3: 30.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Kirsten Woollcott, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:David Cella Consultant of: AbbVie, Alexion Pharmaceuticals, Astellas Pharma, Bayer, Bristol-Myers Squibb, Clovis Oncology, Evidera, Exelixis, Horizon Therapeutics, Janssen, Merck/Schering-Plough, National Academy of Sciences, Novartis Pharma K.K. (Japan), Pfizer Inc, PledPharma and Regeneron, William Lenderking Shareholder of: Pfizer Inc, Employee of: Evidera, Peter Chongpinitchai Employee of: Evidera, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Oluwaseyi Dina Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Victoria Navarro-Compán Speakers bureau: AbbVie, Janssen, Eli Lilly, MSD, Pfizer Inc, UCB, Consultant of: AbbVie, Janssen, Eli Lilly, MSD, Pfizer Inc, UCB, Grant/research support from: AbbVie, Novartis

Objective Conjugated estrogens/bazedoxifene (CE/BZA) has demonstrated benefit in vulvar-vaginal atrophy (VVA, part of genitourinary syndrome of menopause) and the sexual function domain of the Menopause-specific Quality of Life (MENQOL) questionnaire. The study’s objective was to determine the relationship of VVA symptoms and clinical parameters with MENQOL sexual functioning in postmenopausal women receiving VVA treatment. Study design Post hoc analysis data were derived from the 12-week SMART-3 trial, which evaluated CE/BZA’s effect on VVA in nonhysterectomized postmenopausal women (aged 40–65 years) experiencing one or more moderate to severe VVA symptoms (dryness, itching/irritation, pain with intercourse) and vaginal pH > 5.0 (N = 664). Main outcome measures Repeated measures models were used to determine relationships of VVA symptoms and clinical parameters (vaginal pH, parabasal/superficial cells) with sexual functioning; sensitivity analyses were performed to check assumptions of linearity. Results VVA symptoms showed an approximately linear relationship with sexual functioning. A 1-point improvement in pain on intercourse (which has a large effect size [ES] = 0.85) corresponded to medium improvement (ES = 0.57) in MENQOL sexual functioning. Equivalent improvements (in terms of ES) in dryness and itching/irritation corresponded to small to medium (ES = 0.35) and small (ES = 0.27) improvements in sexual functioning, respectively. The same ES improvement in clinical parameters corresponded to small-trivial improvements in sexual functioning. Conclusions VVA symptoms have an approximately linear relationship with sexual functioning. Sexual functioning was most improved when pain on intercourse was reduced. Similar magnitudes of improvements in other VVA symptoms were linked with smaller, though potentially beneficial, improvements in sexual functioning. Changes in clinical parameters had only small or trivial associations with sexual functioning. Trial registration number NCT00238732

The 33-item Overactive Bladder questionnaire (OAB-q; 1-week recall version) has been psychometrically validated in middle-aged, generally healthy patients with overactive bladder. The present analysis was conducted to determine the psychometric validity of the OAB-q in medically complex elderly patients.OAB-q structure was evaluated using a second-order confirmatory factor analysis (CFA) model with five domains and one aggregated domain, using pooled data from two clinical trials (786 observations) for urgency urinary incontinence (UUI). Psychometric validity was evaluated with CFA, Cronbach coefficient α (CCA) for reliability, Spearman correlations for convergent validity, differences in OAB-q scores in relation to UUI severity and Patient Perception of Bladder Condition (PPBC) scores for known-groups validity, and effect size (ES) of differences in mean scores of OAB-q domains over time for treatment responsiveness.Participants were predominantly female (82.2%) and white (85.9%); mean age was 75.0 years. The second-order CFA was confirmed with a Bentler's comparative fit index of 0.90, t values for path coefficients of1.96, and standardized path coefficients of0.40. OAB-q domains demonstrated good internal consistency (CCA0.7). Convergent validity was supported by moderate correlations (0.4-0.7) between OAB-q domain and PPBC scores. Significant differences in OAB-q domain scores between groups with different symptom severity established known-groups validity. Significant changes in mean OAB-q scores from baseline to week 12 with moderate-to-large ES (0.50-0.80) demonstrated treatment responsiveness.The OAB-q demonstrates reliability, concurrent and discriminant validity, and responsiveness to treatment. The evidence shows that the OAB-q is psychometrically sound for use in medically complex elderly patients with overactive bladder.

Annals of hematology 99(6), 1241-1249 (2020). doi:10.1007/s00277-020-04018-1, Published by Springer, Berlin ; Heidelberg ; New York

This study characterizes and quantifies the relationship of vasomotor symptoms (VMS) of menopause with menopause-specific quality of life (MSQOL) and sleep parameters to help predict treatment outcomes and inform treatment decision-making.Data were derived from a 12-week randomized, double-blind, placebo-controlled phase 3 trial that evaluated effects of two doses of conjugated estrogens/bazedoxifene on VMS in nonhysterectomized postmenopausal women (N = 318, mean age = 53.39) experiencing at least seven moderate to severe hot flushes (HFs) per day or at least 50 per week. Repeated measures models were used to determine relationships between HF frequency and severity and outcomes on the Menopause-Specific Quality of Life questionnaire and the Medical Outcomes Study sleep scale. Sensitivity analyses were performed to check assumptions of linearity between VMS and outcomes.Frequency and severity of HFs showed approximately linear relationships with MSQOL and sleep parameters. Sensitivity analyses supported assumptions of linearity. The largest changes associated with a reduction of five HFs and a 0.5-point decrease in severity occurred in the Menopause-Specific Quality of Life vasomotor functioning domain (0.78 for number of HFs and 0.98 for severity) and the Medical Outcomes Study sleep disturbance (7.38 and 4.86) and sleep adequacy (-5.60 and -4.66) domains and the two overall sleep problems indices (SPI: 5.17 and 3.63; SPII: 5.82 and 3.83).Frequency and severity of HFs have an approximately linear relationship with MSQOL and sleep parameters-that is, improvements in HFs are associated with improvements in MSQOL and sleep. Such relationships may enable clinicians to predict changes in sleep and MSQOL expected from various VMS treatments.

Aim: To evaluate outcomes after implementing the women's health assessment tool (WHAT) and clinical decision support toolkit during annual well-women visits. Methods: An observational project involved women aged 45–64 years attending one of three medical sites in Washington (WA, USA). Responses to the WHAT questionnaire and patients' health resource utilization prepost toolkit implementation were analyzed. Results: A total of 110 women completed the WHAT questionnaire. Majority of women were postmenopausal (77.3%) and experienced depressive mood (63.6%), hot flashes (61.8%) or anxiety (60.9%) in the last 3 months. There was a 72.2% increase in the number of diagnoses made during the annual visit versus the previous 12 months. Conclusion: The WHAT/clinical decision support toolkit helped identify conditions relevant to mid-life women.

Background:PsA is a chronic, systemic inflammatory disease with signs and symptoms across multiple domains, including cutaneous manifestations, which can impact health-related quality of life (HQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. In two Phase 3 randomised studies, patients (pts) with active PsA treated with tofacitinib experienced greater improvements in various dermatologic endpoints, compared with placebo. As pruritus is a bothersome symptom of skin disease in pts with PsA, we sought to determine how tofacitinib affects HQoL via clinical improvements in skin symptoms including itch.Objectives:To determine the relationships between tofacitinib treatment, dermatologic symptoms and pt-reported HQoL related to skin disease in PsA.Methods:Analyses used data (mean scores from Months 1 and 3) from two Phase 3 studies (OPAL Broaden [NCT01877668]; OPAL Beyond [NCT01882439]) of pts with active PsA treated with tofacitinib 5 mg twice daily or placebo; pts were tumour necrosis factor inhibitor (TNFi)-naïve or had previous inadequate response (IR) to ≥1 TNFi. All pts were treated continuously with a single conventional synthetic DMARD. Mediation modelling, a statistical method used to assess mechanisms underlying observed relationships between different variables via other explanatory variables (mediators), was applied. The mediation model included: treatment, as the independent (explanatory) binary variable (tofacitinib 5 mg BID vs placebo); HQoL, measured by Dermatology Life Quality Index (DLQI), as the dependent (outcome) variable; and two mediators, pt-reported Itch Severity Index (ISI) and Physician’s Global Assessment of Psoriasis (PGA-PsO) (a latent variable represented by erythema, induration and scaling). The initial model designated the treatment effect on DLQI mediated via ISI and PGA-PsO as an indirect effect, and treatment effects not attributable to ISI or PGA-PsO as a direct effect (Figure 1).Results:Data were collected from 468 pts, pooled from both studies. In the initial model (pooled data), the effect of tofacitinib treatment on DLQI was largely mediated by itch (measured by ISI) and PGA-PsO (indirect effect) (pConclusion:Dermatology-focused mediation modelling showed that a majority of the effect (~80%) of tofacitinib treatment on DLQI is mediated by improvements in itch, with ~20% mediated via improvements in PGA-PsO.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rebecca Germino Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma, Gil Yosipovitch Grant/research support from: Galderma, Kiniksa, Leo, Menlo, Novartis, Pfizer, Sanofi Regeneron, Consultant of: Eli Lilly, Galderma, Kiniksa, Leo, Menlo Therapeutics, Novartis, Pfizer Inc, Sanofi Regeneron, Trevi, Sienna

Background The Short Form-36 Health Survey version 2 (SF-36v2) is a generic health-related quality-of-life (HRQoL) instrument [1]. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In these exploratory analyses the concordance between total and partial Mayo scores and SF-36v2 scores was evaluated in patients with UC in the Phase 3 tofacitinib 8-week OCTAVE Induction 1&2 (NCT01465763; NCT01458951) and 52-week OCTAVE Sustain (NCT01458574) studies. Methods A repeated measures regression model was used to evaluate the relationship between total and partial Mayo scores (as predictor) and SF-36v2 component and domain scores. A sensitivity analysis to assess the linearity assumption was performed using Mayo score as a categorical anchor (represented by integer values 0–12 [total] or 0–9 [partial]). Previous analyses identified clinically important differences (CIDs) in total and partial Mayo scores as changes of 3 points and 2.25 points, respectively [2]. Mean differences in SF-36v2 component and domain scores were compared with their recommended group-level CID thresholds [3]. Results Clinically meaningful differences of 3 points and 2.25 points in total and partial Mayo scores, respectively, were generally associated with clinically meaningful differences in SF-36v2 component and domain scores, with the exception of Role-Emotional with partial Mayo score in the pooled induction studies and with total Mayo score in the maintenance study. In the induction studies, a 3-point difference in total Mayo score was associated with a mean difference exceeding CIDs in both the SF-36v2 Physical Component Summary score (mean improvement 4.5; 95% confidence interval [CI] 4.2, 4.7) and Mental Component Summary score (mean improvement 5.0; 95% CI 4.6, 5.3). Results were closely aligned when Mayo score was used as a categorical or continuous anchor, supporting a linear relationship between Mayo score and SF-36v2 scores (Figure). Similar results were observed in the maintenance study, and when assessing the relationship of partial Mayo score with SF-36v2 scores. Conclusion Clinically meaningful decreases in disease activity, as measured by Mayo score, were associated with clinically meaningful benefits in HRQoL, as measured by SF-36v2 component and domain scores. These findings highlight the impact that disease activity has on HRQoL and may assist with articulating the treatment effect of tofacitinib on specific domains. References

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.

Postmenopausal (PM) women taking therapies using estrogens plus progestogens (EPTs) can experience side effects (breast pain, vaginal spotting/bleeding). Sensitivity of the European Quality of Life Five Dimension Five Level (EQ-5D-5L) in measuring quality of life of PM women experiencing side effects of EPTs is unknown. A crosswalk between the Menopause-Specific Quality of Life (MENQOL) questionnaire and the EQ-5D-5L was assessed.The measures were administered to 352 PM women (side effects = 202; control = 75; untreated = 75) in a non-interventional study. MENQOL total scores, treated as continuous and categorical predictors, were mapped onto EQ-5D-5L utilities using regression. Ordinary least-squares regression using averaged scores over time, goodness of fit, and estimated coefficients was also assessed.Mean age was 53.7 years. The first model (MENQOL as a continuous variable) showed a moderate correlation (-0.589) and statistically significant relationship with the EQ-5D-5L (p 0.001), with an equation of EQ-5D-5L = 0.992 - 0.042 × MENQOL. The EQ-5D-5L mean scores were comparable (side effects = 0.854; control = 0.927; untreated = 0.836) to MENQOL mean scores estimated in the first model (side effects = 0.865 [standard deviation 0.07]; control = 0.909; untreated = 0.833). Linearity assumptions were supported with MENQOL scores as a categorical predictor. Goodness of fit was moderate (RThe crosswalk supports conversion of MENQOL scores to EQ-5D-5L-derived health utilities for group-level analyses in PM women.

Background: Chronic low back pain (CLBP) is estimated to affect about 20% of adults 1 and is the greatest contributor to disability globally. 2 Current pharmacological treatment options may provide limited pain relief or may not be appropriate for long-term use in all patients because of adverse events. 3 Despite the large burden of CLBP, few studies have evaluated the humanistic and economic impact of this condition in Europe, or whether this burden varies for those being treated with prescription (Rx) treatments compared with those who are not Rx treated. Objectives: To assess the burden of CLBP in Europe and to determine whether burden differs by pain severity and treatment status. Methods: A retrospective, cross-sectional study was conducted using data from the 2016 and 2017 National Health and Wellness Survey (NHWS) from five European Union countries (5EU): France, Germany, Italy, Spain, and United Kingdom. NHWS respondents with a self-reported CLBP diagnosis, current pain lasting ≥3 months, and who completed the pain module were identified. Neuropathic and phantom limb pains were excluded. CLBP respondents were categorized into 4 groups by severity of pain and treatment: moderate/severe Rx treated [M/S-Treated]; moderate/severe Rx untreated [M/S-Untreated]; mild Rx treated; and mild Rx untreated (reference). Outcomes of interest included health-related quality of life (HRQoL) (SF-12v2: mental and physical component summary [MCS, PCS]), health status (EQ-5D), productivity loss (Work Productivity and Activity Impairment [WPAI] questionnaire), and health care professional (HCP) visits in past 6 months. Multivariable analyses adjusted for baseline differences between groups (e.g., demographic and health characteristics). Results: A total of 2,086 CLBP patients were identified from the NHWS. CLBP patients reported an average age of 56.4 (SD=13.2) years and most were female (61.2%). Two-thirds of CLBP patients had M/S pain (n=1,403). Stratification by pain and treatment groups resulted in the following groups: M/S-Treated=29.8%, M/S-Untreated=37.4%, Mild-Treated=19.5%, and Mild-Untreated=13.2%. Increased pain severity among both treated and untreated patients showed significantly worse HRQoL, health status, work and activity impairment, and greater HCP visits compared with the reference group (Mild-Untreated) (table 1). Conclusions: Results suggest the majority of European patients with CLBP in this study had moderate to severe pain irrespective of treatment. Whether treated or untreated, those with moderate to severe pain demonstrated a substantial burden related to HRQoL, health status, overall work and activity impairment, and HCP visits compared with those with mild pain. References 1. Meucci RD, et al. Rev Saude Publica2015;49:1–10. 2. GBD. Lancet2017;390(10100):1211–59. 3. Noble, M, et al. Cochrane Database Syst Rev. 2010;20(1):1–68. Disclosure of Interest: M. Doane Grant/research support from: Pfizer Ltd., D. Jaffe Grant/research support from: Pfizer Ltd., E. Dragon Employee of: Pfizer Ltd., L. Abraham Employee of: Pfizer Ltd., L. Viktrup Employee of: Eli Lilly & Company, A. Bushmakin Employee of: Pfizer Ltd., J. Cappelleri Employee of: Pfizer Ltd.

Background: Osteoarthritis (OA) is a chronic, progressive musculoskeletal condition, estimated to affect >40 million people across Europe. OA is a major challenge for health care systems worldwide and is a leading contributor to years lived with disability (YLD) globally.1 Current pharmacological treatment options may provide limited pain relief or may not be appropriate for long-term use in all patients because of adverse events.2 There are few studies on the burden of chronic pain due to OA in Europe and whether this burden varies for those being treated with prescription (Rx) treatments compared with those who are not Rx treated. Objectives: To assess the burden of OA in Europe and to determine whether burden differs by pain severity and treatment status. Methods: A retrospective, cross-sectional study was conducted using data from the 2016 and 2017 National Health and Wellness Survey (NHWS) from five European Union countries (5EU): France, Germany, Italy, Spain, and United Kingdom. NHWS respondents with a self-reported OA diagnosis who completed the pain module were identified. Neuropathic and phantom limb pains were excluded. OA respondents were categorized into 4 groups by severity of pain and treatment: moderate/severe Rx-treated [M/S-Treated]; moderate/severe Rx-untreated [M/S-Untreated]; Mild Rx-treated; and Mild Rx-untreated (reference group). Outcomes of interest included health-related quality of life (HRQoL) (SF-12v2: mental and physical component summary scores [MCS, PCS]), health status (EQ-5D), productivity loss (Work Productivity and Activity Impairment [WPAI] questionnaire), and healthcare utilization in past 6 months. Multivariable analyses adjusted for baseline differences between groups (e.g., demographic and health characteristics). Results: 2,417 OA patients reported a mean age of 61.8 (SD=10.8) years and the majority was female (64.5%). Sixty-percent of OA patients had M/S pain (n=1,440). Stratification by pain and treatment groups resulted in the following: M/S-Treated=27.4%, M/S-Untreated=32.2%, Mild-Treated=22.3%, and Mild-Untreated=18.2%. Those with M/S pain severity, both Rx treated and untreated, showed significantly worse HRQoL, health status and work impairment compared with the reference group (table 1). Further, both Rx treated groups had significantly more health care provider visits compared with OA patients without a Rx. Conclusions: The majority of European patients with OA in this study reported moderate-severe pain irrespective of prescription treatment. Whether treated or untreated, those with moderate to severe OA pain demonstrated a substantial burden on quality of life, health status, and productivity compared with those with mild pain. References 1. Osteoarthritis Research Society International (OARSI). Osteoarthritis: A Serious Disease. New Jersey: December 2016. 2. Noble M, et al. Cochrane Database of Systematic Reviews2010;1:Art. No. CD006605. Disclosure of Interest: M. Doane Grant/research support from: Pfizer Ltd., D. Jaffe Grant/research support from: Pfizer Ltd., E. Dragon Employee of: Pfizer Ltd., L. Abraham Employee of: Pfizer Ltd., L. Viktrup Employee of: Eli Lilly & Company, A. Bushmakin Employee of: Pfizer Ltd., J. Cappelleri Employee of: Pfizer Ltd.

Vulvovaginal atrophy (VVA) is a condition associated with decreased estrogenization of the vaginal tissue, which can result in vaginal dryness, irritation, and dyspareunia. This study quantified the burden associated with VVA symptoms across the United States and Europe and compared this burden with other chronic conditions.Data were analyzed from the International Women's Health Study, a cross-sectional Internet survey of women aged 40-75 years in the United States and Europe. All postmenopausal women aged 40-75 years were included in the analyses (Germany n=970, Spain n=294, France n=1054, Italy n=387, United Kingdom n=1096, United States n=3267). VVA symptom severity (none, mild, moderate, severe) was assessed using the Menopause Rating Scale and included in general linear models to predict EuroQol-5D (EQ-5D) quality of life scores.The prevalence of VVA symptoms varied between 40.00% (Germany) and 54.42% (Spain), with half of women reporting their symptoms as either moderate or severe. Pooling data from all countries together, each incremental level of severity (none through severe) was associated with a significant decrement in EQ-5D scores (none=0.84 vs. mild=0.81 vs. moderate=0.79 vs. severe=0.74; p0.05). The decrements in EQ-5D scores associated with moderate to severe VVA symptoms were comparable to those observed in other serious conditions including arthritis, chronic obstructive pulmonary disease, asthma, and irritable bowel syndrome.VVA symptoms are associated with clinically meaningful decrements in quality of life that may be comparable to serious conditions such as arthritis, chronic obstructive pulmonary disease, asthma, and irritable bowel syndrome. Improved management of VVA symptoms may be required to alleviate the impact of VVA on the quality of life of affected women.

Little is known about the prevalence and cumulative burden of coexisting health conditions including chronic joint and muscular pain, urinary incontinence (UI), depression, osteoporosis risk, moderate/severe vasomotor symptoms, and vulvar/vaginal atrophy (VVA). We surveyed a nationally representative U.S. sample of midlife (age 40-64 years) women to ascertain the prevalence, general health-related quality of life (HRQoL), and health-seeking behaviors associated with these six conditions.This cross-sectional, telephone survey collected data from a sample of English- and Spanish-speaking U.S. women. The survey contained demographic and menopausal status questions, and also five condition-specific symptom/disease risk-screening instruments. The EuroQol 5 dimensions (EQ-5D) questionnaire was used to measure HRQoL. Health-seeking behavior was measured based on clinician discussion of and recent treatment for each condition.Three thousand fifty eight women (mean age 53.4 years) completed the survey. The majority were white (75.6%), married (60.5%), employed full- or part-time (59.0%), and postmenopausal (69.8%; based on self-report). The prevalence [95% confidence interval] of 0, 1, 2, and ≥3 conditions was 35.2% [33.5-36.9], 34.2% [32.5-35.9], 17.9% [16.6-19.3], and 12.7% [11.5-13.9], respectively. Osteoporosis risk (30.6%) was most prevalent, followed by VVA (27.8%) and UI (26.6%). UI and VVA coexisted most frequently (11.3%), followed by osteoporosis risk and VVA (9.8%). EQ-5D scores decreased with increasing number of illnesses (0, 1, 2, and ≥3 conditions, means: 0.92, 0.87, 0.77, 0.61, respectively; p0.01). Health-seeking behavior varied by condition.Over 25% of women surveyed had multiple coexisting conditions. Lower HRQoL was associated with multiple conditions and with each added condition.

To conduct a systematic literature review of the reliability, construct validity, and responsiveness of the SF-36We performed a systematic search of electronic medical databases to identify published peer-reviewed studies which reported scores from the eight scales and/or two summary measures of the SF-36 collected from adult patients with UC. Study findings relevant to reliability, construct validity, and responsiveness were reviewed.Data were extracted and summarized from 43 articles meeting inclusion criteria. Convergent validity was supported by findings that 83% (197/236) of correlations between SF-36 scales and measures of disease symptoms, disease activity, and functioning exceeded the prespecified threshold (r ≥ |0.40|). Known-groups validity was supported by findings of clinically meaningful differences in SF-36 scores between subgroups of patients when classified by disease activity (i.e., active versus inactive), symptom status, and comorbidity status. Responsiveness was supported by findings of clinically meaningful changes in SF-36 scores following treatment in non-comparative trials, and by meaningfully larger improvements in SF-36 scores in treatment arms relative to controls in randomized controlled trials. The sole study of SF-36 reliability found evidence supporting internal consistency (Cronbach's α ≥ 0.70) for all SF-36 scales and test-retest reliability (intraclass correlation coefficient ≥0.70) for six of eight scales.Evidence from this systematic literature review indicates that the SF-36 is reliable, valid, and responsive when used with UC patients, supporting the inclusion of the SF-36 as an endpoint in clinical trials for this patient population.

Background The Functional Assessment of Cancer Therapy–Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) is important to gauge clinical benefit in metastatic renal cell carcinoma (mRCC). Objectives To estimate important difference (ID) in FKSI-DRS scores that is considered to be meaningful when comparing treatment effect between groups, using mRCC trial data. Methods Data were derived from two pivotal phase III mRCC trials comparing sunitinib versus interferon alfa (N = 750) in first-line mRCC, and axitinib versus sorafenib (N = 723) in second-line mRCC. The change from baseline in FKSI-DRS score was examined as a function of a set of anchors using the repeated-measures model. Several anchors were evaluated: FKSI item “I am bothered by side effects of treatment,” EuroQol five-dimensional questionnaire utility score, and adverse events. Results When the “I am bothered by side effects of treatment” score was used as an anchor, the ID ranged between 1.2 and 1.3 points. When change in the EuroQol five-dimensional questionnaire utility score was used as an anchor, the FKSI-DRS ID ranged between 0.62 and 0.63 points. Selecting the adverse events that corresponded to a maximum worsening in the FKSI-DRS score in either trial, the ID ranged between 0.62 and 0.74 points. Conclusions Among patients undergoing treatment for mRCC, between-group differences in FKSI-DRS scores as low as 1 point might be meaningful.

Objective This study aims to confirm the factor structure of the Menopause-Specific Quality of Life (MENQOL) questionnaire by using confirmatory factor analysis (CFA) and to determine whether improvements in menopause-specific health-related quality of life (HRQOL) observed with bazedoxifene (BZA)/conjugated estrogens (CE) relative to placebo are clinically meaningful. Methods Postmenopausal women with seven or more moderate to severe hot flushes per day (or ≥50 per wk) received BZA 20 mg/CE 0.45 mg, BZA 20 mg/CE 0.625 mg, or placebo for 12 weeks. HRQOL and treatment satisfaction were evaluated using the MENQOL questionnaire and the Menopause Symptoms Treatment Satisfaction Questionnaire, respectively. The structure of the MENQOL questionnaire was evaluated using CFA. To estimate clinically important differences (CIDs) in HRQOL, we used a repeated-measures model to estimate changes in MENQOL domain and total scores using Menopause Symptoms Treatment Satisfaction Questionnaire items as anchors. Results The CFA model fits the MENQOL data (Bentler's comparative fit index >0.9). CID estimates ranged from 0.5 to 1.2 for the MENQOL domains and total score. Change from baseline in MENQOL vasomotor domain score for BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg compared with placebo was greater than the estimated CID, as were changes in MENQOL physical domain and total scores for BZA 20 mg/CE 0.625 mg compared with placebo. Conclusions CFA confirms the factor structure of the MENQOL questionnaire. Treatment with BZA/CE provides clinically meaningful improvements in HRQOL in a population of postmenopausal women with bothersome vasomotor symptoms.

Background and Aims Tofacitinib is an oral, small molecule Janus kinase [JAK] inhibitor that is being investigated for ulcerative colitis [UC]. We evaluated health-related quality of life [HRQoL] in tofacitinib UC Phase 3 studies. Methods Patients ≥ 18 years old in OCTAVE Induction 1 [N = 598] and 2 [N = 541] with moderately to severely active UC were randomised [1:4] to placebo or tofacitinib 10 mg twice daily [BID] for 8 weeks. Subsequently, OCTAVE Sustain re-randomised [1:1:1] clinical responders [N = 593] from induction studies to placebo, tofacitinib 5 mg BID, or 10 mg BID, for 52 weeks. Inflammatory Bowel Disease Questionnaire [IBDQ] and SF-36v2® Health Survey [SF-36v2] assessed HRQoL. Results In OCTAVE Induction 1 and 2, mean changes from baseline IBDQ were greater with tofacitinib 10 mg BID at Week 8 [28.9 and 31.5] versus placebo [15.4 and 17.2; p < 0.0001]; mean changes from baseline SF-36v2 Physical and Mental Component Summaries [PCS/MCS] were also greater with 10 mg BID [PCS: 6.8 and 6.8; MCS: 6.8 and 7.6] versus placebo [PCS: 2.5 and 4.6; MCS: 3.5 and 4.4; p < 0.01]. In OCTAVE Sustain atWeek 52, changes in IBDQ were maintained with tofacitinib 5 mg [-1.3] and 10 mg BID [0.6], and larger with placebo [-20.2; p < 0.0001]. Changes in SF-36v2 PCS/MCS were also maintained with 5 mg [PCS: 0.0; MCS: -1.0] and 10 mg BID [PCS: 0.3; MCS: 0.1] versus placebo [PCS: -5.2; MCS: -6.7; p < 0.0001] at Week 52 in OCTAVE Sustain. Conclusions Tofacitinib 10 mg BID induction therapy significantly improved HRQoL versus placebo at Week 8. Improvements were maintained through 52 weeks’ maintenance therapy with tofacitinib 5 mg and 10 mg BID. ClinicalTrials.gov registration numbers NCT01465763, NCT01458951 and NCT01458574

Bazedoxifene/conjugated estrogens (BZA/CE), a novel tissue-selective estrogen complex (TSEC), has been evaluated in the Selective estrogens, Menopause And Response to Therapy (SMART) trials. Secondary outcomes from these trials were evaluated to determine whether the effects of BZA/CE are influenced by years since menopause (YSM).SMART-1 and SMART-2 were randomized, double-blind, placebo (PBO)-controlled phase 3 trials in nonhysterectomized postmenopausal women. Outcomes were evaluated for women5 or ≥5 YSM in SMART-1 (BZA 20 mg/CE 0.45 mg, n=433; BZA 20 mg/CE 0.625 mg, n=414; PBO, n=427) and SMART-2 (BZA 20 mg/CE 0.45 mg, n=127; BZA 20 mg/CE 0.625 mg, n=128; PBO, n=63). Hot-flush frequency and severity, health-related quality of life (HRQoL), sleep, treatment satisfaction, cumulative amenorrhea, and breast pain were assessed for each study individually, using defined statistical analysis protocols.For5 and ≥5 YSM subgroups, BZA 20 mg/CE 0.45 and 0.625 mg showed significant decreases in hot-flush frequency and severity at 3 months compared with PBO (p0.05 for both). Both BZA/CE doses showed significant improvements compared with PBO in HRQoL scores, sleep parameters, and satisfaction with treatment at 3 months irrespective of YSM (p≤0.05 vs. PBO for all). Similar to PBO, BZA/CE showed high proportions of cumulative amenorrhea (SMART-1) and low incidences of breast pain (SMART-1 and SMART-2) for women5 and ≥5 YSM.The positive effects of BZA/CE on secondary outcomes were consistent among women5 or ≥5 YSM.

OBJECTIVE: The current study characterizes health-related quality of life, work productivity, and resource use among postmenopausal women by severity of vasomotor symptoms (VMS). METHODS: Participants were selected from the 2010 US National Health and Wellness Survey. Women aged 40 to 75 years who did not report a history of menstrual bleeding or spotting for 1 year were eligible for analysis (N = 3,267). Cohorts of women with no VMS (n = 1,740), mild VMS (n = 931), moderate VMS (n = 462), and severe VMS (n = 134) were compared after controlling for demographic and health characteristics. Outcome measures were assessed using linear models and included health status, work productivity within the past 7 days, and healthcare resource use within the past 6 months. RESULTS: The mean age of women experiencing severe VMS was 57.92 years. After demographic and health characteristics had been controlled for, women experiencing severe and moderate VMS reported significantly lower mean health status scores compared with women with no symptoms (P < 0.0001). The mean number of menopause symptom-related physician visits was significantly greater among women with severe, moderate, or mild symptoms than among women with no symptoms (P < 0.0001). Among employed women experiencing VMS, women with severe and moderate symptoms had adjusted presenteeism of 24.28% and 14.3%, versus 4.33% in women with mild symptoms (P < 0.001), and activities of daily living impairment of 31.66% and 17.06%, versus 6.16% in women with mild symptoms (P < 0.0001). CONCLUSIONS: In postmenopausal women, a greater severity of VMS is significantly associated with lower levels of health status and work productivity, and greater healthcare resource use.

Determine the direct and indirect effects of conjugated estrogens/bazedoxifene (CE/BZA) treatment on menopause-specific quality of life in a post-hoc analysis of 2 phase 3 Selective estrogens, Menopause, And Response to Therapy (SMART-1, SMART-2) trials.Data from participants in SMART-1 and SMART-2 who received CE 0.45mg/BZA 20mg, CE 0.625mg/BZA 20mg, or placebo were analyzed, including week 12 data from 1274 healthy postmenopausal women in SMART-1 and pooled week 1-4 and 9-12 data from 332 women with moderate to severe vasomotor symptoms (≥7 HFs/d or ≥50/wk) in SMART-2.A statistical mediation model included treatment as a binary predictor variable (pooled active treatment vs placebo), Menopause-Specific Quality of Life (MENQOL) questionnaire domains (vasomotor, sexual, psychosocial, and physical function) as the outcomes variables, and frequency/severity of hot flushes (HFs) as treatment effect mediators on MENQOL.Vasomotor function was affected directly (SMART-1: 35.8%, P0.05; SMART-2: 48.7%, P0.05)] by CE/BZA and indirectly through improvements in HF severity (57.0%, P0.05; 42.1%, P0.05), and to a lesser extent, through reduction in HF frequency (7.2%, P0.05; 9.2%, P0.05). The effects of CE/BZA on the sexual, psychosocial, and physical function domains were fully mediated via improvements in HF severity. Final models for both studies were similar, indicating that direct and indirect effects of CE/BZA on menopause-specific quality of life are consistent and stable in different samples of women.CE/BZA affected the MENQOL vasomotor domain both directly and indirectly, whereas effects on other domains were fully mediated via HF severity reductions.

Introduction: In the ongoing phase 3 BFORE trial (NCT02130557), a significantly higher major molecular response rate at Month 12 was seen with bosutinib vs imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML), and bosutinib treatment was accompanied by improvement or maintenance of health-related quality of life (HRQoL), as assessed by the patient-reported Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) instrument. Diarrhea is a common side effect of bosutinib and occurred more frequently in bosutinib- vs imatinib-treated patients in the primary analysis of the BFORE trial (all grades: 70.1% vs 33.6%). Here, the impact of diarrhea, specifically on HRQoL, was assessed in patients receiving bosutinib or imatinib in the BFORE trial. Methods: Patients with CP CML were randomized 1:1 to receive first-line bosutinib or imatinib. HRQoL was analyzed in the modified intent-to-treat (mITT) population, comprised of Philadelphia chromosome-positive patients with typical BCR-ABL transcripts. The FACT-Leu consists of the 27-item FACT-General (FACT-G) scale with 4 domains (physical, social, emotional, and functional well-being) and the 17-item leukemia-specific subscale; higher scores and changes in scores indicate better HRQoL. Patients completed questionnaires at baseline, every 3 months for the first 2 years and every 6 months thereafter while on treatment, and at treatment completion. In this post hoc analysis, FACT-Leu scores from the first 12 months of treatment were analyzed in patients with diarrhea (any event during treatment) or chronic diarrhea (event lasting ≥28 days). Longitudinal analyses were conducted and standardized effect sizes were calculated to characterize the strength of effect on the FACT-Leu scores for the diarrhea and chronic diarrhea subgroups. Standardized effect sizes of approximately 0.1, 0.2, 0.5, and 0.8 (in absolute values) were considered trivial, small, medium, and large, respectively. Results: In the mITT population (bosutinib: n=246; imatinib: n=241), 163 (66.3%) patients in the bosutinib arm and 74 (30.7%) in the imatinib arm had diarrhea and were evaluable for HRQoL; 34 (13.8%) and 20 (8.3%), respectively, had chronic diarrhea (≥28 days). Among patients who developed diarrhea, the FACT-Leu total score and most subscale scores improved from baseline to Month 12 in both treatment arms, although changes were generally not significant (P>0.05) and could be interpreted as small or trivial, based on effect size (Table). For patients with diarrhea in the bosutinib arm, changes from baseline in the leukemia-specific subscale could be characterized as small improvements starting at Month 6 of treatment; in the imatinib arm, an improvement was not seen until Month 12, and all changes could only be characterized as trivial (Figure). Among patients with chronic diarrhea, the changes from baseline at Month 12 were not significant for all FACT-Leu total or subscale scores in the bosutinib arm and could be interpreted as small or trivial; in the imatinib arm, changes from baseline in all FACT-Leu scores were numerically negative and nonsignificant with the exception of the physical well-being domain (P Conclusions: In this post hoc analysis of the BFORE trial, HRQoL was not negatively affected by diarrhea or chronic diarrhea in the bosutinib arm. Although the analysis is limited by the small number of patients, chronic diarrhea during treatment with imatinib appeared to have a greater impact on HRQoL than chronic diarrhea during treatment with bosutinib, based on the magnitude of the effect sizes and direction of changes, particularly for physical well-being. These data suggest that patients with CP CML treated with bosutinib can preserve or slightly improve HRQoL during therapy, regardless of the presence of diarrhea or chronic diarrhea. Disclosures Brümmendorf: Merck: Consultancy; Janssen: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy. Mamolo:Pfizer: Employment, Equity Ownership. Reisman:Pfizer: Employment, Equity Ownership. Bushmakin:Pfizer: Employment, Equity Ownership. Cappelleri:Pfizer: Employment, Equity Ownership. Crescenzo:Pfizer: Employment. DeAnnuntis:Pfizer Inc: Employment, Equity Ownership. Viquiera:Pfizer: Employment, Equity Ownership. Cortes:Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Arog: Research Funding.

Background: In a randomised phase III trial, sunitinib significantly improved efficacy over interferon-α (IFN-α) as first-line therapy for metastatic renal cell carcinoma (mRCC). We report the final health-related quality of life (HRQoL) results. Methods: Patients (n=750) received oral sunitinib 50 mg per day in 6-week cycles (4 weeks on, 2 weeks off treatment) or subcutaneous IFN-α 9 million units three times weekly. Health-related quality of life was assessed with nine end points: the Functional Assessment of Cancer Therapy–General and its four subscales, FACT–Kidney Symptom Index (FKSI-15) and its Disease-Related Symptoms subscale (FKSI-DRS), and EQ-5D questionnaire's EQ-5D Index and visual analogue scale. Data were analysed using mixed-effects model (MM), supplemented with pattern-mixture models (PMM), for the total sample and the US and European Union (EU) subgroups. Results: Patients receiving sunitinib reported better scores in the primary end point, FKSI-DRS, across all patient populations (P

Introduction The Erection Hardness Score (EHS), a validated single-item patient-reported outcome (PRO), may provide a simple method to capture erectile dysfunction (ED) symptoms and to monitor treatment outcome. Aim To map the relationship between the EHS, which was used as the anchor, and other validated PROs: International Index of Erectile Function (IIEF), Quality of Erection Questionnaire (QEQ), Sexual Experience Questionnaire (SEX-Q), and Self-Esteem and Relationship questionnaire (SEAR). Methods Data were from a trial of flexible-dose sildenafil (50 or 100 mg) in 209 men with ED. Main Outcome Measures A mixed-effects repeated-measures model with EHS as a categorical explanatory variable and each of the other PROs, as a separate dependent variable, was applied to analyze the longitudinal data from randomization to the end of the 10-week, double-blind, placebo-controlled phase and the 6-week open-label phase. EHS data, which were generated at each sexual encounter (event), were averaged per patient over the same recall period that preceded administration of the other PRO questionnaires. Results Scores on all domains of the IIEF and SEX-Q, as well as the SEAR total score and SEAR Sexual Relationship domain, discriminated on all EHS categories. The QEQ total score discriminated on all EHS categories except EHS 1 and EHS 2. Although the model did not impose any functional relationship between PRO score and EHS, an approximately linear relationship existed between the EHS and all other PROs, which was especially pronounced for those PROs that were more directly related to erectile quality or function. Conclusions The relationship between discrete EHS categories and PRO scores demonstrates the close correspondence of erectile hardness with erectile function (IIEF), erection quality (QEQ), overall sexual experience (SEX-Q), and ED-related psychosocial factors (SEAR) in men with ED. Cappelleri JC, Bushmakin AG, Symonds T, and Schnetzler G. S coring c orrespondence in o utcomes r elated to e rectile dysfunction treatment on a 4-point scale (SCORE-4). J Sex Med 2009;6:809–819.

Introduction The absence of a single brief measure that assesses function and health-related quality of life (HRQoL) hinders evaluation of the sexual experience in men with erectile dysfunction (ED). Aim To psychometrically analyze the Sexual Experience Questionnaire (SEX-Q). Methods Two data sets were studied. A randomized, double-blind, placebo-controlled trial of flexible-dose sildenafil for ED treatment provided the final clinical trial data set (213 men enrolled, 4 of whom did not receive treatment) and the interim clinical trial data set (190 men screened and 165 men enrolled). The survey data set consisted of 902 respondents to a U.S. community health survey, of whom two-thirds had ED and one-third did not. Main Outcome Measures Quality and distribution of responses, comparative fit, item-level discriminant testing, internal consistency (Cronbach α), test–retest reliability (intraclass correlation coefficient), known-groups validity (vs. International Index of Erectile Function [IIEF] ED severity groups), convergent validity (Pearson correlation coefficients with scores on the IIEF, Self-Esteem and Relationship [SEAR] questionnaire, and Quality of Erection Questionnaire [QEQ]), responsiveness, and clinically important difference (CID). Results The original 15 items were reduced to 12 items in three domains (erection, individual satisfaction, and couple satisfaction), which demonstrated good quality responses for all items; a strong factor structure; excellent internal consistency; good test–retest reliability; clear known-groups validity across the severity groups; moderate to strong convergent validity against the IIEF, SEAR, and QEQ; and high treatment responsiveness. The estimated CID ranged from 16.0 to 22.3 across domains. Conclusions The SEX-Q is the first questionnaire to solely and exclusively combine functional and HRQoL concepts (erection, individual satisfaction, and couple satisfaction domains) in a brief questionnaire, which allows a more focused and less burdensome evaluation of the sexual experience, making it a potentially useful measure for clinical trial research. Mulhall J, King R, Kirby M, Hvidsten K, Symonds T, Bushmakin A, and Cappelleri J. Evaluating the sexual experience in men: Validation of the Sexual Experience Questionnaire.

Patients with metastatic renal cell carcinoma (RCC) are often treated with cytokine therapy, although the effect is modest and second-line therapy is often warranted. Relatively little is known regarding the impact on health-related quality of life (HRQOL) in cytokine-refractory patients. This study examined the HRQOL of patients with metastatic RCC treated with axitinib, a new targeted therapy that affects the vessels supplying blood to the tumor.Patients with metastatic RCC and progression following first-line cytokine therapy were enrolled into a single-arm, open-label multicenter phase II trial. Axitinib was administered orally twice daily until disease progression or intolerance. The primary endpoint was objective response rate, with secondary endpoints being time to progression, overall survival, safety and HRQOL. The longitudinal analyses of the HRQOL data through 144 weeks of treatment, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, are presented here.Fifty-two patients completed baseline HRQOL assessments. Statistically significant baseline-post-treatment changes were observed on the role, cognitive and social functioning scales as well as on the nausea and vomiting, pain and diarrhea symptoms. All of the changes were less than one-quarter of the category, with diarrhea being the exception at less than half a category, suggesting that the changes as reported by patients were not meaningful.Treatment of metastatic RCC with axitinib demonstrated acceptable disruption in HRQOL functioning and symptoms when compared to baseline levels. From a patient-reported perspective, treatment with axitinib appears to be well tolerated.

Introduction Erection hardness is a fundamental component of erectile function, and is a very specific and easily monitored outcome. The Erection Hardness Score (EHS) is a single-item, patient-reported outcome (PRO) for scoring erection hardness. Aims The aim of this article is to report the psychometric validation of the EHS. Methods The dataset (N = 307) was from a multinational sildenafil trial (efficacy in the treatment of erectile dysfunction [ED]) with a 2-week screening phase, a 6-week double-blind, placebo-controlled treatment phase, and a 6-week open-label extension. Main Outcome Measures Test–retest reliability (intraclass correlation coefficient), quality and distribution of responses, known-groups validity (ability to differentiate between ED severity groups defined by the International Index of Erectile Function [IIEF] questionnaire), convergent validity (Pearson correlation coefficients with domain scores of the IIEF and the Quality of Erection Questionnaire [QEQ]), treatment responsiveness, and clinically important difference. Results The EHS demonstrated good test–retest reliability, acceptable quality and distribution of responses, known-groups validity against the IIEF (including clear differentiation between normal and impaired erectile function), moderate-to-strong convergent validity against the prespecified domains of the IIEF and QEQ, and high treatment responsiveness. Conclusion The EHS has desirable measurement properties, including being highly responsive to treatment. This one-item PRO is robust and easy to use for evaluating erection hardness. Psychometric analysis supports the use of the EHS as a simple, reliable, and valid tool for the assessment of erection hardness in clinical trials research. Mulhall JP, Goldstein I, Bushmakin AG, Cappelleri JC, and Hvidsten K. Validation of the Erection Hardness Score.

Background To assess the prevalence of menopausal symptoms among women prescribed hormone therapy (HT) using electronic medical record data from a regional healthcare organization. Methods Retrospective data from the Reliant Medical Group from 1/1/2006-12/31/2011 were assessed for 102 randomly-selected patients. Study eligibility criteria included: females aged 45 to 65; prescribed oral or transdermal HT; no history of breast cancer, venous thromboembolism, stroke, gynecological cancer, or hysterectomy; continuously enrolled in the health plan for 1 year before and after the first observed HT prescription. Prevalence of menopause-related symptoms was analyzed descriptively at both the patient and visit levels. Results Mean age of patients was 54 years. The most common menopausal symptoms were: hot flushes (40 %), night sweats (17 %), insomnia (16 %), vaginal dryness (13 %), mood disorders (12 %), and weight gain (12 %). Among the 102 patients, 163 individual visits listing menopausal symptoms were identified, of which hot flushes (71 visits) were the most common symptom identified. Conclusion Our findings provide recent data on the types of menopausal symptoms experienced by mid-life women prescribed HT. Electronic medical records may be a rich source of data for future studies of menopausal symptoms in this population.

BACKGROUND Using phase 3 trial data for sunitinib versus interferon (IFN)-α in treatment-naive patients with metastatic renal cell carcinoma, retrospective analyses characterized sunitinib-associated fatigue and its impact on patient-reported health-related quality of life (HRQoL). METHODS Patients received sunitinib at a dose of 50 mg/day on a schedule of 4 weeks on/2 weeks off (375 patients) or IFN-α at a dose of 9 MU subcutaneously 3 times per week (360 patients). HRQoL was self-assessed using the Functional Assessment of Cancer Therapy-Kidney Symptom Index–15-item (FKSI-15) questionnaire, with fatigue assessed using its Disease-Related Symptoms subscale. Fatigue was also assessed by providers using Common Terminology Criteria for Adverse Events (CTCAE). A repeated-measures model (M1) and random intercept-slope model (M2) characterized sunitinib-associated fatigue over time. Another repeated-measures model examined the relationship between HRQoL scores and CTCAE fatigue grade. RESULTS M1 demonstrated that the initial increase in patient-reported fatigue with sunitinib was worst during cycle 1, with mean values numerically better at subsequent cycles; most pairwise comparisons of consecutive CTCAE fatigue cycle means were not found to be statistically significant. M2 demonstrated that the overall trend (slope) for patient-reported and CTCAE fatigue with sunitinib was not statistically different from 0. The relationship between most HRQoL scores and CTCAE fatigue was close to linear regardless of treatment, with lower scores (worse HRQoL) corresponding to higher fatigue grade. The majority of HRQoL scores were better with sunitinib versus IFN-α for the same CTCAE fatigue grade. CONCLUSIONS Patients reported worse fatigue during the first sunitinib cycle. However, in subsequent consecutive cycles, less fatigue was reported with no statistically significant worsening. CTCAE fatigue assessment may not fully capture patient treatment experience. Cancer 2014;120:1871–1880. © 2014 American Cancer Society. Using phase 3 trial data for sunitinib versus interferon-α in treatment-naive patients with metastatic renal cell carcinoma, retrospective analyses characterized sunitinib-associated fatigue and its impact on patient-reported health-related quality of life. Patients reported worse fatigue during the first sunitinib cycle, but in subsequent consecutive cycles less fatigue was reported with no statistically significant worsening; provider-assessed fatigue did not appear to fully capture patient treatment experience.

The Physician Global Assessment (PGA) is a key measure of psoriasis frequently used in clinical trials. A psychometric validation of a three-item (erythema, induration, and scaling) PGA scale was performed using Phase 2 data. Confirmatory factor analysis (CFA) tested the PGA measurement model and appropriateness of equal weighting of the items. PGA test–retest reliability was assessed by estimating the intraclass correlation coefficient (ICC). Internal consistency reliability was gauged by calculating Cronbach’s coefficient α (CCα). Clinically important difference (CID) was defined using the repeated measures model to estimate the relationship between PGA and Patient Global Assessment (PtGA). Known-group, convergent, and divergent validity for the PGA were also assessed. 197 patients with psoriasis were randomized to tofacitinib 2, 5, 15 mg twice daily, or placebo. CFA demonstrated that the PGA measurement model fitted the data using equal weighting of the PGA items. The PGA scale demonstrated good test–retest reliability (ICC > 0.7) and internal consistency reliability (CCα > 0.8). The CID for PGA was estimated at 0.52 (95 % confidence interval: 0.47, 0.56). A robust monotonic relationship between PGA and Psoriasis Area and Severity Index (PASI) data substantiated known-group validity. Relatively high correlations of PGA with PASI and PtGA data (all correlations >0.5 except at baseline) supported convergent validity; relatively low correlations of PGA with the Pain/Discomfort Assessment and the Ocular Comfort Index supported divergent validity. The three-item PGA scale has sound psychometric properties with respect to reliability and validity, with equal weighting of the items being appropriate.