Validated Patient-reported Outcomes Instruments Research Articles

P074 SUSTAINED IMPROVEMENTS IN FATIGUE AND QUALITY OF LIFE IN PATIENTS WITH IBD AND IRON DEFICIENCY ANEMIA FOLLOWING A SINGLE COURSE OF FERUMOXYTOL: RESULTS OF A 6-MONTH EXTENSION STUDY

Iron deficiency anemia (IDA), common in patients with inflammatory bowel disease (IBD) due to blood loss, inflammation and malabsorption, negatively impacts patients’ health-related quality of life (HRQOL). Oral iron is often first-line treatment, but many patients do not tolerate it, or do not adequately respond; many live with chronic anemia and its related negative effects. A Phase 3 double-blind, placebo-controlled trial (NCT01114139) previously found that patients unsuccessfully treated with oral iron, including those with IBD, had very poor baseline HRQOL scores associated with fatigue, and that IV iron treatment resulted in significant, clinically meaningful improvement. To explore the durability of this treatment effect, this subgroup analysis reports on the impact on patient-reported outcomes (PRO) of a single course of IV ferumoxytol, received during the double-blind trial, over the subsequent 6-month extension study (NCT01114217) in patients with IBD. Patients with persistent or recurrent IDA (Hgb <11.0 g/dL and TSAT <20%) at any time during the extension study received ferumoxytol (1 course = 2x510 mg IV, 3 to 8 days apart). The same validated PRO instruments were administered as in the preceding double-blind trial: Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue), and Linear Analogue Scale Assessment (LASA) -Energy, -Activities of Daily Living (ADL) and -HRQOL. This analysis reports on the subgroup of patients who did not receive any additional ferumoxytol during the entire 6-month extension study. Most patients who had received a dose of ferumoxytol in the double-blind trial did not require any further doses during the extension study (285/471; 61% Overall) including 61% (23/30) of those with IBD. Among this cohort, the IBD patients’ mean Hgb had increased from 8.9 ± 0.7 g/dL at Baseline to 12.0 ± 0.8 at Week 5 of the double-blind trial and remained above 12.0 throughout the 6-month extension study visits (Month 7 Hgb 12.1 ± 1.0) despite receiving no further ferumoxytol. At Baseline of the double-blind trial, their FACIT-Fatigue scores were lower (Overall 24.3 ± 12.3; IBD 18.7 ± 12.6) than general (non-anemic) US population norms (40.1-43.6), and comparable to the scores of anemic cancer patients receiving chemotherapy (23.9, Cella 2002). By Week 5, FACIT-Fatigue scores increased significantly (Overall 36.1 ± 11.2; IBD 31.9 ± 13.4), and the improvement was sustained over 6 months (Month 7 score Overall 38.8 ± 11.5; IBD 37.0 ± 13.7). Significant improvements in the LASA domains that were observed in the double-blind study were also maintained. This study found that for the majority of patients, significant improvements in fatigue and quality of life domains, greater than the previously reported Minimal Clinically Important Differences (MID), were achieved and sustained for 6 months following a single treatment of ferumoxytol. Tabled 1Change from Baseline PRO Measures in IBD PatientsPRO InstrumentPretreatment BaselineMean (SD)Month 4 Change Mean (95% CI)Month 7 Change Mean (95% CI)MIDLASA-Energy36.2 (24.15)24.6 (12.8, 36.3)14.7 (4.5, 24.9)9.61LASA-Activity44.4 (23.7)15.9 (5.4, 26.3)13.3 (2.9, 23.8)8.74LASA-QOL46.9 (25.3)18.6 (8.2, 29.1)13.6 (4.5, 22.6)9.81FACIT-Fatigue18.7 (12.6)15.9 (9.3, 22.5)14.2 (8.1, 20.3)3.0PRO = Patient-reported outcomes; CI = confidence interval; MID = Minimum Important Difference (Patrick et al, Euro J Cancer 2003; Norman et al, Med Care 2003; Cella et al, J Pain Symptom Management 2002). Open table in a new tab PRO = Patient-reported outcomes; CI = confidence interval; MID = Minimum Important Difference (Patrick et al, Euro J Cancer 2003; Norman et al, Med Care 2003; Cella et al, J Pain Symptom Management 2002).

Sustained Improvements in Fatigue and Quality of Life in Iron Deficiency Anemia Patients Following a Single Course of Ferumoxytol: Results of a 6-Month Extension Study

Introduction: Iron is essential for the function of many key proteins including hemoglobin (Hgb) and myoglobin (involved in oxygen transport/exchange), cytochromes (involved in energy generation), various enzymes (involved in cell proliferation and neurotransmission), and immune function. Iron deficiency can, therefore, negatively impact patients' health-related quality of life (HRQOL) and requires treatment to replete iron stores. Although oral iron is a common initial treatment, some patients do not tolerate it or fail to adequately respond, and many of these patients live with chronic anemia and the related negative effects on their HRQOL. A Phase 3 double-blind, placebo-controlled trial (NCT01114139) had previously found that patients with iron deficiency anemia (IDA), unsuccessfully treated with oral iron, had very poor baseline HRQOL scores associated with fatigue, and that IV iron treatment with ferumoxytol resulted in clinically meaningful improvements, significantly greater than placebo, over the 5-week study period. To explore the durability of this treatment effect, this analysis reports on the impact on patient-reported outcomes (PRO) of a single course of ferumoxytol therapy over the course of the subsequent 6-month extension study.Methods: A 6-month Phase 3, open-label extension study (NCT01114217) was conducted in patients who had completed the double-blind, placebo-controlled Phase 3 trial. Enrolled patients were evaluated for IDA monthly throughout the study period. Those with persistent or recurrent IDA (Hgb <11.0 g/dL and TSAT <20%) at any evaluation visit, received a course of ferumoxytol (2 x 510 mg, 3-8 days apart). The same validated PRO instruments were administered in this extension study as in the preceding double-blind trial: Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue), Short Form Health Survey (SF-36), and Linear Analogue Scale Assessment (LASA) of Energy, Activities of Daily Living (ADL) and HRQOL. This analysis reports results for the subgroup of patients who did not receive any additional doses of ferumoxytol during the entire 6-month period of the extension study.Results: The majority of patients enrolled in the extension study who had received ferumoxytol in the previous Phase 3 trial (285/471; 61%) did not meet the above-noted re-treatment criteria during the 6-month extension, and did not receive any further doses of ferumoxytol. Reflecting the overall enrollment in the extension study, these patients were predominantly female (90.0%) and white (63.5%), with mean age of 43.6±13.3 years (range 19-88). The most common primary underlying conditions were abnormal uterine bleeding (41.8%), GI disorder (33.0%), and cancer (10%). Their mean Hgb had increased from 9.0±0.8 g/dL at Baseline to 12.1±1.1 at Week 5 of the double-blind trial and remained above 12.0 throughout the 6-month extension study visits (Month 7 Hgb 12.1±1.2) despite receiving no further ferumoxytol.At Baseline of the double-blind trial, their FACIT-Fatigue scores were lower (24.3±12.3) than general (non-anemic) US population norms (40.1-43.6), and comparable to anemic cancer patients receiving chemotherapy (23.9, Cella 2002). By Week 5 following ferumoxytol treatment, their FACIT-Fatigue scores had increased significantly (36.1±11.2), approaching general population norms. This improvement was sustained over the following 6 months (Month 7 score 38.8±11.5).Their SF-36 Vitality scores increased from 37.6 ±11.8 at Baseline of the double-blind trial to 47.7±12.0 at Week 5, approaching the general US population norm (50.0, McHorney 1993) and continued to increase slightly over the next 6 months (Month 4, 50.0±12.0; Month 7, 50.9±11.5). Similarly, the significant improvements in LASA Energy, ADL and HRQOL scores that were observed in the double-blind study were also maintained over the next 6 months.Conclusions:These data suggest that ferumoxytol may provide important clinical benefits to IDA patients with a history of unsatisfactory oral iron therapy; these benefits include reductions in fatigue, increased energy, vitality, and ability to perform ADL and improved HRQOL. This is important especially in light of the poor baseline energy and HRQOL scores of patients who cannot take oral iron. This study found that for the majority of patients, these improvements were sustained for at least 6 months after a single course of therapy. [Display omitted] DisclosuresVadhan-Raj:AMAG Pharmaceuticals, Inc: Other: received funding from Amag to support clinical trial. Dahl:AMAG Pharmaceuticals, Inc: Employment, Equity Ownership. Jiang:AMAG Pharmaceuticals, Inc: Employment, Equity Ownership. Strauss:AMAG Pharmaceuticals, Inc: Employment, Equity Ownership.

Patient-Reported Outcomes with Chimeric Antigen Receptor T Cell Therapy: Challenges and Opportunities.

Patient-reported outcomes (PROs) are an important tool to assess the impact of a new therapy on symptom burden and health-related quality of life (HRQoL). Chimeric antigen receptor T (CAR-T) cell therapies have been approved for use in relapsed or refractory leukemia and lymphoma based on promising efficacy in clinical trials. However, data are lacking on patient-reported toxicity and impact on HRQoL. This review provides an overview of the incorporation of PROs in CAR-T cell therapy and the specific challenges in this context. The first step is to demonstrate feasibility of PRO monitoring in the acute phase after CAR-T cell infusion. Apart from core PRO domains like physical functioning, disease-related symptoms, and symptomatic adverse effects, important measures to consider are cognitive functioning and financial toxicity. Because there are no validated PRO instruments in the setting of CAR-T cell therapy, universally validated measures like Patient-Reported Outcomes Measurement Information System (PROMIS) could be considered, which is also recommended in the setting of hematopoietic stem cell transplantation. Given the timeline of toxicities with CAR-T cell therapy, PRO instruments should be administered at baseline and at least weekly in the first 30 days. Subsequently, frequent monitoring of PROs in the first year might be helpful in identifying short- and intermediate-term toxicities, functional limitations, and neuropsychiatric effects. The major potential challenge in acute phase would be missing data when patients develop severe cytokine release syndrome or neurotoxicity. Designing a strategy for handling missing data is crucial. The long-term safety of CAR-T cell therapy is not well characterized because of short follow-up in most studies reported thus far. PROs should be measured at least yearly after the first year to identify potential late effects like cognitive deficit or autoimmune manifestations. Collaboration between institutions performing cellular therapy and engagement with patients, clinicians, and statisticians with expertise in PROs are crucial for setting a comprehensive agenda on integration of PROs with CAR-T cell therapy.

Systematic literature review and assessment of patient-reported outcome instruments in sickle cell disease

BackgroundSickle cell disease (SCD) is a chronic condition associated with high mortality and morbidity. It is characterized by acute clinical symptoms such as painful vaso-occlusive crises, which can impair health-related quality of life (HRQL). This study was conducted to identify validated patient-reported outcome (PRO) instruments for use in future trials of potential treatments for SCD.MethodsA systematic literature review (SLR) was performed using MEDLINE and EMBASE to identify United States (US)-based studies published in English between 1997 and 2017 that reported on validated PRO instruments used in randomized controlled trials and real-world settings. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the quality of PRO instruments.ResultsThe SLR included 21 studies assessing the psychometric properties of 24 PRO instruments. Fifteen of those instruments were developed and validated for adults and 10 for children (one instrument was used in both children and young adults aged up to 21 years). Only five of the 15 adult instruments and three of the 10 pediatric instruments were developed specifically for SCD. For most instruments, there were few or no data on validation conducted in SCD development cohorts. Of the 24 PRO instruments identified, 16 had strong internal reliability (Cronbach’s α ≥0.80). There was often insufficient information to assess the content validity, construct validity, responsiveness, or test-retest reliability of the instruments identified for both child and adult populations. No validated PRO instruments measuring caregiver burden in SCD were identified.ConclusionsThe evidence on the psychometric properties of PRO instruments was limited. However, the results of this SLR provide key information on such tools to help inform the design of future clinical trials for patients with SCD in the US.

The Bladder Utility Symptom Scale: A Novel Patient Reported Outcome Instrument for Bladder Cancer

Health related quality of life is important in bladder cancer care and clinical decision making because patients must choose between diverse treatment modalities with unique morbidities. A patient reported outcome measure of overall health related quality of life for bladder cancer regardless of disease severity and treatment could benefit clinical care and research. Prospective questionnaire development was completed in 3 parts. In study 1 the BUSS (Bladder Utility Symptom Scale) questions were created by experts using a conceptual framework of bladder cancer health related quality of life generated through patient focus groups. In study 2 patients with bladder cancer, including those treated with surgery, radiation and chemotherapy, completed the BUSS and 5 health related quality of life instruments at baseline and 4 weeks to assess validity and test-retest reliability. External validity was then explored in study 3 by administering the BUSS to 578 patients online and at clinics. Construct validity was assessed by whole and subscale Spearman rank correlations, and by comparisons of BUSS scores across known groups. The BUSS had high whole scale correlation with the FACT-Bl (Functional Assessment of Cancer Therapy-Bladder) (rs = 0.82, p <0.0001) and substantial to high subscale correlations with the EQ-5D™-3L (EuroQol 5 Dimensions Questionnaire-3 Levels) (eg emotional well-being rs = 0.69, p<0.0001). BUSS scores were lower in patients with comorbidity and advanced disease. Cognitive debriefing and the 94% completion rate suggested good comprehensibility. There was excellent test-retest reliability (ICC = 0.79). Limitations included an extended time from diagnosis in many patients. The BUSS is a reliable and valid patient reported outcome instrument for health related quality of life in all patients with bladder cancer regardless of the treatment received or the stage of disease.

Development and content validation of a patient-reported endometriosis pain daily diary

BackgroundEndometriosis is a common gynecological disorder that causes inflammation and pelvic pain. Endometriosis-related pain is best captured with patient-reported outcome (PRO) measures, however, assessment of endometriosis-related pain in clinical trials has been difficult in the absence of a reliable and valid PRO instrument. We describe the development of the Endometriosis Pain Daily Diary (EPDD), an electronic PRO developed as a survey instrument to assess endometriosis-related pain and its impact on patients’ lives.MethodsThe EPDD was initially developed on the basis of an existing Endometriosis Pain and Bleeding Diary, a targeted review of relevant literature, clinical expert interviews, and open-ended (concept elicitation) patient interviews in the United States (US) and Japan which captured patients’ experience with endometriosis. Cognitive interviews of patients with endometriosis were conducted to evaluate patient comprehension of the EPDD items. A conceptual model of endometriosis was developed, and meetings with US and European regulatory authorities provided feedback for validating the EPDD in the context of clinical trials. Translatability assessments of the EPDD were conducted to confirm its appropriate interpretation and ease of completion across 17 languages.ResultsThe iterative development progressed through three versions of the instrument. The EPDDv1 included 18 items relating to dysmenorrhea/pelvic pain, dyspareunia and sexual activity, bleeding, hot flashes, daily activities, and use of rescue medication. The EPDDv2 was a larger 43-item survey tested in cognitive interviews and subsequently revised to yield the current 11-item EPDDv3, consisting of five core items relating to dysmenorrhea, non-menstrual pelvic pain, and dyspareunia, and six extension items relating to sexual activity, daily activities, and use of rescue medication.ConclusionsThe EPDD is a PRO for the evaluation of endometriosis-related pain and its associated impacts on patients’ lives. The EPDD represents an important step in providing a PRO that is relevant to patients with endometriosis-related pain in the context of a clinical study setting (ie, fit-for-purpose), designed to evaluate pain associated with endometriosis, including regulatory agency support for its further exploration in clinical trials.

Psychometric Validation of the BODY-Q in Danish Patients Undergoing Weight Loss and Body Contouring Surgery.

A well-developed patient-reported outcome instrument is needed for use in Danish bariatric and body contouring patients. The BODY-Q is designed to measure changes in important patient outcomes over the entire patient journey, from obesity to post-body contouring surgery. The current study aims to psychometrically validate the BODY-Q for use in Danish patients. The process consisted of 3 stages: translation and linguistic validation, field-test, and data analysis. The translation was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research and World Health Organization guidelines, and field-test data were collected in 4 departments in 2 different hospitals. Field-test data were analyzed using Rasch Measurement Theory. A total of 495 patients completed the Danish BODY-Q field-test 1-4 times, leading to a total of 681 assessments with an overall response rate at 76%. Cronbach α values were ≥ 0.90, and person separation index values were in general high. The Rasch Measurement Theory analysis provided broad support for the reliability and validity of the Danish version of the BODY-Q scales. Item fit was outside the criteria for 34 of 138 items, and of these, 21 had a significant chi-square P value after Bonferroni adjustment. Most items (128 of 138) had ordered thresholds, indicating that response options worked as intended. The Danish version of the BODY-Q is a reliable and valid patient-reported outcome instrument for use in Danish bariatric and body contouring patients.

Burden of Psoriasis as Reported in a Cross-Sectional Study: Association of Psoriasis Severity with Health-Related Quality of Life, Depression, and Work Productivity

Background A significant gap exists in how psoriasis severity is related to validated patient-reported outcomes (PROs), which are critical in characterizing disease burden. Objective Determine the association between psoriasis severity and PROs, including health-related quality of life (HRQoL), depression, and work productivity, from patients’ perspectives. Methods An online survey using validated PRO instruments was administered in 2013. PROs included the Dermatology Life Quality Index, Quick Inventory of Depressive Symptoms-Self-Report (16 items) (QIDS-SR16), and Work Productivity and Activity Impairment Questionnaire-Psoriasis. Results The survey was completed by 1109 patients, 42% of whom had psoriatic arthritis. Respondents reported worse HRQoL and work productivity impairment with greater psoriasis severity ( p &lt; 0.05). Similarly, there was a greater proportion of participants with moderate-or-greater depressive symptoms (QIDS-SR16 total score) among patients with increasing psoriasis severity ( p &lt; 0.05). Conclusion Greater levels of impairment in HRQoL, work productivity, and depressive symptoms were associated with increased psoriasis severity.

Self-reported sexual health: Breast cancer survivors compared to women from the general population \u2013 an observational study

BackgroundCancer survivorship is of increasing importance in post-treatment care. Sexual health (SH) and femininity can be crucial issues for women surviving cancer. We aimed to determine a more complete understanding of the contribution that a breast cancer (BC) diagnosis and its treatment exert on patients’ follow-up SH. For this purpose, self-reported levels and predictors of SH in breast cancer survivors (BCS) were compared with those of women with no previous or current BC (WNBC).MethodsBCS and WNBC underwent a comprehensive, cross-sectional patient-reported outcome (PRO) assessment. Validated PRO instruments were used to measure SH, body image, anxiety and depression and menopausal symptoms. Assessments were performed within the routine clinical setting.Instruments used were the Sexual Interest and Desire Inventory - Female, Sexual Activity Questionnaire, Body Image Scale, Hospital Anxiety and Depression Scale and the Menopause-Specific Quality of Life Questionnaire.ResultsOne hundred five BCS (average time since diagnosis of 3 years) and 97 WNBC with a mean age of 49 years completed the assessment. SH was significantly worse in BCS compared to WNBC (p = 0.005; BCS SIDI-F mean = 24.9 vs. WNBC mean = 29.8). 68.8% of BCS and 58.8% of WNBC met criteria of a hypo-active sexual desire disorder. Higher depressive symptoms, higher age and lower partnership satisfaction were predictive for poorer SH in BCS.ConclusionSH problems are apparent in BCS and differ significantly from those seen in the general population. Consequently, BC survivorship care should include interventions to ameliorate sexual dysfunction and provide help with depressive symptoms and partnership problems, which are associated with poor BCS SH.

Predictors of Patient Reported Outcomes at Two Years Following Revision ACL Reconstruction

Objectives:Revision ACL reconstruction (ACLR) has been documented to have worse outcomes compared with primary ACLRs. The MARS Cohort was formed to elucidate predictors of outcome following revision ACLR. Patient reported outcomes (PROs) are a valid measure of results following revision ACLR. Understanding positive and negative predictors of PROs will allow surgeons to modify and potentially improve outcome for these patients.Methods:Revision ACLR patients were identified and prospectively enrolled by 83 surgeons over 52 sites. Data collected included baseline demographics, surgical technique and pathology, and a series of validated patient reported outcome instruments (IKDC, KOOS, and Marx activity rating score). Patients were followed up at 2 years, and asked to the identical set of outcome instruments. Multivariate regression models were used to determine the predictors (risk factors) of IKDC, KOOS, and Marx scores at 2 years following revision surgery. Regression analysis was used to control for a variety of demographic and surgical factors.Results:1205 patients met the inclusion criteria and were successfully enrolled. 697 (58%) were males, with a median cohort age of 26 years. The median time since their last ACLR was 3.4 years. At 2 years questionnaire follow-up was obtained on 989 subjects (82%), while phone follow-up was obtained on 1112 subjects (92%). Statistically significant (p < 0.05) positive (+) predictors for the Marx activity level included baseline (T0) higher Marx, younger age, male gender, non-smoker, non-traumatic/sudden onset mechanism of injury, 2nd revision, and prior ACL autograft. Negative (-) Marx predictors were having a biologic enhancement. Significant predictors of the IKDC included (+) higher T0 Marx and IKDC, male, never smoked, longer time since last ACL reconstruction and (-) previous lateral meniscectomy, Grade 3 lateral femoral condyle (LFC) chondrosis and Grades 3/4 medial tibial plateau (MTP) chondrosis. Significant predictors for KOOS symptoms subscale included (+) higher T0 KOOS symptom, longer time since ACLR, interference screw tibial fixation and (-) previous medial and/or lateral meniscectomy, Grades 3/4 MTP chondrosis. KOOS Pain predictors (+) higher T0 Marx and KOOS Pain, longer time since ACLR, (-) prior ACL soft tissue graft, suture+button/endobutton fixation, and previous medial and/or lateral meniscectomy. KOOS ADL predictors included (+) higher T0 Marx and KOOS ADL, longer time since ACLR, interference screw femoral fixation and (-) previous lateral meniscectomy, Grade 3 LFC chondrosis, and Grades 3/4 trochlear groove chondrosis. KOOS Sports/Rec predictors included (+) higher T0 Marx and KOOS Sports/Rec score, never smoked, longer time since ACLR and (-) previous lateral meniscectomy and Grades 3/4 MTP chondrosis. KOOS Knee Related Quality of Life (KRQOL) predictors included (+) higher T0 Marx and KOOS KRQOL score, never smoked, longer time since ACLR and (-) previous contralateral ACLR, 2nd revision, previous lateral meniscectomy, and Grade 4 MFC chondrosis.Conclusion:A variety of factors predict PROs both positively and negatively. Surgeon education regarding the findings in this study can result in potentially improved revision ACLR results for our patients. When the results are modifiable by the surgeon then outcomes can improve. When factors are unable to be modified then we can still improve our counseling of patients for their expected outcome.

Development and validation of a modified Korean version of the Pharmacy Services Questionnaire (PSQ-K) for the quality assessment of community pharmacy services.

Patient-reported outcome (PRO) measures and validated instruments have become integral in assessing the quality of healthcare delivery, including pharmaceutical care services. The Pharmacy Services Questionnaire (PSQ) measures patient satisfaction with pharmaceutical care. In this study, we developed a modified Korean version of the PSQ (PSQ-K) and evaluated its validity and reliability. The PSQ-K was developed using a strict translation and cultural-adaptation procedure. A validation study was performed in six community pharmacies in Korea. A total of 300 respondents completed three questionnaires (a brief questionnaire for social demographics and clinical characteristics, the PSQ-K, and the 5-level EuroQoL Group’s 5-dimension [EQ-5D-5L]). Standard validity and reliability analyses were performed. The internal consistency of the PSQ-K was high for all scales (Cronbach’s α > 0.9). The PSQ-K indicated good discriminant and divergent validity. Known-group comparisons revealed that the PSQ-K was able to distinguish between respondents differing in socio-demographic characteristics, such as gender, level of education, and household income. In conclusion, the PSQ-K is a highly reliable and valid PRO instrument for assessing the level of satisfaction with community pharmacy services.

Quality of life of children with lower limb deformities: A systematic review of patient-reported outcomes and development of a preliminary conceptual framework

Background: Lower limb deformities have a substantial impact on the quality of life (QOL) of children. This systematic review was conducted to identify as follows: (a) QOL concepts in existing literature specific to pediatric patients with lower limb deformities; (b) parent-reported outcome and patient-reported outcome (PRO) instruments used to measure QOL in pediatric patients with lower limb deformities; and (c) determinants of QOL in pediatric patients with lower limb deformities. Methods: MEDLINE, EMBASE, CINAHL, and PsycINFO were searched from the inception to January 2016. Studies were included if they (1) had patients with lower limb deformities; (2) included children 18 years of age or under; and (3) measured QOL using a PRO or parent-reported outcome of instruments. Results: Of the 938 publications identified in the search, 10 studies used a total of 24 PRO or parent-reported outcome instruments to measure 1 or more aspects of QOL of pediatric patients with lower limb deformities. Three overarching health concepts (physical, psychological, and social health) and 15 subconcepts were identified. Five studies looked at determinants of QOL including type of deformity, severity of deformity, complications postsurgery, stage of treatment, and type of treatment. Psychological health was measured in 10 studies, social health in 7 studies, and physical health in 6 studies. The most frequently measured subconcepts were physical function, psychological distress, and social function. Conclusion: Existing parent-reported outcome and PRO instruments measure 3 QOL concepts in children with lower limb deformities. There were no validated PRO instruments specifically designed to measure QOL of children with lower limb deformities. Level of Evidence: This was a systematic review of level III studies.

PRS52 - Measuring Treatment Satisfaction and Preference in Patients with Asthma and Copd: Results of A Targeted Literature Review

Treatment satisfaction is an important predictor of real-world medication adherence in chronic medical conditions such as asthma and COPD. The objective of this study was to identify and describe measures used to assess treatment satisfaction and preference in patients with asthma and/or COPD. A targeted literature review was conducted in EMBASE and PubMed to identify studies utilizing validated patient-reported outcome (PRO) instruments or study-specific questionnaires and published in 2000-2015. Domains measured by each PRO/questionnaire were recorded to understand important treatment characteristics related to treatment satisfaction and preference. Of 456 abstracts reviewed, 28 studies met all study inclusion/exclusion criteria. Of 19 studies evaluating treatment satisfaction, 11 used validated PRO instruments, 8 used non-validated questionnaires, and 7 validated PROs were identified. The most commonly used instruments were the Patient Satisfaction and Preference Questionnaire (PASAPQ), the Onset of Effect Questionnaire (OEQ), and the Patient Satisfaction with Asthma Medication (PSAM). Key domains measured were symptom relief, treatment effectiveness, ease of use, side effects, and overall satisfaction. Of 13 studies evaluating treatment preference, 3 used validated PRO instruments and 10 used non-validated questionnaires. Only one validated PRO was identified: the PASAPQ, an instrument which includes both treatment satisfaction and preference items and that was developed for use in clinical trials. It is important to identify and consider factors associated with treatment satisfaction and preference to ensure high levels of medication adherence. The use of disease-specific, validated PROs to demonstrate real-world satisfaction with or preference of asthma and/or COPD treatments can provide a wealth of knowledge for patient care moving forward. Careful consideration should be made in the selection of PROs as there are a limited number of available validated instruments and some may not be appropriate for all study designs (e.g., cross-sectional patient survey).

Rehabilitation Predictors of Clinical Outcome following Revision ACL Reconstruction

Objectives:Revision ACL reconstruction has been documented to have worse outcomes compared with primary ACL reconstructions. The reasons why remain unknown. The purpose of this study was to determine whether rehabilitation-related factors prescribed at the time of ACL revision reconstruction significantly influence two year outcomes, as well as the incidence of incurring a subsequent re-operation. Our hypothesis was that immediate versus passive, active range of motion (ROM) and weightbearing will result in improved outcomes without incidence of subsequent surgery. Use of postoperative and functional return to sport braces will not improve return to sports function.Methods:Revision ACL reconstruction patients were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline demographics, surgical technique and pathology, prescribed post-op and rehabilitation instructions (ie. timing of weightbearing, timing of passive and active ROM, use of postoperative and return to sport braces) and a series of validated patient reported outcome instruments (IKDC, KOOS, and Marx activity rating score). Patients were followed up for 2 years, and asked to complete the identical set of outcome instruments. Because meniscal repair, meniscal transplants, HTOs, concurrent ligamentous reconstructions, and certain chondral treatments (ie. microfracture, abrasion arthroplasty, mosiacplasty, etc) are known to affect prescribed rehab treatments, patients with these pathologies were excluded from the analyses. Regression analysis was used to control for age, gender, activity level, baseline outcome scores, and the above-mentioned rehabilitation-related variables, in order to assess the risk factors for clinical outcomes 2 years after revision ACL reconstruction.Results:A total of 843 patients met the inclusion criteria and were successfully enrolled. 482 (57%) were males, with a median cohort age of 27 years. Baseline characteristics of the cohort are summarized in Table 1. At 2 years, follow-up was obtained on 82% (694/843). There were two rehabilitation-related factors which were found to be influential of 2 year outcomes. Patients who were prescribed an ACL brace for return to sport had significantly better KOOS sports/rec scores at 2 years (odds ratio=1.50; 95% CI=1.07-2.11; p=0.019). Patients who were prescribed an ACL derotation brace to be used in post-op rehab were 2.26 times more likely to have a subsequent surgery by 2 years (OR = 2.26; 95% CI=1.11-4.60; p=0.024). Lower baseline outcome scores, activity level, and female gender all significantly increased the odds of reporting poorer clinical outcomes (IKDC, all KOOS subscales, and Marx activity rating score) at 2 years. Alternatively, whether or not a physician restricted a patient’s passive or active ROM post-operatively, restricted full weight-bearing without support, or prescribed a motion control brace post-op, were all found not to be influential risk factors for 2 year outcomes in this revision cohort.Conclusion:There are rehabilitation-related factors that the physician can control at the time of an ACL revision which have the ability to modify clinical outcomes at 2 years. The odds of having a higher KOOS sports/rec score increases by 50% in patients who wore a functional brace for sports (versus patients who didn’t). However, patients who were prescribed a derotation brace used for post-op rehab were 2.3 times more likely to incur a subsequent surgery by 2 years.

Knee Hyperextension as a Predictor of Failure in Revision ACL Reconstruction

Objectives:We studied the minimum 2 year follow-up outcomes in an ACL revision cohort. The hypothesis is that knees that hyperextend will have a worse outcome and greater odds of graft failure than knees that do not hyperextend. The null hypothesis is that there is no difference in outcomes or graft rupture between the two groups.Methods:Revision ACL reconstruction patients were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline demographics, surgical technique and pathology, and a series of validated patient reported outcome instruments (IKDC, KOOS, WOMAC, and Marx activity rating score). Patients were followed up for 2 years, and asked to complete the identical set of outcome instruments. A regression model using graft failure as the dependent variable included graft type, age, and hyperextension greater than or equal to 5 degrees yes/no (HE) in order to assess these potential surgical risk factors for clinical outcomes 2 years after revision ACL reconstruction.Results:There were 1,145 subjects included in the analyses. The median age of the cohort was 26 (IQR= 20, 35), and 58% were male. The proportion that were enrolled for their first revision surgery was 88%, their second 10%, and third or greater 2%. The number of subjects categorized as HE was 375 (33%). The median age of subjects that failed was 18, compared to 26 for those with intact grafts. All three variables included in our regression model were significant predictors of graft failure: younger age, inter-quartile range odds ratio (IQROR) = 3.32 (95%CI 1.5, 7.2) p= 0.002; use of allograft OR = 3.1 (95%CI 1.4, 6.9) p= 0.01, and HE 2.1 (95%CI 1.02, 4.42) p= 0.04.Conclusion:The MARS Study Group has previously reported that young age and the use of allograft as a graft source are independent predictors (over 3X odds ratio) of graft rupture after revision ACLR. This study found that knee hyperextension greater than or equal to 5 degrees is present in 1/3 of patients who undergo revision ACLR. HE is also an independent predictor of graft failure after revision ACLR. This is the first study to investigate and confirm knee physiologic hyperextension as a risk factor (over 2X odds ratio) of graft rupture in ACL surgery. Future reports on ACL reconstruction results should separately evaluate the group of knees that hyperextend 5 degrees or more as compared to those that do not.

Abstract 278: The China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Prospective Study of Acute Myocardial Infarction: Study Design

Background: The incidence of acute myocardial infarction (AMI) is growing rapidly in China, but there is limited information about the patient experience in the post-acute period. Specifically, long-term outcomes and patient-reported outcomes (PROs), including quality of life, symptoms and mood, after AMI, have not been systematically studied in China. Objectives: To conduct a nationwide prospective study following patients after AMI that 1) measures long-term clinical outcomes, PROs, cardiovascular risk factor control and adherence to medications for secondary prevention; and 2) identifies patient characteristics and hospital attributes that are associated with these outcomes. Methods: The China PEACE Prospective Study of AMI has recruited 4000 consecutive patients from 55 hospitals across China and is following them for 1-year. The first patient was enrolled in December 2012, and the last follow-up visit is scheduled for June 2015. After obtaining informed consent from patients, we abstracted details of their medical history, treatment, and in-hospital outcomes from medical charts. We conducted comprehensive baseline interviews characterizing patient demographics, risk factors, clinical presentation, and healthcare utilization. In addition, we used validated PRO instruments to measure quality of life, symptoms, mood, sleep, cognition and sexual activity. Follow-up interviews, measuring PROs, medication adherence and risk factor control were conducted at 1-, 6-, and 12-months after discharge. At these interviews, patients were asked to self-report major health events and to provide supporting materials (e.g., hospital discharge record for a readmission), which were subsequently validated by a National Coordinating Center. Blood and urine samples were obtained at baseline and 12-month follow-up, and stored for further biomarker analysis and genetic studies. To complement these patient-level data, we surveyed participating hospitals to characterize their facilities, processes and organizational learning culture. Together, these data will be used to identify factors associated with various outcomes following AMI. Conclusion: This study is uniquely positioned to generate new information regarding patient experience and determinants of outcomes after AMI in China.

Meniscal and Articular Cartilage Predictors of Clinical Outcome following Revision ACL Reconstruction

Objectives:Revision ACL reconstruction has been documented to have worse outcomes compared with primary ACL reconstructions. The reasons why remain unknown. The purpose of this study was to determine if both the prevalence and/or degree of meniscal and chondral damage noted at the time of ACL revision reconstruction predicts activity level, sports function, and OA symptoms at two year follow-up.Methods:Revision ACL reconstruction patients were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline demographics, surgical technique and pathology, and a series of validated patient reported outcome instruments (IKDC, KOOS, WOMAC, and Marx activity rating score). Patients were followed up for 2 years, and asked to complete the identical set of outcome instruments. Regression analysis was used to control for age, gender, BMI, smoking status, activity level, baseline outcome scores, revision number, time since last ACLR, previous and current meniscal and articular cartilage pathology, in order to assess the meniscal and AC pathology risk factors for clinical outcomes 2 years after revision ACL reconstruction.Results:1205 patients met the inclusion criteria and were successfully enrolled. 697 (58%) were males, with a median cohort age of 26 years. The median time since their last ACL reconstruction was 3.4 years. Surgeons noted previous pathology in the medial meniscus (39%), lateral meniscus (20%), and articular surfaces (12%) at the time of revision surgery. Surgeons reported current pathology in the medial meniscus (45%), lateral meniscus (37%), MFC (43%), LFC (29%), MTP (11%), LTP (17%), patella (30%), and trochlea (20%). At 2 years, follow-up was obtained on 82% (989/1205). Previous meniscal pathology (both medial and lateral), as well as current AC pathology (in the MFC, LFC, MTP, LTP, and trochlea) were found to be significant drivers of poorer outcomes at 2 years (Table 1). The most consistent cartilage-related factors driving outcome in revision patients were previous lateral meniscus pathology and current trochlea AC pathology. Having a previous excision on the lateral meniscus resulted in significantly poorer outcomes on the IKDC (odds ratio=1.69; 95% CI=1.16-2.44; p=0.005), all KOOS subscales (OR range=1.54-2.08; 95% CI=1.04-3.03; p<0.029), and all WOMAC subscales (OR=1.56; 95% CI=1.06-2.27; p=0.02). Having a current Grade 3-4 AC chondrosis of the trochlea resulted in significantly poorer outcomes in the IKDC (OR=1.89; 95% CI=1.25-2.94; p-0.003), 4 of 5 KOOS subscales (OR range = 1.64-2.70; 95% CI=1.09-4.17; p<0.02), and 2 of 3 WOMAC subscales (OR range = 1.61-2.70; 95% CI=1.04-4.17; p<0.03). Lower baseline outcome scores, lower baseline activity level, and shorter time since the patient’s last ACL reconstruction all significantly increased the odds of reporting poorer clinical outcomes at 2 years. Meniscal and AC pathology was not found to be a significant risk factor for 2 year activity levels. Interestingly, previous AC pathology and current meniscal pathology were not found to be significant risk factors for 2 year outcomes in this revision cohort.Conclusion:Having a previous meniscal excision, as well as grade 3-4 chondral damage noted at the time of ACL revision reconstruction results in decreased sports outcome scores and worse WOMAC scores at two years following revision surgery. However, incidence of meniscal and AC pathology was not found to be a predictor of a patient’s activity level at 2 years.

Patient-Reported Outcomes in Clinical Trials of CKD-Related Therapies: Report of a Symposium Sponsored by the National Kidney Foundation and the US Food and Drug Administration

The National Kidney Foundation and the U.S. Food and Drug Administration (FDA) convened a symposium in September 2010, bringing together more than 70 experts, including representatives from the FDA, the National Institutes of Health, the Critical Path Institute, nephrologists, patients, and the pharmaceutical industry to discuss the feasibility and process of developing patient-reported outcome (PRO) measures to access how patients feel or function to be used in clinical trials for regulatory review of treatment benefit. Three disease areas were evaluated for development of end point models in which PRO measures may be useful: anemia secondary to chronic kidney disease, autosomal dominant polycystic kidney disease (ADPKD), and nephrotic syndrome. The participants thought it valuable to use observational data to generate hypotheses regarding patient baseline characteristics that are likely to predict clinically important changes in PROs in response to anemia treatment and to design adequately powered blinded randomized controlled trials of anemia treatment using PROs as primary rather than secondary end points. Validated PRO instruments that reflect the patient experience in ADPKD and nephrotic syndrome are essential to incorporate into clinical trials of new therapeutic interventions because glomerular filtration rate decline may occur late in the disease course, at which point therapeutic benefit is less likely. Conference attendees addressed how PRO measures could be used to evaluate, monitor, provide care, and facilitate the introduction of treatments for patients with these challenging conditions.

Capturing the Patient's Experience: Using Qualitative Methods to Develop a Measure of Patient-Reported Symptom Burden: An Example From Ovarian Cancer

ContextExperts in patient-reported outcome (PRO) measurement emphasize the importance of including patient input in the development of PRO measures. Although best methods for acquiring this input are not yet identified, patient input early in instrument development ensures that instrument content captures information most important and relevant to patients in understandable terms. ObjectivesThe M. D. Anderson Symptom Inventory (MDASI) is a reliable valid PRO instrument for assessing cancer symptom burden. We report a qualitative (open-ended, in-depth) interviewing method that can be used to incorporate patient input into PRO symptom measure development, with our experience in constructing an MDASI module for ovarian cancer (MDASI-OC) as a model. MethodsFourteen patients with ovarian cancer (OC) described symptoms experienced at the time of the study, at diagnosis, and during prior treatments. Researchers and clinicians used content analysis of interview transcripts to identify symptoms in patient language. Symptoms were ranked on the basis of the number of patients mentioning them and by clinician assessment of relevance. ResultsForty-two symptoms were mentioned. Eight OC-specific items will be added to the 13 core symptom items and six interference items of the MDASI in a test version of the MDASI-OC on the basis of the number of patients mentioning them and clinician assessment of importance. The test version is undergoing psychometric evaluation. ConclusionThe qualitative interviewing process, used to develop the test MDASI-OC, systematically captures common symptoms important to patients with OC. This methodology incorporates the patient experience recommended by experts in PRO instrument development.

Evaluating the quality of supportive oncology using patient-reported survey data.

42 Background: Quality indicators for supportive oncology care are critical for measuring and monitoring improvement in domains such as symptom management and communication. Patient-reported outcome (PRO) data may complement medical record documentation in assessing quality of care patients receive and perceive. To evaluate how PRO data may be used in quality indicators for key supportive oncology domains, we conducted a study using patient-reported data from a national cohort study, the Cancer Care Outcomes Research and Surveillance Consortium initiative. Methods: We analyzed patient survey responses with utilization and outcomes data from 4,174 patients diagnosed with lung or colorectal cancer of any tumor stage between 2003 and 2005, which included a variety of validated PRO instruments administered within approximately five months of diagnosis. We defined existing supportive oncology indicators addressing symptom management and end-of-life discussions, primarily from Cancer Quality-ASSIST and the American Society of Clinical Oncology Quality Oncology Practice Initiative, that could be feasibly obtained from the survey data, with adaptations as needed. For example, all patients were asked whether they had pain; for pain screening, a survey item asked patients who reported pain whether a provider knew about the patient’s pain, and for treatment, the survey asked patients whether the provider provided help for the pain. Results: See Table. Conclusions: In summary, quality of care for symptom management as measured by patient-reported survey data was highest for pain screening and treatment, and lowest for fatigue treatment and significant depressive symptoms. Quality was much lower for end-of-life discussions. Patient-reported outcome data can provide a valuable, patient-centered perspective on the quality of supportive oncology care. [Table: see text]