Consensus on the Need for a Hierarchical List of Patient-reported Pain Outcomes for Metaanalyses of Knee Osteoarthritis Trials: An OMERACT Objective.

OBJECTIVE Although protocol registration for systematic reviews is still not mandatory, reviewers should be strongly encouraged to register the protocol to identify the methodological approach, including all outcomes of interest. This will minimize the likelihood of biased decisions in reviews, such as selective outcome reporting. A group of international experts convened to address issues regarding the need to develop hierarchical lists of outcome measurement instruments for a particular outcome for metaanalyses. METHODS Multiple outcome measurement instruments exist to measure the same outcome. Metaanalysis of knee osteoarthritis (OA) trials, and the assessment of pain as an outcome, was used as an exemplar to assess how Outcome Measures in Rheumatology (OMERACT), the Cochrane Collaboration, and other international initiatives might contribute in this area. The meeting began with formal presentations of background topics, empirical evidence from the literature, and a brief introduction to 2 existing hierarchical lists of pain outcome measurement instruments recommended for metaanalyses of knee OA trials. RESULTS After discussions, most participants agreed that there is a need to develop a methodology for generation of hierarchical lists of outcome measurement instruments to guide metaanalyses. Tools that could be used to steer development of such a prioritized list are the COSMIN checklist (Consensus-based Standards for the selection of health status Measurement Instruments) and the OMERACT Filter 2.0. CONCLUSION We list meta-epidemiological research agenda items that address the frequency of reported outcomes in trials, as well as methodologies to assess the best measurement properties (i.e., truth, discrimination, and feasibility).

Cumulative long-term safety, efficacy and patient-reported outcomes in children with juvenile idiopathic arthritis treated with intravenous abatacept: up to 7 years of treatment

The long-term efficacy and safety of intravenous abatacept in patients (pts) with juvenile idiopathic arthritis (JIA) have been reported previously from the Phase III AWAKEN trial ([1, 2]). Here, we report efficacy, safety and pt-reported outcomes from the open-label, long-term extension (LTE) of AWAKEN, with up to 7 years of follow-up. Pts entered the LTE if they were JIA ACR 30 non-responders (NR) at the end of the 4-month lead-in period (abatacept only), or if they received abatacept or placebo (pbo) in the 6-month double-blind (DB) period. The Child Health Questionnaire was used to evaluate health-related quality of life (HRQoL); physical (PhS) and psychosocial (PsS) summary and pain scores were analyzed. Pain was assessed by parent global assessment using a 100 mm visual analog scale. Efficacy and HRQoL evaluations are reported up to Day 1765 (~ Year 5.5). Safety is presented for the cumulative period (lead-in, DB and LTE), for all pts who received abatacept during the LTE. Of the 153 pts entering the LTE (58 from DB abatacept group, 59 from DB pbo group, 36 NR), 69 completed the trial (29 abatacept, 27 pbo, 13 NR). For pts treated in the LTE, mean (range) exposure to abatacept was 53.6 (5.6–85.6) months. During the LTE, incidence rates of AEs and serious AEs per 100 pt-years were 209.1 and 5.6. Thirty pts (19.6%) had serious AEs; most were unrelated and were musculoskeletal (8.5%) or infectious events (6.5%). No malignancy was reported. There was one death (accidental; unrelated). At Day 169, JIA ACR 50 and 70 response rates were 79.3% and 55.2% in the abatacept group, and 52.5% and 30.5% in the pbo group; 31.0% and 10.2% of pts in the abatacept and pbo groups, respectively, had inactive disease. By Day 1765, JIA ACR 50 and 70 response rates were 93.9% and 78.8% in the abatacept group, and 80.0% and 63.3% in the pbo group; 51.5% and 33.3% had inactive disease. In the NR group, 69.2% and 53.8% of pts achieved JIA ACR 50 and 70 responses at Day 1765, and 30.8% had inactive disease. In pts who entered the LTE, mean baseline PhS scores were below the range for healthy children (abatacept 30.2, pbo 31.0, NR 29.5). At Day 169, 38.3% of pts had reached a PhS score >50 ((1). By the end of the LTE, 43.5% of pts had reached a PhS score >50. At baseline, mean PsS scores for those who entered the LTE were slightly lower than the mean for healthy children (abatacept 43.5, pbo 44.2, NR 47.0). At Day 169, 54.9% of pts had a PsS score >50 (1). By Day 1765, 58.1% of pts had reached a PsS score >50. At baseline, the mean pain score was 42.9. By Day 169, 13.9% of pts were considered pain free (pain score = 0); this was maintained over the LTE (1).

Patient-reported outcomes of patients with advanced biliary tract cancers receiving gemcitabine plus capecitabine: a multicenter, phase II trial of the Swiss Group for Clinical Cancer Research

PURPOSE: To evaluate the effects of palliative chemotherapy with gemcitabine plus capecitabine (GemCap) on patient-reported outcomes measured using clinical benefit response (CBR) and quality-of-life (QOL) measures in patients with advanced biliary tract cancer. PATIENTS AND METHODS: Patients had to manifest symptoms of advanced biliary tract cancer and have at least one of the following: impaired Karnofsky performance score (60 to 80), average analgesic consumption >or= 10 mg of morphine equivalents per day, and average pain intensity score of >or= 20 mm out of 100 mm. Treatment consisted of oral capecitabine 650 mg/m(2) twice daily on days 1 through 14 plus gemcitabine 1,000 mg/m(2) as a 30-minute infusion on days 1 and 8 every 3 weeks until progression. The primary end point was the number of patients categorized as having a CBR or stable CBR (SCBR) during the first three treatment cycles. RESULTS: Forty-four patients were enrolled (bile duct cancer, n = 36; gallbladder cancers, n = 8). The main grade 3 or 4 adverse events included hematologic toxicity and fatigue. After three cycles, 36% of patients achieved a CBR, and 34% achieved an SCBR. Over the full course of treatment, 57% of patients achieved a CBR, and 18% achieved an SCBR. Improved QOL was observed in patients with a CBR or SCBR. The objective response rate was 25%. Median time to progression and overall survival times were 7.2 months and 13.2 months, respectively. CONCLUSION: Chemotherapy with GemCap is well tolerated and effective and leads to a high CBR rate. Patient-reported outcomes are useful for evaluating the effects of palliative chemotherapy in patients with biliary tract cancer.

A patient-reported outcome measure to identify occurrence and distress of post-surgery symptoms of WOMen with vulvAr Neoplasia (WOMAN-PRO) - a cross sectional study.

OBJECTIVE The aim of the study was to describe the (a) symptom experience of women with vulvar intraepithelial neoplasia and vulvar cancer (vulvar neoplasia) during the first week after hospital discharge, and (b) associations between age, type of disease, stage of disease, the extent of surgical treatment and symptom experience. METHODS This cross-sectional study was conducted in eight hospitals in Germany and Switzerland (Clinical Trial ID: NCT01300663). Symptom experience after surgical treatment in women with vulvar neoplasia was measured with our newly developed WOMAN-PRO instrument. Outpatients (n=65) rated 31 items. We used descriptive statistics and regression analysis. RESULTS The average number of symptoms reported per patient was 20.2 (SD 5.77) with a range of 5 to 31 symptoms. The three most prevalent wound-related symptoms were 'swelling' (n=56), 'drainage' (n=54) and 'pain' (n=52). The three most prevalent difficulties in daily life were 'sitting' (n=63), 'wearing clothes' (n=56) and 'carrying out my daily activities' (n=51). 'Tiredness' (n=62), 'insecurity' (n=54) and 'feeling that my body has changed' (n=50) were the three most prevalent psychosocial symptoms/issues. The most distressing symptoms were 'sitting' (Mean 2.03, SD 0.88), 'open spot (e.g. opening of skin or suture)' (Mean 1.91, SD 0.93), and 'carrying out my daily activities' (Mean 1.86, SD 0.87), which were on average reported as 'quite a bit' distressing. Negative associations were found between psychosocial symptom experience and age. CONCLUSIONS WOMAN-PRO data showed a high symptom prevalence and distress, call for a comprehensive symptom assessment, and may allow identification of relevant areas in symptom management.

Patient-reported outcomes of maxillary implant-supported overdentures compared with conventional dentures

OBJECTIVE The aim of the present prospective clinical study was to compare patient-reported outcomes for maxillary conventional dentures and maxillary implant-supported dentures. MATERIAL AND METHODS Twenty-one patients (6 women and 15 men) being edentulous in the maxilla and encountering problems with their existing dentures were included. Twelve patients (4 women and 8 men) received a new set of conventional dentures, due to insufficient dentures. In nine patients (2 women and 7 men), the existing dentures were adjusted by means of relining or rebasing. All patients received implant-supported dentures on two retentive anchors. In total, 42 implants were inserted in the anterior maxilla. The participants rated their satisfaction on their existing conventional dentures, 2 months after insertion of new conventional dentures and 2 months after insertion of implant-supported dentures. Thereby, patients responded to questionnaires capturing the oral health impact profile (OHIP) using visual analog scales. Seven domains (functional limitation, physical pain, psychological discomfort, physical, psychological and social disability and handicap) were assessed. Higher scores implied poorer patient satisfaction. In addition, the questionnaire involved the evaluation of cleaning ability, general satisfaction, speech, comfort, esthetics, stability, and chewing ability. Higher scores implied higher patient satisfaction. RESULTS Patient satisfaction significantly increased for implant-supported dentures compared with old dentures in all seven OHIP subgroups, as well as for cleaning ability, general satisfaction, ability to speak, comfort, esthetics, and stability (P < 0.05). The comparison of new conventional dentures and implant-supported dentures revealed a statistically significantly increased satisfaction for functional limitation (difference of 33.2 mm), psychological discomfort (difference of 36.7 mm), physical disability (difference of 36.3 mm), and social disability (difference of 23.5 mm), (P < 0.05). Additionally, general satisfaction, chewing ability, speech, and stability significantly improved in implant-supported dentures (P < 0.05). CONCLUSIONS Within the limits of this study, maxillary dentures retained by two implants provided some significant short-term improvements over conventional dentures in oral- and health-related quality of life.

Short-term functional versus patient-reported outcome of the bicruciate stabilized total knee arthroplasty: prospective consecutive case series

BACKGROUND The main goals of the standard treatment for advanced symptomatic knee osteoarthritis, total knee arthroplasty (TKA), are pain reduction and restoration of knee motion.The aim of this study was to analyse the outcome of the patient-based Knee Injury and Osteoarthritis Outcome Score (KOOS), and the surgeon-based Knee Society Score (KSS) and its Knee Score (KS) and Knee Functional Score (KFS) components after (TKA) using the Journey knee prosthesis, and to assess the correlation of these scores with range of motion (ROM). METHODS In a prospective case series study between August 1st 2008 and May 31st 2011, 99 patients, all operated by a single surgeon, received Journey bicruciate stabilized total knee prostheses. The female/male ratio was 53/34, the mean patient age at surgery was 68 years (range 41-83 years), and the left/right knee ratio was 55/44. The KOOS, range of motion, and KS and KFS were obtained preoperatively and at 1-year follow-up. The pre- and postoperative levels of the outcome measures were compared using the Wilcoxon signed-rank test. Correlation between ROM and patient outcomes was analysed with the Spearman coefficient. RESULTS All KOOS subscores improved significantly. Ninety percent of patients improved by at least the minimum clinically relevant difference of 10 points in stiffness and other symptoms, 94.5% in pain, 94.5% in activities of daily living, 84.9% in sports and recreation, and 90% in knee-related quality of life. The mean passive and active ROM improved from 122.4° (range 90-145°) and 120.4° (range 80-145°) preoperatively to 129.4° (range 90-145°) and 127.1° (range 100-145°) postoperatively. The highest correlation coefficients for ROM and KOOS were observed for the activity and pain subscores. Very low or no correlation was seen for the sport subscore.There was a significant and clinically relevant improvement of KSS (preop/postop 112.2/174.5 points), and its KS (preop/postop 45.6/86.8 points) and KFS (preop/postop 66.6/87.8 points) components. CONCLUSIONS The Journey bicruciate stabilized knee prosthesis showed good 1-year postoperative results in terms of both functional and patient-based outcome. However, higher knee ROM correlates only moderately with patient-based outcome, implying that functionality afforded by the Journey bicruciate TKA is not equivalent to patient satisfaction.

Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement

Background: In clinical trials, at the group level, results are usually reported as mean and standard deviation of the change in score, which is not meaningful for most readers. Objective: To determine the minimal clinically important improvement (MCII) of pain, patient's global assessment of disease activity, and functional impairment in patients with knee and hip osteoarthritis (OA). Methods: A prospective multicentre 4 week cohort study involving 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. Patients assessed their response to treatment on a five point Likert scale at the final visit. An anchoring method based on the patient's opinion was used. The MCII was estimated in a subgroup of 814 patients ( 603 with knee OA, 211 with hip OA). Results: For knee and hip OA, MCII for absolute ( and relative) changes were, respectively, ( a) -19.9 mm (-40.8%) and -15.3 mm (-32.0%) for pain; ( b) -18.3 mm ( - 39.0%) and -15.2 mm ( -32.6%) for patient's global assessment; ( c) -9.1 ( -26.0%) and -7.9 ( -21.1%) for WOMAC function subscale score. The MCII is affected by the initial degree of severity of the symptoms but not by age, disease duration, or sex. Conclusion: Using criteria such as MCII in clinical trials would provide meaningful information which would help in interpreting the results by expressing them as a proportion of improved patients.

Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state

Background: The patient acceptable symptom state ( PASS) is the value beyond which patients can consider themselves well. This concept can help in interpreting results of clinical trials. Objective: To determine the PASS estimate for patients with knee and hip osteoarthritis (OA) by assessing pain, patient's global assessment of disease activity, and functional impairment. Methods: A 4 week prospective multicentre cohort study of 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment of disease, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. The patients assessed their satisfaction with their current state at the final visit. An anchoring method based on the patient's opinion was used. Results: For patients with knee and hip OA, the estimates of PASS were, respectively, 32.3 and 35.0 mm for pain, 32.0 and 34.6 mm for patient global assessment of disease activity, and 31.0 and 34.4 points for WOMAC function score. The PASS varied moderately across the tertiles of baseline scores but not across age, disease duration, or sex. Conclusion: The use of PASS in clinical trials would provide more meaningful results expressed as a proportion of patients in an acceptable symptom state.

Use of condition-specific patient-reported outcome measures in clinical trials among patients with wrist osteoarthritis : a systematic review

Background. This paper aimed to identify condition-specific patient-reported outcome measures used in clinical trials among people with wrist osteoarthritis and summarise empirical peer-reviewed evidence supporting their reliability, validity, and responsiveness to change. Methods. A systematic review of randomised controlled trials among people with wrist osteoarthritis was undertaken. Studies reporting reliability, validity, or responsiveness were identified using a systematic reverse citation trail audit procedure. Psychometric properties of the instruments were examined against predefined criteria and summarised. Results. Thirteen clinical trials met inclusion criteria. The most common patient-reported outcome was the disabilities of the arm, shoulder, and hand questionnaire (DASH). The DASH, the Michigan Hand Outcomes Questionnaire (MHQ), the Patient Evaluation Measure (PEM), and the Patient-Reported Wrist Evaluation (PRWE) had evidence supporting their reliability, validity, and responsiveness. A post-hoc review of excluded studies revealed the AUSCAN Osteoarthritis Hand Index as another suitable instrument that had favourable reliability, validity, and responsiveness. Conclusions. The DASH, MHQ, and AUSCAN Osteoarthritis Hand Index instruments were supported by the most favourable empirical evidence for validity, reliability, and responsiveness. The PEM and PRWE also had favourable empirical evidence reported for these elements. Further psychometric testing of these instruments among people with wrist osteoarthritis is warranted.

Review : "Quality of life: the assessment, analysis and interpretation of patient-reported outcomes (2nd Ed.)" by Peter M. Fayers & David Machin

An updated version, this excellent text is a timely addition to the library of any nurse researching in oncology or other settings where individuals’ quality of life must be understood. Health-related quality of life should be a central aspect of studies concerned with health and illness. Indeed, considerable evidence has recently emerged in oncology and other research settings that selfreported quality of life is of great prognostic significance and may be the most reliable predictor of subsequent morbidity and mortality. From a nursing perspective, it is also gratifying to note that novel therapy and other oncology studies increasingly recognize the importance of understanding patients’ subjective experiences of an intervention over time and to ascertain whether patients perceive that a new intervention makes a difference to their quality of life and treatment outcomes. Measurements of quality of life are now routine in clinical trials of chemotherapy drugs and are often considered the prime outcome of interest in the cost/benefit analyses of these treatments. The authors have extensive experience in qualityof- life assessment in cancer clinical trials, where most of the pioneering work into quality of life has been conducted. That said, many of the health-related qualityof- life issues discussed are common to many illnesses, and researchers outside of cancer should find the book equally helpful.

A systematic review of patient-reported outcome instruments of dermatologic adverse events associated with targeted cancer therapies

Purpose Dermatologic adverse events (dAEs) in cancer treatment are frequent with the use of targeted therapies. These dAEs have been shown to have significant impact on health-related quality of life (HRQoL). While standardized assessment tools have been developed for physicians to assess severity of dAEs, there is a discord between objective and subjective measures. The identification of patient-reported outcome (PRO) instruments useful in the context of targeted cancer therapies is therefore important in both the clinical and research settings for the overall evaluation of dAEs and their impact on HRQoL. Methods A comprehensive, systematic literature search of published articles was conducted by two independent reviewers in order to identify PRO instruments previously utilized in patient populations with dAEs from targeted cancer therapies. The identified PRO instruments were studied to determine which HRQoL issues relevant to dAEs were addressed, as well as the process of development and validation of these instruments. Results Thirteen articles identifying six PRO instruments met the inclusion criteria. Four instruments were general dermatology (Skindex-16©, Skindex-29©, Dermatology Life Quality Index (DLQI), and DIELH-24) and two were symptom-specific (functional assessment of cancer therapy-epidermal growth factor receptor inhibitor-18 (FACT-EGFRI-18) and hand-foot syndrome-14 (HFS-14)). Conclusions While there are several PRO instruments that have been tested in the context of targeted cancer therapy, additional work is needed to develop new instruments and to further validate the instruments identified in this study in patients receiving targeted therapies.

Patient reported adherence to hypertension treatment: A revalidation study

Background Adherence to hypertension management in patients with hypertension is known to influence their blood pressure control. It is important to measure patients’ adherence behaviours to assist with designing appropriate interventions to improve blood pressure control. Aims The purposes of this study were to use confirmatory factor analysis to revalidate the Therapeutic Adherence Scale for Hypertensive Patients (TASHP), and to calculate the cut-off score for classifying adherence behaviours into two groups: satisfactory and low adherence behaviours. Methods Systematic random sampling was used to recruit patients with hypertension in China. Demographic characteristics, the TASHP and blood pressure were collected. The psychometric tests of the TASHP included: construct validity, criteria-related validity, internal reliability, and split-half reliability. The area under the receiver operating characteristics curve and Youden index were used to identify the cut-off score of the TASHP for blood pressure control. Results This study involved 366 patients. Confirmatory factor analysis supported the four-component structure of the TASHP proposed in the original scale development study. The TASHP has a satisfactory internal reliability (Cronbach’s α > 0.7) and a satisfactory split-half reliability (Spearman–Brown coefficients > 0.7). The patients with overall scores of the TASHP ⩾ 109 points were considered to have satisfactory adherence behaviours. Conclusion The TASHP is a validated and reliable instrument to measure the adherence to hypertension management in Chinese patients with hypertension. The cut-off score of 109 points can be considered as an effective measure to classify the level of adherence into satisfactory and low adherence behaviours.