title: Outcome assessment in clinical trials. Evidence for the sensitivity of a health status measure. Which outcome measures should be used in rheumatoid arthritis clinical trials? Clinical and quality-of-life measures' responsiveness to treatment in a randomized controlled trial. STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT Preliminary core set of domains and reporting requirements for longitudinal observational studies in rheumatology. Responsiveness of the core set, response criteria, and utilities in early rheumatoid arthritis A comparative study of patient-reported functional outcomes in acute rheumatoid arthritis. Development of a methodological PubMed search filter for finding studies on measurement properties of measurement instruments Comparison of two approaches to measuring change in health status in rheumatoid arthritis: the Health Assessment Questionnaire (HAQ) and modified HAQ. Determining minimally important changes in generic and disease-specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis. Responsiveness and validity in health status measurement: a clarification. Clinical improvement as reflected in measures of function and health-related quality of life following treatment with leflunomide compared with methotrexate in patients with rheumatoid arthritis: sensitivity and relative efficiency to detect a treatment effect in a twelve-month, placebo-controlled t A comparison of the full and short versions of the Arthritis Impact Measurement Scales. Sensitivity of a health status measure to short-term clinical changes in arthritis. Cultural adaptation and validation of a German version of the Arthritis Impact Measurement Scales (AIMS2). A comparison of health-related quality-of-life measures for rheumatoid arthritis research. The Auranofin Cooperating Group. Revalidation of the original Cedars-Sinai health-related quality of life in rheumatoid arthritis questionnaire.
abstract: Health status measures are conceptually relevant to the assessment of clinical outcome in the rheumatic diseases , but their ability to detect meaningful changes in health has not been clearly demonstrated . This report describes the performance of a self-administered health status question naire in a r and omized , double-blind , 21-week comparison of placebo , oral gold , and injectable gold in rheumatoid arthritis patients . Outcome was assessed by st and ard clinical measures , including joint count , grip strength , and laboratory tests , and by the Arthritis Impact Measurement Scales , a reliable and valid health status measure that assesses physical disability , psychological status , and pain . Data from the clinical and health status measures produced highly similar conclusions : injectable and oral gold are more effective than placebo for rheumatoid arthritis , and injections are slightly more effective than oral gold . The health status measure was thus quite sensitive to clinical ly meaningful drug-induced improvements . These findings provide justification for the further application of health status measures to clinical trials of chronic disease OBJECTIVE To determine the discriminant validity of the core set of outcome measures proposed by the American College of Rheumatology ( ACR ) and the Outcome Measures in Clinical Trials ( OMERACT ) conference committee to be used in clinical trials of rheumatoid arthritis ( RA ) . METHODS Utilizing data from a multicenter r and omized double-blind clinical trial of low-dose cyclosporine and placebo in RA , we estimated the relative efficiency ( RE ) of measures to detect a treatment effect ( relative to tender joint count , which was assigned a value of 1 ) . Four pain measures ( 10-cm visual analog scale [ VAS ] , 5-point categorical scale , Health Assessment Question naire [ HAQ ] pain index , Arthritis Impact Measurement Scales [ AIMS ] pain score ) and 3 quality -of-life measures ( Problem Elicitation Technique [ PET ] , HAQ , AIMS )  were compared . RESULTS Physician and patient global measures were the most responsive instruments , although neither was statistically superior to tender joint count . Swollen joint count , grip strength , pain measured on a 10-cm VAS , and functional status as measured by the PET and HAQ were all of intermediate responsiveness . Morning stiffness , 5-point pain scale , and erythrocyte sedimentation rate were the least responsive instruments . CONCLUSION This study provides further evidence to support the core set of outcome measures proposed by the ACR and OMERACT In clinical measurement comparison of a new measurement technique with an established one is often needed to see whether they agree sufficiently for the new to replace the old . Such investigations are often analysed inappropriately , notably by using correlation coefficients . The use of correlation is misleading . An alternative approach , based on graphical techniques and simple calculations , is described , together with the relation between this analysis and the assessment of repeatability Observational and longitudinal observational studies ( LOS ) provide essential information about the course and outcome of rheumatic disorders that can not be provided by r and omized controlled trials , and they constitute the major clinical scientific communication in rheumatology . There has been no consensus as to the full and appropriate content of LOS . This report defines a core set of domains and reporting requirements for LOS . At the 1998 OMERACT IV Conference a consensus process evaluated the literature of rheumatology in light of the constructs , variables , and outcomes of rheumatology by using introductory lectures , nominal groups , and plenary sessions . The result of this process was to identify 5 " core " domains that should be included in every LOS : Health Status , Disease Process , Damage , Mortality , and Toxicity/Adverse Reactions . Two additional domains , Work Disability and Costs , were recognized as important , but need not be used in all LOS . Eleven subdomains were identified that divided the domains into convenient clinical and conceptual units . A set of reporting requirements was also determined . The core recommendations , which follow on the WHO ICIDH-2 outline , are not disease-specific ; the substitution of different " disease process " and " damage " measures make them suitable for many rheumatic disorders . The core set is intended to serve as a core for LOS in almost all rheumatic conditions OBJECTIVE Validation of responsiveness and discriminative power of the World Health Organisation/International League of Associations for Rheumatology ( WHO/ILAR ) core set , the American College of Rheumatology ( ACR ) , and European League for Rheumatology ( EULAR ) criteria for improvement/response , and other single and combined measures ( indices ) in a trial in patients with early rheumatoid arthritis ( RA ) . METHODS Ranking of measures by response ( st and ardised response means and effect sizes ) and between-group discrimination ( unpaired ttest and χ2 values ) at two time points in the COBRA study . This study included 155 patients with early RA r and omly allocated to two treatment groups with distinct levels of expected response : combined treatment , high response ; sulfasalazine treatment , moderate response . RESULTS At week 16 , st and ardised response means of core set measures ranged between 0.8 and 3.5 for combined treatment and between 0.4 and 1.2 for sulfasalazine treatment ( 95 % confidence interval ±0.25 ) . Performance of patient oriented measures ( for example , pain , global assessment ) was best when the questions were focused on the disease . The most responsive single measure was the patient 's assessment of change in disease activity , at 3.5 . Patient utility , a generic health status measure , was moderately ( rating scale ) to poorly ( st and ard gamble ) responsive . Response means of most indices ( combined measures ) exceeded 2.0 , the simple count of core set measures improved by 20 % was most responsive at 4.1 . Discrimination performance yielded similar but not identical results : best discrimination between treatment groups was achieved by the EULAR response and ACR improvement criteria ( at 20 % and other percentage levels ) , the pooled index , and the disease activity score ( DAS ) , but also by the Health Assessment Question naire ( HAQ ) and grip strength . CONCLUSIONS Responsiveness and discrimination between levels of response are not identical concepts , and need separate study . The WHO/ILAR core set comprises responsive measures that discriminate well between different levels of response in early RA . However , the performance of patient oriented measures is highly dependent on their format . The excellent performance of indices such as the ACR improvement and EULAR response criteria confirms that they are the preferred primary end point in RA clinical trials OBJECTIVE To assess the performance of the Barthel Index ( BI ) in patients with rheumatoid arthritis ( RA ) in the acute care hospital , as compared to the Stanford Health Assessment Question naire ( HAQ ) and the Hannover Functional Question naire ( Funktionsfragebogen Hannover , FFbH ) . METHODS A prospect i ve study of 97 patients with RA admitted to an acute rheumatology hospital with new onset or acute flare of RA . Patients were required to self-complete the BI , the HAQ , and the FFbH.  Disease activity was measured using the Disease Activity Score ( DAS28 ) . RESULTS Seventy-eight percent of patients were female , average age was 61.5 ( SD 12.5 ) years , and 72.2 % were rheumatoid factor-positive . The median HAQ was 1.29 ( range 0 - 3 ) , median FFbH was 50 % ( 6 - 100 % ) , and median BI was 95 ( 0 - 100 ) , and distribution was highly skewed . All measures of physical functioning were significantly correlated with each other and with the DAS28 ; however , the BI discriminated poorly between low and high disease activity . CONCLUSION The BI is not a useful instrument to assess physical functioning in patients with acute symptoms of RA , but may have a role in assessing patients with comorbidities and in assessing nursing care needs in the acute care hospital Objectives For the measurement of  patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields As an alternative to the calculation of change scores for health status question naires used in clinical trials or longitudinal studies , transitional questions have been developed for patients to assess changes directly themselves . Here the original Health Assessment Question naire ( HAQ ) is compared with a modified version of the HAQ ( MHAQ ) which contains transition questions used at follow up . These , together with a set of st and ard rheumatological tests , were all completed by 100 patients with rheumatoid arthritis on two occasions , three months apart . Change scores were calculated for the HAQ and for the clinical measures and compared with the MHAQ . The results were strikingly in favour of encouraging patients to assess their own degree of change through the use of transition questions in the MHAQ OBJECTIVE To define clinical ly meaningful changes in 2 widely used health-related quality of life ( HQL ) instruments in studies of patients with rheumatoid arthritis ( RA ) . METHODS Patients with RA ( n = 693 ) who were enrolled in 2 double-blind , placebo-controlled clinical trials completed the Short Form 36 ( SF-36 ) modified health survey and the Health Assessment Question naire ( HAQ ) disability index at baseline and 6-week followup assessment s. Data on 5 RA severity measures were also collected at baseline and at 6 weeks ( patient and physician global assessment s , joint swelling and tenderness counts , and global pain assessment ) . Comparison of changes in the SF-36 scales and HAQ scores was made between groups of patients known to differ in the level of change on each RA severity measure . RESULTS With few exceptions , changes in the SF-36 and HAQ scores were different between patients who differed in the level of change on each RA severity measure . Changes in the SF-36 and HAQ scores were more strongly related to changes in the patient and physician global assessment s and patient pain assessment than to changes in the joint swelling and tenderness counts . CONCLUSION Based on these results , minimally important changes in the SF-36 scales and HAQ disability scores were determined , which will be useful in interpreting HQL results in clinical trials We present data from two studies which clarify the relationship between the responsiveness and validity of instruments design ed to measure health status in clinical trials . In a controlled trial of  long vs short duration adjuvant chemotherapy for women with Stage II breast cancer , the Breast Cancer Chemotherapy Question naire ( BCQ ) proved valid as a measure of subjective health status and was able to distinguish long vs short arms . Well vali date d measures of physical and emotional function developed by the R and Corporation were unable to distinguish between the two groups . The Eastern Co-operative Oncology Group Criteria ( ECOG ) distinguished the two groups , but failed criteria of clinical sensibility as a measure of subjective health status . In a study of patients with Crohn 's disease and ulcerative colitis , the Inflammatory Bowel Disease Question naire ( IBDQ ) showed small intrasubject variability over time . Gobal ratings of change showed moderate to high correlations with changes in IBDQ score , and patients who reported overall improvement or deterioration showed large changes in IBDQ score . Each of these findings support , in different ways , the reproducibility , validity , and responsiveness of the question naire . While the same data can at times bear on both validity and responsiveness , when assessing evaluative instruments it is useful to make a conceptual distinction between the two OBJECTIVE To examine correlations between clinical improvement as defined by the American College of Rheumatology ( ACR ) responder analysis and clinical improvement as determined by 4 function and /or health-related quality of life measures , and to estimate the sensitivity and relative efficiency of these measures compared with changes in the tender joint count in patients with rheumatoid arthritis ( RA ) . METHODS A 52-week , multicenter , double-blind controlled trial was conducted to compare treatment with leflunomide ( n = 182 ) , methotrexate ( n = 180 ) , or placebo ( n = 118 ) in patients with active RA .  ACR response rates and improvement in scores on the  Health Assessment Question naire ( HAQ ) , Problem Elicitation Technique ( PET ) , and Medical Outcomes Survey Short Form 36 ( SF-36 ) were compared in 438 of the patients . RESULTS In comparing leflunomide with placebo , the patient global assessment , HAQ disability index , and SF-36 bodily pain scale were most responsive to treatment group differences . The modified HAQ ( M-HAQ ) , PET Top 5 , SF-36 physical component score , physician global assessment , pain intensity scale , and SF-36 physical functioning scale were more responsive to treatment group differences than was the tender joint count . In comparing methotrexate with placebo , the patient and physician global assessment s were most responsive . These 2 measures , as well as the pain intensity scale and the C-reactive protein level , were more responsive to treatment group differences than was the tender joint count , while the SF-36 mental health component score was least responsive . A close correlation between changes in the M-HAQ and HAQ scores indicated that the M-HAQ was similarly responsive to change over time . Improvements in the PET , SF-36 physical component score , bodily pain , and physical functioning scales correlated with the ACR responder status . CONCLUSION Both disease-specific and generic measures of function and health-related quality of life detect improvements in RA patients . Using both types of measures for evaluating therapies will identify discernible changes that are important to patients , and will facilitate comparisons across different disease states This study examined the validity and reliability of full and short versions of the Arthritis Impact Measurement Scales ( AIMS ) .  One hundred fifty-five patients with Rheumatoid Arthritis followed at a University Hospital Rheumatology Clinic completed the full AIMS at baseline , 6 months , 12 months , and 18 months . After reducing the 45-item AIMS to 22 , alpha reliabilities and test-retest correlations showed that , with the exception of test-retest correlations for mobility at 6 months and for pain at 12 and 18 months , the full and short scales were comparably reliable . Convergent validity correlations with theoretically related scales were also comparable . However , some of the short scales did not detect the same differences over time that the full scales did . Specifically , the short mobility , pain , anxiety , and depression scales were not as sensitive to change as the full scales . Except for these four scales , the short version appears to be a viable alternative for use by health professionals and research ers To assess the sensitivity of the Arthritis Impact Measurement Scales ( AIMS ) , we analyzed data from 3 clinical trials . One trial involving 255 patients with rheumatoid arthritis ( RA ) was a 12-week , r and omized controlled trail of diclofenac , naproxen , and aspirin . Two trials were open-label studies of 24 weeks duration that included 165 RA and 355 osteoarthritis ( OA ) patients , all of whom were treated with diclofenac .  In addition to the AIMS , tender joint count , morning stiffness , and erythrocyte sedimentation rate were used as outcome measures in the trials . The AIMS results showed substantial improvements in Physical Function , Psychological Status , and Pain , as well as in overall Arthritis Impact . These improvements were detected by the time of the initial outcome assessment at 4 weeks or 8 weeks , and were detected in patients with either OA or RA . These AIMS results closely parallel improvements shown by traditional clinical measures , and demonstrate that the AIMS health status measure is sensitive to improvements in OA as well as in RA . The AIMS also detects responses produced by therapy with nonsteroidal antiinflammatory drugs ( NSAIDs ) , and these improvements can be demonstrated in as short a treatment time as 4 weeks . These findings confirm the utility of the AIMS for assessing outcome in rheumatic disease studies , and they have implication s for the design of future clinical trials of NSAIDs OBJECTIVE To vali date a translated and culturally adapted version of the Arthritis Impact Measurement Scale ( AIMS ) 2 in primary care patients with osteoarthritis ( OA ) of the hip and knee . METHOD The AIMS 2 was translated into German and culturally adapted . The question naire then was administered to 220 primary care patients with OA of the knee or hip . Two hundred and nine question naires were returned and analysed . Test-retest reliability was tested in 50 r and omly selected patients , of those 42 completed the question naire after 2 weeks for a second time . RESULTS Item-scale correlations were reasonably good as well as the discriminative power of separate scales . The assessment of internal consistency reliability also revealed satisfactory values ; Cronbach 's alpha was 0.77 or higher for all scales . The test-retest reliability , estimated in an intraclass correlation coefficient ( ICC ) , exceeded 0.90 , except the " social activities " scale ( 0.87 ) . Since only patients with OA of the lower limb were enrolled , substantial floor effects occurred in the " arm function " ( 28.2 % ) and the " h and and finger function " scale ( 29.2 % ) . The principal factor analysis confirmed the postulated three-factor structure with a physical , physiological and social dimension , explaining 48.5 % , 13.9 % and 6.8 % of the variation , respectively . External validity was assessed by calculating correlations to the Western Ontario and MacMaster ( WOMAC ) osteoarthritis question naire a pain visual analogue scale ( VAS ) and the Kellgren score as well as to disease duration . Spearman 's " R " achieved satisfactory values for the corresponding WOMAC scales and the pain-VAS . Correlations with disease duration as well as with the radiological grading were low . CONCLUSION The GERMAN- AIMS 2 is a reliable and valid instrument to assess the quality of life ( QoL ) in primary care patients suffering from OA Twenty-eight instruments measuring pain , clinical , functional , and global characteristics  were administered to 303 patients in a six-month r and omized clinical trial of auranofin and placebo in the treatment of patients with rheumatoid arthritis . The instruments were compared with respect to their responsiveness in detecting a treatment effect , the time involved in administering the instrument , the need for the presence of an interviewer , and ease of administration . The instruments ' ability to detect a treatment effect was the deciding characteristic in the clinical , pain , and global categories in choosing the preferred instrument . The counts of tender and swollen joints were found to be the most responsive clinical measures , the 10-cm pain line was the most responsive and the fastest to administer of the pain instruments , and the categorical self- assessment of arthritis was the most responsive global measure . In the functional ability category , the Health Assessment Question naire ( HAQ ) , the Keitel Functional Assessment , and the Quality of Well-Being ( QWB ) Question naire were equally responsive . The HAQ was the shortest and the only self-administered question naire . The QWB has had the most extensive validation work but was a complex instrument requiring intensive interviewer training . The Keitel was the most time-consuming instrument , but had the advantage of high interobserver agreement . The design of future trials can be guided by the information obtained in this study on their relative efficiencies and ease of use OBJECTIVE To assess the psychometric characteristics of the original 33-item Cedars-Sinai Health-Related Quality of Life in Rheumatoid Arthritis Question naire ( O-CSHQ-RA ) and 11-item CSHQ-RA Short Form ( SF ) using a representative population of patients with rheumatoid arthritis ( RA ) from 55 sites across the United States . METHODS Data were from a 24-week multicenter , open-label , single-arm study of 312 RA patients receiving anakinra .  Cronbach 's alpha coefficient was used to indicate the internal consistency . Test-retest reliability was assessed by establishing the intraclass correlation coefficient ( ICC ) for screening and baseline visit responses . Convergent validity was tested with the Pearson correlation coefficient . Analysis of variance was performed to determine discriminant validity . A Wilcoxon signed-rank test and analysis of covariance were used to assess the responsiveness . A discriminant function was generated to determine the clinical ly meaningful change . RESULTS Test-retest reliability was demonstrated for both versions of the CSHQ-RA , with ICC ranging from 0.82 to 0.94 . Cronbach 's alpha coefficients were > or = 0.9 , indicating good internal consistency . Pearson correlations between health-related quality of life instruments and CSHQ-RA measures ranged from -0.33 to -0.73 and 0.39 to 0.76 , demonstrating good convergent validity . Scores on both versions of the CSHQ-RA differed significantly ( p < 0.0001 ) for patients with different levels of physical disability as measured by the Stanford Health Assessment Question naire . Both instruments were responsive to differences in patient health as measured by the general health question ( p < 0.0001 ) . Clinical ly meaningful changes were calculated for all 5 domains of the O-CSHQ-RA ( 6.9 - 14.0 ) and the overall O-CSHQ-RA SF ( 12.7 ) . CONCLUSION These results support the validity and reliability of both the original CSHQ-RA and the 11-item CSHQ-RA SF when tested in a representative patient population
target: Conclusion Based on this literature review , the disease-specificHAQ and the generic SF-36 can currently be most confidently recommended to measure PF in RA for most research purpose s. The HAQ , however , was frequently associated with considerable ceiling effects while the SF-36 has limited content coverage .
background: Background The aim of this study was to systematic ally review the content validity and measurement properties of all physical function ( PF ) scales which are currently vali date d for use with patients with rheumatoid arthritis ( RA ) .