The patient-oriented eczema measure: development and initial validation of a new tool for measuring atopic eczema severity from the patients' perspective. Online video improves clinical outcomes in adults with atopic dermatitis: a randomized controlled trial. Validation of the Eczema Area and Severity Index for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% randomized controlled clinical trials programme The validity and reliability of an asthma knowledge questionnaire used in the evaluation of a group asthma education self-management program for adults with asthma. Use of Condition-Specific Patient-Reported Outcome Measures in Clinical Trials among Patients with Wrist Osteoarthritis: A Systematic Review A pilot study on the use of wet wraps in infants with moderate atopic eczema Eczema workshops reduce severity of childhood atopic eczema 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. Outcome assessment in clinical trials. Evidence for the sensitivity of a health status measure. Pediatric atopic eczema: the impact of an educational intervention. Disease severity and associated family impact in childhood atopic dermatitis Asthma outcomes workshop: overview. Validation of the Dermatology Life Quality Index as an outcome measure for urticaria-related quality of life. The REal Life EVidence AssessmeNt Tool (RELEVANT): development of a novel quality assurance asset to rate observational comparative effectiveness research studies Clinical outcomes of a diagnostic and treatment protocol in allergy/sensitivity patients. Systematic review of outcome measures in pediatric eosinophilic esophagitis treatment trials Preliminary validation of clinical remission criteria using the OMERACT filter for select categories of juvenile idiopathic arthritis.
OBJECTIVE To develop a simple , valid , repeatable , and readily underst and able patient-oriented assessment measure for monitoring disease activity in children and adults with atopic eczema . DESIGN Qualitative semistructured patient interviews identified a list of symptoms of atopic eczema . These symptoms were quantitatively analyzed in a larger patient population to identify which symptoms were important to patients and amenable to monitoring as part of a scoring system . SETTING The outpatient Department of Dermatology at the Queen 's Medical Centre , University Hospital , Nottingham , Engl and , and 5 local general practice s. PATIENTS Four hundred thirty-five patients with atopic eczema . RESULTS Seven symptoms were incorporated into the final patient-oriented eczema measure using a simple 5-point scale of frequency of occurrence during the previous week , with a maximum total score of 28 . Validity testing against the Dermatology Life Quality Index , Children 's Dermatology Life Quality Index , and patients ' global severity assessment s showed good correlation ( r = 0.78 , r = 0.73 , and r = 0.81 , respectively ; P<.001 ) . Internal consistency was high ( Cronbach alpha = 0.88 ) , and test-retest reliability was good , with 95 % of scores falling within 2.6 points on repeat testing ( mean score difference , 0.04 ; SD , 1.32 ) . Individual variables in the measure demonstrated sensitivity to change during a 4-week in-clinic period and an 18-week r and omized controlled clinical trial . CONCLUSION The patient-oriented eczema measure is a practical self-assessed measurement tool for monitoring aspects of atopic eczema that are important to patients in routine clinical practice or in the clinical trial setting BACKGROUND Atopic dermatitis ( AD ) is a chronic inflammatory skin disorder characterized by intense pruritus that causes significant disease and psychosocial burden in patients . Patient education has the potential to improve clinical outcomes and patient knowledge of this condition . OBJECTIVES We sought to assess the effectiveness of online video education at improving AD knowledge and disease severity compared with a written pamphlet , and to determine the usefulness and appeal of the two educational delivery vehicles . METHODS In a r and omized controlled trial , 80 participants were r and omized to receive either online video-based patient education or written pamphlet education about AD and its management . We assessed AD disease severity using the patient-oriented eczema measure ( POEM ) scale . AD knowledge was assessed with st and ardized question naires at baseline and after the 12-week intervention . RESULTS All participants had similar baseline knowledge and AD severity at the beginning of the study . On study completion , improvements in AD knowledge assessed by question naire were significantly greater in the video group than the pamphlet group ( 3.05 vs 1.85 , P = .011 ) . Online video-based education result ed in greater improvement in clinical outcome , as measured by POEM , compared with pamphlet-based education ( POEM score reduction of 3.30 vs 1.03 , P = .0043 ) . Finally , although the usefulness of both interventions was rated equally ( P = .77 ) , the online video was significantly more appealing than the pamphlet ( P = .0086 ) . LIMITATIONS This study is limited to AD in adults . CONCLUSION Online video for patient education is an effective and appealing tool for improving clinical outcomes in adult patients with AD Objective To vali date the Eczema Area and Severity Index ( EASI ) by assessing its internal consistency , reliability and sensitivity to change and by correlating it to other efficacy parameters . This paper reports aspects of the validity and reliability of an asthma general knowledge question naire for adults ( AGKQA ) , developed as one of the outcome measures for a r and omized controlled effectiveness trial of an asthma education program for adults with asthma . It also illustrates how study data can provide a valuable , generally neglected opportunity to assess the validity and reliability of a measure where re sources are not available for the extensive investigation of these properties prior to administration of the measure in a study . The AGKQA was demonstrated to have good content and face validity . Construct validity assessed using the principal components method for factor analysis suggested the scale was unidimensional . Criterion-related validity , assessed using the contrasted groups method , demonstrated a significant difference ( p < 0.0001 ) in total score and for 68 % of item responses for the adults with and without direct experience of asthma . The Kuder-Richardson 20 reliability coefficient for internal consistency calculated using responses at baseline , immediately , and 12 months post-intervention were , respectively , 0.56 , 0.80 , and 0.75 , indicating excellent reliability . The AGKQA is an acceptably valid and reliable measure for the assessment of program content mastery that it was design ed to test Background . This paper aim ed to identify condition-specific patient-reported outcome measures used in clinical trials among people with wrist osteoarthritis and summarise empirical peer- review ed evidence supporting their reliability , validity , and responsiveness to change . Methods . A systematic review of r and omised 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 h and question naire ( DASH ) . The DASH , the  Michigan H and Outcomes Question naire ( 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 H and Index as another suitable instrument that had favourable reliability , validity , and responsiveness . Conclusions . The DASH , MHQ , and AUSCAN Osteoarthritis H and 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 Wet wrap therapy ( WWT ) is a well‐established treatment for  severe atopic dermatitis ( AD ) . However little evidence exists to justify widespread use in the community for less severe eczema . We compared the efficacy of WWT with a st and ard regime of hydrocortisone , to control moderate AD in children . We carried out a single‐observer , r and omized , controlled pilot study in 19 children under 5 years of age , with AD of 30 % or more body surface area , using only 1 % hydrocortisone ( HC ) prior to the study . Group one applied HC once in the morning for 2 weeks , with wet wraps twice daily for week 1 , but only at night for week 2 . Group two applied HC twice daily without wet wraps . Both applied emollient twice daily and as necessary . The primary outcome measure was the Six Area , Six Sign Atopic Dermatitis ( SASSAD ) severity score , and the secondary outcome measures were the Infants Dermatology Quality of Life Index ( IDQOL ) , the Dermatitis Family Impact ( DFI ) score and the weight of topical steroids and emollients used . Over the 2‐week active therapy period the mean fall in SASSAD was 8 [ 95 % confidence interval ( CI ) , −18 to + 2 ; P = 0.11 ] more in the non‐WWT group , the median change in the IDQOL was 2 for Group one and 7 for Group two ( 95 % CI for difference , −10 to + 3 ; P = 0.24 ) and the median change in DFI score was 2 for Group one and 5 for Group two ( 95 % CI for difference , −14 to + 2 ; P = 0.42 ) . This small study has shown that conventional therapy with HC and emollients alone is as effective as WWT for infants with moderately severe , widespread AD , and provides weak evidence to suggest that it may be more effective . We would not advocate routine use of WWT for moderate eczema without further evaluation An intervention study was conducted to assess the effectiveness of a nurse‐led eczema workshop in reducing the severity of atopic eczema in infants , children and adolescents . Ninety‐nine new patients referred to the Dermatology Department of The Royal Children 's Hospital in Melbourne , Australia , for the management of atopic eczema were r and omized to receive care from an eczema workshop or a dermatologist‐led clinic .  Patients were followed‐up 4 weeks after the intervention . The primary outcome was the severity of eczema as determined by scores obtained using the Scoring of Atopic Dermatitis ( SCORAD ) index at a 4‐week follow‐up visit . The secondary outcome was a comparison of treatments used in both clinics . At the 4‐week review the mean improvement in SCORAD was significantly greater in those patients attending the eczema workshop than those attending the dermatologist‐led clinic ( −9.93 , 95 % confidence interval −14.57 to −5.29 , P < 0.001 ) . Significantly more patients from the eczema workshop improved from moderate severity eczema at baseline to mild at review . There was greater adherence to eczema management in the eczema workshop compared with the dermatologist‐led clinic . In this study , patients attending the eczema workshop had a greater improvement in eczema severity than patients attending a dermatologist‐led clinic , supporting collaborative models of service provision 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 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 Patient education has been regarded as having a key role in the self-management of atopic eczema . However , the relationship between the educational interventions and clinical outcomes including severity of eczema , quality of life , and family impact has not been rigorously examined . The purpose of this longitudinal r and omized controlled study was to evaluate the impact of an intensive education program with a focus on dermatology and immunology design ed for parents and children diagnosed with atopic eczema . The intention of this study was not to change treatment regimes prescribed by the patient 's physician . The Scoring Atopic Dermatitis rating system was used for assessment of disease impact , and the impact on quality of life was quantified by using the Children 's Dermatology Life Quality Index , Infants ' Dermatology Quality of Life Index , and Dermatitis Family Impact .  A total of 61 pediatric patients ( 0 - 16 years ) diagnosed with atopic eczema from the metropolitan area of Adelaide were r and omized to either the control or intervention group . Results of the study showed that the intervention group had a significant improvement in the scoring atopic dermatitis measure when compared to the control group at week 4 and week 12 . Quality of life measures did not significantly improve with decreased severity of eczema except in the group of children aged 5 - 16 years which , despite small numbers , showed a significant improvement in quality of life scores . These findings suggest that education provides an important role in decreasing the severity of eczema Aim : To examine the association between childhood atopic dermatitis ( AD ) severity and family impact at baseline and after an intervention by a physician specialist , using vali date d measures of both severity and family impact . Methods : Cross sectional self administered survey of parent – caregivers of 49 r and omly selected children with AD ; 35 parents were available for follow up .  Family impact was measured using a modified AD Family Impact Scale completed by the parent – caregiver . The child ’s disease severity was measured using both the investigator ’s assessment via the Eczema Area and Severity Index ( EASI ) and the caregiver ’s assessment via the recently vali date d Self Assessment Eczema Area and Severity Index ( SA-EASI ) . Results : The parent – caregiver ’s assessment of severity of the child was the most significant correlate of the family impact of the child ’s AD ( p = 0.65 at baseline and p = 0.38 at follow up ) . In multivariate regression models , the parent – caregiver ’s estimate of severity remained the single strongest predictor of family impact before and after receipt of dermatologist care , as well as the difference in impact between pre and post-dermatologist care . Conclusions : There is evidence to support the ability of parent – caregivers of children with AD to accurately determine severity of their child ’s AD ; perceived severity is the driver of the family impact of this condition . Treatment of a child by a physician specialist is associated with reductions in both perceived severity , as well as family impact of this condition BACKGROUND Asthma clinical research will highly benefit from st and ardization of major outcomes in terms of definition and assessment methodology . This will permit useful comparisons across interventional or observational studies and will allow more effective data sharing . OBJECTIVE National Institutes of Health ( NIH ) institutes and the Agency for Healthcare Research and Quality convened a workshop involving 7 expert subcommittees to propose which asthma outcomes should be assessed with st and ardized methodology in future asthma clinical research studies . METHODS Each subcommittee utilized comprehensive literature review s and expert opinion to compile a list of asthma outcomes and classified them as either core ( required in future studies ) , supplemental ( to be used according to study aims and st and ardized ) , or emerging ( requiring validation and st and ardization ) . This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011 . RESULTS Outcomes for study participant characterization , as well as for prospect i ve clinical trial intervention and observational studies , were proposed for adults and children , and method ologies for outcome collection and reporting were determined . Furthermore , the workshop identified areas in which new outcomes or instruments for their measurement need to be developed and vali date d. CONCLUSIONS St and ardized outcomes for clinical research in asthma have been proposed . Participating NIH institutes and other federal agencies will consider these recommendations in future clinical research initiatives in asthma BACKGROUND Chronic idiopathic urticaria ( CIU ) is a debilitating skin disease that affects patients ' quality of life ( QOL ) . The Dermatology Life Quality Index  ( DLQI ) assesses QOL parameters across several types of dermatologic conditions . However , an evaluation of the validity of the DLQI for use in CIU patients has not been undertaken , because CIU , unlike other chronic skin conditions , is subject to daily or weekly symptom fluctuations . OBJECTIVE To test the reliability and validity of the DLQI in 2 sample s of CIU patients treated with fexofenadine hydrochloride ( 20 , 60 , 120 , or 240 mg twice daily ) . METHODS Data were obtained from 2 similar multicenter , double-blind , r and omized , placebo-controlled , parallel-group studies of CIU patients ( n = 418 and n = 439 ) . Patients completed the 10-item DLQI during 3 clinic visits ( approximately 2 weeks apart ) . Clinic personnel also recorded patients ' symptoms . RESULTS The results of the DLQI items were similar to those obtained with other skin disease population s , indicating the presence of relatively symmetrical distributions . Reliability was high , demonstrating the lack of excessive r and om measurement error ( alpha coefficient = .89 and .87 for sample s 1 and 2 ) . Factor analysis result ed in a unidimensional pattern , supporting the use of a total DLQI score . Most DLQI items distinguished patients with varying degrees of QOL impairment , highlighting the sensitivity of this instrument . Construct validity was moderate , providing evidence that the DLQI was responsive to changes in patients ' clinical status . CONCLUSIONS The DLQI is a valid , reliable , and clinical ly useful outcome measure for assessing QOL in CIU patients Abstract Background Evidence from observational comparative effectiveness research ( CER ) is ranked below that from r and omized controlled trials in traditional evidence hierarchies . However , asthma observational CER studies represent an important complementary evidence source answering different research questions and are particularly valuable in guiding clinical decision making in real-life patient and practice setting s. Tools are required to assist in quality appraisal of observational CER to enable identification of and confidence in high- quality CER evidence to inform guideline development . Methods The REal Life EVidence AssessmeNt Tool ( RELEVANT ) was developed through a step-wise approach . We conducted an iterative refinement of the tool based on Task Force member expertise and feedback from pilot testing the tool until reaching adequate inter-rater agreement percentages . Two distinct pilots were conducted — the first involving six members of the Respiratory Effectiveness Group ( REG ) and European Academy of Allergy and Clinical Immunology ( EAACI ) joint Task Force for quality appraisal of observational asthma CER ;  the second involving 22 members of REG and EAACI membership . The final tool consists of 21 quality sub-items distributed across seven methodology domains : Background , Design , Measures , Analysis , Results , Discussion /Interpretation , and Conflict of Interest . Eleven of these sub-items are considered critical and named “ primary sub-items ” . Results Following the second pilot , RELEVANT showed inter-rater agreement ≥ 70 % for 94 % of all primary and 93 % for all secondary sub-items tested across three rater groups . For observational CER to be classified as sufficiently high quality for future guideline consideration , all RELEVANT primary sub-items must be fulfilled . The ten secondary sub-items further qualify the relative strengths and weaknesses of the published CER evidence . RELEVANT could also be applicable to general quality appraisal of observational CER across other medical specialties . Conclusions RELEVANT is the first quality checklist to assist in the appraisal of published observational CER developed through iterative feedback derived from pilot implementation and inter-rater agreement evaluation . Developed for a REG-EAACI Task Force quality appraisal of recent asthma CER , RELEVANT also has wider utility to support appraisal of CER literature in general ( including pre-publication ) . It may also assist in manuscript development and in educating relevant stakeholders about key quality markers in observational CER OBJECTIVES This level II outcome study was conducted to examine the efficacy and toxicity of a diagnostic and treatment protocol using electrodermal screening ( EDS ) in allergy/sensitivity patients . METHODS Ninety-six patients with a diagnosis of allergy or sensitivity entered the study between 1994 and 1998 ; 90 participants completed the study . All participants followed the same protocol , and all interactions were with a single clinician at a single site . The Allergy Symptom Severity Index ( ASSI ) was developed to record symptomatic information .  EDS - conductance measurement 1/ ( - of specific acupuncture points was used as an objective endpoint ( indicator of outcome ) and for identification of antigens , according to Voll criteria . All measurements were taken before and after treatment , and EDS was carried out at all treatment sessions . Outcome criteria suggesting efficacy were reduction in ASSI score , reduction in number of items testing positive , and normalization of conductance measurements . A statistical analysis of the outcomes was performed using the student 's paired t-test . RESULTS There was a statistically significant change in pre- and post-treatment measurements of the ASSI . The conductance measurements normalized and the number of items testing positive decreased compared to pre-treatment testing . In addition to these parameters , 87.2 percent of subjects rated efficacy as good to excellent , and less than one-percent rated the outcome as poor . The outcome demonstrated longevity , meaning that people who had their post-treatment evaluation up to three years after primary treatment were still showing minimal ASSI scores , with no additional treatment . The treatment appeared to work equally well across age groups and gender . Forty-eight percent of participants had an aggravation of symptoms after treatment , lasting an average of 10 hours , with reactions described as mild to moderate . Average cost of the desensitization protocol ( all costs included ) was $ 822.16 . CONCLUSIONS This protocol demonstrated efficacy without serious toxicity and no long-term adverse effects . It is natural , non-invasive , and does not require long periods of avoidance of offending foods or environmental stimuli . The desensitization protocol is a low-cost , effective therapy for the treatment of patients suffering from symptoms of allergy/sensitivity disease Abstract Background Heterogeneity has been noted in the selection and reporting of disease-specific , pediatric outcomes in r and omized controlled trials ( RCTs ) . The consequence is invalid results or difficulty comparing results across trials . The primary objective of this systematic review was to assess primary outcome and outcome measure selection and reporting , in pediatric eosinophilic esophagitis ( EoE ) treatment trials . As secondary objectives , we compared trial disease definition to established concensus guidelines , and the efficacy of current EoE treatments . Methods We search ed MEDLINE , EMBASE , The Cochrane Library , Cochrane Central Register of Controlled Trials ( CENTRAL ) , and CINAHL since 2001 . We also search ed clinical trial registries ( portal.nihr.ac.uk ; clinical trials.gov ; is rct n.com ; and anzctr.org.au ) and references of included studies . We included RCTs of EoE treatment in patients 0–18 years . Two authors independently assessed articles . Results Eleven studies met inclusion criteria . All identified primary outcomes , however , of 9 unique primary outcomes , only 2 were used in more than one study . In total , 25 unique primary and secondary outcome measures were employed for pediatric EoE treatment trials . Measurement properties and rationale for their selection was rarely provided . Uptake of consensus-based diagnostic criteria was 25 % in trials initiated after 2011 . Due to the small number and heterogeneity of studies obtained , no meta- analysis of treatment efficacy could be undertaken . This SR was limited to exclusively pediatric RCTs . Conclusions The results of this study confirm the need for a st and ardized set of core outcomes that are universally reported in pediatric EoE trials . Consistent disease definition and st and ardized outcome reporting will facilitate meta-analyses across similar trials and inform future clinical decision-making . Systematic review registration number OBJECTIVE To begin the validation process of the preliminary criteria for inactive disease ( ID ) , clinical remission on medication ( CRM ) , and clinical remission off medication ( CR ) in children with select forms of juvenile idiopathic arthritis ( JIA ) . METHODS We used the OMERACT filter paradigm to estimate the validity of the criteria within each of the filter 's 3 components : truth , discrimination , and feasibility , in 5 categories of JIA : systemic arthritis , persistent and extended oligoarthritis , and rheumatoid factor-positive and negative polyarthritis . Data sources for determining validity estimates included a Delphi question naire survey sent to 246 pediatric rheumatologists in 34 countries , a consensus conference attended by 20 senior pediatric rheumatologists representing 9 countries , a retrospective chart review of 437 patients with JIA from 3 tertiary care clinics who had been followed between 4 and 22 years , and the literature . RESULTS Truth component : face and content validity . These aspects of validity were largely established via the Delphi question naire exercise and the consensus conference . Using an 80 % consensus level , participants felt that a set of non-redundant variables could effectively differentiate the clinical states of ID , CRM , and CR . Criterion validity could not be irrefutably established because no gold st and ard for inactive disease exists for JIA . As an alternative , published investigations of remission in JIA were used to estimate concurrent and convergent validity , as surrogates for criterion validity and as indicators of overall construct validity . Correlational analyses revealed the new criteria to have good construct validity . Discrimination component : the criteria demonstrated moderate to high levels of classification , prognosis , and responsiveness ( sensitivity to change ) using data from the chart review . Patients who were able to attain CR remained disease-free for substantially longer periods than did those who attained only ID or CRM . Responsiveness was evidence d by the ability of the criteria to allow movement of most patients between the disease states , consistent with what is known of the course of the disease . Feasibility component : Results of the Delphi and consensus conference produced a set of criteria that are easily , quickly , and inexpensively completed in the physician 's office , and present minimal or no risk to the patient . CONCLUSION The preliminary criteria demonstrated moderate to excellent validity characteristics in some , but not all components of the OMERACT filter . Prospect i ve validation studies are under way
CLINICAL IMPLICATION S Only SCORAD , EASI , and POEM currently perform adequately .
BACKGROUND Valid and reliable outcome measurements are a prerequisite for evidence -based practice .
The comparative validity and reliability of outcome measurements for assessing atopic eczema ( AE ) severity is unclear .
OBJECTIVE We sought to assess the validity , reliability , sensitivity to change , and ease of use of outcome measurements for AE .
We also sought to give recommendations on which outcomes to use in clinical research and for clinical monitoring .