1. Assessment Methodology: Lessons from OMERACT Meetings Vibeke Strand, MD Biopharmaceutical Consultant Adjunct Clinical Professor, Division of Immunology, Stanford University

2. OMERACT: Outcome Measures in Rheumatology Clinical Trials I: 1992: Rheumatoid Arthritis Clinical Trials II: 1994:Adverse Events → Establishment of Registries Health Related Quality of Life Economic Evaluations III:1996:Osteoarthritis Osteoporosis Psychosocial Measures IV:1998:Longitudinal Observational Studies RA Response Criteria / Imaging Ankylosing Spondylitis → ASAS Systemic Lupus Erythematosus 5:2000:MCID Economics: Cost Effectiveness Imaging: Radiography and MRI 6:2002:Economic Evaluations Imaging

3. What is OMERACT? Data driven process to define outcome measures to be used in RCTs and LOS for each clinical indication Domains derived from the “Ds”: Discomfort Disability Dollar cost Death Literature reviews, data available from LOS and RCTs: Validity of currently defined instruments to assess outcome “Data mining” to better understand clinical response Correlation of patient reported responses with other outcome measures Definition of “minimally clinically important improvement” = MCID

4. What is OMERACT? Presentation of evidence and development of consensus at each conference: Representatives from: Academia, Clinical Investigators, Regulatory Agencies, Sponsors, Clinical Rheumatologists Goal: To Develop Recommendations for: “Core Set” of minimum number of domains / outcome measures assessed in RCTs and LOS Working agenda identifying ‘need’ to focus future work Previous OMERACT Recommendations have been ratified by WHO / ILAR in RA, OA, SLE, including HRQOL and Economic evaluations

5. The OMERACT ‘Umbrella’ OSTEOARTHRITIS: OARSI ANKYLOSING SPONDYLITIS: ASAS PAIN: IMMPACT RHEUMATOID ARTHRITIS: EULAR ACR JRA: PRCSG SLE: SLICC EULAR

6. The OMERACT Filter TRUTH: Face, content, construct and criterion validity Is the measure truthful? Does it measure what is intended? DISCRIMINATION: Reliability and sensitivity to change Does the measure discriminate between situations [states] of interest? FEASIBILITY: Can the outcome easily be measured given constraints of time, money and interpretability? Boers et al: JRheum 1998: 25: 198-9

7. Rheumatoid Arthritis: OMERACT I, 1992 RCTs available, but data limited Only a few included a measure of physical function General ‘belief’ that none had demonstrated convincing efficacy “Paper patients” derived from actual RCT data → [healthy] arguments regarding changes reported Clear disagreement about importance of MD Global assessments Participants ranked patient reported physical function and SJC highest when assessing efficacy Facilitated recognition that ‘perception’ of benefit variable

8. ACR Response Criteria Defined and Ratified after OMERACT I Data driven nominal group process Based on Paulus criteria and statistical analyses of CSSRD and MTX RCTs best differentiating active therapy from placebo Require ≥20% improvement in 5 of 7 measures: Tender Joint Count and Swollen Joint Count and 3 of the following 5: MD Global Physical function: HAQ Pain by VAS Patient Global ESR and/or CRP Defined and Ratified after OMERACT I Data driven nominal group process Based on Paulus criteria and statistical analyses of CSSRD and MTX RCTs best differentiating active therapy from placebo Require ≥20% improvement in 5 of 7 measures: Tender Joint Count and Swollen Joint Count and 3 of the following 5: MD Global Physical function: HAQ Pain by VAS Patient Global ESR and/or CRP

9. EULAR Response Definition >3.2 and ≤5.1 >5.1 ≤3.2 DAS28 Score >1.2≤0.6>0.6 to ≤1.2 Decrease in DAS28 Good Moderate None Van Gestel et al. Arth Rheum 1996; 26:705-11 DIscriminant function analysis of patients w/active; inactive RA Disease activity state determined by treatment changes

10. As Demonstrated in RA, Responder Analyses Have Face and Content Validity Allow assessment of multiple domains Facilitate comparison of efficacy across: Products Heterogeneous populations, and Disease indications May lead to tiered approach to label indications Precedent: ACR Responder Index in RA DAS28 both confirms active disease at baseline and ‘clinical responses’ Additional data by x-ray and HRQOL Allow assessment of multiple domains Facilitate comparison of efficacy across: Products Heterogeneous populations, and Disease indications May lead to tiered approach to label indications Precedent: ACR Responder Index in RA DAS28 both confirms active disease at baseline and ‘clinical responses’ Additional data by x-ray and HRQOL

11. Rheumatoid Arthritis: Later Efforts Demonstrated that ‘generic’ measures of HRQOL sensitive to change in RA RCTs Identified ‘MCID’ for HAQ and SF-36……facilitating: Comparisons across products, disease populations Economic evaluations Helped to show impact of ‘Rheumatic Diseases’ to WHO In this Bone and Joint Decade Identified importance of Rheumatic Diseases relative to CV, DM, HTN, OP…. [Hopefully] → allocation of more resources to identify and treat Rheumatic Diseases…..

12. Minimum Clinically Important Differences [MCID] Degree of improvement Perceptible to patients = clinically important/ meaningful Defined by patient query, delphi technique OMERACT: 33-36% improvement;18% > placebo Confirmed by statistical correlations with patient global assessments in RCTs in RA and OA Determination of proportion of patients with clinically important improvement provides a more interpretable result with direct clinical implications Degree of improvement Perceptible to patients = clinically important/ meaningful Defined by patient query, delphi technique OMERACT: 33-36% improvement;18% > placebo Confirmed by statistical correlations with patient global assessments in RCTs in RA and OA Determination of proportion of patients with clinically important improvement provides a more interpretable result with direct clinical implications

13. 1 Guzman et al. Arth Rheum. 1996; 39:5208 2 Kosinski et al. Arth Rheum. 2000; 43:1478-87 3 Redelmeier et al. Arch Intern Med. 1993; 153:1337-42 4 Wells et al. J Rheumatol. 1993; 20:557-60 5 Kosinski et al. Arth Rheum. 2000; 43:S140 6 Samsa et al. Pharmacoeconomics. 1999; 15:141-155 7 Thumboo et al. J Rheumatol. 1999; 26:97-102. Minimum Clinically Important Differences [MCID] HAQ DI 1-4 0 - 3 –0.22 SF-36 2, 5-7 0 - 100 +5 - 10 points PCS/MCS mean 50 ± 10 +2.5 - 5 points HAQ DI 1-4 0 - 3 –0.22 SF-36 2, 5-7 0 - 100 +5 - 10 points PCS/MCS mean 50 ± 10 +2.5 - 5 points ScoreDirectionMCID Range of ScoringLiterature ScoreDirectionMCID Range of ScoringLiterature

14. Health Assessment Questionnaire (HAQ) Widely accepted, validated, rheumatology-specific instrument to assess physical function in RA Gold Standard: OMERACT/FDA Guidance 20 questions covering 8 types of activities Dressing + Grooming; Arising; Eating; Walking; Hygiene; Reaching; Gripping, Activities of Daily Living HAQ Disability Index (HAQ DI) Scores the worst items within each of the eight scales Based on use of aids and devices Widely accepted, validated, rheumatology-specific instrument to assess physical function in RA Gold Standard: OMERACT/FDA Guidance 20 questions covering 8 types of activities Dressing + Grooming; Arising; Eating; Walking; Hygiene; Reaching; Gripping, Activities of Daily Living HAQ Disability Index (HAQ DI) Scores the worst items within each of the eight scales Based on use of aids and devices

15. Mean Improvement in HAQ Disability Index Year-2 Cohorts at 24 Months Improvement Worsening Mean Change from Baseline LEFMTX US301MN302/304 SSZ MN301/303/305 *LEF vs MTX; p=0.01 -0.5 0 -0.22 -0.73 -0.56 -0.6 -0.37 -0.48 -0.56 * (248) (273) (51)(46) (97) (101) % Achieving MCID 84% 69% 86% 82% 74% 78%

16. Mean Improvement through Week 102 ATTRACT: HAQ Disability Index Mean Improvement through Week 102 MTX + Placebo 3 mg/kg q8w 3 mg/kg q8w 3 mg/kg q4w 3 mg/kg q4w 10 mg/kg q8w 10 mg/kg q8w 10 mg/kg q4w 10 mg/kg q4w < 0.001 p-value vs. MTX + Placebo 0.2 0.4 0.5 0.4 0.45 0 0.1 0.2 0.3 0.4 0.5 All infliximab All infliximab Mean improvement

17. ERA: Mean Change in HAQ DI at Month 12 -0.80 Mean Change from BL MTX ETN -0.70 -0.8 -0.7 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 MCID Baseline HAQ DI: 1.6 1.6 Kosinski et al. AJMC. 2002;8:231-240

18. Mean Changes in HAQ DI at Weeks 24 and 52 Anakinra+MTX -0.18 -0.15 -0.29 -0.28 -0.8 -0.7 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 0.0 Mean Change from Baseline Placebo+MTX Anakinra+MTX 24 weeks52 weeks MCID Baseline: 1.38 Placebo 1.43 Active Fleishman et al. Arth Rheum. 2002;46:S574.

19. Mean Changes in HAQ DI at Weeks 24 and 52 DE019: Adalimumab+MTX -0.24 -0.25 -0.6 -0.61 -0.56 -0.59 -0.8 -0.7 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 0.0 Mean Change from Baseline Placebo BL 1.48 Adalimumab 20 mg weekly BL 1.45 Adalimumab 40 mg eow BL 1.44 24 weeks52 weeks MCID Keystone E. Arthritis & Rheum 2002; 46(9) suppl.

20. Mean Changes in HAQ DI from Weeks 30 to 54 ASPIRE RCT -0.79 -0.75 Mean Change from BL; Wks 30-54 MTX MTX+INF 3 mg/kg MTX+INF 6mg/kg -0.78 -0.8 -0.7 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 MCID Baseline HAQ DI: 1.5 1.5 1.5 % Achieving MCID: 65 76 76 Smolen et al. Ann Rheum Ds 2003;62:S64

21. Mean Changes in HAQ DI at Weeks 52 TEMPO RCT -0.97 -0.61 Mean Change from BL MTX ETN MTX+ETN -0.66 -0.8 -0.7 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 MCID Baseline HAQ DI: 1.7 1.7 1.8 -0.9

22. SF-36: Short Form 36 Health Survey Validated, widely used generic measure of HRQOL 8 Domains: Scored 0 - 100; age, sex adjusted rates 2 Summary Scores Physical Component: PCS –Measures how decrements in physical function affect day to day activities –Impact of physical impairment/disability on HRQOL Mental Component: MCS –Impact of mental affect, symptoms of pain on HRQOL Normative based scoring (Mean: 50, SD: 10) Validated, widely used generic measure of HRQOL 8 Domains: Scored 0 - 100; age, sex adjusted rates 2 Summary Scores Physical Component: PCS –Measures how decrements in physical function affect day to day activities –Impact of physical impairment/disability on HRQOL Mental Component: MCS –Impact of mental affect, symptoms of pain on HRQOL Normative based scoring (Mean: 50, SD: 10)

23. SF-36 Two-Component Model Physical Component Mental Component Physical Function Role Physical Bodily Pain General Health Vitality Social Function Role Emotion Mental Health

24. US 301: Baseline SF-36 Scores US Norms vs US301 Population 0 Physical Function Role Physical Bodily Pain General Health Perception VitalitySocial Function Role Emotion Mental Health Study US301 PopulationUS Norms (A/S Adjusted) 10 20 30 40 50 60 70 80 90 100

25. US301: Mean Improvement in SF-36: Year-2 Cohorts Leflunomide and Methotrexate Better Mean Scores PhysicalRoleBodilyGeneralVitalitySocialRoleMental FunctionPhysicalPainHealthFunctionEmotionHealth Perception 0 10 20 30 40 50 60 70 80 90 LEF 24 Months (n = 93) MTX 24 Months (n = 89) US Norms (A/S Adjusted) Baseline Year-2 Cohort

26. 35Placebo Adalimumab (40 mg) QOW 5.2 13.5 8.2 14.6 28.1 23.3 0 5 10 15 20 25 30 Mean Change From Baseline 3.5 8.7 9.0 16.9 7.5 13.4 5.2 15.5 2.3 6.7 Mean Changes in SF-36 Scores DE019: Adalimumab+MTX MCID Vitality Physical Functioning Physical Role Bodily Pain General Health Social Functioning Emotional Health Mental Health Keystone E. Arthritis & Rheum 2002; 46 suppl.

27. Leflunomide and Methotrexate: Mean Changes in SF-36 PCS Year-2 Cohort (US301) 60 US Norm 2 SDs below US Norm LEF (93)MTX (97) BL12 M24 M BL12 M24 M Improved Mean Scores 0 10 20 30 40 50 30.9 42.7 41.7 30.2 38.6 38.8

28. Etanercept and Methotrexate: Mean Changes SF-36 PCS at 12 Months (ERA) 60 US Norm 2 SDs below US Norm Improved Mean Scores 0 10 20 30 40 50 BL 12M Kosinski et al. AJMC. 2002;8:231-240. ETN 25mg (193) MTX (199) 28.0 38.7 29.2 38.8

29. Infliximab: Median Improvement in SF-36 PCS at Month 24 (ATTRACT) Baseline: 23.9 –30.8 Kavanaugh et al. Arth Rheum. 2000;43:S147. p-value vs. placebo MTX + Placebo (n=88) 3 mg/kg q 8 wks (n=86) 0.011 3 mg/kg q 4 wks (n=86) <0.001 10 mg/kg q 8 wks (n=87) <0.001 10 mg/kg q 4 wks (n=81) <0.001 Median (IQR) 0 4 8 12 16 2.8 4.6 6.8 6.9 6.7

30. Anakinra+MTX: Mean Improvement in SF-36 PCS at Month 12 Baseline:29.9 PL 28.8 Active Fleishman et al. Arth Rheum. 2002;46:S574.

31. Correlation Between HAQ and SF-36 ReferenceStudyScalesCorrelation Ruta 1 —PCS-0.77 Talamo 2 —PF-0.72 Kavanaugh 3 Infliximab/ATTRACT PCS-0.51 PF-0.54 Kosinski 4 Etanercept/ERAPCS-0.60 PF-0.61 Lubeck 5 Etanercept/RAPOLOPCS-0.79 PF-0.82 Strand 6 Leflunomide/US301PCS-0.60 PF-0.74 1 Ruta et al. Br J Rheum. 1998;37:425-436. 2 Talamo et al. Br J Rheum. 1997;36:463-469. 3 Kavanaugh et al. A&R. 2000;43:S147. 4 Kosinski et al. Medical Care. 1999;37:MS23-39. 5 Lubeck et al. Value in Health. 2001;4:MS2,163. 6 Strand et al. A&R. 2001;44:S187.

32. MCID Values Are Consistent in RCTs in RA Improvements in HAQ DI and SF-36 in RA with newly approved therapies are statistically significant; more importantly, CLINICALLY MEANINGFUL MCID values are consistent across agents and patient populations Disease specific [‘relevant’] measure: HAQ Generic measure: SF-36 Improvements in disease specific highly correlated with generic measures Improvements in HAQ DI and SF-36 in RA with newly approved therapies are statistically significant; more importantly, CLINICALLY MEANINGFUL MCID values are consistent across agents and patient populations Disease specific [‘relevant’] measure: HAQ Generic measure: SF-36 Improvements in disease specific highly correlated with generic measures

33. MCID Workshop: Identifying Candidate Measures to Define ‘Low Disease Activity State’ Pain Function Inflammation Health Related Quality of life Structure damage Toxicity Co-morbidity Fatigue

34. Osteoarthritis OMERACT III: 1996 Candidate instruments to assess: Pain Stiffness Physical Function Limited data from RCTs; treatments offering only symptomatic benefit Identification of a ‘Core Set’ of 4 Domains as a foundation for future work Research Agenda: Identification of ‘Disease Control’, ‘Biologic Markers’ of Response

35. Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index Self-administered questionnaire Developed querying patients with hip or knee OA Reflects physical activities most affected by symptoms, disease manifestations Composite score based on 24 questions; subscores: Pain (5 questions) Joint stiffness (2 questions) Physical function (17 questions) Scored by 0 - 4 Likert or 0 - 10 cm VAS scales Improvement = negative change Self-administered questionnaire Developed querying patients with hip or knee OA Reflects physical activities most affected by symptoms, disease manifestations Composite score based on 24 questions; subscores: Pain (5 questions) Joint stiffness (2 questions) Physical function (17 questions) Scored by 0 - 4 Likert or 0 - 10 cm VAS scales Improvement = negative change

36. BIOLOGIC MARKERS HRQOL / UTILITY PAIN PHYSICAL FUNCTION PATIENT GLOBAL IMAGING (≥1YR) INFLAM- MATION Placement  Consequence INNER Core  CORE SET MIDDLE Core  HRQOL/ Utility (Strongly Recommended) OUTER Core  OPTIONAL Placement  Consequence INNER Core  CORE SET MIDDLE Core  HRQOL/ Utility (Strongly Recommended) OUTER Core  OPTIONAL ≥ 90% ≥30% - <90% 0% - <30% ≥ 90% ≥30% - <90% 0% - <30% % Voting for inclusion    8%36%90% OTHER Eg, Performance based Flares Time to Surgery Analgesic Count MD GLOBAL STIFFNESS

37. Pain:WOMAC pain / stiffness subscales Differentiating pain from stiffness Physical function: WOMAC physical function subscale Patient Global Assessment: How to phrase question? Signal joint In all the ways arthritis affects you, how are you doing today? Transition question HRQOL/Utilities:WOMAC Composite Score SF-36 EQ5D / Utilities MD Global Assessment Pain:WOMAC pain / stiffness subscales Differentiating pain from stiffness Physical function: WOMAC physical function subscale Patient Global Assessment: How to phrase question? Signal joint In all the ways arthritis affects you, how are you doing today? Transition question HRQOL/Utilities:WOMAC Composite Score SF-36 EQ5D / Utilities MD Global Assessment Outcome Measures in OA: OARSI Guidelines OMERACT Core Set and ‘Strongly Recommended’

38. WOMAC Scores in OA RCTs: Identifying MCID MCID in WOMAC composite score, Likert scale: Anchored to Patient Global Assessment 12 wk pivotal OA RCTs with Celecoxib: 10.1 [0 – 89] Pain, Stiffness, Physical Fxn: 2.1, 1.2, 6.5 [0 – 20] [0 – 8] [0 – 61] MCID in WOMAC VAS: Anchored to Patient Response to Rx [0-4 Likert scale] 6 wk RCTs OA hip, knee; Rofecoxib v Ibuprofen v PL: Pain, Stiffness, Physical Fxn: 9.7, 10, 9.3 mm, VAS 11 mm VAS for Patient Global Assessment MCID in WOMAC composite score, Likert scale: Anchored to Patient Global Assessment 12 wk pivotal OA RCTs with Celecoxib: 10.1 [0 – 89] Pain, Stiffness, Physical Fxn: 2.1, 1.2, 6.5 [0 – 20] [0 – 8] [0 – 61] MCID in WOMAC VAS: Anchored to Patient Response to Rx [0-4 Likert scale] 6 wk RCTs OA hip, knee; Rofecoxib v Ibuprofen v PL: Pain, Stiffness, Physical Fxn: 9.7, 10, 9.3 mm, VAS 11 mm VAS for Patient Global Assessment Ehrich et al: JRheum 2000;27: 2635-2641 Zhao et al. Pharmacother 1999;19:1269-78

39. Improvement in WOMAC Composite Scores at Week 12 : Pivotal OA RCTs, Celecoxib Improved Scores * P <.05 v placebo * * * * * * * * * * * * MCID = 10.1 (SE=0.4) Zhao et al Pharmacother 1999;19:1269-78

40. WOMAC Physical Function Subscale, knee or hip OA at 12 months: Pivotal RCT, Rofecoxib R = randomization P < 0.05 for all groups; treatment response compared with baseline Cannon GW, et al. Arthritis Rheum. 2000;43:978–987. R = randomization P < 0.05 for all groups; treatment response compared with baseline Cannon GW, et al. Arthritis Rheum. 2000;43:978–987. Mean Change (mm) -30 -35 -25 -20 -15 -10 -5 0 0 R R 2 2 4 4 8 8 12 26 39 52 Week Rofecoxib 12.5 mg Rofecoxib 25 mg Diclofenac 150 mg Rofecoxib 12.5 mg Rofecoxib 25 mg Diclofenac 150 mg Mean baseline = 69.6 mm MCID = 9.3

41. SF-36 in Osteoarthritis RCTs Truth or Validity Domains, especially Bodily Pain discriminated differences/ changes in symptoms over time Closer correlation with patient assessed outcomes Feasibility or Reliability Ceiling effects minimal; floor effects for RP and RE domains Able to detect effects of arthritis in community sample Discrimination or Responsiveness In longitudinal tests, BP domain and PCS summary score most responsive, even within 2-6 weeks Valid and responsive measure of TKR, esp long term Short term treatment → significant improvement in MCS Truth or Validity Domains, especially Bodily Pain discriminated differences/ changes in symptoms over time Closer correlation with patient assessed outcomes Feasibility or Reliability Ceiling effects minimal; floor effects for RP and RE domains Able to detect effects of arthritis in community sample Discrimination or Responsiveness In longitudinal tests, BP domain and PCS summary score most responsive, even within 2-6 weeks Valid and responsive measure of TKR, esp long term Short term treatment → significant improvement in MCS Brooks et al, A+R 1997; 40:S110 Ehrich et al: JRheum 2000;27: 2635-2641 Ware et al: A+R 1996; 39:S90 Bellamy et al, A+R 2000; S221 Ware et al: A+R 1996; 39:S90 Hill et al: JRheum 1999; 26:2029-35

42. PF RPPAINGHP VITALSOCRE MH Mean Improvement in SF-36: All Rofecoxib v Normative Data US Population Improvement Difference between ages 45-54 and 55-64 US population. Ware et al 1993

43. Change in SF-36 Scores at Week 12: OA of knee Pivotal Trial with Celecoxib * * * * * * * * * * * * ** * * * * * * p <.05 v placebo

44. Use of WOMAC and SF-36 in RCTs of OA Conclusions Based on the COX-2 Experience WOMAC Questionnaire reflects clinical improvement consistent with other patient assessed measures Proved valid, reliable and sensitive to change Pain and stiffness subscales reflect symptoms Physical function subscale dominates composite score WOMAC Composite score is a disease specific measure of HRQOL Correlates closely with improvements reported by generic SF-36 Based on MCID calculations, Likert and VAS versions similarly sensitive to change WOMAC Questionnaire reflects clinical improvement consistent with other patient assessed measures Proved valid, reliable and sensitive to change Pain and stiffness subscales reflect symptoms Physical function subscale dominates composite score WOMAC Composite score is a disease specific measure of HRQOL Correlates closely with improvements reported by generic SF-36 Based on MCID calculations, Likert and VAS versions similarly sensitive to change

45. OMERACT 4 SLE Module 1998: Goal To develop consensus on required outcome domains to be assessed in clinical trials in SLE Paucity of data from Randomized Controlled Trials [RCTs]; Most evidence derived from Longitudinal Observational Studies [LOS] To develop consensus on required outcome domains to be assessed in clinical trials in SLE Paucity of data from Randomized Controlled Trials [RCTs]; Most evidence derived from Longitudinal Observational Studies [LOS] Strand et al: J Rheum 1999; 26: 490-497 Smolen et al: J Rheum 1999; 26: 504-507

46. Disease Activity Indices BILAG, ECLAM, LAI, SLAM, SLEDAI Good evidence for validity, discrimination, feasibility in published cohort [LOS] studies Changes in one index correlated with others Recommendation to use index of choice – Computer generation of all 5 indices facilitates: Clinical research efforts: SLICC ESCICIT EURO-LUPUS Exchange of information:interested parties biotech / pharma Some limitations when used as primary outcome measures in RCTs; ongoing efforts to improve Good evidence for validity, discrimination, feasibility in published cohort [LOS] studies Changes in one index correlated with others Recommendation to use index of choice – Computer generation of all 5 indices facilitates: Clinical research efforts: SLICC ESCICIT EURO-LUPUS Exchange of information:interested parties biotech / pharma Some limitations when used as primary outcome measures in RCTs; ongoing efforts to improve

47. Baseline domain scores low in SLE –v. age/gender matched norms for Canada, Norway, UK, US –v. serious medical problems (IDDM, CAD) In cohort studies reflects changes in disease activity measures –  disease activity  in PF, BP, GHP –  disease activity  SF-36 domain scores, esp. PF Decrements in multiple domains correlate with increased disease activity and damage –Immunosuppressive use –ESRD Baseline domain scores low in SLE –v. age/gender matched norms for Canada, Norway, UK, US –v. serious medical problems (IDDM, CAD) In cohort studies reflects changes in disease activity measures –  disease activity  in PF, BP, GHP –  disease activity  SF-36 domain scores, esp. PF Decrements in multiple domains correlate with increased disease activity and damage –Immunosuppressive use –ESRD SF-36: Sensitive to Change in LOS in SLE Gladman et al: J Rheum 1995; 23:1953-5 Gordon et al: A+R 1997; 40:S112 Gladman et al: Clin Exp Rheum 1995; 14:305-8 Stoll et al: J Rheum 1997; 24:309-13 and 1608-14 Fortin et al: Lupus 1998; 7:101-7 Abu-Shakra et al J Rheum 1999; 26:306-9 Thumboo et al J Rheum 1999; 26:97-102 Wang et al J Rheum 2001; 28:525-32 Rood et al J Rheum 2000; 27:2057-9 Vu, Escalante J Rheum 1999; 26:2595-2601

48. Domains Recommended by OMERACT 4 Disease activity: Disease Activity Scores: SLEDAI, BILAG, ECLAM, SELENA SLEDAI, SLAM-R Definitions of Active Nephritis by U/A, 24 hour CCr, proteinuria, «Renal flare» «Major SLE Flare» Damage: ACR/SLICC Damage Index End Stage Renal Disease [ESRD] Doubling of Serum Creatinine Chronicity Index on Biopsy Bone loss due to disease activity and/or corticosteroids HRQOL: SF-36 [Should also include: Adverse events Economic costs including health utilities] Disease activity: Disease Activity Scores: SLEDAI, BILAG, ECLAM, SELENA SLEDAI, SLAM-R Definitions of Active Nephritis by U/A, 24 hour CCr, proteinuria, «Renal flare» «Major SLE Flare» Damage: ACR/SLICC Damage Index End Stage Renal Disease [ESRD] Doubling of Serum Creatinine Chronicity Index on Biopsy Bone loss due to disease activity and/or corticosteroids HRQOL: SF-36 [Should also include: Adverse events Economic costs including health utilities] As reviewed in Schiffenbauer et al: EBM Treatment of SLE; BJR: in press

49. Ankylosing Spondylitis: ASAS A successful and relevant example To be discussed by Robert Landewe Juergen Braun

50. Systemic Sclerosis Workshop: OMERACT 6 Absence of data: Few ‘failed’ RCTs Limited information from LOS Assessment by organ system involvement Renal Cardio-pulmonary Muscle HRQOL Skin GI

51. OMERACT 7 May 12-16, 2004 Asilomar, California Module: RA: Definition of Low Disease Activity Module Updates: Imaging in Ankylosing Spondylitis [ASAS] Working Group on Safety Workshops: Outcome Measures in Psoriatic Arthritis Outcome Measures in Fibromyalgia Outcome Measures in Gout The Patient Perspective in Outcome Measures