Measuring Patient Outcomes:

Transcription

1 Measuring Patient Outcomes: Interplay of science, policy and marketing Chapel Hill, November 22, 22 Dr. Claire Bombardier Professor of Medicine, University of Toronto Senior Scientist, Institute for Work & Rheumatologist, Mount Sinai Hospital, and University Network Toronto, Canada 1. Purpose and models of outcomes 2. Standardization of outcomes 3. Stakeholders interests and goals Scientists Policy-makers (regulatory, reimbursement agencies) Providers (Pharma, HMO ) 4. Current and future challenges 1 2 Short Term vs Long Term Short term: Clinical trials ethics of placebo and weak drugs Drop out rates (median drug survival < 2years) Long term: Monitoring the course of disease Outcome measures progress relatively slowly 3 Years 15 Development of a Successful New Drug Source: PhRMA Development Basic Research Introduction Registration (Total Cost ~$8 mm) to 2 Substances 5, - 1, Substances J. DiMasi, 21 Product Surveillance Clinical Tests (Human) Preclinical Tests (Animal) Synthesis Examination & Screening Phase IV Phase III Phase II Phase I 4 Implementing a New Innovation into Practice Entire Phase IV Population What Is an Outcome? Years 15 Long-term Surveillance Introduction To Market Development 5 Early Majority Early Adoptors Champions Preclinical & Clnical Testing Phase III Phase II Phase I Product Surveillance That which represents the goal of all treatments: "to make the patient better" - Fries, 1993 Source: PhRMA C. Bombardier, 22 5 Institute for Work &, 2 6

2 Choice of a Drug Based on Cost-Effectiveness Usual Drug Outcomes EXPECTED Effectiveness/Safety Costs Cost What do we know about effectiveness? New Drug Effectiveness/Safety Cost Least Cost Drug Effectiveness/Safety Cost 7 8 Efficacy versus Effectiveness Efficacy: The extent to which a specific intervention produces a beneficial effect under ideal conditions Usually based on results of randomized clinical trials Effectiveness: The extent to which a specific intervention produces beneficial effects when used in the community. Usually based on results of observational studies 9 study design What Can be Learned from Various Study Designs? Course of disease Loss of Toxicity care productivity utilization Clinical trial X XXX X XX X X Observational study Efficacy Effectiv eness XXX X XXX XX XXX XXX 1 Measures of Outcome Model 1. Which Outcome Do You Want to Measure? X-Ray damage Nerve conduction Range of motion Pain Stiffness Ability to perform specified tasks Patients subjective global rating 11 12

3 Measures of Outcome Model SF-36 Two-Component Factor Model Characteristics of Individual Values Preferences Physical Function Role Physical Bodily Pain Physic Component Mental Component Mental Role Emotional Social Function Characteristics of Environment Non-clinical factors Vitality Work Productivity condition Self Report / SF-36 Sickness Impact Profile Quality of Well-being Impairment radiographic damage pain stiffness Activity Limitations ability Participation restriction Roles Productivity Loss Indicators Number of disability days Self-rating of percent effectiveness at work Environmental Factors Conceptual relationship ICF -2 Personal Factors Purpose and models of outcomes Standardization of outcomes Stakeholders interests and goals Scientists Policy-makers (regulatory, reimbursement agencies) Providers (Pharma, HMO ) Current and future challenges 17 American College of Rheumatology (ACR) Core Set Tender joint count Swollen joint count Pain assessment MD global assessment Patient global assessment Patient self-assessment of disability ESR or CRP Felson DT, Anderson JJ, Boers M, Bombardier C et al. The American College of Rheumatology preliminary core set of disease activity measures for use in rheumatoid arthritis clinical trials. Arthritis & Rheum 1993;36(6):

4 1. Which Outcome Do You Want to Measure? Comparative Efficacy of Second-Line Drugs for RA Tender joints Swollen joints ESR or CRP Pain Ability to perform specified tasks Patients & MD subjective global rating 6 5 MTX LEF SSZ D-Pen IM Gold AZ HCQ CsA Oral Gold 19 Modified from Felson et al. Arthritis Rheum 1995;38:S283 2 Tender jts, ESR, grip strength A proposed "core set" of instruments for clinical researchers Domain Pain symptoms Back-related function Generic well-being Satisfaction with care Specific instrument Bothersomeness or severity and frequency of low back pain and leg pain (sciatica) Roland and Morris Disability Scale, or Oswestry Disability questionnaire (SF-12) SF-36; also, "If you had to spend the rest of your life with the symptoms you have right now, how would you feel about it?" Single question on overall satisfaction (optional) 1. Which Outcome Do You Want to Measure? Pain Ability to perform specified tasks Patients subjective global rating Deyo et al, Spine 1998; 23: Bombardier, Spine 2; 25: 31 Deyo et al, Spine 1998; 23: Bombardier, Spine 2; 25: 31 Rheumatoid Arthritis Disease activity score over time Illustrating a patients response to injections of new biologic medication Includes: tender joint count, swollen joint count, sedimentation rate, global assessment Definition of ACR2 Response Worse Remission Better DAS: Disease Activity Score DAS28 =.56 * sqrt(tender28) +.28 * sqrt(swollen28) +.7 * ln(esr) * GH Source: 2% or greater improvement in Tender joint count Swollen joint count Three of the following five Pain assessment MD global assessment Patient global assessment Patient self-assessment of disability ESR or CRP Arthritis Rheum 1995;38:

5 Efficacy 1 of biologics and leflunomide when added to methotrexate % ACR 2 responders Hochberg et al.ann Rheum Dis 21;6:iii Cyclosporin Etanercept Infliximab Leflunomide 1 at 24 to 3 weeks Active drug Placebo iii Efficacy 1 of biologics and leflunomide when added to methotrexate % ACR 5 responders Etanercept Infliximab Leflunomide Anakinra 1 at 24 to 3 weeks 26 6 Hochberg et al. EULAR Abstract, Active drug Placebo Purpose and models of outcomes Standardization of outcomes Stakeholders interests and goals Scientists Policy-makers (regulatory, reimbursement agencies) Providers (Pharma, HMO ) Current and future challenges 27 1 Ontario Survey 1 Duke Profile 1 Nottingham Profile 1 SF-36 1 Sickness Impact Profile Physical Function Score Clinical Dimensions Beaton et al. Am J of Ind Med 1996;29: Sensitivity of Clinical Change YOUR TOOL CAN COLOUR YOUR RESULTS Overall 5 Generic Measures Pain Physical Standardized Response Mean* 29 SF36 Nottingham Duke Ontario Survey Sickness Impact * Standardized Response Mean = Mean(test2 - test1)/standard Deviation(test2 - test1) Beaton et al. J Clin Epidemiol 1997;5(1)

6 Physical function: generic vs disease specific Low Back Lower Extremity Upper Extremity Standardized Response Mean, SF-36 Disease-specific 95% confidence Purpose and models of outcomes Standardization of outcomes Stakeholders interests and goals Scientists Policy-makers (regulatory, reimbursement agencies) Providers (Pharma, HMO ) Current and future challenges Beaton et al. Arthritis & Rheum 1995;38(9 Suppl):S Goals of Treatment of RA FDA Guidance for Industry: Response Over Time vs Landmark Treatment of active rheumatoid arthritis to: 1. Improve signs and symptoms 2. Retard joint destruction 3. Improve functional ability 4. Lessen disability 5. Improve health-related quality of life 33 Methods that evaluate response over time are preferable to methods that incorporate only the baseline and final observation. Food and Drug Administration (FDA( FDA) Primary Signs and s Endpoint ACR-N AUC Mean ACR-N Enbrel 25 mg MTX Months P=.2 over 6 months P=.9 over 12 months An example: visual analog scale used as a primary outcome measure in a randomized trial of a new anti-inflammatory drug: Rofecoxib Max MTX dose 35 36

7 Results: Low Back Pain Intensity Scale (VAS) Mean change from baseline (± SE) Protocol 12 Protocol 121 S R Study week Placebo p<.1 rofecoxib vs placebo Rofecoxib 25 mg Mean change from baseline (± SE) S R Study week Rofecoxib 5 mg Ju et al, AAPM Presentation Katz et al, APS Presentation 21 Anakinra Monotherapy Study Total Productivity Days Gained Over 24 Weeks Days Placebo 3 mg 75 mg 15 mg All Anakinra Study Week p-value <.5 for comparison with placebo Productivity measured as work and domestic activity * * 38 Bresnihan, B et al. EULAR 21 Abstract SAT242 Drug Industry Seeks Cure Through Marketing Dancing With the Porcupine The industry will become increasingly reliant on costly marketing plans, and relatively less on its research operations. But the drug industry still spends far more on salespeople than it does on scientists. Its army of nearly 7, U.S. Salespeople costs $7-billion a year. Clinical Research & the University-industry Relationship The Wall Street Journal July, CMAJ Madison ave plays growing role in drug research You cannot separate their advertising and marketing from the science anymore. New Engl J Med Dr Arnold Relman, Prof emeritus Harvard Medical School Former editor NEJM 42 NYT, November 22, 22

8 Response: Patient Satisfaction Scale (PSS) 1 items assessing satisfaction with aspects of care Information Emotional support and assurance Effectiveness of prescribed medication Does not include: Access to care Coordination among caregivers Involvement in decision-making Trust in one s clinician Satisfaction with the outcome of care Global question assessing satisfaction with outcome of care All things considered, how satisfied are you with the results of your treatment for back pain.. Response: Strongly agree Strongly disagree 43 Extremely satisfied Very satisfied Somewhat satisfied Mixed dissatisfied Somewhat dissatisfiedv Very dissatisfied Extremely dissatisfied 44 Purpose and models of outcomes Standardization of outcomes Stakeholders interests and goals Scientists Policy-makers (regulatory, reimbursement agencies) Providers (Pharma, HMO ) Current and future challenges 45 Issues in defining a responder Minimally clinically important difference (MCID) % change Minimally clinically important threshold (MCIT) Pain Baseline 2 weeks 4 weeks 3 months 1 year Group 1 Group 2 16 MCID (2%) 16 MCID (4%) MCIT 46 Thank You claire.bombardier@utoronto.ca