560 likes | 575 Views
Developing Best Standardized Treatments Carol A. Wallace MD Professor Emeritus, Pediatrics University of Washington School of Medicine Seattle Children’s Hospital and Research Institute Past Chair of CARRA. Disclosures. No disclosures. 8. 6. 4. ( ). IRSG. NWTSG. 2.
E N D
Developing Best Standardized TreatmentsCarol A. Wallace MDProfessor Emeritus, PediatricsUniversity of Washington School of MedicineSeattle Children’s Hospital and Research Institute Past Chair of CARRA
Disclosures • No disclosures
8 6 4 ( ) IRSG NWTSG 2 SWOG Pediatric Division POG CALGB Pediatric Division CCG The National Childhood Cancer Mortality Rate and the Pediatric Cooperative Groups Annual USA Cancer Mortality Rate Children <15 Years Mortality per 100,000, Age- Adjusted COG 1950 1960 1970 1980 1990 2000 2005
Why do we want Best Standardized Treatments? • Standardized treatments result in decreased variation in patient care, which improves quality and outcomes • Enable comparative effectiveness research to identify the safest, most effective and most cost effective treatments • Prevent complications by use of safest possible treatments • Disseminated widely to improve overall standards of patient care
8 6 4 ( ) IRSG NWTSG 2 SWOG Pediatric Division POG CALGB Pediatric Division CCG The National Childhood Cancer Mortality Rate and the Pediatric Cooperative Groups Annual USA Cancer Mortality Rate Children <15 Years Mortality per 100,000, Age- Adjusted COG 1950 1960 1970 1980 1990 2000 2005
A Research Network Can… Improve the standard of care through clinical studies Promote a “culture” of research at Pediatric Rheumatology sites Develop Best Standard Treatments for better patient outcomes
How do we develop Best Standard Care or Standardized Treatments? • Analyze data from large clinical trials • Analyze data from large prospective cohorts followed from initial presentation with detailed information on treatment and outcomes We have neither available data sources…
In the absence of data, one approach is to start with development of “Consensus Standardized Treatment Plans” • Consensus formed; with broad input • Reasonable, common and practical • Facilitate the development of evidence basedBestStandard Treatments by: • Use of large numbers of physicians with collection of patient data • Decreasing treatment variation • Enabling analysis of prospectively collected data
Brian Feldman MD, MSc, FRCPC 2005 Chair JDM committee Won the Friends of CARRA award in 2005 with a Project to develop Consensus Treatment Plans for Moderate JDM
Proposal for Friends of CARRA Sponsored Study—New Onset Treatment--- Step 1 and 2 1. Survey of current practice 2. Consensus conference to determine 1-3 possible treatment protocols
Development of Consensus Standardized Treatments • Not rigorous protocols- but rather menus of standardized treatments • Not perfect or exactly what each physician might do, but what he/she can live with • The goal is to reduce variation so we can treat in a standardized fashion, collect data and compare patient outcomes
Consensus Treatment Plans - Guiding Principles • Evidence-based when possible • Considered the best available literature • Compatible with the current practice • Assessed by surveys • Consensus agreement • Delphi Questionnaires • Nominal group technique
Development of ConsensusStandardized Treatments • Distill what we do- using collective judgment and consensus processes • Forces us to: • Think critically about what we do • Use facts when present, not beliefs or rely on “this is how I always do it” • Emphasis on decreased variation
Comparative Effectiveness Research in Pediatric Rheumatic Diseases: Leveraging CARRA for Improved Child Health In response to NIAMS RFA 05-AR-102 (2009 ARRA funds) “ ” CARRA-
Specific Aims CARRA- • Funding for disease committee chairs and co-chairs to develop multiple standardized treatment plans for use in new onset patients with: JIA, SLE, JDM and localized scleroderma • Use of consensus methodology • Specify of outcome measures, data collection details and time points • Develop mechanisms to enable rapid dissemination and use of the consensus developed treatment plans • Develop analysis plans for the data collected to determine the clinical efficacy and safety of patients treated with these plans
Overall Vision of CARRA- • When a new patient presents, a physician would choose to use one of the standardized treatment plans that most fits what they would normally do • Data would be collected on the patients treated with these standardized treatments • Data would be analyzed to determine the most efficacious treatment with the least side effects • Thru this process, we would create evidence based “Best Standard Treatment”
Consensus Methodology Choices • Convene a panel of experts • NIH model: • Public discussion of questions and evidence before an expert panel, followed by private unstructured deliberations of the panel • Delphi Questionnaire Technique • Nominal Group Technique • Combination of the Delphi Questionnaires and Nominal Group Technique
Delphi Questionnaire Technique • Systematic collection of judgments on a particular topic through a set of sequential questionnaires • First questionnaire is relatively unstructured • F/U questionnaires build on results from the first, with results fed back to respondents • Each subsequent questionnaire becomes more specific as consensus builds • 2-3 questionnaires practical, takes months • Delphi process frequently serves as preliminary work and clarifies questions leading up to a face-to-face consensus conference
Development process for Consensus Treatment Plans ***** Workgroup*****
Development process for Consensus Treatment Plans Review of literature ***** Workgroup*****
Development process for Consensus Treatment Plans Initial CARRA wide surveys to establish current treatment practice patterns for cases of new onset: Systemic JIA SLE nephritis Moderate to severe disease JDM Localized scleroderma ***** Workgroup*****
Treatment of Linear Scleroderma: Survey of Current Practice Case 1:4yo F with 2 mo history of linear scleroderma of lower leg. Lesion crosses ankle and initially had erythematous- violaceous border. Warm with SQ tissue loss. Labs show ESR, other wise normal
Treatment of Linear Scleroderma: Survey of Current Practice 4% use MTX only Case 1:4yo F with 2 mo history of linear scleroderma of lower leg. Lesion crosses ankle and nitially had erythematous- violaceous border. Warm with SQ tissue loss. Labs show ESR 96% use methotrexate (MTX) + corticosteroid (CS) This looks pretty good. But what about treatment specifics? Li et al. J Rheum 2010;37: 175-81
What type of CS were chosen? Case 1: 4 yo F with linear scleroderma of leg 4% do not use CS How about specific CS doses and dosing regimens?
CS use in LS: Dosing regimens and duration 3 main oral CS regimens: -1 mg/kg/d (28) -2 mg/kg/d (18) -0.5 mg/kg/d (11) 4 IV CS regimens: -3d/mo (33) -1/wk (19) -3d/wk (19) -1/mo (5)
MTX Treatment Regimens in LS 13 different initial doses 27 different initial doses and routes
Development process for Consensus Treatment Plans Review of literature ***** Workgroup*****
Nominal Group Technique • 1968 by Delbecq and Van de Ven to formalize and facilitate group decisions • Widely used in government, education, business, health and social services to achieve group decision making • Particularly useful where there is lack of agreement or incomplete knowledge
Nominal Group Technique • Facilitated, structured face to face meeting • Handles individuals with diverse backgrounds and viewpoints • Allows optimal expression of ideas • Balanced participation - no one person can dominate • Final group judgment utilizes mathematical voting techniques (private or public) • “Consensus” is usually 80% agreement (SJIA 78-85%; LSC majority for non med issues, 80% for meds; poly JIA 80%)
NGT – Uses in Medicine • Disease activity and outcome measures in rheumatology: • Improvement adult RA and JIA • Outcome measures in pedi and adult SLE • Disease activity and damage in JDMS • Definitions of flare for JIA • Treatment guidelines: • Coronary artery disease • Cholecystectomy • Total hip replacement • Breast and prostate cancer
CARRA- • Consensus methodologies facilitated and promoted the highest quality team work • However, this is REALLY hard and time consuming!
Common Work • Define the patient characteristics and exclusions for use of the treatment plans • Essential data to be collected • Essential labs to be collected • Key data collection time points • What to do at visits if the patient is better, worse or has an adverse event
Challenges • Steroids • How to standardize dosages and routes • How to standardize steroid tapers • Systemic JIA: • Patient characteristics: how early to allow treatment - may need to treat before fulfilling ILAR criteria for JIA • Include a new medication not yet approved? • SLE: Induction and maintenance, or just induction? • Linear scleroderma: • Lack of outcome measures • Lack of definitions for improvement, worsening
Development process for Consensus Treatment Plans Review of literature ***** Workgroup*****
Initial Consensus Treatment Plans developed for new onset: • Systemic JIA • Steroids • MTX +/- steroids • Anakinra +/steroids • Tocilizumab +/steroids • Juvenile Dermatomyositis • Pred + MTX • Pred + MTX + IV methylpred • Pred + MTX + IV methylpred + IVIG • Renal disease in SLE • Cellcept induction • IV cytoxan induction • Linear Scleroderma • MTX • MTX +Oral steroid • MTX + IV methyl pred
Vision for Implementation of Consensus Treatment Plans • All CARRA members encouraged to use the CTP for appropriate new patients • A CARRA database (registry) would be developed to collect data from patients • Protocol and consent form for the CARRA database (registry) allow for data collection that would cover the basic registry and additional sub-studies.
Data Collection • Parallel to this effort was the development of a large foundational pediatric rheumatology registry: CARRA Registry • 60 participating pediatric rheumatology sites • 9,000 patients enrolled • New CARRA registry • New onset patients treated with one of the Consensus Treatment Plans had specific data collected into the foundational CARRA Registry • Funding secured to pilot the use of these treatment plans and data entry