Diabetes MultiCenter Research Consortium DMCRC

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Diabetes Multi-Center Research Consortium (DMCRC)

• Coordinating Center
• HMO Research Network DEcIDE Center
• PI Joe Selby, MD
• Co-PI Patrick OConnor MD
• Affiliate Center
• Johns Hopkins University DEcIDE Center
• PI Jodi Segal, MD
• Co-PI Eric Bass, MD

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The Case for CER in Diabetes

• HIGH BURDEN OF DISEASE
• High, rising prevalence of diabetes (gt23 million
  diagnosed cases, 10 prevalence in adults)
• Chronicity life expectancy with diabetes gt20
  years age at diagnosis decreasing
  complication-related morbidities lead to many
  years with high annual costs

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The Case for CER in Diabetes

• UNCERTAINTY ? Variation in Practice
• Multiple therapeutic choices (6 classes of oral
  agents, two classes of injectables)
• Several options are relatively new and costly
• Treatments vary in mechanisms of action,
  relative effectiveness and safety uncertain
• Optimal treatment strategies unclear timing
  of pharmacotherapy treatment targets sequencing
  and combination TX

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The Case for CER in Diabetes

• Complexity in Optimizing Effectiveness
• Self-care, including medication adherence is
  central to effectiveness, but difficult to
  optimize
• Out-of-pocket medication costs interfere with
  medication adherence and self-care
• Blood pressure, lipid control, and aspirin each
  more effective than tight glycemic control in
  preventing most diabetic complications
• Weight management is important, but several
  medication classes cause weight gain

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The Case for CER in Diabetes

• Complexity in Optimizing Effectiveness
• Systems Approaches may enhance self-care and
  improve adherence and care coordination
• Depression common in diabetes, but role of
  depression therapy in improving control unclear
• Role of tight control in preventing CVD
  complications thrown into question in 2008 by
  three RCTs ACCORD, ADVANCE, VADT
• Other adverse consequences of tight control - wt.
  gain, hypoglycemia, fractures
• Benefits may vary by patient age, DM duration

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The Case for CER in Diabetes

• PREVENTION AND EARLY DETECTION
• Reservoir of undiagnosed cases, but the net
  benefits of screening various populations for
  diabetes not entirely clear
• Diabetes can be prevented or postponed by
  lifestyle and/or pharmacotherapy but optimal
  real world programs not fully clarified

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DMCRC Structure
Executive Committee Includes AHRQ,
Coordinating, Affiliate Center Leadership
Data Committee
Methods Committee
Administrative Committee Project Manger
Clinical Committee
Stakeholder Committee
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DMCRC Structure
Executive Committee Includes AHRQ,
Coordinating, Affiliate Center Leadership
Data Committee
Methods Committee
Administrative Committee Project Manger
Clinical Committee
Stakeholder Committee
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Expanded Executive Committee

• Also includes
• Vanderbilt DEcIDE Center Marie Griffin MD, PI
  Comparative Effectiveness of Oral Agents in Type
  2 Diabetes
• RTI DEcIDE Center Suzanne West Ph.D.
  Comparative Effectiveness of Oral Hypoglycemics
  on Chronic Kidney Disease and on Time to
  Initiation of Maintenance Insulin

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DMCRC Work Assignments

• Comparative Effectiveness of Bariatric Surgery
  vs. Usual Care in Type 2 Diabetes (two projects)
• Proposal for New Statistical Briefs - using
  representative data to characterize trends in
  diabetes treatment and outcomes (joint)
• Form and Convene Stakeholders Group (HMORN)
• Form and Convene Data Committee (JHU) with
  HMORN, Vanderbilt, RTI participation
• Comparative Effectiveness Study of Intensive
  Glycemic Control vs. Less Intensive Control in
  presence vs. absence of tight blood pressure and
  lipid control (two projects)

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DMCRC Stakeholder Committee

• Government Agencies AHRQ, NIDDK, CMS, FDA, CDC,
  VA
• Clinicians ACP,AAFP, AADE
• Patients - ADA, individual patient rep.
• Expanded DMCRC Executive Committee

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Stakeholder - Developed Priorities
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Stakeholder - Developed Priorities

• Effectiveness of eliminating co-pay for effective
  drugs (statins, ACE-Is, beta blockers,
  anti-diabetic meds) on outcomes and total drug
  burden?
• Patient reported outcomes, HRQoL in relation to
  therapy
• Optimal timing for metformin initiation on the
  continuum of pre-DM -gt DM
• Best strategies for behavior change. Who should
  do it and where should it be done?
• Understanding patient attitudes toward insulin
  use

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Work Assignment 1

• Health outcomes of bariatric surgery in
  individuals with type 2 diabetes
• HMORN PI David Arterburn MD
• (Group Health Cooperative)
• Johns Hopkins U PI Jodi Segal MD

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WA 1 Primary Aims

• Compare short-term outcomes between patients
  under-going BS and comparable patients who dont
• Resolution of diabetes (no meds, nl FPGs
• Medication use
• BMI Change
• Glycemic, BP, and lipid Control
• Compare longer-term outcomes between patients
  under- going BS and comparable patients who
  dont
• Recurrence of diabetes (abnormal labs or
  re-initiation of diabetes medications)
• Death, hospitalization, re-operation
• Examine differences in these outcomes by type of
  BS Bypass, banding, gastric sleeve

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WA 1 Secondary Aims

• Compare a variety of shorter- and longer-term
  outcomes between patients under- going BS and
  comparable patients who dont (HMORN and JHU)
• Development and progression of CKD and DN
• Development and progression of diabetic
  retinopathy
• Development of incident cardiovascular disease
• Long-term health care utilization
• Incidence of various cancers
• Incidence of osteoporotic fracture
• Incidence of urolithiasis
• Examine differences in these outcomes by type of
  BS Bypass, banding, gastric sleeve

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WA 1 Study Design

• Cohort Study in 180,000 patients with evidence
  of Type 2 diabetes, BMI gt35, aged 18-30
• Note presence of BMI in EMR required
• Approximately 3,100 BS with BMI 2002 08

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WA 1 The Cohort
Enters cohort when T2 DM and BMI gt 35 identified
Bypass
Banding
BS
No BS
Sleeve
No BS
2002-2008
2002-2008
End 2009
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WA 1 Analysis Plan

• Propensity Score (time dependent) calculated for
  each cohort member
• Probabilities associated with each decile of PS
  examined, with possible trimming of very low
  probability deciles
• Modeling of outcomes in remaining cohort examined
  using time-varying predictors for BS and key
  covariates
• For comparisons by type of surgery, separate
  cohort analyses restricted to persons having BS
• Treatment heterogeneity examined by age group,
  presence of prior comorbid conditions

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WA 1 Key Points in Analysis

• Multi-variable models predicting outcome will NOT
  use PS
• For discrete analyses, models will evaluate
  non-proportional (i.e., time-varying hazards)
• Will also examine effect heterogeneity by year of
  surgery and volume of surgeon
• Many more BS patients without pre-surgical BMI,
  who may contribute to some analyses where BMI
  less likely to confound.