Clinical Practice Guidelines: Implications for Vulnerable Patients Development of Geriatric Diabetes Guidelines

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Clinical Practice Guidelines Implications for
Vulnerable PatientsDevelopment of Geriatric
Diabetes Guidelines

• Arleen F. Brown, MD, PhD
• Associate Professor of Medicine
• Division of GIM and HSR
• UCLA, Los Angeles, CA

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Outline

• Challenges in developing and disseminating
  guidelines meaningful for the care of vulnerable
  patients
• Example of geriatric diabetes guideline
  development
• Strategies for identifying and addressing
  limitations of the literature
• Examples of RCTs that have been used to develop
  care practice recommendations for vulnerable
  populations
• Recommendations for improving the
  trustworthiness of clinical practice guidelines

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Challenges in Developing / Disseminating
Clinical Practice Guidelines Pertinent to
Vulnerable Populations

• Lack of inclusion of typical patients in many
  RCTs and some high quality observational studies
• Clinically dissmilar
• e.g., new onset disease no/few comorbid
  conditions
• Demographically dissimilar
• Under-representation of vulnerable subgroups of
  patients
• Older persons
• Racial/ethnic minorities
• Low income / education / literacy
• Extrapolation from existing data is often
  required
• Double or triple extrapolation
• Where minority or low income patients receive care

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Diagnosed Diabetes Standardized Prevalence
Diabetes Affects Older Persons and Racial/Ethnic
Minorities
Non-Hispanic Whites Non-Hispanic Blacks Mexican Americans
40-59 years
Men 5.5 9.6 11.0
Women 3.7 12.7 12.0
gt 65 years
Men 14.3 29.2 25.6
Women 14.3 28.0 24.3
NHANES 1999-2002, Cowie CC et al.. Diabetes
Care 29(6)1263-1268, 2006
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Prevalence () of Diagnosed and Undiagnosed
Diabetes and Impaired Fasting Glucose (IFG)
Among Adults, Aged 65 years
16 Diagnosed
6 Undiagnosed
40 IFG
39 All others
NHANES 1999-2002, Cowie CC et al.. Diabetes
Care 29(6)1263-1268, 2006
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CHCF/AGS Geriatric DiabetesGuideline Development
Process

• Synthesized and evaluated results from randomized
  controlled trials and observational studies
• Reviewed existing guidelines
• Rated the evidence and guidelines with validated
  consensus panel methods
• Modified existing guidelines and developed new
  guidelines specific to older persons with
  diabetes
• Peer reviewed

JAGS, 51S265-S280, 2003
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CHCF/AGS Geriatric DiabetesGuideline Development
Process

• Synthesized and evaluated results from randomized
  controlled trials and observational studies
• Reviewed existing guidelines
• Rated the evidence and guidelines with validated
  consensus panel methods
• Modified existing guidelines and developed new
  guidelines specific to older persons with
  diabetes
• Peer reviewed

JAGS, 51S265-S280, 2003
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Development of Care Recommendations Required
Extrapolation

• Very little research directed at older, minority
  adults with diabetes
• Required extrapolation from studies of
• Older adults in the general population
• Younger persons with diabetes
• Minority adults with diabetes
• Older minority adults with diabetes
• Developed evidence tables that indicated
• whether older persons / persons with diabetes
  were included in the original studies
• estimated the effect size / number needed to
  treat (NNT) for older persons with diabetes

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Randomized Controlled Trials that Included Older
Adults with Diabetes
CHCF/AGS Guidelines, 2003
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Why We Cannot Always Extrapolate RCT Findings to
Older, Minority Adults with Diabetes

• Clinical Heterogeneity
• Comorbid conditions variation between
  racial/ethnic groups
• Functional status, Cognitive status
• Geriatric Syndromes more common in older adults
  with diabetes
• Polypharmacy Drug-drug or Drug-disease
  interactions
• Depression
• Cognitive Decline
• Injurious Falls
• Life expectancy in relation to
• time to incidence or progression of \
  complications
• time to expected benefit of intervention
• Factors that influence uptake of therapies among
  patients / clinicians
• Patient preferences / Cultural factors
• Socioeconomic factors

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Diabetes Prevention Program (DPP)

• N3234
• Mean age 50.6 years (10.7), 20 gt 60 years
• White 54.7 African American 19.9 Latino
  15.7 American Indian 5.3 Asian / Pacific
  Islander 4.4

Treatment effects varied by age, but not race/ethnicity Treatment effects varied by age, but not race/ethnicity Treatment effects varied by age, but not race/ethnicity Treatment effects varied by age, but not race/ethnicity
Placebo Metformin Lifestyle Modification
Incidence of T2DM ( per year) 11.0 6.8 4.8
Reduction in incidence (vs. placebo) ---- 31 58
25-44 years ---- 44 48
45-59 years ---- 31 59
gt 60 years ---- 11 71

Knowler, NEJM, 2002
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ACCORD Study Action to Control Cardiovascular
Risk in Diabetes

• 10,251 patients
• Mean age 62.2 years (33.9 gt 65 years)
• 64.4 White, 19.7 Black, 4.9 Latino
• Conclusions
• Intensive therapy (Goal A1c lt 6.0) for 3.5
  years
• No reduction in CVD events
• Higher all-cause mortality
• Higher rates of other serious adverse events
• Hypoglycemic and non-hypoglycemic)
• Findings did not vary by race/ethnicity or age

ACCORD Study Group, NEJM 35824.
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BiDil

• BiDil (hydralazineisosobide dinitrate)
• Not efficacious in V-HeFT Trials
• Post hoc subgroup analysis suggested greater
  efficacy in blacks
• A-HeFT - BiDiL reduced mortality in
  African-American patients with advanced heart
  failure. No racial/ethnic comparison group.
• Controversial departure from usual practice
• FDAs stated purpose was to reduce disparities
• Used disparities reduction to create an
  expensive new medication
• Incorporated into the AHA/ACC guidelines for
  symptomatic African American patients, with
  caveats that race is imprecise concept and that
  others may benefit.

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Recommendations for Improving the
Trustworthiness of Clinical Practice Guidelines

• Improve the quality and scope of the evidence
• Increased representation of racial/ethnic
  minority, older, and other potentially vulnerable
  patients
• Rating (or weighting) recommendations to indicate
  the representativeness of the RCT evidence
• Obtain evidence in real world settings to
  improve the feasibility of implementing the
  guideline in heterogeneous clinical settings
• Assist clinicians with understanding the likely
  effect size (e.g. use of NNT) of a proposed
  intervention for important subgroups
• Incorporate time horizon for different subgroups
  (e.g. time to benefit vs. longevity)
• Address patient burden disproportionate effect
  on vulnerable subgroups
• Cost, polypharmacy, competing demands
• Address patient preferences
• Address quality of life

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Time Needed to Benefit

• Microvascular Macrovascular
• Complications Complications
• (Median Years) (Median Years)
• Control of
• Glycemia 4.5 10
• Blood Pressure 4.5 3
• Lipids -- 3 to 6

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Polypharmacy

• Several medications for diabetes Additional
  medications for comorbid conditions
• Polypharmacy may contribute to or exacerbate
  several other geriatric syndromes such as
  depression, cognitive decline, and injurious
  falls
• Quality of life
• Costs of medical care may be prohibitive for
  elders on fixed incomes

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Number of Prescription Medications Used by Older
Adults with Diabetes
Number of Prescription Medications
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Clinical Recommendations

• Screen for physical and cognitive disability
• Look for easily reversible causes of disability
  (e.g. uncorrected visual impairment, untreated
  depression)
• Treat hypertension first
• Treat lipids second
• Aspirin
• Screen for evidence of microvascular disease
• For those with microvascular disease and good
  functional status, apply the younger age targets
  for glycemia
• For everyone else, clinical judgment and patient
  preference should drive choices in the absence of
  evidence
• Consider costs

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Number Needed to Treat (NNT) to Prevent One Event

• DM DM MI CHD CVA
  All-cause
• Endpts Deaths Events
  Deaths Mortality
• Glucose 31 111 46 - 172
  125
• Control1
• HTN 11 20 29
  27 28
• Treatment2
• Lipid Rx (1o)3 6 - 49
• Lipid Rx (2o)3 5 - 13
  149 32

1 UKPDS 33 2 UKPDS 38 3 RCTs of lipid
management with diabetes subgroup analyses
plt0.05
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Prevalence () of Diagnosed and Undiagnosed
Diabetes and Impaired Fasting Glucose (IFG)
Among Adults, Aged 65 years
16 Diagnosed
6 Undiagnosed
40 IFG
39 All others
NHANES 1999-2002, Cowie CC et al.. Diabetes
Care 29(6)1263-1268, 2006