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

1. 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

2. 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

3. 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

4. Diagnosed Diabetes – Standardized Prevalence Diabetes Affects Older Persons and Racial/Ethnic Minorities * NHANES 1999-2002, Cowie CC et al.. Diabetes Care 29(6):1263-1268, 2006

5. Prevalence (%) of Diagnosed and Undiagnosed Diabetes and Impaired Fasting Glucose (IFG) Among Adults, Aged 65+ years* ~ 6 in 10 16% Diagnosed 6% Undiagnosed 40% IFG 39% All others * NHANES 1999-2002, Cowie CC et al.. Diabetes Care 29(6):1263-1268, 2006

6. 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, 51:S265-S280, 2003

7. 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, 51:S265-S280, 2003

8. 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

9. Randomized Controlled Trials that Included Older Adults with Diabetes CHCF/AGS Guidelines, 2003

10. 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

11. Diabetes Prevention Program (DPP) • N=3234 • Mean age 50.6 years (10.7), 20% > 60 years • White 54.7%; African American 19.9%; Latino 15.7%; American Indian 5.3%; Asian / Pacific Islander 4.4% Knowler, NEJM, 2002

12. ACCORD StudyAction to Control Cardiovascular Risk in Diabetes • 10,251 patients • Mean age 62.2 years (33.9% > 65 years) • 64.4% White, 19.7% Black, 4.9% Latino • Conclusions: • Intensive therapy (Goal A1c < 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; 358:24.

13. BiDil • BiDil (hydralazine+isosobide 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 • FDA’s 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.

14. 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

17. 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

18. 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

19. Number of Prescription Medications Used by Older Adults with Diabetes Number of Prescription Medications

20. 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

21. 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 * p<0.05

22. Prevalence (%) of Diagnosed and Undiagnosed Diabetes and Impaired Fasting Glucose (IFG) Among Adults, Aged 65+ years* ~ 6 in 10 16% Diagnosed 6% Undiagnosed 40% IFG 39% All others * NHANES 1999-2002, Cowie CC et al.. Diabetes Care 29(6):1263-1268, 2006