1. Clinical Practice Guidelines: Implications for Vulnerable Patients Development 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 Non-Hispanic Whites Non-Hispanic Blacks Mexican Americans 40-59 years Men5.5%9.6%11.0% Women3.7%12.7%12.0% > 65 years Men14.3%29.2%25.6% Women14.3%28.0%24.3% * NHANES 1999-2002, Cowie CC et al.. Diabetes Care 29(6):1263-1268, 2006

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

6. CHCF/AGS Geriatric Diabetes Guideline 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 Diabetes Guideline 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% Treatment effects varied by age, but not race/ethnicity: PlaceboMetforminLifestyle 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% > 60 years----11%71% Knowler, NEJM, 2002

12. ACCORD Study Action 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 (Median Years) Control of: Glycemia4.5 10 Blood Pressure4.5 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 DeathsEvents DeathsMortality Glucose 31*111 46 - 172 125 Control 1 HTN 11* 20 29 27* 28 Treatment 2 Lipid Rx (1 o ) 3 6* - 49 Lipid Rx (2 o ) 3 5* - 13* 149* 32 1 UKPDS 33; 2 UKPDS 38; 3 RCTs of lipid management with diabetes subgroup analyses * p<0.05

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