Application of Principles of Diversity In Clinical Research to Clinical Practice

1. Application of Principles of Diversity In Clinical Research to Clinical Practice William L. Daley, MD, MPHExecutive Director, Cardiovascular-MetabolismUS Clinical Development & Medical AffairsNovartis Pharmaceuticals CorporationEast Hanover, NJ

2. Diversity in Clinical Development • Relationship between research data and clinical practice • Lack of diversity in clinical data and disparity in healthcare • Lack of diversity in clinical data and stereotyping • Diversity in Novartis clinical study populations • Diversity in our clinical trial investigators • Diversity in our clinical development advisors

3. There is a direct relationship between clinical research data and the practice of evidence based clinical medicine

4. Guidelines • AHA guidelines • ISHIB hypertension guidelines • JNC 7 • ADA • NKF • NCEP

5. Lack of Diversity in Clinical Trials Contributes to Disparities in Healthcare:

6. Evidence of Racial and Ethnic Disparities in Healthcare Racial and ethnic disparities are found: • Consistently across wide range of disease areas and clinical services • Even when clinical factors taken into account • Stage of disease presentation, co-morbidities, age, severity of disease, etc. • Across a range of clinical settings • Public and private hospitals, teaching and non-teaching hospitals, etc. • In higher mortality rates among minorities • E.g., Bach et al., 1999; Peterson et al., 1997; Bennett et al., 1995

7. Lack of Diversity in Clinical Data Contributes to Stereotyping

8. Stereotyping: A Definition • The process by which people use social categories (e.g. race, sex) in acquiring, processing, and recalling information about others

9. Stereotyping: Risks Stereotyping can exert… • Powerful effects on thinking and actions at an implicit, unconscious level, even among well-meaning, well-educated persons who are not overtly biased • Influence on how information is processed and recalled • “Self-fulfilling” effects, as patients’ behavior may be affected by providers’ overt or subtle attitudes and behaviors

10. Evidence: Physician Biases & Stereotypes May Influence the Clinical Encounter • Rathore et al. (2000) • Medical students more likely to evaluate a white male “patient” with symptoms of cardiac disease as having “definite” or “probable” angina, relative to a black or white female “patient” with objectively similar symptoms

11. Angiotensin Converting Enzyme (ACEi) Misperception in Blacks

12. “Patients” with hypertension (Schulman et al., 1999)

13. “Patients” with hypertension and angina (Schulman et al., 1999)

14. The 4S Phenomena

15. 4S • Scandinavian Simvastatin Survival Study (4s) • Randomized trial of cholesterol lowering • Population: 4444 males with history of CAD • Objective: Assess the effects of lipid lowering on mortality and cost effectiveness • Exclusion: Premenopausal women

16. Cardiovascular DiseaseThe Leading Cause of Death in US Women in 1999 Total CVD 512,904 Cancer 264,006 Chronic lowerrespiratory diseases 61,766 Diabetes mellitus 37,249 Influenza andpneumonia 36,012 0 100 200 300 400 500 600 Deaths (in thousands) American Heart Association. 2002 Heart and Stroke Statistical Update.

17. What are those principles that are applicable and transferable to improve patient care?

18. “Patient First”Know your patient population

19. Site of Care: Hospital outpatient departments and emergency rooms Source: Medical Expenditure Survey, 1997, as cited in Lillie-Blanton et al., 2001

20. Diversity in Patients • Patients enrolled in a clinical program in the US should reflect prevalence in the US for that disease - at a minimum! • Moreover, in regulatory submissions to FDA, subgroup analyses by age, gender and race are required. Therefore, sufficient numbers of patients must be enrolled to support these analyses.

21. Diversity in Advisors • Ensure appropriate representation on our advisory boards • Ensure appropriate representation on trial committees • Ensure appropriate representation as authors on publications

22. Diversity a the Top • It is imperative that there is a diverse group of healthcare providers and community personnel on committees.

23. Diversity in Investigators • Diversity in trial investigators facilitates enrollment of a diverse patient population • Provides a diverse set of physicians with hands on experience with products • Novartis is partnering with ABC and others to identify minority physicians who are interested in becoming clinical investigators • Novartis has designed new investigator training to be provided to new investigators just prior to participation in a clinical trial. • How do we capture this information on existing investigators?

24. To ensure success,diversity in healthcare providers is essential

25. How are we doing on diversity in clinical trials at Novartis

26. So how are we doing? • Development program for new diabetes drug • Caucasian – 59% • Black – 14% • Hispanic/Latino – 22.5% • Other – 4.5% • Development program for new antihypertensive drug • Caucasian – 62% • Black – 27% • Hispanic/Latino – 7.5% • Other – 3.5% • For marketed antihypertensive and diabetes products • Several trials conducted specifically in Blacks and Hispanics - Patients enrolled in US clinical trial sites

27. Summary: • There is direct relationship between research data and clinical practice • Lack of data in a diverse population can lead to racial and ethnic disparities in health care… • May result from bias, stereotyping, prejudice, and clinical uncertainty on the part of healthcare providers • Clinical practice can benefit from the learning's of the Industry • Know your patients • Diversity on committees • Diversity in healthcare provider

28. Questions ? ? ?