Eliminating Disparities in Clinical Trials

1. Eliminating Disparities inClinical Trials • Dan Bustillos, J.D., Ph.D. (c). • Postdoctoral Fellow, IRB member. • Baylor College of Medicine; • Adjunct Professor of Law, • Health Law & Policy Institute, • University of Houston Law Center

2. Objectives for this presentation • Review the history of human subjects research (HSR) in the “modern” era • Identify the social justice issues • Review Baylor College of Medicine’s E.D.I.C.T. Project

3. HSR Ethics in the 19th Century • While the field of “Medical Ethics” existed in the Nineteenth Century, it roughly followed the same male-centered, paternalistic lines of medical science. • There was no need to ask for a patient’s consent, after all, the physician knew best.

4. HSR Ethics in the 19th Century • This is not to say that these issues weren’t already being vehemently debated. • The first American document dealing with the ethics of human subject research (HSR) was published by William Beaumont in 1833.

5. HSR Ethics in the 19th Century • In 1865, world-renowned French physiologist Claude Bernard said:“never [perform] on man an experiment which might be harmful to him to any extent, even though the result might be highly advantageous to science.”-An Introduction to the Study of Experimental Medicine (1865)

6. Setting the stage • Late 1800s: Darwinian evolutionary theory devolves into “Social Darwinism” • a thinly-veiled racism. • Many men of medical science see women, children, the disabled, and minority racial groups as akin to the animals whose most noble purpose is to serve mankind as research subjects.

7. HSR Ethics in the 19th Century • 1880-1910: African-American myth of “Night Doctors” traced to fears of medical experimentation in the years following the Civil War. • 1891: “Infecting” healthy breast tissue with cancerous grafts to determine if cancer was contagious.

8. History of Research on the Disadvantaged • Early in the Twentieth Century, some physicians cited the “considerable cost” of acquiring and maintaining animal research subjects, to justify experimentation on orphaned children instead. • Orphans, the mentally disabled, and foreign immigrants were often exploited at the turn of the century.

9. Legal Bases for Research Participant Protections • 1914: Schloendorff v. Society of New York Hospital, • Justice Benjamin Cardozo: “Every human being of adult years and sound mind has a right to determine what shall be done with his own body.” • Established the doctrine of assault for unauthorized or unconsented to medical intervention.

10. Legal Setbacks for HSR Protections • In 1902, bills were introduced to regulate human subject research in America. • Arguing that this would stunt medical progress, the bills were defeated.

11. Informed Consent • The birth of “informed consent”: Walter Reed’s yellow fever experiments in Cuba and Panama. • Unfortunately, the documents de-emphasized the risks and exaggerated the inevitability of naturally contracting the disease.

12. HSR’s “Golden Age” • 1900-1940s: Medical research flourishes in America. • While many protest scientific abuse, America is caught up in a progressivist, industrial age whose medical discoveries appear as being fueled by little regulation. • Medical Triumphalism rules the day

13. Tuskegee Study

14. The last 100 years • Tuskegee Syphilis study begins: 1932 • Nazi experiments in WWII. • Nuremburg Trial: 1946 • The Nuremburg Code1947 • Thalidomide tragedy 1960s • Tuskegee study exposé 1972 • The Belmont Report 1979 • Consolidated HHS/FDA regulations: 1981 • Common Rule: 1991

15. The Pendulum Swing • While originally the disadvantaged (women, children, poor, immigrant, physically and/or mentally challenged, etc.) composed a far too great percentage of those enrolled in medical research, now the pendulum has swung in the opposite direction.

16. The Pendulum Swing • 1993: NIH Revitalization Act: • Mandated the inclusion of Women and Minorities in Clinical Trials. • Designed to bring the “Pendulum” back to the center. • Designed to enhance the science.

17. The Pendulum Swing • 1997: FDA Modernization Act: • Required that the Director of Center for Drug Evaluation and Research (CDER) convene a working group to advise on the problem of underrepresentation in clinical trials. • Conclusion: “...[T]he working group does not find evidence of barriers to the enrollment of minorities in clinical trials that are regulatory in nature or could be addressed by regulatory guidance.”

18. Project EDICT • A 4-year collaboration between BCM, Intercultural Cancer Council. • Funded by Genentech, Inc.

19. Organizing Framework: • The Three “R’s”: • Recruitment - In addition to issues of active recruitment, this “R” also includes issues of access. • Retention - Keeping participants satisfied and “on protocol.” • Return - Giving back to our participant populations.

20. Recruitment: • The 2005 AHRQ report on the recruitment of underrepresented populations to cancer clinical trials identified 118 barriers to effective recruitment including barriers to opportunity, awareness, and acceptance. Only 59 promoters of enrollment were identified in the literature. • There is a lack of effective recruitment stratagies reported in the literature • There is also a lack of relevant clinical trial availability for these groups

21. Retention: • While there are few studies devoted to the problem of retaining the underrepresented in clinical trials, there remains plenty of room for policies that enhance the overall experience of participants in clinical trials and remove all manner of barriers to their continued participation. • E.g.: Culturally-appropriate care.

22. Return: • Should the clinical trial enterprise provide for the continued benefit to underrepresented populations and their communities? • Should communities that make medical research possible be rewarded for their participation with continued access to FDA-approved drugs and biologics?

23. Return: • The clinical trial enterprise should forge relationships with under-represented communities. • These bonds can then be a platform from which future patients will be encouraged to participate in clinical trials. • This will in turn benefit the clinical trials enterprise; a symbiotic relationship is formed.

25. We conducted a thorough literature review in the areas of law, ethics, and policy. We convened a large “Roundtable” comprised of 150 stakeholders. Diversee perspectives enriched the dialogue. The Roundtable spawned 10 “Opportunity Teams” organized around different facets of the issue. A Year Into The Project:

26. Our Policy-oriented working groups (Opportunity Teams) will craft policy recommendations by Fall of 2007. Next phase begins: Policy Dissemination/ Implementation phase. April 2008: Large-scale Public Rollout of policy recommendations/ EDICT Recognition Program /Policy successes, at ICC Biennial Conference, DC The Next Year Of The Project: