1. 1 Sex/Gender and Minority Inclusion in NIH Clinical Research What Investigators Need to Know! Presenter: Miriam F. Kelty, PhD, National Institute on Aging, 2/2006

2. 2 Overview Review and Rationale of Policy Recent Up-Dates & Implications –Definition of Clinical Research –OMB Standards –NIH-Defined Phase III Trials Resources and Getting Help

3. 3 NIH Policy on Inclusion of Women & Minorities in Clinical Research Why does NIH have this policy? –Mandated by Congress, 1993 PL 103- 43 –Ethical principal of justice and importance of balancing research burdens and benefits

4. 4 Public Law PL 103-43 Women and Minorities must be included in all clinical research studies Women and Minorities must be included in Phase III clinical trials & the trial must be designed to permit valid analysis Cost is NOT allowed as an acceptable reason for exclusion NIH to support outreach efforts to recruit and retain women, minorities, and their subpopulations in clinical studies

5. 5 NIH Policy on Inclusion NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research – Amended October, 2001 http://grants.nih.gov/grants/funding/ women_min/guidelines_amended_10 _2001.htmhttp://grants.nih.gov/grants/funding/ women_min/guidelines_amended_10 _2001.htm

6. 6 Updates to Inclusion Policy NIH Definition of Clinical Research New OMB Standards for Data on Ethnicity and Race Further Clarification about NIH- Defined Phase III Clinical Trials

7. 7 NIH Definition of Clinical Research (1) Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, and (d) development of new technologies;

8. 8 NIH Definition of Clinical Research ( continued) (2) Epidemiologic and behavioral studies; (3) Outcomes research and health services research.

9. 9 Update to NIH Policy for Inclusion New OMB Standards OMB Directive 15 Issued 1997 –Racial and Ethnic Standards for Federal Statistics and Administrative Reporting –Effective Date No Later Than January 1, 2003

10. 10 Update to NIH Policy for Inclusion OMB Directive 15 Issued 1997 –Collecting Data by Self-Report: –Two Separate Questions Question 1: Ask about Ethnicity Question 2: Ask about Race WITH OPTION to select more than one racial designation

11. 11 NIH Policy for Inclusion OMB Directive 15 Issued 1997 –Ethnic Categories: Hispanic or Latino Not Hispanic or Latino –Racial Categories: American Indian or Alaska Native Asian Black or African American Native Hawaiian or Other Pacific Islander White

12. 12 OMB Directive 15 1997 Where can you find examples of data collection instruments that use the new OMB standards? –Many examples exist including: PHS 398 Personal Data Form questions 2000 US Census questions –Do not use the 5/01 Inclusion Enrollment Table or Target Table in PHS 398 to collect data from subjects

13. 13 Update to NIH Inclusion Policy NIH-Defined Phase III Clinical Trials –Evidence must be reviewed to show whether clinically important sex/gender and race/ethnicity differences in intervention effect are expected –Plans for valid analysis must be included in the design –Results of analyses must be reported to NIH

14. 14 Requirements for NIH-Defined Phase III Clinical Trials Research plan must include one of the following: –Prior studies support significant differences between subgroups: –Need plans to conduct valid analyses to detect significant differences between sex/gender and/or racial/ethnic subgroups For the purpose of this policy, Significant Difference is defined as a difference that is of clinical or public health importance based on substantial scientific data. This is not the same as “statistically significant difference.”

15. 15 Requirements for NIH- Defined Phase III Clinical Trial Applications OR: –Prior studies support no significant differences between subgroups: Representation as subject selection criterion is not required; however, inclusion and analyses are encouraged

16. 16 Requirements for NIH- Defined Phase III Clinical Trial Applications OR: –Prior studies neither support nor negate significant differences in intervention effect between subgroups: –Plans to conduct valid analyses of the intervention effect in sex/gender and/or racial/ethnic subgroups (Does not require high statistical power) For the purpose of this policy, Valid Analysis means an unbiased assessment that does not require high statistical power and should be conducted for both large and small studies.

17. 17 Instructions in PHS 398 Best source of information for investigators http://grants.nih.gov/ grants/funding/phs398 /phs398.htmlhttp://grants.nih.gov/ grants/funding/phs398 /phs398.html

18. 18 Instructions in PHS 398 Section E: Human Subjects Research Inclusion of Women Inclusion of Minorities Failure to include = Return Application Prior to Review

19. 19 Instructions in PHS 398 Inclusion of Women and Minorities Sections must include: –Subject Selection Criteria & Rationale –Rationale for Any Exclusions –Enrollment dates (start and end) –Outreach Plans for Recruitment –Proposed Composition Using New Tables

20. 20 Instructions in the 398 NIH-Defined Phase III Clinical Trials –Evidence must be reviewed to show whether clinically important sex/gender and race/ethnicity differences in intervention effect are expected –Plans for valid analysis must be included in the design

21. 21 Reviewer Instructions Reviewers evaluate the Inclusion Plans http://grants.nih.gov/grants/peer/hs_review_ inst.pdf Unacceptable plans must be reflected in the priority score

22. 22 Reviewer Instructions for Phase III Clinical Trials Reviewers evaluate inclusion AND analysis plans http://grants.nih.gov/grants/peer/hs_review_ inst.pdf Unacceptable plans must be reflected in the priority score

23. 23 Funding Decisions Applications with Unacceptable Plans cannot be funded – must revise plans!

24. 24 Monitoring Progress Progress Reports must include Cumulative Enrollment –Reported using the Enrollment tables

25. 25 Requirements for NIH- Defined Phase III Clinical Trial Applications Progress Reports need to include Both: –Enrollment Table –Statement in text about progress in data analyses for sex/gender and ethnicity/racial effects.

26. 26 Additional Guidance on New Tables NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical Research http://grants.nih.gov/grants/guide/ notice-files/NOT-OD-01-053.htmlhttp://grants.nih.gov/grants/guide/ notice-files/NOT-OD-01-053.html

27. 27 Additional Guidance on New Tables New Application or Competing Continuation Involving Collection of New/Additional Data –Must use new 5/01 Table

28. 28 Additional Guidance on New Tables New Application or Competing Continuation with No Plans to Collect New/Additional Data –May use Either: New 5/01 Table 4/98 Version of the Inclusion Table –Use form appropriate for your data

29. 29 Additional Guidance on New Tables Non-Competing Applications (Progress Reports) for grants that began before FY 2002 –May use Either: New 5/01 Table 4/98 Version of the Inclusion Table –Use form appropriate for your data

30. 30

31. 31 Complying with the NIH Inclusion Policy Principal Investigators Review Staff and Reviewers Program Staff Grants Management Staff NIH Tracking and Inclusion Committee Congress Public

32. 32 Monitoring Compliance with the NIH Inclusion Policy Annual Comprehensive Report: Monitoring Adherence to the NIH Policy on the Inclusion of Women and Minorities as Subjects in Clinical Research http://www4.od.nih.gov/orwh/inclusion. html

33. 33 Resources and Getting Help PHS 398 Instructions http://grants.nih.gov/grants/funding/ph s398/phs398.html PHS 2590 Instructions http://grants.nih.gov/grants/funding/25 90/2590.htm

34. 34 Resources and Getting Help Inclusion of Women and Minorities – Implementation Page http://grants.nih.gov/grants/fund ing/women_min/women_min.h tm CONTACT IC PROGRAM STAFF!