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Sex/Gender and Minority Inclusion in NIH Clinical Research

What Investigators Need to Know!

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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

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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

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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

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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.htm

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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

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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;

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NIH Definition of Clinical Research

(continued)(2)  Epidemiologic and behavioral studies;

(3)  Outcomes research and health services

research.

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Instructions in PHS 398

• Best source of information for investigators

• http://grants.nih.gov/grants/funding/phs398/phs398.html

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Instructions in PHS 398

• Section E: Human Subjects ResearchInclusion of WomenInclusion of Minorities

• Failure to include = Return Application Prior to Review

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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

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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

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Funding Decisions

• Applications with Unacceptable Plans cannot be funded – must revise plans!

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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

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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

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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

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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 to collect data from subjects

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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.html

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Additional Guidance on New Tables

• New Application or Competing Continuation Involving Collection of New/Additional Data

– Must use new 5/01 Table

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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

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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

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Principal Investigator/Program Director (Last, first, middle):

PHS 398/2590 (Rev. 05/01) Page _______ Inclusion Enrollment Report Format Page

Inclusion Enrollment Report Table This report format should NOT be used for data collection from study participants.

Study Title: Total Enrollment: Protocol Number:

Grant Number:

PART A. TOTAL ENROLLMENT REPORT: Number of Subjects Enrolled to Date (Cumulative) by Ethnicity and Race

Sex/Gender Ethnic Category

Females Males Unknown or

Not Reported Total

Hispanic or Latino **

Not Hispanic or Latino Unknown (Individuals not reporting ethnicity)

Ethnic Category: Total of All Subjects* *

Racial Categories

American Indian/Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

More than one race

Unknown or not reported

Racial Categories: Total of All Subjects* *

PART B. HISPANIC ENROLLMENT REPORT: Number of Hispanics or Latinos Enrolled to Date (Cumulative)

Racial Categories Females Males Unknown or

Not Reported Total

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

More Than One Race

Unknown or not reported

Racial Categories: Total of Hispanics or Latinos** ** * These totals must agree. ** These totals must agree.

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4/98 INCLUSION TABLE

This report format should NOT be used for data collection from study participants.

Principal Investigator/Project Director _____________________________________________________ (Last, First, Middle) Grant Number (if known): ____________________________ STUDY TITLE: _______________________________________________________________________________ Total Enrollment: ________________________ Protocol Number: ____________________________

American Indian or

Alaskan Native Asian or

Pacific Islander

Black, not of Hispanic Origin Hispanic

White, not of Hispanic Origin

Other or Unknown Total

Female

Male

Unknown

Total

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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

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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.”

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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

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Requirements for NIH-Defined Phase III Clinical

Trial ApplicationsOR:

– 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.

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Reviewer Instructions for Phase III Clinical

Trials• Reviewers evaluate inclusion

AND analysis planshttp://grants.nih.gov/grants/peer/

hs_review_inst.pdf

• Unacceptable plans must be reflected in the priority score

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Funding Decisions for Phase III Clinical Trials• Applications with Unacceptable

Plans cannot be funded – must revise plans!

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Requirements for NIH-Defined Phase III Clinical

Trial Applications• Progress Reports need

to includeBoth:– Enrollment Table– Statement in text about

progress in data analyses for sex/gender and ethnicity/racial effects.

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Complying with the NIH Inclusion Policy

• Principal Investigators• Review Staff and Reviewers• Program Staff• Grants Management Staff• NIH Tracking and Inclusion

Committee• Congress• Public

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Monitoring Compliance with the NIH Inclusion

PolicyAnnual 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

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Resources and Getting Help

• PHS 398 Instructionshttp://grants.nih.gov/grants/funding/phs398/phs398.html

• PHS 2590 Instructionshttp://grants.nih.gov/grants/funding/2590/2590.htm

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Resources and Getting Help

• Inclusion of Women and Minorities – Implementation Page

http://grants.nih.gov/grants/funding/women_min/women_min.htm

• CONTACT PROGRAM STAFF!