# Presentation: 278309

## OHRP/OPRR(http://grants.nih.gov/oprr/oprr.htm)

**OFFICE FOR HUMAN RESEARCH PROTECTIONS, DHHS**
*formerly*
**OFFICE FOR PROTECTION FROM RESEARCH RISKS, NIH**
**SBIR/STTR: HUMAN SUBJECT REQUIREMENTS**
**(****http://grants.nih.gov/grants/oprr/humansubjects/assurance/sbirsttr/requirements.htm****)**
**Clifford C. Scharke, D.M.D., M.P.H.**
**July 11, 2000**

## Introduction and Overview

**Why   -  Concepts**
**When -  Applicability **
**What  -  Process**
**How   -  Resources**
**Who   -  Human Assistance**
**Wow  -  Things That Can Go Wrong**

## Concepts

**Volunteers - Human Subjects**
**Permission - Informed Consent**
**Oversight - Institutional Review Boards**
**Documentation - Assurance and Records**
**Self-Interest - What’s it to you?**

## Volunteers - Human Subjects

**Other people and their private information don’t belong to the PI **
**The sheer value of the research does not automatically trump rights of people **
**Ask before you take unless IRB approves**
**Definition of a human subject**

## Definition of a Human Subject

**Human subject**** means a living individual about whom an investigator (whether professional or student) conducting research obtains:**
**  ****data through ****intervention**** or **** interaction****  with the individual, or**
**  ****identifiable private information**

## Permission - Informed Consent

**From the Nuremberg Code on, the right to say “no” is the first right of a subject**
**Permission of a duly informed volunteer is required unless the IRB says otherwise**
**Volunteers who are not of legal age for the intended procedure must also grant permission (if they’re able to do so)**
**Definitions of consent and assent**

## Definitions of Consent and Assent

- Consent - legally effective agreement of the subject or the subject's legally authorized representative based on information that is given to the subject or the representative in language that is understandable
- Assent - child’s affirmative agreement to participate in research
- Permission - agreement of parent(s) or guardian to the participation of their child or ward in research

## Oversight - Institutional Review Boards

**A local and objective review panel**
**Voting members are free of conflict**
**Suitably composed for subject context**
**Competent for review of science & ethics**
**Adequate in number and composition**
**Definitions of IRB and Local Review**

## Oversight - Institutional Review Boards

**IRB**** - an ****Institutional Review Board**** established in accord with and for the purposes expressed in 45 CFR 46 (**http://grants.nih.gov/grants/oprr/humansubjects/45cfr46.htm#46.102**) **
**Local Review**** - an IRB that possesses ****sufficient knowledge**** of the ****local research context**** ****(see guidance found at ****http://grants.nih.gov/grants/oprr/humansubjects/guidance/local.htm****)**

## Documentation - Assurance and Records

**Prior written promise to meet minimum Federal standards to protect subjects**
**IRB minutes in required detail**
**Ongoing IRB certification and enduring records of all required reportable events**
**If it isn’t documented, it didn’t happen**
**Definitions of Assurance and Records**

## Documentation - Assurance and Records

**Assurance**** - a ****legally binding written document**** that commits a public or private ****entity**** to compliance with applicable ****Federal minimum standards**** for the protection of human subjects ****prior to engagement**** in Department or Agency conducted or supported research (i.e., ****prior binding promise to follow applicable rules****) and includes citation of ****ethical principles****, ****designated IRB****, list of ****IRB members****, ****IRB procedures,**** and institutional and investigator ****responsibilities**

## Documentation - Assurance and Records

**Records**** - **An institution, or when appropriate an IRB, shall prepare and maintain:
**Copies of all ****research proposals**** reviewed, any ****scientific evaluations****, ****approved sample consent documents****, ****progress reports**** submitted by investigators, and ****reports of injuries**** to subjects**
**Minutes of IRB meetings**** which shall be in sufficient detail to show attendance; actions taken; the vote on these actions; the basis for requiring changes in or disapproving research; and a written summary of the discussion of controverted issues and their resolution**

## Documentation - Assurance and Records

**Records**** - **An institution, or when appropriate an IRB, shall prepare and maintain:
**Records of continuing review activities**
**Copies of all ****correspondence**** between the IRB and the investigators**
**A ****list of IRB members**** in the same detail as described in §46.103(b)(3)**
**Written procedures for the IRB**** in the same detail as described in §46.103(b)(4) and §46.103(b)(5).**

## Self-Interest - What’s it to you?

**Valid research is ethical research**
**Rules that protect subjects protect the PI**
**PI integrity is measured by compliance**
**The reputation of the PI’s institution is at stake**
**Future funding can be jeopardized**
**Funding authority credibility can be questioned**
**As goes the public’s trust, so goes research**

## Applicability

**Research**** - a ****systematic**** investigation, including research development, testing and evaluation, ****designed**** to develop or contribute to ****generalizable**** knowledge (regardlesss of what it might be called) ****(****http://grants.nih.gov/grants/oprr/humansubjects/45cfr46.htm#46.102****)**
**Human subject  +  DHHS research  -  Exemptions ****(****http://grants.nih.gov/grants/oprr/humansubjects/guidance/decisioncharts.htm****)**** **
**Awardees**** of DHHS-supported human subject research and ****all entities**** that ****interact**** with, ****intervene**** upon, or have potential access to ****private identifiable information**** of ****living persons**** are ****engaged**** and are required to possess an applicable Assurance prior to human subjects ****(****http://grants.nih.gov/grants/oprr/humansubjects/assurance/engage.htm****)**

## Process

**Preparation - it’s never too early to consult with the population, institutions, and IRB Chair(s) when planning the research design**
**Pre-application - Assurance and IRB approvals are **_***not***_** required (needed prior to any award)**

## Process

**SBIR/STTR Application entries - don’t miss:**
**Face Page/Item 4**** - leave IRB date blank and do **_***not***_** enter Assurance number for the institution with the designated IRB (enter “None”); if **_***applicant***_** possesses a Multiple Project Assurance, then enter either an IRB date or “Pending” and applicable MPA number ****(****http://grants.nih.gov/grants/funding/sbirsttr1/11instructions.htm#11b****)**
**Research Plan/Item G**** - respond to all numbered items or, if exemption claimed, explain (see below) ****(****http://grants.nih.gov/grants/funding/sbirsttr1/11instructions.htm#11b****)**
**Human Subjects**** - exemptions and investigator’s role ****(****http://grants.nih.gov/grants/funding/sbirsttr1/11instructions.htm#11j****)**

## Process

**Pre-award assurance to comply with 45 CFR 46**
**Applicant will be notified in writing of award**
**Award held until Assurances confirmed for:**
** ****Awardee**
** ****All sites engaged in human subject research**
**Funding authority notifies OHRP/OPRR**
**OHRP/OPRR seeks Assurances through PI**
**Awardee/PI need not contact OHRP/OPRR**

## Resources

**Sneak Preview - OHRP/OPRR’s request; review in detail to be ready and then wait ****(****http://grants.nih.gov/grants/oprr/humansubjects/assurance/spainfo.htm****)**
**Options to finding an IRB to designate:**
**Establish your own (potential conflicts) **
**Rely on suitable IRB of  a collaborating site**
**Locate willing MPA institution near subjects ****(****http://grants.nih.gov/grants/oprr/library_human.htm#ASS****)**** **
**Seek out an independent IRB that is “local” ****(****http://grants.nih.gov/grants/oprr/humansubjects/guidance/local.htm**)

## Resources

**OHRP/OPRR Website ****(****http://grants.nih.gov/grants/oprr/oprr.htm****) - ****seek, find, and fill needs**
**Belmont Report (ethical principles)**
**IRB Guidebook (topics of interest to PIs)**
**Training Video-tapes and Workshops**
**Links to other Websites**
**Commercial Institutional Review Boards ****(****http://www.himanet.com/irb.htm****) - **_***not***_** endorsed by OHRP/OPRR  ****URL provided as a courtesy; not all listed IRBs necessarily conform to OHRP/OPRR “local” IRB and conflict-free requirements ****(****http://grants.nih.gov/grants/oprr/humansubjects/guidance/local.htm****)**

## Human Assistance

**IRB Chair**
**Pre-protocol planning to enhance and prevent problems**
**Arrange for investigator training to preserve integrity**
**Advice on exemptions and expedited review**
**Expertise on human subject issues**
**Referral to other sources of expertise**
**OHRP/OPRR Staff **
**	****(****http://grants.nih.gov/grants/oprr/ab-staff.htm#Table1****)**
**General SBIR/STTR questions - Helen Gordon**
**Assurance negotiation - Assurance Coordinators (ACs)**** ****(****http://grants.nih.gov/grants/oprr/ab-staff.htm#Table2****) **
**	****Note: Click on geographic location of awardee for correct AC**

## Things That Can Go Wrong

**Doesn’t see PI and subject interests are same**
**Investigator waits too long for IRB input**
**Underestimates the value added by the IRB to the integrity of the process and reputation of all**
**PI’s unaware of accrual restrictions by funding authority or erroneous lack until it’s too late**
**PI falls victim to miscellaneous investigator shortcomings (e.g., special protections, protocol revisions, adverse events, and progress reports)**** ****(****http://grants.nih.gov/grants/oprr/findings.pdf****)**

## Conclusions

**Volunteers grant permission with IRB oversight that is assured in advance**
**Prepare early for human subject issues**
**Know when and from where to get help**
**Prepare your application with confidence**
**Let the system work for you; know when it isn’t & confirm with funding authority**
**What’s good for subjects is good for you!**