Stanford University
Research Compliance Office
46.111(a)(3)
Reviewer Tool - Medical
Considerations for Review
45 CFR 46.111 [OHRP]*
AID-17
Purpose of Study: (eP 1)
 The study likely to achieve its aims/feasibility of research
 What is the importance of the knowledge
 Need for human subjects
46.111(a)(1)(i) Description of Study Background (eP 3(a) and (b))
- Past experimental/clinical finding, animal experimentations
 Procedures and Study Design (sound design) (eP 2(b))
- Resources available to address harms
- Risks minimized
- No unnecessary exposure to risk
- Multi-site study? If yes, is Stanford the lead site?
Investigational Drug or Device (eP 5 and 6)
 IND documented – for unapproved drug or for off-label use of approved drug (eP 6)
- Sponsor-Investigator?
- IB/Sponsor Protocol attached?
- Drug controlled by pharmacy? If no, procedures to prevent drug being used by others?
 Commercial drug (eP 6)
- Using according to labeling
- New use of approved drug – all IND statements true? If no, needs IND.
 IDE documented (eP 5)
- Sponsor-Investigator?
- Device Manual attached?
 If NSR, justify ((i) not an implant; (ii) not used to support/sustain life; (iii) not used to
diagnose, cure, mitigate or treat disease; (iv) does not present potential for serious risk to
health, safety and welfare of subject) (refer to lavender laminate) (eP 5)
 Commercial device – indicates under which category this device is exempt from IDE
requirements (eP 5)
46.111(a)(3) Participant Population – Equitable Selection (eP 8(c) and (f))
 No group inappropriately targeted or excluded
 Inclusion/exclusion criteria appropriate (eP 8(h) and (i))
 Target numbers of participants sufficient
- Numbers support proposed statistical analysis
 Special Problems addressed if vulnerable populations involved (Refer to laminates if study
includes prisoners, pregnant women, fetuses and neonates, children (OHRP), children
(FDA) and VA checklist)
46.111(b)
Participant Population – Vulnerable Participants (eP 8(c)-(f))
 Additional safeguards included if applicable for vulnerable participants
- Rationale for inclusion of vulnerable populations
 Refer to laminates if study includes prisoners, pregnant women, fetuses and neonates,
children (OHRP) and children (FDA).
Recruitment (eP 8(g))





Clinic patients
Referrals
Faculty approaching students
Laboratory personnel
Advertisements - language appropriate (flyers, internet postings, radio)
- Telephone screen
- No “cold calling”
File: AID01017
04/08
1 of 3
*See also 21 CFR 56.111 [FDA]
Stanford University
Research Compliance Office
Reviewer Tool - Medical
Considerations for Review
45 CFR 46.111 [OHRP]*
AID-17
Incentives or reimbursements (eP 8(k))




Amount is justified
Amount is reasonable (not likely to be coercive)
Payment pro-rated, if appropriate
Refer to “Payment – Ethical Considerations” guidance
Risk:
Consider level of risk: Low, Medium, or High
 If more than low risk, does not qualify for Expedited or Exempt review
 If high risk, does the protocol need additional, expert review?
46.111(a)(1) Risks to participants are minimized (eP 9(c))
 Least risky procedures to answer research question
 Use of standard of care procedures when possible
 Avoids exposure to unnecessary risks
 Consider physical, psychological, legal, social, and economic risks
 Any additional concerns for overseas research
46.111(a)(2) Risks are reasonable in relation to the anticipated benefits
 Consider anticipated benefits
 Risks justified by the benefits?
46.111(a)(6) Data Monitoring Plan (eP 9(e))
 Plan provides adequate monitoring
 Plan addressing reporting requirements
 When will the data be monitored?
 What data will be monitored?
 Who will do the monitoring?
or Not required (Low risk study)
46.111(a)(7) Privacy & Confidentiality (eP 11)
 Privacy protections adequate
- Sensitivity of information collected
- Participants privacy in research setting
- Procedures for identifying participants for recruitment
 Plan to protect confidentiality of data adequate
- Restricted access (Locks/passwords)
- Protection against loss, theft, or unauthorized access
- Certificate of confidentiality
- Safe transmittal and storage
- Encryption
- Statistical techniques
46.111(a)(4) Informed consent is sought from each participant (eP 13)
 Consent form clearly and adequately describes the study
 Consenting process appropriate
 Not applicable - waiver of consent and/or documentation requested
 Provisions included for non-English speaking participants (refer to pink laminate)
- Full translated consent document
- Use of short form process
46.111(a)(5) Informed consent is documented for each participant (eP 13)
File: AID01017
04/08
2 of 3
*See also 21 CFR 56.111 [FDA]
Stanford University
Research Compliance Office
Reviewer Tool - Medical
Considerations for Review
45 CFR 46.111 [OHRP]*
AID-17
Waiver or alteration of consent requested
 Not permitted on FDA regulated studies
- Waiver of consent (e.g. Retrospective chart reviews, no interaction with participants,
research on existing specimens and data) (refer to blue laminate)
- All must be true: Minimal risk; will not affect rights/welfare of participants and
impracticable w/out waiver
 Alteration of consent (e.g. deception) (refer to blue laminate)
- All must be true: Minimal risk; will not affect rights/welfare of participants and
impracticable w/out waiver
 Waiver of HIPAA applicable (e.g. Retrospective chart reviews, no interaction with
participants, research on existing specimens and data (when access to identifiers or the
link))
- All must be true: Minimal risk to privacy; impracticable w/out waiver; impracticable
w/out PHI (refer to grey laminate)
Waiver of Documentation
 Requested for telephone screening or oral consent for entire study (refer to blue laminate)
 Waiver of HIPAA for recruitment applicable (e.g. Telephone screening) (All must be true:
Minimal risk to privacy; impracticable w/out waiver; impracticable w/out PHI) (refer to
grey laminate)
Assent (eP 14)
 Assent will be obtained from all children aged 7-17 or only those capable
 Assent not applicable (children under 7)
 Assent document written in age appropriate language
Children’s Findings (eP 9)
(refer to children (OHRP) or children (FDA) laminates)
 Appropriate rationale provided
 For an Expedited or Exempt protocol application, the finding must be 46.404/50.51.
If not, protocol must be moved to Regular review.
- Minimal Risk. 45 CFR 46.404 or 21 CFR 50.51 (FDA)
- Above minimal risk, but prospect of direct benefit and no riskier than alternatives.
45 CFR 46.405 or 21 CFR 50.52 (FDA)
- Above minimal risk, no prospect of benefit, but yields knowledge about condition.
45 CFR 46.406 or 21 CFR 50.53 (FDA)
- Research not otherwise approvable, but presents opportunity to prevent or alleviate
serious problem affecting children.
45 CFR 46.407 or 21 CFR 50.54 (FDA)
______________________________________________________________________________________________________
Approval Recommendation
Does this protocol meet criteria for protocols that will generally be reviewed more often
than annually? Is it a:




Novel high-risk study involving new therapeutic modality;
Phase I study of a new drug or biologic that has never been tested in humans;
Study involving a novel significant risk medical device that has never been tested in humans;
High-risk study as IRB members deem appropriate (includes research for which IRB
determines that reports to the IRB of monitoring data should be more frequent than annually).
Does the study warrant approval? If “yes”:
For a period of one year or
For a period of [less than 1 yr]
or
For
subjects
Notes/Comments/Points for Discussion:
File: AID01017
04/08
3 of 3
*See also 21 CFR 56.111 [FDA]