Practical issues in IRB review

Bernard Lo, M.D.

August 16 and 19, 2010

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Topics to cover

When is IRB review not necessary?

How to avoid delays in IRB review? IRB review of multisite trials Tips for IRB approval

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Infections related to central venous catheters

80,000 bacteremia episodes annually

Cost $45,000 per infection

28,000 deaths

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Reducing ICU catheter-related infections

Handwashing

Clorhexidine

Full-barrier precautions when inserting

central lines

Avoid femoral sites

Remove unnecessary catheters

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Reducing ICU catheter-related infections

Standard recommendations not

followed

Quality improvement project in 108

ICUS in 67 Michigan hospitals

Checklist

Monthly feedback

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Reducing ICU catheter-related infections

Catheter-related bloodstream infections /

1000 catheter-days (mean)

Baseline 7.7

After 16-18 months 1.4

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Reducing ICU catheter-related infections

After publication, OHRP investigation Project was research: grant, publication IRB review required Consent from subjects

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Is IRB review necessary?

No risk to patients Checklist procedures standard practice Efforts to improve adherence not harm

patients Researchers receive hospital infection rates,

no identifiable patient information

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Is IRB review necessary?

Primary goal of QI is to improve patient

care, not generate knowledge Intervention could be implemented as part

of clinical care Obligation to do QI Instituting interventions without analyzing

whether they work makes little sense

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Is IRB review necessary?

IRB review not feasible 45% of hospitals in project had no IRB HIPAA does not require consent for QI Review by clinical service directors

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When is IRB review not necessary?

1. Not research

2. Not human subjects research

3. Exempt from federal regulations Certain survey, interview research Certain research with existing data and

biological specimens

Definition of research

“Systemic investigation … designed to

develop or contribute to genralizable

knowledge”

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1. Not research(hence no IRB review)

Innovative clinical practice

Public health practice Surveillance, epidemiology, investigate

outbreaks May publish findings

Quality improvement?

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Infertility in cancer survivors

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Induced pluripotent stem cells (iPS cells)

Reproductive research with iPSC derivatives

Differentiate iPSCs into oocytes and

sperm

Carry out IVF, observe embryo to see if

normal development

Use iPSCs that are easy to work with

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Questions for audience

Do regulations permit using de-

identified somatic cells to derive iPSCs

and gametes and fertilize gametes in

vitro, without consent of somatic cell

donors? Yes /No / Unsure

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Questions for audience

Should regulations permit using de-

identified somatic cells to derive iPSCs

and gametes and fertilize gametes in

vitro, without consent of somatic cell

donors? Yes /No / Unsure

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Definition of human subjects

Living individuals about whom an

investigator obtains Data through intervention or interaction OR Identifiable private information

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What is human subjects research?

Interact with person OR

Use identifiable private information Not human subjects research if exisiting

data and materials cannot be identified Examples of tissue from cancer surgery

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What is identifiable?

None of 18 HIPAA identifiers

Data and materials are coded but

researcher cannot access keys to code Code may be retained by database or

biobank

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Ethical rationale for no IRB review

If no human subject, no one can be

harmed

Hence IRB review would not protect

participants But would pose administrative burdens

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2. Not human subjects research:Examples

Collect hospital-specific data on

infection rates

Reproductive research with de-

identified iPSCs

Coded neonatal spots

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Reproductive research with iPSC derivatives

Not human subjects research if de-

identified

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Reproductive research with iPSC derivatives: concerns

Reproduction very private

Some object if such reproductive

research done without their consent

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Reproductive research with iPSC derivatives: concerns

Deeply held beliefs about reproduction: Some believe that IVF is immoral Some believe that embryos have moral

status of persons, should not created or destroyed for research

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Reproductive research with iPSC derivatives: concerns

Such individuals object to use of their

biological materials in such research Even if de-identified Respect their values and preferences by

asking their consent

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Warning

Research permitted under federal

regulations may not meet ethical

standards Ultimately researcher is responsible

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3. Exempt from federal regulations

Most survey and interview research Unless subjects can be identified and

responses could put respondents at risk• Not if ask about illegal activities, sensitive or

private topics

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3. Exempt from federal regulations

Certain existing data or materials Publicly available Researcher records information in manner

than subjects cannot be identified• Can look at medical records

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3. Exempt from federal regulations

Much research in educational settings

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How can we avoid delays in IRB review?

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Expedited IRB review

Reviewed by chair or designate, not

full committee

Shorter time to approval

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When may IRB review be expedited?

1. Must be minimal risk

2. On list approved by DHHS

Definition of minimal risk

Probability and magnitude of harm or

discomfort

Not greater than encountered in daily

life or routine physical exam

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Examples of minimal risk

Answering (non-sensitive) questions

over telephone

Routine blood tests, EKG

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Significance of minimal risk

May be eligible for Expedited IRB review Waiver of informed consent

In pediatrics, different categories of

review and approval

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When may IRB review be expedited?

2. On list approved by DHHS Noninvasive collection of specimens

• Urine, buccal swabs

Noninvasive clinical procedures• EKG, ultrasound

• Not x-rays

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When may IRB review be expedited?

2. On list approved by DHHS Venipuncture Interview, focus group research Research with existing data, specimens

collected for nonresearch purposes Minor changes to approved protocol

• Changes in questionnaire, tests run

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Questions?

IRB review of multisite studies

Review at each site causes long

delays, requires great effort

Inconsistent requirements

May push clinical trials to clinical

research organizations, independent

IRB

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Review of multisite studies

Cooperative arrangements Defer review to other UC IRBs

Facilitated review by central IRB NCI sends detailed review to sites

• May be useful in other types of studies

Facilitated review by single IRB member

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Top 5 problems with IRB submissions

1. Study procedures not clear Reader should be able to replicate study

2. Recruitment and consent process

unclear Who, where, when, how? Vulnerable populations

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Top 5 problems with IRB submissions

3. Inconsistency within protocol Methods and consent sections not agree

4. Missing information

5. Undefined acronyms

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Tips for IRB submissions

Know what CHR requires Use correct templates and form Special regulations for children, prisoners

Anticipate IRB concerns Write for nonspecialists Reviewers do not want to re-read to figure

out what you are doing

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Tips for IRB submissions

Ask the IRB questions Find out what they are likely to have

concerns about

Get it right the first submission If difficult or sensitive issues, show that

you considered alternatives and give reasons for your approach

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Take home points

IRB review process will be easier for

you if You understand when expedited and waiver

are permitted Avoid common problems with IRB

submissions

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