Transcript PowerPoint

Strategies for Success with the IRB
Tips to Help Get Your Protocol Approved
Susan S. Fish, PharmD, MPH
Associate Director, Office of Clinical Research
Director, Human Subjects Protection
March 16, 2005
Tips to Help Get Your Protocol Approved
1. Give the IRB what it needs
2. Expedited vs Exempt
3. Study Procedure
4. Risks are Reasonable in Relation to Benefit
5. Sample Size
6. DSMP vs DSMB
7. Study Specific Justifications
8. Informed Consent
9. Attachments
10. Human Subjects Protection Certification
11. Amendments
12. Modification Memo Reply
1. Give the IRB What it Needs
• Review Criteria
– 45 CFR 46.111
– 21 CFR 56.111
• How do I know what the IRB needs?
Criteria For Approval
45 CFR 46.111
21 CFR 56.111
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Minimized risks
Reasonable risk/benefit relationship
Equitable subject selection
Informed consent process
Informed consent documentation
Data monitored for safety
Confidentiality/privacy maintained
Vulnerable populations protected
www.bumc.bu.edu/irb
Take IRB Application Seriously
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Allow enough time
Review spelling and grammar
Review for consistency and completeness
IRB only knows what the investigator is saying
through what is in the application
• Give the same attention and care to the IRB
application as an NIH grant application
2. Expedited vs Exempt - Section B
(English doesn’t work here!)
Does this study involve greater than minimal
risk to the subject?
– If Yes (skip to Section C)
– If No, then complete EITHER Section B1 or B2
Section B1- Exempt
• For further information see Federal
guidance for exempt categories (linked).
• Common issues:
– Anonymous (different from confidential)
– Existing data
– If Exempt, no need to complete Section J4
Waiver of Informed Consent
– You do need HIPAA form(s)
Master Code List
Subject
Mary
Roz
Karen
MRN
1234567
2345678
3456789
ID
001
002
003
ID
001
002
003
RESULTS
534
723
421
Anonymous Data
Subject
Mary
Roz
Karen
MRN
1234567
2345678
3456789
ID
001
002
003
RESULTS
534
723
421
Section B2- Expedited
• If charts/records not existing at time of IRB
application
• If master code list linking study ID with
subject identifiers
• If identity could be ascertained in “rich”
database
• If Expedited, must have either
– Consent form – Section Q, or
– Waiver of Informed Consent – Section J4
Confidentiality and Code List
Samples will be collected and stored in the PI' s
laboratory at the XXX, then will be shipped in
batches to Laboratory of Dr. XXX for further
analysis. Samples will be coded, and the code
will be held by the PI. The list of the codes will
be kept confidential and secured in password
protected computer in locked office. The link to
codes and names will be destroyed after the
study completion and after the acceptance for
publication, if appropriate.
3. Study Procedure
Section F2
• Describe in detail the experimental design,
including all materials and all procedures
to be performed in sequential order as
they will be performed. Clarify which
procedures/test articles are investigational
and which are part of standard clinical
care.
Research vs Standard of Care
• Clearly describe standard of care (what
would happen if subject does not consent
to the research)
• Clearly describe what is research
• Caution re: therapeutic misconception
– Research, not therapy or treatment
– Researcher or Investigator, not doctor
Section F2:
This description may include:
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Methods
Specific information re: experimental interventions, such as dose and frequency of
drug/placebo
Number, frequency and duration of subject contacts
Any additional requirements of the subject (post treatment follow-up, diary cards,
questionnaires, etc.)
Outcomes (primary, secondary and how they will be measured)
Will any of the research be done outside BUMC (see A6a).
Entire duration of participation for a single subject
Estimated duration of recruitment and enrollment
Estimated duration of entire study (from initial IRB approval through data analysis to
close of study)
Attach copies in Section S of any surveys, questionnaires, and other data collection
instruments.
Describe what is going to happen in
the research. Tell us what you are
going to do.
Study Summary
Section C
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300 word summary in lay language
Describe study
Overview of study
Abstract
Used by reviewers
4. Risks are Reasonable in
Relation to Benefit
• Explain HOW the risks are outweighed by (or
are reasonable in relation to) the benefits
• Background- justify the statement of benefits
• Consistency of risks section (H) with statement
of minimal risk (B)
5. Sample Size
Section G
• Please indicate why you chose the
sample size proposed.
• “Pilot” or Exploratory/Descriptive
– Justify design regarding what conclusions will
be drawn (i.e. feasibility, adverse effects)
– Inform subjects of purpose
– Sample size may be justified by the need to
assess variability in the sample or to look for
large effects
6. DSMP vs DSMB
Section H
• All studies > minimal risk need PLAN
• Studies with substantial risk need BOARD
– Risk
– Subjective outcome, unblinded researchers
• Some studies may need independent
safety assessor, but not BOARD
Data Safety Monitoring Plan
Indicate what measures will be taken to prevent
or to minimize the effects of hazards,
discomforts or inconveniences. Include a
detailed description of your Data Safety
Monitoring Plan (DSMP). The DSMP must
minimally include
a) a description of the risks and safety
assessments of the study,
b) specifics regarding who will be monitoring the
data and the frequency of monitoring, and
c) a clear description of the safety findings that
would cause the study to be suspended.
GCRC DSMP
www.bumc.bu.edu/gcrc
Data Safety Monitoring Board
• An independent group of experts who
review accumulating study data for early
indication of
– Safety issues
– Indication of efficacy
– Futility
• DSMB charter, SOPs, interim analysis
rules, stopping rules
7. Study Specific Justifications
• J3- Waiver of Documentation
• J4- Waiver of Informed Consent, or
Waiver of individual elements
• O – FDA approved drug used off-label
without IND
Waiver of Documentation
Section J3
If yes, please explain how your study meets one of
the following two criteria [see 45 CFR 46.117(c)] :
(1) That the only record linking the subject to the research
would be the consent document and the principal risk of
having a signed consent form would be potential harm
resulting from a breach of confidentiality… [must have
consent form in Section Q to offer subject]; or
(2) That the research presents no more than minimal risk of
harm to subjects and involves no procedures for which written
consent is normally required outside of the research context.
Waiver of Consent or an Element
Section J4
• Explain how waiving the requirements for informed
consent presents no more than minimal risk to study
subjects.
• Explain how waiving the requirements for informed
consent will not adversely affect the rights and welfare of
study subjects.
• Explain why the research could not practicably be
carried out without a waiver of informed consent or
alteration of the informed consent process.
• Provide a plan to disseminate pertinent information to
subjects after the study is completed if consent is
waived.
New Use of FDA Approved Drug
Section O
• If yes, insert the IND number in the IND box
above and insert the drug/biological agent
name, the name of the manufacturer, and who is
holding the IND in the text box below.
• If you feel that an IND is not required, justify
how this study meets all of the criteria for
21CFR 312.2. A copy of the investigator's
brochure or the drug package insert must be
attached to Section S.
21 CFR 312.2
8. Informed Consent
• Reading level too high, language legalistic
• Needs extensive revision (put yourself in
subject’s shoes)
• Explain all procedures and risks
• Explain implications rather than simply
stating risks (i.e. liver function test
abnormalities)
• Flow chart as addendum?
Consent Form
• Copy into Word for
– Spell check
– Grammar check
– Readability
How to Check Readability-1
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Tools
Spelling and grammar
Options
Show readability statistics
Flesch-Kincaid grade level
• Syllables per word
• Words per sentence
How to Check Readability-2
How to Check Readability-3
How to Check Readability-4
Use Approved Valid Consent Form
9. Attachments – Section S
• Use Appropriate Category
• Only attach:
.doc
.jpg
.pdf
.xls
Attachment Categories-1
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Back translation #1-4
Consent form previously approve #1-6
Device brochure, and version 2
Drug brochure, and version 2
Drug enclosure, and version 2
Educational materials #1, 2
Final letter #1
Follow up letter #1
Attachment Categories-2
• Foreign language consent form #1-4
• FWA/IRB approval letter from another
institution #1-3
• Grant application
• Informational brochures
• Instruction sheet(s) #1,2
• Letter(s) to subjects #1, 2
• Medical record release form(s)
• Note to IRB office #1-4
Attachment Categories-3
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Other #1-20
Recruitment materials #1,2
SAE at BUMC #1, 2
Safety reports #1
Section F- Investigator’s detailed protocol
Section F2 – GCRC DSMP
Section F2 –DSMP
Section F2 -- Procedure
Attachment Categories-4
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Section F3: Sponsor’s protocol
Section K: Certificate of Confidentiality
Section K2: HIPAA form(s), and #2
Spanish Consent #1-3
Subject contact letter #1-4
Survey instrument/questionnaires #1, 2
VA consent form #1-4
10. Are You Certified in
Human Subjects Protection?
www.bumc.bu.edu/irb
www,bumc.bu.ed
11. Amendments
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Summarize major changes in amendment
State if change in risk to subjects
State if change in consent form
Attach details of amendment
Revise IRB protocol to reflect all aspects
of amendment.
• Be sure that all changes are stated either
in cover sheet or attachment.
12. Modification Memo Reply
1. IRB’s statement
PI’S RESPONSE
2. IRB’s statement
PI’S RESPONSE
3. IRB’s statement
PI’S RESPONSE
• Make changes in IRB protocol , ICF
Do’s and Don’t’s
Richard Saitz, MD, MPH 2001
• If not written down the Board doesn’t know it
(IRB cannot make [best or worst case]
assumptions)
• All protocol issues need to be in the protocol (i.e.
not just in the ICF)
• Address regulations explicitly
• Tell the IRB what is part of the research and
what is not, explicitly
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Don’t try to bypass the process (i.e. don’t send directly to Chair); materials will get lost, delayed
• Specifically define inclusion and exclusion
criteria
Do’s and Don’t’s
Richard Saitz, MD, MPH 2001
• Be clear when a study is not testing a treatment,
not testing treatment efficacy
• Avoid cut and paste errors (very common) and
checking off the wrong boxes
• Be explicit when study will pay for care, and
particularly regarding payment for screening
procedures for ineligibles
• Be explicit about differences between sponsor
protocol/grant proposal and local study
procedures
• If research lab used, address any delays
Do’s and Don’t’s
Richard Saitz, MD, MPH 2001
• Avoid typographical errors
• Be explicit about why a drug study is
exempt from an IND
• Consistency throughout application
• Avoid saying what has been approved in
the past
• Avoid asking for speedy review (whose
protocol should be delayed)?
Do’s and Don’t’s
Richard Saitz, MD, MPH 2001
• When pregnancy an exclusion, state how and
when tested. In protocol (and consent) state
risks to pregnant woman/fetus justifying
exclusion. If there are genetic or fetal risks
address partner risks
• Don’t forget to address controls (when counting
subjects, for recruitment, for ICF)
• Ask substantive questions (many help features
now)