Upload
ibrahim-stiverson
View
217
Download
0
Tags:
Embed Size (px)
Citation preview
IRB Approval for FMT What does an IRB look for
in FMT Protocols?
William Tremaine, M.D. Mayo ClinicRochester, MN
Disclosure of ABIM Service: William Tremaine, MD
I am a current member of the Gastroenterology Board Exam Committee.
To protect the integrity of certification, ABIM enforces strict confidentiality and ownership of exam content.
As a current member of the Gastroenterology Board Exam Committee, I agree to keep exam information confidential.
As is true for any ABIM candidate who has taken an exam for certification, I have signed the Pledge of Honesty in which I have agreed to keep ABIM exam content confidential.
No exam questions will be disclosed in my presentation.
IRB Review of an FMT Protocol
• Is FMT human research?
• Is an IND required
• Is the proposal scientifically valid?
• Are the risks minimized?
• Will potential participants receive sufficient information to make an informed decision?
• Will the privacy of the participants and donors be protected?
What Constitutes Research?
OHRP
• Systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge
FDA
• Any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the FDA...or the results of which are intended to be later submitted to, or held for inspection by, the FDA as part of an application for a research or marketing permit. food and color additives, drugs for human use, medical devices for human use, biological products for human use, …
Is FMT Human Research?
Yes if any of these apply No if all of these apply
An IND is required No IND is required
Systematic collection of data for analysis
Just for treatment
For publication Not for main purpose of publication
Clinical Registry versus
Research Database
Clinical Registry Research Database
Plausible Clinical Need Laboratory monitoring Scheduling follow-up visits Contacting patients about updates
No Clinical Use Hypothesis driven Consent required For publication
Clinical Registry versus
Research Database
Clinical Registry Research Database
Plausible Clinical Need Laboratory monitoring Scheduling follow-up visits Contacting patients about updates
No Clinical Use Hypothesis driven Consent required For publication
Research IRB ApprovalMinimal RiskRetrospectiveWaiver of Consent and HIPAA
IRB Review of an FMT Protocol
• Is FMT human research?
• Is an IND required
• Is the proposal scientifically valid?
• Are the risks minimized?
• Will potential participants receive sufficient information to make an informed decision?
• Will the privacy of the participants and donors be protected?
Smith MB et al. Nature 2014: 506: 290-1
Listed Fecal Transplant TrialsJuly 27, 2014
68 Listed Fecal Transplant Clinical Trials
Diagnosis Number of studies
C difficile 19
IBD 17
Pouchitis 1
Fecal Incontinence 2
IBS 2
Diabetes 1
Metabolic Syndrome 1
Chronic diarrhea 2
Ileus 1
Graft vs Host 1
Incorrect Listing 21
Clinicaltrials.gov July 27, 2014
4747
Safety, Tolerability, and Clinical Response After Fecal Transplantation in Children and
Young Adults with Ulcerative Colitis
• Prospective, uncontrolled, single center
• Grand Rapids, MI
• Investigator-initiated IND for fecal transplant in UC
• Local IRB approved
• Fecal retention enemas
• Cohort• 10 children ages 7-21• Mild to moderate
activity• Stable on
maintenance Rx for 2 months
• Donors• Family or friends• Exclusion criteria in
the IND
Kunde S et al. JPGN 2013: 56: 597-601
FMT for C. difficile FDA Guidance July 2013
Enforcement discretion
No IND required provided that
• Treating physician obtains informed consent
• Informed consent includes• A statement that FMT for C difficile is
investigational• Potential risks are discussed
This enforcement discretion is temporary until an FDA policy regarding FMT is implemented
FMT and Clinical Trials
Diagnosis Number of studies
C difficile 19
IBD 17
Pouchitis 1
Fecal Incontinence 2
IBS 2
Diabetes 1
Metabolic Syndrome 1
Chronic diarrhea 2
Ileus 1
Graft vs Host 1
Clinicaltrials.gov July 27, 2014
IND
17 IBD Studies Clinicaltrials.gov
Active, Recruiting
ActiveNot Recruiting
Completed Terminated
UC 5 1 1
Crohn’s 1 1
IBD 3 2 1
Pouchitis
1
17 IBD Studies Clinicaltrials.gov
Active, Recruiting
ActiveNot Recruiting
Completed Terminated
UC 5 1 1
Crohn’s 1 1
IBD 3 3 1
Pouchitis
1
Fecal Microbiota Transplant for IBD 9 Active Recruiting Trials
IND No IND No Response
U.S. 3
Non U.S. * 5 1
*Finland, China, Netherlands, Israel
FMT for C. difficile FDA Guidance July 2013
• Enforcement discretion policy does not extend to other uses of FMT
• FDA will continue to work with any sponsors who wish to submit INDs for this use (C. difficile treatment) of FMT
Clinical Research Trials
Diagnosis Number of studies
C difficile 19
IBD 17
Pouchitis 1
Fecal Incontinence 2
IBS 2
Diabetes 1
Metabolic Syndrome 1
Chronic diarrhea 2
Ileus 1
Graft vs Host 1
IND
IND?
Is and IND Required for FMT?
Yes if Maybe No if
The treatment isn’t for C. difficile
The treatment is a research study for C.
difficile, not primarily for clinical care
The treatment is for C. difficile for clinical care
Investigator Initiated INDRegulatory Burden
Investigator Initiated INDRegulatory Burden
Safety Reports Annual Reports
Any Adverse experience associated with the use of the drug that is both serious and unexpected
Annual Report
IRB Review of an FMT Protocol
• Is FMT human research?
• Is an IND required
• Is the proposal scientifically valid?
• Are the risks minimized?
• Will potential participants receive sufficient information to make an informed decision?
• Will the privacy of the participants and donors be protected?
Is the FMT Proposal Scientifically Valid?
• Plausible Hypothesis
• Meaningful endpoints
• Sufficient statistical power
• Adequate resources
Scientifically valid?Comparison Group Issues
Comparator Pro Con
Placebo Power Ethics
Active Ethics Feasibility
Historical Easy Questionable validity
IRB Review of an FMT Protocol
• Is FMT human research?
• Is an IND required
• Is the proposal scientifically valid?
• Are the risks minimized?
• Will potential participants receive sufficient information to make an informed decision?
• Will the privacy of the participants and donors be protected?
Risks of FMT
Observed Potential
Abdominal discomfortBloatingFlare of ulcerative colitis Fever Worse diarrhea Increased CrP Orthostasis Pancreatitis
HepatitisHIVAutoimmune diseasesObesity
Rubin DT Amer J Gastro 2013. 108: 1631-2
Smith MB et al. Nature 2014: 506: 290-1
IRB Review of an FMT Protocol
• Is FMT human research?
• Is an IND required
• Is the proposal scientifically valid?
• Are the risks minimized?
• Will potential participants receive sufficient information to make an informed decision?
• Will the privacy of the participants and donors be protected?
Elements of Informed ConsentOHRP
This is research Benefits
Purpose Alternatives
Duration Confidentiality
Procedure details Compensation for injury
Experimental procedures Whom to contact
Risks Voluntary
IRB Review of an FMT Protocol
• Is FMT human research?
• Is an IND required
• Is the proposal scientifically valid?
• Are the risks minimized?
• Will potential participants receive sufficient information to make an informed decision?
• Will the privacy of the participants and donors be insured?
FMT Donor Registry
• Sarah
• Location: New York City, NY, USA
• Gender: Female
• Age: 49
• Have Donated Previously: No
• Liability Agreement Required: Yes
• Cost: All fees associated with required testing & negotiable ‘per donation’ fee
• Why Donating: I believe in the theory of FMT and have been a pristine eater all my life so I figure I can help others.
thepowerofpoop.com
Recommendations for FMT Donors
Inclusion Criteria Exclusion Criteria
Intimate longtime partnerAdult first degree relativeClose family friendWell-screened universal donor
Antibiotic use in < 3 monthsKnown GI diseaseAutoimmune or atopic illnessChronic pain syndromeMetabolic Syndrome or malnutritionHistory of malignant disease
HAV-IgM C difficile toxin B
HBsAg + stool culture
Anti-HCV-ab + O & P
HIV-EIA
RPR
AGA, ACG, ASGE, NASPGHAN, IDSA July 15, 2013
FMT Research StudiesSafeguarding Privacy
Recipient Donor
Written informed consent Written informed consent
HIPAA HIPAA
IRB Review of an FMT Protocol
• Is FMT human research?
• Is an IND required
• Is the proposal scientifically valid?
• Are the risks minimized?
• Will potential participants receive sufficient information to make an informed decision?
• Will the privacy of the participants and donors be insured?
IRB Approval for FMT Summary
• The divide between FMT for clinical practice and research is complicated
• The FDA rules on INDs for FMT are not finalized
• The usual IRB concerns for human research studies apply for the:
• Recipient• Donor