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FROM ADVERSARIES TO ALLIES:
EFFECTIVE COMMUNICATION BETWEEN
INVESTIGATORS AND IRBS
LY N N M . R O S E , P H . D .
D I R E C TO R , S C I E N T I F I C A D M I N I ST R AT I O N
B E N A R OYA R E S E A R C H I N ST I T U T E
1. General Perceptions of IRB and Investigator
2. Discuss common areas of misunderstanding
between investigators and IRB
3. Present some tools for improved
communication of medical risk to IRB
AGENDA
The IRB is a committee formally designated by the
FDA and DHHS to review, approve, and monitor
biomedical and behavioral research involving
humans with the aim of protecting the rights and
welfare of the research subjects.
INSTITUTIONAL REVIEW BOARD
Risk Averse
Anti-science
Bureaucratic “Black Box”
Unnecessary administrative delays
Don’t get it!
WORDS USED TO DESCRIBE IRBS
PERCEPTION OF INVESTIGATOR BY IRB
Can’t follow basic simple instructions
Provide incomplete information
Overly focused on efficacy – not safety
A bit fuzzy on the regulations
Don’t get it!
WORDS USED TO DESCRIBE APPLICANTS
THE REALITY
IRB, Investigator and Subject after
the same thing
Advance medicine
Improve human health
Be safe
Be part of something that is
meaningful
COMMUNICATE EFFECTIVELY
I R B
User-friendly submission forms
Make questions easily
understandable
Avoid verbatim recitation of
regulations
Be Timely
Provide a Transparent Process
I N V E ST I G ATO R
Provide complete answers to questions asked – Don’t assume, no “cut and paste”
Write clearly, concisely, and consistently
Supplement application with information, when necessary
Respect Timelines
Be aware of regulations
Medical Device Studies
Significant risk (SR) or an non-significant risk (NSR)?
Interventional Drug Studies
IND or no IND?
Tissue Collection Studies
Exempt, Not Exempt, Non-human subject research?
Chart Review Studies
Human Subject Research or Quality Improvement?
FREQUENT AREAS OF MISUNDERSTANDING
Implants (e.g., pacemaker) and present a potential for serious risk
to the health, safety, or welfare of a subject
Support or sustain or sustaining human life and presents a
potential for …
Diagnose, cure, mitigate, or treat disease, or otherwise prevent
impairment of human health and present a …
Otherwise presents a potential for …
MEDICAL DEVICES SIGNIFICANT RISK DETERMINATION
Investigator/Sponsors make initial determination and present to
IRB
Unless FDA has already determined risk level, it is the
responsibility of the IRB to make the final determination
FDA is available to consult with sponsor or IRB
In cases of disagreement, FDA trumps IRB
MEDICAL DEVICES WHO DECIDES?
Provide IRB with rationale for proposed determination
Provide sufficient data to help the IRB evaluate the risk of the
device
Description of device
Prior investigations with device
Proposed investigational plan
Subject selection criteria
MEDICAL DEVICES INVESTIGATOR CAN FACILITATE THE PROCESS
Provide Users Manual
Provide Diagrams – let them see!
Briefly describe regulatory status
Provide risk information from literature
Make it easy for the IRB to find and review the relevant
information.
MEDICAL DEVICE EXAMPLE: EUROPEAN DEVICE
The investigation will not support a new indication or other change in the product label or
advertising
The investigation does not involve a route of administration or dosage level or patient
population that significantly increases the risks (or decreases the acceptability of risks)
associated with use of the drug
The investigation is conducted in compliance with the requirements for institutional
review
The investigation is conducted in compliance regulations governing promotion and
charging for investigation drugs
THERAPEUTIC INTERVENTIONS IND WAIVERS FOR STUDIES WITH APPROVED MEDICATIONS IF
When the investigation does involve a route of administration or dosage level or
use in a patient population or other factor that significantly increases the risks (or
decreases the acceptability of risks) associated with use of the drug
The investigational drug is a dietary supplement
The investigational drug is a botanical substance
Clinical practice is “off-label”
Lack of an IND may slow process unless risks are clearly presented and
acceptable
THERAPEUTIC INTERVENTIONS WHERE IT GETS PROBLEMATIC:
Changes in route of administration can alter safety risks
• Target Organ may change (i.e. inhaled vs. parenteral)
• Pharmacokinetics may be altered (i.e. increased renal exposure)
Doses may exceed those in the label
• May limit usefulness of study if dose limited to the approved dose
Patient population is in an untested age range
Patient population has a disease condition that would put it at different and/or
greater risk than the population(s) studied for the approval
THERAPEUTIC INTERVENTIONS THINGS FOR IRB AND INVESTIGATOR TO CONSIDER
Provide the data needed to assess risks!
Know the safety findings for the original indication
Discuss relevance for the condition under study
Read the label!
Review the regulations
Dietary supplements are considered “drugs” if they are used to treat, cure, or mitigate disease
Understand difference between the label and clinical practice
THERAPEUTIC INTERVENTIONS HELP THE IRB
Discuss program with local IRB
Some IRBs require a letter of exemption from FDA OR the IND Number
Some IRBs will review the investigator’s rationale and make a decision
Submit “Request for Exemption”
A call can tell you if the division will entertain a Request for Exemption
Submit a request for a pre-IND meeting
Include rationale and request for exemption as part of submission
THERAPEUTIC INTERVENTIONS STILL NOT SURE?
Not a lot of regulatory guidance so the “it depends” rule comes into play
Need clear institutional policies, so investigators are not confused about what is eligible for
waiver of consent and what is not
Lack of clarity on the recipient investigators
Laboratory personnel often working outside of the clinical context, may lack training in Good
Clinical Practice, Consent Processes, and HIPAA
Conflicting Regulatory Processes for Secondary Uses of Stored Tissue
Waiver of consent appropriate for anonymous samples and possibly coded samples; however,
access to more information may become a research need
Requests for secondary uses often outstrip the initial purpose of the repository
TISSUE REPOSITORIES COMMON PROBLEMS
Unclear separation between quality initiatives and human subjects research
Need institution policies in place with clear definitions of research
Internally focused data versus generalizable results
Unanticipated Needs for Secondary Uses of Stored Data
Data collected for clinical or quality purposes may “morph” into human subject research and
require IRB review
Original data collected without consent may now require consent
Data collected without proper consent may not be eligible for publication
CHART REVIEW COMMON PROBLEMS:
1. IRBs and Investigators work together to protect human subjects in research.
2. IRBs need to understand what you are doing and why; no matter the type of
research.
3. Investigators must anticipate the focus on safety, either to the subjects
themselves or subject data
4. IRB includes lay members of the community so the language must be clear.
5. Be clear, don’t obscure. There is no point in altering a study to avoid human
subjects protections!
CONCLUSIONS
Clear Concise Consistent