External IRB Review Practice Exam
Questions & Answers.
Introduction - CORRECT ANSWER -In designing our study, we had anticipated that multi-institutional IRB
review would be a necessary, time-consuming, sometimes complicated, and often frustrating prelude to
our research. Our expectations, on balance, proved to be modest. At times we found ourselves
wandering through bureaucratic mazes that made us think we were re-enacting Franz Kafka's classic
novel, The Trial, rather than engaging in social science research
IRB history - CORRECT ANSWER -The history of Institutional Review Boards (IRBs) shows a tension
between the desirability of central review for studies conducted across multiple sites and the need for
consideration of local conditions at each institution.
The Road from Local to External Review - CORRECT ANSWER -IRBs are so named because they were
originally located within the institution conducting the studies. The principle of local review was central
to IRBs from their inception in 1966 to about 2000. This made complete sense when local communities,
practices, and laws could be quite different; when institutions with a federal assurance of compliance
were primarily major academic medical centers with large research portfolios; and when there were
very few large multi-center trials.
-This gradually shifted. In 1979, the second issue of IRB: A Review of Human Subjects Research included
the article cited in the introduction about coordinating multiple IRBs (Kavanagh et al. 1979, 1-3). In
January 1981, U.S. Department of Health and Human Services (HHS) regulations (45 CFR 46) were
updated and in the preamble there was discussion of cooperative review. The decision, embodied in
46.114, was that "cooperating institutions may use joint review, reliance upon the review of another
qualified IRE (sic), or similar arrangements aimed at avoiding duplication of effort" (HHS 1981, 8381).
-On the same day in 1981, the U.S. Food and Drug Administration (FDA) published its regulations (21 CFR
50 and 56), harmonizing as much as possible with 45 CFR 46. A major distinction was that FDA included a
requirement that each investigator was required to have separate IRB approval. Recognizing that
investigators in practice may not have an institutional board, the FDA said that they could "use an IRB
created by the sponsor."
Defining Centralized Review through Nomenclature and Models - CORRECT ANSWER -The history of
external review has led to a variety of structures with no single model and no single accepted
terminology. People talking about an external IRB may be referring to very different relationships.
, Saying, "Central IRB," creates different pictures for people depending upon their background and
viewpoint. The meaning is very dependent on one's position in the research and IRB world. For example,
IRB administrators at an active hospital might deal with their institutional IRB, several independent IRBs,
the National Cancer Institute's (NCI) Central Institutional Review Board (CIRB), and perhaps other
consortia or collaborative IRBs.
Nomenclature - CORRECT ANSWER -There are a number of concepts that overlap and terms that have
not been adequately defined. During the Public Responsibility in Medicine and Research (PRIM&R)
conference in 1998, there seemed to be some confusion about what a Central Review Board (CRB) was
and where it could operate. The "National Conference on Alternative IRB Models" (OHRP et al. 2006)
attempted to develop some models of relationships. There is still no clear standardized nomenclature,
and the language used often mixes functions and relationships.
-Without any accepted systematic definitions describing IRBs and their relationships, here are some
basics terms to describe external IRBs:
-A Central IRB is a single board that reviews research studies for multiple sites. A central IRB can be any
registered IRB that functions to review multiple sites but most commonly the term central IRB
references an independent IRB.
-Single IRB of Record is a term adopted by the Clinical Trials Transformation Initiative (CTTI). Their
website states, a central IRB is "a single IRB of record for a given protocol. The central IRB assumes all of
the usual IRB responsibilities including all reviews of all relevant documents" (CTTI 2014). A single IRB of
record oversees the same research protocol across a number of locations. Single IRB of record generally
operates within an FWA situation. It might be a consortium or cooperative IRB, an IRB from another
institution, or a federal IRB. Central IRB and Single IRB of Record seem to be synonymous but used at
different times.
-Centralized IRB review is a function performed by a Central IRB. Regardless of the group providing it,
centralized IRB review is one review for a number of sites. Commonly, the sponsor determines which
sites are to participate and suggests or requires those sites to use the central IRB selected to perfor
Cooperative Inter-Institutional Models - CORRECT ANSWER -Any institution may create a written
agreement to use another institution's IRB for some or all reviews. An entity or group of institutions can
organize an IRB to review all or a subset of studies. These are closed systems available to only named
institutions. There are several examples.
Questions & Answers.
Introduction - CORRECT ANSWER -In designing our study, we had anticipated that multi-institutional IRB
review would be a necessary, time-consuming, sometimes complicated, and often frustrating prelude to
our research. Our expectations, on balance, proved to be modest. At times we found ourselves
wandering through bureaucratic mazes that made us think we were re-enacting Franz Kafka's classic
novel, The Trial, rather than engaging in social science research
IRB history - CORRECT ANSWER -The history of Institutional Review Boards (IRBs) shows a tension
between the desirability of central review for studies conducted across multiple sites and the need for
consideration of local conditions at each institution.
The Road from Local to External Review - CORRECT ANSWER -IRBs are so named because they were
originally located within the institution conducting the studies. The principle of local review was central
to IRBs from their inception in 1966 to about 2000. This made complete sense when local communities,
practices, and laws could be quite different; when institutions with a federal assurance of compliance
were primarily major academic medical centers with large research portfolios; and when there were
very few large multi-center trials.
-This gradually shifted. In 1979, the second issue of IRB: A Review of Human Subjects Research included
the article cited in the introduction about coordinating multiple IRBs (Kavanagh et al. 1979, 1-3). In
January 1981, U.S. Department of Health and Human Services (HHS) regulations (45 CFR 46) were
updated and in the preamble there was discussion of cooperative review. The decision, embodied in
46.114, was that "cooperating institutions may use joint review, reliance upon the review of another
qualified IRE (sic), or similar arrangements aimed at avoiding duplication of effort" (HHS 1981, 8381).
-On the same day in 1981, the U.S. Food and Drug Administration (FDA) published its regulations (21 CFR
50 and 56), harmonizing as much as possible with 45 CFR 46. A major distinction was that FDA included a
requirement that each investigator was required to have separate IRB approval. Recognizing that
investigators in practice may not have an institutional board, the FDA said that they could "use an IRB
created by the sponsor."
Defining Centralized Review through Nomenclature and Models - CORRECT ANSWER -The history of
external review has led to a variety of structures with no single model and no single accepted
terminology. People talking about an external IRB may be referring to very different relationships.
, Saying, "Central IRB," creates different pictures for people depending upon their background and
viewpoint. The meaning is very dependent on one's position in the research and IRB world. For example,
IRB administrators at an active hospital might deal with their institutional IRB, several independent IRBs,
the National Cancer Institute's (NCI) Central Institutional Review Board (CIRB), and perhaps other
consortia or collaborative IRBs.
Nomenclature - CORRECT ANSWER -There are a number of concepts that overlap and terms that have
not been adequately defined. During the Public Responsibility in Medicine and Research (PRIM&R)
conference in 1998, there seemed to be some confusion about what a Central Review Board (CRB) was
and where it could operate. The "National Conference on Alternative IRB Models" (OHRP et al. 2006)
attempted to develop some models of relationships. There is still no clear standardized nomenclature,
and the language used often mixes functions and relationships.
-Without any accepted systematic definitions describing IRBs and their relationships, here are some
basics terms to describe external IRBs:
-A Central IRB is a single board that reviews research studies for multiple sites. A central IRB can be any
registered IRB that functions to review multiple sites but most commonly the term central IRB
references an independent IRB.
-Single IRB of Record is a term adopted by the Clinical Trials Transformation Initiative (CTTI). Their
website states, a central IRB is "a single IRB of record for a given protocol. The central IRB assumes all of
the usual IRB responsibilities including all reviews of all relevant documents" (CTTI 2014). A single IRB of
record oversees the same research protocol across a number of locations. Single IRB of record generally
operates within an FWA situation. It might be a consortium or cooperative IRB, an IRB from another
institution, or a federal IRB. Central IRB and Single IRB of Record seem to be synonymous but used at
different times.
-Centralized IRB review is a function performed by a Central IRB. Regardless of the group providing it,
centralized IRB review is one review for a number of sites. Commonly, the sponsor determines which
sites are to participate and suggests or requires those sites to use the central IRB selected to perfor
Cooperative Inter-Institutional Models - CORRECT ANSWER -Any institution may create a written
agreement to use another institution's IRB for some or all reviews. An entity or group of institutions can
organize an IRB to review all or a subset of studies. These are closed systems available to only named
institutions. There are several examples.
