13.6 Brief outline of audit types
Audits are conducted either for a specific trial or to
evaluate an entire system in clinical research and
development. Both approaches are value-adding
and ensure that clinical trials are conducted accord-
ing to accepted principles, that trial participants are
treated ethically and the trial data are valid.
Trial-related audits focus on a particular trial to
assess compliance with the protocol, with related
SOPsandapplicableGCP regulations. Ofparticular
interest is how trial participants are informed of the
trial, the study activities conducted at the investi-
gator sites and the procedures of clinical data hand-
ling, recording, processing, analysis and reporting.
Systems audits are not specifically conducted for
a particular trial, but may use a clinical trial as a
guidance to assess the system. These audits evalu-
ate whether a system (e.g. clinical monitoring) is
capable of delivering the desired result (e.g. ade-
quate oversight of investigator sites and appropri-
ate documentation of monitoring activities). To
this end, the adequacy and practicality of processes
and procedures followed within a system is ana-
lyzed and SOPs, working instructions and process
descriptions are assessed for their suitability to lead
to consistent services, documentation and output.
SOPs are checked for compliance with GCP reg-
ulations and guidelines, and the education, training
and qualification of involved personnel are
reviewed during systems audits. And finally, the
interfaces to other internal departments and to
external service providers and contractors are eval-
uated to identify potential process weaknesses or
gaps which may impair or even invalidate the
clinical trial and its data.
Trial-related audits
Protocol audit
Protocolauditsarebestscheduledwhentheprotocol
is still in draft stage, immediately prior to finaliza-
tion. The purpose of protocol auditsistoassess ifthe
protocol compliesICHGCP(1995),ICHE3 (1995),
ICH E9 (1998), the Declaration of Helsinki (2006),
national regulations (e.g. FDA CFR requirements
(FDA 21 CFR Part 50; FDA 21 CFR Part 54; FDA
21 CFR Part 56; FDA 21 CFR Part 312; FDA 21
CFR Part 314)) and company SOPs regarding for-
mat and contents of protocols. The audit also eval-
uates if trial procedures are accurately, completely,
clearly and consistently described in the protocol so
that misinterpretations are prevented.
If a generic subject information sheet and
informed consent form are attached to the protocol,
these documents should also be reviewed for com-
pliance with any requirements for informed con-
sent, such as GCP, SOPs and the Declaration of
Helsinki, and for consistency with the trial proto-
col. The information sheet and informed consent
forms must be written in a language understand-
able to the trial participant and should include
information on data protection/privacy. Further
information on protocol and informed consent
audits is available in literature (Bohaychuk and
Ball, 1999; DGGF, 2003).Case report form (CRF) auditCRF audits should also be conducted on a draft
version, just before finalization of the CRF. As the
CRF is ‘the’ data collection tool in a clinical trial,
errors and inconsistencies in its contents and design
and inconsistencies with the trial protocol may lead
to serious problems if they are not identified prior to
the CRF being used. This holds true for paper CRFs
and electronic CRFs, as well as the use of remote
data entry (RDE) or web-based data collection and
transmission tools. The latter requires careful con-
sideration of related guidelines (FDA 21 CFR Part
11; FDA Guidance for Industry, 1999).
The focus of the CRF audit is on consistency
with the protocol, ease of completion (e.g. module-
based style, chronology of events) and compliance
with SOPs and any requirements outlined by data
management (DGGF, 2003).TMF auditTMF audits can be conducted at any stage of a
clinical trial, for example before shipping investi-
gational medicinal products (IMPs) to a clinical13.6 BRIEF OUTLINE OF AUDIT TYPES 169