subjects to the datasets analyzed and to treatment
groups must be traceable and comply with the ran-
domization scheme and the outcome of the data
review meeting, if such a meeting occurred.
In contrast to GLP regulations, GCP does not
require an audit for all trial reports. The number of
report audits may depend on the audit plan, the
importance of the trial for a regulatory submission
and the confidence in the procedures followed for
evaluating clinical study data and writing reports,
just to name a few.
Systems audits
The purpose of systems audits is to assess proce-
dures and systems across clinical studies and
departments to evaluate that adequate procedures
are followed which are likely to produce a quality
product or result.
Systems audits focus on the verification of qual-
ity control steps incorporated in the procedures, on
interfaces between different functions and depart-
ments and on relationship to external providers.
While noncompliance may be detected in systems
audits, such audits aim to assess the capability of a
system to deliver a quality output.
Based on the above-described trial-related
audits, systems audits can be composed of such
‘core audit elements’ and ‘enriched’ by additional
elements to form a systems audit. In general, the
scope of any study-related audit can be broadened
into a systems audit. The following paragraphs
describe selected systems audit; further informa-
tion is available in literature (DGGF, 2003).
Phase I/clinical pharmacology unit
Early-phase clinical trials, including first-in-man
studies, are often conducted in dedicated phase I
CROs or clinical pharmacology units. Because of
the very limited information on the drug’s toxico-
logical and pharmacological effects on one hand
and the importance of the trials to the entire drug
development program on the other hand, audits of
such trials are a valuable component of the audit
program.
In addition to the components verified for inves-
tigator site audits, the QA auditor should check the
quality management and SOP systems, compliance
with particular requirements for early-phase clin-
ical trials (FDAGuidance for Industry, 1995, 2006;
Draft FDA Guidance for Industry, 2006; ABPI),
recruitment and informed consent procedures for
volunteers (e.g. volunteer panels or database),
medical oversight (particularly on dosing days)
and access to resuscitation equipment and proxi-
mity to emergency units and typical facilities for
phase I trials (e.g. sleeping and recreational rooms,
standardized meals).Clinical monitoringClinical monitoring is one of the core activities in
clinical research and regular verification of the
capability of the monitoring processes is recom-
mended. A systems audit in clinical monitoring
can be based on investigator site audits where
clinical monitoring activities are assessed in
detail. In addition, the systems audit should verify
if adequate SOPs are available for clinical mon-
itoring which comply with GCP requirements
(FDA Guidance for Industry, 1988). The SOPs
should also address procedures for SDV and
document and facility review. Training proce-
dures and documentation for monitors should be
reviewed to ensure that CRAs are adequately
trained in GCP, SOPs and protocol procedures.
This includes the review of activities such as co-
monitoring or supervised visits.
The systems audits should also evaluate proce-
dures followed for investigator site selection and
initiation, the scope and frequency of monitoring
visits and the SDV procedures applied as well as
the timing of and process for conducting close-
out visits. Handling of safety information (AEs,
SAEs) by clinical monitors at the site and in-
house is also an important area to review. Doc-
umentation of monitoring visits is essential, and
the audit should therefore evaluate the contents of
monitoring reports and their timely preparation
and also check if contacts with the investigator
sites between monitoring visits are adequate
recorded.172 CH13 QUALITY ASSURANCE, QUALITY CONTROL AND AUDIT