time points related to a clinical trial: before a trial
starts (e.g. to evaluate the adequacy of the selected
site), during an ongoing trial (i.e. surveillance
inspection) or as part of a Marketing Authorization
Application (MAA) (i.e. pre-approval inspection)
(European Union Clinical Trials Directive, 2001;
GCP Directive, 2005).
The assistance of QA auditors in preparing,
managing and following up GCP inspections is
vital. Auditors are familiar with audit and inspec-
tion situations and know how to interact with
inspectors. The presence of QA auditors during
regulatory inspections (in-house as well as at exter-
nal facilities) is strongly encouraged. A wealth of
information about approaches, needs and expecta-
tions of GCP inspectors can be gained. This knowl-
edge may be very helpful for preparing
forthcoming inspections and for formulating
responses to inspection reports.
Inspection readiness is another area where the
QA function can contribute considerably to estab-
lish systems and procedures which ensure that a
company is always ready for an inspection. This
includes a dependable SOP system in full compli-
ance with guidelines and regulations, up-to-date
training programs and documented training for
all employees with complete training files, current
CVs for all persons involved in clinical research,
current organizational charts and job descriptions,
contracts in placewith all external providers and so
on. QA auditors can help establish and maintain a
state of inspection readiness in the company.
Suspected misconduct and fraud
Misconduct or fraud is a rare occurrence in clinical
research, but when misconduct or fraud is con-
firmed the consequences can be disastrous (Lock
et al., 2001; Eichenwald and Kolata, 2004).
Fraudulent practices in clinical trials can lead to
trial subjects being exposed to safety risks, to sub-
mitted or published clinical data being jeopardized
and, if the product has been licensed based on false
data, this may result in compromised patient safety.
Therefore, any suspected case of misconduct or
fraud should be taken seriously and be assessed –
this is when QA auditors should be involved.
Anyone who has access to or responsibility for
collecting, transcribing, monitoring or reporting
data and who is motivated to deceive can commit
fraud. Although misconduct and fraud is reported
to occur rather at investigator sites than elsewhere,
this should not preclude from finding obscure and
questionable situations and documentation in
other areas.
It is important to distinguish clearly between
misconduct, fraud and honest error. FDA provides
the following examples for fraud:1.Altered data: Data that have been legitimately
obtained, but that have been subsequently chan-
ged to bias the results.2.Omitted data: The non-reporting of data, which
has an impact on study outcome, for example,
the non-reporting of adverse events.3.Fabricated data: Data that have been deliber-
ately invented without performing the work, for
example making entries in case record forms
when no data were obtained or patients not seen.QA auditors should help investigate suspected
fraud or misconduct by means of data and docu-
ment review and audits at the concerned sites. Their
independent and objective perspective of the situa-
tion will be important to provide an unbiased view
and a valid assessment. Investigations of fraud
should always be conducted by two auditors.
Training on how to detect and, even more impor-
tant, prevent fraud is another area where QA should
be involved (Hattemer-Apostel, 2004). QA audi-
tors should play an active role in fraud prevention
and awareness training measures so that all
employees are adequately sensitized to reliably
identify such occurrences.13.5 Audits from A to Z
Audit program
Audits should be carefully planned and scheduled
to maximize the potential and the use of QA
resources. Ideally, the audit program should be13.5 AUDITS FROM A TO Z 165