Basics of Quality Management in CT

3. Audits

Even though SOPs are an important part of quality management activities, they cannot stand alone. Imagine you are writing an SOP and you have misunderstood the procedure! You might be very skilled in producing good descriptions of the work to be performed, but if you have misunderstood the process, your instructions might lead to a situation where the procedure is repeatedly performed incorrectly.

So how can we avoid this situation? One possibility is to invite independent experts to supervise the organisation and operational procedures of the clinical trial. This will provide an impartial view on how the trials are or should be performed. This supervision is called ‘audit’ and the independent experts are called ‘auditors’. It is the responsibility of the sponsor to ensure that audits are performed on a regular basis.

According to the GCP-guideline an ‘independent’ auditor means that the sponsor and the auditor should not be working within the same organisational unit. A sponsor may hire an external auditor, but many pharmaceutical companies often employ their own auditors. In this case, the auditors work in a completely separate department.

In practice an audit may be performed in two different ways:
  • The auditor uses one trial as an example and evaluates all the procedures that have been used in that trial.
  • The auditor looks at one specific procedure. For example, they might look at the procedure for ‘reporting of adverse reactions’ and then evaluate a number of trials where this has been performed.
Auditors normally work systematically with both types of audits. A thorough audit of a trial normally takes several days as the auditors have to examine all activities and documents of the trial. The audit will evaluate trial conduct and compliance with what has been described in:
  • The relevant SOPs.
  • The protocol of the trial.
  • GCP-guideline.
  • Applicable regulatory requirements.
Definition of an audit in the GCP-guideline

‘A systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data were recorded, analysed and accurately reported according to the protocol, sponsor's standard operating procedures (SOPs), good clinical practice (GCP), and the applicable regulatory requirement(s).’

An audit may be initiated for two reasons: either as a part of a routine supervision or in response to a special concern that has been raised about a certain trial. The latter type of audit is called ‘for cause audit’ and may be a useful tool for a trial sponsor if they have a concern about malpractice in a trial.

The most important part of the audit is often what takes place afterwards. Each deviation from the intended trial conduct is described. These are called ‘findings’ and are always graded in two to three categories expressing how serious they are. These findings are described in an audit report. If a deviation can compromise the trial result or the patients’ safety or rights, the sponsor must describe concretely how the situation will be handled. It is equally important that the sponsor implements so called ‘corrective actions’ to ensure that the deviation will not happen again. When the audit is completed the auditor will issue an audit certificate which confirms that the audit has taken place.