Database audits

Systems audits in this late phase in clinical trials aim at assessing related procedures to ensure that capable procedures exist for managing and cleaning clinical trial data, for conducting statistical analyses and for preparing the final study report which represents properly the data collected and reported in the clinical trial. Such systems audits are performed across functional boundaries. Such systems audit can be combined with a database audit and/or an audit of the final study report. 

Workload status and the justification of equipment Regulatory agency compliance Audit trail for all database transactions Security class or hierarchy... 

Now you can reconsider the material balance equations by adding those additional factors identified in the previous step. If necessary, estimates of unaccountable losses will have to be calculated. Note that, in the case of a relatively simple manufacturing plant, preparation of a preliminary material-balance system and its refinement (Steps 14 and 15) can usefully be combined. For more-complex P2 assessments, however, two separate steps are likely to be more appropriate. An important rule to remember is that the inputs should ideally equal the outputs - but in practice this will rarely be the case. Some judgment will be required to determine what level of accuracy is acceptable, and we should have an idea as to what the unlikely sources of errors are (e.g., evaporative losses from outside holding ponds may be a materials loss we cannot accurately account for). In the case of high concentrations of hazardous wastes, accurate measurements are needed to develop cost-effective waste-reduction options. It is possible that the material balance for a number of unit operations will need to be repeated. Again, continue to review, refine, and, where necessary, expand your database. The compilation of accurate and comprehensive data is essential for a successful P2 audit and subsequent waste-reduction action plan. Remember - you can t reduce what you don t know is therel... 

Surveillance audits Consultancy Auditor database Auditor qualification Audit reports Minimum audit man-days... 

Gilks WR, Audit B, De Angelis D, Tsoka S, Ouzounis CA. Modeling the percolation of annotation errors in a database of protein sequences. Bioinformatics 2000 18 1641-9. 

Each data point must be transferred from data sheets into spreadsheets or databases. Verification of each datum should be performed by an individual who did not enter the data being verified. Audits of each phase of the study should be performed (i.e. preparation of collection forms, application calibration, each type of sample collection, sample transport, each type of chemical analysis, data recording, data entry, data verification and data storage). 

Hardcoding overrides the database controls in a clinical data management system. With hardcoding there is no clear audit trail of data change and CFR 21 - Part 11 controls might be considered compromised. 

The tangible data retrieved from databases, reports and forms in an organization are (safety ) incidents, inspections, audits. 

From a practical viewpoint, there are two key benefits to this technology. First, it makes retrieval of data very fast and simple. No one wants to search through reports and notebooks in order to find the associated data for a result that is in question. Second, during a regulatory audit it is crucial that your laboratory is able to produce the specific information with as much detail as is required by the auditor. Again, this task is much simpler when a relational database is managing the information (see Figure 7). 

Time invested by both the data manager and statistician in designing the structure of the database should also reap rewards at the analysis stage. In addition, a good-quality database is essential if the study is to pass the auditing process. 

Samples should be accessioned into a computerized database, consistent with federal regulations (21CFR). Most rules concerning a compliant database have to do with whether the structure provides for an audit trail, so that anyone who has viewed or written to the database can be traced. Handwritten accessioning procedures are strongly encouraged as well. 

With automated databases it is possible to replace a data point with an alternate value without leaving any apparent record of the change. To avoid possible fraud or error and restore the same level of data security, Part 11 requires the inclusion of an audit trail. An automated audit trail will record any change in data values and provide a field for recording the reason, date, and authorization for the change. 

As databases were automated that review function became increasingly problematic, and increasingly a concern of both outside FDA and internal QA auditors. As a response to the difficulty in tracking a data point change in an electronic file automated audit trails were developed, encouraged, and finally (in Part 11) required. 

The use of time-stamped audit trails (Part 11.10(c) and (e) to keep track of any record modifications carried out by the database administrator. 

Third parties can provide custom code, which can be integrated within most common database systems in order to implement audit trails. This approach provides a technological foundation for the proper administration of electronic records, without replacing the application that manages them. 

For example, audit trails may be implemented by using database triggers. A trigger is a feature of the Oracle database, which allows code written by the user to be executed based on an event. The concept implies that the edition of a record will produce an event. The event may be defined as an insert, update, or deletion of data from a database table. 

Data coding—Adverse events (AE), medications Incorporation of local laboratory data into database Investigation and resolution of data discrepancies Data validation and quality control audit Data transfers (test and final)... 

The quality assurance component is vital. Quality assurance (QA) is a process that involves the prevention, detection, and correction of errors or problems, and quality control (QC) is a check of the process (Prokscha, 2007). The data stored in the database need to be complete and accurate. Processes that check data and correct them (i.e., make a change to the database) where necessary need to be documented, and all corrections need to be documented in an audit trail such that a later audit can reveal exactly how the final database was created. 

Qualifications of personnel Services available Offered procedures Capability to complete project Quality controls program Quality assurance program Review and approve contracts Future compliance audits Database management Validation/verification needs Contract laboratories Procedures Facilities/equipment Personnel qualification Training Methodology... 

What audit trail will be created to document data conventions and database corrections ... 

Returning to the clinical activities listed in Table 3, some thoughts on the level of support that is realistic to obtain from CROs are as follows. A number of the labor-intensive activities, such as monitoring, auditing, database management, programming for listings and tables, and statistical interpretation are relatively easy to outsource, and many CROs will have the necessary experience and capacity. 

Hybrid audit trails electronically logging last changed by with date and link to related paper-based change records are acceptable for critical records so long as previous versions of the record are maintained. It may be possible in some cases to fulfill the audit trail requirements with a transaction database log. Some database designs require the user to execute a commit record step, while others commit the data as soon as the next field is tabbed to. In cases where a conscious decision to commit the record is required, data entered should not be defined as an electronic record until this action is taken, thus potentially simplifying the audit trail. In cases where there is no commit step, the audit trail should start as soon as each data item is entered. 

The XXXX computer system. .. lacked audit trail function of the database, to ensure against possible deletion and loss of records. [FDA Warning Letter, 2001]... 

The most common observation made by the FDA concerns the lack of (or incomplete) audit trails. This is often associated with the incorrect identification of electronic records. Specifically, the Warning Letters referred to Chromatography Data Systems (CDS), Electronic Document Management Systems (EDMS), Databases, Batch Records, Change Records, and Device History Records. 

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