Clinical trials auditing

Assessment tools identify, measure and record impairments, disabilities, handicaps and quality of life. Assessment is the first step in rehabilitation, and measurement of outcome is crucial for clinical trials, audit and comparison of different institutions. Patients present levels of functioning must be compared with their premorbid levels, taking account of the numerous comorbidities often present in the elderly (Collen and Wade 1991). 

In accordance to GCP, the sponsor should appoint clinical trial monitors. These act as the main communication interface between the sponsor and the trial site, and should regularly visit the site to oversee that the trials are being conducted and correctly documented in accordance with the protocol and GCP. Reports should be supplied to the sponsor after each visit. It is also good practice for the sponsor to establish an auditing system for independently verifying that the activities in relation to the collection and processing of data at the trial site, and at related laboratories or sponsor s facilities, are conducted in accordance with applicable protocols, procedures, regulations, GCP and GLP. 

CRAs achieve these tasks through frequent visits to the clinical trial site. During these visits, the monitor will verify source data, audit regulatory documents for accuracy and completion, perform drug accountability assessments, and communicate any concerns, problems, or new information with the study staff. 

Most clinical trials have problems, sometimes detected by inspection and audit. These can usually be resolved and, if so, the regulatory submission must include a full explanation of how they were dealt with. Therefore, an audit trail with all the data should be available, accompanied by a statement by QA confirming that the procedures have been audited. 

The new European Directive (2001/20/EC) has reinforced the need for European agencies, as well as those of the United States and Japan, to conduct inspections of clinical trials. Sponsors, mindful of the implications of failed inspections, are carrying out audits by their QA units to try to ensure that standards at a particular site meet the regulatory requirements of GCP, and of any future regulatory inspection. Frequently, the inspections will occur 2 or more years after the end of the study. 

In a similar manner, QA departments and consultants paid for by the sponsor will conduct audits of investigator sites. Again, as with the clinical trial monitor, there may be some annoyance among the investigator and his staff that some person, who may not be a physician, should be appointed by the sponsor to review the clinical trial documentation at the site. 

The new GCP requires that sponsors shall compile plan and operating procedures on auditing and implement auditing in conformity with the plan and the procedures, thus auditors audit not only the sponsor s in-house process but also processes at study sites. Within the sponsoring company, usually aU CRFs and study reports are subject to the audit. Study sites are selected for audit based on auditors SOP, usually based on sampling methodology. Audit certificate for each clinical trial is required to be incorporated into new drug submission dossier. 

In addition, the Office of Scientific Investigations (CDER) conducts biomedical audits of clinical investigator s sites. These investigations focus primarily on sites involved in pivotal clinical trials, but may also involve other sites. Investigators should be informed that they should contact the applicant when the FDA notifies them of an upcoming inspection. The spon-sor/applicant is generally not permitted to be involved in an FDA inspection of an investigator s site. Refer to Chap. 3 for an extensive overview of the FDA s expectations of clinical trial activities. 

Good Clinical Practice (GCP) is a standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials. For more information on the FDA s GCP program, go to http //... 

It is ultimately the sponsor s responsibility to ensure that cGCP is followed in its clinical trials, even though some of the work is contracted out to CROs and other service providers. With regard to analytical laboratories, GCP guidances require that all laboratories have full documentation, data-audit trails, standard procedures, trained staff, archives of samples and data, and routine quality assurance inspections (Prokscha, 2007). If multiple laboratories were to be used, the sponsor would need assurance that GCP requirements were met for every one. In contrast, if a central laboratory is used and all samples are shipped to it, the sponsor only needs to check GCP compliance at that laboratory. 

For clinical trial and audit purposes in large samples, three simple questions group patients into those who are completely recovered, those who are still symptomatic but independent, and those who are dependent, or dead (Dermis et al. 1997a,b). Various more detailed assessment instruments are available that are designed to test different domains (Lyden and Hantson 1998 Warlow et al. 1996) ... 

A declaration to assure the process and methods of the clinical trial conform to GCP or to equivalent standards used is also necesseiry. Moreover, any inspection results by the health authority or equivalent body in the country concerned should be submitted. The audit certification... 

Before 1990, clinical trials conducted in Russia were characterized by a number of peculiarities. Many trials had no protocol and were carried out following the recommendations of the MOH. No ethics committees existed. There was no communication between the sponsor and the investigator, and the latter had no idea about the monitoring or audits, as if no such things existed. Moreover, the clinical data (study reports) would go directly to the Pharmacological Committee without being circulated to the sponsor. 

Program Guidance Manual, 2006), stating Clinical trial quality assurance units (QAUs) are not required by regulation. However, many sponsors have clinical QAUs that perform independent audits/data verifications to determine compliance with clinical trial SOPs and FDA regulations . 

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