Initial assessments conducted at the sites revealed a range of causes for poor compliance follow-up, from nonsubmission of a completed CRF to inefficiencies in basic site procedures, and also included:

• Scheduling appointments outside visit window periods
• Appointments not recorded in appointment books
• Contact details for subjects not recorded
• No process in place to determine if visit had been missed
• No process in place for contacting subjects who missed visits.

These inefficiencies were addressed with a compilation of procedures and guidelines that could be applied across sites. Training was provided in January 2006, and clinical trial site staff were assigned the responsibility of follow-up of missed visits.

Once these corrective measures had been implemented, persistent missed visits were once again analyzed. Sites were able to track and follow up on missed visits, but participants were still not attending scheduled visits. Analysis revealed the following underlying causes:

• Access to clinics posed a problem for participants especially in the rural sites with traveling distances in excess of 200 km. This was, however, not unique to the rural sites but was found in large central hub sites that serviced a large geographical area. Participants experienced problems with access to transport, cost of transport, travel time to and from sites, and time away from work.
• Participants in advanced stage of the disease or experiencing opportunistic infections were too weak to travel even short distances and then wait to be seen in a clinic.
• Clinics were extremely busy and extended waiting periods caused participants to default on appointments.
• Side effects of study drugs/poor compliance resulted in participants not wanting to attend visits.

Advances and limits

Each section of the Phidisa research team has found value in the benchmark assessment tool, which is now routinely used to evaluate, monitor, and report on various aspects of clinical trials. But objective benchmarks have limitations.

Resource requirements. Study monitors, site staff, the DM team, and study leadership must all dedicate time to the assessment of benchmarks. Initially, resources are required to develop and assess the implementation of the benchmarks. Apart from this initial implementation phase, resources are then spent on the preparation for each monitoring visit, assessment of benchmarks during the monitoring visit, and the subsequent collation of results and formulation of the tables and reports. Average additional time required to implement benchmarks at a given site for this study:

• Monitoring visit preparation: 10%
• Monitoring time on site: 25%
• Collation of results and formulation of the report: 35% to 40%.

At times this may seem to divest resources from achieving the standard in order to measure the performance. However, many of the activities included in the benchmark reports are ones that would require site follow-up in any case. The reporting mechanism simply provides an added incentive to focus the resources into this review and quality control process.

Limitations in the interpretation of the benchmarks. Benchmark figures cannot be interpreted in isolation. It requires a comprehensive assessment, which necessitates the benchmark report be evaluated in synchronization with the monitoring visit report for a complete and accurate understanding.

The analysis of figures (benchmark report) must be compared with action information (monitoring visit report). The benchmark reports serve as a tool to measure performance, and once standards have been set, sites are encouraged to maintain those standards or improve on them. This requires understanding by all site personnel with respect to benchmark report objectives. It is expected, however, that fluctuations in the benchmarks obtained will occur.