Ensuring protocol compliance in an Alzheimer’s study with complex vendor management

A drug development sponsor sought help in recruiting patients for a study on the efficacy of a recombinant humanised Igg4P monoclonal antibody in prodomal to mild Alzheimer’s disease (AD). The study required screening 1,000 patients to enrol 450 across 3 study arms at 125 sites. The sites were located in ten countries in North America and Europe. There was a 60 day screening window with three subsequent steps comprising AD scales, MRI scan and PET scan with radioligand.

The tracer, radioligand, has a limited production managed by five cyclotrons globally. The number of doses manufactured per day is restricted. Its limited stability contributed to the vendor management complexity. Managing the supply and demand was critical to the successful completion of the study. As the study was randomised, predicting where and when the tracer would be required was not feasible. The main challenge was that if there were a large number of patients at one site, it could reduce the availability of the tracer elsewhere, thus, balancing the number of patients at each site, and other factors, such as site distance from the tracer manufacturing site, increased the logistical complexity.

Alongside this, there was a higher than anticipated screen failure (SF) rate. The sponsor’s expectation was 55% SF rate but the actual rate was 75%.

ICON implemented a site activation strategy over the 125 sites with a proactive management approach to the recruitment for each site. ICON’s regulatory team provided support during the submission process to expedite approval timelines. As an international study, there were multiple languages involved, sometimes even at the same location. The patient recruitment team developed a suite of materials for the investigators, patients and their carers and ensured that all materials were appropriately translated and available in the local languages.

During start-up, there was intensive, focussed communication with vendors and sites. Collaborative and supportive relationships were developed between all stakeholders before the maintenance phase. Any potential issues were identified early, so that mitigating strategies were in place. Support from ICON”s local clinical research associates (CRAs) was critical, they communicated frequently with the sites and provided additional support in the local language. The CRAs were proactive and when necessary, arranged meetings with the vendors and site staff to address any remaining obstacles.

A detailed end to end tracker was implemented by ICON. This followed the steps from tracer production to scan completion and was uploaded to the ICON-managed imaging vendor.

Recruitment was completed three months ahead of time with 1,667 patients screened and 466 randomised. During the double-blind period 97% completion of all scans was achieved. This compliance rate was higher than what was seen earlier in the study.

ICON’s flexible project management pivoted to mitigate against emerging risks and challenges. With little notice on the availability of the tracer, the team worked with sites to ensure protocol compliance. The supply of radioligand was beyond ICON’s control, but with solutions in place we ensured compliance throughout the life of the study.