In a double-blind multiple system atrophy (MSA) study, the site profile required sites with previous experience in neurodegeneration studies or in similar rare CNS studies. Some countries were mandated by the client due to marketing considerations. One of the key selection criteria was to have access to patients via patient database. The client completed start-up in the US and ICON completed start-up in the EU and APAC. Site contract negotiations were lengthy due to selection of multiple academic sites in the US. 

Numerous site activation barriers were encountered as many scales required pre-qualifications. Additionally, an MRI qualification was also required factoring in another department’s availability for contracts. 

MSA patients are quite impaired and traveling to attend the site appointments with their caregivers was challenging for many of them.

In order to meet recruitment timelines during the COVID-10 pandemic, the ICON team implemented the following mitigation plans to ensure continuation of enrollment:

• Targeted solutions to expedite start-up and fast track site activation: Cloned site contacts to expedite contract negotiations and signature 
• Site engagement strategy based on global communication on study progress including study newsletters, global and regional on-line meetings used for study updates and for training, and client attendance at major neurodegenerative and neurology meetings. Regular site contact by client including one-to-one meetings with every site regarding impact of COVID-19 for each patient as well as strong CRA ongoing site support during start up to expedite site activation and throughout the study lifecycle including training for common issues/problems. 
• Patient recruitment: A patient travel reimbursement system was established from the outset and home nurse support was provided for visits where efficacy assessment was not conducted (r/t COVID-19 issues). An open-label extension added to the study to support all patients that wished to continue participation. Site optimisation calls were implemented in the US, Austria, France, Germany and the UK.

Sites were provided with clinical enrollment manager support: 29/29 sites were contacted and 121/121 calls completed. ROW calls started in Jan 20 and were completed in July 20 (with a hold for 2 months due to Covid-19): 18/22 sites were contacted, 19/110 calls completed

By implementing the specific site communication strategy, contracting timelines were decreased by up to 50% for the initial contract with the US sites. A total of 48 sites were activated and all 48 actively screened patients in the 6 countries selected. 

Enrollment went exceedingly well and generally patients and sites were very interested to join the study. US enrollment would have completed 3 months early before COVID-19 delays began and EU sites likely would not have been unable to enroll without COVID- 9 delays. Sites had patients that were waiting for sites to re-open post COVID-19 lockdown and finally enrollment ended over 6 weeks ahead of the planned end of screening with randomisation in the double-blind study 4 weeks early with nearly 85 additional patients (336) randomised over the patients initially planned. One hundred percent of US sites screened patients and more than 50% screened more than contracted. Eighty-six percent of ROW sites screened patients and all US sites that received more than CEM calls screened more than 10 patients.