ICON operationalised a fully decentralised clinical trial for a midsized pharmaceutical company running a proof of concept to evaluate self-directed scalable electronic health platform methods for communicating Alzheimer’s Disease (AD) gene and biomarker results. ICON enrolled 600 participants in the US through two remote sites using digital recruitment methods, pulling from a sponsor derived participant pool. Throughout the trial, participants engaged with a digital platform to complete eConsent, ePROs, and telehealth visits. The primary and secondary endpoints were captured via the digital platform. 

Digital recruitment 

The digital recruitment process faced significant challenges around enrolment and diversity targets while under pressure to improve the overall recruitment timelines. ICON engaged potential participants with digital invitations to enrol in the decentralised clinical trial. If a participant consented to be contacted regarding inclusion in the trial, the ICON Concierge Services (CS) team reached out to welcome them and referred them to a remote site with the appropriate multi-state licensure. If potential participants did not respond, the CS team made a total of three attempts at contact before deeming them lost to follow-up. Despite these efforts, enrolment rates were slower than expected to reach the target of 600 participants and the population was disproportionately Caucasian.

ePRO compliance 

The ePRO compliance process encountered challenges, particularly at Visit 5, which was a critical visit for the trial's progress as participants learned their APOE genotype. A significant number of participants were not completing the assessments within the defined visit window. 

Notably, there was a 10% drop in compliance from Visit 5 to Visit 6, which complicated the trial's data collection and analysis efforts as a result of missing data.

ICON’s Digital Risk Detection (DRD) team monitored the enrolment data, identified opportunities to improve the enrolment process and collaborated with the trial team to implement compliance strategies. 

Optimised enrolment efficiency

The DRD team created an enrolment forecasting model that applied success rates to each step in the digital recruitment process. This modelling provided insight into bottlenecks for targeted intervention that would have higher impacts on recruitment results. This model highlighted the need to revise recruitment outreach, including updated language and clear information about trial design and participant time commitment upfront. We also identified key points for efficiency improvement. 

These five solutions were implemented and tracked throughout enrolment as illustrated in Figure 1 below:

1. Adjust language in invites: Improved enrolment after refining invite language for inclusivity and providing important participation information upfront.
2. Reduce CS outreach attempts: Increased enrolment by optimising outreach resources, changing to 2 calls + 1 email.
3. Increase volume of invites: Dynamically identify the number of invites that need to be sent each week to remain on target which boosted enrolment by increasing weekly invitations.
4. Redefining source of truth: Enhanced enrolment rates by ensuring accurate enrolment data is continuously updated.
5. Protocol amendment: Significant enrolment rise following a protocol amendment for more accessible inclusion/exclusion criteria, widening the pool of potential participants.

Increased critical compliance

Analysis of the compliance issues at Visit 5-6 uncovered a time corelation. The solution was to expand the Visit 5 ePRO compliance window from 7 days to 40 days, affording participants more time to complete the ePRO and providing the study team with an actionable follow-up window to ensure the capture of critical missing data.

ICON’s Digital Risk Detection identified risks early, allowing for rapid implementation of mitigation measures to improve data integrity and support a successful digital trial. The process improvement strategies recommended by Digital Risk Detection analysis yielded significant positive results. The enrolment period was reduced by 60% – from 10 months to 4 months. The expanded Visit 5 ePRO compliance window led to a substantial increase in compliance rates, rising from 65% to 93%. These outcomes demonstrate the effectiveness of the mitigation strategies in enhancing both the efficiency and inclusivity of the trial. Furthermore, through cross functional collaboration, ICON exceeded client compliance expectations by 25% on average and have seen continuous improvement in compliance metrics.