Parkinson disease (PD) is highly prevalent among neurodegenerative diseases, affecting a diverse patient population. Despite a general willingness of patients to participate in clinical trials, only a subset of patients enroll in them.¹

ICON partnered with a drug development sponsor to conduct an early Parkinson’s disease (PD) study in over 544 patients. As the trial was conducted during the COVID-19 pandemic, there were many site activation and patient recruitment challenges which presented a risk of enrollment delay. ICON’s prompt evaluation and proactive solutions, along with the strong, collaborative partnership with the sites and sponsor helped mitigate delays which resulted in completion of study enrollment and a positive study outcome. The recruitment objective was to randomise 544 patients in 18 months; however, recruitment was impacted by the COVID-19 pandemic, and the recruitment rate was reduced from the expected 0.33 patients per site per month initially to 0.19 patients per site per month putting the initially planned timelines for last patient in at risk.

The most significant recruitment challenge the sites encountered was identifying early Parkinson’s (PD) patients who had not yet started symptomatic-PD medication. While general practitioners (GPs) and general neurologists evaluate and treat clear-cut de novo early PD patients, movement disorders experts still see many de novo early PD cases for either diagnosis or confirmation of diagnosis.

Additional issues encountered that impacted recruitment, were those of patients who preferred an already existing and approved PD treatment rather than an investigational drug, as well as the absence of an open label extension of the main study.

Since delays in recruitment threatened overall enrollment timelines, ICON and the client initiated a series of strategies to be applied and tailored to the different sites to have a noticeable effect on recruitment. 

Patient recruitment and retention

• Although most subjects were recruited from each site’s routine patient pool, ICON worked with the sites to either optimise their routine patient pathways or to add new pathways for patients to their sites.
• Sites were asked to actively engage with their referral networks and ICON provided them with doctor-to-doctor letter and study fact sheet templates to customise and distribute to their existing referral networks.
• Sites were also provided with a clinical presentation covering the study and the investigational drug which PIs could use at meetings with local GPs/neurologists. All sites were made aware that reimbursement was available if they did a mass mailing or held a lunch/dinner meeting.
• A digital marketing campaign was launched in the US including banners/ads placed on selected websites frequented by potential subjects searching for information regarding early PD. After clicking on the advertisement or the banner, patients were requested to complete an online questionnaire regarding their disease and provide their contact details. If subjects met preliminary eligibility criteria, permission was requested to send their survey results to the closest site. Leads were centrally reviewed on a weekly basis and the digital marketing partner followed up with sites where the leads were not progressing.
• A direct-to-patient digital campaign resulted in candidates that were not comparable in quality as the sites own subjects. Only 8% of subjects from the direct-to-patient digital campaign were ultimately randomised, however, ineligible candidates were identified and removed by sites and a central eligibility committee. Several sites did not agree to the service due to the quality of the referrals and the follow-up work required. In the US, 45 out of 380 subjects (12%) came from this digital recruitment service, which is a significant number of subjects who would not have otherwise been recruited.

Other patient facing recruitment strategies included:

• Tailored advertisement/flyer template provided to allow the sites use a paper or online format.
• Distribution of patient brochures were the most popular for sites as the collateral could be left in waiting rooms or other locations where PD subjects are seen.
• Many sites held annual symposiums requiring sponsorship and in return, sites would host research round tables where the coordinator would be present to hand out brochures and talk to interested attendees.
• Some sites held in-person or virtual meetings for recently diagnosed patients where they presented the currently available trial options.
• Travel reimbursement was provided for patients to help ease the financial burden of participation.

Decentralised study implementation

• Decentralisation of the study procedures was successful as most of the assessments were questionnaires with scales. The only exception were assessments related to the primary endpoint (MDS-UPDRS) which could not be performed remotely.
• Blood pressure devices were provided to patients so they could take their own vital signs.
• Both sites and subjects were able to seamlessly move from on-site to remote (telemedicine visits) after the start of the first wave of COVID.
• Both, the sites, and ICON were able to adapt very quickly to implement the required remote monitoring due to restrictions arising from COVID decentralised recruitment strategies.
• During the pandemic many sites could not be visited for an extended period, so it was decided to schedule 10–15-minute weekly video calls with the PIs and SCs for each of the US sites (with key stakeholder from ICON and Sponsor company present).
• The video calls proved to be a low-cost and low-resource way for the Sponsor (and CRO) to speak directly to the sites and ensure clear communication, identify issues or opportunities at select sites and generally encourage the sites to recruit subjects for the study.
• Another reasonably low-cost recruitment strategy used to help bolster enthusiasm for the study was to have three regional remote “pizza parties” for the sites using services where you can make food orders for individuals in different states so that they all arrive at the same time.
• Utlised Webex / Zoom virtual meetings to present the latest study information and sites were encouraged to participate using their video cameras.

Central eligibility committee (CEC)

• Sponsor aligned themselves with CEC for their PD expertise and to give credibility to the Sponsor and study.
• Each time a subject was enrolled, sites needed to complete and submit a 26 question “randomisation authorisation form” which consisted mostly of check boxes with specific details regarding their disease, medical history, and medications. The forms were first routed to ICON for a quick, straight-forward review to ensure all required information was present. Accurate forms were then forwarded to the eligibility committee and always reviewed by a Movement Disorders expert usually within an hour of receipt. If the patient was approved or rejected a signed RAF would be sent back to site. If there were questions, an ICON representative would act as intermediary between site and the committee, and the site called directly if required.
• Approval by the eligibility committee was part of the eligibility criteria and it was by far the main reason why subjects failed screening. However, we still had a modest screen fail rate overall (20%) and it appears the eligibility committee was able to weed-out borderline or questionable cases. Ultimately the study was a success, so the EC played a significant role in ensuring suitable patients were being enrolled.
   

By carefully assessing the main challenges encountered during the study, understanding the very specific patient population, and mitigating the impact of the pandemic, ICON was able to systematically develop and implement a multipronged strategy to address these obstacles. The study team proactively kept the sites engaged which resulted in completion of study enrollment and a positive study outcome.