The Precision Blog

Strategies that Work in Rare Diseases

Written by Vincent Shortino | Jun 7, 2023 7:44:00 AM

DCT strategies for rare disease studies 

Decentralized clinical trials (DCTs) have become increasingly common, rising from 250 studies in 2012 to an estimated 1,425 studies in 2022, according to GlobalData’s Clinical Trial Database.1 The global lockdowns triggered by COVID-19 accelerated adoption of this approach to clinical research, as sponsors and CROs turned to virtual, remote, or hybrid study methods to overcome pandemic-related restrictions and incorporate remote data collection and monitoring.1 

For rare diseases, where the patient populations are small and globally dispersed, DCTs can be an effective method for attracting participants and increasing retention as patients and caregivers do not have to visit sites as often or even at all. Incorporating decentralized approaches also increases access, equity, and diversity by facilitating clinical trial participation for patients who might not otherwise be able—or willing—to travel to geographically distant sites or specialized centers. 

FDA Guidance on Decentralized Clinical Trial Strategies

On May 2, 2023, the U.S. Food and Drug Administration (FDA) released draft guidance with recommendations on implementing DCTs. Whether used alone or in combination, the decentralized strategies below can help improve recruitment, enrollment, and retention in rare disease studies. 

Telemedicine visits 

Siteless or hybrid approaches can be attractive for rare disease trials because patients and caregivers may prefer not to be in a hospital, and condition severity, mobility challenges, and long-distance travel—sometimes across borders—may otherwise limit study participation. Siteless trials rely on remote telemedicine visits and do not require patients to travel to a physical site, while hybrid trials combine telemedicine and in-person visits.

Where telemedicine is not possible, engaging local healthcare providers to participate in patient monitoring, local laboratories to assist with sample collection, and home healthcare services to collect, process and ship lab samples for analysis may be an option for limiting travel to sites. These models can reduce the burden on patients and families, while still allowing for collection of high-quality data. 

Home health nursing support 

If the protocol includes assessments that can be performed in the patient’s home or preferred location, mobile nurses can be used to collect those data. Appropriately trained home health nurses can assist with sample collection, limited physical examination, and investigative product (IP) administration and accountability. Home health nurses can also provide personal support to patients and caregivers, building a rapport and sense of trust which keeps study participants engaged. If possible, utilizing the same nurse for each patient throughout the study can further strengthen compliance and retention. 

 

Electronic patient reported outcomes (ePROs) 

Digital tools such as electronic patient reported outcomes (ePROs), eConsent, and electronic clinical outcomes assessments (eCOA) can be applied to DCTs to further reduce patient burden. ePROs and eCOA enable sites to capture outcomes such as pain scales or quality of life questionnaires using a smartphone, tablet, computer, or other device. These systems may improve data integrity as they generally offer input validation to check that entries are valid and complete. They also have the added benefit of being less time consuming for patients to fill out and for investigators to analyze. 

Any digital tool utilized in a DCT should be fit for purpose and the data collected from it should be acceptable from a regulatory perspective. The FDA has released draft guidance on Digital Health Technologies for Remote Data Acquisition in Clinical Investigations with recommendations on selecting and validating digital tools used to collect data for clinical trial endpoints. Patients should also be trained on how to use any devices, applications, or wearables used to collect data. 

Home IP shipment 

Where possible and when it can be safely administered by either the patient, caregiver, or home healthcare provider, delivering IP directly to the patient’s home can spare a site visit. To ensure proper administration and protocol adherence, training would be provided to the patient and/or caregiver. In addition, a robust logistics strategy is necessary for ensuring supply chain integrity and patient confidentiality.  

Concierge services 

When site visits are required, providing concierge services to assist with visit coordination and travel planning can alleviate patient and caregiver burden and minimize stress. Concierge services can even be extended to the site visit itself, whether it is offering valet parking or limiting procedure wait times to optimize the patient’s overall study experience.  

Considerations for pediatric rare disease studies 

Of the more than 6,800 rare diseases that have been identified, 70% are genetic disorders that start in childhood. Recruitment and retention in pediatric rare disease trials is particularly challenging due to the need to juggle school schedules, work responsibilities, and family obligations to accommodate study participation. While decentralization offers opportunities in pediatric trials, it also creates new obstacles for sponsors and CROs. Some of these obstacles are intrinsic to the developmental variability within the pediatric population. In addition, the needs of participants under age 18 vary not only from adults, but also across the pediatric age spectrum. 

Technology 

Any technology incorporated into the study should be adapted to the language and comprehension levels of the target patient age ranges. Each age group cluster within the under-18 age range may have unique needs. For instance, if a trial involves wearable devices, it is important to ensure the device is appropriate and comfortable for all age groups to avoid it being removed by the trial participant. Very young patients may not understand the importance of wearing the device and teenagers may feel self-conscious about wearing one if it is conspicuous.1  

 

PROs 

For DCTs that involve self-reported outcomes, such ePRO, eCOA, or eDiaries, it is important to consider when a child is old enough to be reliable data source. Any electronic assessment should have age-appropriate language and vocabulary and may need to be adapted to different age ranges. Given the inherent subjectivity of self-reported outcomes, it may be useful to include varying sources of data—such as objective endpoints, observer-reported outcome measures performed by caregivers, or performance outcome measures scored by study staff—to bolster the integrity of the results.1  

Considerations for global studies 

While the regulatory frameworks for DCTs in the US and EU share some similarities, factors related to informed consent, data collection, and how to handle missing data may vary. For example, the EU’s General Data Protection Regulation (GDPR) requires strict data privacy and any DCT technology must protect patient confidentiality and comply with GDPR guidelines. Further, in the EU, regulatory requirements for DCTs vary across member states and this fragmented landscape can be difficult to navigate. Sponsors should ensure they are familiar with the specific requirements and guidelines that apply to each region or country involved in their study.  

Key takeaway 

By reducing patient burden, DCT approaches help maximize access, enrollment, and engagement in rare disease studies. However, DCTs require careful planning and implementation. When considering decentralized approaches for a rare disease clinical trial, it is important to evaluate each element of the protocol and assess whether a decentralized methodology can be implemented without sacrificing data quality.  
 
At Precision for Medicine, we have been conducting DCTs for rare diseases since 2014, with experience in global studies across more than 80 disease conditions. We have also built a qualified network of over 30 DCT vendors spanning across patient services to streamline study implementation.

Speak with an expert about DCT strategies for your study >

Reference:

1. Clinical Trials Arena. 2022 projected to be a leading year for decentralised clinical trials, October 11, 2022. Available at https://www.clinicaltrialsarena.com/comment/2022-decentralised-trials/.