The rare disease clinical trial landscape faces unprecedented challenges in patient recruitment and retention, as demonstrated by recent experiences with alkaptonuria (AKU) research initiatives. With only approximately 1,000 known cases worldwide, the search for eligible trial participants resembles finding needles in a haystack, requiring innovative approaches to both identification and engagement.
Strategic Patient Identification Approaches
The National Alkaptonuria Centre (NAC) and DevelopAKUre trials have implemented multi-faceted recruitment strategies. The NAC, an NHS-funded Centre of Excellence established in 2012, has successfully enrolled 36 patients, with seven more in the pipeline. Meanwhile, DevelopAKUre's ambitious program requires 156 participants for its three-study series investigating nitisinone's effectiveness.
Primary recruitment methods include systematic outreach to healthcare providers through fax campaigns targeting GPs across England and Scotland. However, these efforts have yielded modest results, with only a 6% response rate. The challenges stem from multiple factors, including limited physician awareness of AKU and occasional reluctance to refer patients to specialist centers.
Digital Innovation in Patient Outreach
To overcome traditional recruitment barriers, the research teams have developed a strong online presence. A dedicated DevelopAKUre microsite complements their main website, both featuring patient contact forms. This digital strategy has proven effective in building patient communities and facilitating direct communication with potential participants.
The Retention Challenge
Patient retention has emerged as an even more significant challenge than initial recruitment. The NAC program requires participants to commit to four-day visits in the first year, followed by three to four-day visits in subsequent years. Similarly, SONIA 2 trial participants must complete six visits over four years, often requiring international travel.
Innovative Retention Strategies
To address retention challenges, the programs have implemented several key initiatives:
- Dedicated support staff providing personalized assistance
- Comprehensive pre-visit information packages
- Travel and accommodation coordination
- Between-visit home support services
- Regular communication about trial benefits and progress
Trial Design Considerations
The DevelopAKUre project, co-funded by the European Union and a consortium of 13 European organizations, encompasses three distinct studies:
- SONIA 1: A four-week dosing optimization trial
- SONIA 2: A four-year effectiveness study
- SOFIA: A cross-sectional study examining disease progression
A particular challenge in the SONIA 2 trial design is the inability to use placebos due to nitisinone's visible effect on urine color, requiring transparent communication about treatment assignment.
Future Directions
The research teams continue to evolve their recruitment strategies, including testing new approaches such as traditional mail campaigns to complement existing methods. This adaptive approach, combined with strong patient support systems, represents a potential model for other rare disease trials facing similar challenges.
