Achieving success in rare respiratory disease clinical trials

In recent years, there has been a renewed focus on rare respiratory diseases in clinical development, as patients with these diseases often face long term symptoms and limited treatment options. This has motivated the drug developers to put time and resources behind developing more methods of treatment for conditions including: 

• Idiopathic pulmonary fibrosis (IPF) 
• Pulmonary arterial hypertension (PAH) 
• Pulmonary hypertension associated with interstitial lung disease (PH-ILD) 
• Cystic fibrosis (CF) 
• Alpha-1 antitrypsin deficiency (AATD) 

However, developing these therapies through to market comes with many common challenges that sponsors must be ready to tackle.  

Understanding rare respiratory disease clinical trials and their challenges 

The hurdles sponsors face 

In the search for novel therapies for rare respiratory diseases, sponsors need to have a clear understanding of the common issues that arise during the clinical development process in these disease areas. The most prevalent of these challenges include: 

Complexity of trial design 

Designing and strategizing clinical trials is often complex, especially for rare respiratory diseases, where enrolling appropriate patients and collecting high-quality data to meet complex endpoints is crucial. It is often a tall order for sponsors to find the medical and clinical trial expertise that enables success. There is intense competition for experts that have experience, in-depth knowledge of trial endpoints and the ability to devise strategies to avoid protocol amendments down the line. Clinical teams must also be able to design a trial that focuses on both the critical endpoints required by regulators and the patient burden, ensuring that the protocol is designed appropriately to take both factors into consideration. 

Site location and management 

It is not unusual for studies to include sites that may have limited experience in running rare respiratory clinical trials. In addition, these sites may be understaffed and need additional resources to complete these trials. It is critical that sponsors identify sites that are equipped to handle the specific needs of this therapy area and provide protocol specific team training. Without the experience and knowledge needed to navigate this process smoothly, sponsors may experience delays and higher costs. 

Patient recruitment and retention 

For rare diseases, in general, it is often difficult to find the required number of patients needed to participate in a trial. Rare respiratory clinical trials are no exception. Sponsors need to have access to the resources that allow them to design equitable trials that represent relevant patient populations. Patient groups should reflect the demographics of the disease population so that the resulting therapies adequately serve the affected patients. Sponsors must also have the expertise needed to design studies that prioritize patient retention by minimizing burden where possible without compromising collection of key endpoint data.  

Understanding the needs of rare respiratory patient groups 

The hurdles that patients face 

It is important for sponsors to fully understand the patient experience to successfully overcome the challenges in this area of drug development, including a knowledge of the pathway to diagnosis. Knowing how to design trials around the patient’s everyday experiences is essential to properly addressing common hurdles. Sponsors that genuinely understand the patient perspective are able to implement solutions that result in trial success and retain patients for the full duration of their studies.  

Daily struggles of living with a rare respiratory disease 

Rare disease patients often have to become experts in their own conditions in order to navigate the diagnostic pathway and access the treatment they need. Many rare respiratory patients face: 

• Difficulty breathing and physical limitations, making everyday tasks harder. 
• A lack of options for disease reversal or cures—often medications will only slow disease progression. 
• Long and complex diagnostic journeys. 
• Limited access to the specialists they need. 
• Additional comorbidities. 

Many rare respiratory conditions are long term and degenerative, with no cure. This means that patients must endure frequent medical appointments, treatments, and the burdens that come along with ongoing care. For many patients, this also has a significant negative impact on their emotional and psychological health.  

Common challenges for patients participating in clinical trials 

Participation in clinical trials can be extremely time-intensive for patients. It is often difficult to balance numerous appointments and the time it takes to travel to them with the daily commitments of school or work. Participation is further complicated for patients who are unable to drive themselves to appointments, and others that carry oxygen and struggle with everyday tasks. 

Endpoints, such as spirometry and the six-minute walk test, may be difficult to complete for patients with severe respiratory symptoms due to the physical demands of these assessments. 

Recruitment of inclusive patient populations 

It is essential that patient groups for clinical trials reflect the wider patient population. Patient-centered approaches that are tailored toward equity are essential to advancing rare respiratory therapies. Some patient groups have issues with access to these trials due to the regions where they live, their socio-economic status, or a lack of trust in the medical establishment. Sponsors must address these specific problems with solutions that focus on access, community outreach and education.  

Designing trials for pediatric populations 

Participating in rare respiratory clinical trials can be daunting for pediatric patients and their caregivers, as understanding complex trial details may be overwhelming for both children and their parents. Parents need to be able to navigate the process of giving consent and ensuring their children are comfortable providing assent. Additionally, it is often difficult to administer study drugs to pediatric patients, particularly for young children who may have a hard time swallowing pills, often requiring the development of alternative administration methods. Extensive procedures and blood draws further add to the stress of the experience for young patients. All of these medical needs must be balanced with everyday activities, such as school and play, which adds another layer of complexity. By proactively addressing these challenges, sponsors may better ensure that pediatric patients and their caregivers feel supported and understood throughout the clinical trial journey. Further, this helps ensure that patients remain for the duration of the trial so critical data is collected.  

Real World Challenges

Pulmonary arterial hypertension in children 

Pulmonary arterial hypertension affects both adults and children, but most current therapies are designed for adults, often falling short for pediatric patients. Although many existing drugs are used off label for children, these therapies have not been studied to determine if they adequately meet the specific needs of pediatric populations. Adapting adult protocols for pediatric use in clinical trials also presents significant challenges, and placebo-controlled trials are commonly less favored by parents. Furthermore, the underlying causes of PAH often differ between children and adults. In children, PAH frequently stems from congenital heart disease, adding another complex layer of symptoms for sponsors to consider. 

Strategies for success in rare respiratory disease trials

How to overcome patient and sponsor hurdles 

In this rare disease landscape, there are multiple solutions that sponsors should employ when optimizing their path to market. These center around risk mitigation and flexibility, patient centricity and digital and decentralized solutions. Each area requires specific strategies and extensive resources for successful implementation.  

Risk mitigation and flexibility 

Creating flexible study designs and inclusive protocols requires deep and proven expertise. Teams with a history of success in clinical development are able to use their knowledge to create customized, proactive strategies that reduce patient burden with a particular focus on reducing the number of trials assessments and the frequency and duration of trial visits. They are also able to build the foundational elements needed to enable success, like well-defined endpoints and alignment with regulatory expectations. An early focus on overall trial strategy enables sponsors to avoid protocol amendments later on, thus streamlining timelines.  

Patient-centric approaches 

To succeed in rare respiratory clinical trials, sponsors must understand and expertly navigate the health care infrastructure and cultural, geographic and socio-economic characteristics of patient populations. Structuring visits with consideration of age groups and patient disease characteristics can significantly improve patient participation.  

Pediatric-centric solutions include: 

• Designing materials tailored to different age groups, such as puzzles for young children or communicating via text for teens.  
• Scheduling functional assessments earlier in the visit and more invasive elements later to manage patient comfort and cooperation.  
• Using micro assays to accommodate blood volume limitations in young kids. 
• Leveraging digital solutions to track compliance with study drug dosing and trial assessments. 
• Scheduling clinic visits around school and work commitments (evening and weekend visits where possible and appropriate). 
• Providing compensation for patient travel time, cost burden and other participation difficulties. 
• Understanding how disease severity makes trial participation difficult for patients with symptoms that significantly affect their daily lives. 

Designing patient-centric and culturally sensitive outreach campaigns is essential for trial success. Engaging with patients, caregivers, physicians, and patient advocacy groups early on — and conducting patient surveys and interviews — ensures that the trial design meets patient needs from the start. Customizing patient concierge services to ease logistical burdens further enhances the patient experience.  

Digital and decentralized solutions 

Digital and decentralized solutions offer promising avenues for improving rare respiratory clinical trials. Electronic Clinical Outcome Assessments (eCOA), electronic consent (e-consent), and telehealth appointments facilitate seamless communication and high-quality data collection. Wearable devices also enable remote monitoring, allowing patients to participate without the need for frequent clinic visits. With the right set of tools, clinical development teams are able to conduct assessments (like spirometry) remotely, reducing the need for in-person visits. Home nursing and other home health care options provide additional support, ensuring patients receive necessary care in a comfortable environment. Hybrid approaches, tailored to patient needs, combine the best of both digital and traditional methods, enhancing trial efficiency and patient experience. 

Benefits of an experienced partner

How the right contract research organization (CRO) enables these solutions 

Choosing the right CRO partner is crucial for the success of rare respiratory clinical trials. A highly experienced CRO service provider offers significant benefits through their expertise and comprehensive trial management. The key qualities sponsors should look for in a partner include: 

• Expertise in respiratory disease indications, endpoints, and patient recruitment and retention. 
• Collaboration with academia, regulators, and advocacy groups to enhance trial design and execution. 
• The ability to stay updated with evolving regulations and years of experience in rare respiratory disease clinical trials. 
• Strong relationships with specialist vendors and knowledgeable, dedicated cross-functional teams that streamline the trial process. 

The right CRO partner should have a proven track record of success and a suite of tools and resources specifically designed for rare respiratory clinical trials: 

• Complete support from Phase I through peri- and post-approval stages for seamless trial management. 
• Global reach and access to patient groups that accurately represent the studied population, ensuring proper representation. 
• Digital and decentralized tools to facilitate clinical trial participation, enhancing patient engagement and retention. 
• A history of successfully recruiting and retaining the necessary patient population. 
• Expertise in navigating regulatory pathways from start to finish, ensuring compliance and efficiency. 
• The ability to design trials around the needs of pediatric populations. 
• Proven success in bringing products to market, showcasing their ability to achieve successful outcomes for sponsors and patients alike. 

By considering these qualities, sponsors are able to ensure that their chosen CRO partner provides the necessary expertise and resources to drive their rare respiratory clinical trial success. 

Partner with the leader in rare respiratory disease trials 

The PPD™ clinical research business of Thermo Fisher Scientific is a leader in rare respiratory disease trials due to our proven history and comprehensive capabilities. With a long track record of successful rare respiratory disease studies, we have conducted more than 500 rare disease studies, 240 pediatric studies, and 27 IPF studies across 883 sites, enrolling more than 3,000 patients. We have also brought more than 20 respiratory products to market, including first in-class medications for rare respiratory diseases. Our expertise in recruiting and retaining small, globally dispersed populations further underscores our proficiency. 

Our global reach and end-to-end services accelerate drug development with 360-degree solutions, streamlining the process through our deep understanding of regulatory requirements. By leveraging our global network of key sites and investigators, we ensure comprehensive coverage around the clock. Our Pediatric Investigator Network (PIN) and Patient First Digital Solutions focus on accelerating patient recruitment, driving retention and increasing data quality. With specialized capabilities in rare diseases, we offer innovative AI-driven solutions for patient recruitment, engagement and retention through our digital and decentralized platforms.     

We have highly qualified experts within our Rare Disease and Pediatric Center of Excellence that bring cross-functional regulatory, clinical, and operational expertise to meet timelines and realize cost efficiencies. We have also developed specialized roles such as clinical science liaisons, and patient navigator services, which provide unparalleled support by fostering smooth communication between sites and sponsors. With expertise spanning from PAH, IPF, ILD, CF, and beyond, we are ready to bring your rare respiratory clinical trial to life.