Using Technology to Accelerate Rare Disease Drug Development: an Expert Interview with Iryna Ziabreva at Advanced Clinical

Collectively, more than 7,000 rare diseases are known to affect greater than 400 million people globally, and yet, a recent analysis found that only ~550 FDA approved orphan products are available to treat rare diseases.

This is not surprising given that the pharmaceutical industry traditionally sidestepped rare disease drug development due to multiple known obstacles that would slow the path to approval and add significantly to drug development costs. However, with the rise of proven, innovative clinical trial technologies and methodologies for supporting rare disease clinical trial development, the pharmaceutical industry has been increasing its focus on developing novel rare disease therapies.

In this Q&A, we interviewed Iryna Ziabreva, PhD, Program Director at Advanced Clinical, a full-service global CRO with a strong focus in rare disease. Dr. Ziabreva answers questions related to Advanced Clinical’s approach to rare disease clinical trials, including how they identify, recruit, and retain patients, and how their partnership with Medidata has allowed them to overcome some common challenges in rare disease research. Advanced Clinical is an accredited build partner for Medidata Rave, Coder, and RTSM.

Can you briefly describe Advanced Clinical’s work in supporting rare disease clinical trials?

Advanced Clinical develops patient-centric operational strategies to accelerate the development of rare disease therapies for sponsors. This can be challenging due to the rarity of these patients and the complexity of protocol designs. Our mission is to create a better clinical experience for everyone impacted by rare diseases, directly or indirectly. In sum, when it comes to rare diseases, Advanced Clinical excels at:

• assessing decentralized strategies to ease burden and promote patient centricity;
• planning for patient and family needs during the research process;
• leveraging advocacy and support group relationships to increase awareness of rare disease; and
• providing support to clinical trial participants, including travel concierge service, tailored mobile apps and SMS text messaging, at-home support, and local testing.

What are some unique challenges associated with rare disease clinical research?

Rare disease clinical trials face several unique challenges, ranging from identifying and retaining patients to adjusting studies to meet the specific needs of pediatric and adult patient populations. Identifying eligible patients can be very challenging given that there are usually only a few dedicated sites/centers that treat specific rare diseases. Further, these sites may be involved in other clinical studies that “compete” for eligible patients, and local data protection laws should be carefully considered during feasibility/site selection when it comes to obtaining genetic information.

Clinical trial enrollment at each site is often low, placing tremendous pressure on sites and sponsors to build strategic measures into the study design to maximize enrollment and retention but minimize the burden on participants. Special considerations are often necessary for pediatric patients and it is important to educate both patients and their caregivers to ensure an overall positive experience.

Data collection and analysis is another challenge due to the minimal patient population, which increases the risk that the study data could be incomplete due to early withdrawals, missed visits, and/or study-specific procedures.

What are some ways Advanced Clinical helps its clients identify and recruit rare disease patients?

We have many years of experience and expertise in identifying centers with rare disease patients. Over the years, we have built a database of potential investigators, including feedback on their performance and recommendations for future research.

With respect to recruitment, it is crucial to design the study around the needs of patients and their caregivers. We help sponsors address patient needs and design materials for sites and patients that engage investigators and educate patients about the importance of clinical research, while also explaining what their experience will be during the trial. Our pre-screening process and tools help minimize screen failures.

The ongoing COVID-19 pandemic put pressure on sponsors and regulatory authorities to embrace technologies, such as the use of Medidata eConsent, and virtual visits to reduce burden on patients and maximize enrollment.

Patient retention is critical for rare disease clinical trials. How do you help maximize retention?

Educating patients and engaging clinical sites and investigators are critical to patient retention. Using newsletters, investigator support calls, meetings, and site feedback helps us ensure that we are continuously supporting sites through a transparent and effective exchange of information.

In addition, when a patient understands the expectations and experience associated with participation, we know that this affects retention success rates. We collaborate closely with investigative sites when collecting patient feedback and we also use a diverse set of patient engagement strategies to enhance the experience (e.g., flipcharts and reminders of study visits and assessments, home nurse support, and resources tailored to a pediatric population).

Why is high-quality data collection so important for rare disease clinical trials?

It is crucial during the earliest stages of a study to understand how data will be collected so we can mitigate the risk of data loss. Our dedicated biometrics and biostatistics team supports clinical operations by providing data and site metric analyses to ensure continuous collection of high-quality data. Due to the smaller size of the patient population, high-quality data becomes even more important.

How can clinical trial technology help with these challenges?

The proven, innovative technology on Medidata’s Clinical Cloud Platform has certainly enhanced the patient experience and the quality of data collected. This has been an important factor ensuring success for some of our rare disease clinical trials. While working with Medidata, we have implemented a variety of their clinical trial technologies, including Medidata eConsent, ePRO, and Rave Imaging. We are actively working together to implement virtual study visits, dosing schedule reminders, and interactive data collection (questionnaires, study drug diaries, and study procedures) to provide patients with flexibility and real-time data to investigators and sponsors—and, overall, to reduce the burden on patients and site resources.

Summary

Embarking on a rare disease clinical trial can present unique challenges and building an effective clinical strategy requires careful planning from the very beginning. To provide the best opportunity for success, you should consider engaging in discussions as early as possible with partners that have experience and expertise in conducting rare disease trials. Join us at Medidata NEXT from October 5 - 7 to learn more from life science leaders across the industry on how they are overcoming the challenges in rare disease clinical development and accelerating change in engaging with rare disease patients.