Randomized clinical trials remain the cornerstone of evidence generation, but in rare diseases they often face fundamental limitations, including small patient populations, difficulties in recruitment, and limited long-term follow-up.
In our new expert interview series, Sqilline Health speaks with leading specialists about how real-world data (RWD) is helping bridge these gaps and expand the evidence base beyond traditional clinical research. From understanding natural disease progression to supporting regulatory decisions and accelerating access to therapies, real-world evidence (RWE) is becoming an essential component of rare disease innovation.
In this edition, Prof. Daniela Avdjieva-Tzavella, shares her perspective on how real-world insights are reshaping rare disease research and what it will take to integrate RWD into clinical development and decision-making.
Genetics and Rare Diseases
Rare genetic disorders often remain underdiagnosed. What are the main challenges clinicians face in identifying rare diseases in routine paediatric and genetic practice, such as Hypophosphatasia?
A major problem for all patients with rare diseases is delayed diagnosis. This is due to the nonspecific, often heterogeneous clinical presentation of these diseases and the lack of awareness among healthcare professionals. The small number of conditions included in neonatal screening and limited access to genetic testing in Bulgaria are additional factors that delay diagnosis.
In rare diseases, patient populations are small, heterogenous and broadly geographically dispersed, also clinical trials have often certain limitations. How can the real-world data support the bridge of evidence gap?
The small number of patients makes it very difficult to obtain reliable results from clinical trials for orphan drugs, making them very expensive and sometimes taking years to complete. The challenges associated with clinical trials mean that the post-approval monitoring process—when we actually begin treating patients in real-world practice—becomes even more important to ensure that the drugs work effectively and adequately meet patients’ real needs.
How can data collected in routine clinical practice contribute to generating real-world evidence that supports earlier detection and a better understanding of rare disease progression and treatment outcomes?
Often, the information we have about a rare disease is very limited, based on only 10 to 20 published cases worldwide. European reference networks are very helpful, as they enable specialists from different countries to exchange expertise and conduct online consultations for patients with complex conditions.
What types of clinical or genetic data are most valuable when building datasets for rare disease research?
Any information regarding clinical symptoms, the course of the disease, and treatment outcomes is important. The full picture of a rare disease becomes clear over the course of years as a result of the accumulated knowledge of many specialists around the world.
Clinical Practice and Data Integration
What are the main barriers to collecting structured clinical and genetic data in everyday medical practice?
Collecting structured clinical and genetic data is generally difficult for these diseases due to their low prevalence. An additional challenge in Bulgaria is the lack of registries for patients with rare diseases.
Future of Rare Disease Research
Looking ahead, what developments in genetics or data science do you believe will have the greatest impact on improving outcomes for patients with rare diseases?
Hundreds of rare diseases can now be diagnosed through genetic testing. Knowledge of the natural course of these diseases has been improved through the creation of registries for some of them. Researchers are increasingly working through networks to share their research findings and advance more effectively.
Prof. Daniela Avdjieva-Tzavella, MD, PhD, is a Bulgarian specialist in paediatrics and medical genetics. She is Head of the Department of Paediatrics at Medical University of Sofia and Head of the Genetics Clinic at Prof. Ivan Mitev University Children’s Hospital.
She leads expert centres for rare metabolic diseases and rare malformities syndromes in paediatrics and plays an active role in national healthcare policy as Chief Coordinator of the Expert Council on Paediatrics at the Ministry of Health of Bulgaria. She also serves as Scientific Secretary of the Bulgarian Paediatric Association.
Prof. Avdjieva-Tzavella has authored more than 170 scientific publications and is actively involved in advancing paediatric and rare disease research and policy in Bulgaria.
