Rare disease studies, especially those conducted in paediatric populations, present considerable challenges at a country, site and patient level due to their complexity and the fact that many stakeholders need to be involved. 

A thorough and well-planned feasibility will allow sponsors to gain valuable insights enabling important decisions to be made, most importantly if the study is feasible to be conducted at all and if yes, where it will be conducted, under which conditions, how much support and intervention will be required and how long recruitment 

will take. All these factors will also affect the cost of the study. 

Only when a robust feasibility is conducted can these important questions be answered and an appropriate study execution strategy be developed. The more accurate the feasibility data the more likely any risks can be mitigated. Clinical trial feasibility is the best means for predicting the speed at which Investigators will enrol patients. The outcome may also be useful for pre-identification of patient pools for future studies, registries or for marketed products. 

In the industry, it is common practice that feasibilities are performed quickly and usually are superficial in nature, where the focus is on immediate study start and quick site set-up. Investors for example prefer to see more near-term KPIs which allows them to validate their investment progress as early as possible. Consequently, instead of focusing on when the last patient will enter the study, more attention is paid to when the first patient will be recruited which in the worst case scenario can lead to slipping timelines for drug approval. 

According to recent studies, identifying sites in rare disease studies is one of the most difficult tasks. 

A well-designed and executed feasibility which builds on validated data is crucial for a successful clinical trial and the design of a solid product development plan. Ideally, the feasibility should be impartial and results should solely be data-driven. 

This white paper explores critical factors that should be taken into consideration when conducting feasibilities. 

Data Review, Epidemiology and Patient Identification 

A high-level strategy would be to determine where patients with a particular rare disease are located around the world and to find where the highest concentrations of the patients exist, keeping in mind that practicalities like patient’s access to join the clinical trial are highly significant.  

The importance of data searches to pre- identify possible countries and sites is paramount, especially when no established database of Investigators for many of the rare disease indications exists and when information is scattered. 

In case very few patients are scattered globally, which may be the case in ultra-rare diseases, one strategy can be to first target countries with a high population and density, relying on probability of finding more affected patients. Considering all aspects, it may still be useful to conduct feasibility in many countries and not be too restrictive. In some cases, pockets of a disease are found in certain regions, which may be due to factors such as consanguinity.