Background: Tuberous sclerosis complex (TSC) is an incurable genetic condition that affects approximately 2 million people worldwide. Quality of life, burden of illness, and socio-economic impact are poorly researched.

Methods: A priority-setting partnership in TSC was established and a multi-stakeholder dialogue for setting research priorities was conducted. Research questions were developed based on input from all stakeholders using focus groups, individual in-depth interviews and an online Delphi procedure, completed with data from literature. Priority setting was carried out using online voting in combination with facilitated deliberation workshops.

Results: Focus groups and interviews with 24 patients and caregivers resulted in 350 uncertainties which were translated into 62 researchable questions. These were submitted for refinement and prioritization to a panel of representatives of six international patient organizations, resulting in 39 researchable questions and eight urgent needs. In parallel, individual interviews of 19 healthcare-practitioners and researchers resulted in a list of >250 uncertainties translated into 39 researchable questions, which were submitted for review and further input to 30 TSC experts. Integration of >200 comments and refinements led to 49 researchable questions which were then prioritized by online voting. The top 15 research priorities in TSC were agreed during a workshop that involved ten patients and caregivers as well as 11 researchers and healthcare practitioners.

Conclusion: These 15 priorities are intended for researchers, funding bodies, and industry to ensure that future research funding and research activities focus on questions that are important to patients and families with TSC as well as their healthcare-providers.