Disease Burden Mapping In Rare Diseases: An Example of Hypophosphatasia

OBJECTIVE: Rare diseases are often characterised by complex pathophysiology, a wide range of symptoms and outcomes, and a poorly understood patient experience. The authors sought to develop a new approach to describe the relationship between disease pathophysiology and patient outcomes, so as to maximise the value of sparse disease data and to visually communicate complex disease burden information to non-specialist audiences.The approach was applied using hypophosphatasia (HPP) as an example. METHODOLOGY: A literature review was conducted to identify all consequences of the disease. A disease burden map was created which visually linked specific manifestations with the impact on patients. Disease elements were categorised according to the proximity of the manifestations to the underlying pathophysiology (organs and systems affected, primary symptomology, morbidity, mortality and Health Related Quality of Life (HRQoL). Frequency and severity of disease manifestations were represented visually through proportional area boxes. Clinical expert opinion was used along with published evidence to inform the structure of the map and the relative importance of the elements. PRACTICAL IMPLEMENTATION: Three separate maps were developed for HPP according to age of onset: infantile, juvenile and adult. A structured qualitative and semi-quantitative process was undertaken to elicit input from five clinical experts. In juvenile HPP, the element with the highest burden was functional disability, resulting mainly from bone and muscle pathologies and associated with significant morbidity and reduced HRQoL. In infantile HPP, where patients rarely survive into late childhood, mortality represented the largest component of disease burden. The burden maps were utilised as part of a Highly Specialised Technology submission to NICE in the UK. CONCLUSION: Despite inherent issues of subjectivity, this approach has proved a useful tool in building consensus among clinical experts on the nature of disease manifestations and for communicating burden to non-specialist audiences.