Table 1 ASTERIX clustering of orphan medical conditions

(1) Conditions with single acute episode

Incident cases with single acute episode, with rapid onset and rapid endpoint: longer recruitment (incident cases) than follow-up for a given subject. Well-known and predictable course in absence of treatment, often a serious or life-threatening event. The condition is serious because of lack of effective standard of care. Recovery generally returns to baseline health status with or without sequels. Generally led by one organ/system that may develop to multiorgan impairment.

Acute leukaemias

Treatment of acute angioedema

Closure of patent ductus arteriosus

Primary apnoea of premature newborns

Treatment of anthracycline extravasations^a

(2) Conditions with recurrent acute episodes

Prevalent conditions with clear-cut repeated episodes separated by relatively healthy periods. The condition often has a known predictable clinical course. Baseline status may deteriorate over time due to repeated episodes. The number and severity of the episodes is relevant for assessment of disease activity and subject well-being. May include two different indications: treatment of acute episodes and prevention of new episodes.

Cystic fibrosis: acute lung infection

Narcolepsy

Sickle cell sindrome

Systemic sclerosis (scleroderma)

Cryopirin-associated periodic syndromes^a

(3) Chronic conditions with stable or slow progression

Chronic conditions that are generally life-long and affecting mainly a single function or system/organ, often due to a single deficiency or impairment, which may be inherited. The condition is relatively mild or has an acceptable standard of care that converts a serious condition into a mild condition. The clinical course is often predictable and well-known, and relatively stable so that it does not rapidly deteriorate the subject’s function or life-expectancy. However, if the standard treatment is not optimal, further deterioration may occur over time. Prevalence is higher than incidence, so there is short recruitment duration as regards to subject follow-up.

Acromegaly

Essential thrombocythaemia

Short bowel sindrome

Chronic iron overload

Lipoprotein lipase deficiency^a

(4) Chronic progressive conditions led by one system/organ

Chronic progressively-worsening conditions where main impairment is led by one system/organ, which may or not involve others over time. The condition progressively reduces quality and/or quantity of life, typically subjects are seriously disabled due to disease. Clinical course is longer than acute conditions, usually year(s). May include inherited defects. Prevalent cases may be identified from registries where available. Current standard of care is symptomatic or supportive, but not curative. Frequent heterogeneity in clinical expression and poor predictability of clinical course.

Atypical haemolytic uremic syndrome

Chronic myeloid leukaemia

Cystic fibrosis: treatment of lung function decline

Duchenne muscular dystrophy

Inborn errors of primary bile acid synthesis^a

(5) Chronic progressive conditions led by multiple system/organs

Life-lasting diseases, often inherited defects of metabolism that may start as paediatric conditions or in (young) adults. Often the standard of care is poor or not available. Many are ultrarare conditions. Prevalent cases may be identified from registries where available. May have highly variable clinical course, with impact on multiple system/organs, requiring multidimensional assessment and endpoints relying on subjective assessments from caregivers/patients on clinical or functional status and quality of life.

Cystic fibrosis: receptor estabilization

Tuberous sclerosis

Castleman’s disease

Mucopolysaccharidosis^a

Other lysosomal storage diseases^a

(6) Chronic staged conditions

The condition initially is limited to one system/organ and then progresses/expands to life-threatening multi system/organ impairment, with clearly defined clinical stages, as defined by disease extension, each with different prognosis and different standards of care. Malignancies are generally included in this cluster. Staging is determined by disease extension or burden as measured directly by imaging, or indirectly by function as a surrogate for extension. The condition may evolve either to progression, stagnation or reversal of the condition, with time in each stage as a relevant measure of disease.

Familial Adenomatous Polyposis

Pulmonary arterial hypertension

Thyroid cancer, other rare solid cancers

Myelodysplastic syndromes

Multiple myeloma