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Table 1 ASTERIX clustering of orphan medical conditions

From: Evidence supporting regulatory-decision making on orphan medicinal products authorisation in Europe: methodological uncertainties

Cluster Description Example 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 extravasationsa
(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 syndromesa
(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 deficiencya
(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 synthesisa
(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 Mucopolysaccharidosisa Other lysosomal storage diseasesa
(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
  1. aultrarare medical conditions (prevalence < 1/100,000)
  2. Please refer also to Additional file 1: Table S2