Table 1 Description of criteria used in this study

Rarity

Based on published prevalence data: 1:2,000–1:20,000

1

1:20,000–1:200,000

2

<1:200,000

3

Level of research undertaken

“Blue sky”

1

Building on previous knowledge

2

Literature review

3

Level of uncertainty of effectiveness

Immature but promising data

1

Appropriate surrogate endpoints

2

Robust clinical endpoints

3

Manufacturing complexity

Not complex; small molecule

1

Moderately complex

2

Highly complex, biological and galenic form

3

Follow-up measures

Safety and efficacy studies, and size and duration of study

1

Designed to answer specific, defined delineated question

2

Moderate to none

3

Disease severity

Morbidity

1

Mortality, severe invalidity in adulthood

2

Mortality/severe invalidity as an infant

3

Available alternatives/Unmet needs

Alternatives with similar characteristics

1

Alternatives - but this offer strong innovation to disease treatment

2

No alternative

3

Treatment impact on disease

Low

1

Medium

2

Strong

3

Unique indication or not

Existing orphan or non-orphan indication for the same molecule

1

Potential for multiple indications

2

Unique indication. No other possible use

3