SAQ 1 — Classification and the governance pathway

Stem (20 marks; suggested 15 minutes): ^[6]

A 3-month-old infant is started on propranolol oral solution for a proliferating infantile haemangioma. The propranolol product is licensed for hypertension in adults. Separately, the neonatal unit where you work prepares a caffeine citrate solution in the hospital pharmacy because no licensed preparation exists at the required strength for preterm infants. ^{[6] [5]}

(a) Define licensed, off-label and unlicensed medicine use, and classify each of the two scenarios above into one of these categories. (8 marks) ^[1]

(b) Outline the stepwise governance pathway a prescriber should follow when a medicine is needed outside its licence. (8 marks) ^[7]

(c) State the pharmacovigilance duty that applies when a child on an off-label or unlicensed medicine has a suspected adverse drug reaction, and name one national reporting scheme. (4 marks) ^[8]

Model answer — SAQ 1

(a) Definitions and classification (8 marks). ^[1]

• Licensed (on-label) use — a medicine used within all the terms of its marketing authorisation: the approved age or weight band, indication, route, dose and formulation. (1 mark)
• Off-label use — a licensed product used outside one or more of those terms (different age or weight, indication, route, dose, or formulation). (1 mark)
• Unlicensed use — a medicine with no valid marketing authorisation for that product or formulation in the jurisdiction: specials, imported products, extemporaneous compounding, or an investigational product. (1 mark)
• Propranolol for the infantile haemangioma is off-label: the product is licensed (for adult hypertension) but used outside the licensed age, indication and dose. (2 marks — must name the licensed-product-outside-a-term reasoning)
• The pharmacy-prepared caffeine citrate is unlicensed: no marketing authorisation exists for that formulation; it is compounded because no licensed preparation is available at the required strength. (2 marks — must name the no-licence-for-the-formulation reasoning)
• Make explicit that both are legal, common and often evidence-based — they are prescribing categories, not errors. (Concept-recognition mark embedded above; do not award if the candidate conflates off-label with unlicensed or with error.) ^{[1] [6]}

(b) Governance pathway (8 marks — 1 mark per named step, capped at 8). ^[7]

1. Check whether a licensed alternative that meets the clinical need exists and is locally available; if so, prefer it. ^[7]
2. Confirm the evidence base for the proposed off-label or unlicensed use — a guideline, systematic review or formulary monograph. If the evidence is thin, seek alternatives or specialist/Medicines Committee advice. ^[6]
3. Choose the safest formulation — prefer a licensed product used off-label over an unlicensed compounded or imported product where possible; confirm stability and strength with pharmacy. ^[5]
4. Document the indication, evidence base, weight-based dose (child weighed in kilograms), family discussion and local approval status. ^[7]
5. Counsel the family and obtain consent (and assent where the child is competent); explain the medicine is off-label and why it is the best choice. ^[7]
6. Monitor efficacy and adverse drug reactions; intensify monitoring where the dose is uncertain. ^[8]
7. Report suspected adverse drug reactions to the national pharmacovigilance scheme. ^[8]
8. For high-risk off-label or unlicensed use (narrow therapeutic index, neonate, IV inotrope/sedative, compounded formulation), obtain senior sign-off and notify the local Medicines Committee before the first dose. ^[7]

(c) Pharmacovigilance duty (4 marks). ^[8]

• Off-label and unlicensed medicines are associated with a higher rate of adverse drug reactions (Bellis 2013), and the post-marketing database for these uses is thin, so every suspected reaction should be reported. (2 marks)
• Reporting is on suspicion, not proof. (1 mark)
• Name one national scheme: the Yellow Card (UK), the Blue Card / ADRS scheme (Australia), or MedWatch (US). (1 mark) ^{[8] [4]}

SAQ 2 — The evidence gap and the regional regulatory response

Stem (20 marks; suggested 15 minutes): ^[6]

A fellowship examiner asks: "Why is so much paediatric prescribing outside the product licence, and what have regional regulators done about it?" ^{[1] [6]}

(a) Explain the structural reasons why off-label and unlicensed medicine use is common in children. (10 marks) ^[6]

(b) Describe the regulatory mechanisms introduced in the European Union and the United States to close the paediatric evidence gap, and summarise the evidence on whether they have reduced off-label use. (10 marks) ^[10]