Intended for healthcare professionals

Rapid response to:

Editorials

Off label prescribing in children

BMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7349.1290 (Published 01 June 2002) Cite this as: BMJ 2002;324:1290

Rapid Response:

Medicines for Children

EDITOR - Not only n the USA(1)but also in the EU, drug regulations
fail a significant proportion of the population, namely children.
Companies understandably develop a product in such a way as to get
earliest returns on their research investment. Where a paediatric
indication is not envisaged for a new drug, studies in this population are
not mandated. Thus, in contrast to adults, children are unable to benefit
from therapeutic agents which have been shown to be adequately safe and
effective for their own requirements. This violates their human rights.
(2)

The EU Directives allow a doctor to prescribe outside the approved
indications “on his own responsibility”. (3) This gives children access to
important medicines which would otherwise be denied them, but puts an
additional legal and ethical burden on the prescribing doctor. In the
absence of controlled and validated paediatric studies, the doctor has to
make his own professional assessment of the available data, possibly
anecdotal or theoretical in nature. Use by other specialists or inclusion
in a Hospital Formulary gives only prima facie evidence of satisfying the
legal standard of care. In addition, it is even more difficult than usual
to determine the level of disclosure of relevant information which would
ensure valid (‘informed’) consent. While the fact that a product does not
have regulatory approval for the proposed use probably constitutes ‘…a
significant risk which would affect the judgement of a reasonable patient”
(4) it is less certain how many patients or their parents would fully
understand the implications of this information.

Until it gains Regulatory approval for a given indication or patient
population, a drug is technically an experimental entity. A doctor is
must decide whether it is ethically more acceptable to withhold such a
product or to treat the patient essentially as a subject in an
uncontrolled clinical trial. The use of experimental treatment in
children clearly should be subject to a higher level of ethical review.

The FDA has been trying to remedy this situation since 1994 (1) , but
the EU has only recently issued a consultative document. (5) Doctors and
their paediatric patients have existed in this regulatory vacuum for too
long. It is imperative that the legislators expedite the legal framework
for mandatory paediatric studies, for both new and generic compounds.
Until then, we must hope that the increasingly global nature of
pharmaceutical development will result in studies from other regulatory
areas providing the necessary reassurance that children are receiving
adequately researched drug treatment.

(1) Banner W. Off label prescribing in children: a view from the
United States. BMJ 2002; 324: 1290-1

(2) UN Convention on the Rights of the Child Article 24 – “right of
the child to the enjoyment of the highest attainable standards of
healthcare’

(3) European Directive 65/65 EC as amended by Directive 89/341 EC

(4) Pearce v United Bristol Healthcare NHS Trust (1990) 48 BMLR 118
(CA)

(5) Better Medicines for Children: Proposed Regulatory Actions on
Paediatric Medicinal Products (2002) http://pharmacos.eudra.org/F2

Competing interests: No competing interests

07 June 2002
Valerie L Isitt
Regulatory Affairs Consultant
(self employed) - 32 The Avenue, Radlett, Herts WD7 7DW