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. 2000 Apr 29;320(7243):1210.

Use of unlabelled and off licence drugs in children

Use of unlicensed drugs may be recommended in guidelines

F Andrew I Riordan 1
PMCID: PMC1127597  PMID: 10784559

Editor—Conroy et al report the widespread use of drugs that are either not licensed for use in children or are prescribed outside the terms of their product licence (off label prescribing) in children admitted to hospital.1 Although it is not illegal to use medicines in this way, the responsibility for any adverse events becomes the clinician's or the pharmacist's rather than the manufacturer's. However, much unlicensed use may be recommended in local or national guidelines.

As part of our trust's response to the use of unlicensed drugs in children, I reviewed all drugs recommended in our local paediatric medical guidelines. These contained 69 guidelines for acute management and elective investigation of children. The guidelines recommended 86 drugs, but only 47 (55%) were licensed for use in children. A further 14 drugs were licensed only for children above a certain age or weight, 24 were unlicensed or off label, and the status of one drug (methylcellulose) was unknown. Five drugs used for investigations were not licensed or the licence was restricted. National guidelines also recommend drugs that are unlicensed for use in children.

The British Thoracic Society guidelines for treating tuberculosis recommend that pyrazinamide is given routinely, although this drug is not licensed for use in children.2 Primaquine is recommended by national guidelines for use in vivax malaria, although it is unlicensed.3

Paediatric guidelines (both local and national) need to acknowledge the licensed status of the drugs they recommend. Linking guidelines to the Royal College of Paediatrics and Child Health's formulary (Medicines for Children4) might facilitate this.

References

  • 1.Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane AR, et al. Survey of unlicensed and off label drug use in paediatric wards in European countries. BMJ. 2000;320:79–82. doi: 10.1136/bmj.320.7227.79. . (8 January.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Thorax. 1998;53:536–548. [PMC free article] [PubMed] [Google Scholar]
  • 3.Benign malarias (treatment). British National Formulary 38, September 1998:283-4.
  • 4.Royal College of Paediatrics and Child Health. Medicines for children. London: RCPCH Publishing; 1999. [Google Scholar]
BMJ. 2000 Apr 29;320(7243):1210.

A European paediatric rule is needed to protect children

Nicolino Ruperto 1,2, Alberto Martini 1,2

Editor—Drugs for the paediatric rheumatic diseases are now used in new dosages, through new routes of administration, or in new combinations, but data on safety and efficacy tend to be from small, uncontrolled series. Moreover, most if not all of the drugs for the paediatric rheumatic diseases are prescribed outside the terms of their product licence (used off label) in most European countries, as described by Conroy et al.1-1

Childhood chronic illnesses with high morbidity should be the target of intense research aimed at ameliorating or curing the disease. Yet securing funding for trials in children is difficult: the pharmaceutical industry has little interest in funding these trials, the potential market is small, the enrolment period is long, and most childhood chronic conditions are rare illnesses.

To address these problems, in 1996 a European network called the Paediatric Rheumatology International Trials Organisation was founded to facilitate and coordinate the development, conduct, and reporting of clinical trials with or without the support of pharmaceutical companies. Thirty two countries now belong to the organisation.

In 1997 the organisation obtained a three year grant from the European Union for a randomised controlled clinical trial of medium and high dose parenteral methotrexate in children with juvenile chronic arthritis that does not respond to standard doses. This trial is built on the current standard of care where the costs of insurance coverage, medications, clinic visits, and laboratory tests are paid by the usual method of medical reimbursement—that is, through a national health system or medical insurance system. Interestingly, approval by an ethics committee has been denied in four countries because of lack of insurance coverage, because of lack of support by a pharmaceutical company, and because drugs were not given free of charge.

The problems faced by the organisation, and surely by other paediatric groups, in dealing with pharmaceutical companies and ethics committees underline the difficulties of designing and conducting clinical trials for children, especially if the issue is to seek approval from regulatory agencies.

As stated by Conroy et al,1-1 the European Medicines Evaluation Agency1-2 issued guidance on the clinical investigation of medicinal products in children that simply encourages companies to investigate drugs in children when clinically appropriate.1-3 The same difficulties led the Food and Drug Administration to issue the “paediatric rule,”1-4,1-5 by which manufacturers of products likely to be used in children have to test those products in the relevant paediatric population.

Like Conroy et al, we urge the European Union and the European Medicines Evaluation Agency to issue a similar paediatric rule for the European Community to assure children and their families the same rights as adults to receive drugs that have been fully tested.

References

  • 1-1.Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane AR, et al. Survey of unlicensed and off label drug use in paediatric wards in European countries. BMJ. 2000;320:79–82. doi: 10.1136/bmj.320.7227.79. . (8 January.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 1-2.European Medicines Evaluation Agency. Report on the experts round table on the difficulties related to the use of new medicinal products in children held on 18 December 1997. London: EMEA; 1998. . (27164/98 Rev 1.) [Google Scholar]
  • 1-3.European Medicines Evaluation Agency. Note for guidance on clinical investigation of medicinal products in children. London: EMEA; 1997. [Google Scholar]
  • 1-4.Connor JD. A look at the future of pediatric therapeutics: an investigator's perspective of the new pediatric rule. Pediatrics. 1999;104:610–613. [PubMed] [Google Scholar]
  • 1-5.Food and Drug Administration. Regulations requiring manufacturers to assess the safety and effectiveness of new drugs and biologic products in pediatric patients (21 CFR Parts 201, 312, 314, and 601). Washington, DC: Federal Register; 1998. p. 63. [PubMed] [Google Scholar]

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