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Ensuring its success will help improve the use of medicines in children
The importance of clinical trials in children in providing a scientific evidence base for drug therapy is accepted by health professionals, regulatory authorities, the pharmaceutical industry, and the parents of children. Legislation in the USA alongside government investment in research has resulted in a significant increase in paediatric clinical trials in North America.1 European legislation is currently being proposed that will provide a financial incentive to the pharmaceutical industry to study medicines in Europe. The proposal has been prepared by the European Commission following extensive consultation. Within the UK the establishment of a Medicines for Children Research Network will hopefully also ensure that more clinical trials are performed in paediatric patients of all ages.
REGISTRATION OF CLINICAL TRIALS
There is increasing recognition that as well as performing clinical trials, registration is essential.2,3 Many completed clinical trials are never published. A group of researchers in North America have studied the publication of clinical trials that had been presented as abstracts at the Society for Pediatric Research. They found that 28% of abstracts were subsequently not published.4 This however may have been an underestimate as they relied on the return of questionnaires from authors who had presented the abstracts. A British study of the publication rate following presentation at two national meetings found that 22% and 49% of the presentations were subsequently not published as full papers.5 In the majority of cases the authors did not submit their findings for publication.
The lack of publication of completed clinical trials adversely affects the evidence base on which decisions regarding choice of drugs and dosage in relation to efficacy and toxicity are made. In order to ensure that children receive the safest and most effective treatment, health professionals need the complete information. The existence of the European Paediatric Clinical Trials Register does not ensure publication.6 It does, however, alert health professionals to the fact that a clinical trial has been completed. This then allows researchers who are carrying out systematic reviews to contact the investigators directly and obtain unpublished data. The existence of a register also prevents duplication by investigators and encourages collaboration. Additionally, it allows sponsors (medical charities, Department of Health) to ensure that duplicate studies are not funded.
Concern has been raised that clinical trials which produce negative results are deliberately suppressed by the pharmaceutical industry.7,8 In the UK, the Association of the British Pharmaceutical Industry (ABPI) has established a Clinical Trial Register. This register, however, is only voluntary and not all companies are supporting it. It is only public pressure or legislation that will ensure that the pharmaceutical industry fully supports the concept of registration of clinical trials.
Several leading adult medical journals have declared that clinical trials submitted for publication will need to have been registered in order for their findings to be published.9,10 This is a welcome step and will ensure that clinical trials registers are used. The International Committee of Medical Journal Editors (ICMJE) has not advocated a particular register but has suggested that the register sponsored by the United States National Library of Medicine (www.clinicaltrials.gov) meets all their necessary requirements.9 Concerns have, however, been expressed in that this register is quite restrictive as to which trials can be registered10 (the register was primarily designed for American trials which were being submitted to the Food and Drug Administration (FDA)).
An additional development in Europe is that all new clinical trials involving medicines need to be registered with the EMEA. This legislation affects both the pharmaceutical industry and academic investigators who carry out independent research. What is not known at this stage is how much of the information available on the European Clinical Trials Register will be accessible to academia, health professionals, and the public. A register that is only accessible to the regulatory authorities will not benefit children.
DO PAEDIATRIC CLINICAL TRIALS NEED A SEPARATE REGISTER?
Health professionals who work with children are well aware that many medicines used in paediatric patients are either unlicensed or used off label.11 It is well recognised that drug toxicity in children is different to that in adults.12 Additionally, the design of paediatric clinical trials is different to that in adults, where healthy volunteers can be used.13 Recruitment to paediatric clinical trials involves patients and therefore is usually slower, requiring more emphasis on safety than corresponding studies in adults.14 For these reasons, there is a clear need for a separate register of paediatric clinical trials.
EUROPEAN PAEDIATRIC CLINICAL TRIALS REGISTER
There is currently only one clinical trials register that exclusively deals with paediatric clinical trials. This register was established with funding from the European Community.6 The project commenced in January 2003 and currently involves four countries: Italy, France, Spain, and the UK. The lead centre is in Milan and the register went live on 1 July 2004.15 It can be accessed through the website www.dec-net.org.
The register is freely available to both health professionals and the public. Trial information is available in two different formats, a simple one aimed at parents and the public and a more advanced one aimed at health professionals. Users are, however, free to choose whether they obtain the simple or advanced information. Information listed in the register is as follows:
Title of protocol
Status of the clinical trial
Age and sex of patients being studied
Aim of the study
Contact details for lead investigator
The advanced view contains more details and includes administrative information about the trial (local protocol number, EUDRACT number, ISRCTN number). Also included are the following:
Name of the drug
Type of trial (therapeutic efficacy, pharmacokinetic, safety/toxicity)
Since the official launch of the register, the website has seen an average of 400–500 hits each month. As of January 2005 the website had had over 3700 visits. This illustrates the importance of ensuring that the website is user friendly.
The register currently contains details of over 60 clinical trials. These range from double blind randomised controlled trials to pilot studies and open observational studies. A wide range of clinical conditions are covered, several of which involve analgesia following surgery, the treatment of asthma, gastro-oesophageal reflux, attention deficit hyperactivity disorder, HIV, and diabetes mellitus. The status of the vast majority of these trials is that they are currently recruiting patients and in only a few cases have the clinical trials been completed.
Within the UK there has been considerable support for the register from the Royal College of Paediatrics and Child Health, the Neonatal and Paediatric Pharmacists Group, and the ABPI. Over 40 of the clinical trials on the register are studies from the UK. More than 20 different academic units and NHS hospitals have already provided information on clinical trials that they are involved in. Ensuring the success of the only Paediatric Clinical Trials Register worldwide will help improve the use of medicines in children.
Ensuring its success will help improve the use of medicines in children
Competing interests: none declared
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