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From prioritisation of research in paediatrics towards a more rational, evidenced-based and “European” drug use in the general practice
- Federico Marchetti, Jenny Bua (30 November 2008)
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A missed opportunity
- Antonio Clavenna, Maurizio Bonati (2 December 2008)
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Federico Marchetti, Attending physician Department of Paediatrics, Institute of Child Health, IRCCS Burlo Garofolo, Trieste, Italy, Jenny Bua
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We read with interest the important survey on drug use in children conducted in three European countries (1). In their conclusions, the Authors underline that their data support the conclusions of the EMEA consensus/expert derived list of research priorities, which emphasised the need for paediatric studies of the safety of topical, systemic, and inhaled steroids. We disagree with this latest statement. As an example, in Italy anti- asthmatics are the second most prescribed drug class, representing together with antibiotics 80% of all prescriptions (2). In particular inhaled beclometasone is the second most prescribed drug, with a large utilization in the first year of life. The prevalence of anti-asthmatic prescriptions resulted much higher than prevalence of disease, indicating that anti-asthmatics are over-prescribed (2). Moreover, nebulised steroids are mainly prescribed only once in a year, suggesting they are not prescribed for asthma, which would imply a recurrent use, given its chronic nature. These data suggest that the use of inhaled steroids is far from being rational, warranting an educational campaign addressed to family paediatricians, rather than requiring more paediatric studies. In fact, searching on PubMed “clinical trials” on “inhaled steroids” including “all children: 0-18 years”, 478 clinical trials have been published in the last 10 years, of which 130 in last 3. We believe the focus of future research should be more on the reasons why inhaled steroids are prescribed for conditions different from asthma, such as viral wheezing and non specific cough, two conditions where there is no evidence of efficacy (3,4). Similar considerations on the importance of understanding the discrepancies between country-prescriptions and on the need of European public health measures for guarantying that available evidence is put into medical practice could be formulated with regard to salbutamol prescriptions, the prevalence of which varies widely between the 3 countries in the study (1), or to antibiotic use, the classes and frequencies of which again vary largely (1,5). We think that the coordination between European countries in the process for the identification and harmonisation of the best practice in the management of common diseases in children should be made a priority. Federico Marchetti, Jenny Bua Department of Paediatrics, Institute of Child Health, IRCCS Burlo Garofolo, Trieste via dell’Istria 65/1. 34100 Trieste, Italy Corresponding Author: Federico Marchetti, MD. marchetti@burlo.trieste.it References 1. Sturkenboom MC, Verhamme KM, Nicolosi A, et al. Drug use in children: cohort study in three European countries. BMJ 2008 Nov 24;337:a2245 doi:10.1136/bmj.a2245. 2. Clavenna A, Berti A, Gualandi L, Rossi E, De Rosa M, Bonati M. Drug utilisation profile in the Italian paediatric population. Eur J Pediatr 2008 Apr 30. [Epub ahead of print] 3. Chavasse RJ, Bastian-Lee Y, Seddon P. How do we treat wheezing infants? Evidence or anecdote. Arch Dis Child 2002;87(6):546-7 4. Tomerak AA, McGlashan JJ, Vyas HH, McKean MC. Inhaled corticosteroids for non-specific chronic cough in children. Cochrane Database Syst Rev 2005;CD004231. 5. Spyridis N, Sharland M. The European Union Antibiotic Awareness Day: the paediatric perspective. Arch Dis Child 2008;93(11):909-10 Competing interests: None declared |
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Antonio Clavenna, Researcher "Mario Negri" Institute for Pharmacological Research, via Giuseppe La Masa 19, 20156 Milan, Italy, Maurizio Bonati
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A missed
opportunity Dear Editor, the collaborative study by
Sturkenboom et al represents a novelty in the field of paediatric pharmacoepidemiology
in that it compares three cohorts of children in three countries in the same 6-year
observation period, even if it confirms that differences exist in the
prescribing profile in the Netherlands, UK and Italy, as reported in previous
national studies and in systematic reviews.[1-3] These differences have been
attributed to a few, between-country variable as: prescribers’ attitudes,
therapeutic needs of the population and national drug regulations and policies. The present study has important
limitations, that have not been acknowledged by the authors. There are between-country
differences in: data collected, age groups selected, and samples that are not
comparable and may not be representative of the national paediatric populations.
These methodological aspects can affect the overall findings, since each
country contributes in a different manner to the “contents” of the study. Moreover, there are some
technical enquiries that should be clarified. 1. Prevalence rate is
calculated using person years as the denominator. However, a figure on the
trend of the prevalence rate in the 2000-2005 period would be useful to better
understanding and supporting general findings. 2. There are differences in
the prevalence rates presented in figure 1 and figure 2. Figure 2, in
particular, is confounding, since the overall prevalence is not the sum of the
prevalence in each of the 3 countries, as reported. 3. The major strength of a
multi-country database is that it permits the prescribing profiles in different
countries to be compared, but this was done only in part. No quantitative or
qualitative differences in prescriptions were discussed by the authors for the
main therapeutic classes (table 3 of the study), i.e. antibiotics and
anti-asthmatics, as already done by others for the same countries [3,4]. 4. The authors did not
provide any details concerning the percentage of prescriptions covered by
therapeutic classes (table 3) and drugs (tables 4,5, and 6). In fact, the
percentage of prescriptions covered by the first five drugs could vary
according to therapeutic class and country. 5. It is difficult to
understand data reported in table 4, 5, and 6. If they are prevalence rates (as
stated in the methods), then it is odd that there are figures higher than 1000.
However, even if the data represent the number of prescriptions per 1000
children, the figures seem too high. In any case, the rate in the
overall population (last column of tables 4,5, and 6) cannot be the sum of the
rates in the different age groups, as reported in the paper. Doing so, for
example, levonorgestrel/oestrogen results as one of the most used drugs in the
Netherlands, even though its use is negligible in children < 12 years. 6. The percentage of
off-label use cannot be only 0 or 100, as reported in tables 4, 5, and 6. The
authors considered three age groups (<2, 2-11, 12-18), while the lowest age
for which a drug is licensed could fall in-between these ranges. For example,
fluoxetine in the UK is licensed for children ≥ 8 years old, but the
percentage of off-label use in the 2-11 year population was 0. Moreover, different formulations
of the same drug can be licensed for different ages. In Italy, for example, inhaled
beclometasone is licensed for children of all ages, while intranasal
beclometasone is licensed for children ≥ 6 years. Thus, this should be
taken into account in calculating the percentage of off-label use of
beclometasone. 7. Two bibliographic
references (1 and 41; 39 and 42) are duplicates. We listed in table 1 below the
10 most used drugs in the three countries, according to data reported in the
paper. It is interesting to note that only salbutamol was among the 10 most
used drugs in all the countries, with a rate that ranged between 1813/1000 in
the Netherlands and 22034/1000 in the UK. Other drugs seems to be country
specific. Moreover, it is interesting
to note that 4 out of the 10 most used drugs in the Netherlands are not
licensed for use in children. However, fusidic acid (dermatological) and
hydrocortisone, are widely used also in the UK, and in this country they are
licensed for children. Evidence concerning effectiveness and safety of these
drugs in the paediatric population is not lacking. We therefore think that findings
from this study should be used not only for prioritization of research, but,
first of all, for asking for an harmonization of the drug licenses at the European
level and for identifying which drugs could be considered “essential” (i.e. according to the World Health
Organization definition) on the basis of physician practices across Europe. Moreover, these data
underline that the difference in the prescribing pattern is not explained only,
or mainly, by the different drug licensing statuses, as proposed by the
authors. On the contrary, we think that different prescribing attitudes are the
main determinant of intra- and inter-country differences. In conclusion, this study had the potential to provide information
useful at different levels (for health care professionals and health
authorities) for identifying therapeutic needs and improving the rational use
of drugs. However, from this point of
view, the study by Sturkenboom et al represents a missed opportunity, since too
much data were presented, often in an unclear manner, and with some
methodological flaws. Only few data were discussed, in particular concerning
the differences in prescribing profiles between countries, and little input was
provided to the scientific and lay communities in order to guarantee safe and
effective therapies for children and their families. Finally, findings from this
study underline that an international paediatric formulary is needed.[5] Antonio
Clavenna (clavenna@marionegri.it), Maurizio Bonati Laboratory for Mother and
Child Health, Department of Public Health, “Mario Negri” Institute, Milan,
Italy Competing interest: none References 1.
Schirm E, van den Berg P, Gebben H, Sauer P, De Jong-van den Berg L. Drug
use of children in the community assessed through pharmacy dispensing data. Br
J Clin Pharmacol 2000;50:473-8 2.
Cazzato T, Pandolfini C, Campi R, Bonati M. Drug
prescribing in out-patient children in Southern Italy. Eur J Clin Pharmacol 2001; 57:611-616. 3.
Rossignoli A, Clavenna
A, Bonati M Antibiotic prescription and prevalence rate in the outpatient
paediatric population: analysis of surveys published during 2000-2005. Eur J
Clin Pharmacol 2007;63:1099-106. 4.
Clavenna A, Rossi
E, Berti A et al. Inappropriate
use of anti-asthmatic drugs in the Italian paediatric
population. Eur J Clin Pharmacol 2003; 59:565-9. 5.
Bonati
M, Pandolfini C. Children need international formulary to guarantee rational
use of drugs. BMJ. 2004;328:227 The 10 most commonly used
drugs in the Netherlands, United Kingdom and Italy (data extracted from the
paper by Sturkenboom et al).
* unlicensed for use in the paediatric population Competing interests: None declared |
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