Effectiveness of a multiple intervention to reduce antibiotic prescribing for respiratory tract symptoms in primary care: randomised controlled trial
BMJ 2004; 329 doi: https://doi.org/10.1136/bmj.38182.591238.EB (Published 19 August 2004) Cite this as: BMJ 2004;329:431
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Dear Sir,
Indeed the decline in use of narrow spectrum and older penicillins
and the increase in prescribing more broad-spectrum and new
chemotherapeutics is one of the major problems in modern health care
relating to the growing problem of antimicrobial resistance of bacterial
agensts. However, even in the Netherlands about half of the antibiotic
prescriptions for respiratory tract infections are unnecessary and
inappropriate. This has not only been suggested by de Melker (1), but has
recently been shown by our own research group (2). So, we believe the
reached reduction is suboptimal; a higher reduction is possible as well as
improving the choice of antibiotics is needed.
Sincerely Yours,
Ineke Welschen
Marijke M Kuyvenhoven
Arno W Hoes
Theo JM Verheij
1. De Melker RA. Effectiviteit van antibiotica bij veel voorkomende
luchtweginfecties in de huisartspraktijk. Ned Tijdschr Geneeskd 1998;142:
452-6.
2. Akkerman AE, Kuyvenhoven MM, van der Wouden JC, Verheij TJM. Het
voorschrijven van antibiotica door de huisarts bij luchtweginfecties,
astma en COPD. Submitted 2004
Competing interests:
None declared
Competing interests: No competing interests
Dear Sirs,
Implementing guidelines requires comprehensive approaches at
different levels (GPs, practices and peer review groups). Thus
intervention studies on the effectiveness of quality improvement
programmes should be pragmatic and embedded in existing structures.
Conaty states that the used randomisation scheme is not a
randomisation in the sense of random allocation of peer review groups
aiming to make two groups comparable regarding known and unknown potential
confounders. We agree that our scheme is not randomisation in that
classical sense. However randomisation of peer review groups without
matching or clustering was not an attractive option because randomisation
of the - only - twelve peer review groups almost certainly would lead to
differences in the important prognostic factors (or if you wish
‘confounders’) between the intervention and control group.
That is why we developed a method to ensure comparability of the
three major potential confounders (a) degree of urbanisation
(rural/urban), (b) group size (above / below median) and (c) volume of
antibiotic prescriptions (above / below median) between the two groups.
Otherwise sample sizes would not have been feasible. This ended up with
two comparable groups of GP peer review groups, which were randomly
allocated to the experimental and control group. The solution chosen after
consultation of several statisticians and epidemiologists was perhaps
unusual, but did in their and our firm opinion not bias the results and
Conaty seems to agree with that. Consequently we defined to present the
trial as a randomised controlled trial; using the concept of “controlled
trial” would neglect the random allocation of the combined groups of GP
peer review groups.
Bland critizes the statistical analysis at the level op GPs, while
allocation and randomisation was carried out at the level of combined
groups of GP peer review groups. The randomisaton scheme we applied to
obtain comparable groups does not imply that the unit of statistical
analysis had to be the combined groups of GP peer review groups; even if
this was statistically possible it would result in clinically irrelevant
results, since the intervention was directed to individual GPs within peer
review groups and was aimed to change GP behaviour. So we calculated
effectiveness at GP level “controlling” for practice and GP peer group
level. Importantly, taking these two “clustering” factors into account
did not clearly influence the results.
Sincerely Yours,
Ineke Welschen
Marijke M Kuyvenhoven
Arno W Hoes
Theo JM Verheij
Competing interests:
None declared
Competing interests: No competing interests
Conaty is right to criticise the design of this trial. It is a
randomised trial, in that something is allocated to treatment at random.
In such a trial, the thing which is allocated is known as the experimental
unit and is the smallest thing which can have a different treatment from
another, similar unit. Here this is not the GP or the peer review group
but the combined group of six peer review groups.
In a cluster randomised trial, the cluster forms the experimental
unit and should be used as the unit of analysis or have the variation
between clusters included in some equivalent way. Welschen and colleagues
have done this, taking the peer review group as the cluster. But it is
not, it is the super-cluster of six peer review groups that is the
experimental unit and should be the unit of analysis. Hence they have
only two observations, one in each treatment group, and cannot estimate
the variation between them. Hence then cannot tell whether the difference
between the treatment groups is greater than would be likely to arise
given the variation between experimental units. Hence they cannot analyse
this as a randomised trial.
The authors could have attempted to balance their two groups of six
peer review groups by minimisation. They could then have analysed the
trial as a cluster randomised trial in the usual way.
Competing interests:
None declared
Competing interests: No competing interests
The aphorism among epidemiologists "never leave randomisation to
chance" seems to have been taken seriously by Welshen and colleagues in
their study of an educational intervention to reduce antibiotic
prescribing in GP peer groups. (1) The randomisation process in their
study seems to have been reduced to a single coin toss after they had
divided 12 GP peer groups into roughly equal camps with respect to three
factors - rurality, prescribing and number of GPs. They seem to have done
a good allocation job judging by the baseline characteristics in the two
groups. However, none of the balance between groups is attributable to
randomisation.
The objective of randomisation is to achieve a balance between two
comparison groups at baseline with respect to factors we know are
important (i.e. can influence the outcome) and (this is the crunch)
factors that we don't know about but are still important. Unfortunately in
this trial we can't be confident that this high standard of balance was
achieved because allocation to intervention or control group was not
random. The only random element in this study (coin toss) simply decided
which of these potentially imbalanced groups got the intervention.
Randomisation is no guarantee of perfect balance and this is why
epidemiologists and statisticians try to insure against gross imbalance by
various means (2) – hence the aphorism above.
The BMJ should consider carefully which trials deserve the label
"randomised controlled trial" because this is often interpreted as a mark
of quality. I think this trial is better labelled a "controlled trial" -
no shame there.
1. Welschen I, Kuyvenhoven MM, Hoes AW, Verheij TJM. Effectiveness of
a multiple intervention to reduce antibiotic prescribing for respiratory
tract symptoms in primary care: randomised controlled trial. BMJ
2004;329:431-3.
2. Altman D, Bland M. Statics notes: Treatment allocation in
controlled trials: why randomise? BMJ 1999;318:1209.
Competing interests:
None declared
Competing interests: No competing interests
Dear Sir,
the authors Kuyvenhoven and Verheij cite their own work (1).
Here they point to the real problem:
"The international trend of a decline in the use of narrow-spectrum
and older penicillins and prescribing more broad-spectrum and new
chemotherapeutics."
And they ask for the right solution:
"More emphasis on implementation of guidelines aimed at prescribing
narrower spectrum and older penicillins in respiratory tract infections
and especially lower respiratory tract infections seems to be needed.."
Penicillin is the treatment of choice in most cases.
Nothing else.
Sincerily Yours
Friedrich Flachsbart
1. MM. Kuyvenhoven, FAM van Balen, TJM Verheij:
Outpatient antibiotic prescriptions from 1992-2001 in The Netherlands.
Journal of Antimicrobial Chemotherapy 2003;52:675-678
Competing interests:
None declared
Competing interests: No competing interests
Re: The experimental unit is wrong
Dear Sir,
Implementing guidelines requires comprehensive approaches at
different levels (GPs, practices and peer review groups). Thus
intervention studies on the effectiveness of quality improvement
programmes should be pragmatic and embedded in existing structures.
Conaty states that the used randomisation scheme is not a
randomisation in the sense of random allocation of peer review groups
aiming to make two groups comparable regarding known and unknown potential
confounders. We agree that our scheme is not randomisation in that
classical sense. However randomisation of peer review groups without
matching or clustering was not an attractive option because randomisation
of the - only - twelve peer review groups almost certainly would lead to
differences in the important prognostic factors (or if you wish
‘confounders’) between the intervention and control group.
That is why we developed a method to ensure comparability of the
three major potential confounders (a) degree of urbanisation
(rural/urban), (b) group size (above / below median) and (c) volume of
antibiotic prescriptions (above / below median) between the two groups.
Otherwise sample sizes would not have been feasible. This ended up with
two comparable groups of GP peer review groups, which were randomly
allocated to the experimental and control group. The solution chosen after
consultation of several statisticians and epidemiologists was perhaps
unusual, but did in their and our firm opinion not bias the results and
Conaty seems to agree with that. Consequently we defined to present the
trial as a randomised controlled trial; using the concept of “controlled
trial” would neglect the random allocation of the combined groups of GP
peer review groups.
Bland critizes the statistical analysis at the level op GPs, while
allocation and randomisation was carried out at the level of combined
groups of GP peer review groups. The randomisaton scheme we applied to
obtain comparable groups does not imply that the unit of statistical
analysis had to be the combined groups of GP peer review groups; even if
this was statistically possible it would result in clinically irrelevant
results, since the intervention was directed to individual GPs within peer
review groups and was aimed to change GP behaviour. So we calculated
effectiveness at GP level “controlling” for practice and GP peer group
level. Importantly, taking these two “clustering” factors into account
did not clearly influence the results.
Sincerely Yours,
Ineke Welschen
Marijke M Kuyvenhoven
Arno W Hoes
Theo JM Verheij
Competing interests:
None declared
Competing interests: No competing interests