Decision making, evidence, audit, and education: case study of antibiotic prescribing in general practiceCommentary: What can we learn from narratives of implementing evidence?
BMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7242.1114 (Published 22 April 2000) Cite this as: BMJ 2000;320:1114
All rapid responses
Dr Jay Herbert makes a point about the licensed indications for
trimethoprim, but may mislead readers as to the legal implications of
prescribing a drug outside the product licence (as stated in its SPC).
In the unfortunate event of a mishap with a drug, proving negligence
on the part of the prescriber requires the injured party to prove that the
prescriber acted in a way that was not consistent with the practice of a
reasonable body of his/her peers of similar professional standing. This is
also the case for drugs used within the terms of their product licence.
In the case of three days of trimethoprim for a simple UTI, I think
any prescriber can be assured that they are not acting in such a way....3
days of trimethoprim for a simple UTI is indeed considered best practice
as has been reiterated by previous correspondents, and the recent guidance
issued by SMAC and the Public Health Laboratory Service (both would
probably serve as evidence in a court of law as providing a 'reasonable
body of peers of similar professional standing').
The product licence only governs the way in which the manufacturer
can promote the product. Clearly, licensed indications have been approved
by the licensing authority who are satisfied that the data in support of
such indications are robust. This, therefore, acts as a 'reasonable body’
of evidence. As Dr Herbert says, there is no incentive for the
manufacturers of trimethoprim to finance a 3-day license submission and it
is unlikely to happen.
Prescribers should not be misled into thinking that they are
necessarily acting in a negligent fashion by using a product outside its
product licence. However, they must be sure that the use of a product in
such a way is defensible, as outlined above.
sincerely
Jonathan Underhill
Competing interests: No competing interests
Editor,
We were interested in the study by Lipman and Price into the prescribing
of trimethoprim for urinary tract infections (1). We have recently carried
out a study using the General Practice Research Database (GPRD),
investigating resistance associated with various antibiotics used to treat
young women with a diagnosis of a urinary tract infection.
The GPRD
contains the anonymised patient records of over 4 million people resident
throughout the United Kingdom and has been described elsewhere (2). Our
study included all women aged 15-44 years with a record of UTI or
cystitis between 1992 and 1998 and an accompanying prescription for an
antibiotic. Patients were selected to have at least six months data prior
to the diagnosis and no record of cystitis/UTI during this period. Only
the first infection in each patient in the study period was included. All
patients with a diagnosis plus a prescription were followed for 28 days
and the need for any further prescriptions of an antibiotic were taken as
a failure of treatment. Patients with a first infection and a prescription
for trimethoprim were analysed based on whether 3, 5 or 7 days of
treatment were prescribed. A Cox regression analysis was carried out,
adjusting for age, comparing the treatment durations and the results are
presented in Table 1.
There were 76,629 first prescriptions of
trimethoprim associated with a diagnosis of UTI in the study period where
the duration of the prescription or the number of tablets of 200mg
trimethoprim were recorded. Only 8.2% of prescriptions were for 3 days,
60.0% were for 5 days and 31.8% were for 7 days. The percentage of all
trimethoprim prescriptions written in any one year for 3 days increased
from 6.3% in 1992 to 14.6% in 1998. As can be seen from table 1, there was
a 1.4% difference in the percentage of patients being prescribed a second
course of antibiotics within 14 days of the initial prescription i.e. a
NNT of 71 patients. However, if an adjustment is made for the length of
the prescription there is no significant difference between relapse rates.
This study was retrospective and patients were not randomised between
treatments. It is possible that the duration of treatment reflected
symptom severity rather than the prescribing preferences of individual
GPs. Nevertheless, we would suggest 3 days of treatment with trimethoprim
to be as effective as 5 or 7 days of treatment and we would support this
as the preferred option for uncomplicated UTIs in young women.
Table 1. Percentage of treatment failures (+95% confidence intervals)
in women treated for urinary tract infections with 3, 5 and 7 days of
200mg trimethoprim.
____________________________________________________________
3 days 5 days 7 days
____________________________________________________________
Percentage failure
within 14 days of
start of initial
prescription 11.6 10.5 10.2
(10.8,12.4) (10.3,10.8) (9.9,10.6)
Percentage failure
within 14 days of
end of initial
prescription 12.8 12.4 12.9
(12.0,13.7) (12.1,12.7) (12.5,13.4)
____________________________________________________________
References.
1) Lipman T, Price D. Decision making, evidence, audit and education: case
study of antibiotic prescribing in general practice. BMJ 2000; 320: 1114-8
2) Lawrenson RA, Williams T, Farmer RD. Clinical information for
research; the use of general practice databases. Journal of Public Health
1999; 21(3): 299-304
Ross Lawrenson
Professor of Primary Health Care
John Logie
Research Fellow
Postgraduate Medical School,
University of Surrey,
Stirling Road,
Guildford,
Surrey
GU2 7DJ
Competing interests: Table 1. Percentage of treatment failures (+95% confidence intervals)in women treated for urinary tract infections with 3, 5 and 7 days of 200mg trimethoprim.____________________________________________________________ 3 days 5 days 7 days____________________________________________________________Percentage failure within 14 days ofstart of initialprescription 11.6 10.5 10.2 (10.8,12.4) (10.3,10.8) (9.9,10.6)Percentage failurewithin 14 days ofend of initialprescription 12.8 12.4 12.9 (12.0,13.7) (12.1,12.7) (12.5,13.4)____________________________________________________________
EDITOR - The case study by Lipman and Price on antibiotic prescribing
in urinary tract infections in general practice raised some
interesting issues regarding decision making and policy implementation in
general practice, along with the potential dangers of
accepting guidelines without looking closely at the underlying evidence
(1). However, the paper also contributes to the collection of
poor quality data cocerning the length of antibiotic treatment.
The
authors state their results are reassuring in that 3 day courses of
trimethoprim for uncomplicated urinary tract infections do not seem to
increase the rate of treatment failure. Unfortunately, the results
cannot be accepted as reassuring as the methodology is fundamentally
flawed. The analysis was retrospective, and the decision
about treatment length was unrandomised, leading to all kinds of potential
bias. For example, the decision to treat for 7 days rather
than 3 may have been made subconsciously because the patient appeared to
be less well, or have more severe symptons. Almost
twice as many people who had a 3 day course returned returned for a second
consultation compared to those who had had 5 days
(14% versus 7.2 %) - apparently a non-significant difference but a
suggestion perhaps of a lack of power in the study to demonstrate
a significance.
It was disappointing that the authors did not acknowledge
these fairly obvious flaws in their discussion as I felt this
undermined the overall quality of the paper which otherwise had some good
points to make.
David Grimshaw
General Practitioner
Langford Medical Practice,
9 Nightingale Place,
Bicester,
Oxon
OX6 0XX
david@dgrimshaw.freeserve.co.uk
1 Lipman T, Price D. Decision making, evidence, audit, and
education: case study of antibiotic prescribing in general practice. BMJ
2000; 320: 1114 - 18 (22 April)
Competing interests: No competing interests
Sir
Drs Lipman and Price provide an interesting account of how difficult
life can be when you start applying modern standards of analysis to the
scientific data used to support elderly medicinal products.
There is, however, one aspect of this conflict they have overlooked.
Trimethoprim, licensed as it was at a time of very differing standards in
clinical and financial management, has a recommended dose schedule that
does not include a 3-day treatment regimen.
Health care professionals are encouraged to look at the Summary of
Product Characteristics for a product before prescribing it (in a previous
incarnation the SPC was known as the Data Sheet). If they do this for
trimethoprim they will see it is recommended that "treatment should
continue for at least one week..."* or similar.
In adopting a practice protocol recommending a 3-day course of
treatment for uncomplicated UTI, the authors are suggesting their
colleagues use a medicinal product outside the terms of its product
licence. Legally, the manufacturer's liability is limited and the
prescriber is using the product on their own responsibility. The
situation is similar to using an unlicensed product on "named patient" or
"compassionate supply" basis.
I am not suggesting that the authors' partnership is not encouraging
best practice. The problem is that the British legal system may not see
it the same way. A treatment protocol with a seven-day course of
treatment might prove cheaper in the long term.
This is not the only instance of a medicine widely used in a manner
not covered by its product licence. There are no sound commercial reasons
why manufacturers should go to the trouble and expense of changing their
licences. These are mostly patent-expired products with small sales and
even smaller profits.
As the authors discovered the supporting data is not robust. A
company trying to change its trimethoprim licence to include 3-day
treatment for simple UTI is unlikely to succeed anyway.
Yours
Jay Herbert
* Monotrim Summary of Product Characteristics 1997: Solvay Healthcare
Limited.
Competing interests: No competing interests
Often in general practice we take the evidence for the way we
practice for granted. Even if it is "evidence-based" how sound is this
evidence? It is helpful to read narratives written by GPs of their own
practices particularly when they are ready to admit their shortcomings and
when they investigate the evidence.
The ability to justify what we as doctors do, and when we do and do not
prescribe, is increasingly asked of us.
There are a few points about Lipman's paper I wish to raise.
Although he perhaps rightly concludes that small group educational
processes are better at making management decisions I am not sure it is a
safe conclusion that they are better at implementing them. I would be
concerned that my partners and I had "by consensus" agreed to a protocol
(ie to prescribe Trimethoprim for 3 days in uncomplicated UTI) but a year
later "some GPs claimed not to have heard the new policy". Lipman does not
mention how many GPs are in Westerhope Medical Group but given this
communication breakdown amongst the parners would the use of stronger
evidence necessarily be better implemented?
Secondly I would have misgivings that Trimethoprim was prescribed for
seven days in 16 cases when no growth was obtained on culture and in 31
cases when no culture was taken. The group selected by definition is women
of child-bearing age or older. Trimethoprim is a folate antagonist and
contra-indicated in pregnancy as per the BNF. There is no mention of
whether pregnancy had been excluded and clearly the group could have
included women who, in the early stages were unaware they were pregnant
and not taking folate supplementation.
Thirdly I would question whether as a practice too few urine cultures
were done both before and after treatment. As doctors we strive to
optimize our antibiotic usage within the constraints of (general) practice
and often have to treat empirically. This however should be backed where
possible with laboratory evidence, and treatment often has to be commenced
before cultures are available. By their protocol a patient could have
required a third course of antibiotics before their "uncomplicated" UTI
was successfully treated.
It is interesting that urinalysis was dismissed as "not reliable".
Finally the term "uncomplicated" is not particularly useful and
disliked by many microbiologists as all infections have the potential for
complication especially if they are being treated "blindly" and with no
urine culture awaited.
David Carvel
Competing interests: No competing interests
David Syme's point that we can use computerised formularies to ensure
consistency of prescribing is well made. Since our paper was written we
have had PRODIGY installed in EMIS and (provided we first code "urinary
tract infection") are given a first choice of 3 days of trimethoprim.
However our original question was not only to do with consistency, it was
about clinical effectiveness, and we asked the question: do 3 day courses
of trimethoprim in women with uncomplicated lower urinary tract infection
lead to higher second consultation rates? That is why our first step was
to critically appraise the evidence and to search for more when we found
it flawed. Of course we discovered that no evidence exists that can
reliably answer our question so, given that we still had to make a
decision one way or the other, audited prescribing, investigations and
outcomes as described in the paper in order to give us more information to
help us decide whether or not to continue with 3 day courses.
David Taylor draws a different conclusion than ours - that because
there was a (non-significant) trend towards higher second consultation
rates in patients given a 3 day course, he would change back to 5 days. As
he points out, the confidence intervals were wide so, had this been a
randomised controlled trial, a better interpretation would have been that
the study was underpowered and that no valid conclusion could be drawn.
However this was not a randomised controlled trial. It was a
retrospective analysis of routinely recorded data together with a
narrative of the practice's decision making and implementation processes.
We relied upon our memory and our knowledge of how the practice functions
in writing the narrative. Our intention was to present a realistic picture
of our experiences and describe the context in which we made our
decisions. This has the advantage that the picture which emerged may be
more "true to life" than in a formal study and, in particular, avoids the
"Hawthorne effect" in which the process of being observed changes the
behaviour of the participants. But it has disadvantages too, in that we
could not retrospectively investigate the questions that it raised.
For example we formed the impression that some doctors (and perhaps
patients) did not fully trust the 3 day regime. Why for example did 10 out
of 49 patients in the 3 day group whose urine culture grew trimethoprim
sensitive organisms return for a second visit, at which only one was
prescribed a further course of antibiotics? Why was there such a highly
significant difference in second consultation rates among patients who had
urine culture performed at the first consultation compared to those who
did not (15% compared to 4%)? This mistrust and the behaviour of the GPs
("We'll send off a urine and book you an appointment for next week")
rather than a difference in effectiveness may explain the differences in
second consultation rates.
Narratives and other descriptive studies can enumerate measurable
outcomes, give us new information which may help to inform our decisions,
and identify areas for further research. They are not substitutes for
properly conducted randomised controlled trials, nor for appropriate
qualitative studies, and are biased by the viewpoint of the authors.
However they illuminate the context of everyday practice in a way that
more formal methods cannot, because of the fact that such studies
inevitably change the practice they are trying to investigate. I would be
interested to hear any views on the methodological issues raised by
narrative studies, in particular how they can be critically appraised for
validity and applicability.
Toby Lipman
Competing interests: No competing interests
Dear Sir
I enjoyed Toby Lipman and Dawn Price's article. And I enjoyed Trish
Greenhalgh's dramatic meta response to it.
However, I come to a different conclusion. The shorter course did
seem to result in more patients returning, as the nurses remarked, even if
the confidence limits were wide. A quick calculation showed this to add up
to 14 consultations over the year period. If you cost this out at 20
pounds a visit, the cost of a 3 days course as against an average of the 5
and 7 days courses, is 280 pounds a year. This is also at a time when the
present administration seems to be making much political capital over GP
appointment times.
No Sir, I'm going back to 5 day courses. The evidence from this paper
seems stronger than that of the Cochrane Library!
yours
David Taylor
Competing interests: No competing interests
All my prescriptions, except those for controlled drugs, are computer
generated. GPASS, the commonest practice computer system in Scotland, has a
"formulary" option which allows me to preset the dose of drug and length
of course. I use this option extensively because it saves me time. (It
can of course be over-ridden) By spending a minute or two converting the
formulary entry, I have made sure that 100% of my prescriptions for
trimethoprim for UTI are for 3 days only. Presumably other systems could
have a similar facility. Computers don't get bored or forget that they
ought to change behaviour. This simple and basic procedure might help to
remove some of the angst in this situation and remove the need for
"computerised reminders..loose leaf practice manuals...and educational
activities" to implement this particular change.
Competing interests: No competing interests
Trimethoprim for UTI
To the Editor - Drs Lipman and Price1 have produced a fascinating
study of the difficulties encountered when trying to implement "evidence
based practice", They found that the evidence base was not as clear cut as
they would have hoped.
The Standing Medical Advisory Committee 2 (SMAC) recommended that
uncomplicated urinary tract infection should be treated with three days of
trimethoprim. However as has been pointed out, no randomised controlled
trials of this regimen were identified to support this recommendation.
There is good evidence, summarised in a systematic review of clinical
trials in UTI 3 that (i) 7 days trimethoprim is as good as 7 days co-
trimoxazole, and (ii) that 3 days co-trimoxazole is as good as 7 days co-
trimoxazole.
There are also published guidelines which examine the validity of using
evidence comparing the drugs within a class to determine if they are
equivalent 4
Thus although there are no direct comparisons of trimethoprim to co-
trimoxazole prescribed for three days, on the basis of the efficacy
evidence available, the comparison of drugs within a class, and the safety
profile of trimethoprim as compared to co-trimoxazole it is reasonable to
recommend 3 days of trimethoprim for uncomplicated urinary tract
infection.
As Dr Greenhalgh points out in her illuminating commentary, there are
always new twists in the story of the search for the evidence and the
process of changing practice. Since the publication of the SMAC report a
double blind, randomized study dating from 1985 has been brought to our
attention5. This compares three days to ten days trimethoprim therapy in
the treatment of acute dysuria-frequency syndrome. It concluded that in
"adult nonpregnant females with no history of underlying urinary tract or
other disease, few previous UTI episodes, and easy access to close
clinical and bacteriologic follow up." three days of trimethoprim should
be preferred for the treatment of acute urinary tract infection. This
study clearly supports the recommendation of three days of trimethoprim.
Making recommendations in the real world can be difficult as has been
illustrated. Randomised controlled trials may not have been done, or not
identified; advice may have to be based upon the best evidence available.
This is why recommendations such as those in the SMAC report should be
kept under review, and changed appropriately as the evidence base
accumulates.
Refs
1. Lipman, T. Price, D. Decision making, evidence, audit, and
education: case study of antibiotic prescribing in general practice BMJ
2000;320:1114-1118
2. Standing Medical Advisory Committee, Sub-Group on Antimicrobial
Resistance. The path of least resistance. London: Department of Health ,
1998
3. Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, and
StammWE. Guidelines for Antimicrobial Treatment of Uncomplicated Acute
Bacterial Cystitis and Acute Pyelonephritis in Women. Clinical Infectious
Diseases 1999;29:745-58
4. McAlister FA, Laupacis A, Wells GA, Sackett DL. Users' Guides to
the Medical Literature: XIX. Applying clinical trial results B. Guidelines
for determining whether a drug is exerting (more than) a class effect.
JAMA. 1999 Oct 13;282:1371-7.
5. Gossius G, Vorland L. The treatment of acute dysuria-frequency
syndrome in adult women: Double blind, randomized comparison of three day
vs ten day trimethoprim therapy. Current Thrapeutic Research. 37 34-42
1985
6. Greenhalgh T, Commentary: What can we learn from narratives of
implementing evidence? BMJ 2000;320:1114-1118
Julius Weinberg on behalf of the Clinical Prescribing Sub-Group of
the Interdepartmental Steering Group on Antimicrobial Resistance
Competing interests: No competing interests