Randomised control trial
Dee Richards, Les Toop, Stephen Chambers, Lynn FletcherResponse to antibiotics of women with symptoms of urinary tract infection but negative dipstick urine test results: double blind randomised controlled trial
British Medical Journal
7-16-2005, pages 143-147
- Submitted by:Steven TenElshof - EM resident
- Institution:GRMERC
- Date submitted:9th March 2006
1
Objectives and hypotheses
1.1
Are the objectives of the study clearly stated?
Yes. Determine the effectiveness of antibiotic treatment of women with symptoms of UTI but negative urine dipstick tests.
2
Design
2.1
Is the study design suitable for the objectives
Yes. Double blind, randomized, placebo-controlled trial
2.2
Who / what was studied?
Females who presented as outpatients with UTI symptoms and negative urine dipstick tests / their clinical response to antibiotics.
2.3
Was this the right sample to answer the objectives?
90% of the women in this study reported having previous, similar episodes; so this population may not be representative of patients with "simple" UTIs.
2.4
Is the study large enough to achieve its objectives? Have sample size estimates been performed?
Marginally. Power studies showed that 30 patients in each arm would suffice, and the two arms had 26 and 33 patients.
2.5
Were all subjects accounted for?
Yes. All patients completed 7-day questionnaires.
2.6
Were all appropriate outcomes considered?
Yes. Symptom resolution. Adverse events.
2.7
Has ethical approval been obtained if appropriate?
Yes
2.8
Were the patients randomised between treatments?
Yes.
2.9
How was randomisation carried out?
Random alphanumerical code blocks, with a pharmacist preparing identical appearing treatment and placebo pills. Neither physician nor nurse were aware of the nature of the pills dispensed.
2.10
Are the outcomes clinically relevant?
Yes. Symptom abatement is relevant.
3
Measurement and observation
3.1
Is it clear what was measured, how it was measured and what the outcomes were?
The main outcome was resolution of dysuria in the intervention and control groups at three and seven days, and median time to resolution. Secondary outcomes were resolution of other symptoms.
3.2
Are the measurements valid?
Participants received a seven day diary to record their symptoms and return by mail. They recorded the presence or absence of individual symptoms each day. Investigators contacted all women after seven days and administered a structured telephone questionnaire, recording the presence or absence of each symptom.
3.3
Are the measurements reliable?
Subjective resolution of symptoms.
3.4
Are the measurements reproducible?
Yes
3.5
Were the patients and the investigators blinded?
Yes.
4
Presentation of results
4.1
Are the basic data adequately described?
Yes. Figure 1 shows the flow of participants through the trial.
4.2
Were groups comparable at baseline?
Yes (Table 1).
4.3
Are the results presented clearly, objectively and in sufficient detail to enable readers to make their own judgement?
Yes (Tables 2 and 3).
4.4
Are the results internally consistent, i.e. do the numbers add up properly?
Yes.
4.5
Were side effects reported?
Yes, Six patients (18%) in the placebo arm and three (12%) in the treatment arm reported minor symptoms (nausea, sore mouth, itching skin, sedation after taking medication, mouth ulceration, and thrush).
5
Analysis
5.1
Are the data suitable for analysis?
Yes.
5.2
Are the methods appropriate to the data?
Median test and Number Needed to Treat where applicable.
5.3
Are any statistics correctly performed and interpreted?
Yes
6
Discussion
6.1
Are the results discussed in relation to existing knowledge on the subject and study objectives?
Yes. The discussion section references other, related medical literature.
6.2
Is the discussion biased?
No
7
Interpretation
7.1
Are the authors' conclusions justified by the data?
Yes.
7.2
What level of evidence has this paper presented? (using CEBM levels)
2b
7.3
Does this paper help me answer my problem?
Yes
8
Implementation
8.1
Can any necessary change be implemented in practice?
Yes. It is reasonable to treat otherwise healthy females presenting with UTI symptoms but with negative urine dipstick tests with 3 days of trimethoprim. Trimethoprim reduced the duration of dysuria in women with symptoms of uncomplicated urinary tract infection and negative dipstick result by a median time of two days
8.2
What aids to implementation exist?
Journal publication and dissemination of these study results.
8.3
What barriers to implementation exist?
The entrenched dogma of not treating those females with UTI symptoms who have negative urine dipstick tests; increasing resistence to trimethoprim; the unexpectedly high positive response to antibiotics reduced the power to assess predictors of response to treatment, as there were so few non-responders.