Using external data to assess the external validity of a randomised controlled trial

Abstract

Background

Few studies have addressed external validity of randomized controlled trials in infectious diseases. We aimed to assess the external validity of an investigator-initiated trial on treatment for uncomplicated urinary tract infection.

Methods

In the original study, women (n = 513) with urinary tract infection were randomized to nitrofurantoin or fosfomycin treatment in three countries between 2013 and 2017. In the present study we compared women who were screened for enrolment but excluded to women who participated in the trial, both groups in Israel. The primary outcome was the rate of emergency department index visits resulting in hospitalization within 28 days.

Results

We compared 127 included to 110 excluded patients. The most common reasons for exclusion were logistic difficulties in recruitment and antibiotic use in the preceding month. Included patients tended to be older [39 (IQR 29–59) vs. 35.5 (IQR 24–56.25 years)], more likely to have history of recurrent infection and had more urinary symptoms. Among excluded patients, 13.6% (15/110) had initial visits resulting in hospitalization compared to 3.1% (4/127) of included participants (p = .003). The rate of emergency department visits within 28 days was similar in both groups. Clinical and microbiological failures were significantly more common in included patients [26% (33/127) vs. 1.8% (2/110), p < .001; 7.9% (10/127) vs. 0% (0/110), p = .003; respectively].

Conclusions

While differences were observed between included and excluded patients, the excluded group did not represent a more ‘complicated’ population. The present study shows the importance of collecting data on patients excluded from randomized controlled trials.

Keywords:

• Urinary tract infection
• external validity
• randomized controlled trial
• inclusion criteria
• exclusion criteria

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

The study was funded with the assistance of the Israel National Institute for Health Policy and Health Services Research (NIHP) (grant number 2016/80). The funding source had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report and in the decision to submit the manuscript for publication. The RCT was funded by the European Commission under the Life Science Health Priority of the Seventh Framework Programme (Assessment of Clinical Efficacy by a Pharmacokinetic/Pharmacodynamic Approach to Optimise Effectiveness and Reduce Resistance for Off-Patent Antibiotics project, grant agreement 278348).