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Open Access Research article

Results from a blind and a non-blind randomised trial run in parallel: experience from the Estonian Postmenopausal Hormone Therapy (EPHT) Trial

Piret Veerus1*, Krista Fischer2, Matti Hakama3, Elina Hemminki4 and The EPHT Trial

Author Affiliations

1 Department of Epidemiology and Biostatistics, National Institute for Health Development, Hiiu 42, 11619 Tallinn, Estonia

2 Estonian Genome Center, University of Tartu, Tiigi 61b, 50411 Tartu, Estonia

3 Tampere School of Public Health, University of Tampere, Medisiinarinkatu 3, FIN-33520 Tampere, Finland

4 National Institute for Health and Welfare (THL), P.O. Box 30, FIN-00271 Helsinki, Finland

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BMC Medical Research Methodology 2012, 12:44  doi:10.1186/1471-2288-12-44

Published: 4 April 2012

Abstract

Background

The Estonian Postmenopausal Hormone Therapy (EPHT) Trial assigned 4170 potential participants prior to recruitment to blind or non-blind hormone therapy (HT), with placebo or non-treatment the respective alternatives. Before having to decide on participation, women were told whether they had been randomised to the blind or non-blind trial. Eligible women who were still willing to join the trial were recruited. After recruitment participants in the non-blind trial (N = 1001) received open-label HT or no treatment, participants in the blind trial (N = 777) remained blinded until the end of the trial. The aim of this paper is to analyse the effect of blinding on internal and external validity of trial outcomes.

Methods

Effect of blinding was calculated as the hazard ratio of selected chronic diseases, total mortality and all outcomes. For analysing the effect of blinding on external validity, the hazard ratios from women recruited to the placebo arm and to the non-treatment arm were compared with those not recruited; for analysing the effect of blinding on internal validity, the hazard ratios from the blind trial were compared with those from the non-blind trial.

Results

The women recruited to the placebo arm had less cerebrovascular disease events (HR 0.43; 95% CI: 0.26-0.71) and all outcomes combined (HR 0.76; 95% CI: 0.63-0.91) than those who were not recruited. Among women recruited or not recruited to the non-treatment arm, no differences were observed for any of the outcomes studied.

Among women recruited to the trial, the risk for coronary heart disease events (HR 0.77; 95% CI: 0.64-0.93), cerebrovascular disease events (HR 0.66; 95%CI: 0.47-0.92), and all outcomes combined (HR 0.82; 95% CI: 0.72-0.94) was smaller among participants in the blind trial than in the non-blind trial. There was no difference between the blind and the non-blind trial for total cancer (HR 0.95; 95% CI: 0.64-1.42), bone fractures (0.93; 95% CI: 0.74-1.16), and total mortality (HR 1.03; 95% CI: 0.53-1.98).

Conclusions

The results from blind and non-blind trials may differ, even if the target population is the same. Blinding may influence both internal and external validity. The effect of blinding may vary for different outcome events.

Trial registration

[ISRCTN35338757]

Keywords:
Clinical trial; Blinding; Internal and external validity