Statistical analysis plan for the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM)

Abstract

Background: Current management for men with lower urinary tract symptoms (LUTS) is a pathway that results in prostate surgery in a significant proportion. While helpful in relieving benign prostatic obstruction (BPO), surgery may be ineffective for men suffering from difficulties not relating to BPO. The UPSTREAM trial started recruitment in October 2014 with the aim of establishing whether a care pathway including urodynamics (a diagnostic tool for BPO and thus an indication of whether surgery is needed) is no worse for men, in terms of symptomatic outcome, than one without (routine care).

Methods/design: This analysis plan outlines the main outcomes of the study and specific design choices, such as non-inferiority margins. The trial is currently recruiting in 26 hospitals across the UK, randomising men to either urodynamics or routine care, with recruitment set to end on the 31 December 2016. All outcomes will be measured 18 months after randomisation to allow sufficient time for surgical procedures and recovery. The primary outcome is based on a non-inferiority design with a margin of 1 point on the International Prostate Symptom Score (IPSS) scale. The key secondary outcome for this trial is surgery rate per arm, which is estimated to be at least 18% lower in the urodynamics arm. Surgery rates, adverse events, flow rate, urinary symptoms and sexual symptoms are secondary outcomes to be assessed for superiority. This is an update to the UPSTREAM protocol, which has already been published in this journal.

Discussion: This a priori statistical analysis plan aims to reduce reporting bias by allowing access to the trial's objectives and plans in advance of recruitment end. The results of the trial are expected to be published soon after the trial end date of 30 September 2018.

Trial registration: ISRCTN registry, ISRCTN56164274 . Registered on 8 April 2014.

Keywords: Lower urinary tract symptoms; Non-inferiority trial; Randomised controlled trial; Statistical analysis plan; Urodynamics.

Conflict of interest statement

Ethics approval and consent to participate

The UPSTREAM trial will obtain informed consent from all participants in the study. The Chief Investigator (CI) obtained approval from the South Central – Oxford B Research Ethics Committee (14/SC/0237). The study must be submitted for site-specific assessment (SSA) at each participating National Health Service (NHS) Trust. The CI will require a copy of the Trust Research and Development (R&D) approval letter before accepting participants into the study from that Trust. The study will be conducted in accordance with the recommendations for physicians involved in research on human subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions. All 26 centres in UPSTREAM are approved by a centralised ethics committee (REC reference: 14/SC/0237). Full details of all participating hospitals and supporting NHS Trusts that provided local R&D approval can be found in the Additional file of the protocol paper [1].

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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