A randomised placebo controlled trial of anakinra for treating pustular psoriasis: Statistical analysis plan for stage two of the APRICOT trial

Suzie Cro; Prakash Patel; Jonathan Barker; David A. Burden; Christopher E.M. Griffiths; Helen J. Lachmann; Nick J. Reynolds; Richard B. Warren; Francesca Capon; Catherine Smith; Victoria Cornelius

doi:10.1186/s13063-020-4103-z

A randomised placebo controlled trial of anakinra for treating pustular psoriasis: Statistical analysis plan for stage two of the APRICOT trial

Suzie Cro^*, Prakash Patel, Jonathan Barker, David A. Burden, Christopher E.M. Griffiths, Helen J. Lachmann, Nick J. Reynolds, Richard B. Warren, Francesca Capon, Catherine Smith, Victoria Cornelius

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

7 Citations (Scopus)

Abstract

Background: Current treatment options for Palmoplantar Pustulosis (PPP), a debilitating chronic skin disease which affects the hands and feet, are limited. The Anakinra for Pustular psoriasis: Response in a Controlled Trial (APRICOT) aims to determine the efficacy of anakinra in the treatment of PPP. This article describes the statistical analysis plan for the final analysis of this two-staged trial, which was determined prior to unblinding and database lock. This is an update to the published protocol and stage one analysis plan. Methods: APRICOT is a randomised, double-blind, placebo-controlled trial of anakinra versus placebo, with two stages and an adaptive element. Stage one compared treatment arms to ensure proof-of-concept and determined the primary outcome for stage two of the trial. The primary outcome was selected to be the change in Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. Secondary outcomes include other investigator-assessed efficacy measures of disease severity, participant-reported measures of efficacy and safety measures. This manuscript describes in detail the outcomes, sample size, general analysis principles, the pre-specified statistical analysis plan for each of the outcomes, the handling of missing outcome data and the planned sensitivity and supplementary analyses for the second stage of the APRICOT trial. Discussion: This statistical analysis plan was developed in compliance with international trial guidelines and is published to increase transparency of the trial analysis. The results of the trial analysis will indicate whether anakinra has a role in the treatment of PPP. Trial registration: ISCRTN, ISCRTN13127147. Registered on 1 August 2016. EudraCT Number 2015-003600-23. Registered on 1 April 2016.

Original language	English
Article number	158
Journal	Trials
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s13063-020-4103-z
Publication status	Published - 10 Feb 2020

Keywords

Adaptive trial
Anakinra
Palmoplantar pustulosis
Psoriasis
Randomised controlled trial
Statistical analysis plan

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10.1186/s13063-020-4103-z

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Cro, S., Patel, P., Barker, J., Burden, D. A., Griffiths, C. E. M., Lachmann, H. J., Reynolds, N. J., Warren, R. B., Capon, F., Smith, C., & Cornelius, V. (2020). A randomised placebo controlled trial of anakinra for treating pustular psoriasis: Statistical analysis plan for stage two of the APRICOT trial. Trials, 21(1), Article 158. https://doi.org/10.1186/s13063-020-4103-z

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title = "A randomised placebo controlled trial of anakinra for treating pustular psoriasis: Statistical analysis plan for stage two of the APRICOT trial",

abstract = "Background: Current treatment options for Palmoplantar Pustulosis (PPP), a debilitating chronic skin disease which affects the hands and feet, are limited. The Anakinra for Pustular psoriasis: Response in a Controlled Trial (APRICOT) aims to determine the efficacy of anakinra in the treatment of PPP. This article describes the statistical analysis plan for the final analysis of this two-staged trial, which was determined prior to unblinding and database lock. This is an update to the published protocol and stage one analysis plan. Methods: APRICOT is a randomised, double-blind, placebo-controlled trial of anakinra versus placebo, with two stages and an adaptive element. Stage one compared treatment arms to ensure proof-of-concept and determined the primary outcome for stage two of the trial. The primary outcome was selected to be the change in Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. Secondary outcomes include other investigator-assessed efficacy measures of disease severity, participant-reported measures of efficacy and safety measures. This manuscript describes in detail the outcomes, sample size, general analysis principles, the pre-specified statistical analysis plan for each of the outcomes, the handling of missing outcome data and the planned sensitivity and supplementary analyses for the second stage of the APRICOT trial. Discussion: This statistical analysis plan was developed in compliance with international trial guidelines and is published to increase transparency of the trial analysis. The results of the trial analysis will indicate whether anakinra has a role in the treatment of PPP. Trial registration: ISCRTN, ISCRTN13127147. Registered on 1 August 2016. EudraCT Number 2015-003600-23. Registered on 1 April 2016.",

keywords = "Adaptive trial, Anakinra, Palmoplantar pustulosis, Psoriasis, Randomised controlled trial, Statistical analysis plan",

author = "Suzie Cro and Prakash Patel and Jonathan Barker and Burden, {David A.} and Griffiths, {Christopher E.M.} and Lachmann, {Helen J.} and Reynolds, {Nick J.} and Warren, {Richard B.} and Francesca Capon and Catherine Smith and Victoria Cornelius",

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doi = "10.1186/s13063-020-4103-z",

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T1 - A randomised placebo controlled trial of anakinra for treating pustular psoriasis

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AU - Cro, Suzie

AU - Patel, Prakash

AU - Barker, Jonathan

AU - Burden, David A.

AU - Griffiths, Christopher E.M.

AU - Lachmann, Helen J.

AU - Reynolds, Nick J.

AU - Warren, Richard B.

AU - Capon, Francesca

AU - Smith, Catherine

AU - Cornelius, Victoria

PY - 2020/2/10

Y1 - 2020/2/10

N2 - Background: Current treatment options for Palmoplantar Pustulosis (PPP), a debilitating chronic skin disease which affects the hands and feet, are limited. The Anakinra for Pustular psoriasis: Response in a Controlled Trial (APRICOT) aims to determine the efficacy of anakinra in the treatment of PPP. This article describes the statistical analysis plan for the final analysis of this two-staged trial, which was determined prior to unblinding and database lock. This is an update to the published protocol and stage one analysis plan. Methods: APRICOT is a randomised, double-blind, placebo-controlled trial of anakinra versus placebo, with two stages and an adaptive element. Stage one compared treatment arms to ensure proof-of-concept and determined the primary outcome for stage two of the trial. The primary outcome was selected to be the change in Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. Secondary outcomes include other investigator-assessed efficacy measures of disease severity, participant-reported measures of efficacy and safety measures. This manuscript describes in detail the outcomes, sample size, general analysis principles, the pre-specified statistical analysis plan for each of the outcomes, the handling of missing outcome data and the planned sensitivity and supplementary analyses for the second stage of the APRICOT trial. Discussion: This statistical analysis plan was developed in compliance with international trial guidelines and is published to increase transparency of the trial analysis. The results of the trial analysis will indicate whether anakinra has a role in the treatment of PPP. Trial registration: ISCRTN, ISCRTN13127147. Registered on 1 August 2016. EudraCT Number 2015-003600-23. Registered on 1 April 2016.

AB - Background: Current treatment options for Palmoplantar Pustulosis (PPP), a debilitating chronic skin disease which affects the hands and feet, are limited. The Anakinra for Pustular psoriasis: Response in a Controlled Trial (APRICOT) aims to determine the efficacy of anakinra in the treatment of PPP. This article describes the statistical analysis plan for the final analysis of this two-staged trial, which was determined prior to unblinding and database lock. This is an update to the published protocol and stage one analysis plan. Methods: APRICOT is a randomised, double-blind, placebo-controlled trial of anakinra versus placebo, with two stages and an adaptive element. Stage one compared treatment arms to ensure proof-of-concept and determined the primary outcome for stage two of the trial. The primary outcome was selected to be the change in Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. Secondary outcomes include other investigator-assessed efficacy measures of disease severity, participant-reported measures of efficacy and safety measures. This manuscript describes in detail the outcomes, sample size, general analysis principles, the pre-specified statistical analysis plan for each of the outcomes, the handling of missing outcome data and the planned sensitivity and supplementary analyses for the second stage of the APRICOT trial. Discussion: This statistical analysis plan was developed in compliance with international trial guidelines and is published to increase transparency of the trial analysis. The results of the trial analysis will indicate whether anakinra has a role in the treatment of PPP. Trial registration: ISCRTN, ISCRTN13127147. Registered on 1 August 2016. EudraCT Number 2015-003600-23. Registered on 1 April 2016.

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KW - Randomised controlled trial

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DO - 10.1186/s13063-020-4103-z

M3 - Review article

C2 - 32041649

AN - SCOPUS:85079238660

SN - 1745-6215

VL - 21

JO - Trials

JF - Trials

IS - 1

M1 - 158

ER -

A randomised placebo controlled trial of anakinra for treating pustular psoriasis: Statistical analysis plan for stage two of the APRICOT trial

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