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Comments on ‘standard and reference-based conditional mean imputation’: Regulators and trial statisticians be aware!

Cro S, Morris TP, Roger JH, Carpenter JR

This paper describes how reference-based conditional mean imputation, with variance estimation justified solely by its frequentist performance, has the surprising and undesirable property that the estimated variance becomes smaller the greater the number of missing observations; as explained under jump-to-reference it effectively forces the true treatment effect to be exactly zero for patients with missing data.

Pharmaceutical Statistics

Publication Date:

Apr 17, 2024

How inclusive were UK-based randomised controlled trials of COVID-19 vaccines? A systematic review investigating enrolment of Black adults and adult ethnic minorities

Hibba Herieka, Daphne Babalis, Evangelia Tzala, Shyam Budhathoki and Nicholas A. Johnson

This is a systematic review designed to establish if Black adults and adult ethnic minorities, defined as any group except White British, were represented in UK-based COVID-19 vaccination randomised controlled trials (RCTs) when compared to corresponding UK population proportions, based on 2011 census data.


Publication Date:

Apr 12, 2024

The ICH E9 estimands framework: a primer

Kahan B, Hindley J, Edwards M, Cro S, Morris T

This paper provides an overview of the estimands framework, as outlined in the addendum, with the aim of explaining why estimands are beneficial; clarifying the terminology being used; and providing practical guidance on using estimands to decide the appropriate study design, data collection, and estimation methods.


Publication Date:

Jan 23, 2024

We must let the research question drive study methods

Kahan B, Morris T, Cro S

This article described how estimands help researchers to pinpoint their exact research question.


Publication Date:

Jan 23, 2024

Adaptive designs in critical care trials: a simulation study

Li W, Cornelius V, Finfer S, Venkatesh B & Billot L.

Using two large critical care trials (ADRENAL and NICE-SUGAR), this paper assesses the performance of three frequentist and two Bayesian adaptive trial design approaches.

BMC Medical Research Methodology

Publication Date:

Oct 18, 2023

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Comment on Oberman & Vink: Should we fix or simulate the complete data in simulation studies evaluating missing data methods?

Morris T, White I, Cro S, Bartlett JW, Carpenter JR, My Pham T

For simulation studies that evaluate methods of handling missing data, the authors argue in this letter that generating partially observed data by fixing the complete data and repeatedly simulating the missingness indicators is a superficially attractive idea but only rarely appropriate to use.

Biometrical Journal

Publication Date:

Oct 12, 2023

Starting a conversation about estimands with public partners involved in clinical trials: a co-developed tool

Cro S, Kahan BC, Patel A, Henley A, C J, Hellyer P, Kumar M, Rahman Y, Goulão B

This paper presents a co-developed a tool for researchers and public partners to use to facilitate the involvement of public partners in estimand discussions. And public partner views on being invovled in estimand discussions in a trial design context.


Publication Date:

Jul 6, 2023

Handling intercurrent events and missing data in non-inferiority trials using the estimand framework: A tuberculosis case study

Rehal S, Cro S, Phillips PPJ, Fielding K, Carpenter JR.

Using a tuberculosis clinical trial as a case study, this paper proposes a primary estimand, and an additional estimand suitable for non-inferiority studies.

Clinical Trials

Publication Date:

Jun 5, 2023

Fluid Optimisation in Emergency Laparotomy (FLO-ELA) Trial: study protocol for a multi-centre randomised trial of cardiac output-guided fluid therapy compared to usual care in patients undergoing major emergency gastrointestinal surgery,

Edwards MR, Forbes G, Walker N, Morton DG, Mythen MG, Murray D, Anderson I, Mihaylova B, Thomson A, Taylor M, Hollyman M, Phillips R, Young K, Kahan BC, Pearse RM, Grocott MPW for the FLO-ELA investigators

The FLO-ELA trial is a multi-centre, parallel-group, open, randomised controlled trial. 3138 patients aged 50 and over undergoing major emergency gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intra-venous fluid, or usual care without cardiac output monitoring. In this paper, authors demonstrate application of the estimand framework to clearly define the treatment effect estimate for the primary outcome.


Publication Date:

May 6, 2023

CONSORT Harms 2022 statement, explanation, and elaboration: updated guideline for the reporting of harms in randomized trials

Junqueira DR, Zorzela L, Golder S, Loke Y, Gagnier JJ, Julious SA, Li T, Mayo-Wilson E, Pham B, Phillips R, Santaguida P, Scherer RW, Gøtzsche PC, Moher D, Ioannidis JPA, Vohra S

In this article, we describe CONSORT Harms 2022 and how it was integrated into the main CONSORT checklist, and elaborate on each item relevant to complete reporting of harms in randomised controlled trials. Until future work from the CONSORT group produces an updated checklist, authors, journal reviewers, and editors of randomised controlled trials should use the integrated checklist presented in this paper.


Publication Date:

Apr 24, 2023

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