Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Nov 21;217(10):526-531.
doi: 10.5694/mja2.51715. Epub 2022 Sep 11.

Changes to design and analysis elements of research plans during randomised controlled trials in Australia

Affiliations

Changes to design and analysis elements of research plans during randomised controlled trials in Australia

Xanthi Coskinas et al. Med J Aust. .

Abstract

Objectives: To investigate the frequency and legitimacy of substantive changes to the research plans of published randomised controlled trials (RCTs) undertaken in Australia.

Design: Comparison of methodology and analysis plans for RCTs specified in protocol documents (full protocols, published protocol articles, statistical analysis plans, Australian New Zealand Clinical Trials Registry [ANZCTR] registration entries) and described in publications of primary results.

Setting, participants: 181 RCTs registered with the ANZCTR, 1 September 2007 - 31 December 2013, for which primary results had been published.

Main outcome measure: Changes made to research plan, both overall and by specific item (primary outcome, analysis set, eligibility criteria, sample size, primary analysis method, and treatment arms included in the primary comparison in multi-arm trials); trial characteristics associated with changes.

Results: Protocol documents were available for 124 of 181 eligible RCTs (69%; 46 publicly available, 78 provided by trial groups on request). Full audit of RCTs with protocols found clear or probable changes in 111 trials (90%), for 101 of which (91%) it was unclear whether changes had been made blinded to treatment outcomes. After seeking clarification from investigators, changes to 78 trials were confirmed (63%), for 61 of which (78%) changes were made blinded to treatment outcomes. Any change was less likely for trials with publicly available protocols than for trials for which we needed to request protocols (odds ratio, 0.22; 95% CI, 0.06-0.77). Limited reviews of trials without protocols identified that changes had been made to 42 of 57 trials (74%).

Conclusion: Changes to RCT study plans in Australia are both frequent and usually made appropriately blinded to treatment outcomes. However, the documentation of changes made to RCT protocols should be formalised to improve transparency.

Keywords: Randomized controlled trial as topic; Registries.

PubMed Disclaimer

Comment in

References

    1. National Health and Medical Research Council ; Australian Research Council; Universities Australia. National statement on ethical conduct in human research 2007 (updated 2018). July 2018. https://www.nhmrc.gov.au/about‐us/publications/national‐statement‐ethica... (viewed Dec 2021).
    1. Chan AW, Tetzlaff JM, Gøtzsche PC, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013; 346: e7586. - PMC - PubMed
    1. International Committee of Medical Journal Editors . Recommendations for the conduct, reporting, editing, and publication of scholarly work in medical journals. Updated May 2022. https://www.icmje.org/icmje‐recommendations.pdf (viewed July 2022).
    1. Coskinas X, Simes J, Schou M, Martin AJ. Changes to aspects of ongoing randomised controlled trials with fixed designs. Trials 2020; 21: 457. - PMC - PubMed
    1. Coskinas X, Schou IM, Simes J, Martin A. Reacting to prognostic covariate imbalance in randomised controlled trials. Contemp Clin Trials 2021; 110: 106544. - PubMed