Edinburgh Clinical Trials
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Clinical Trials Methodology

The ECTU medical statistics, trial management, health economics and IT specialist teams also engage in clinical trials methodology research which aims to improve the quality and efficiency of trial design, analysis, conduct and reporting.

Activities in these four areas of trials methodology include:

Trial design
  • Supporting the use of efficient model-based designs (e.g. continual reassessment method) for early phase trials, instead of traditional algorithm-based “A+B” designs

Love SB, Brown S, Weir C, Harbron C, Yap C, Gaschler-markefski B, Matcham J, Caffrey L, Mckevitt C, Clive S, Craddock C, Spicer J, Cornelius V. (2017) Embracing model-based designs for dose-finding trials. British Journal of Cancer 117:332-339. doi:10.1038/bjc.2017.186  

  • Review and development of statistical methods for the evaluation of potential surrogate outcome measures in clinical trials

Ensor H, Lee RJ, Sudlow C, Weir CJ. (2015) Statistical approaches for evaluating surrogate outcomes in clinical trials: a systematic review. Journal of Biopharmaceutical Statistics, published online 21 September 2015. DOI: 10.1080/10543406.2015.1094811

Ensor H, Weir C. (2017) Two categorical endpoints.  In: Applied surrogate endpoint evaluation methods with SAS and R. Alonso, A. (ed.). Boca Raton: Chapman and Hall/CRC, pp. 145-155.

  • Highlighting advantages and practical implementation of efficient trials with an adaptive design

Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, Holmes J, Mander AP, Odondi L, Sydes MR, Villar SS, Wason JMS, Weir CJ, Wheeler GM, Yap V, Jaki T. (2018) Adaptive designs in clinical trials: why use them, and how to run and report them. BMC Medicine 16:29. doi:10.1186/s12916-018-1017-7

Holm Hansen C, Warner P, Parker RA, Walker BR, Critchley HOD, Weir CJ. (2017)  Development of a Bayesian response-adaptive trial design for the Dexamethasone For Excessive Menstruation (DexFEM) study. Statistical Methods in Medical Research, 26:2681–2699. DOI: 10.1177/0962280215606155 Weir CJ. (2015) Adaptive clinical trials and their potential to improve drug development efficiency. Clinical Investigation, 5:359-361. DOI: 10.4155/cli.14.134

 

Trial conduct
  • ECTU is registered with Trial FORGE (www.trialforge.org), a collaboration undertaking a series of “Studies Within a Trial” (SWATs) to evaluate important aspects of trial conduct such as methods for recruiting and retaining trial participants.  SWAT activity is embedded within ongoing clinical trials and at ECTU is led by the trial management team.  
  • One example of a SWAT was PRIME, which evaluated a complex intervention: the combination of support from a recruitment coordinator with use of bespoke reports based on national audit data to provide investigators with lists of potentially eligible patients for the RESTART trial.  
Maxwell AE, Parker R, Drever J, Rudd A, Dennis M, Weir C, Salman R. (2017) Promoting Recruitment using Information Management Efficiently (PRIME): a stepped wedge cluster randomised trial of a complex recruitment intervention embedded within the RESTART or Stop Antithrombotics Randomised Trial (RESTART). Trials 18:623. doi:10.1186/s13063-017-2355-z  
  • Developing guidance for the anonymising and sharing of individual patient data following the completion of a clinical trial.
Keerie C, Tuck C, Milne G, Eldridge S, Wright N, Lewis SC. (2018) Data sharing in clinical trials - practical guidance on anonymising trial datasets. Trials 19:25. doi:10.1186/s13063-017-2382-9
  • Ongoing work includes the development of Good Clinical Practice training, tailored to specific topics relevant to clinical trials statisticians

 

Trial analysis
  • Presenting guidelines for the content of clinical trial Statistical Analysis Plans
Gamble C, Krishan A, Stocken D, Lewis S, Juszczack E, Doré C, Williamson PR, Altman DG, Montgomery A, Lim P, Berlin J, Senn S, Day S, Shanahan D, Barbachano Y, Loder E. (2017) Guidelines for the content of Statistical Analysis Plans in clinical trials. JAMA 318(23):2337-43. doi:10.1001/jama.2017.18556
  • Review of statistical methods for recovering mean or standard deviation values not reported in clinical trial publications, so that those studies may still be included in meta-analysis
Weir CJ, Butcher I, Assi V, Lewis SC, Murray GD, Langhorne P, Brady MC. (2018)  Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review. BMC Med Res Methodol. 18(1):25. doi: 10.1186/s12874-018-0483-0.

 

Trial reporting
  • Investigation of how the function of Trial Steering Committees in clinical trials is reported, and recommendations regarding standards of reporting of Trials Steering Committee activity
Conroy EJ, Arch B, Harman NL, Lane, JA, Lewis SC, Norrie J, Sydes MR, Gamble C. (2017) A cohort examination to establish reporting of the Remit and Function of Trial Steering Committees in Randomised Controlled Trials. Trials 18:590. doi: 10.1186/s13063-017-2300-1  
  • Collaborating on development of an extension to the CONSORT reporting guidance for clinical trials which have an adaptive design
Dimairo M, Todd S, Julious S, Jaki T, Wason J, Hind D, Mander A, Weir C, Koenig F, Altman D, Hamasaki T, Proschan M, Scott J, Walton M, Ando Y, Biggs K, Pallmann P & Coates E (2017) Journeying through the development of an adaptive designs reporting guidance: findings from Delphi process. CEN ISBS Vienna 2017 (pp 94-94), 28 August 2017 - 1 September 2017.