Complex designs in randomised clinical trials - a case study in dentistry

Complex designs in randomised clinical trials - a case study in dentistry

PhD Project - Dr Beatriz Goulão

Oral health research is often a source of challenging data: statistical errors in the design, analysis and conclusions of dental research are frequently reported; when clinical outcomes are collected, they have an inherently hierarchical structure (e.g. teeth nested within people who are often nested within dental practices) with often non-normal distributions that can be challenging to analyse and present; outcome assessment becomes a challenge due to measurement errors and reliability of the data collected.

IQuaD is a randomised controlled trial (RCT) in dentistry using a complex design and is the motivating example for this PhD. IQuaD uses a split-plot design with cluster-level (68 dental practices) and individual-level (1,877 dental patients) randomisation that presents challenges for sample size calculation, analysis and reporting. IQuaD’s primary outcome is bleeding on probing, a measure of gingivitis collected through clinical assessment.

The PhD will address challenges in split-plot designs and the difficulty and costs of measuring clinical gingival bleeding in a large scale, multicentre pragmatic RCT by investigating the methodological implications for different ways of clinically measuring gingival bleeding and by assessing the diagnostic performance of several new self-reported measures.

The thesis will be focused on the following objectives:

  • Conduct a systematic review to identify split-plot designs used in healthcare research and describe their methodology and develop guidance on its report
  • Develop simulation methods to calculate a sample size in a split-plot design under a variety of assumptions and provide guidance on how to do it
  • Assess the diagnostic performance of a set of new self-reported bleeding questions compared to clinical bleeding on probing and update a systematic review about the diagnostic performance of other self-reported bleeding measures
  • Assess the statistical implications of collecting repeated clinical bleeding measures in the IQuaD RCT and inform future trials based on this

Supervision: Professor Craig Ramsay and Professor Graeme MacLennan





Papers Published

Goulão, B., MacLennan, G. & Ramsay, C. 'The split-plot design was useful for evaluating complex, multi-level interventions but there is need for improvement in its design and report'. Journal of Clinical Epidemiology. [ONLINE] DOI: 10.1016/J.JCLINEPI.2017.10.019

Goulão, B. (2020) ‘Statistical and methodological aspects of complex randomised controlled trials in oral health', PhD Thesis, HSRU, University of Aberdeen.

Published Abstracts

Goulão, B. MacLenann, G. Ramsay, C. (2017) Split-plot designs: sample size considerations. Trials Vol 18, Suppl 1.  

Goulão, B. MacLennan, G. Ramsay, C. (2016) Split-plot designs in healthcare: an overview. Young researchers using statistics Symposium 2016 Programme.


Implementation research design: an introduction to the split-plot randomised controlled trial. 1st UK Implementation Science Conference. 19th July 2018, London.

Split-plot designs: sample size considerations. International Society of Clinical Biostatistics Conference. Vigo, 9th – 13th July 2017.

Split-plot designs: sample size considerations. Society of Clinical Trials / International Conference of Trial Methodology. Liverpool, 7-10th May 2017.

Split-plot designs in healthcare: an overview, International Conference of Clinical Biostatistics, Birmingham 22nd – 25th Sept 2016

Strengths and limitations of split-plot designs: an application in oral health research, 7th International Conference in Methodological Issues in Oral Health Research, Bergen 11-13 May 2016


Santander Mobility awards to travel and collaborate with a research team at Munster University, 2017.