Statistical methods for randomised surgical trials

Lead Research Organisation: University of Aberdeen
Department Name: School of Medical Sciences

Abstract

Randomised Controlled Trials (RCTs) have played a very important role in advancing health care by allowing accurate assessment of a new treatment by comparison with a standard treatment. The field of surgery has been slower to use RCTs than Medicine in general. There are number of features about surgery which make it more difficult to assess, and influence the planning stage of a trial, the day to day running, and also the analysis of the results. The surgeons undertaking the procedure may vary in both experience and inherent surgical ability. The availability of a surgical theatre and the surgical team are limited and therefore the surgery may be delayed. Surgery also differs is in the way that it is administered and a number of apparently valid variations of a particular procedure may be possible. Individually and collectively these issues have inhibited surgical RCTs. This work would look to address each of these issues from a statistical point of view and, by furthering our understanding, can facilitate the uptake and enhance the quality of RCTs in surgery. By doing so our knowledge of the best way to treat patients where surgery is an option will be enlarged.

Technical Summary

The randomised controlled trial (RCT) is now widely accepted as the gold-standard design for the evaluation of health care interventions. Whilst the RCT has been accepted into medical practice for many years, there is continuing resistance to its uptake in surgical practice. The design and conduct of randomised controlled trials in surgery is undoubtedly more complex than drug trials for a number of reasons.

A programme of work on statistical methods in surgical randomised controlled trials is proposed to address key issues related to the design, conduct and analysis of surgical trials. This work will be undertaken in collaboration with experts in the UK, Germany and Canada. The specific aims of this work are:

To develop and evaluate new statistical techniques for quantifying expertise in randomised surgical trials
A Bayesian hierarchical models will be developed to investigate the relationship between (surgical) simulator results and various proxy measures (such as operation time) for predicting performance in a randomised controlled trial. Training on a laparoscopic simulator will be undertaken by a sample of surgeons prior to participation in the UKUFF trial.

To create a database of intracluster correlation coefficients for surgical techniques to inform study designs
This database will include intracluster correlation coefficients (ICCs) for a variety of surgical procedures and would also allow investigation of the relationship between surgeon effects and centre effects by comparing ICCs of surgeons and centres.

To build a Bayesian predictive model of recruitment patterns to take into account waiting list effects
The recruitment details from a set of surgical trials will be used as training data for producing and refining the recruitment model. Issues particularly relevant to surgical trials such as delays due to limited availability of resources, a waiting list effect, will be incorporated.

To develop and evaluate the impact of prior distributions for the treatment effect dependent upon different stages of the learning curve
Methods to statistically adjust the surgical trial treatment effect for the learning curve have been previously developed will be extended to incorporate a prior distribution for the treatment effect to investigate the likely influence of learning on the treatment effect.

To test the usefulness of efficacy estimators in randomised surgical trials
The influence of incorporating efficacy estimates within trial cost-effectiveness analysis and decision analytic models will be investigated. The properties of the complier average causal effect approach to estimating efficacy will be empirically investigated using a number of surgical trials.

Publications

10 25 50
 
Description HTA Clinical Evaluation and Trials Board
Amount £1,503,000 (GBP)
Funding ID 08/24/02 
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 01/2010 
End 12/2014
 
Description HTA Clinical Evaluation and Trials Board
Amount £2,701,000 (GBP)
Funding ID 08/14/08 
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 01/2010 
End 12/2016
 
Description HTA Clinical Evaluation and Trials Board
Amount £373,000 (GBP)
Funding ID 09/22/111 
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 01/2011 
End 09/2012
 
Description MRC Methodology Fellowship
Amount £298,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2011 
End 08/2014
 
Description MRC hubs for trial methodology research network grants
Amount £17,875 (GBP)
Organisation Medical Research Council (MRC) 
Department Network of Hubs for Trials Methodology Research (HTMR)
Sector Academic/University
Country United Kingdom
Start 04/2014 
End 06/2018
 
Description Methodology panel grant
Amount £149,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2010 
End 03/2012
 
Title Surgical trials ICC database 
Description Data from 10 surgical (randomised) trials was collated and intra-cluster correlation (ICC) coefficients were calculated for a range of outcomes which will inform future surgical trial design. The database is freely available online: http://www.abdn.ac.uk/hsru/documents/Surgical_trial_ICC_database_-_website_version_Nov_2011.xls 
Type Of Material Improvements to research infrastructure 
Year Produced 2012 
Provided To Others? Yes  
Impact None to date. 
URL http://www.abdn.ac.uk/hsru/documents/Surgical_trial_ICC_database_-_website_version_Nov_2011.xls
 
Description Balliol Collaboration 
Organisation Heidelberg University Hospital
Department Department of General, Visceral and Transplantation Surgery
Country Germany 
Sector Hospitals 
PI Contribution The fellowship holder was a member of collaboration and participated in the meetings, gave an oral presentation, was contributed to the outlining of the paper series and was a named co-author on one of the papers.
Collaborator Contribution A partner initiated the collaboration, organised the meeting and oversaw the production of the paper series. Members of partner organisations were part of the collaboration and contributed to the output of the collaboration and co-authors on one the three papers.
Impact This collaboration has led to the production of a three paper series on "Evaluating Surgery" which was published in the Lancet journal. The PMIDs are: 19782874, 19782875 and 19782876.
Start Year 2008
 
Description Balliol Collaboration 
Organisation McGill University
Department Department of Surgery
Country Canada 
Sector Academic/University 
PI Contribution The fellowship holder was a member of collaboration and participated in the meetings, gave an oral presentation, was contributed to the outlining of the paper series and was a named co-author on one of the papers.
Collaborator Contribution A partner initiated the collaboration, organised the meeting and oversaw the production of the paper series. Members of partner organisations were part of the collaboration and contributed to the output of the collaboration and co-authors on one the three papers.
Impact This collaboration has led to the production of a three paper series on "Evaluating Surgery" which was published in the Lancet journal. The PMIDs are: 19782874, 19782875 and 19782876.
Start Year 2008
 
Description Balliol Collaboration 
Organisation University of Bristol
Department School of Clinical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution The fellowship holder was a member of collaboration and participated in the meetings, gave an oral presentation, was contributed to the outlining of the paper series and was a named co-author on one of the papers.
Collaborator Contribution A partner initiated the collaboration, organised the meeting and oversaw the production of the paper series. Members of partner organisations were part of the collaboration and contributed to the output of the collaboration and co-authors on one the three papers.
Impact This collaboration has led to the production of a three paper series on "Evaluating Surgery" which was published in the Lancet journal. The PMIDs are: 19782874, 19782875 and 19782876.
Start Year 2008
 
Description Balliol Collaboration 
Organisation University of Oxford
Department Department of Statistics
Country United Kingdom 
Sector Academic/University 
PI Contribution The fellowship holder was a member of collaboration and participated in the meetings, gave an oral presentation, was contributed to the outlining of the paper series and was a named co-author on one of the papers.
Collaborator Contribution A partner initiated the collaboration, organised the meeting and oversaw the production of the paper series. Members of partner organisations were part of the collaboration and contributed to the output of the collaboration and co-authors on one the three papers.
Impact This collaboration has led to the production of a three paper series on "Evaluating Surgery" which was published in the Lancet journal. The PMIDs are: 19782874, 19782875 and 19782876.
Start Year 2008
 
Description Balliol Collaboration 
Organisation University of Zurich
Department Department of Surgery
Country Switzerland 
Sector Academic/University 
PI Contribution The fellowship holder was a member of collaboration and participated in the meetings, gave an oral presentation, was contributed to the outlining of the paper series and was a named co-author on one of the papers.
Collaborator Contribution A partner initiated the collaboration, organised the meeting and oversaw the production of the paper series. Members of partner organisations were part of the collaboration and contributed to the output of the collaboration and co-authors on one the three papers.
Impact This collaboration has led to the production of a three paper series on "Evaluating Surgery" which was published in the Lancet journal. The PMIDs are: 19782874, 19782875 and 19782876.
Start Year 2008
 
Description OHRICEP 
Organisation Ottawa Hospital Research Institute
Department Clinical Epidemiology Program
Country Canada 
Sector Academic/University 
PI Contribution This partnership was facilitated through a 12 months secondment period for training and developing research collaboration. Two research projects are ongoing in this collaboration. Funding for Canadian collaborators received for two different projects (total £73000).
Collaborator Contribution The partner institution hosted the fellowship holder for 12 months and provided access to senior researchers who provided mentorship and facilitated networking.
Impact This work has led to one publication to date: PubMed ID 19200379. Additionally the collaboration has also led to a successful funding application to the MRC UK (G0902147 - £149000)
Start Year 2008