Skip to main content
Top
Published in: Trials 1/2017

Open Access 01-12-2017 | Research

The INVEST project: investigating the use of evidence synthesis in the design and analysis of clinical trials

Authors: Gemma L. Clayton, Isabelle L. Smith, Julian P. T. Higgins, Borislava Mihaylova, Benjamin Thorpe, Robert Cicero, Kusal Lokuge, Julia R. Forman, Jayne F. Tierney, Ian R. White, Linda D. Sharples, Hayley E. Jones

Published in: Trials | Issue 1/2017

Login to get access

Abstract

Background

When designing and analysing clinical trials, using previous relevant information, perhaps in the form of evidence syntheses, can reduce research waste. We conducted the INVEST (INVestigating the use of Evidence Synthesis in the design and analysis of clinical Trials) survey to summarise the current use of evidence synthesis in trial design and analysis, to capture opinions of trialists and methodologists on such use, and to understand any barriers.

Methods

Our sampling frame was all delegates attending the International Clinical Trials Methodology Conference in November 2015. Respondents were asked to indicate (1) their views on the use of evidence synthesis in trial design and analysis, (2) their own use during the past 10 years and (3) the three greatest barriers to use in practice.

Results

Of approximately 638 attendees of the conference, 106 (17%) completed the survey, half of whom were statisticians. Support was generally high for using a description of previous evidence, a systematic review or a meta-analysis in trial design. Generally, respondents did not seem to be using evidence syntheses as often as they felt they should. For example, only 50% (42/84 relevant respondents) had used a meta-analysis to inform whether a trial is needed compared with 74% (62/84) indicating that this is desirable. Only 6% (5/81 relevant respondents) had used a value of information analysis to inform sample size calculations versus 22% (18/81) indicating support for this. Surprisingly large numbers of participants indicated support for, and previous use of, evidence syntheses in trial analysis. For example, 79% (79/100) of respondents indicated that external information about the treatment effect should be used to inform aspects of the analysis. The greatest perceived barrier to using evidence synthesis methods in trial design or analysis was time constraints, followed by a belief that the new trial was the first in the area.

Conclusions

Evidence syntheses can be resource-intensive, but their use in informing the design, conduct and analysis of clinical trials is widely considered desirable. We advocate additional research, training and investment in resources dedicated to ways in which evidence syntheses can be undertaken more efficiently, offering the potential for cost savings in the long term.
Appendix
Available only for authorised users
Literature
2.
go back to reference Cooper NJ, Jones DR, Sutton AJ. The use of systematic reviews when designing studies. Clin Trials. 2005;2:260–4.CrossRefPubMed Cooper NJ, Jones DR, Sutton AJ. The use of systematic reviews when designing studies. Clin Trials. 2005;2:260–4.CrossRefPubMed
4.
go back to reference Jones AP, Conroy E, Williamson PR, Clarke M, Gamble C. The use of systematic reviews in the planning, design and conduct of randomised trials: a retrospective cohort of NIHR HTA funded trials. BMC Med Res Methodol. 2013;13:50.CrossRefPubMedPubMedCentral Jones AP, Conroy E, Williamson PR, Clarke M, Gamble C. The use of systematic reviews in the planning, design and conduct of randomised trials: a retrospective cohort of NIHR HTA funded trials. BMC Med Res Methodol. 2013;13:50.CrossRefPubMedPubMedCentral
5.
go back to reference DerSimonian R. Meta-analysis in the design and monitoring of clinical trials. Stat Med. 1996;15:1237–48.CrossRefPubMed DerSimonian R. Meta-analysis in the design and monitoring of clinical trials. Stat Med. 1996;15:1237–48.CrossRefPubMed
6.
go back to reference Clarke M. Doing new research? Don’t forget the old—Nobody should do a trial without reviewing what is known. PLoS Med. 2004;1:100–2.CrossRef Clarke M. Doing new research? Don’t forget the old—Nobody should do a trial without reviewing what is known. PLoS Med. 2004;1:100–2.CrossRef
7.
go back to reference Bhurke S, Cook A, Tallant A, Young A, Williams E, Raftery J. Using systematic reviews to inform NIHR HTA trial planning and design: a retrospective cohort. BMC Med Res Methodol. 2015;15:108.CrossRefPubMedPubMedCentral Bhurke S, Cook A, Tallant A, Young A, Williams E, Raftery J. Using systematic reviews to inform NIHR HTA trial planning and design: a retrospective cohort. BMC Med Res Methodol. 2015;15:108.CrossRefPubMedPubMedCentral
8.
go back to reference Sutton A, Cooper N, Abrams K. Evidence based sample size calculations for future trials based on results of current meta-analyses. Control Clin Trials. 2003;24:88S–S. Sutton A, Cooper N, Abrams K. Evidence based sample size calculations for future trials based on results of current meta-analyses. Control Clin Trials. 2003;24:88S–S.
9.
go back to reference Maxwell SE, Kelley K, Rausch JR. Sample size planning for statistical power and accuracy in parameter estimation. Annu Rev Psychol. 2008;59:537–63.CrossRefPubMed Maxwell SE, Kelley K, Rausch JR. Sample size planning for statistical power and accuracy in parameter estimation. Annu Rev Psychol. 2008;59:537–63.CrossRefPubMed
10.
go back to reference Turner RM, Thompson SG, Spiegelhalter DI. Prior distributions for the intracluster correlation coefficient, based on multiple previous estimates, and their application in cluster randomized trials. Clin Trials. 2005;2:108–18.CrossRefPubMed Turner RM, Thompson SG, Spiegelhalter DI. Prior distributions for the intracluster correlation coefficient, based on multiple previous estimates, and their application in cluster randomized trials. Clin Trials. 2005;2:108–18.CrossRefPubMed
11.
go back to reference Turner RA, Omar RZ, Thompson SG. Constructing intervals for the intracluster correlation coefficient using Bayesian modelling, and application in cluster randomized trials. Stat Med. 2006;25:1443–56.CrossRefPubMed Turner RA, Omar RZ, Thompson SG. Constructing intervals for the intracluster correlation coefficient using Bayesian modelling, and application in cluster randomized trials. Stat Med. 2006;25:1443–56.CrossRefPubMed
12.
go back to reference Clarke M, Hopewell S, Chalmers I. Reports of clinical trials should begin and end with up-to-date systematic reviews of other relevant evidence: a status report. J R Soc Med. 2007;100:187–90.CrossRefPubMedPubMedCentral Clarke M, Hopewell S, Chalmers I. Reports of clinical trials should begin and end with up-to-date systematic reviews of other relevant evidence: a status report. J R Soc Med. 2007;100:187–90.CrossRefPubMedPubMedCentral
13.
go back to reference Sutton AJ, Donegan S, Takwoingi Y, Garner P, Gamble C, Donald A. An encouraging assessment of methods to inform priorities for updating systematic reviews. J Clin Epidemiol. 2009;62:241–51.CrossRefPubMed Sutton AJ, Donegan S, Takwoingi Y, Garner P, Gamble C, Donald A. An encouraging assessment of methods to inform priorities for updating systematic reviews. J Clin Epidemiol. 2009;62:241–51.CrossRefPubMed
14.
go back to reference Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF, Grp Q. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Lancet. 1999;354:1896–900.CrossRefPubMed Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF, Grp Q. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Lancet. 1999;354:1896–900.CrossRefPubMed
15.
go back to reference Hrobjartsson A, Thomsen ASS, Emanuelsson F, Tendal B, Hilden J, Boutron I, Ravaud P, Brorson S. Observer bias in randomised clinical trials with binary outcomes: systematic review of trials with both blinded and non-blinded outcome assessors. BMJ. 2012;344:e1119.CrossRefPubMed Hrobjartsson A, Thomsen ASS, Emanuelsson F, Tendal B, Hilden J, Boutron I, Ravaud P, Brorson S. Observer bias in randomised clinical trials with binary outcomes: systematic review of trials with both blinded and non-blinded outcome assessors. BMJ. 2012;344:e1119.CrossRefPubMed
16.
go back to reference Welton NJ, Ades AE, Carlin JB, Altman DG, Sterne JAC. Models for potentially biased evidence in meta-analysis using empirically based priors. J R Stat Soc Ser A Stat Soc. 2009;172:119–36.CrossRef Welton NJ, Ades AE, Carlin JB, Altman DG, Sterne JAC. Models for potentially biased evidence in meta-analysis using empirically based priors. J R Stat Soc Ser A Stat Soc. 2009;172:119–36.CrossRef
17.
go back to reference Tierney JF, Pignon JP, Gueffyier F, Clarke M, Askie L, Vale CL, Burdett S, Cochrane IPD Meta-Analysis Methods Group. How individual participant data meta-analyses have influenced trial design, conduct, and analysis. J Clin Epidemiol. 2015;68:1325–35. Tierney JF, Pignon JP, Gueffyier F, Clarke M, Askie L, Vale CL, Burdett S, Cochrane IPD Meta-Analysis Methods Group. How individual participant data meta-analyses have influenced trial design, conduct, and analysis. J Clin Epidemiol. 2015;68:1325–35.
18.
go back to reference Welton NJ, Ades AE, Caldwell DM, Peters TJ. Research prioritization based on expected value of partial perfect information: a case-study on interventions to increase uptake of breast cancer screening. J R Stat Soc Ser A Stat Soc. 2008;171:807–34.CrossRef Welton NJ, Ades AE, Caldwell DM, Peters TJ. Research prioritization based on expected value of partial perfect information: a case-study on interventions to increase uptake of breast cancer screening. J R Stat Soc Ser A Stat Soc. 2008;171:807–34.CrossRef
19.
go back to reference Pope C, Mays N. Reaching the parts other methods cannot reach—an introduction to qualitative methods in health and health-services research. Br Med J. 1995;311:42–5.CrossRef Pope C, Mays N. Reaching the parts other methods cannot reach—an introduction to qualitative methods in health and health-services research. Br Med J. 1995;311:42–5.CrossRef
20.
go back to reference Nasser M, Clarke M, Chalmers I, Brurberg KG, Nykvist H, Lund H, Glasziou P. What are funders doing to minimise waste in research? Lancet (London, England). 2017;389:1006–7.CrossRef Nasser M, Clarke M, Chalmers I, Brurberg KG, Nykvist H, Lund H, Glasziou P. What are funders doing to minimise waste in research? Lancet (London, England). 2017;389:1006–7.CrossRef
21.
go back to reference Feeley N, Cossette S, Cote J, Heon M, Stremler R, Martorella G, Purden M. The importance of piloting an RCT intervention. Can J Nurs Res. 2009;41:85–99.PubMed Feeley N, Cossette S, Cote J, Heon M, Stremler R, Martorella G, Purden M. The importance of piloting an RCT intervention. Can J Nurs Res. 2009;41:85–99.PubMed
22.
go back to reference Leon AC, Davis LL, Kraemer HC. The role and interpretation of pilot studies in clinical research. J Psychiatr Res. 2011;45:626–9.CrossRefPubMed Leon AC, Davis LL, Kraemer HC. The role and interpretation of pilot studies in clinical research. J Psychiatr Res. 2011;45:626–9.CrossRefPubMed
24.
go back to reference Ganann R, Ciliska D, Thomas H. Expediting systematic reviews: methods and implications of rapid reviews. Implement Sci. 2010;5:10–9.CrossRef Ganann R, Ciliska D, Thomas H. Expediting systematic reviews: methods and implications of rapid reviews. Implement Sci. 2010;5:10–9.CrossRef
25.
go back to reference Khangura S, Polisena J, Clifford TJ, Farrah K, Kamel C. Rapid review: an emerging approach to evidence synthesis in health technology assessment. Int J Technol Assess Health Care. 2014;30:20–7.CrossRefPubMed Khangura S, Polisena J, Clifford TJ, Farrah K, Kamel C. Rapid review: an emerging approach to evidence synthesis in health technology assessment. Int J Technol Assess Health Care. 2014;30:20–7.CrossRefPubMed
26.
go back to reference Bindels J, Ramaekers B, Ramos IC, Mohseninejad L, Knies S, Grutters J, Postma M, Al M, Feenstra T, Joore M. Use of value of information in healthcare decision making: exploring multiple perspectives. Pharmacoeconomics. 2016;34:315–22.CrossRefPubMed Bindels J, Ramaekers B, Ramos IC, Mohseninejad L, Knies S, Grutters J, Postma M, Al M, Feenstra T, Joore M. Use of value of information in healthcare decision making: exploring multiple perspectives. Pharmacoeconomics. 2016;34:315–22.CrossRefPubMed
27.
go back to reference Parmar MKB, Carpenter J, Sydes MR. More multiarm randomised trials of superiority are needed. Lancet. 2014;384:283–4.CrossRefPubMed Parmar MKB, Carpenter J, Sydes MR. More multiarm randomised trials of superiority are needed. Lancet. 2014;384:283–4.CrossRefPubMed
28.
go back to reference Jansen JP, Fleurence R, Devine B, Itzler R, Barrett A, Hawkins N, Lee K, Boersma C, Annemans L, Cappelleri JC. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: Part 1. Value Health. 2011;14:417–28.CrossRefPubMed Jansen JP, Fleurence R, Devine B, Itzler R, Barrett A, Hawkins N, Lee K, Boersma C, Annemans L, Cappelleri JC. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: Part 1. Value Health. 2011;14:417–28.CrossRefPubMed
29.
go back to reference Ramsey SD, Willke RJ, Glick H, Reed SD, Augustovski F, Jonsson B, Briggs A, Sullivan SA. Cost-effectiveness analysis alongside clinical trials II—An ISPOR Good Research Practices Task Force Report. Value Health. 2015;18:161–72.CrossRefPubMed Ramsey SD, Willke RJ, Glick H, Reed SD, Augustovski F, Jonsson B, Briggs A, Sullivan SA. Cost-effectiveness analysis alongside clinical trials II—An ISPOR Good Research Practices Task Force Report. Value Health. 2015;18:161–72.CrossRefPubMed
30.
go back to reference Claxton KP, Sculpher MJ. Using value of information analysis to prioritise health research—Some lessons from recent UK experience. Pharmacoeconomics. 2006;24:1055–68.CrossRefPubMed Claxton KP, Sculpher MJ. Using value of information analysis to prioritise health research—Some lessons from recent UK experience. Pharmacoeconomics. 2006;24:1055–68.CrossRefPubMed
31.
go back to reference Chalmers I. Randomized controlled trials of aprotinin in cardiac surgery: could clinical equipoise have stopped the bleeding? Comment Clin Trials. 2005;2:229–31. Chalmers I. Randomized controlled trials of aprotinin in cardiac surgery: could clinical equipoise have stopped the bleeding? Comment Clin Trials. 2005;2:229–31.
32.
go back to reference Ferreira ML, Herbert RD, Crowther MJ, Verhagen A, Sutton AJ. When is a further clinical trial justified? BMJ. 2012;345:e5913. Ferreira ML, Herbert RD, Crowther MJ, Verhagen A, Sutton AJ. When is a further clinical trial justified? BMJ. 2012;345:e5913.
33.
go back to reference Salanti G, Higgins JPT, Ades AE, Ioannidis JPA. Evaluation of networks of randomized trials. Stat Methods Med Res. 2008;17:279–301.CrossRefPubMed Salanti G, Higgins JPT, Ades AE, Ioannidis JPA. Evaluation of networks of randomized trials. Stat Methods Med Res. 2008;17:279–301.CrossRefPubMed
34.
go back to reference Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R. Analyses of cancer data from three Ezetimibe trials. N Engl J Med. 2008;359:1357–66.CrossRefPubMed Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R. Analyses of cancer data from three Ezetimibe trials. N Engl J Med. 2008;359:1357–66.CrossRefPubMed
35.
go back to reference Savovic J, Jones HE, Altman DG, Harris RJ, Juni P, Pildal J, Als-Nielsen B, Balk EM, Gluud C, Gluud LL, Ioannidis JPA, Schulz KF, Beynon R, Welton NJ, Wood L, Moher D, Deeks JJ, Sterne JAC. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Ann Intern Med. 2012;157:429–U97.CrossRefPubMed Savovic J, Jones HE, Altman DG, Harris RJ, Juni P, Pildal J, Als-Nielsen B, Balk EM, Gluud C, Gluud LL, Ioannidis JPA, Schulz KF, Beynon R, Welton NJ, Wood L, Moher D, Deeks JJ, Sterne JAC. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Ann Intern Med. 2012;157:429–U97.CrossRefPubMed
36.
Metadata
Title
The INVEST project: investigating the use of evidence synthesis in the design and analysis of clinical trials
Authors
Gemma L. Clayton
Isabelle L. Smith
Julian P. T. Higgins
Borislava Mihaylova
Benjamin Thorpe
Robert Cicero
Kusal Lokuge
Julia R. Forman
Jayne F. Tierney
Ian R. White
Linda D. Sharples
Hayley E. Jones
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Trials / Issue 1/2017
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-017-1955-y

Other articles of this Issue 1/2017

Trials 1/2017 Go to the issue