Hostname: page-component-8448b6f56d-mp689 Total loading time: 0 Render date: 2024-04-24T22:56:03.837Z Has data issue: false hasContentIssue false
  • English
  • Français

50 Tips for Clinical Trialists

Published online by Cambridge University Press:  05 December 2017

Lisa A. Harvey ,
Joanne V. Glinsky  and
Robert D. Herbert
Lisa A. Harvey*
Affiliation:
John Walsh Centre for Rehabilitation Research, Kolling Institute, University of Sydney, New South Wales, Australia
Joanne V. Glinsky
Affiliation:
John Walsh Centre for Rehabilitation Research, Kolling Institute, University of Sydney, New South Wales, Australia
Robert D. Herbert
Affiliation:
Neuroscience Research Australia (NeuRA), Sydney, New South Wales, Australia
*
Address for correspondence: Professor Lisa Harvey, John Walsh Centre for Rehabilitation Research, Kolling Institute, University of Sydney, Sydney Medical School/Northern, c/o Royal North Shore Hospital, Pacific Highway, St Leonards, New South Wales 2065, Australia. E-mail: l.harvey@usyd.edu.au
Get access

Abstract

This paper presents ‘Tips’ for researchers of brain impairment who are interested in conducting randomised controlled trials. The paper is intended for researchers who are planning to undertake their first trial, but may also be of interest to more experienced trialists or clinicians who want to further their understandings of clinical trials. The Tips include suggestions for how to design, conduct, analyse and report clinical trials.

Keywords

clinical trialsmethodology
Type
Articles
Information
Brain Impairment , Volume 19 , Special Issue 1: Quantitative Data Analysis; by Robyn Tate and Michael Perdices , March 2018 , pp. 59 - 69
Copyright
Copyright © Australasian Society for the Study of Brain Impairment 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abraha, I., Cherubini, A., Cozzolino, F., De Florio, R., Luchetta, M.L., Rimland, J.M., . . . Montedori, A. (2015). Deviation from intention to treat analysis in randomised trials and treatment effect estimates: Meta-epidemiological study. British Medical Journal, 350, h2445.CrossRefGoogle ScholarPubMed
Altman, D.G., & Gardner, M.J. (2000). Statistics with confidence: confidence intervals and statistical guidelines (2nd ed.). London: BMJ.Google Scholar
Altman, D.G., & Schulz, K.F. (2001). Statistics notes: Concealing treatment allocation in randomised trials. British Medical Journal, 323, 446–447.CrossRefGoogle ScholarPubMed
Andrade, C. (2015). The primary outcome measure and its importance in clinical trials. Journal of Clinical Psychiatry, 76, e1320–1323.CrossRefGoogle ScholarPubMed
An-Wen, C., Jennifer, M.T., Peter, C.G., Douglas, G.A., Howard, M., Jesse, A.B., . . . David, M. (2013). SPIRIT 2013 explanation and elaboration: Guidance for protocols of clinical trials. British Medical Journal, 346, e7586.Google Scholar
Arain, M., Campbell, M.J., Cooper, C.L., & Lancaster, G.A. (2010). What is a pilot or feasibility study? A review of current practice and editorial policy. BMC Medical Research Methodology, 10, 67.CrossRefGoogle ScholarPubMed
Barrett, B., Brown, D., Mundt, M., & Brown, R. (2005). Sufficiently important difference: Expanding the framework of clinical significance. Medical Decision Making, 25, 250–261.CrossRefGoogle ScholarPubMed
Bland, J.M. (2009). The tyranny of power: Is there a better way to calculate sample size?. British Medical Journal, 339, 1133–1135.CrossRefGoogle Scholar
Bland, J.M., & Altman, D.G. (2011). Comparisons against baseline within randomised groups are often used and can be highly misleading. Trials, 12, 264.CrossRefGoogle ScholarPubMed
Boutron, I., Altman, D.G., Hopewell, S., Vera-Badillo, F., Tannock, I., & Ravaud, P. (2014). Impact of spin in the abstracts of articles reporting results of randomized controlled trials in the field of cancer: The SPIIN randomized controlled trial. Journal of Clinical Oncology, 32, 4120–4126.CrossRefGoogle ScholarPubMed
Bragge, P., Synnot, A., Maas, A.I., Menon, D.K., Cooper, D.J., Rosenfeld, J.V., & Gruen, R.L. (2016). A state-of-the-science overview of randomized controlled trials evaluating acute management of moderate-to-severe traumatic brain injury. Journal of Neurotrauma, 33, 1461–1478.CrossRefGoogle ScholarPubMed
Burke, J.F., Sussman, J.B., Kent, D.M., & Hayward, R.A. (2015). Three simple rules to ensure reasonably credible subgroup analyses. British Medical Journal, 351.Google ScholarPubMed
Carpenter, L.M. (1993). Is the study worth doing?. The Lancet, 342, 221–223.CrossRefGoogle Scholar
Cook, J.A., Hislop, J., Altman, D.G., Fayers, P., Briggs, A.H., Ramsay, C.R., . . . Delta group, . (2015). Specifying the target difference in the primary outcome for a randomised controlled trial: Guidance for researchers. Trials, 16, 526.CrossRefGoogle ScholarPubMed
Cumming, G. (2012). Understanding the new statistics: Effect sizes, confidence intervals and meta analysis. London, UK: Routledge.Google Scholar
DAMOCLES Study Group. (2005). A proposed charter for clinical trial data monitoring committees: Helping them to do their job well. Lancet, 365, 711–722.CrossRefGoogle Scholar
Day, S.J., & Altman, D.G. (2000). Statistics notes: Blinding in clinical trials and other studies. British Medical Journal, 19, 504.CrossRefGoogle Scholar
De Vet, H.C., & Terwee, C.B. (2010). The minimal detectable change should not replace the minimal important difference. Journal of Clinical Epidemiology, 63, 804–805.CrossRefGoogle Scholar
Dwan, K., Gamble, C., Williamson, P.R., Kirkham, J.J., & Reporting Bias Group. (2013). Systematic review of the empirical evidence of study publication bias and outcome reporting bias – an updated review. PLoS One, 8, e66844.CrossRefGoogle ScholarPubMed
Eldridge, S.M., Chan, C.L., Campbell, M.J., Bond, C.M., Hopewell, S., Thabane, L., Lancaster, G.A., & Group, P.C. (2016). CONSORT 2010 statement: Extension to randomised pilot and feasibility trials. British Medical Journal, 355, i5239.CrossRefGoogle ScholarPubMed
Elkins, M. (2013). Concealed allocation in randomised trials. Journal of Physiotherapy, 59, 134–136.CrossRefGoogle ScholarPubMed
Ellenberg, S., Fleming, T., & DeMets, D. (2002). Data monitoring committees in clinical trials: A practical perspective. Chichester: J. Wiley. CrossRefGoogle Scholar
European Medicines Agency. (2002). ICH Topic E6 (R1): Guidelines for good clinical practice. London, UK.Google Scholar
Fergusson, D., Aaron, S.D., Guyatt, G., & Hebert, P. (2002). Post-randomisation exclusions: The intention to treat principle and excluding patients from analysis. British Medical Journal, 325, 652–654.CrossRefGoogle ScholarPubMed
Ferreira, M.L., Herbert, R.D., Crowther, M.J., Verhagen, A., & Sutton, A.J. (2012). When is a further clinical trial justified?. British Medical Journal, 345, e5913.CrossRefGoogle ScholarPubMed
Ferreira, M.L., Herbert, R.D., Ferreira, P.H., Latimer, J., Ostelo, R.W., Nascimento, D.P., & Smeets, R.J. (2012). A critical review of methods used to determine the smallest worthwhile effect of interventions for low back pain. Journal of Clinical Epidemiology, 65, 253–261.CrossRefGoogle ScholarPubMed
Friedman, L.M., Furberg, C.D., & DeMets, D.L. (1998). Fundamentals of clinical trials. New York: Springer-Verlag.CrossRefGoogle Scholar
Gardner, M.J., & Altman, D.G. (1986). Confidence intervals rather than P values: Estimation rather than hypothesis testing. British Medical Journal, 292, 746–750.CrossRefGoogle Scholar
Gluud, L. (2006). Bias in clinical intervention research. American Journal of Epidemiology, 163, 493–501.CrossRefGoogle ScholarPubMed
Godwin, M., Ruhland, L., Casson, I., MacDonald, S., Delva, D., Birtwhistle, R., Lam, M., & Seguin, R. (2003). Pragmatic controlled clinical trials in primary care: The struggle between external and internal validity. BMC Medical Research Methodology, 3, 1–7.CrossRefGoogle ScholarPubMed
Goffin, J. (2009). Introduction to clinical trials. In Gad, S. (Ed.), Clinical trials handbook (pp. 1–21). Hoboken, NY: Wiley.Google Scholar
Goodman, S. (1999). Toward evidence-based medical statistics. 1: The P value fallacy. Annals of Internal Medicine, 130, 995–1004.CrossRefGoogle ScholarPubMed
Greenland, S. (2011). Null misinterpretation in statistical testing and its impact on health risk assessment. Preventive Medicine, 53, 225–228.CrossRefGoogle ScholarPubMed
Guyatt, G. (2006). Preparing a research protocol to improve chances for success. Journal of Clinical Epidemiology, 59, 893–899.CrossRefGoogle ScholarPubMed
Harvey, L.A. (2015). Spin kills science. Spinal Cord, 53, 417.CrossRefGoogle ScholarPubMed
Hauck, W.W., Anderson, S., & Marcus, S.M. (1998). Should we adjust for covariates in nonlinear regression analyses of randomized trials?. Controlled Clinical Trials, 19, 249–256.CrossRefGoogle ScholarPubMed
Herbert, R. (2000). How to estimate treatment effect from reports of clinical trials. 1: Continuous outcomes. Australian Journal of Physiotherapy, 46, 229–235.CrossRefGoogle Scholar
Herbert, R. (2009). Explanatory and pragmatic clinical trials. In Gad, S.C. (Ed.), Clnical trials handbook. Hoboken, NY: John Wiley and Sons, Inc.Google Scholar
Hoenig, J.M., & Heisey, D.M. (2001). The abuse of power: The pervasive fallacy of power calculations for data analysis. American Statistician, 55, 19–24.CrossRefGoogle Scholar
Hoffer, M.E., Szczupak, M., & Balaban, C. (2016). Clinical trials in mild traumatic brain injury. Journal of Neuroscience Methods, 272, 77–81.CrossRefGoogle ScholarPubMed
Hollis, S., & Campbell, F. (1999). What is meant by intention to treat analysis? Survey of published randomised controlled trials. British Medical Journal, 319, 670–674.CrossRefGoogle ScholarPubMed
Irving, E., van den Bor, R., Welsing, P., Walsh, V., Alfonso-Cristancho, R., Harvey, C., . . . GetReal Work, P. (2017). Collecting and reporting safety data and monitoring trial conduct in pragmatic trials. Journal of Clinical Epidemiology. doi: 10.1016/j.jclinepi.2017.05.004.Google ScholarPubMed
Jones, A.H. (2003). Can authorship policies help prevent scientific misconduct? What role for scientific societies?. Science and Engineering Ethics, 9, 243–256.CrossRefGoogle ScholarPubMed
Julious, S.A., & Campbell, M.J. (2012). Tutorial in biostatistics: Sample sizes for parallel group clinical trials with binary data. Statistics in Medicine, 31, 2904–2936.CrossRefGoogle ScholarPubMed
Lachin, J.L. (2000). Statistical considerations in the intent-to-treat principle. Controlled Clinical Trials, 21, 167–189.CrossRefGoogle ScholarPubMed
Lai, R., Chu, R., Fraumeni, M., & Thabane, L. (2006). Quality of randomized controlled trials reporting in the primary treatment of brain tumors. Journal of Clinical Oncology, 24, 1136–1144.CrossRefGoogle ScholarPubMed
Leon, A.C., Davis, L.L., & Kraemer, H.C. (2011). The role and interpretation of pilot studies in clinical research. Journal of Psychiatric Research, 45, 626–629.CrossRefGoogle ScholarPubMed
Maas, A.I.R., Murray, G.D., Roozenbeek, B., Lingsma, H.F., Butcher, I., McHugh, G.S., . . . Steyerberg, E.W. (2013). Advancing care for traumatic brain injury: Findings from the IMPACT studies and perspectives on future research. The Lancet Neurology, 12, 1200–1210.CrossRefGoogle ScholarPubMed
Maher, C., Sherrington, C., Herbert, R., Moseley, A., & Elkins, M. (2003). Reliability of the PEDro scale for rating quality of randomized controlled trials. Physical Therapy, 83, 713–721.CrossRefGoogle ScholarPubMed
Matthews, J.N., & Altman, D.G. (1996). Statistics notes. Interaction 2: Compare effect sizes not P values. British Medical Journal, 313, 808.CrossRefGoogle Scholar
Moher, D., Hopewell, S., Schulz, K.F., Montori, V., Gøtzsche, P.C., Devereaux, P.J., . . . Altman, D.G. (2012). CONSORT 2010 explanation and elaboration: Updated guidelines for reporting parallel group randomised trials. International Journal of Surgery, 10, 28–55.CrossRefGoogle ScholarPubMed
Montori, V.M., Devereaux, P.J., Adhikari, N.K.J., Burns, K.E.A., Eggert, C.H., Briel, M., . . . Guyatt, G.H. (2005). Randomized trials stopped early for benefit: A systematic review. Journal of the American Medical Association, 294, 2203–2209.CrossRefGoogle ScholarPubMed
Montori, V.M., Jaeschke, R., Schünemann, H.J., Bhandari, M., Brozek, J.L., Devereaux, P.J., & Guyatt, G.H. (2004). Users' guide to detecting misleading claims in clinical research reports. British Medical Journal, 329, 1093–1096.CrossRefGoogle ScholarPubMed
Montori, V.M., Kleinbart, J., Newman, T.B., Keitz, S., Wyer, P.C., Moyer, V., & Guyatt, G. (2004). Tips for learners of evidence-based medicine: 2. Measures of precision (confidence intervals). Canadian Medical Association Journal, 171, 611–615.CrossRefGoogle ScholarPubMed
Moseley, A., Herbert, R., Maher, C., Sherrington, C., & Elkins, M. (2010). Reported quality of randomised controlled trials of physiotherapy interventions has improved over time. Journal of Clinical Epidemiology, 64, 594–601.CrossRefGoogle ScholarPubMed
Motulsky, H. (2014). Intuitive biostatistics: A nonmathematical guide to statistical thinking. Oxford, UK: Oxford University Press.Google Scholar
Nickerson, R.S. (2000). Null hypothesis significance testing: A review of an old and continuing controversy. Psychological Methods, 5, 241–301.CrossRefGoogle ScholarPubMed
Piantadosi, S. (2005). Clinical trials: A methodologic perspective (2nd ed.). Hoboken, NJ: Wiley-Interscience.CrossRefGoogle Scholar
Pocock, S.J. (1983). Clinical trials. A practical approach. Chichester: Wiley.Google Scholar
Pocock, S.J. (1997). Clinical trials with multiple outcomes: A statistical perspective on their design, analysis, and interpretation. Controlled Clinical Trials, 18, 530–545.CrossRefGoogle ScholarPubMed
Rajasekaran, S., Li Pi Shan, R., & Finnoff, J.T. (2014). Honorary authorship: Frequency and associated factors in physical medicine and rehabilitation research articles. Archives of Physical Medicine and Rehabilitation, 95, 418–428.CrossRefGoogle ScholarPubMed
Richardson, W.S., Wilson, M.C., Nishikawa, J., & Hayward, R.S. (1995). The well-built clinical question: A key to evidence-based decisions. ACP Journal Club, 123, A12–A13.CrossRefGoogle ScholarPubMed
Robinson, K.A., Dennison, C.R., Wayman, D.M., Pronovost, P.J., & Needham, D.M. (2007). Systematic review identifies number of strategies important for retaining study participants. Journal of Clinical Epidemiology, 60, 757–765.CrossRefGoogle ScholarPubMed
Schulz, K.F., Chalmers, I., Hayes, R.J., & Altman, D.G. (1995). Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA, 273, 408–412.CrossRefGoogle ScholarPubMed
Schwartz, D., & Lellouch, J. (2009). Explanatory and pragmatic attitudes in therapeutical trials. Journal of Clinical Epidemiology, 62, 499–505.CrossRefGoogle ScholarPubMed
Sedgwick, P. (2015). Intention to treat analysis versus per protocol analysis of trial data. British Medical Journal, 350, h681.CrossRefGoogle ScholarPubMed
Sim, J., & Reid, N. (1999). Statistical inference by confidence intervals: Issues of interpretation and utilization. Physical Therapy, 79, 186–195.CrossRefGoogle ScholarPubMed
Thabane, L., Ma, J., Chu, R., Cheng, J., Ismaila, A., Rios, L.P., . . . Goldsmith, C.H. (2010). A tutorial on pilot studies: The what, why and how. BMC Medical Research Methodology, 10, 1.CrossRefGoogle ScholarPubMed
Thorpe, K.E., Zwarenstein, M., Oxman, A.D., Treweek, S., Furberg, C.D., Altman, D.G., . . . Chalkidou, K. (2009). A pragmatic-explanatory continuum indicator summary (PRECIS): A tool to help trial designers. Canadian Medical Association Journal, 180, E47–E57.CrossRefGoogle ScholarPubMed
Treweek, S., & Zwarenstein, M. (2009). Making trials matter: Pragmatic and explanatory trials and the problem of applicability. Trials, 10, 37.CrossRefGoogle ScholarPubMed
Tugwell, P., & Knottnerus, J.A. (2016). Are triallists guilty of ‘imbalanced salami slicing’ – by favouring positive results in secondary publications?. Journal of Clinical Epidemiology, 79, 1–2.CrossRefGoogle ScholarPubMed
Turner, E.L., Perel, P., Clayton, T., Edwards, P., Hernandez, A. V., Roberts, I., . . . Collaborators, C.T. (2012). Covariate adjustment increased power in randomized controlled trials: An example in traumatic brain injury. Journal of Clinical Epidemiology, 65, 474–481.CrossRefGoogle ScholarPubMed
Wallace, S., Myles, P.S., Zeps, N., & Zalcberg, J.R. (2016). Serious adverse event reporting in investigator-initiated clinical trials. Medical Journal of Australia, 204, 231–233.CrossRefGoogle ScholarPubMed
White, I.R., Horton, N.J., Carpenter, J., & Pocock, S.J. (2011). Strategy for intention to treat analysis in randomised trials with missing outcome data. British Medical Journal, 342, 910–912.CrossRefGoogle ScholarPubMed
Whitehead, J.R. (2004). Stopping clinical trials by design. Nature Reviews Drug Discovery, 3, 973–977.CrossRefGoogle ScholarPubMed