Treatment success in pragmatic randomised controlled trials: a review of trials funded by the UK...
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ORAL PRESENTATION Open Access Treatment success in pragmatic randomised controlled trials: a review of trials funded by the UK Health Technology Assessment programme Louise Dent 1* , James Raftery 2 From Clinical Trials Methodology Conference 2011 Bristol, UK. 4-5 October 2011 Background Equipoise implies that given a random unbiased sample of trials, no significant difference would be expected in the proportion favouring the new treatment to the pro- portion favouring the standard treatment [1-3]. Previous research reviewed treatment success and whether the collective uncertainty principle is met in RCTs in the US National Cancer Institute portfolio [4-6]. This paper classifies clinical trials funded by the UK HTA pro- gramme by results using the method applied to the US Cancer Institute trials, and compares the two portfolios [7]. Methods Data on all completed randomised controlled trials funded by the HTA programme 1993-2008 were extracted. Each trial’s primary results was classified into six categories; 1) statistically significant in favour of the new treatment, 2) statistically significant in favour of the control treatment 3) true negative, 4) truly inconclusive, 5) inconclusive in favour of new treatment or 6) incon- clusive in favour of control treatment. Trials were classi- fied by comparing the 95% confidence interval for the difference in primary outcome to the difference specified in the sample size calculation. The results were com- pared with Djulbegovic’s analysis of NCI trials. Results Data from 51 superiority trials were included, involving over 48,000 participants and a range of diseases and interventions. 85 primary comparisons were available because some trials had more than two randomised arms or had several primary outcomes. The new treat- ment had superior results (whether significant or not) in 61% of the comparisons (52/85 95% CI 49.9% to 71.6%). The results were conclusive in 46% of the comparisons (19% statistically significant in favour of the new treat- ment, 5% statistically significant in favour of the control and 22% true negative). The results were classified as truly inconclusive (i.e. failed to answer the question asked) for 24% of comparisons (20/85). HTA trials included fewer truly inconclusive and statistically signifi- cant results and more results rated as true negative than NCI trials. Conclusions The pattern of results in HTA trials is similar to that of the National Cancer Institute portfolio. Differences that existed were plausible given the differences in the types of trials -HTA trials are more pragmatic. The results indicate HTA trials are compatible with equipoise. This classification usefully summarises the results from clini- cal trials and enables comparisons of different portfolios of trials. Author details 1 University of Southampton Clinical Trials Unit, MP131, Southampton General Hospital, SO16 6YD, UK. 2 NIHR Evaluation, Trials and Studies Coordinating Centre, University of Southampton, Southampton, SO16 7NS, UK. Published: 13 December 2011 References 1. Kumar A, Soares H, Wells R, Clarke M, Hozo L, Bleyer A, et al: Are experimental treatments for cancer in children superior to established treatments? Observational study of randomised controlled trials by the Children’s Oncology Group. British Medical Journal 2005, 331(7528):1295-1298B. * Correspondence: [email protected] 1 University of Southampton Clinical Trials Unit, MP131, Southampton General Hospital, SO16 6YD, UK Full list of author information is available at the end of the article Dent and Raftery Trials 2011, 12(Suppl 1):A97 http://www.trialsjournal.com/content/12/S1/A97 TRIALS © 2011 Dent and Raftery; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Transcript of Treatment success in pragmatic randomised controlled trials: a review of trials funded by the UK...
ORAL PRESENTATION Open Access
Treatment success in pragmatic randomisedcontrolled trials: a review of trials funded by theUK Health Technology Assessment programmeLouise Dent1*, James Raftery2
From Clinical Trials Methodology Conference 2011Bristol, UK. 4-5 October 2011
BackgroundEquipoise implies that given a random unbiased sampleof trials, no significant difference would be expected inthe proportion favouring the new treatment to the pro-portion favouring the standard treatment [1-3]. Previousresearch reviewed treatment success and whether thecollective uncertainty principle is met in RCTs in theUS National Cancer Institute portfolio [4-6]. This paperclassifies clinical trials funded by the UK HTA pro-gramme by results using the method applied to the USCancer Institute trials, and compares the two portfolios[7].
MethodsData on all completed randomised controlled trialsfunded by the HTA programme 1993-2008 wereextracted. Each trial’s primary results was classified intosix categories; 1) statistically significant in favour of thenew treatment, 2) statistically significant in favour of thecontrol treatment 3) true negative, 4) truly inconclusive,5) inconclusive in favour of new treatment or 6) incon-clusive in favour of control treatment. Trials were classi-fied by comparing the 95% confidence interval for thedifference in primary outcome to the difference specifiedin the sample size calculation. The results were com-pared with Djulbegovic’s analysis of NCI trials.
ResultsData from 51 superiority trials were included, involvingover 48,000 participants and a range of diseases andinterventions. 85 primary comparisons were available
because some trials had more than two randomisedarms or had several primary outcomes. The new treat-ment had superior results (whether significant or not) in61% of the comparisons (52/85 95% CI 49.9% to 71.6%).The results were conclusive in 46% of the comparisons(19% statistically significant in favour of the new treat-ment, 5% statistically significant in favour of the controland 22% true negative). The results were classified astruly inconclusive (i.e. failed to answer the questionasked) for 24% of comparisons (20/85). HTA trialsincluded fewer truly inconclusive and statistically signifi-cant results and more results rated as true negative thanNCI trials.
ConclusionsThe pattern of results in HTA trials is similar to that ofthe National Cancer Institute portfolio. Differences thatexisted were plausible given the differences in the typesof trials -HTA trials are more pragmatic. The resultsindicate HTA trials are compatible with equipoise. Thisclassification usefully summarises the results from clini-cal trials and enables comparisons of different portfoliosof trials.
Author details1University of Southampton Clinical Trials Unit, MP131, Southampton GeneralHospital, SO16 6YD, UK. 2NIHR Evaluation, Trials and Studies CoordinatingCentre, University of Southampton, Southampton, SO16 7NS, UK.
Published: 13 December 2011
References1. Kumar A, Soares H, Wells R, Clarke M, Hozo L, Bleyer A, et al: Are
experimental treatments for cancer in children superior to establishedtreatments? Observational study of randomised controlled trials by theChildren’s Oncology Group. British Medical Journal 2005,331(7528):1295-1298B.
* Correspondence: [email protected] of Southampton Clinical Trials Unit, MP131, Southampton GeneralHospital, SO16 6YD, UKFull list of author information is available at the end of the article
Dent and Raftery Trials 2011, 12(Suppl 1):A97http://www.trialsjournal.com/content/12/S1/A97 TRIALS
© 2011 Dent and Raftery; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.
2. Djulbegovic B: Articulating and responding to uncertainties in clinicalresearch. Journal of Medicine and Philosophy 2007, 32(2):79-98.
3. Djulbegovic B: The paradox of equipoise: the principle that drives andlimits therapeutic discoveries in clinical research. Cancer Control 2009,16(4):342-347.
4. Djulbegovic B, Kumar A, Soares HP, Hozo I, Bepler G, Clarke M, et al:Treatment success in cancer. Archives of Internal Medicine 2008,168(6):632-42.
5. Joffe S, Harrington DP, George SL, Emanuel EJ, Budzinski LA, Weeks JC:Satisfaction of the uncertainty principle in cancer clinical trials:retrospective cohort analysis. BMJ 2004, 328(7454):1463.
6. Soares HP, Kumar A, Daniels S, Swann S, Cantor A, Hozo I, et al: Evaluationof new treatments in radiation oncology: are they better than standardtreatments? JAMA 2005, 293(8):970-978.
7. Dent L, Raftery J: Treatment success in pragmatic randomised controlledtrials: a review of trials funded by the UK Health TechnologyAssessment programme. Trials 2011, 12:109.
doi:10.1186/1745-6215-12-S1-A97Cite this article as: Dent and Raftery: Treatment success in pragmaticrandomised controlled trials: a review of trials funded by the UK HealthTechnology Assessment programme. Trials 2011 12(Suppl 1):A97.
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