How do clinical researchers’ and patients’ preferences influence study hypotheses and reported outcome results for clinical randomised controlled trials? A critical appraisal
2015
ABSTRACT
Background
Studies designed to promote unbiased research increasingly show that human preferences exert a major influence on randomised controlled trials (RCTs) [ , , ]. More information is needed on how preferences influence clinical trial design and conduction [ , , ]. To fill the information gap between what researchers seek and report and what patients want [ , ], in this study we investigated how researchers’ and patients’ preferences influence study hypotheses and outcome results of published clinical RCTs. Because conventional critical appraisal seemed inappropriate for addressing our research question, in this pilot study we developed a novel assessment method and applied it in an RCT sample.
Methods
We collected 20 unselected and consecutive RCTs published in a high impact paediatric journal from July to November 2013. Two experienced reviewers identified the following five domains and a grading method to score discrepancy between what authors state in clinical trial registries (CTRs) and report in published RCTs: reported funding (1 point), study hypotheses, information on patients enrolled and study conduction (3 points); primary and secondary outcomes, early study completion, and upgrading or downgrading outcome results (5 points). Higher scores implied marked discrepancy. Two reviewers then independently applied the method on the RCT sample by mapping and coding information for the domains identified and reported discrepancies by comparing CTRs and RCTs (Table).
Results
Of the 20 RCTs collected and CTRs compared, 14 studies had high total preference discrepancy scores (7 scored 10-12, and 7 scored 16 or more) and 4 had discrepancy in declaring funding. In 12 studies researchers completed the study early and in 8 studies they downgraded or upgraded outcomes. Only 5 CTRs were updated but they neglected to include published RCT results. Only in 5 CTRs, dataset supervisors indicated the RCT URL. None of the 20 RCTs allowed us to assess patients’ preferences (no information reported for non-response and refusal). No difference was found in discrepancy scores among the five CTR databases.
Conclusions
The high discrepancy scores obtained by comparing what researchers stated in CTRs and published in RCTs suggest possible misconduct. Patients’ preferences during RCT enrolment and conduction remain undetectable owing to the lack of targeted protocols to elicit this issue. These results, if confirmed in further studies, should prompt international regulation developers [2] to encourage researchers to explore patients’ preferences as a strategy to enhance informed decision-making and to improve reporting in RCTs and CTRs.
Table. Reviewers’ estimated discrepancy score between issues reported by authors in clinical trials registries and what they report in published randomised controlled trials
National Registries and
number of trial registration First author and reference in RCTs published in Pediatrics Total preference discrepancy score
High 10-20
Medium 5-9
Low <5
International Standard Randomised Controlled Trial Number Register, BioMed Central, UK ISRCTN 31707342
www.controlled-trials.com
McCarthy LK et al. 132, 1, e135-e141 July 2013
0 Low
US National Controlled Trials
NCT 01822626
https://clinicaltrials.gov
Davoli A.M. et al. 132, 5, e1236-e1245 Oct 2013
2 Low
International Standard Randomised Controlled Trial Number Register, BioMed Central, UK ISRCTN 59061709
www.controlled-trials.com
McCarthy LK et al. 132, 2, e389-e395 Aug 2013
2 Low
Australian New Zealand Clinical Trial Registry ACTRN 12608000056392
https://www.anzctr.org.au
Daniels LA et al. 132, 1, e109- e118 July 2013
3 Low
Netherlands Trial Registry
NTR1613
www.trialregister.nl
Van der Veek et al. 132, 5, e1163-e1172 Nov 2013
3 Low
US National Controlled Trials
NCT 00409448
https://clinicaltrials.gov
Kurowski et al.
132, 1, e158-e166 Jul 2013
6 Medium
US National Controlled Trials
NCT00548379
https://clinicaltrials.gov
Aluisio A.R. et al. 132,4, e832-e840 Oct 2013
10 High
International Standard Randomised Controlled Trial Number Register, BioMed Central, UK
ISRCTN 72635512
www.controlled-trials.com
Field 132, 5, e1247-e1256 Nov 2013
12 High
US National Controlled Trials
NCT 01307293
https://clinicaltrials.gov
Shaw RJ et al. 132, 4, e886-e894 Oct 2013
12 High
International Standard Randomised Controlled Trial Number Register, BioMed Central, UK
ISRCTN 03981121
www.controlled-trials.com
Wake M et al. 132, 4, e895-e904 Oct 2013
12 High
Clinical Trials Registry India CTRI/2010/091/001417
www.ctri.nic.in
Malik A et al.
132, 1, e46-e52 July 2013
12 High
US National Controlled Trials
NCT 01351064
https://clinicaltrials.gov
Carroll A.E. 132, 3, e623-e 629 Sept 2013
12 High
Netherlands Trial Registry
NTR 2061 www.trialregister.nl
and
Australian New Zealand Clinical Trial Registry
ACTRN 12610000230055 https://www.anzctr.org.au
Kamlin COF et al. 132, 2, e381-e388 Aug 2013
12 High
US National Controlled Trials
NCT 01403623
https://clinicaltrials.gov
Leadford AE et al. 132, 1, e128-e134 Jul 2103
16 High
US National Controlled Trials
NCT 01810978
https://clinicaltrials.gov
Dilli D. et al. 132, 4, e932-e938 Oct 2013
17 High
US National Controlled Trials
NCT 00334737
https://clinicaltrials.gov/
Ohls RK et al. 132, 1, e119-e127 Jul 2013
17 High
US National Controlled Trials
NCT 01065272
https://clinicaltrials.gov
Alansari K. et al. 132,4, e810-e816 Sept 2013
17 High
Australian New Zealand Clinical Trial Registry
ACTRN 12612000976886 https://www.anzctr.org.au
McIntosh CG et al. 132, 2, 326-331 Aug 2013
17 High
US National Controlled Trials
NCT 00551642
https://clinicaltrials.gov
Durrmeyer X et al. 132,3, e695-e703 Sept 2013
18 High
US National Controlled Trials
NCT 01604460
https://clinicaltrials.gov
Belsches et al 132, 3, e656-e661 Sept 2013
18 High
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