Discontinuation and non-publication of surgical randomised controlled trials: observational study
BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g6870 (Published 09 December 2014) Cite this as: BMJ 2014;349:g6870
- Stephen J Chapman, academic foundation trainee1,
- Bryony Shelton, medical student2,
- Humza Mahmood, medical student3,
- J Edward Fitzgerald, general surgery registrar4,
- Ewen M Harrison, senior lecturer in general surgery5,
- Aneel Bhangu, clinical lecturer in colorectal surgery2
- 1University of Leeds, School of Medicine, Leeds LS2 9JT, UK
- 2University of Birmingham, College of Medical and Dental Sciences, Birmingham B15 2TH, UK
- 3St George’s University Hospital Medical School, London SW17 0RE, UK
- 4Royal Free Hospital NHS Trust, Barnet Hospital Campus, High Barnet EN5 3DJ, UK
- 5Clinical Surgery, University of Edinburgh, Edinburgh EH16 4SA, UK
- Correspondence to: A Bhangu, Academic Department of Surgery, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK aneelbhangu{at}doctors.org.uk
- Accepted 4 November 2014
Abstract
Objective To determine the rate of early discontinuation and non-publication of randomised controlled trials involving patients undergoing surgery.
Design Cross sectional observational study of registered and published trials.
Setting Randomised controlled trials of interventions in patients undergoing a surgical procedure.
Data sources The ClinicalTrials.gov database was searched for interventional trials registered between January 2008 and December 2009 using the keyword “surgery”. Recruitment status was extracted from the ClinicalTrials.gov database. A systematic search for studies published in peer reviewed journals was performed; if they were not found, results posted on the ClinicalTrials.gov results database were sought. Email queries were sent to trial investigators of discontinued and unpublished completed trials if no reason for the respective status was disclosed.
Main outcome measures Trial discontinuation before completion and non-publication after completion. Logistic regression was used to determine the effect of funding source on publication status, with adjustment for intervention type and trial size.
Results Of 818 registered trials found using the keyword “surgery”, 395 met the inclusion criteria. Of these, 21% (81/395) were discontinued early, most commonly owing to poor recruitment (44%, 36/81). The remaining 314 (79%) trials proceeded to completion, with a publication rate of 66% (208/314) at a median time of 4.9 (interquartile range 4.0-6.0) years from study completion to publication search. A further 6% (20/314) of studies presented results on ClinicalTrials.gov without a corresponding peer reviewed publication. Industry funding did not affect the rate of discontinuation (adjusted odds ratio 0.91, 95% confidence interval 0.54 to 1.55) but was associated with a lower odds of publication for completed trials (0.43, 0.26 to 0.72). Investigators’ email addresses for trials with an uncertain fate were identified for 71.4% (10/14) of discontinued trials and 83% (101/122) of unpublished studies. Only 43% (6/14) and 20% (25/122) replies were received. Email responses for completed trials indicated 11 trials in press, five published studies (four in non-indexed peer reviewed journals), and nine trials remaining unpublished.
Conclusions One in five surgical randomised controlled trials are discontinued early, one in three completed trials remain unpublished, and investigators of unpublished studies are frequently not contactable. This represents a waste of research resources and raises ethical concerns regarding hidden clinical data and futile participation by patients with its attendant risks. To promote future efficiency and transparency, changes are proposed to research governance frameworks to overcome these concerns.
Footnotes
Contributors: SJC, JEF, EH, and AB conceptualised the study. SJC, BS, and HM did searches and extracted data, which were verified by AB. SJC and AB prepared the initial manuscript drafts, which were subsequently edited by all authors. All authors agreed to submission. AB is the guarantor.
Funding: None.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: No additional data available.
Transparency: The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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