Phillip C. Copley and Andreas K. Demetriades
Aimun A. B. Jamjoom, Angus B. Gane and Andreas K. Demetriades
This study aimed to determine the trial discontinuation and publication rate of randomized controlled trials (RCTs) in neurosurgery.
Trials registered from 2000 to 2012 were identified on the website clinicaltrials.gov using a range of key words related to neurosurgery. Any trials that were actively recruiting or had unknown status were excluded. Included trials were assessed for whether they were discontinued early on the clinicaltrials.gov database; this included trials identified as withdrawn, suspended, or terminated in the database. For included trials, a range of parameters was identified including the subspecialty, primary country, study start date, type of intervention, number of centers, and funding status. Subsequently, a systematic search for published peer-reviewed articles was undertaken. For trials that were discontinued early or were found to be unpublished, principal investigators were sent a querying email.
Sixty-four neurosurgical trials fulfilled our inclusion criteria. Of these 64, 26.6% were discontinued early, with slow or insufficient recruitment cited as the major reason (57%). Of the 47 completed trials, 14 (30%) remained unpublished. Discontinued trials showed a statistically significant higher chance of remaining unpublished (88%) compared with completed trials (p = 0.0002). Industry-funded trials had a higher discontinuation rate (31%) compared with non–industry-funded trials (23%), but this result did not reach significance (p = 0.57). Reporting of primary outcome measures was complete in 20 (61%) of 33 trials. For secondary outcome measures, complete reporting occurred in only 11 (33.3%) of 33.
More than a fifth (26.6%) of neurosurgical RCTs are discontinued early and almost a third of those that are completed remain unpublished. This result highlights significant waste of financial resources and clinical data.
Ingrid Hoeritzauer, Matthew Wood, Phillip C. Copley, Andreas K. Demetriades and Julie Woodfield
Cauda equina syndrome (CES) is a surgical emergency requiring timely operative intervention to prevent symptom progression. Accurately establishing the incidence of CES is required to inform healthcare service design and delivery, including out-of-hours imaging arrangements.
A systematic literature search of MEDLINE, EMBASE, and Scopus was undertaken to identify original studies stating the incidence of CES, and the estimates were combined in a meta-analysis as described in the protocol registered with PROSPERO (registration no. CRD42017065865) and reported using the PRISMA guidelines.
A total of 1281 studies were identified, and 26 studies were included in the review. Data about CES incidence were available from 3 different populations: asymptomatic community populations, patients with nontraumatic low-back pain, and patients presenting as an emergency with suspected CES. The incidence of CES was 0.3–0.5 per 100,000 per year in 2 asymptomatic community populations, 0.6 per 100,000 per year in an asymptomatic adult population, and 7 per 100,000 per year in an asymptomatic working-age population. CES occurred in 0.08% of those with low-back pain presenting to primary care in 1 study, and a combined estimate of 0.27% was calculated for 4 studies of those with low-back pain presenting to secondary care. Across 18 studies of adults with suspected CES, 19% had radiological and clinical CES. Difficulties in comparison between studies resulted from the heterogeneous definitions of CES and lack of separation of more advanced CES with retention, which is unlikely to be reversible. In the studies of patients with suspected CES, the small sample size, the high number of single-center studies (18/18), the high number of studies from the United Kingdom (17/18), the retrospective nature of the studies, and the high number of abstracts rather than full texts (9/18) reduced the quality of the data.
From current studies, it appears that CES occurs infrequently in asymptomatic community populations and in only 19% of those presenting with symptoms. Determining accurate incidence figures and designing a bespoke service for investigation of patients with suspected CES would require a consensus clinical and radiological definition of CES and international multisite studies of patient pathways of investigation and management.