Trials In Neurosurgery Research Articles

Rapid qualitative analysis of recruitment obstacles in the FORVAD (Posterior Cervical Foraminotomy surgery versus Anterior Cervical Discectomy surgery in the treatment of cervical brachialgia) randomised, controlled trial

BackgroundThe number of surgical trials is increasing but such trials can be complex to deliver and pose specific challenges. A multi-centre, Phase III, RCT comparing Posterior Cervical Foraminotomy versus Anterior Cervical Discectomy and Fusion in the Treatment of Cervical Brachialgia (FORVAD Trial) was unable to recruit to target. A rapid qualitative study was conducted during trial closedown to understand the experiences of healthcare professionals who participated in the FORVAD Trial, with the aim of informing future research in this area.MethodsSemi-structured interviews were conducted with 18 healthcare professionals who had participated in the FORVAD Trial. Interviews explored participants’ experiences of the FORVAD trial. A rapid qualitative analysis was conducted, informed by Normalisation Process Theory.ResultsFour main themes were generated in the data analysis: (1) individual vs. community equipoise; (2) trial set-up and delivery; (3) identifying and approaching patients; and (4) timing of randomisation. The objectives of the FORVAD trial made sense to participants and they supported the idea that there was clinical or collective equipoise regarding the two FORVAD interventions; however, many surgeons had treatment preferences and lacked individual equipoise. The site which had most recruitment success had adopted a more structured process for identification and recruitment of patients, whereas other sites that adopted more “ad hoc” screening strategies struggled to identify patients. Randomisation on the day of surgery caused both medico-legal and practical concerns at some sites.ConclusionsOrganisation and implementation of a surgical trial in neurosurgery is complex and presents many challenges. Sites often reported low recruitment and discussed the logistical issues of conducting a complex surgical RCT. Future trials in neurosurgery may need to offer more flexibility and time during set-up to maximise opportunities for larger recruitment numbers. Rapid qualitative analysis informed by Normalisation Process Theory was able to quickly identify key issues with trial implementation so rapid qualitative analysis may be a useful approach for teams conducting qualitative research in trials.Trial registrationISRCTN, ISRCTN reference: 10,133,661. Registered 23rd November 2018.

Randomized controlled trials in neurosurgery.

Randomized controlled trials (RCTs) have become the standard method of evaluating new interventions (whether medical or surgical), and the best evidence used to inform the development of new practice guidelines. When we review the history of medical versus surgical trials, surgical RCTs usually face more challenges and difficulties when conducted. These challenges can be in blinding, recruiting, funding, and even in certain ethical issues. Moreover, to add to the complexity, the field of neurosurgery has its own unique challenges when it comes to conducting an RCT. This paper aims to provide a comprehensive review of the history of neurosurgical RCTs, focusing on some of the most critical challenges and obstacles that face investigators. The main domains this review will address are: (1) Trial design: equipoise, blinding, sham surgery, expertise-based trials, reporting of outcomes, and pilot trials, (2) trial implementation: funding, recruitment, and retention, and (3) trial analysis: intention-to-treat versus as-treated and learning curve effect.

Neurosurgical Study Design: Past and Future

Clinical trials are performed to determine the safety, efficacy, or effectiveness of a medical or surgical intervention. A clinical trial is, by definition, prospective in nature with a uniform treatment of a defined patient cohort. The outcomes assessment should also be uniform. Often a control group is included. At present, the number of neurosurgical clinical trials is increasing, and the study designs have become more sophisticated. Historically, the standard of neurosurgical care has evolved from the findings from many case series and retrospective comparative studies. However, in the present report, we have focused exclusively on prospective clinical trials. An urgent need exists to understand how clinical trials have been performed in the past and how they can be improved to advance our neurosurgical practice. In the present review, we have discussed the barriers, successes, and failures regarding prospective clinical trials in neurosurgery with an outlook to the future.

Use of Sham Interventions in Randomized Controlled Trials in Neurosurgery.

The use of sham interventions in randomized controlled trials (RCTs) is essential to minimize bias. However, their use in surgical RCTs is rare and subject to ethical concerns. To date, no studies have looked at the use of sham interventions in RCTs in neurosurgery. This study evaluated the frequency, type, and indication of sham interventions in RCTs in neurosurgery. RCTs using sham interventions were also characterized in terms of design and risk of bias. From a total of 1,102 identified RCTs in neurosurgery, 82 (7.4%) used sham interventions. The most common indication for the RCT was the treatment of pain (67.1%), followed by the treatment of movement disorders and other clinical problems (18.3%) and brain injuries (12.2%). The most used sham interventions were saline injections into spinal structures (31.7%) and peripheral nerves (10.9%), followed by sham interventions in cranial surgery (26.8%), and spine surgery (15.8%). Insertion of probes or catheters for a sham lesions was performed in 14.6%.In terms of methodology, most RCTs using sham interventions were double blinded (76.5%), 9.9% were single blinded, and 13.6% did not report the type of blinding. Sham-controlled RCTs in neurosurgery are feasible. Most aim to minimize bias and to evaluate the efficacy of pain management methods, especially in spinal disorders. The greatest proportion of sham-controlled RCTs involves different types of substance administration routes, with sham surgery the less commonly performed.

Epilepsy surgery at its best: randomised prospective controlled trials in neurosurgery are no magic

Three fields of neurosurgery have truly lived up to the aspirations of evidence-based medicine with multiple randomised controlled trials published in top impact journals: epilepsy surgery and movement disorder surgery...

Randomized controlled trials in neurosurgery: an observational analysis of trial discontinuation and publication outcome.

OBJECTIVE This study aimed to determine the trial discontinuation and publication rate of randomized controlled trials (RCTs) in neurosurgery. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Magnetic Resonance–Guided Focused Ultrasound Surgery

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel combination of technologies that is actively being realized as a noninvasive therapeutic tool for a myriad of conditions. These applications are reviewed with a focus on neurological use. A combined search of PubMed and MEDLINE was performed to identify the key events and current status of MRgFUS, with a focus on neurological applications. MRgFUS signifies a potentially ideal device for the treatment of neurological diseases. As it is nearly real time, it allows monitored provision of treatment location and energy deposition; is noninvasive, thereby limiting or eliminating disruption of normal tissue; provides focal delivery of therapeutic agents; enhances radiation delivery; and permits modulation of neural function. Multiple clinical applications are currently in clinical use and many more are under active preclinical investigation. The therapeutic potential of MRgFUS is expanding rapidly. Although clinically in its infancy, preclinical and early-phase I clinical trials in neurosurgery suggest a promising future for MRgFUS. Further investigation is necessary to define its true potential and impact.

Standards for reporting randomized controlled trials in neurosurgery

The Consolidated Standards for Reporting of Trials (CONSORT) criteria were published in 1996 to standardize the reporting and improve the quality of clinical trials. Despite having been endorsed by major medical journals and shown to improve the quality of reported trials, neurosurgical journals have yet to formally adopt these reporting criteria. The purpose of this study is to evaluate the quality and reporting of randomized controlled trials (RCTs) in neurosurgery and the factors that may affect the quality of reported trials. The authors evaluated all neurosurgical RCTs published in 2006 and 2007 in the principal neurosurgical journals (Journal of Neurosurgery; Neurosurgery; Surgical Neurology; Journal of Neurology, Neurosurgery, and Psychiatry; and Acta Neurochirurgica) and in 3 leading general medical journals (Journal of the American Medical Association, Lancet, and the New England Journal of Medicine). Randomized controlled trials that addressed operative decision making or the treatment of neurosurgical patients were included in this analysis. The RCT quality was evaluated using the Jadad score and the CONSORT checklist. In 2006 and 2007, 27 RCTs relevant to intracranial neurosurgery were reported. Of these trials, only 59% had a Jadad score ≥ 3. The 3 major medical journals all endorsed the CONSORT guidelines, while none of the neurosurgical journals have adopted these guidelines. Randomized controlled trials published in the 3 major medical journals had a significantly higher mean CONSORT score (mean 41, range 39-44) compared with those published in neurosurgical journals (mean 26.4, range 17-38; p < 0.0001). Jadad scores were also significantly higher for the major medical journals (mean 3.42, range 2-5) than neurosurgical journals (mean 2.45, range 1-5; p = 0.05). Despite the growing volume of RCTs in neurosurgery, the quality of reporting of these trials remains suboptimal, especially in the neurosurgical journals. Improved awareness of the CONSORT guidelines by journal editors, reviewers, and authors of these papers could improve the methodology and reporting of RCTs in neurosurgery.

Randomized controlled trials in neurosurgery—how good are we?

The strongest evidence in medical clinical literature is represented by randomized controlled trials (RCTs). This study was designed to evaluate neurosurgically relevant RCTs published recently by neurosurgeons. A literature search in MEDLINE and EMBASE included all clinical studies published up to 30 June 2006. RCTs with neurosurgical relevance published by at least one author with affiliation to a neurosurgical department were selected. The number and characteristics of individual trials were recorded, and the quality of the trials with regard to study design, quality of reporting, and relevance for clinical practice was assessed by two different investigators using a modification of the Scottish Intercollegiate Guidelines Network methodology checklist. Changes of RCT quality over time as well as factors influencing the quality were analyzed. From the initial search results (MEDLINE n = 3,860, EMBASE n = 3,113 articles), 159 RCTs published by neurosurgeons were extracted for final evaluation. Of the RCTs, 62% have been published since 1995; 52% came from the USA, UK, and Germany. The median RCT sample size was 78 patients and the median follow-up 35.7 weeks. Fifty-two percent of all RCTs were of good, 37% of moderate, and 11% of bad quality, with an improvement over time. RCTs with financial funding and RCTs with a sample size of >78 patients were of significantly better quality. There were no major differences in the rating of the studies between the two investigators. Only a fraction of neurosurgically relevant literature consists of RCTs, but the quality is satisfying and has significantly improved over the last years. An adequate sample size and sufficient financial support seem to be of substantial importance with regard to the quality of the study. Our data also show that by using a standardized checklist, the quality of trials can be reliably assessed by observers of different experience and educational levels.

History of Randomized Clinical Trials in Neurosurgery

The randomized clinical trial is a treatment evaluation technique that has been available in clinical research since 1946. Its first application in neurosurgery seems to have occurred in 1960 by McKissock and colleagues. Neurosurgery has been slow to adopt the technique, particularly in the evaluation of surgical therapy, but its use has increased in recent years.

Randomized clinical trials in neurosurgery.

Fifty-one randomized trials of neurosurgical topics have been identified. These have been analyzed for content, quality of reporting, and quality of statistical design and analysis. In general, there were major omissions in the reporting of critical portions of the studies, the statistical analysis was highly variable in quality, and the statistical power was low. Few, if any, major neurosurgical questions have been answered by clinical trials. This may reflect the generally low quality of these trials. To improve the quality of such trials, neurosurgeons must seek biostatistical advice in planning and conducting trials and must cooperate in multi-institutional trials to increase statistical power.

Randomized clinical trials in neurosurgery

Randomized clinical trials in neurosurgery

Randomized clinical trials in the evaluation of surgical innovation

Randomized clinical trials are widely accepted as the standard for evaluation of therapeutic innovation in many fields of medicine. The three basic components of such trials (concurrent comparison, random allocation, and objective observation) are designed to control four forms of bias (chronology bias, susceptibility bias, compliance bias, and observation bias) that may interfere with the interpretation of the results of a study. Only 2% of the articles evaluating therapeutic maneuvers published in the Journal of Neurosurgery have attempted to use concurrent controls. Only one of 863 such articles met the criteria for a randomized clinical trial. Reasons for underutilization of such trials in neurosurgery are discussed and suggestions for their wider use are offered.