Surgical Randomized Controlled Trials Research Articles

Adaptive clinical trials in surgery: A scoping review of methodological and reporting quality.

Adaptive surgical trials are scarce, but adopting these methods may help elevate the quality of surgical research when large-scale RCTs are impractical. Randomized-controlled trials (RCTs) are the gold standard for evidence-based healthcare. Despite an increase in the number of RCTs, the number of surgical trials remains unchanged. Adaptive clinical trials can streamline trial design and time to trial reporting. The advantages identified for ACTs may help to improve the quality of future surgical trials. We present a scoping review of the methodological and reporting quality of adaptive surgical trials. We performed a search of Ovid, Web of Science, and Cochrane Collaboration for all adaptive surgical RCTs performed from database inception to October 12, 2023. We included any published trials that had at least one surgical arm. All review and abstraction were performed in duplicate. Risk of bias (RoB) was assessed using the RoB 2.0 instrument and reporting quality was evaluated using CONSORT ACE 2020. All results were analyzed using descriptive methods. Of the 1338 studies identified, six trials met inclusion criteria. Trials were performed in cardiothoracic, oral, orthopedic, and urological surgery. The most common type of adaptive trial was group sequential design with pre-specified interim analyses planned for efficacy, futility, and/or sample size re-estimation. Two trials did use statistical simulations. Our risk of bias evaluation identified a high risk of bias in 50% of included trials. Reporting quality was heterogeneous regarding trial design and outcome assessment and details in relation to randomization and blinding concealment. Surgical trialists should consider implementing adaptive components to help improve patient recruitment and reduce trial duration. Reporting of future adaptive trials must adhere to existing CONSORT ACE 2020 guidelines. Future research is needed to optimize standardization of adaptive methods across medicine and surgery.

Quality assurance in surgical trials of arteriovenous grafts for haemodialysis: A systematic review, a narrative exploration and expert recommendations.

Introducing new procedures and challenging established paradigms requires well-designed randomised controlled trials (RCT). However, RCT in surgery present unique challenges with much of treatment tailored to the individual patient circumstances, refined by experience and limited by organisational factors. There has been considerable debate over the outcomes of arteriovenous grafts (AVG) compared to AVF, but any differences may reflect differing practice and potential variability. It is essential, therefore, when considering an RCT of a novel surgical procedure or device that quality assurance (QA) is defined for both the new approach and the comparator. The aim of this systematic review was to evaluate the QA standards performed in RCT of AVG using a multi-national, multi-disciplinary approach and propose an approach for future RCT. The methods of this have been previously registered (PROSPERO: CRD420234284280) and published. In summary, a four-stage review was performed: identification of RCT of AVG, initial review, multidisciplinary appraisal of QA methods and reconciliation. QA measures were sought in four areas - generic, credentialing, standardisation and monitoring, with data abstracted by a multi-national, multi-speciality review body. QA in RCT involving AVG in all four domains is highly variable, often sub-optimally described and has not improved over the past three decades. Few RCT established or defined a pre-RCT level of experience, none documented a pre-trial education programme, or had minimal standards of peri-operative management, no study had a defined pre-trial monitoring programme, and none assessed technical performance. QA in RCT is a relatively new area that is expanding to ensure evidence is reliable and reproducible. This review demonstrates that QA has not previously been detailed, but can be measured in surgical RCT of vascular access, and that a four-domain approach can easily be implemented into future RCT.

Evidence-Based Surgery: What Can Intra-Operative Images Contribute?

Evidence-based medicine integrates results from randomized controlled trials (RCTs) and meta-analyses, combining the best external evidence with individual clinical expertise and patients' preferences. However, RCTs of surgery differ from those of medicine in that surgical performance is often assumed to be consistent. Yet, evaluating whether each surgery is performed to the same standard is quite challenging. As a primary issue, the novelty of this review is to emphasize-with a focus on orthopedic trauma-the advantage of having complete intra-operative image documentation, allowing the direct evaluation of the quality of the intra-operative technical performance. The absence of complete intra-operative image documentation leads to the inhomogeneity of case series, yielding inconsistent results due to the impossibility of a secondary analysis. Thus, comparisons and the reproduction of studies are difficult. Access to complete intra-operative image data in surgical RCTs allows not only secondary analysis but also comparisons with similar cases. Such complete data can be included in electronic papers. Offering these data to peers-in an accessible link-when presenting papers facilitates the selection process and improves publications for readers. Additionally, having access to the full set of image data for all presented cases serves as a rich resource for learning. It enables the reader to sift through the information and pinpoint the details that are most relevant to their individual needs, allowing them to potentially incorporate this knowledge into daily practice. A broad use of the concept of complete intra-operative image documentation is pivotal for bridging the gap between clinical research findings and real-world applications. Enhancing the quality of surgical RCTs would facilitate the equalization of evidence acquisition in both internal medicine and surgery. Joint effort by surgeons, scientific societies, publishers, and healthcare authorities is needed to support the ideas, implement economic requirements, and overcome the mental obstacles to its realization.

Determining the Effectiveness of Fibrin Sealants in Reducing Complications in Patients Undergoing Lateral Neck Dissection (DEFeND): A Randomised External Pilot Trial.

High-quality randomised controlled trials (RCT) to support the use of Fibrin Sealants (FS) in neck dissection (ND) are lacking. The DEFeND trial assessed critical pilot/feasibility questions and signals from clinical outcomes to inform a future definitive trial. The study design piloted was a blinded surgical RCT. All participants underwent unilateral ND for head and neck cancer. Interventional arm: ND with application of FS. ND alone. Feasibility outcomes included recruitment, effectiveness of blinding, protocol adherence and evaluating administrative processes. Clinical outcomes included surgical complications (primary outcome), drainage volume, time to drain removal, length of hospital stay, pain and the Neck Dissection Impairment Index. Recruitment completed ahead of time. Fifty-three patients were recruited, and 48 were randomised at a rate of 5.3 patients/month. Blinding of patients, research nurses and outcome assessors was effective. Two protocol deviations occurred. Two patients were lost to follow-up. The mean (SD) Comprehensive Complication Index in the interventional arm was 6.5 (12.8), and it was 9.9 (14.2) in the control arm. The median (IQR) time to drain removal (days) was shorter in the interventional arm (2.67 (2.42, 3.58) vs. 3.40 (2.50, 4.27)). However, this did not translate to a clinically significant reduction in median (IQR) length of hospital stay in days (intervention: 3.48 (2.64, 4.54), control: 3.74 (3.11, 4.62)). The proposed trial design was effective, and a definitive surgical trial is feasible. Whilst there was a tendency for FS to improve clinical outcomes, the effect size did not reach clinical or statistical significance. (ISRCTN99181100).

The Fragility of Statistical Significance in Sham Orthopaedic Surgery: A Systematic Review of Randomized Controlled Trials.

The purpose of this study was to determine the stability of statistical findings among sham surgery randomized controlled trials (RCTs) in orthopaedic surgery using fragility analysis. PubMed systematic review was conducted to include studies reporting dichotomous outcomes pertaining to sham surgery. The final review included eight RCTs involving only partial meniscectomies and vertebroplasties from 2009 to 2020. With a fixed sample size with dichotomous outcome measures (events versus non-events), the Total Fragility Index (TFI), which is composed of the fragility index (FI) and reverse fragility index (RFI), was calculated by altering the ratio of events to non-events in an iterative fashion until results were reversed from significant to nonsignificant findings (FI) or vice versa (RFI). The TFI, FI, and RFI were divided by their sample sizes to obtain the respective total fragility quotient, fragility quotient (FQ), and reverse fragility quotient. Median fragility indices and quotients were reported for all studies. The eight RCTs included 50 dichotomous outcomes involving either partial meniscectomies or vertebroplasties, with a median TFI and total fragility quotient of 5 [interquartile range (IQR) 4 to 6] and 0.035 (IQR 0.028 to 0.048), respectively, indicating that a median of five total patients or 3.5 per 100 patients would need to experience a different outcome to reverse significant or insignificant findings for each of the eight trials. Among the 8 statistically significant ( P < 0.05) outcome events (16%), the respective FI and FQ were 2 (IQR 1 to 5) and 0.018 (IQR 0.010 to 0.044). Among the 42 statistically insignificant outcome events (84%), the respective RFI and reverse fragility quotient were 5 (IQR 4 to 6) and 0.04 (IQR 0.034 to 0.048). The median number of patients lost to follow-up was 1.5 (IQR 0.5 to 2). The unstable findings in partial meniscectomy and vertebroplasty sham surgical RCTs undermine their study conclusions and recommendations. We recommend using fragility analysis in future sham surgical RCTs to contextualize statistical findings. Level IV; Systematic Review.

Methods of Recruitment for Surgical and Perioperative Randomized Controlled Trials: A Rapid Review.

Due to the complex nature of surgical randomized controlled trials (RCTs), reaching target recruitment can be challenging. The primary objective was to report on characteristics of successful pilot surgical and perioperative RCTs and the methodological strategies implemented to optimize recruitment. The secondary objective was to provide recommendations for successful recruitment strategies for future surgical RCTs. Ovid MEDLINE, Ovid EMBASE, and Web of Science (via Ovid) databases were searched from 2012 to 2022. This review included surgical and perioperative pilot studies that met their recruitment targets. Study and recruitment characteristics were summarized, and potential relationships between study design and recruitment rate were assessed. Optimized recruitment strategies were extracted when reported. Of 4156 total articles identified, 255 underwent full-text screening, and 52 articles were included. Of the included pilot studies, 21% (n = 11) did not indicate a target sample size or recruitment rate. Recruitment methods were minimally reported in pilot studies for perioperative or surgical RCTs. Strategies to optimize recruitment included internal iterative evaluations of the recorded recruitment appointments and staged introduction of the study. Recruitment rate was not associated with invasiveness of intervention or burden of participation. Patient involvement is absent from current reports on methodological design and offers valuable opportunity to optimize recruitment. Recruitment strategies in perioperative and surgical RCTs can be optimized with iterative qualitative evaluation of the recruitment methods with input from the interdisciplinary research team.

Incisional negative pressure wound therapy for the prevention of surgical site infection: an up-to-date meta-analysis and trial sequential analysis

The evidence on prophylactic use of negative pressure wound therapy on primary closed incisional wounds (iNPWT) for the prevention of surgical site infections (SSI) is confusing and ambiguous. Implementation in daily practice is impaired by inconsistent recommendations in current international guidelines and published meta-analyses. More recently, multiple new randomised controlled trials (RCTs) have been published. We aimed to provide an overview of all meta-analyses and their characteristics; to conduct a new and up-to-date systematic review and meta-analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment; and to explore the additive value of new RCTs with a trial sequential analysis (TSA). PubMed, Embase and Cochrane CENTRAL databases were searched from database inception to October 24, 2022. We identified existing meta-analyses covering all surgical specialties and RCTs studying the effect of iNPWT compared with standard dressings in all types of surgery on the incidence of SSI, wound dehiscence, reoperation, seroma, hematoma, mortality, readmission rate, skin blistering, skin necrosis, pain, and adverse effects of the intervention. We calculated relative risks (RR) with corresponding 95% confidence intervals (CI) using a Mantel-Haenszel random-effects model. We assessed publication bias with a comparison-adjusted funnel plot. TSA was used to assess the risk of random error. The certainty of evidence was evaluated using the Cochrane Risk of Bias-2 (RoB2) tool and GRADE approach. This study is registered with PROSPERO, CRD42022312995. We identified eight previously published general meta-analyses investigating iNPWT and compared their results to present meta-analysis. For the updated systematic review, 57 RCTs with 13,744 patients were included in the quantitative analysis for SSI, yielding a RR of 0.67 (95% CI: 0.59-0.76, I2=21%) for iNPWT compared with standard dressing. Certainty of evidence was high. Compared with previous meta-analyses, the RR stabilised, and the confidence interval narrowed. In the TSA, the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit, confirming the robustness of the summary effect estimate from the meta-analysis. In this up-to-date meta-analysis, GRADE assessment shows high-certainty evidence that iNPWT is effective in reducing SSI, and uncertainty is less than in previous meta-analyses. TSA indicated that further trials are unlikely to change the effect estimate for the outcome SSI; therefore, if future research is to be conducted on iNPWT, it is crucial to consider what the findings will contribute to the existing robust evidence. Dutch Association for Quality Funds Medical Specialists.

Choosing the Best Design in Surgical Research.

Choosing the Best Design in Surgical Research.

Development of a risk-tailored approach and dashboard for efficient management and monitoring of investigator-initiated trials

BackgroundMost randomized controlled trials (RCTs) in the academic setting have limited resources for clinical trial management and monitoring. Inefficient conduct of trials was identified as an important source of waste even in well-designed studies. Thoroughly identifying trial-specific risks to enable focussing of monitoring and management efforts on these critical areas during trial conduct may allow for the timely initiation of corrective action and to improve the efficiency of trial conduct. We developed a risk-tailored approach with an initial risk assessment of an individual trial that informs the compilation of monitoring and management procedures in a trial dashboard.MethodsWe performed a literature review to identify risk indicators and trial monitoring approaches followed by a contextual analysis involving local, national and international stakeholders. Based on this work we developed a risk-tailored management approach with integrated monitoring for RCTs and including a visualizing trial dashboard. We piloted the approach and refined it in an iterative process based on feedback from stakeholders and performed formal user testing with investigators and staff of two clinical trials.ResultsThe developed risk assessment comprises four domains (patient safety and rights, overall trial management, intervention management, trial data). An accompanying manual provides rationales and detailed instructions for the risk assessment. We programmed two trial dashboards tailored to one medical and one surgical RCT to manage identified trial risks based on daily exports of accumulating trial data. We made the code for a generic dashboard available on GitHub that can be adapted to individual trials.ConclusionsThe presented trial management approach with integrated monitoring enables user-friendly, continuous checking of critical elements of trial conduct to support trial teams in the academic setting. Further work is needed in order to show effectiveness of the dashboard in terms of safe trial conduct and successful completion of clinical trials.

Study protocol for a prospective, multi-centered randomized controlled trial comparing pelvic fascia-sparing radical prostatectomy with conventional robotic-assisted prostatectomy: The PARTIAL trial

BackgroundPelvic fascia-sparing robotic-assisted radical prostatectomy (PFS-RARP) is a novel approach that spares the endopelvic fascia ventral to the prostate. The preservation of more native structures compared to conventional robotic-assisted radical prostatectomy (RARP) may lead to faster recovery of urinary function, fewer penile changes, and decreased inguinal hernia sequelae, but may have a higher risk for positive surgical margins and poorer cancer control. However, high-level evidence is absent. The PARTIAL trial is a surgical randomized controlled trial (RCT) aiming to bridge this evidence gap (NCT05155501). MethodsWe describe a prospective RCT with a projected enrollment of 600 men randomized to PFS-RARP vs. RARP. The primary outcome is cancer control (positive surgical margins and prostate-specific antigen failure) and secondary outcomes include health-related quality of life pertaining to urinary and sexual function, decision regret, and adverse events (30-day complications, inguinal hernias, penile shortening, and Peyronie's disease). The anticipated duration of trial participation is 24 months. Study participation is incentivized with the use of innovative methodologies such as a novel, two-stage informed consent and a validated web-based interface to monitor patient-reported symptoms and empower individuals to improve their recovery. ConclusionIf PFS-RARP is non-inferior to RARP in terms of cancer control and has better functional outcomes, it should be the surgical standard of care for men with localized prostate cancer. Using the innovative two-stage consent process, completion of the trial will not only provide much needed evidence on one of the most common cancer surgeries but also insight on improving surgical RCT methodology.Trial statusThis trial is registered at ClinicalTrials.gov (NCT05155501; first posted on December 13, 2021); Institutional approval number: WCM IRB # 21-07023781, BRANY's initial approval event ID # 186333. The trial is not yet recruiting.

The Importance of Pragmatic Study Design to the Scholarly Influence of Surgical Hip Fracture Randomized Controlled Trials

Surgical randomized controlled trials (RCTs) have potential drawbacks, leading some to question their role in filling the information gap in orthopaedic surgery. Pragmatism in study design was introduced to increase the clinical applicability of study results. The purpose of this study was to examine how pragmatism affects the scholarly influence of surgical RCTs. A search for surgical hip fracture-related RCTs published between 1995 and 2015 was done. Journal impact factor, citation number, research question, significance and type of outcome, number of centers involved, and the Pragmatic-Explanatory Continuum Indicator Summary-2 level of pragmatism score were recorded for each study. Scholarly influence was estimated by a study's inclusion into orthopaedic literature or guidelines or through the study's average yearly citation rate. One hundred sixty RCTs were included in the final analysis. A multivariate logistic regression identified large study sample size as the only predictor of an RCT being used in clinical guidance texts. Large sample size and multicenter RCTs were predictors of high yearly citation rates. The level of pragmatism in study design did not predict scholarly influence. Pragmatic design is not independently associated with increased scholarly influence; however, large study sample size was the most important study characteristic affecting scholarly influence.

Predictors of Increased Fragility Index Scores in Surgical Randomized Controlled Trials: An Umbrella Review.

The fragility index (FI) is defined as the minimum number of patients or subjects needed to switch experimental groups for statistical significance to be lost in a randomized control trial (RCT). This index is used to determine the robustness of a study's findings and recently as a measure of evaluating RCT quality. The objective of this review was to identify and describe published systematic reviews utilizing FI to evaluate surgical RCTs and to determine if there were common factors associated with higher FI values. Three databases (PubMed, MEDLINE [Ovid], Embase) were searched, followed by a subsequent abstract/title and full-text screening to yield 50 reviews of surgical RCTs. Authors, year of publication, name of journal, study design, number of RCTs, subspecialty, sample size, median FI, patients lost to follow-up, and associations between variables and FI scores were collected. Among 1007 of 2214 RCTs in 50 reviews reporting FI (median sample size 100), the pooled median FI was 3 (IQR: 1-7). Most reviews investigated orthopaedic surgery RCTs (n = 32). There was a moderate correlation between FI and p value (r = 0.-413), a mild correlation between FI and sample size (r = 0.188), and a mild correlation between FI and event number (r = 0.129). Based on a limited sample of systematic reviews, surgical RCT FI values are still low (2-5). Future RCTs in surgery require improvement to study design in order to increase the robustness of statistically significant findings.

Has the degree of outcome reporting bias in surgical randomized trials changed? A meta-regression analysis.

Outcome reporting bias in individual trials can compromise the validity of pooled estimates within systematic reviews. Recent strategies have attempted to address outcome reporting bias, which favours the full reporting of statistically significant outcomes over non-significant outcomes. We examined whether the association between full outcome reporting and statistical significance in surgical trials has changed from 2009 to 2019. We systematically searched for 350 surgical randomized controlled trials (RCTs) from 2009 and 350 surgical RCTs from 2019. Outcomes were classified as fully reported, partially reported, qualitatively reported or unreported. For each outcome, a contingency table was populated with full outcome reporting (yes/no) and statistical significance (yes/no). We combined odds ratios in random effects meta-analysis to estimate the association between full outcome reporting and statistical significance in 2009 compared with 2019. Twenty-eight percent of outcomes in 2009 were incompletely reported, compared with 30% in 2019. In 2009, significant outcomes were more likely to be fully reported than non-significant outcomes (OR=2.4, 95% CI 1.7-3.4, I2 = 35%), but the opposite association was seen in 2019 (OR=0.51, 95% CI 0.34-0.77, I2 = 43%). RCTs from 2019 were less likely to demonstrate outcome reporting bias favouring significant outcomes (OR=0.21, 95% CI 0.12-0.35, P < 0.001). Outcome reporting bias favouring the full reporting of significant over non-significant outcomes was demonstrated in 2009, but the opposite association was seen in 2019. There remains a high prevalence of incomplete outcome reporting. We recommend ongoing adherence to trial protocol guidelines to improve outcome reporting transparency and completeness.

OGC P35 Reporting of core outcomes in gastric cancer surgery trials over the past 25 years

Abstract Background Gastric cancer presents a significant health burden as the fifth most common malignancy and a significant cause of cancer-related mortality worldwide. A multi-modal approach has led to modest improvement in survival in recent years but surgery remains the cornerstone of curative treatment. A variety of surgical approaches are available, including newer minimally-invasive techniques: laparoscopic and robotic surgery. Determining the optimal approach requires appraisal of high-quality evidence, such as randomised controlled trials (RCTs) and systematic reviews with meta-analyses. However, heterogeneity within the literature hinders this, allowing little consensus. Surgical trials often report different outcomes and even the same outcome may be defined or measured differently. This challenge spans specialties and has been addressed by the development of core outcome sets (COS): a standardised set of outcomes that should be measured and reported as a minimum. The GASTROS group developed a COS for gastric cancer surgical trials. This process involved key stakeholders, patients and clinicians, better reflecting their priorities. These core outcomes are disease-free survival, disease-specific survival, surgery-related death, recurrence, completeness of tumour removal, overall quality of life, nutritional effects, and ‘serious’ adverse events. The aim of this review was to determine what proportion of trials report these core outcomes. Methods This review was an update of an earlier systematic review by our group spanning years 1996 to 2016. We systematically reviewed databases Evidence Based Medicine Reviews, MEDLINE, EMBASE and CINAHL from the years 2016 to 2021, specifically focusing on ‘type 2’ surgical RCTs: trials comparing two or more therapeutic surgical interventions. We separately reviewed systematic reviews of RCTs. The data extracted was outcomes reported, definitions, measuring tools used and when outcomes were measured. Results A total of 2213 abstracts were screened and 295 included. After full paper review this yielded 53 relevant articles. A further 47 articles from our previous systematic review were included. Twenty-two systematic reviews of RCTs were also identified. Of the 101 trials, no trial reported all core outcomes. Serious adverse events were reported by nearly all trials, 98.4%, but these were reported heterogeneously; as pooled and individual complications and graded using different severity tools. Other commonly reported outcomes were surgery-related death, 85.3%, and completeness of tumour resection, 73.8%. Survival outcomes were often reported as overall survival. Only 54.1% reported disease-free survival 54.10% and even fewer, 4.9%, reported disease-specific survival. Tumour recurrence was reported by just over a third of trials. Outcomes likely to be most important to patients, quality of life and nutritional effects, were reported least at 23% and 16.4% respectively. Over the past 25 years there has been no significant improvement in the reporting of core outcomes. An expectedly similar spread of outcome reporting was seen in systematic reviews of RCTs, with serious adverse events and surgery-related death reported most and quality of life, nutritional effects and survival outcomes reported least. Conclusions Surgical trials must report outcomes relevant to key stakeholders, importantly patients as well as surgeons. This review demonstrates that outcomes from the COS are poorly reported at present. The value of the COS needs to be disseminated to the wider research community in order to increase its uptake. As part of this, we intend to contact ongoing trials with the results of this review. Consistent reporting of core outcomes in future will allow for meaningful appraisal of evidence, ultimately improving clinical outcomes.

Examining the empirical evidence for IDEAL 2b studies: the effects of preceding prospective collaborative cohort studies on the quality and impact of subsequent randomized controlled trials of surgical innovations – protocol for a systematic review and case–control analysis

Randomized controlled trials (RCTs) in surgery face methodological challenges, which often result in low quality or failed trials. The Idea, Development, Exploration, Assessment and Long-term (IDEAL) framework proposes preliminary prospective...

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.

Alternative Randomized Trial Designs in Surgery: A Systematic Review.

Introduction:Randomized controlled trials (RCTs) yield the highest level of evidence but are notoriously difficult to perform in surgery. Surgical RCTs may be hampered by slow accrual, the surgical learning curve, and lack of financial support. Alternative RCT designs such as stepped-wedge randomized controlled trials (SW-RCTs), registry-based randomized controlled trials (RB-RCTs), and trials-within-cohorts (TwiCs) may overcome several of these difficulties. This review provides an overview of alternative RCT designs used in surgical research.Methods:We systematically searched PubMed, EMBASE, and Cochrane Central for surgical SW-RCTs, RB-RCTs, and TwiCs. A surgical RCT was defined as a randomized trial that studied interventions in patients undergoing general surgery, regardless of the affiliation of the corresponding author. Exponential regression analysis was performed to assess time trends.Results:Overall, 41 surgical RCTs using alternative designs were identified, including 17 published final RCT reports and 24 published protocols of ongoing RCTs. These included 25 SW-RCTs (61%), 13 RB-RCTs (32%), and 3 TwiCs (7%). Most of these RCTs were performed in Europe (63%) and within gastrointestinal/oncological surgery (41%). The total number of RCTs using alternative designs exponentially increased over the last 7 years (P<0.01), with 95% (n=39/41) of the total number published within this time frame. The most reported reasons for using alternative RCT designs were avoidance of contamination for SW-RCTs and generalizability of the trial population for RB-RCTs and TwiCs.Conclusions:Alternative RCT designs are increasingly used in surgical research, mostly in Europe and within gastrointestinal/oncological surgery. When adequately used, these alternative designs may overcome several difficulties associated with surgical RCTs.

Success rate of acquiring informed consent and barriers to participation in a randomized controlled trial of laparoscopic versus open surgery for non-curative stage IV colon cancer in Japan (JCOG1107).

Successful achievement of randomized controlled trials (RCTs) is dependent on the acquisition of informed consent (IC) from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed acquisition of IC. A 50-insitution RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage IV colon cancer (JCOG1107: UMIN-CTR 000000105). The success rate of obtaining IC was evaluated in eight periods between January 2013 and January 2021. In addition, reasons for failed acquisition of IC were identified from questionnaires. In total, 391 patients were informed of their eligibility for the trial, and 168 (42%) were randomly assigned to either the laparoscopic surgery group (n=84) or open surgery group (n=84). The success rate of IC acquisition ranged from 33 to 58% in three periods. The most common reasons for failed IC acquisition were the patients' preference for one approach of surgery based on recommendations from referring doctors and family members, and anxiety/unhappiness about randomization. The success rate of acquiring IC from patients for an RCT of laparoscopic versus open surgery for stage IV colon cancer was lower than the expected rate planned in the protocol. To obtain the planned rate, investigators should make efforts to inform patients and their families about the medical contributions a surgical RCT can make and recognize that the period in equipoise may be limited.

Staff training to improve participant recruitment into surgical randomised controlled trials: A feasibility study within a trial (SWAT) across four host trials simultaneously

Objective To test the feasibility of undertaking a simultaneous Study Within A Trial (SWAT) to train staff who recruit participants into surgical randomised controlled trials (RCTs), by assessing key uncertainties around recruitment, randomisation, intervention delivery and data collection. Study design and setting Twelve surgical RCTs were eligible. Interested sites (clusters) were randomised 1:1, with recruiting staff (surgeons and nurses) offered training or no training. The primary outcome was the feasibility of recruiting sites across multiple surgical trials simultaneously. Secondary outcomes included numbers/types of staff enrolled, attendance at training, training acceptability, confidence in recruiting and participant recruitment rates six months later. Results Four RCTs (33%) comprising 91 sites participated. Of these, 29 sites agreed to participate (32%) and were randomised to intervention (15 sites, 29 staff) or control (14 sites, 29 staff). Research nurses attended and found the training to be acceptable; no surgeons attended. In the intervention group, there was evidence of increased confidence when pre- and post- training scores were compared (mean difference in change 1.42; 95% CI 0.56, 2.27; p = 0.002). There was no effect on recruitment rate. Conclusion It was feasible to randomise sites across four surgical RCTs in a simultaneous SWAT design. However, as small numbers of trials and sites participated, and no surgeons attended training, strategies to improve these aspects are needed for future evaluations.

Special considerations in randomized trials investigating neonatal surgical treatments

Randomized controlled trials (RCTs) are challenging, but are the studies most likely to change practice and benefit patients. RCTs investigating neonatal surgical therapies are rare. The Necrotizing Enterocolitis Surgery Trial (NEST) was the first surgical RCT conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN), and multiple lessons were learned. NEST was conducted over a 7.25-year enrollment period and the primary outcome was death or neurodevelopmental impairment (NDI) at 18-22 months corrected age. Surgical investigators designing clinical trials involving neonatal surgical treatments have many considerations to include, including how to study eligible but non-randomized patients, heterogeneity of treatment effect, use of frequentist and Bayesian analyses, assessment of generalizability, and anticipating criticisms during peer review. Surgeons are encouraged to embrace these challenges and seek innovative methods to acquire evidence that will be used to improve patient outcomes.