Clinical Trials in Hepatopancreatobiliary Surgery: Assessing Trial Characteristics, Early Discontinuation, Result Reporting, and Publication

BACKGROUND: Hepatopancreaticobiliary (HPB) diseases carry high morbidity despite efforts aimed at their reduction. An assessment of their trial characteristics is paramount to determine trial design adequacy and highlight areas for improvement. As such, the aim of this study is to assess HPB surgery trial characteristics, summarize logistic, financial, and practical reasons behind early discontinuation, and propose potential interventions to prevent this in the future. METHODS: All clinical trials investigating HPB surgery registered on ClinicalTrials.gov from October 1st, 2007 (inclusive), to April 20th, 2021 (inclusive), were examined. Trial characteristics were collected including, but not limited to, study phase, duration, patient enrollment size, location, and study design. Peer-reviewed publications associated with the selected trials were also assessed to determine outcome reporting. RESULTS: A total of 1776 clinical trials conducted in 43 countries were identified, the majority of which were conducted in the USA. Of these trials, 32% were reported as completed whereas 12% were discontinued. The most common cause of trial discontinuation was low accrual, which was reported in 37% of terminated studies. These resulted in 413 published studies. Most trials had multiple assignment, randomized, or open-label designs. Treatment was the most common study objective (73%) with pharmacological therapy being the most commonly studied intervention. CONCLUSIONS: The main reasons for early discontinuation of clinical trials in HPB surgery are poor patient recruitment and inadequate funding. Improved trial design, recruitment strategies and increased funding are needed to prevent trial discontinuation and increase publication rates of HPB surgery clinical trials

Robotic Distal Pancreatectomy, a Novel Standard of Care?: Benchmark Values for Surgical Outcomes from 16 International Expert Centers

BACKGROUND AND OBJECTIVE: Robotic distal pancreatectomy (DP) is an emerging attractive approach, but its role compared to laparoscopic or open surgery remains unclear. Benchmark values are novel and objective tools for such comparisons. The aim of this study was to identify benchmark cutoffs for many outcome parameters for DP with or without splenectomy beyond the learning curve. METHODS: This study analyzed outcomes from international expert centers from patients undergoing robotic DP for malignant or benign lesions. After excluding the first 10 cases in each center to reduce the effect of the learning curve, consecutive patients were included from the start of robotic DP up to June 2020. Benchmark patients had no significant comorbidities. Benchmark cutoff values were derived from the 75 th or the 25 th percentile of the median values of all benchmark centers. Benchmark values were compared to a laparoscopic control group from four high-volume centers and published open DP landmark series. RESULTS: Sixteen centers contributed 755 cases, whereof 345 benchmark patients (46%) were included the analysis. Benchmark cut-offs included: operation time ≤300min, conversion rate ≤3%, clinically relevant POPF ≤32%, 3 months major complication rate ≤26.7% and lymph node retrieval ≥9. The CCI ® at 3 months was ≤8.7 without deterioration thereafter. Compared to robotic DP, laparoscopy had significantly higher conversion rates (5x) and overall complications, while open DP was associated with more blood loss and longer hospital stay. CONCLUSION: This first benchmark study demonstrates that robotic DP provides superior postoperative outcomes compared to laparoscopic and open DP. Robotic DP may be expected to become the approach of choice in minimally invasive DP