Addressing the quality of submissions to ClinicalTrials.gov for registration and results posting: The use of a checklist.

BACKGROUND: US Federal regulations since the late 1990s have required registration of some clinical trials and submission of results for some of these trials on a public registry, ClinicalTrials.gov. The quality of the submissions made to ClinicalTrials.gov determines the duration of the Quality Control review, whether the submission will pass the review (success), and how many review cycles it will take for a study to be posted. Success rate for all results submitted to ClinicalTrials.gov is less than 25%. To increase the success of investigators' submissions and meet the requirements of registration and submission of results in a timely fashion, the Johns Hopkins ClinicalTrials.gov Program implemented a policy to review all studies for quality before submission. To standardize our review for quality, minimize inter-reviewer variability, and have a tool for training new staff, we developed a checklist. METHODS: The Program staff learned from major comments received from ClinicalTrials.gov and also reviewed the Protocol Registration and Results System review criteria for registration and results to fully understand how to prepare studies to pass Quality Control review. These were summarized into bulleted points and incorporated into a checklist used by Program staff to review studies before submission. RESULTS: In the period before the introduction of the checklist, 107 studies were submitted for registration with a 45% (48/107) success rate, a mean (SD) of 18.9 (26.72) days in review, and 1.74 (0.78) submission cycles. Results for 44 records were submitted with 11% (5/44) success rate, 115.80 (129.33) days in review, and 2.23 (0.68) submission cycles. In the period after the checklist, 104 studies were submitted for registration with 80% (83/104) success rate, 2.12 (3.85) days in review, and 1.22 (0.46) submission cycles. Results for 22 records were submitted with 41% (9/22) success rate, 39.27 (19.84) days in review, and 1.64 (0.58) submission cycles. Of the 44 results submitted prior to the checklist, 30 were Applicable or Probable Applicable Clinical Trials, with 10% (3/30) being posted within 30 days as required of the National Institutes of Health. For the 22 results submitted after the checklist, 17 were Applicable or Probable Applicable Clinical Trials, with 47% (8/17) being posted within 30 days of submission. These pre- and post-checklist differences were statistically significant improvements. CONCLUSION: The checklist has substantially improved our success rate and contributed to a reduction in the review days and number of review cycles. If Academic Medical Centers and industry will adopt or create a similar checklist to review their studies before submission, the quality of the submissions can be improved and the duration of review can be minimized.

Analysis of risk factors for morbidity in children undergoing the Kasai procedure for biliary atresia.

OBJECTIVE: To evaluate the perioperative risk factors for 30-day complications of the Kasai procedure in a large, cross-institutional, modern dataset. STUDY DESIGN: The 2012-2015 National Surgical Quality Improvement Program Pediatric database was used to identify patients undergoing the Kasai procedure. Patients' characteristics were compared by perioperative blood transfusions and 30-day outcomes, including complications, reoperations, and readmissions. Multivariable logistic regression was used to identify risk factors predictive of outcomes. Propensity matching was performed for perioperative blood transfusions to evaluate its effect on outcomes. RESULTS: 190 children were included with average age of 62 days. Major cardiac risk factors were seen in 6.3%. Perioperative blood transfusions occurred in 32.1%. The 30-day post-operative complication rate was 15.8%, reoperation 6.8%, and readmission 15.3%. After multivariate analysis, perioperative blood transfusions (OR 3.94; p < 0.01) and major cardiac risk factors (OR 7.82; p < 0.01) were found to increase the risk of a complication. Perioperative blood transfusion (OR 4.71; p = 0.01) was associated with an increased risk of reoperation. Readmission risk was increased by prematurity (OR 3.88; p = 0.04) and 30-day complication event (OR 4.09; p = 0.01). After propensity matching, perioperative blood transfusion was associated with an increase in complications (p < 0.01) and length of stay (p < 0.01). CONCLUSION: Major cardiac risk factors and perioperative blood transfusions increase the risk of post-operative complications in children undergoing the Kasai procedure. Further research is warranted in the perioperative use of blood transfusions in this population. LEVEL OF EVIDENCE: IV.

Creating a Program to Support Registering and Reporting Clinical Trials at Johns Hopkins University.

PROBLEM: The Food and Drug Administration Amendments Act of 2007 (FDAAA) and the National Institutes of Health (NIH) require that many clinical trials register and report results on ClinicalTrials.gov. Noncompliance with these policies denies research participants and scientists access to potentially relevant findings and could lead to monetary penalties or loss of funding. After discovering hundreds of potentially noncompliant trials affiliated with the institution, the Johns Hopkins University School of Medicine (JHUSOM) sought to develop a program to support research teams with registration and reporting requirements. APPROACH: JHUSOM conducted a baseline assessment of institutional compliance in 2015, launched the ClinicalTrials.gov Program in June 2016, and expanded the program to the Sidney Kimmel Comprehensive Cancer Center in April 2018. The program is innovative in its comprehensive approach, and it was among the first to bring a large number of trials into compliance. OUTCOMES: From September 2015 to September 2020, JHUSOM brought completed and ongoing trials into compliance with FDAAA and NIH policies and maintained almost perfect compliance for new trials. During this period, the proportion of trials potentially noncompliant with the FDAAA decreased from 44% (339/774) to 2% (32/1,304). NEXT STEPS: JHUSOM continues to develop and evaluate tools and procedures that facilitate trial registration and results reporting. In collaboration with other academic medical centers, JHUSOM plans to share resources and to identify and disseminate best practices. This report identifies practical lessons for institutions that might develop similar programs.

Minimally invasive repair of pectus excavatum: Analysis of the NSQIP database and the use of thoracoscopy.

BACKGROUND: The minimally invasive repair of pectus excavatum (MIRPE) has been widely accepted and has become a viable alternative to the open Ravitch technique. MIRPE has evolved over time with some advocating that a safe repair can be accomplished without direct visualization utilizing thoracoscopy. The MIRPE with and without a thoracoscopic approach has not been previously analyzed from a nationwide database to determine differences in safety and short-term outcomes. METHODS: The American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) 2012-2015 database was used in identifying patients that had MIRPE using Current Procedural Terminology (CPT) codes and ICD-9CM/ICD-10CM postoperative diagnosis codes. Outcomes of interest were readmissions, reoperations, complications, cardiothoracic injury, operative time, and duration of hospital stay after surgery for MIRPE with and without thoracoscopy. Descriptive statistics, simple and multivariable logistic regressions, Fisher's exact, and Wilcoxon rank sum test were used to determine any differences in 30-day postoperative outcomes. RESULTS: There were 1569 MIRPE cases included. 15.9% (N=249) of MIRPE were done without thoracoscopy. There were no significant differences with the use of thoracoscopy compared to without thoracoscopy in the rate of readmissions (2.5 vs 4.8%; p=0.06), reoperations (1.4 vs 2.0%; p=0.57), postoperative complications (2.6% vs 3.2%; p=0.52), and cardiothoracic injuries (0.2% vs 0.0%; p=1.00). Unadjusted odds ratios (ORs) for readmission and reoperation comparing MIRPE with thoracoscopy to MIRPE without thoracoscopy were 0.51 (p<0.05) and 0.71 (p=0.50), respectively. Adjusted ORs were 0.49 (p=0.04) and 0.71 (p=0.50), respectively. There were no reported deaths, but two cardiothoracic injuries were recorded in the group with thoracoscopy. MIRPE with thoracoscopy was associated with longer operative time (mean 13.0min; p=0.00) and longer hospital stay (mean 0.37days; p<0.01) compared to MIRPE without thoracoscopy. No data were available for the severity of the pectus defect. CONCLUSION: MIRPE has a low adverse event rate with no difference in reoperations, postoperative complications, and cardiothoracic injuries with or without the use of thoracoscopy. There may be a higher rate of readmissions in the nonthoracoscopic group. While the technique used remains the surgeon's decision, the use of thoracoscopy may be unnecessary and is at an added cost. TYPE OF STUDY: Treatment study (retrospective comparative study). LEVEL OF EVIDENCE: Level III.

Minding the Gaps in Cancer Pain Management Education: A Multicenter Study of Clinical Residents and Fellows in a Low- Versus High-Resource Setting.

PURPOSE: Inadequate pain management training has been reported as a major cause of undertreatment of cancer pain. Yet, past research has not comprehensively compared the quality of cancer pain management education among physicians in training in high-resource countries (HRCs) with those in low-resource countries (LRCs). The purpose of this study was to examine and compare gaps in cancer pain management education among physician trainees in an HRC (United States) versus an LRC (Ghana). METHODS: A cross section of physicians at four major academic medical centers completed surveys about the adequacy of cancer pain training. Participation in the study was completely voluntary, and paper or online surveys were completed anonymously. RESULTS: The response rate was 60% (N = 120). Major gaps were identified in cancer pain management education across the spectrum of medical school training. Training was rated as inadequate (by approximately 80% of trainees), although approximately 10% more trainees in HRCs versus LRCs felt this way; 35% said residency training was inadequate in both settings; and 50% in LRCs versus 44% in HRCs said fellowship training was less than good. On the basis of the lowest group means, the three key areas of perceived deficits included interventional pain procedures (2.34 ± 1.12), palliative care interventions (2.39 ± 1.12), and managing procedural and postoperative pain (2.94 ± 0.97), with significant differences in the distribution of deficits in 15 cancer-pain competencies between LRCs and HRCs (P < .05). CONCLUSION: This study identifies priority areas that could be targeted synergistically by LRCs and HRCs to advance cancer care globally. The findings underscore differential opportunities to broaden and improve competencies in cancer pain management via exchange training, in which physicians from HRCs spend time in LRCs and vice versa.