A retrospective study: screening failure analysis of 1,058 healthy volunteers in phase I clinical trials.

BACKGROUND: Phase I clinical trials play an important role in the follow-up clinical trials and even the drug registration and marketing. However, the screening success ratio in phase I clinical trials is low, and the screening process of the trials consumes a significant amount of human and material resources, but the results are unsatisfactory. At present, there is no large sample data analysis for screening failure in phase I clinical trials. It is therefore urgent to find the reasons for screening failure in phase I clinical trials. METHODS: A total of 1,058 healthy volunteers who failed the screening in 11 phase I clinical trials were retrospectively collected from October 2018 to June 2021 in Cangzhou Central Hospital. Data on all participants who failed screening for the study were analyzed (descriptive analysis) and reasons for their non-randomization were classified, as well as the differences of main screening failures between four years. RESULTS: A total of 1,466 healthy volunteers were enrolled in the 11 trials, and among them 1,058 subjects failed the screening. The total screening success ratio of our study was only 27.8%, the highest being 38.5% and the lowest being 18.2%. The top 3 reasons for non-randomization were abnormalities in blood biochemistry tests (23.3%), vital sign examination (19.3%), and electrocardiogram (ECG) (16.6%). Abnormal blood biochemistry was the main reason between 2019 and 2021, except for 2018 in which it was the second reason. CONCLUSIONS: Screening failure is a burdensome issue which various clinical trial sites must contend with. Investigators can still take some effective measures by strengthening the in-depth understanding of informed consent, paying attention to the quality of test samples, a correcting definition of no clinical significance (NCS). Also, low-cost and non-invasive examinations can be arranged first to better protect the volunteers and reduce the screening costs of clinical trials. To our delight, we find people's attention to the annual physical examination may help to screen healthy volunteers. Overall, this study shows that it is crucial and professional to develop a screening plan to minimize the resultant impact on timelines and budgets of phase I clinical trials enrolling healthy volunteers.

Favorable Effects of Endoscopic Ligation Combined with Drugs on Rebleeding and Mortality in Cirrhotic Patients: A Network Meta-Analysis.

BACKGROUND: To assess the effects of combination therapies (endoscopic plus drug[s], drug combinations) on variceal/any-cause rebleeding and mortality among cirrhotic patients with one previous episode of variceal hemorrhage. SUMMARY: We searched PubMed, Embase, Cochrane Library, and Web of Science for eligible studies. We included 26 randomized controlled trials involving 2,536 adults using OR to measure the effects. Endoscopic variceal ligation (EVL) plus nadolol ranked first for reducing recurrent bleeds. Both EVL + nadolol and EVL + drugs (nadolol, sucralfate) decreased the risk of any-cause rebleeding than EVL alone (OR 0.34, 95% CI 0.12-0.97; OR 0.40, 95% CI 0.18-0.88, respectively). Meanwhile, EVL + drugs ranked first lowering mortality rates (P-score >0.85) with a marginal superiority over EVL alone (OR 0.52, 95% CI 0.26-1.01). Beta-blockers with isosorbide mononitrate (ISMN) also reached a marginal superiority (OR 0.78, 95% CI 0.56-1.09) for improving mortality. Key Messages: Our findings indicated that EVL + nadolol might be the preferred choice to cirrhotic patients with one previous episode of variceal hemorrhage for preventing rebleeding. EVL + nadolol + sucralfate and beta-blockers + ISMN may be potential alternatives to improve mortality. Further, well-controlled studies are warranted to compare the promising combination therapies.