Development and validation of an intraoperative bleeding severity scale for use in clinical studies of hemostatic agents.

BACKGROUND: Clinical studies investigating topical hemostatic agents have not used standardized definitions for intraoperative bleeding. The Food and Drug Administration has recently sought use of a validated, clinician-reported scale to standardized bleeding sites in these clinical studies. The intent of a scale is to reduce patient risk, generate labeling claims, and allow comparisons among study results. We describe the development and validation of an intraoperative bleeding severity scale. METHODS: A concept phase defined the framework of the scale. A feasibility and validation phase investigated the usability, clarity, relevance, and reliability (ie, intra- and interobserver concordance) among surgeons and surgical specialties as required by the Food and Drug Administration for the validation of a clinician-reported scale. Data were collected using an online tool. A total of 144 surgeons participated in the 3 phases. RESULTS: The scale developed during the concept phase achieved an average intraobserver concordance of 0.97 and an interobserver concordance of 0.89 in the feasibility phase (N = 33); a concordance of 1.0 is perfect. The scale was refined and then achieved an average intraobserver concordance of 0.98 and an interobserver concordance of 0.91 in the validation phase with unanimous agreement by surgeons from multiple surgical specialties that the scale can be implemented into clinical studies (N = 102). CONCLUSION: This study validated an intraoperative bleeding severity scale for use in clinical studies investigating hemostatic agents. The scale was usable, clear, and clinically relevant with excellent reliability. The scale fulfills requirements of the Food and Drug Administration for a clinician-reported scale and can be used to generate clinically meaningful labeling claims.

Arbaclofen placarbil in GERD: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: It has been shown that arbaclofen placarbil (AP) inhibits reflux in gastroesophageal reflux disease (GERD) following single oral dosing. This study evaluated the efficacy and safety of AP over 4 weeks in subjects with symptomatic GERD. METHODS: One hundred fifty-six subjects with heartburn and/or regurgitation ≥3 days/week and either no history of taking proton pump inhibitors (PPIs naive, n=58) or at least partial symptom response to PPI therapy (PPI responsive, n=98) were enrolled in this randomized, double-blind, placebo-controlled trial. All GERD therapies including PPIs were discontinued 2 weeks before randomization to AP 20, 40, or 60 mg daily, 30 mg twice daily, or placebo for 4 weeks. Randomization was stratified by prior PPI use. RESULTS: In the primary analysis, change from baseline in weekly heartburn events between AP and placebo for the entire study group was not statistically significant. However, a significant interaction was observed between prior PPI use and response to AP treatment. In pre-planned secondary analyses of the PPI-responsive subgroup, percent reductions from baseline in weekly heartburn events were greater for each AP dose vs. placebo (P<0.05) and the percentage of subjects who reported complete resolution of heartburn during week 4 was higher in each AP treatment group (21, 28, 30, and 50% for AP 20, 40, 60 mg daily, and 30 mg twice daily, respectively) compared with placebo (6%) (P<0.05 for 30 mg twice daily). Corresponding analyses of the PPI-naive subgroup showed no significant differences. AP was well tolerated; withdrawals due to adverse events were infrequent. CONCLUSIONS: AP was not superior to placebo in reducing the number of weekly heartburn events over 4 weeks in the primary analysis of the entire study population. Exploratory subgroup analyses suggest that response to PPI treatment before the study was associated with a response to AP treatment.