Combined-Indications Significance Level of Multiple Related Indications Developed Simultaneously.

BACKGROUND: Typically, regulatory requirements include 2 confirmatory studies, each at a 1-sided .025 significance level, for a medicine to be approved for a specific indication. When the same medicine has been approved in related indications, 1 confirmatory study at a 1-sided .025 significance level could constitute adequate evidence of efficacy for a new indication. METHODS: This article does not contain any studies with human or animal subjects performed by any of the authors. For multiple related indications developed simultaneously to constitute sufficient evidence of clinical efficacy, the combined-studies significance level can be set at the same level as if those indications are developed sequentially. RESULTS: This article establishes possible strategies to develop a few related indications at the same time for marketing registration approval, maintaining a desired combined-studies significance level; for example, 1-sided .0000156 for 2 indications, with 1 option having each indication assessed with 1 confirmatory study at .00395 significance level. CONCLUSION: It is possible to develop a few indications at the same time for marketing registration approval, where the combinedstudies significance level is less stringent than that of the usual paradigm with 2 confirmatory studies each at 1-sided .025 significance level for every indication.

Effect of oxygen-absorbing packaging on the shelf life of a liquid-based component of military operational rations.

Oxygen within the sealed package can reduce the quality of liquid-based food products with high oil content such as hot-filled meal-ready-to-eat (MRE) cheese spread, a component of military operational rations. The aim of this study was to test a novel oxygen absorber-containing laminate material and its ability to maintain and/or extend shelf life of a cheese-spread MRE item. An iron-based oxygen absorber (ABSO(2)RB(R)) activated by moisture was incorporated into the laminate and used to pack hot-filled cheese spread MREs. The kinetics of oxygen absorption due to humidity and temperature were characterized and peel tests performed to ensure pouch seal integrity. Accelerated shelf-life tests of ABSO(2)RB and regular MRE pouches without the O(2)-absorber were conducted for 3 mo at 51.7 degrees C (125 degrees F), and 6 mo at 37.8 degrees C (100 degrees F) by measuring oxygen concentration (Mocon O(2)-analyzer), microbiological, and physicochemical quality characteristics, including color, texture, moisture, free fatty acid (FFA), pH, water activity, and vitamins and A. Pouches stored at 26.7 degrees C (80 degrees F) for 12 mo served as calibrated controls. Consumer tests were conducted in-house and a confirmatory sensory test was conducted at Natick by a trained panel using a 9-point hedonic scale. ABSO(2)RB-laminates maintain the same seal integrity and strength as those of the control samples. The headspace oxygen concentrations in these pouches reached (P < 0.05) < 0.5% in 11 d of storage at 26.7 degrees C (80 degrees F) and remained below this level throughout the storage period (1 y). No microbial growth (aerobic, coliforms, yeast, and molds) was detected (P < 0.05) for both packages. Overall, the ABSO(2)RB-pouches indicate an improved reduction in oxygen and vitamin C retention compared with MRE controls and maintained product quality (physicochemical and organoleptic). ABSO(2)RB-laminates met the accelerated shelf-life requirement of 1 mo at 51.7 degrees C (125 degrees F), and 6 mo at 37.8 degrees C (100 degrees F). This study clearly shows the benefits of using active packaging technology on retaining nutrition and prolonging shelf life of high-fat, liquid content MRE items.