Reproducibility

Abstract: The work mainly focused on a validation of the method for determining the content of salicylic acid and individual unknown impurities in new pharmaceutical product-tablets containing: 75, 100 or 150 mg of acetylsalicylic acid and glycine in the amount of 40 mg for each dosage. The separation of the components was carried out by means of HPLC, using a Waters Symmetry C18 column (4.6 × 250 mm, 5 μm) as the stationary phase. The mobile phase consisted of a mixture of 85% orthophosphoric acid, acetonitrile and purified water (2:400:600 V/V/V). Detection was carried out at a wavelength of 237 nm, with a constant flow rate of 1.0 ml min-1. In order to verify the method, linearity, precision (repeatability and reproducibility), accuracy, specificity, range, robustness, system precision, stability of the test and standard solution, limit of quantification and forced degradation were determined. Validation tests were performed in accordance with ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) guidelines. The method was validated successfully. It was confirmed that the method in a tested range of 0.005-0.40% salicylic acid with respect to acetylsalicylic acid content is linear, precise and accurate.

Abstract: Reproducibility and validity are prerequisites for a useful clinical scale. We therefore prospectively tested the reproducibility and validity of the New York Heart Association criteria and the Canadian Cardiovascular Society criteria for the assessment of cardiac functional class and compared these criteria with a new Specific Activity Scale based on the metabolic costs of specific activities. The New York Heart Association estimates made by two physicians had a reproducibility of only 56%, and only 51% of the estimates agreed with treadmill exercise performance. Functional estimates based on the Canadian Cardiovascular Society criteria were significantly more reproducible (73%), but not significantly more valid. The Specific Activity Scale was as reproducible as the Canadian Cardiovascular Society criteria, and its 68% validity was significantly higher than the validities of the other systems. The easily administered Specific Activity Scale was equally reproducible and valid when used by a nonphysician. It was especially better than the other systems for the evaluation of true class II patients and was significantly less likely to underestimate treadmill performance. Although no set of questions can perfectly predict exercise tolerance, the Specific Activity Scale deserves wider prospective testing.

Abstract: Reproducibility is essential to reliable scientific discovery in high-throughput experiments. In this work we propose a unified approach to measure the reproducibility of findings identified from replicate experiments and identify putative discoveries using reproducibility. Unlike the usual scalar measures of reproducibility, our approach creates a curve, which quantitatively assesses when the findings are no longer consistent across replicates. Our curve is fitted by a copula mixture model, from which we derive a quantitative reproducibility score, which we call the “irreproducible discovery rate” (IDR) analogous to the FDR. This score can be computed at each set of paired replicate ranks and permits the principled setting of thresholds both for assessing reproducibility and combining replicates. Since our approach permits an arbitrary scale for each replicate, it provides useful descriptive measures in a wide variety of situations to be explored. We study the performance of the algorithm using simulations and give a heuristic analysis of its theoretical properties. We demonstrate the effectiveness of our method in a ChIP-seq experiment.