Reporting the analysis

ICH E3(1995) Structure and Content of Clinical Study Reports sets down the structure, down to the numbering of the sections and precisely what goes in each of those sections, required within the regulatory setting for reporting each study. Medical writers will work with statisticians to put these reports together. 

ICH E9 (1998) Note for Guidance on Statistical Principles for Clinical Trials  

There will be a number of areas of the clinical report where the statistician will contribute but, in particular, Section 11 Efficacy Evaluation and Section 12 Safety Evaluation will require statistical oversight. Section 16 of the report contains the Appendices and Subsection 16.1.9 entitled Documentation of Statistical Methods will usually be written by the trial statistician. 

Within Section 11, Subsection 11.4.2 entitled Statistical/Analytical Issues contains a series of items covering many of the areas of complexity within most statistical analyses  

Each of these will clearly require input from the statistician. 

---

Beyer (B8) has recently reported the analysis of arc-imaging-furnace data obtained on a variety of composite-propellant formulations. He showed the data could be correlated by the expression... 

Applications Quantitative dry ashing (typically at 800 °C to 1200°C for at least 8h), followed by acid dissolution and subsequent measurement of metals in an aqueous solution, is often a difficult task, as such treatment frequently results in loss of analyte (e.g. in the cases of Cd, Zn and P because of their volatility). Nagourney and Madan [20] have compared the ashing/acid dissolution and direct organic solubilisation procedures for stabiliser analysis for the determination of phosphorous in tri-(2,4-di-t-butylphenyl)phosphite. Dry ashing is of limited value for polymer analysis. Crompton [21] has reported the analysis of Li, Na, V and Cu in polyolefins. Similarly, for the determination of A1 and V catalyst residues in polyalkenes and polyalkene copolymers, the sample was ignited and the ash dissolved in acids V5+ was determined photo-absorptiometrically and Al3+ by complexometric titration [22]. 

Fuoco et al. [539] has reported the analysis of priority pollutants in seawater using online supercritical fluid chromatography, cryotrap gas chromatogra-phy-mass spectrometry. Using this system polynuclear aromatic hydrocarbons and polychlorobiphenyls were measured in seawater with recoveries better than 75%. 

Many studies have reported the analysis of estrogens and progestogens in WW and other water samples, but for solid samples, little is found in the literature. This chapter briefly reviews the methods described for WW samples and discuss the very few methods used up to now to analyze solid samples (sediments, sludge, and soil). For more detailed data we refer to the reviews ... 

In early 2007, the EMEA reported the analysis of GMP deficiencies in its document entitled Good Manufacturing Practice An Analysis of Regulatory Inspection Findings in the Centralised Procedure. It detailed the deficiencies reported in 435 inspections of manufacturers of medicinal products and starting materials in the European Union and third countries in the period 1995 to 2005. Altogether there were 9465 deficiencies, of which 193 were critical (2%), 989 major (10%), and 8283 (88%) others. The top 20 deficiencies are presented in Table 10.1. 

Studies by Farina and associates (1992) reported the analysis of buspirone and related compounds using a Cl 8 analytical column with an elution solvent containing a phosphate buffer with an ion-pairing reagent (sodium dodecyl sulphate or SDS) and acetonitrile run in gradient mode. Detection was measured using fluorescence with excitation and emission wavelengths of 237 and 374 nm respectively. Bianchi and Caccia... 

Small molecule crystallographers are familiar with these concepts, since it is routine to measure data at low temperature to improve precision by reduction of thermal motion, and structures are often done at multiple temperatures to assess the origins of disorder in atomic positions. Albertsson et al. (1979) have reported the analysis of the crystal structure of Z)(-l-)-tartaric acid at 295, 160, 105, and 35 K. Figure 22 shows the individual isotropic. S-factors for the atoms in the structure at each of these temperatures the smooth variation of B with T is apparent. Below 105 K, B is essentially identical for all atoms and is also temperature independent the value of B = 0.7 agrees well with the expected zero-point vibradonal value. However, even for this simple structure, not all of the atoms show B vs T behavior at high temperature which extrapolates to 0 A at 0 K. 

The analysis of soils and plant material are common examples used to demonstrate ICP applications. Dahlquist and Knoll(43) compared the preparation and ICP analyses of botanicals (16 elements) and soils (11 elements) with few exceptions the ICP values for the CII botanicals were in excellent agreement with the assigned values, and the soil analyses were in excellent agreement with FAA analyses of soil digests. )ones( 4) reported the analysis of 17 elements in plant material and soils but confirmation of the two analyses was not given. Alder, et. aJ.(75) describe the unique analysis of ammonia-nitrogen in soils by gas evolution into an ICP no interferences were observed from the concomitants evaluated and acceptable recoveries were obtained. Irons et. al.(76) compared the ICP analyses of 13 elements in NBS orchard leaves and bovine liver to the data obtained by FAA and energy dispersive x-ray. 

Cyclopentanes, Iridoids.— Two papers report the analysis and separation of iri-doids. - ... 

Yamada et al. reported the analysis of serum benzoate and hippurate in normal human and patients with chronic liver disease by using a HPLC method [40], The conditions for the analysis are given in Table 8. 

El-gizawy reported the analysis of diloxanide furoate in its dosage forms by a HPLC method [40]. Furazol tablets containing 200 mg of metronidazole and 250 mg of diloxanide furoate were treated with 50 mL of methanol, sonicated for 10 minutes, and diluted to 100 mL with methanol. A portion of the resulting solution was centrifuged, and a 20 pL portion of the clear supernatant solution diluted to 10 mL with the mobile phase. This process yielded a final analyte concentration equivalent to 5 pg/mL. 20 pL aliquots of the solution were annualized by HPLC using a stainless steel column (10 cm x 4.6 mm) packed with Cyclobond I. The mobile phase consisted of 13 7 0.05 M phosphate buffer (pH 7) methanol (flow rate of 1 mL/min), and detection was performed at 254 nm. 

The temperature and frequency dependence of the complex dielectric permittivity a for both 2-chlorocydohexyi isobutyrate (CCHI) and poly(2-chlorocyclohexyl acrylate) (PCCHA) is reported. The analysis of the dielectric results in terms of the electric modulus suggests that whereas the conductive processes in CCHI are produced only by free charges, the conductivity observed in PCCHA involves both free charges and interfacial phenomena. The 4x4 RIS scheme presented which accounts for two rotational states about the CH-CO bonds of the side group reproduces the intramolecular correlation coefficient of the polymer. 

Tsai and Sue [177] designed a micro-RT-PCR chip for quantitative detection of tumor viruses. The authors integrated test sample reservoirs, RT-PCR meanders, and electrophoresis on an SU-8-based monolithic chip. Kolivoska et al. [178] reported the analysis of human rhinovirus serotype 2 (HRV2) on a... 

Barrosa (133) has reported the analysis of a mixture of pyridoxine and isoniazid in tablet formulation. Pyridoxine is determined by differential spectrophotometry at 324 nm. 

Hooijschuur et al. (54) also reported the analysis of the hydrolysis products of sulfur mustard homologues (11), using micro-LC/ESI/MS (triple quadrupole) and micro-LC/FPD in sulfur mode. To improve sensitivity, large-volume injection was used with peak compression by adding suitable coeluting alcohols. LC employed a 0.28-mm ID packed C18 column, eluted isocratically with water-methanol (80 20 v/v)-0.2% formic acid, flow rate 6 xl/min. Spectra were dominated by MH+, [MH — H20]+,... 

D Agostino and coworkers (92) reported the analysis of several biologically active peptides, such... 

Some 20 years ago Schramel [85] reported the analysis of milk by ICP-AES just by diluting the samples in water and using direct nebulization. It was eventually proved, though, that in ICP-AES the direct dilution of milk samples with... 

As a result, most of the pirate boxes have long ceased to be a hazard in clinical trials. Certainly, the real shockers — changing to a one-sided test or selectively reporting the analysis of one sub-group — are dead and buried. 

Recently we have reported the analysis of crystal structures of single crystals of DyMnOj [3] and LnMnOj (Ln = Nd, Sm, Eu and Gd) [4] using a four cycle X-ray diffractometer. In this study the growth of single crystals of PrMnOj and TbMnOj and the refined crystal structures are described. Since praseodymium and terbium have several valence states, some considerations about the atmospheric conditions are necessary. 

Reactions of Mns have also been reported. The analysis of the observed emissions served essentially to unravel the complex spectroscopy of the manganese halides rather than investigating the dynamics of the corresponding reactions. 

Ninety-three percent of laboratories submitted their data to either (or both) the ExPASy or Propsearch Internet sites. One laboratory used its own identification software and 4 did not attempt identification. Forty-one facilities reported the analysis of a calibration protein of their choice that was analyzed along with the experimental sample. Both the methods of analysis and search programs contain many variables, and it is necessary that all data be treated similarly to allow comparisons. To allow for comprehensive comparisons, the AAA committee recalculated the mol % and error data as described in Materials and Methods and submitted all data sets to both search programs. For the ExPASy site, data were submitted with and without the calibration protein to determine the benefit of a calibrant. The conclusions drawn below are from the committee s resubmissions. 

Barnes and coworkers pioneered in this area. They reported the analysis of diflubenzuron in mushrooms [39], and of diflubenzuron and clofentezine in various fmit drinks [73], and the development of a multiresidue study for ten pesticides in fmit, involving ionization polarity switching in LC-APCI-MS [123]. In these studies, significant attention is paid to matrix-dependent ion suppression or enhancement effects (Ch. 6.7), which is observed even in APCI. Matrix effects in food analysis must be studied in detail for each fmit or vegetable. Obviously, optimization of the sample pretreatment procedures plays an important role in method development for pesticide residue analysis in food. 

Ferguson et al. [40] reported the analysis of APEO metabolites in estuarine water and sediments. Compounds like nonylphenols, octylphenols, their mono-, di-, and triethoxylates, halogenated nonylphenols, and NPEC were found in water samples after SPE. Individual APEO metabolite concentrations of 1-320 ng/1 in water and 5-2000 ng/g in sediment were found. 

Petrovic and Barcelo [33] reported the analysis of AEO, APEO, and their degradation products in sewage sludge. Ultrasonic solvent extraction with 70% methanol in dichloromethane was applied to achieve recoveries better than 84%. SPE was performed for clean-up and fractionation into two fractions. In the sewage sludge samples analysed, 25-600 pg/g nonylphenol, 10-190 pg/g AEO, and 2-135 pg/g NPEO were detected. 

---