Common use of Materials and Methods Clause in Contracts

Materials and Methods. The Ethics Committee of Xxxx University approved the study protocol. Informed consent was obtained from all participants or participant´s guardian, after the nature of the procedures had been fully explained. This is a prospective observational study of real-time live ultrasound examinations of adnexal masses. Consecutive patients referred for an ultrasound examination and found to have an adnexal mass judged to need surgical removal were scanned according to the research protocol by sonologist 1 (PS) as part of the clinical ultrasound examination. A second ultrasound examination was carried out before surgery by sonologist 2 (LV). Both examiners used the standardized IOTA examination and measurement technique and the IOTA terminology (11) to describe their ultrasound findings and noted their results in a dedicated paper form. Sonologist 2 was blinded to the results of sonologist 1. Information on the clinical variables included in LR1 and LR2 (personal history of ovarian cancer, current hormonal therapy, age of the patient), was obtained at the preoperative ultrasound examination by sonologist 2. All patients were operated on within 90 days after the preoperative ultrasound examination performed by sonologist 2. The excised tissues underwent histological examination and tumors were classified according to the criteria recommended by the International Federation of Gynecology and Obstetrics (16). Borderline tumors were classified as malignant. The patients were examined in the lithotomy position with an empty urinary bladder (11). Abdominal ultrasound examination was added when needed. The ultrasound variables assessed with regard to interobserver reproducibility are shown in Table 1. The size of the lesion and that of its largest solid component were measured (largest diameter and mean of three orthogonal diameters) using calipers on the frozen ultrasound image. A color score was assigned on the basis of subjective assessment of the color content of the tumor scan at power Doppler ultrasound examination. A color score of 1 indicates absence of color Doppler signals, a color score of 2 a minimal amount of color Doppler signals, a color score of 3 a moderate amount of color Doppler signals and a color score of 4 a large amount of color Doppler signals in the tumor (11). The ultrasound systems used were GE Voluson 730 Expert or GE Voluson E8 (GE Healthcare, Xxxx, Austria) with a 5–9-MHz transvaginal transducer. For power Doppler ultrasound examinations the following settings were used: for the Voluson 730 Expert system frequency 6-9 ( normal ) MHz; pulse repetition frequency 0.6 kHz; gain 0.8; wall motion filter low 1 (40 Hz), and for Voluson E8 frequency 6-9 ( normal ) MHz, pulse repetition frequency 0.6 kHz, gain -4.0, wall motion filter low 1 (40 Hz). Statistical analysis The IOTA3 study screen (astraia GMBH, Munich, Germany) was used to calculate the risk of malignancy according to LR1. Weighted Kappa indices were calculated using the statistical program Stata, Version 10.1 for Windows (StataCorp LP, College Station, TX, USA). For all other statistical calculations including calculation of the risk of malignancy when using LR2 we used the Statistical Package for the Social Sciences (SPSS program, IBM corp., New York, NY, USA, PASW version 18.0). Inter-observer agreement in the assessment of categorical variables was estimated by calculating the percentage agreement. Xxxxx'x kappa was used to estimate by how much the observed agreement exceeded that expected by chance (17). Weighted kappa values are presented where appropriate (18). It has been suggested that Kappa values >0.81 indicate very good agreement beyond chance, kappa values between 0.61 and 0.80 good agreement beyond chance, kappa values between 0.41 and 0.60 moderate agreement beyond chance, kappa values between 0.21 and 0.40 fair agreement beyond chance, and kappa values <0.20 poor agreement beyond chance (19). Inter-observer reproducibility of measurement results, including the calculated risks of malignancy using LR1 and LR2, was described as the difference between two measurement results. The differences between the measured values were plotted against the mean of the two measurements (Xxxxx-Xxxxxx plots) to assess the relationship between the differences and the magnitude of the measurements (20). Systematic bias between two measurements was estimated by calculating the 95% confidence interval (CI) of the mean difference (mean difference ±2 SE). If zero lay within this interval, no bias was assumed to exist between the two measurements. Inter-observer agreement was expressed as the mean difference and limits of agreement (20). Ninety-five percent of differences between any future measurements are estimated to fall between the lower and upper limit of agreement. Inter-observer reliability of measurements results was estimated by calculating the intra-class correlation coefficient (ICC) using analysis of variance (two way random model - absolute agreement; this allows generalization of the results to a population of observers). The ICC indicates the proportion of the total variance in measurement results that can be explained by differences between the individuals examined. It depends both on the magnitude of measurement errors and the true heterogeneity in the population in which measurements are made. The more variable the population investigated, the greater the ICC and the less variable the population, the smaller the ICC (21). It has been suggested that ICC values >0.90 are needed for a test to be used in clinical practice (22). The sensitivity and specificity with regard to malignancy of LR1 and LR2, calculated using the information of sonologist 1 and 2, were calculated.