Current Standard Operating Procedures Research Articles

Quality assurance metrics in clinical trial conduct.

274 Background: Quality assurance (QA) in clinical trials is a safeguard against non-compliance, which impacts patient safety and data integrity. On an institutional level, compiling quality findings provides insight to gaps within existing processes, protocol compliance, and educational content. A QA metrics methodology has been implemented, which is streamlined with the ICH-GCP, and institutional Standard Operating Procedures (SOPs) and policies. Methods: Individual findings are assigned an alphanumerical code, based on severity and category, and a reference for each Quality Assurance Review (QAR). Annual data is tracked for all QAR findings. Different data sets are created to allow for analysis of quality gaps and quality changes over time. Results are used in the creation or revision of educational content, SOPs, and to drive process improvement. Results: To date, a total of 1608 QAR observations between 2014 and mid-2015 have been coded and tracked across 22 studies. Areas of quality gaps, such as most-cited categories (e.g. 27% in Source Documentation and 13% in Regulatory) and references (e.g. 30% on SOPs and 14% on guidelines), are communicated to the Quality and Education team regularly and incorporated into training content. This has also prompted the development of new SOPs, processes, and research tools, after which QA metrics continues to be used to monitor program wide quality improvement. For example, following the implementation of Electronic Source Documentation, the proportion of findings on delays in Adverse Event sign off has seen a decline. For individual QARs, a personalized trends summary is provided to the study team with an overview of the quality of the study conduct. The report displays the distribution of findings across different categories and severity levels. Lastly, quality metrics has increased the efficiency of tracking and reporting program wide QA activity. Conclusions: The regular analysis of quality metrics has proven to be a pivotal step in the Quality Management Cycle. It presents a quick snap shot of the quality of individual research studies under review. When implemented on an institutional scale, it offers valuable feedback on the current SOPs, processes, and training content.

Ultrasound use in Kent, Surrey and Sussex Air Ambulance: a survey

Kent Surrey and Sussex (KSS) air ambulance utilize a portable ultrasound (US) scanning machine with a high frequency linear probe. Current standard operating procedure (SOP) states it should be used as an adjunct to chest assessment. Formal indications for pre-hospital US use are not yet established despite many theoretical uses in the literature.

Cyphenothrin Flea and Tick Squeeze-On for Dogs: Evaluation of Potential Health Risks Based on the Results of Observational Biological Monitoring

An observational biomonitoring study was conducted involving adults and children in households that purchased and applied a cyphenothrin-containing spot-on product for dogs as part of their normal pet care practices. The 3- to 6-yr-old children had greater exposure than the adult applicators in the same house, 3.8 and 0.6 μg/kg body weight, respectively. The mean measured values in children were 13-fold lower than those estimated using the U.S. Environmental Protection Agency (EPA) current standard operating procedures (SOP) for pet products (assuming 5% dermal absorption), although the maximum absorbed dosage of one child on one day was equivalent to the default value derived from the SOPs. With regard to potential human health risks, it can be concluded that despite the inherent conservatism in both the exposure and toxicology data, the margins of exposure (MOE) were consistently greater than 100 for average, 95th percentile, and maximum exposures. More specifically, the results of this study demonstrated that the MOE were consistently greater than 1,000 for mean exposures and exceeded 100 for 95th percentile and maximum measured exposures, which clearly indicates a reasonable certainty of no harm when using the cyphenothrin spot-on products. It is also noteworthy that Sergeant’s spot-on products containing cyphenothrin currently sold in the United States have lower weight percentages of active ingredient and lower applied amounts than those used by all but two of the participant households in this study.

Substantiation of 25 kGy radiation sterilization dose for banked air dried amniotic membrane and evaluation of personnel skill in influencing finished product bioburden

Preparation of amniotic membrane (AM) by air drying method followed by radiation sterilization is simple and valuable approach; sterility and quality of the final AM product are depending on the quality management system at the tissue bank. Validation and substantiation of radiation sterilization dose (RSD) for tissue allografts is an essential step for the development and validation of the standard operating procedures (SOP). Application of SOP is perfectly relying on trained staff. Skills differences among personnel involved in AM preparation could have an effect on microbiological quality of the finished product and subsequently on the RSD required. AM were processed by four different couples of the tissue bank technicians. The AM grafts were randomly selected and subjected to bioburden test to validate and substantiate the 25 kGy RSD. Bioburden test for AM grafts were also useful to evaluate the skill of the tissue bank technicians and thus, to validate the current SOP for air dried AM. Moreover, the effect of placental source on bioburden counts on AM grafts was assessed. Substantiation of the 25 kGy RSD at a sterility assurance level of 10−1, and sample item portion = 1, was carried out using Method VDmax25 of the International Organization for Standardization, document no. 11137-2 (ISO in Sterilization of healthcare products—radiation—part 2: establishing the sterilization dose, Method VDmax—substantiation of 25 kGy or 15 kGy as the sterilization dose, International Standard Organization, 2006). The results showed that there were no significant differences in the bioburdens of the four batches (α = 1 %), this means no significant differences in the skill of the four couples of the tissue bank technicians in terms of their ability to process AM according to the air dried AM SOP. The 25 kGy RSD was validated and substantiated as a valid sterilization dose for the AM prepared with the current established SOP at the Biotechnology Research Center experimental tissue bank. The donor’s type of delivery, normal or caesarean, showed no significant effect on the levels of microbial counts on the tested AMs (α = 1 %).

Automatically determining accidental falls in field surveying: A case study of integrating accelerometer determination and image recognition

Nowadays, many construction engineering-related students participate in field surveying. For practical exercises, since some students are injured in accidental falls, protecting their health and safety is of utmost importance. After investigating the current standard operating procedure (SOP) regarding accident management and common information techniques (e.g., object tracking, vision monitoring, geographic information), this study recognized a major problem. Unclear on-site status during fall accidents affects faculty advisors to respond to emergency situations. Therefore, this study constructed a safety practicum information system. The applied accelerometer determination-based mechanism automatically monitored the behavior of on-site students via mobile phones. For occurring accidental falls, the used image recognition-based mechanism visually highlighted the falling students through surveillance facilities. Relying on the test results in a surveying practicum, this study indicated that the safety practicum information system actively informed faculty advisors of accidental falls and clearly detailed on-site status (i.e., accident sites and falling students). Consequently, this study is a useful reference for similar applications in promoting safety education and training in field surveying and the construction industry.

Abstract A214: Creating clinical target validation groups via quality assured transfer of robust clinical pharmacodynamic (PD) assays from the NCI: Improved performance of the Top1 immunoassay for analysis of tumor biopsies.

Abstract Robust pharmacodynamic (PD) assay results are valuable for informing go/no[[Unable to Display Character: ‐]]go decisions about preclinical and clinical development of new agents and for identifying optimal combinations of targeted agents. The NCI's Division of Cancer Treatment and Diagnosis (DCTD) develops and validates PD assays to obtain accurate information about target engagement in first-in-human clinical trials. The Pharmacodynamic Assay Development and Implementation Section (PADIS) and National Clinical Target Validation Laboratory (NCTVL) were established at the Frederick National Laboratory to create robust PD assays for the research community by validating analytical performance, demonstrating fitness-for[[Unable to Display Character: ‐]]purpose for the clinical assay protocol in preclinical xenograft models, and finalizing companion standard operating procedures (SOPs) for clinical specimen handling and processing. Proven clinical assays are transferred from the NCI to requesting sites in academia and industry through laboratory[[Unable to Display Character: ‐]]based certification and training, centralized access to current SOPs, assistance with assay transfer, and participation in the assay's Quality Assurance Plan. A quantitative immunoassay for intra-tumoral topoisomerase 1 (Top1) levels that allows direct measurement of target engagement is one such assay. Initial evaluation of the Top1 immunoassay using tumor needle biopsies was complicated by high baseline variability in clinical samples and lower than expected protein yields. Top1 levels in baseline biopsies from multiple patients were near the assay's lower limit of quantitation, and therefore did not provide an adequate threshold to quantify decreased Top1 levels following Top1 inhibitor treatment. A more efficient extraction method was developed and validated with xenograft tumors that allowed for larger volumes of lysate to be loaded into the immunoassay without matrix interference. Analysis of second pass biopsies from a subset of the same patients was used to confirm that the new assay procedure increased assay sensitivity by ∼3-fold. Based on this evaluation, the revised set of SOPs is estimated to increase the proportion of clinical biopsies that will be evaluable with the assay to > 80%, compared to approximately 65% with the original procedure. PD assay training on the validated Top1-Immunoassay SOPs is now being offered by NCI's Division of Cancer Treatment and Diagnosis. Funded by NCI Contract No HHSN261200800001E. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A214. Citation Format: Ralph E. Parchment, Katherine Ferry-Galow, Jay Ji, Yiping Zhang, Thomas D. Pfister, Robert J. Kinders, Yvonne A. Evrard, Shivaani Kummar, Joseph E. Tomaszewski, James H. Doroshow. Creating clinical target validation groups via quality assured transfer of robust clinical pharmacodynamic (PD) assays from the NCI: Improved performance of the Top1 immunoassay for analysis of tumor biopsies. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A214.

Abstract 1186: Creating clinical target validation groups via quality assured transfer of robust clinical pharmacodynamic (PD) assays from the NCI: clinical implementation of a HIF1α immunoassay in tumor biopsies.

Abstract Robust pharmacodynamic (PD) assay results are valuable for informing go/no-go decisions about preclinical and clinical development of new agents and for identifying optimal combinations of targeted agents. The NCI's Division of Cancer Treatment and Diagnosis (DCTD) develops and validates PD assays to obtain accurate information about target engagement in first-in-human clinical trials. The Pharmacodynamic Assay Development and Implementation Section (PADIS) and National Clinical Target Validation Laboratory (NCTVL) were established at SAIC-Frederick to develop and validate PD assays by validating analytical performance, demonstrating fitness-for-purpose for the clinical protocol, and finalizing companion standard operating procedures (SOPs) for specimen handling and processing. Proven clinical assays are transferred from the NCI to requesting sites in academia and industry through laboratory-based certification and training, centralized access to current SOPs, assistance with assay transfer, and participation in the assay's Quality Assurance Plan. One such validated assay is the HIF1α Immunoassay, which is currently in clinical evaluation at NCTVL. Procedures to clinically implement HIF1α analysis in tumor biopsies from patients treated with angiogenesis inhibitors required consideration of many factors including the low abundance and oxygen sensitivity of the analyte. A customized extraction process for HIF1α was developed and optimized using mouse xenograft biopsies. Use of a customized extraction buffer containing 2-hydroxyglutarate, which was degassed to minimize dissolved oxygen, was shown to improve analyte recovery. Optimized extraction procedures also include use of an automated ceramic bead homogenizer to improve both the efficiency and reproducibility of extraction of HIF1α over sonication. The immunoassay procedure uses lyophilized reagents from a commercially available kit and a modified procedure together with quality control specimens that serve to qualify the performance of each run. Finally, pre-defined data analyses and quality control evaluation criteria are used to perform a semi-automated process to analyze data and evaluate acceptability of performance for both the assay run and individual clinical specimens. In total, five SOPs have been developed to define procedures from collection and freezing of the needle biopsies in the radiology suite to data analyses and reporting. Together, these defined procedures are being used to perform PD analyses as key parts of two clinical trial evaluations at the NCI and will be launched to the community once clinical utility is demonstrated. Funded by NCI Contract No HHSN261200800001E. Citation Format: Ralph E. Parchment, Robert J. Kinders, Sook Ryun Park, Katherine V. Ferry-Galow, Yvonne A. Evrard, Jiuping Ji, Shivaani Kummar, Joseph E. Tomaszewski, James H. Doroshow. Creating clinical target validation groups via quality assured transfer of robust clinical pharmacodynamic (PD) assays from the NCI: clinical implementation of a HIF1α immunoassay in tumor biopsies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1186. doi:10.1158/1538-7445.AM2013-1186

Cloning cattle.

Over the past six years, hundreds of apparently normal calves have been cloned worldwide from bovine somatic donor cells. However, these surviving animals represent less than 5% of all cloned embryos transferred into recipient cows. Most of the remaining 95% die at various stages of development from a predictable pattern of placental and fetal abnormalities, collectively referred to as the "cloning-syndrome." The low efficiency seriously limits commercial applicability and ethical acceptance of somatic cloning and enforces the development of improved cloning methods. In this paper, we describe our current standard operating procedure (SOP) for cattle cloning using zona-free nuclear transfer. Following this SOP, the output of viable and healthy calves at weaning is about 9% of embryos transferred. Better standardization of cloning protocols across and within research groups is needed to separate technical from biological factors underlying low cloning efficiency.