Sensitivity and robustness

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

The following quote follows on from that on missing data  

In certain cases more specific guidance is given. The FDA, for example, discuss various sensitivity analyses in relation to the analysis of progression-free survival in FDA (2005) Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologies . 

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In order to achieve flexibility, sensitivity, and robustness, I plot departures of the variables of interest from specified reference values. A bar projecting to the right of the middle of the panel indicates a value larger than the reference value. A bar projecting to the left indicates a smaller value. The length of the bar is proportional to... 

Molecular mechanisms underlying the early- and late-phase expressions of LTP. While opening the NMDA receptors is crucial for coincidence-detection, the sensitivity and robustness of coincidence-detection is not solely determined by the opening time-window. It is dependent on at least three other features summation of the opening duration, the peak amplitude and proper intracellular signal transduction. 

In addition, many other aspects must be considered when developing a catalytic reaction for industrial use these include catalyst separation, stability and poisoning, handling problems, space-time yield, process sensitivity and robustness, toxicity of metals and reagent, and safety aspects, as well as the need for high-pressure equipment. 

The official EPA method for monitoring carbamate pesticides (Method 531.1) has seldom been used in Europe, although it is a highly sensitive and robust method. 

A lot of sensitivity and robustness can be gained by carefully designing the injection procedure, so do put some time and effort in this during method development. Do not forget to test injection parameters during the robustness evaluation. There are plenty of examples for... 

Atmospheric pressure chemical ionization (APCI) interface for LC-MS became a reality at the end of the 1980s [42]. Its sensitivity and robustness were immediately impressive in comparison with all the other interface mechanisms present on the market. 

Typical parameters that are generally considered most important for validation of analytical methods are specificity, selectivity, precision, accuracy, extraction recovery, calibration curve, linearity, working range, detection limit, quantification limit, sensitivity, and robustness. 

Matrix effects (ME), caused by co-eluting endogenous and exogenous matrix components, significantly affect the efficiency and reproducibility of the ionization process of target analytes. This phenomenon represents a major concern for LC-MS bioana-lytical method precision, accuracy, sensitivity, and robustness. Amongst the atmospheric pressure ionization interfaces used in LC-MS systems, ESI source is more prone to signal alteration (ion suppression or enhancement) due to matrix. Therefore, careful evaluation and correction for ME must be considered particularly with ESI-MS. 

Carboxylic groups positioned at the open ends of SWCNTs were coupled to amines to form AFM probes with basic or hydrophobic functionalities by Wong et al. [117] (Scheme 1.8). Force titrations recorded between the ends of the SWCNT-AFM tips and hydroxy-terminated SAMs confirmed the chemical sensitivity and robustness of the AFM tips. Images recorded on patterned SAM allowed real molecular-resolution imaging [117]. 

The example described above supports the general statement made in the introduction that EIAs which have to fulfill high quality requirements with regard to sensitivity and robustness likewise need sophisticated techniques and/or automation. 

Immunochemical methods can be considered exact, fast, sensitive, and robust. However, they still show decreased analytical specificity because of the... 

Finally, the selected compounds are purchased or synthesized and then tested. If the goal is to identify weakly binding small molecules, it is important to ensure that the biological assay is sensitive and robust enough to pick up these molecules. Measurements using 100-1000 pM concentration of the ligand frequently cause problems due to the limited solubility of the ligands in water. To compensate for this, the assay is often carried out in the presence of 1-5% dimethyl sulfoxide (DMSO) (see, e.g.. Ref. 14). 

The early developed LC/MS interfaces as described above have played important roles in the evolution of LC/MS interfaces. However, their apphcability, sensitivity, and robustness are very limited. The overwhelming popularity of LC/MS today is largely due to the development of atmospheric pressure ionization (API) interfaces, including ESI and APCI. 

P. Sajonz, T. K. Natishan, Y. Wu, N. T. McGachy, and D. DeTora, Development and validation of a sensitive and robust wipe-test method for the detection and quantification of the antibiotic Ertapenem and its primary degradates in a pharmaceutical manufacturing environment, /. Liq. Chromatogr. Relat. Technol. 28 (2005), 713-725. 

Some of the methods that are currently available and that are developing rapidly include passive sampling, and rapid measurement techniques based on developments in combinations of biotechnological and biophysical systems to provide increased sensitivity and robustness. 

Sensors and other devices were developed on optical fibers by incorporating metallic and semiconducting nanoparticles on the surface of optical fibers. Several ways of forming sensitive and robust chemical sensors based on plasmon resonances of metallic islands and nanoparticles were demonstrated. Development of in-line optical fiber stractmes, involving single mode or multimode optical fibers fused to an arrangement of coreless... 

Zhao C, Vinh TN, McManus K, et al. Identification of the most sensitive and robust immunohistochemical markers in different categories of ovarian sex cord-stromal tumors. Am J Surg Pathol. 2009 33 354-366. 

The focus is on the outcome, rather than on the method used to achieve that outcome. An acceptable level of performance is defined for a particular analysis using criteria such as accuracy, precision, detection limits, specificity, sensitivity, and robustness. If a laboratory can demonstrate that it meets the criteria, the method becomes an accepted one. See Chapter 4 for more details on getting a method validated. 

The reproducibility, sensitivity, and robustness of a fully online SPE and LC/PAD (SAMOS) system have been demonstrated for monitoring pesticides in surface water. The robustness of the SAMOS system was illustrated by the fact that no major problem was encountered in the course of over 1000 determinations. 

Golla, R., and R. Seethala. 2004. A sensitive and robust high-throughput electrochemilumines-cence assay for rat insulin. Journal of Biomolecular Screening 9 62-70. 

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