Control of bias

A description of the experimental design, including the methods for the control of bias. 

Specimen sampling procedures, including randomization techniques (for control of bias), methods and equipment to be used ... 

The "feedback loop in the analytical approach is maintained by a quality assurance program (Figure 15.1), whose objective is to control systematic and random sources of error.The underlying assumption of a quality assurance program is that results obtained when an analytical system is in statistical control are free of bias and are characterized by well-defined confidence intervals. When used properly, a quality assurance program identifies the practices necessary to bring a system into statistical control, allows us to determine if the system remains in statistical control, and suggests a course of corrective action when the system has fallen out of statistical control. 

Statistical Control. Statistical quahty control (SQC) is the apphcation of statistical techniques to analytical data. Statistical process control (SPC) is the real-time apphcation of statistics to process or equipment performance. Apphed to QC lab instmmentation or methods, SPC can demonstrate the stabihty and precision of the measurement technique. The SQC of lot data can be used to show the stabihty of the production process. Without such evidence of statistical control, the quahty of the lab data is unknown and can result in production challenging adverse test results. Also, without control, measurement bias cannot be determined and the results derived from different labs cannot be compared (27). 

Amplitude of controlled variable Output amplitude limits Cross sectional area of valve Cross sectional area of tank Controller output bias Bottoms flow rate Limit on control Controlled variable Concentration of A Discharge coefficient Inlet concentration Limit on control move Specific heat of liquid Integration constant Heat capacity of reactants Valve flow coefficient Distillate flow rate Limit on output Decoupler transfer function Error... 

Quality control elements required by the instrumental analyzer method include analyzer calibration error ( 2 percent of instrument span allowed) verifying the absence of bias introduced by the sampling system (less than 5 percent of span for zero and upscale cah-bration gases) and verification of zero and calibration drift over the test period (less than 3 percent of span of the period of each rim). 

Prospective sources include encounter data, which may or may not be contained in EHRs patient data input and randomized, prospective clinical trials. Advantages of prospective sources to inform interactive software include the ability to control and monitor the circumstances of data collection reduction (as a result of randomization) of sources of bias potential minimization of missing data potential to modify design of data collection ability to verify data accuracy and ability to validate and further test assumptions and modify existing programs. 

Randomization refers to the process of assigning subjects by chance to treatments. This eliminates known and unknown sources of bias that could interfere with accurate interpretation of the study results. The main problem that randomization is intended to prevent is bias in subject selection. Without randomization, investigators might consciously or subconsciously select subjects to receive the active treatment, which, they believe, are most likely to respond. History shows that uncontrolled studies are much more likely to provide exaggerated support in favor of the effectiveness of a treatment than properly controlled trials (Pocock, 1983). Therefore, whenever possible, randomization should be used in order to help insure a fair and unbiased evaluation of the intervention under study. 

Theoretically IQC should be the front-line approach to quality. If a method has been adequately validated and shown to meet the requirements of the user and kept in analytical control with IQC to detect intrusion of bias or imprecision, then the EQA needs to provide the occasional, independent, objective reassurance. In practice however, the EQA is likely to play an equal role with IQC, both in confirming problems brought to the attention of the analyst by the IQC and in stimulating further action. 

Lithography With the STM Electrochemical Techniques. The nonuniform current density distribution generated by an STM tip has also been exploited for electrochemical surface modification schemes. These applications are treated in this paper as distinct from true in situ STM imaging because the electrochemical modification of a substrate does not a priori necessitate subsequent imaging with the STM. To date, all electrochemical modification experiments in which the tip has served as the counter electrode, the STM has been operated in a two-electrode mode, with the substrate surface acting as the working electrode. The tip-sample bias is typically adjusted to drive electrochemical reactions at both the sample surface and the STM tip. Because it has as yet been impossible to maintain feedback control of the z-piezo (tip-substrate distance) in the presence of significant faradaic current (vide infra), all electrochemical STM modification experiments to date have been performed in the absence of such feedback control. 

Using the unique four-electrode STM described above, Bard and coworkers (Lev, 0. Fan, F-R.F. Bard, A.J. J. Electroanal. Chem.. submitted) have obtained the first images of electrode surfaces under potentiostatic control. The current-bias relationships obtained for reduced and anodically passivated nickel surfaces revealed that the exponential current-distance relationship expected for a tunneling-dominated current was not observed at the oxide-covered surfaces. On this basis, the authors concluded that the nickel oxide layer was electrically insulating, and was greater than ca. 10 A in thickness. Because accurate potential control of the substrate surface is difficult in a conventional, two-electrode STM configuration, the ability to decouple the tip-substrate bias from... 

Friedland, B. (1969). Treatment of bias in recursive filtering. IEEE Trans. Autom. Control AC-14,359-367. Gelb, A. (1974). Applied Optimal Estimation. MIT Academic Press, Cambridge, MA. 

The absence of observed activity may represent either a true or false negative effect. If an assay is valid for the particular test article and fails to indicate activity, it is an appropriate indicator of future events (Green, 1997). However, if the assay is insensitive or incapable of response, the test represents a form of bias, albeit unconscious. Many biological products demonstrate a specificity of response that limits the utility of commonly employed safety studies. Specificity for many biologies arises from both their physicochemical properties and their similarity to endogenous substances that are regulated in a carefully controlled manner. To... 

Bias. (1) A point of view that prevents impartial judgement on issues relating to that point of view. Clinical trials attempt to control this through double blinding. (2) Any tendency for a value to deviate in one direction from the tme value. Statisticians attempt to prevent this type of bias by various techniques, including randomization. 

It will be seen that, as in the case of the LED, control of the bias voltage gives simple modulation of the laser output intensity. This is particularly useful in phase-modulation fluorometry. However, a measure of the late awareness of the advantages of IR techniques in fluorescence is that only recently has this approach been applied to the study of aromatic fluorophores. Thompson et al.(51) have combined modulated diode laser excitation at 670 and 791 nm with a commercial fluorimeter in order to measure the fluorescence lifetimes of some common carbocyanine dyes. Modulation frequencies up to 300 MHz were used in conjunction with a Hamamatsu R928 photomultipler for detecting the fluorescence. Figure 12.18 shows typical phase-modulation data taken from their work, the form of the frequency response curves is as shown in Figure 12.2 which describes the response to a monoexponential fluorescence decay. 

In addition, a bipotentiostat is used to control the tip potential with respect to the surface and independent of control of the surface potential with respect to the reference electrode. The tip potential E, is given by E, = Eg + E , where Eg is the bias potential that generates the tnnneling current between tip and surface, and E (a vital variable not typical of other applications of STM and AFM) is the potential of the surface relative to the reference electrode. 

Another practice is to blind the trial, which means that the subjects are not privy to whether they receive the placebo or drug. In some trials, even the investigator is unaware of whether the subject is in the control or active group. This is called a double-blind trial. The rationale is to ehminate the possibihty of bias affecting the trial results. 

Information bias (observation bias) Occurs when there are quality (accuracy) problems in the collection, recording, coding, or analysis of data among comparison groups. Interviewers might, e.g., interview the cases with more diligence than they interview the control, or a person with a disease may recall previous exposures better than persons who are healthy (this type of bias is called recall bias). 

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