Observational bias

Preferably the transferring lab provides a sample which has already been analyzed, with the certainty of the results being known (41). This can be either a reference sample or a sample spiked to simulate the analyte. An alternative approach is to compare the test results with those made using a technique of known accuracy. Measurements of the sample are made at the extremes of the method as well as the midpoint. The cause of any observed bias, the statistical difference between the known sample value and the measured value, should be determined and eliminated (42). When properly transferred, the method allows for statistical comparison of the results between the labs to confirm the success of the transfer. 

The quality of differential staining will determine the ease and accuracy of SCE scoring, and, to eliminate variation, results from different observers should occasionally be compared. Furthermore, to avoid observer bias, scorers should have slides from different treatment groups equally distributed among them, as with all cytogenetic studies. 

Observational bias of convalescence (e.g., severe pain causing insomnia may require morphine causing compensatory hypersomnia in excess of that caused by morphine alone). 

Observational bias by halo effects. Perception of an ADR may be swamped by the symptoms of the disease, thus as the disease symptoms resolve the ADR becomes apparent. 

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). 

Thus, Lind showed the importance of the comparative trial and Evans and Hoyle showed the importance of the placebo effect in evaluating drug response. Gold et at. then showed the importance of observer bias and introduced the concept of the double-blind study in 1937 in a study of treatments for angina patients. They wrote ... 

This option assumes a comparable or even standard placebo response rate for historical data and the current trial. The historical improvement rate (on placebo or without any treatment) is then used for purposes of comparison with results of subsequent non-placebo-controlled studies involving the same investigator and protocol design but different drugs. For historical placebo response data it is recommended that a small placebo treatment arm is used for safety data purposes and to avoid observer bias although this proposal may resolve or diminish some ethical concerns, it raises a number of scientific problems ... 

Today, clinical trials must adhere to nationally and internationally agreed codes of good clinical practice, which define ethical and scientific standards. Good clinical trial design and conduct should apply scientific methods. Skilful analysis can never correct for poor design. The purpose of the trial should be defined and specific hypotheses stated in the written study protocol, which will also include details of how the trial will be conducted. Errors in the data have two components, purely random errors and systemic errors or bias, which are not a consequence of chance alone. Randomisation of subjects is important both to avoid observer bias and to prevent or minimise the influence of unknown factors that might influence the results. 

Filters are required for dissolution sample collection. It is necessary to filter out the excipents that may cause interference in sample analysis. Appropriate recovery studies should be performed and documented. Any observed bias should be addressed. Filtration must be performed when the sample aliquots are withdrawn, not at a later time. 

Reduces selection bias and observer bias (nonrandom error). 

The sex-linked recessive-lethal test is a highly objective scoring procedure with minimal observer bias. Scoring of a few thousand F2 cultures per day by an adequately trained technician is routine. 

The importance of observer bias was addressed in 1937 when the concept of the double-blind study was introduced, also in a study of treatments of angina patients. The authors indicate in their methods that In a further attempt to eliminate the possibility of bias, the questioner usually refrained from informing himself as to the agent that had been issued until after the patient s appraisal of the period had been obtained. ... 

Differential misclassification occurs when the classification of disease is dependent on the exposure status or the classification of exposure is dependent on the disease status. Differential misclassification can bias the RR in either direction, and often the direction is unknown. Some examples of differential misclassification of exposure are recall bias and observer bias. Recall bias, which is limited to case-control studies, occurs when the cases remember exposure differently than healthy controls this type of bias usually results in finding a greater effect than what is real. Observer bias can occur if the observers, such as study interviewers, incorrectly assign exposure because they know the outcome status of an individual, or it can occur in the follow-up of disease if the observer knows the exposure status of the subject. Ideally, the observer should be blind to the outcome or exposure status of the study subjects. 

Study Design Factors Affecting Exposure Variability 33 Specific Requirements for Guideline Studies 34 Label Compliance 34 Sample Size 34 Observational Bias 35 Motivational Bias 35... 

When evaluating data from the Harvey (1952) study, Johns (1952) reported on the occurrence of miosis in exposed individuals. Regression analysis of 150 observations, including 55 controls, indicated that the concentration at which a 50% decrease in pupil diameter would be attained was approximately 4.1 mg-min/m, with 90% confidence limits of about 2.7 and 5.7 mg-min/m. Johns (1952) defined mild miosis as a decrease of 1 to 2 mm in pupil diameter, which usually disappeared within 24 h. While mild miosis as defined above was observed in some subjects at the lowest Ct tested (Ct = 1.0 mg-min/m ), other subjects exhibited mean maximal pupil decreases of < 1 mm, indicating attainment of a response threshold at this level of exposure. Untreated controls exhibited a pupil diameter decrease of >0.33 mm Johns (1952) attributed this difference to observer bias and pointed out that there was still a relative difference between the control group and the exposed groups. 

Placebo effect or placebo response has been referred to as the lie that heals.It is the change in patient condition due to a symbolic intervention and increased awareness (e.g., consultation, procedure) rather than pharmacologic or physiologic intervention. It is used to eliminate observational bias in many clinical trials. " Elements of placebo response exist in almost every patient encounter. Variables that have been shown to affect patient outcomes... 

It is true that the AutoAnalyzer sample probe cannot differentiate in its action between a standard, a control, and a patient s specimen, and it might be argued that no observer bias will enter into the reading and recording of the peaks on the chart record. The AutoAnalyzer standard curve itself, however, cannot be used for control purposes unless, as with manual methods, it clearly reveals that the overall system is functioning so imperfectly (e.g., showing such loss of sensitivity) that analyses cannot be interpreted. If, as an independent check of the instrument s performance, one of the standards is itself subsequently analyzed as a true control solution, this will at most serve to show that the within-batch... 

However, the treatments were similar in patients or physicians perception of benefit over baseline and proportions of withdrawals due to lack of efficacy. However, the lack of blinding may have introduced patient and observer bias. ... 

If repeated measures are performed, a predefined percentage of the diluted samples also needs to meet the specified 20% criterion (e.g., at least two-thirds). The precision (CV) of the cumulative back-calculated concentrations should also be within 20%. If a systematic deviation is found after dilution, additional investigation may be warranted to explain the observed bias. Dilutional QC samples are utilized sometimes during in-study analyses. In these situations, it is important to have a priori criteria for run acceptance. 

The vibration sensation test is purported to be a quantitative measure of perception of a vibrating stimulus. It is used to see if a person can volitionally tell the examiner when a stimulus is first perceived. It is intended to reveal impairment in the ability of a peripheral nerve to conduct an impulse. If the subject has a high threshold for this test, it is suggested by the amount of time the subject requires for acknowledging his/her perception of the stimulus. This testis subject to embellishment by the examinee and to observer bias by the test administrator. Such impairments detected on screening tests such as this must be correlated with other more objective tests for evidence of peripheral neuropathy such as nerve conduction velocities, tendon reflex responses, and patterns of sensory loss detected by pin prick perception. 

Estimation of the enthalpy of activation of a chemical reaction is not very difficult because we know that we are making more energy available as we heat a reaction mixture, and if we determine how much faster it gets as more energy becomes available, it is not particularly hard to convert this into a measure of the enthalpy of activation. Experiment shows that many reactions, whether uncatalyzed or catalyzed by enzymes or other catalysts, increase their rates by about a factor of two for each 10°C increase in temperature, for temperatures around the everyday temperatures at which we live. This could mean that many reactions of all kinds have similar enthalpies of activation, which would have important implications about the sort of events that are taking place at the level of the atoms involved. Flowever, it could also just mean that the reactions that behave in this way are the ones that are easiest to study at convenient temperatures, and if so we may be talking about observer bias rather than anything more fundamental about the world. 

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