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Improving efficiency of a small forensic DNA laboratory: validation of robotic assays and evaluation of microcapillary array device.

AIM: To present validation studies performed for the implementation of existing and new technologies to increase the efficiency in the forensic DNA Section of the Palm Beach County Sheriff's Office (PBSO) Crime Laboratory. METHODS: Using federally funded grants, internal support, and an external Process Mapping Team, the PBSO collaborated with forensic vendors, universities, and other forensic laboratories to enhance DNA testing procedures, including validation of the DNA IQ magnetic bead extraction system, robotic DNA extraction using the BioMek2000, the ABI7000 Sequence Detection System, and is currently evaluating a micro Capillary Array Electrophoresis device. RESULTS: The PBSO successfully validated and implemented both manual and automated Promega DNA IQ magnetic bead extractions system, which have increased DNA profile results from samples with low DNA template concentrations. The Beckman BioMek2000 DNA robotic workstation has been validated for blood, tissue, bone, hair, epithelial cells (touch evidence), and mixed stains such as semen. There has been a dramatic increase in the number of samples tested per case since implementation of the robotic extraction protocols. The validation of the ABI7000 real-time quantitative polymerase chain reaction (qPCR) technology and the single multiplex short tandem repeat (STR) PowerPlex16 BIO amplification system has provided both a time and a financial benefit. In addition, the qPCR system allows more accurate DNA concentration data and the PowerPlex 16 BIO multiplex generates DNA profiles data in half the time when compared to PowerPlex1.1 and PowerPlex2.1 STR systems. The PBSO's future efficiency requirements are being addressed through collaboration with the University of California at Berkeley and the Virginia Division of Forensic Science to validate microcapillary array electrophoresis instrumentation. Initial data demonstrated the electrophoresis of 96 samples in less than twenty minutes. CONCLUSION: The PBSO demonstrated, through the validation of more efficient extraction and quantification technology, an increase in the number of evidence samples tested using robotic/DNA IQ magnetic bead DNA extraction, a decrease in the number of negative samples amplified due to qPCR and implementation of a single multiplex amplification system. In addition, initial studies show the microcapillary array electrophoresis device (microCAE) evaluation results provide greater sensitivity and faster STR analysis output than current platforms.

California↗

Reliability and descriptive validity of PSE syndromes.

Despite extensive research use of the Present State Examination (PSE), the validity of classification based on PSE data has not been studied extensively. We have examined a consecutive series of functional psychiatric admissions using the PSE and systematically gathered clinical and demographic data in order to study not only the reliability but the descriptive (construct) validity of classification based on PSE data. We have found that the PSE can be used in a psychiatric hospital to reliably describe and classify schizophrenic and affective syndromes with considerable descriptive validity in terms of clinical and demographic variables. We believe that this type of validity is an important step in establishing validity of clinical disease entities. The interrelationship among different kinds of validity (descriptive, concurrent, predictive) might provide clinical disease concepts with more definitive validity.

Adult↗

Using survey results to improve the validity of the standard psychiatric nomenclature.

Measuring the validity of psychiatric diagnoses is still an unsolved problem. Yet, revisions of the Diagnostic and Statistical Manual of Mental Disorders and of chapter V of the International Classification of Diseases are now under way, with the hope of improving the validity of the current systems. This article suggests data that could be used to assist in this goal. This article has 3 objectives. (1) To show that although the validity of the interview protocols used in collecting epidemiologic survey data has not itself been proven, the data banks they have collected are well suited to raising questions about the validity of the existing diagnostic nomenclature. This is the case because they faithfully operationalize the current nomenclature in large interview studies of diverse general populations. (2) To show the kinds of changes that appropriate analysis of these data may suggest as ways to improve the validity of the nomenclature. (3) To show how suggested changes that emerge from such analyses should be tested to learn whether they actually improve validity before they are implemented. The data sets from large epidemiologic studies have hardly been tapped for testing the validity of the current nomenclature. It is feasible to use them for this purpose because they are in the public domain and because they assess the presence or absence of each of the criteria in the manuals before applying the manuals' algorithms for combining them to make a diagnosis. Thus, these data banks allow exploration of the effects of combining and splitting diagnoses, of omitting criteria or reweighting them, and of choosing altered algorithms with respect to age at onset, number of symptoms, and duration of episodes. Assessing the consequences of these alterations can be tested by applying some of the criteria of Robins and Guze and Kendell.

Age of Onset↗

The pediatric cancer quality of life inventory-32 (PCQL-32): I. Reliability and validity.

BACKGROUND: Multidimensional measurement of pediatric cancer patients' health-related quality of life (HRQOL) in Phase III randomized controlled clinical trials is being recognized increasingly as an essential component in evaluating the comprehensive health outcomes of modern antineoplastic treatment protocols. The Pediatric Cancer Quality of Life Inventory-32 (PCQL-32) is a standardized patient self-report and parent proxy-report assessment instrument designed to assess systematically pediatric cancer patients' HRQOL outcomes. METHODS: To validate a patient-report form and a parent-report form, the PCQL-32 was administered to 291 pediatric cancer patients and to their parents. Both forms yield a total score and five a priori multidimensional scales. Clinical validity was determined by the known-groups approach by comparing patients classified as either on or off treatment. To determine construct validity, a battery of standardized psychosocial measures was administered and a multitrait-multimethod matrix was constructed. RESULTS: For both patient and parent forms, internal consistency reliability of the PCQL-32 total scale was high (0.91 and 0.92, respectively). The internal consistency reliabilities of the five component scales for both patient and parent forms were in the acceptable range for group comparisons. With regard to clinical validity, the PCQL-32 total scale and the disease/treatment and physical functioning scales of the PCQL-32 distinguished between patients on and off treatment for both patient- and parent-report. The results of the multitrait-multimethod matrix approach were consistent with hypotheses and lent evidence for the construct validity of the patient and parent forms of the PCQL-32 total scale and the psychological functioning, social functioning, cognitive functioning, physical functioning, and disease/treatment scales. CONCLUSIONS: The PCQL-32 has demonstrated acceptable internal consistency reliability, clinical validity, and construct validity for both patient-report and parent-report forms. Further field testing of the PCQL-32 will determine its practicality and utility in multisite pediatric cancer randomized controlled clinical trials.

Adolescent↗

Extracting maximum validity from the WAIS.

Recent research (Feingold, 1982) on the incremental validity of the WAIS has found that the Vocabulary and Information subtests are each as valid as the Full Scale IQ. The present WAIS review demonstrated that weighting subtests that differ in validity equally in the computation of the IQ is responsible for reducing potential validity. Two main conclusions emerged from these data. One, Vocabulary and Information in concert yield a measure that has greater validity than either subtest by itself. Two, the addition of a third test in a stepwise multiple regression in which Vocabulary and Information already have been added will not result in a consistent increase in validity. These findings must be considered tentative, but can serve as a guide for devising research designs to validate the recent revision of the WAIS (WAIS-R).

Achievement↗

Convergent validity of the eating disorder inventory and the anorexia nervosa inventory for self-rating in an Austrian nonclinical population.

This study assesses the convergent and divergent validity of the Eating Disorder Inventory (EDI--German version) and the Anorexia Nervosa Inventory for Self-Rating (ANIS) in a German-speaking nonclinical population. One hundred fifty-five female and 224 male Austrian medical students were surveyed. Validity was studied at a dimensional level, separately for both sexes, by correlating with conceptually related as well as distinct scales. These instruments included the General Health Questionnaire (GHQ). The intercorrelation coefficients of the EDI and the ANIS were similar to the original samples. In women, the convergent validity of the EDI and the ANIS was confirmed, especially for the subscales measuring the specific psychopathology (r = .43 to .84) and for ineffectiveness/feelings of inadequacy (r = .63). The EDI subscales Maturity Fears and Interpersonal Distrust and the ANIS subscales Obsessive-Compulsive Traits and Sexual Anxiety address traits not included in the other test and these showed divergent validity. Divergent validity of the ANIS and to a lesser degree the EDI with the GHQ was established. Both tests can be equally recommended for female subjects. In males however, the validity indices of both tests were generally lower and convergent and divergent validity was not established.

Adult↗

Assessing dissociative symptoms in eating disordered patients: construct validation of two self-report measures.

Dissociative symptomatology has been reported among patients with eating disorders, necessitating the availability of valid assessment instruments. In the current investigation, we examined the construct-related validity of two self-report instruments for assessing dissociative symptoms: the Dissociative Experiences Scale and the Trauma Symptom Checklist-40. The instruments were administered, along with instruments measuring depressive, anorexic, and bulimic symptomatology, to a sample of 125 eating disordered subjects. The dissociation measures demonstrated good convergent and discriminant validity, with a convergent validity coefficient (r = .73) that was approximately equal to that for the instruments measuring each of the three other psychological constructs. A principal components analysis further supported the construct-related validity of the dissociation scales. Severity of dissociative symptoms was generally unrelated to anorexic or bulimic symptomatology, but was significantly associated with depression. The results supported the construct validity of the dissociation instruments and the general status of dissociation as a valid and well-defined psychological phenomenon.

Adolescent↗

Registration and validity of surgical complications in colorectal cancer surgery.

BACKGROUND: Population-based quality registers have become an important tool in quality assessment during the past decade. For registers to be reliable, however, data must be checked carefully for validity. METHODS: The present study describes the validity of surgical complications registered in a national register run by the National Board of Health and Welfare (NBH), a register run by Regional Oncological Centres (ROC) and, for comparison, a local quality assurance system at Uppsala University Hospital (UUH). A specialized, independent surgeon checked 10 per cent of patient records against datasheets from the registers. RESULTS: The local quality assurance system at UUH showed the best validity for surgical complications. Data for complications of colonic cancer surgery were more valid than those for rectal cancer surgery. Registration of serious complications was more valid than that of wound infections. The calculated proportion of missed surgical complications was 0.69, 0.64, 0.40, 0.22 and 0.07 for rectal and colonic cancer in the NBH register, rectal and colonic cancer in the ROC register, and the UUH register respectively. Corresponding figures for reoperation were 0.45, 0.48, 0.04, 0.09 and 0.21. CONCLUSION: Local interest and routine use of data for quality assurance are crucial factors for valid registers. Careful monitoring of validity is necessary for use of registry data in structured systems for improvement of surgical results.

Colonic Neoplasms↗

Validity of weight distribution and sway measurements of the Balance Performance Monitor.

BACKGROUND AND PURPOSE: The Balance Performance Monitor (BPM) is a device which provides auditory and visual feedback on weight distribution and the magnitude of lateral and anterior-posterior sway during quiet standing. This study investigated the validity of the measurements provided by the BPM using a Kistler force plate (KFP) as the gold standard. METHOD: Percentage weight distribution between the BPM foot plates was validated using both a series of calibration weights and the vertical component of ground reaction force, measured by the KFP, during normal standing in 18 young normal subjects. The lateral and anterior-posterior sway indices from the BPM were validated against the standard deviation of the position of the centre of pressure, again obtained using the KFP, during normal standing with eyes open and eyes closed and standing with feet together with eyes open. Concurrent validity of the percentage weight distribution measurements was assessed by calculating the 'limits of agreement' between the corresponding measurements from the BPM and KFP and the 95% confidence intervals for these 'limits'. Differences in the units of measurement obtained from the BPM and KFP resulted in the concurrent validity of the sway indices being assessed using correlation and regression. RESULTS: Excellent agreement was found between the percentage weight distribution values provided by the BPM and the KFP, which showed that the BPM may read only 3% of body weight above or below that given by the KFP. High correlations (r = 0.61-0.99) were found between both the lateral and anterior-posterior sway indices from the BPM and the motion of the centre of pressure from the KFP in the respective direction. Despite this, further analysis of regression equations and the 95% prediction intervals showed poor concurrent validity of the BPM sway indices in relation to KFP measurements. This was thought to be due to the different methods by which the sway indices and the motion of the centre of pressure were calculated. CONCLUSIONS: The BPM may be used to provide a valid measure of the symmetry aspect, but not necessarily the steadiness aspect of postural control.

Adult↗

Use of real-time quantitative PCR to validate the results of cDNA array and differential display PCR technologies.

Real-time reverse transcription polymerase chain reaction (RT-PCR) methods that monitor product accumulation were adapted for the validation of differentially expressed genes. We describe a real-time quantitative PCR assay that uses SYBR Green I dye-based detection and product melting curve analysis to validate differentially expressed genes identified by gene expression profiling technologies. Since SYBR Green I dye is a nonspecific intercalating dye, the reaction is made specific by using "hot-start" PCR and empirically determined annealing and signal acquisition temperatures for each gene-specific primer. Relative expression levels were quantified by constructing a standard curve using cDNA dilutions of a highly expressed gene. Using this approach, real-time PCR validated 17 of 21 (71%) genes identified by DNA arrays, and all but 1 of 13 (91%) genes identified by differential display PCR (DD-PCR). Validation of differentially expressed genes detected by array analysis was related to hybridization intensity. Real-time RT-PCR results suggest that genes identified by DNA arrays with a two to fourfold difference in expression cannot be accepted as true or false without validation. Validation of differentially expressed genes detected by DD-PCR was not affected by band intensities. Regardless of the gene expression profiling technology (microarrays, DD-PCR, serial analysis of gene expression and subtraction hybridization), once the sequence of gene of interest is known, the real-time RT-PCR approach is well suited for validation of differential expression since it is quantitative and rapid and requires 1000-fold less RNA than conventional assays.

Animals↗

Validity of residents' self-reported cardiovascular disease prevention activities: the Preventive Medicine Attitudes and Activities Questionnaire.

BACKGROUND: This article describes the development, reliability, and validity of three cardiovascular disease (CVD) prevention subscales-CVD prevention behaviors, perceived importance, and perceived effectiveness-of the Preventive Medicine Attitudes and Activities Questionnaire (PMAAQ). METHODS: The PMAAQ was administered three times to University of Minnesota family practice residents (178) over 2 years (91% response rate). Stability measures were calculated, and validity was demonstrated in four ways: content validity through an expert panel; calculation of internal consistency reliabilities; demonstration of divergent validity; and external validation via a separate chart review. RESULTS: High internal consistency reliabilities among the subscales were seen (Cronbach's alpha = 0.77 to 0.92). Divergent validity was verified by low intercorrelations among the subscales (r = -0.23 to 0.27). Two-month test-retest scores ranged from Cronbach's alpha = 0.47 to 0.64. Significant correlations were seen between the chart review scale and both the CVD behaviors subscale and the PMAAQ smoking scale (r = 0.25 and 0.36, respectively). CONCLUSIONS: Results indicate that the PMAAQ can validly and reliably measure residents' CVD prevention behaviors and provide insight into their preventive health care attitudes. Further, the independence among the subscales suggests that importance and effectiveness by themselves do not affect behavior and that other factors are likely to be important in influencing physician behavior change.

Adult↗

Analytical methods validation: bioavailability, bioequivalence and pharmacokinetic studies. Conference report.

This is a summary report of the conference on Analytical Methods Validation: Bioavailability, Bioequivalence and Pharmacokinetic Studies. The conference was held from December 3 to 5, 1990 in the Washington, DC area and was sponsored by the American Association of Pharmaceutical Scientists, US Food and Drug Administration, Federation International Pharmaceutique, Health Protection Branch (Canada) and Association of Official Analytical Chemists. The purpose of the report is to represent our assessment of the major agreements and issues discussed at the conference. The report is also intended to provide guiding principles for validation of analytical methods employed in bioavailability, bioequivalence and pharmacokinetic studies in man and animals. The objectives of the conference were: 1. To reach a consensus on what should be required in analytical methods validation and the procedures to establish validation; 2. To determine processes of application of the validation procedures in the bioavailability, bioequivalence and pharmacokinetic studies; 3. To develop a report on analytical methods validation (which may be referred to in developing future formal guidelines). Acceptable standards for documenting and validating analytical methods with regard to processes, parameters or data treatments were discussed because of their importance in assessment of pharmacokinetic, bioavailability and bioequivalence studies. Other topics which were considered essential in the conduct of pharmacokinetic studies or in establishing bioequivalency criteria, including measurement of drug metabolites and stereoselective determinations, were also deliberated.

Biological Availability↗

Issues of validity in the Diagnostic Interview Schedule.

The Diagnostic Interview Schedule, the chief instrument in contemporary studies in psychiatric epidemiology, enhances the reliability of psychiatric diagnosis and enables lay interviewers to closely reproduce psychiatric interviews. However, despite frequent references in the literature to the validity of the Diagnostic Interview Schedule, most studies fundamentally represent variations of reliability paradigms to the neglect of criterion-related validity. Mistaken assertions of validity persist in the psychometric language used to describe the Diagnostic Interview Schedule. This article examines the basis for claims and counterclaims of validity in accordance with standard psychometric definition, and identifies sources of erroneous reasoning in attempts to infer validity from reliability. The article presents a general framework organizing the process of diagnostic validation and discusses strategies for research seeking to validate psychiatric diagnoses achieved through the Diagnostic Interview Schedule.

Humans↗

Validation criteria for animal models of human mental disorders: learned helplessness as a paradigm case.

Three sets of criteria are proposed for assessing animal models of human mental disorders: predictive validity (performance in the test predicts performance in the condition being modelled), face validity (phenomenological similarity) and construct validity (theoretical rationale). The problems inherent in each of these validation procedures are discussed, and their application to the learned helplessness model of depression is examined. It is concluded that whilst the model has good predictive validity, important questions about face validity remain unanswered, and construct validity has not yet been established. The distinctions between animal models and some related experimental procedures are also discussed.

Animals↗

Application issues in bioanalytical method validation, sample analysis and data reporting.

Although some degree of consensus has been reached concerning the requirements for acceptable method validation, the procedures used to establish them vary significantly between laboratories. Also, issues arising from application of these requirements during validation and subsequent sample analysis need to be addressed. The purpose of this paper is to discuss application issues concerning prerequisites to method validation, and all validation criteria for evaluation of method reliability and overall performance. Other poorly addressed issues such as re-validation, cross-validation, partial sample volume, multicomponent analysis and reporting will also be discussed. Although many issues discussed are of a general nature, the scope of this presentation is primarily to address issues arising from the validation and routine application of chromatographic methods.

Animals↗

Reliability and changes in validity of self-reported cardiovascular disease risk factors using dual response: the behavioral risk factor survey.

The authors previously studied the validity of self-reported cardiovascular disease (CVD) risk factors assessed by telephone surveys, and found the validity low, especially for self-reported hypertension and hypercholesterolemia. One way to improve validity is to combine repeated measurements (dual response) into a single measure. The authors explored this and the reliability of self-reported CVD data collected by the Behavioral Risk Factor Survey in three New York counties from January 1989 to May 1990. Nine hundred and eleven subjects were interviewed by telephone to collect CVD risk factor and health behavior information. Interviewees were offered physical examination and laboratory testing to verify self-reported CVD risk factors; 628 participated. Subjects were also reinterviewed to assess the test-retest reliability of the survey, and to study how validity of self-reported CVD data changes by dual response. Reliability coefficients for CVD risk factors, preventive health practices, and knowledge of risk factor levels ranged from 0.42 to 0.99. Minimal improvement in sensitivity of self-reported risk factors was found using dual response, and it did not improve specificity. Also, for prevalence of risk factors, dual response minimally improved self-reported rates compared to objective estimates. Combining self-reported measurements causes minimal changes in the validity of these variables. Physiological assessment for hypertension and hypercholesterolemia, or correction for misclassification, is needed for valid individual measurement and for community prevalence estimates from telephone surveys. Self-reported cigarette smoking, obesity, and diabetes mellitus have better validity, but physiological assessment or correction for misclassification may supplement these self-reported risk factors.

Adult↗

The assessment of anhedonia in clinical and non-clinical populations: further validation of the Snaith-Hamilton Pleasure Scale (SHAPS).

BACKGROUND: Anhedonia, the inability to experience pleasure, is a major endophenotype of depression. In addition to this, it is an important clinical feature of schizophrenia and substance abuse disorders. Valid instruments to measure anhedonia are sparse. METHODS: In the present study, a short, 14-item instrument, the Snaith-Hamilton Pleasure Scale (SHAPS) to measure anhedonia in normal and clinical samples was further validated. Various aspects of the reliability and validity of the SHAPS that have not been addressed before, were examined in three separate studies. First, we assessed the internal consistency, convergent and discriminative validity of the SHAPS in a non-clinical sample. Second, the test-retest reliability of the SHAPS was investigated in another sample. In the third study, the internal consistency, convergent and discriminative validity of the SHAPS was tested by administering the scale in three clinical samples of psychiatric inpatients. RESULTS: The SHAPS was found to be highly reliable in terms of internal consistency and test-retest stability. Further, the SHAPS correlated in a theoretically meaningful way with other measures of affect and personality. Patients with a depression, psychosis or substance dependence scored significantly higher on the SHAPS than non-patient controls. Patients with a depression displayed the highest SHAPS-score. LIMITATIONS: The absence of structured assessment data to validate the clinical diagnoses. CONCLUSIONS: The current study shows that the SHAPS is a reliable and valid questionnaire to assess hedonic tone in patient and non-patient populations. Because it is a brief scale it seems to be a very useful instrument for measuring anhedonia in clinical and research settings.

Adolescent↗

Validation by simulation of a clinical trial model using the standardized mean and variance criteria.

OBJECTIVE: To develop and validate a model of a clinical trial that evaluates the changes in cholesterol level as a surrogate marker for lipodystrophy in HIV subjects under alternative antiretroviral regimes, i.e., treatment with Protease Inhibitors vs. a combination of nevirapine and other antiretroviral drugs. METHODS: Five simulation models were developed based on different assumptions, on treatment variability and pattern of cholesterol reduction over time. The last recorded cholesterol level, the difference from the baseline, the average difference from the baseline and level evolution, are the considered endpoints. Specific validation criteria based on a 10% minus or plus standardized distance in means and variances were used to compare the real and the simulated data. RESULTS: The validity criterion was met by all models for considered endpoints. However, only two models met the validity criterion when all endpoints were considered. The model based on the assumption that within-subjects variability of cholesterol levels changes over time is the one that minimizes the validity criterion, standardized distance equal to or less than 1% minus or plus. CONCLUSION: Simulation is a useful technique for calibration, estimation, and evaluation of models, which allows us to relax the often overly restrictive assumptions regarding parameters required by analytical approaches. The validity criterion can also be used to select the preferred model for design optimization, until additional data are obtained allowing an external validation of the model.

Anti-Retroviral Agents↗