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Evaluating interpretive inquiry: reviewing the validity debate and opening the dialogue.

Designing and carrying out effective and valid research are the desired goals of all researchers, and demonstrating the trustworthiness of one's dissertation research is a requirement for all doctoral candidates. For qualitative researchers, reaching the desired goal and meeting the requirement of trustworthiness become particularly problematic due to the considerable debate about what it means to do valid research in the field of qualitative inquiry. This article reviews the various approaches to the validity problem in the hope of turning this debate into a dialogue. Validity is traced from its origins in the realist ontology and foundational epistemology of quantitative inquiry to its reformulations within the lifeworld ontology and non-foundationalism of interpretive human inquiry. Various recent qualitative approaches to validity are considered, and interpretive reconfigurations of validity are reviewed. Interpretive approaches to validity are synthesized as ethical and substantive procedures of validation.

Ethics↗

Development and preliminary validation of Brace Questionnaire (BrQ): a new instrument for measuring quality of life of brace treated scoliotics.

BACKGROUND: The quality of life among children with idiopathic scoliosis during their adolescence has been reported to be affected by the brace itself. However, a controversy exists whether brace treated scoliotics experience a poor quality of life, thus there is a need for the development of a brace-oriented instrument, as the now-existing questionnaires that are commonly used, such as the SRS -22, take into consideration the effects of both the conservative and the surgical treatment on quality of life of scoliotic children. The aim of the present study is to assess the validity and reliability of Brace Questionnaire (BrQ), a new instrument for measuring quality of life of scoliotic adolescents who are treated conservatively with a brace. MATERIAL-METHOD: Methodology of development involved literature review, patient and health care professionals' in-depth interviews and content validity analysis on patients. A validation study was performed on 28 brace treated scoliotic children aged between 9 and 18 years old. BrQ was assessed for the following psychometric properties: item convergent validity, floor and ceiling effects, internal consistency reliability, clinical validity and responsiveness to change. RESULTS: BrQ is self administrated and developmentally appropriate for ages 9 to 18 years old and is consisted of 34 Likert-scale items associated with eight domains: general health perception, physical functioning, emotional functioning, self esteem and aesthetics, vitality, school activity, bodily pain and social functioning of scoliotic children treated conservatively with a brace. The subscales of these eight dimensions can be combined to produce a total score. Higher scores mean a better quality of life. An item convergent validity >/= 0.40 was satisfied by all items in the present study. A satisfactory internal consistency reliability for the BrQ was recorded (Cronbach's alpha coefficient was 0.82). There were no floor or ceiling effects. The correlation between BrQ overall scores and mild and moderate scoliosis was statistically significant (p < 0.001), revealing high clinical validity. An increase in effect sizes for the patient with improved scoliotic curves indicates that the BrQ is responsive to change in health status. CONCLUSION: BrQ is reliable, valid and responsive to change in adolescents with IS who are treated conservatively with a brace.

Journal Article↗

Validity and reliability of retrospective assessment of disease activity and flare in observational cohorts of lupus patients.

BACKGROUND: The use of validated retrospective tools to assess disease activity in an observational cohort of patients would allow researchers the flexibility to analyze unique exploratory questions. Valid, reliable tools exist for assessing disease activity and flare for Systemic Lupus Erythematosus (SLE) patients. However, these tools have been designed for use in structured settings. Many of these populations under study are subject to strict inclusion, exclusion criteria and disease management protocols. The ability to apply these tools to populations not subject to such control would allow researchers to explore questions about unique populations, new treatment applications or predictors of clinical outcomes. This study sought to establish the reliability and validity of retrospective medical record abstraction of SLE disease activity and flare instruments by two rheumatologists. METHODS: From university rheumatology outpatient clinics, 22 patients were randomly selected to establish intra-rater reliability and 26 patients were selected to establish inter-rater reliability. Two rheumatologists using a Physician Global Assessment (PGA), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Safety of Estrogens in Lupus Erythematosus-National Assessment (SELENA) flare tool retrospectively abstracted patient charts. Agreement between the tools was evaluated to assess validity. RESULTS: The mean patient age was 39 y; 96% were female, 54% Caucasian, 27% Hispanic, 19% Asian; median PGA was 1.4 (on a 0-3 scale) and median SLEDAI score was 4 (range 0-27). Intra-rater reliability for PGA, SLEDAI and the SELENA flare tool was 0.88, 0.87 and 0.52, respectively. Inter-rater reliability for PGA, SLEDAI, and SELENA flare was 0.79, 0.75, and 0. 50, respectively. To assess validity, the tools were compared against each other to assess agreement. From the parent study sample (n=54 patients), the disease activity measures, PGA and SLEDAI demonstrated adequate agreement (r=0.60). However, the SELENA flare tool demonstrated poor agreement with either PGA-defined flare or SLEDAI-defined flare (weighted kappa, 0.29 and 0.40 respectively). PGA-defined and SLEDAI-defined flare also demonstrated poor agreement (weighted kappa, 0.35). CONCLUSIONS: These data suggest that investigators can reliably reproduce patient disease activity through retrospective chart abstraction using PGA and SLEDAI. Assessing flare is a more difficult concept. The validity of assessing flare at a specific patient-visit is poor. Retrospective assessment of patient flare risk over a specified time period is conceptually more valid and avoids difficulties assessing timing and duration of flare. As there have been no similar published prospective analyses of validity using the SELENA flare tool, it is not clear if this problem was unique to the method of retrospective chart abstraction, the nature of non-protocol study patient visits, the tool itself or a combination of all three aspects.

Adult↗

Construct validity of physical activity and sedentary behaviors staging measures for adolescents.

PURPOSE: To evaluate the construct validity of physical activity (PA) and sedentary behaviors (SB) staging measures for adolescents that incorporate the current national recommendations. METHOD: The Progressive Aerobic Cardiovascular Endurance Run, Actigraph accelerometer, and self-reported hours of TV viewing served as criterion measures. Participants were 878 adolescents (M age = 12.74, 53.6% girls, 39.9% non-White). RESULTS: The PA staging measure had mixed evidence of convergent validity and strong evidence of divergent validity. The SB staging measure had strong and generalized evidence of convergent validity but weak evidence of divergent validity, which could be related to inaccurate assumptions about the relation of SB to PA and fitness. Results were generally in the expected direction and provide preliminary evidence for the construct validity and generalizability of both staging measures. However, more research is warranted to validate the staging measures with Actigraph-measured PA and sedentary time. Effect sizes (eta(2) values) ranged from small to large (.02-.63). CONCLUSION: PA and SB stage-of-change measures that are congruent with current national recommendations and appropriate for use among adolescents were partially supported for their construct validity.

Adolescent↗

Validation through self and other ratings on dimensions of six nonstressful multi-scaled personality instruments.

Six nonstressful personality instruments were concurrently validated using respondent and close friend ratings on specific scale dimensions. Tests were administered to 203 predominantly Caucasian college students. Prior to testing, the individual and a close friend through self-ratings and ratings of the respondents had estimated the strengths of the tested personality Variables on a seven-point scale. The definitions of the various personality dimensions were taken from publisher's manuals. An estimated whole test validity was obtained by an average of the individual scale validities using a conversion of Pearson's r to z'. Significant differences among and between subtest validities were found by ANOVA. All "self-rating" validities were significant (.001), with two of these self-rating validities significantly different (.01) than the other four tests. Only two "other-rating" validities were significant. All six tests appeared to be valid for college population use From preliminary analysis, counselees could rate themselves accurately on most test measures. In some cases self-ratings might be used in lieu of giving the test.

Journal Article↗

Validity of a 5-meter multiple shuttle run test for assessing fitness of women field hockey players.

The aim of this study was to establish validity of a 5-m multiple shuttle test (5-m MST) using indirect (criterion and construct) and direct measures of performance. For criterion validity, comparisons were made between data from established fitness tests and a 5-m MST. Construct validity was determined by comparing results from a 5-m MST with subjects of different playing abilities. Direct validity was determined by comparing values attained from a 5-m MST with data from a time-motion study of field hockey. For criterion validity, the strongest relationship existed between the 20-m MST (42.7 +/- 7.1 ml.kg(-1).min(-1)) and total distance from the 5-m MST (650.9 +/- 59.2 m; r = 0.92). For construct validity, regional representative players covered more distance than club-level players (689.9 +/- 46.6 m vs. 661.1 +/- 31.0 m; p < 0.01). For direct validity, the highest correlation was found between total distance from the 5-m MST (706.0 +/- 37.5 m) and mean displacement during matches (61.0 +/- 6.0 m; r = 0.74). It was concluded that the 5-m MST had both indirect and direct validity for the fitness assessment of field hockey players. The data obtained from the 5-m MST directly relates to the physical fitness of the players during competition.

Adult↗

Validity and reliability of self-reported drinking behavior: dealing with the problem of response bias.

This work assesses the validity and reliability of self-reported survey data on drinking behavior. There is evidence to suggest that data are adversely affected by bias from underreporting. This bias affects the validity of measures of consumption of alcohol and can have deleterious effects on the results of some forms of statistical estimation. Data for this study were collected at an isolated military base. The remoteness of this site and the fact that it is a military station made it possible to estimate the actual level of consumption of alcohol for the population by assessing apparent consumption through officially recorded sales of alcohol. The results of eight measures of consumption of alcohol were compared with apparent consumption, as established by documented sales, and the validity and reliability of the various measures were determined using the classical correlational approach. The validity and reliability of the data generated by the self-report survey were also analyzed using LISREL, the measurement model in particular. The results indicate that various instruments used to assess the consumption of alcohol produce very different outcomes in terms of their validity and reliability, some questions being considerably more valid and reliable than others. Two of the more salient characteristics of questions that affect validity and reliability were isolated, namely a question's ability to aid recall and its ability to mitigate the effects of persons providing socially desirable responses. The LISREL results show that these are two underlying factors for the measurement of the consumption of alcohol. It is concluded that questions that produce valid and reliable responses do so for identifiable reasons, and measurement instruments can be improved by incorporating particular features.

Alcohol Drinking↗

Development and validation of an acceptability and satisfaction questionnaire for a contraceptive vaginal ring, NuvaRing.

OBJECTIVE: To validate an acceptability questionnaire for NuvaRing, a new combined contraceptive vaginal ring. METHODS: A 21-item questionnaire was developed covering: ease of ring use, ease of package use, clarity of instructions, sexual comfort, cycle-related characteristics, compliance and satisfaction. A total of 2145 women completed the questionnaire after 3, 6 or 13 cycles of NuvaRing use. The psychometric properties and predictive value of the questionnaire were assessed using cycle 3 data (n = 1950). The quality of completed questionnaires, item content analysis, construct validity, internal consistency reliability, known groups validity and predictive validity were evaluated. RESULTS: Excluding non-ordinal items, 0.6% of the data were missing. Principal component analysis of 15 ordinal items indicated that two hypothesised dimensions ('ease of package use' and 'clarity of instructions') were consistently linked and so were combined into a single 'ease of comprehension' scale. Item convergent validity (the degree of correlation between an item and its own scale) was 100% for 'ease of ring use' (r = 0.44) and 'satisfaction' (r = 0.58), 83% for 'ease of comprehension' (r = 0.25-0.62) and 67% (r = 0.38-0.54) for 'sexual comfort', but 0% for 'cycle-related characteristics' (r = 0.31). Item discriminant validity (the degree to which an item correlates with its own scale compared with other scales) was >/=96% for all dimensions. Internal consistency reliability was acceptable for all dimensions (adjusted Cronbach's alpha coefficient >0.70). Satisfaction was higher than in the complementary groups for respondents who had no adverse events, chose NuvaRing as the best method of contraception or completed the study; this indicated good known groups validity. Low satisfaction with the method was a good predictor of early discontinuation after cycle 3, indicating that the questionnaire had good predictive validity. CONCLUSIONS: The acceptability questionnaire has good psychometric properties and can predict early discontinuation of the NuvaRing vaginal ring method of contraception.

Adolescent↗

Asymptotic optimality of likelihood-based cross-validation.

Likelihood-based cross-validation is a statistical tool for selecting a density estimate based on n i.i.d. observations from the true density among a collection of candidate density estimators. General examples are the selection of a model indexing a maximum likelihood estimator, and the selection of a bandwidth indexing a nonparametric (e.g. kernel) density estimator. In this article, we establish a finite sample result for a general class of likelihood-based cross-validation procedures (as indexed by the type of sample splitting used, e.g. V-fold cross-validation). This result implies that the cross-validation selector performs asymptotically as well (w.r.t. to the Kullback-Leibler distance to the true density) as a benchmark model selector which is optimal for each given dataset and depends on the true density. Crucial conditions of our theorem are that the size of the validation sample converges to infinity, which excludes leave-one-out cross-validation, and that the candidate density estimates are bounded away from zero and infinity. We illustrate these asymptotic results and the practical performance of likelihood-based cross-validation for the purpose of bandwidth selection with a simulation study. Moreover, we use likelihood-based cross-validation in the context of regulatory motif detection in DNA sequences.

Journal Article↗

Measuring the significance of field validation in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology: how good are the experts?

CONTEXT: Expert opinion is often used as a gold standard for gynecologic cytology in the evaluation of new technologies, in the legal setting, and in the validation of cases for use in educational programs and proficiency testing. However, the reliability of expert opinion alone in selecting slides of a specific cytodiagnosis that can be reproducibly and reliably identified by subsequent reviewers has not been determined. OBJECTIVE: To assess the ability of expert opinion to select slides that are validated in subsequent reviews. DESIGN: In the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, each case in every cytodiagnostic category is accepted for circulation only after review by 3 expert cytopathologists. The percentage of these cases that could not be reliably and reproducibly identified by program participants for each cytodiagnostic category ("failed field validation") was determined during the duration of the program from 1989 to 2004. RESULTS: More than 10,000 conventional smears and ThinPrep cases were selected by the expert panel for circulation. Of these selected slides, 19% of conventional smears and 15% of ThinPrep specimens failed field validation. Compared with the overall slide performance, significantly higher percentages (P < .001) of conventional smears with reference diagnoses of unsatisfactory (51.7%), repair (58%), or low-grade intraepithelial lesion (31.8%) and of ThinPrep specimens with reference diagnoses of unsatisfactory (54.5%) and repair (76.9%) failed field validation. In contrast, significantly lower percentages of conventional smears with reference diagnoses of squamous cell carcinoma (4.5%), high-grade squamous intraepithelial lesion (9%), Trichomonas vaginalis infection (11.7%), or herpes (9.9%) and of ThinPrep specimens with reference diagnoses of adenocarcinoma (5.1%), herpes (2.1%), and fungal organism consistent with Candida (8.4%) failed field validation (P < .001 for all). CONCLUSIONS: Between 15% and 19% of gynecologic cytologic cases that have been selected by expert cytopathologists as good examples of cytodiagnostic abnormalities fail field validation. The proportion of cases failing field validation varies with cytodiagnostic category, but it occurs in all cytodiagnostic entities.

Clinical Competence↗

'Truthsets' for clinical validation of large-scale functional assays: Practice recommendations from Cancer Variant Interpretation Group UK (CanVIG-UK).

BACKGROUND: Large-scale functional assays, including multiplex assays of variant effect, have substantial potential to resolve variants of uncertain significance (VUS), particularly for rare missense variants where clinical and population evidence are limited. The ClinGen assay-level clinical validation framework described by Brnich et al provided baseline guidance for the use of functional data for variant classification. However, clear consensus regarding construction of variant 'truthsets' by which to clinically validate functional data remains lacking. METHODS: CanVIG-UK developed consensus recommendations for truthset construction through an iterative national consultation process involving the CanVIG Steering Advisory Group (CStAG), wider CanVIG-UK membership, and engagement with international functional genomics experts. Consultation was based on previous analyses of 2,120 truthset constructions examining the impact of truthset composition on evidence point allocation within the ClinGen assay-level clinical validation framework. RESULTS: Across several consultations, CanVIG-UK established nine guiding principles and seven best-practice recommendations for assay-level clinical validation, using the assumed context of an assay for a cancer susceptibility gene where loss-of-function is the mechanism of pathogenicity. The principal recommendation stipulates, where assays are intended for use in interpretation of largely missense variants, the truthset used to validate should comprise only missense variants. Rather than mixtures of different variant types which may serve to over-estimate assay performance. Additional recommendations support option for relaxation of truthset stringency to improve power, augmentation of benign missense truthsets with systematically derived 'proxy-clinical' benign variants, independent clinical validation separate from assayist-defined validation, and careful evaluation of missense score distributions against that of protein-truncating and synonymous variants. Guidance is also provided for scenarios with limited pathogenic truthset availability and for assays reporting multiple deleterious zones or readouts. CONCLUSIONS: The CanVIG-UK principles and recommendations for truthset construction upon the ClinGen assay-level clinical validation framework, while aiming to form a baseline for future discussion regarding other functional and disease contexts and helping to address the gap between publication of new data and routine clinical implementation.

Journal Article↗

Two by two hour creatinine clearance--repeatable and valid.

AIM: The purpose of this study was to determine the repeatability and validity of 2 x 2 hour creatinine clearance, and the validity of creatinine clearances estimated by equations. PATIENTS AND METHODS: In 30 patients two 2 x 2 h and two 24-h creatinine clearances were performed on consecutive days. In addition, creatinine clearances estimated by 4 different equations were calculated. Two by two hour creatinine clearance provided a measurement of GFR as valid as 24-h creatinine clearance. RESULTS: We found, that 2 x 2 h creatinine clearance was well repeatable with a mean difference between 2 repeated measurements of 0.8 ml/min and low coefficients of repeatability of 14.5 ml/min. The validity of 2 x 2 h creatinine clearance, assessed by the mean difference between 2 x 2 and 24-h creatinine clearances, was 1.2 ml/min with tight 95% limits of agreement with a range from -8.1 to 10.5 ml/min. This high degree of repeatability and validity was present over the entire range of renal function (6-141 ml/min). As 2 x 2 h creatinine clearance is more simple and rapid than 24-h creatinine clearance, results are obtained on the same day and easy, but repeatable and valid day-to-day monitoring of renal function is possible. In addition, the two times two hour clearances allow for quality control. In contrast, estimated creatinine clearances show only poor validity. CONCLUSION: Because of the high degree of repeatability and validity, 2 x 2 h creatinine clearance may replace 24-h creatinine clearance as the standard method to determine renal function in clinical practice.

Adolescent↗

Evaluation of LabRespond, a new automated validation system for clinical laboratory test results.

BACKGROUND: Manual validation of laboratory test results is time-consuming, creating a demand for expert systems to automate this process. We have started to set up the program "LabRespond", which covers five validation levels: administrative, technical, sample, patient, and clinical validation. We present the evaluation of a prototype of an automated patient validation system based on statistical methods, in contrast to the commercially available program "VALAB", a rule-based automated validation system. METHODS: In the present study, 163 willfully altered, erroneous test results out of 5421 were submitted for validation to LabRespond, VALAB, and to a group of clinical chemists (n = 9) who validated these test results manually. The test results rejected by three or more clinical chemists (n = 281) served as a secondary reference standard. RESULTS: The error recovery rates of clinical chemists ranged from 23.9% to 71.2%. The recovery rates of LabRespond and VALAB were 77.9% and 71.8%, respectively (difference not significant). The false-positive rates were 82.7% for LabRespond, 83.6% for VALAB, and 27.8-86.7% for clinical chemists. Using the consensus of three or more clinical chemists as the secondary reference standard, we found error recovery rates of 64.8% for LabRespond and 72.2% for VALAB (P = 0.06). Compared with VALAB, LabRespond detected more (P = 0.003) erroneous test results of the type that were changed from abnormal to normal. CONCLUSIONS: The statistical plausibility check used by LabRespond offers a promising automated validation method with a higher error recovery rate than the clinical chemists participating in this study, and a performance comparable to VALAB.

Clinical Laboratory Techniques↗

[Development of prediction models for three in vitro embryotoxicity tests which are evaluated in an ECVAM validation study]

In 1997 ZEBET started the co-ordination of a study funded by the European Centre for the Validation of Alternative Methods (ECVAM) with the aim of pre-validation and validation of three in vitro embryotoxicity tests. These tests employ the cultivation of post-implantation whole rat embryos (WEC test), cultures of primary limb bud cells of rat embryos (micromass test, MM-Test), and cultures of a pluripotent mouse embryonic stem cell line (embryonic stem cell test, EST). In the current Validation Study each of the tests is evaluated in four laboratories under blind conditions. In an initial phase of the validation study six out of 20 test chemicals comprising different embryotoxic potential (non, weak and strong embryotoxic) were tested. The results were used to improve the prediction models (PM) for the WEC test and the MM-Test in order to identify the embryotoxic potential of test chemicals. In addition, the existing PM for the EST was evaluated using the results from testing of the initial six chemicals. The PM for the EST was developed using the results of a previous pre-validation study (Scholz et al.,1999), in which 94% of the learning sample were classified correctly. Applying this PM to the results of the initial phase of the current validation study, 80% of the experiments were classified correctly according to the embryotoxic potential of the tested chemicals in vivo. Applying the PM for the MM-Test and the WEC test that were developed during the current validation study in both tests, 79% correct classifications were achieved. Since the PM of the WEC-Test took into account only parameters of growth and development, but not cytotoxicity data, a second PM (PM2) for the WEC was developed that was improved by incorporating cytotoxicity data of the differentiated mouse fibroblast cell line 3T3 derived from the EST. This approach, which has previously never been used as an adjunct to the WEC test, resulted in an increase of correct classifications to 96%.

Journal Article↗

[French validation study of the levels of emotional awareness scale].

According to a thesis based on the idea of an influence of cognitions in the structuring of internal reality, emotional awareness, ie the capacity of representing your own emotional experience and that of others, is a cognitive process that goes into maturation. Defining this concept, Lane and Schwartz present a cognitivo-developmental model in five stages of the processes of symbolization, accounting for the differences in levels of emotional awareness observed in individuals. The organization of these cognitive processes would thus be structured in well differentiated stages, in which the development of the emotions would be inseparable from the development of ego and of the relation to others. These authors focus on the capacity of representing in a conscious way the emotional experience and consider that verbal representations used to describe the contents of what is experience constitute a good reflection of the organization structural of the emotional awareness. Therefore, they worked out an instrument of evaluation: the Levels of Emotional Awareness Scale (LEAS), which measures the capacity to describe your own emotional experience and the one you allow to others, in an emotional situation. The system of quotation of this scale is based on the analysis of the verbal contents of the provided answers, in direct reference to the authors' theory of the levels of differentiation and integration of the emotional experience. It is therefore an empirical measurement which is centered specifically on the structural organization of the emotional experience. The various studies of validation of this instrument show that it presents solid metrological properties. This work presents the validation of the French version of Lane and Schwartz's LEAS. Validity and fidelity were studied in a group of 121 healthy subjects. This setting is part of a larger clinical evaluation, also including a collection of socio-demographic and clinical data, and other instruments of self-evaluation (Beck Depression Inventory, BDI, Hospital Anxiety and Depression Scale, HAD, and Toronto Alexithymia Scale, TAS). The face validity appears correct: the questionnaire was well accepted and seemed easy to complete. A principal components analysis of the correlation matrix of the set of items was used as the method of extraction of the various factors and made it possible to confirm the unidimensionality of the instrument. The number of factors to be retained was given according to Kaiser and Cattell criteria. The internal consistency was evaluated through computation of the Cronbach coefficient, whose value is 0.75 for the scale's global score. The confidence interval of the margin of error of LEAS scores was also measured; for the global score it is IC=[m 6.1]. The measure given by this rating scale may therefore be considered sufficiently accurate, since this interval is weak. A study of the frequency of quotation of each item of the instrument was carried out, in order to check the homogeneity and the uniformity of quotations, as well as a diagram of distribution of the score, showing that it follows a law which is close to a normal law. The concurrent validity could only be studied via the similar concept of alexithymia, measured with the TAS, for there is not other instrument validated in French evaluating the levels of emotional awareness, and these two instruments seem to measure different notions, because none of the correlations between the scores of these two questionnaires are significant. Concerning discriminant validity, the Pearson correlation coefficients between the global score for the LEAS, the BDI score and the HAD sub-scores for depression and anxiety were measured; it is clear that the level of emotional awareness is independent from negative affects. Furthermore, the study of the reliability made it possible to highlight excellent intra-class correlation coefficients (r=0.993). The French version of the Levels of Emotional Awareness Scale thus appears to be valid and accurate and should allow the study of levels of emotional awareness on psychopathology. It is about an easily acceptable and simple questionnaire of use in varied clinical circumstances.

Adolescent↗

The preparation and validation of stock cultures of mammalian cells.

The utilization of continuous cell substrates is now widely accepted for the production of biologics. As part of the evaluation and licensing process of these products, the regulatory agencies are requiring extensive validation of the production system. That production system begins with the validation or qualification of a defined cell bank. This includes the validation of the stability cells at both the genetic and biochemical levels during cell culture production. Process validation plus cell bank validation provide the necessary assurance that the final product will be free of contaminating viruses and other adventitious agents. A combination of cell bank characterization and product characterization (peptide mapping or amino acid sequencing, or a combination thereof) will also demonstrate the stability of the production process. The validation of a cell bank for adventitious agents and cell line stability will not, in itself, ensure that the product is sterile and stable. However, cell bank validation is critical for demonstrating the safety of a product when combined with both process validation and end-product testing.

Animals↗

Industrial perspective on validation of tangential flow filtration in biopharmaceutical applications. Technical Report No. 15. Parenteral Drug Association. Biotechnology Task Force on Purification and Scale-up.

Validation of tangential flow filtration is required to ensure the process delivers a product of consistent quality, safety, and efficacy. A thorough and sound validation program not only satisfies regulatory requirements, but also provides a valuable source of information which facilitates development of future processes, training of production personnel, and trouble shooting for the validated process. Validation of TFF shares many common elements with validation of other traditional operations and equipment. Existing personnel and procedures should be readily adapted to execute the TFF validation protocols. IQ's and OQ's will most likely follow familiar formats. In performance qualification, key areas needing attention include: assessment of compatibles, testing of parameters affecting membrane retention and selectivity, cleaning, sanitization, and membrane lifetime. Finally, the hallmark of a sound validation program is the quality of its scientific approach and its congruence with the definition of validation contained in the 1987 guidelines (6).

Filtration↗

Development of a framework for international certification by OIE of diagnostic tests validated as fit for purpose.

Historically, the OIE has focused on test methods applicable to trade and the international movement of animals and animal products. With its expanding role as the World Organisation for Animal Health, the OIE has recognised the need to evaluate test methods relative to specific diagnostic applications other than trade. In collaboration with its international partners, the OIE solicited input from experts through consultants' meetings on the development of guidelines for validation and certification of diagnostic assays for infectious animal diseases. Recommendations from the first meeting were formally adopted and have subsequently been acted upon by the OIE. A validation template has been developed that specifically requires a test to be fit or suited for its intended purpose (e.g. as a screening or a confirmatory test). This is a key criterion for validation. The template incorporates four distinct stages of validation, each of which has bearing on the evaluation of fitness for purpose. The OIE has just recently created a registry for diagnostic tests that fulfil these validation requirements. Assay developers are invited to submit validation dossiers to the OIE for evaluation by a panel of experts. Recognising that validation is an incremental process, tests methods achieving at least the first stages of validation may be provisionally accepted. To provide additional confidence in assay performance, the OIE, through its network of Reference Laboratories, has embarked on the development of evaluation panels. These panels would contain specially selected test samples that would assist in verifying fitness for purpose.

Animal Diseases↗