SEARCH · PubMed Health

Results for “Internal validation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources

PubMed2005

Construction and validation of the APOCHIP, a spotted oligo-microarray for the study of beta-cell apoptosis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a autoimmune disease caused by a long-term negative balance between immune-mediated beta-cell damage and beta-cell repair/regeneration. Following immune-mediated damage the beta-cell fate depends on several genes up- or down-regulated in parallel and/or sequentially. Based on the information obtained by the analysis of several microarray experiments of beta-cells exposed to pro-apoptotic conditions (e.g. double stranded RNA (dsRNA) and cytokines), we have developed a spotted rat oligonucleotide microarray, the APOCHIP, containing 60-mer probes for 574 genes selected for the study of beta-cell apoptosis. RESULTS: The APOCHIP was validated by a combination of approaches. First we performed an internal validation of the spotted probes based on a weighted linear regression model using dilution series experiments. Second we profiled expression measurements in ten dissimilar rat RNA samples for 515 genes that were represented on both the spotted oligonucleotide collection and on the in situ-synthesized 25-mer arrays (Affymetrix GeneChips). Internal validation showed that most of the spotted probes displayed a pattern of reaction close to that predicted by the model. By using simple rules for comparison of data between platforms we found strong correlations (rmedian= 0.84) between relative gene expression measurements made with spotted probes and in situ-synthesized 25-mer probe sets. CONCLUSION: In conclusion our data suggest that there is a high reproducibility of the APOCHIP in terms of technical replication and that relative gene expression measurements obtained with the APOCHIP compare well to the Affymetrix GeneChip. The APOCHIP is available to the scientific community and is a useful tool to study the molecular mechanisms regulating beta-cell apoptosis.

Algorithms↗

PubMed2002

Internal and external validation of the NOSEP prediction score for nosocomial sepsis in neonates.

OBJECTIVE: To evaluate the performance of a scoring system (NOSEP) to predict nosocomial sepsis in neonates at the hospital where the score was developed (internal validation) and in an independent data set from other centers (external validation). DESIGN: Multiple center prospective cohort study. SETTING: Six neonatal intensive care units from the Flanders in Belgium. PATIENTS: We analyzed two groups of patients: 62 episodes of presumed nosocomial sepsis in the internal validation cohort and 93 episodes of presumed nosocomial sepsis in a multiple center external validation cohort. INTERVENTIONS: Assessment of the predictive power of the NOSEP score 24 hrs preceding sepsis workup and the patients' basic demographic characteristics and co-morbidity was performed. Diagnosis of nosocomial sepsis and the microbiology results were registered. MAIN RESULTS: The NOSEP score's discriminative capability was very good in the internal validation (area under receiver operating characteristic curve = 0.73 +/- 0.08 [sem]). The NOSEP score performed satisfactory in the external validation (area under receiver operating characteristic curve = 0.66 +/- 0.06). The calibration capability in both validation sets as measured by goodness-of-fit tests (internal validation, p =.56; external validation, p =.48) was good. An improvement of the NOSEP score was obtained for the external centers by redefining the cut-off of the items of the NOSEP score (area under receiver operating characteristic curve for NOSEP-NEW-I = 0.71 +/- 0.05) or adding co-morbidity factors (area under receiver operating characteristic curve for NOSEP-NEW-II = 0.82 +/- 0.04), with good calibration performance (goodness-of-fit test, p >.50). Finally, the fit of the NOSEP score demonstrated no significant variation across subgroups of patients. CONCLUSIONS: The predictive power of the original NOSEP score is very good in neonates at the original neonatal intensive care unit. In other neonatal intensive care units, its discriminatory performance is satisfactory but could be improved after modification of the variables in the model or adding additional variables. To use such a NOSEP score in other neonatal intensive care units, its accuracy has to be validated and adjusted if necessary.

Cross Infection↗

PubMed2001

Dimensionality, responsiveness and standardization of the Bech-Rafaelsen Mania Scale in the ultra-short therapy with antipsychotics in patients with severe manic episodes.

OBJECTIVE: Typical antipsychotics have their indication in the ultra-short (first week) treatment of severe episodes of mania. In this setting the Bech-Rafaelsen Mania Scale (MAS) was psychometrically compared with the Clinical Global Impression scale (CGI) to assess its ability to measure response. METHOD: Ratings on patients with marked to severe mania (n = 80) who participated in the clinical trials to evaluate the ultra-short antimanic effect of zuclopenthixol acetate were assessed. The MAS was analysed for internal validity (total score a sufficient statistic) and for external validity. RESULTS: The MAS was shown to have a high internal validity showing onset of action already after days of treatment. After 6 days of treatment 53% of the patients responded according to the MAS but only 30% according to the CGI. The difference was statistically significant. CONCLUSION: The MAS has been found to be a valid scale to measure early onset of action and response in the ultra-short antimanic treatment with typical antipsychotics.

Aged↗

PubMed1978

Validity of the 24-hr. dietary recall and seven-day record for group comparisons.

The internal validity of a 24-hr. dietary recall and a seven-day dietary record was investigated among a group of non-institutionalized elderly subjects who were participating in a congregate meals program. Internal validity was assessed by comparing reported intake with unobtrusively obtained data on actual intake. Validity results suggest that the recall is prone to over-reporting low intakes and under-reporting high intakes. This pattern has been referred to as the "flat-slope syndrome." Records collected during the first few dyas were less prone to this syndrome; however, validity declined by the fifth, sixth, and seventh record days. Also, as the record progressed to the seventh day, the demographic nature of the sample became biased due to drop-outs and decreased usability of the records.

Aged↗

PubMed2005

Evaluation of a revised instrument to assess the needs of men diagnosed with prostate cancer.

BACKGROUND: This study was conducted to assess the face, content and construct validity and the internal validity of the revised version of an instrument to measure the perceived needs of men diagnosed with prostate cancer [Prostate Cancer Needs Questionnaire version 2 (PCNQv2)]. The PCNQ was constructed in two parts with Part 1 measuring needs at diagnosis and initial treatment and Part 2 measuring current needs. METHODS: A random sample of 650 men diagnosed with prostate cancer attending a Urologist of the Hunter Urology Group in Newcastle, New South Wales, Australia, were invited to participate in the study and sent by post the self-administered PCNQ. Information was provided on 145 men who were considered ineligible to participate. Completed questionnaires were received from 300 men. RESULTS: The principal components method of factor analysis with varimax orthogonal rotation identified eight factors with eigenvalues greater than 1, which together accounted for 68% of the variance in Part 1 of the PCNQ. Likewise, six factors were identified in Part 2 which accounted for 68% of the variance. Internal reliability coefficients (Cronbach's alpha) were adequate for identified factors with values ranging from 0.71 to 0.90 for Part 1, and from 0.80 to 0.92 for Part 2. CONCLUSIONS: These results support the validity and reliability of the PCNQv2 to assess the perceived needs experienced by men diagnosed with prostate cancer.

Adult↗

PubMed2004

New trends in HDF therapies: validity of internal filtration-enhanced hemodialysis.

Internal filtration-enhanced hemodialysis (IFEHD), defined as HD therapy using a dialyzer designed for enhanced internal filtration, seems to be more convenient in comparison with HDF therapies. In this paper, the validity of IFEHD was discussed during an analytical study and experimental studies. As a result, the maximum internal filtration flow rate (Q(IF)) value increased with a smaller inner diameter (D), a longer effective length (L(eff)), and a larger density ratio (DR) value of the hollow fibers. The validity of IFEHD was clarified by an analytical study and experimental studies. Development of a dialyzer with enhanced internal filtration, however, should take account of the patient's safety, and hemolysis and endotoxin invasion form the dialysate to the patient should be avoided.

Equipment Design↗

PubMed2003

Internal and external validation of predictive models: a simulation study of bias and precision in small samples.

We performed a simulation study to investigate the accuracy of bootstrap estimates of optimism (internal validation) and the precision of performance estimates in independent validation samples (external validation). We combined two data sets containing children presenting with fever without source (n=376+179=555; 120 bacterial infections). Random samples were drawn from this combined data set for the development (n=376) and validation (n=179) of logistic regression models. The models included statistically significant predictors for infection selected from a set of 57 candidate predictors. Model development, including the selection of predictors, and validation were repeated in a bootstrapping procedure. The resulting expected optimism estimate in the receiver operating characteristic (ROC) area was compared with the observed optimism according to independent validation samples. The average apparent ROC area was 0.74, which was expected (based on bootstrapping) to decrease by 0.07 to 0.67, whereas the observed decrease in the validation samples was 0.09 to 0.65. Omitting the selection of predictors from the bootstrap procedure led to a severe underestimation of the optimism (decrease 0.006). The standard error of the observed ROC area in the independent validation samples was large (0.05). We recommend bootstrapping for internal validation because it gives reasonably valid estimates of the expected optimism in predictive performance provided that any selection of predictors is taken into account. For external validation, substantial sample sizes should be used for sufficient power to detect clinically important changes in performance as compared with the internally validated estimate.

Bias↗

PubMed2005

Extending McNemar's test: estimation and inference when paired binary outcome data are misclassified.

McNemar's test is popular for assessing the difference between proportions when two observations are taken on each experimental unit. It is useful under a variety of epidemiological study designs that produce correlated binary outcomes. In studies involving outcome ascertainment, cost or feasibility concerns often lead researchers to employ error-prone surrogate diagnostic tests. Assuming an available gold standard diagnostic method, we address point and confidence interval estimation of the true difference in proportions and the paired-data odds ratio by incorporating external or internal validation data. We distinguish two special cases, depending on whether it is reasonable to assume that the diagnostic test properties remain the same for both assessments (e.g., at baseline and at follow-up). Likelihood-based analysis yields closed-form estimates when validation data are external and requires numeric optimization when they are internal. The latter approach offers important advantages in terms of robustness and efficient odds ratio estimation. We consider internal validation study designs geared toward optimizing efficiency given a fixed cost allocated for measurements. Two motivating examples are presented, using gold standard and surrogate bivariate binary diagnoses of bacterial vaginosis (BV) on women participating in the HIV Epidemiology Research Study (HERS).

Biometry↗

PubMed2004

Preoperative probability model for predicting overall survival after resection of pulmonary metastases from colorectal cancer.

BACKGROUND: The aim of this study was identify readily available factors most helpful in predicting survival and to develop a prognostic nomogram for patients with pulmonary metastases from colorectal cancer who are candidates for thoracotomy. METHODS: Pretreatment data on 313 patients with metastases who underwent thoracotomy were analysed. Fourteen preoperative clinical and pathological variables were used to develop a probability model, in which their association with 3-year survival was tested. A nomogram to predict median, 1- and 3-year survival was constructed and validated internally using the concordance index (c-index). The nomogram was then validated with an external data set. RESULTS: Five variables were identified as independent predictors of 3-year survival: prethoracotomy carcinoembryonic antigen level, number of pulmonary tumours, presence of hilar or mediastinal tumour-infiltrated lymph nodes, histology of the primary tumour and presence of extrathoracic disease. The nomogram was well calibrated for predicting 3-year overall survival. The internal validated c-index of the nomogram was 0.72. Applied to another data set, the external validated c-index was 0.66. CONCLUSION: This model has moderate predictive ability to discriminate between patients who are likely to survive after thoracotomy for pulmonary metastases from colorectal cancer.

Adult↗

PubMed2006

Comparative residue interaction analysis (CoRIA): a 3D-QSAR approach to explore the binding contributions of active site residues with ligands.

A novel approach termed comparative residue-interaction analysis (CoRIA), emphasizing the trends and principles of QSAR in a ligand-receptor environment has been developed to analyze and predict the binding affinity of enzyme inhibitors. To test this new approach, a training set of 36 COX-2 inhibitors belonging to nine families was selected. The putative binding (bioactive) conformations of inhibitors in the COX-2 active site were searched using the program DOCK. The docked configurations were further refined by a combination of Monte Carlo and simulated annealing methods with the Affinity program. The non-bonded interaction energies of the inhibitors with the individual amino acid residues in the active site were then computed. These interaction energies, plus specific terms describing the thermodynamics of ligand-enzyme binding, were correlated to the biological activity with G/PLS. The various QSAR models obtained were validated internally by cross validation and boot strapping, and externally using a test set of 13 molecules. The QSAR models developed on the CoRIA formalism were robust with good r (2), q (2) and r (pred) (2) values. The major highlights of the method are: adaptation of the QSAR formalism in a receptor setting to answer both the type (qualitative) and the extent (quantitative) of ligand-receptor binding, and use of descriptors that account for the complete thermodynamics of the ligand-receptor binding. The CoRIA approach can be used to identify crucial interactions of inhibitors with the enzyme at the residue level, which can be gainfully exploited in optimizing the inhibitory activity of ligands. Furthermore, it can be used with advantage to guide point mutation studies. As regards the COX-2 dataset, the CoRIA approach shows that improving Coulombic interaction with Pro528 and reducing van der Waals interaction with Tyr385 will improve the binding affinity of inhibitors.

Binding Sites↗

PubMed2006

Quality criteria were proposed for measurement properties of health status questionnaires.

OBJECTIVES: Recently, an increasing number of systematic reviews have been published in which the measurement properties of health status questionnaires are compared. For a meaningful comparison, quality criteria for measurement properties are needed. Our aim was to develop quality criteria for design, methods, and outcomes of studies on the development and evaluation of health status questionnaires. STUDY DESIGN AND SETTING: Quality criteria for content validity, internal consistency, criterion validity, construct validity, reproducibility, longitudinal validity, responsiveness, floor and ceiling effects, and interpretability were derived from existing guidelines and consensus within our research group. RESULTS: For each measurement property a criterion was defined for a positive, negative, or indeterminate rating, depending on the design, methods, and outcomes of the validation study. CONCLUSION: Our criteria make a substantial contribution toward defining explicit quality criteria for measurement properties of health status questionnaires. Our criteria can be used in systematic reviews of health status questionnaires, to detect shortcomings and gaps in knowledge of measurement properties, and to design validation studies. The future challenge will be to refine and complete the criteria and to reach broad consensus, especially on quality criteria for good measurement properties.

Evaluation Studies as Topic↗

PubMed2002

Reliable and valid self-report outcome measures in sexual (dys)function: a systematic review.

This paper examines the published reliability and validity of non-disease specific, self-report measures of sexual function. Relevant papers were found in a search of the Embase electronic bibliographic database, for English language papers (published 1980-99) reporting on the psychometric testing of sexual function questionnaires. Existing published reviews or collections of such instruments were also searched, and the reference lists of all papers obtained were "back-searched" to identify other measures. Included measures were evaluated in a systematic manner using published standards concerning the validity, internal consistency, and reproducibility of health measurement scales and quality of life measures. Twenty-three self-report measures were identified for inclusion in this review. A further 2 measures were identified by reviewers of this paper after the main searches were undertaken. One measure was found not to be exclusively self-report. Eleven (46% of 24 included measures) did not meet minimum published standards for reliability, internal consistency, and validity. However one of these was reliable and valid in the female-version only. Of the 14 reliable and valid measures, or versions thereof (58% of 24), 2 (8% of 24) met "superior" psychometric standards. Many measures were developed for use with patients in sex or marital therapy, and are mainly suitable for administration to people with long-term sex partners. It is sensible to assume that instruments are only reliable and valid in the often specialized populations in which they were developed.

Female↗

PubMed2005

Practical clinical trials for translating research to practice: design and measurement recommendations.

RATIONALE: There is a pressing need for practical clinical trials (PCTs) that are more relevant to clinicians and decision-makers, but many are unaware of these trials. Furthermore, such trials can be challenging to conduct and to report. OBJECTIVE: The objective of this study was to build on the seminal paper by Tunis et al (Practical clinical trials. Increasing the value of clinical research for decision making in clinical and health policy. JAMA. 2003;290:1624-1632.) and to provide recommendations and examples of how practical clinical trials can be conducted and the results reported to enhance external validity without sacrificing internal validity. KEY ISSUES: We discuss evaluating practical intervention options, alternative research designs, representativeness of samples participating at both the patient and the setting/clinician level, and the need for multiple outcomes to address clinical and policy implications. CONCLUSIONS: We provide a set of specific recommendations for issues to be reported in PCTs to increase their relevance to clinicians and policymakers, and to help reduce the gap between research and practice.

Clinical Trials as Topic↗

PubMed2006

Classification of breast cancer using genetic algorithms and tissue microarrays.

PURPOSE: A multitude of breast cancer mRNA profiling studies has stratified breast cancer and defined gene sets that correlate with outcome. However, the number of genes used to predict patient outcome or define tumor subtypes by RNA expression studies is variable, nonoverlapping, and generally requires specialized technologies that are beyond those used in the routine pathology laboratory. It would be ideal if the familiarity and streamlined nature of immunohistochemistry could be combined with the rigorously quantitative and highly specific properties of nucleic acid-based analysis to predict patient outcome. EXPERIMENTAL DESIGN: We have used AQUA-based objective quantitative analysis of tissue microarrays toward the goal of discovery of a minimal number of markers with maximal prognostic or predictive value that can be applied to the conventional formalin-fixed, paraffin-embedded tissue section. RESULTS: The minimal discovered multiplexed set of tissue biomarkers was GATA3, NAT1, and estrogen receptor. Genetic algorithms were then applied after division of our cohort into a training set of 223 breast cancer patients to discover a prospectively applicable solution that can define a subset of patients with 5-year survival of 96%. This algorithm was then validated on an internal validation set (n=223, 5-year survival=95.8%) and further validated on an independent cohort from Sweden, which showed 5-year survival of 92.7% (n=149). CONCLUSIONS: With further validation, this test has both the familiarity and specificity for widespread use in management of breast cancer. More generally, this work illustrates the potential for multiplexed biomarker discovery on the tissue microarray platform.

Algorithms↗

PubMed1998

The problem of protocol driven costs in pharmacoeconomic analysis.

The increasing number of economic evaluations of healthcare interventions and of drug therapies in particular has been well documented. Surveys of the quality of studies have demonstrated that standards of conduct of such studies have not similarly increased. Concerns over the standards have led to increased calls that economic analyses be more closely linked to randomised controlled clinical trials (RCT). Seven potential threats to the external validity of results limit the generalisability of studies based on RCTs. One such threat is the existence of protocol driven costs. There are two main types of protocol driven costs. Protocol prescribed costs arise as a result of resource use mandated by the clinical trial design. Protocol derived costs occur when increased clinical investigations mandated by trial protocols lead to atypical disease management. Methods to control for protocol driven costs within pharmacoeconomic study designs are available. Modelling studies can be based on data within clinical trials combined with observational data representing more typical resource use. The adoption of pragmatic clinical trial designs provide greater external validity though reduced internal validity. Refinements to explanatory clinical trials can also lead to reduced protocol driven costs. The extent that current studies control for such costs is unclear due to the lack of transparency in the reporting of study methods. A review of published studies found little consideration of protocol driven costs although in several studies there was evidence of their existence. Future studies conducted alongside RCTs should explicitly address how the issue of protocol driven costs was handled within the study framework.

Economics, Pharmaceutical↗

PubMed1976

Health care from a behavioral-ecological viewpoint.

While the intended thrust of this paper has been to elicidate the tremendous potential of the behavioral-ecological perspective for health care research and application, the intent has not been to underplay the important role of the biological sciences in the same venture. However, it is my contention that a behavioral-ecological approach to the study of health care has been widely neglected in health care functions and research. In terms of conventional research designs and terminology, the behavioral-ecological research implications can be summarized as follows: a behavioral-ecological perspective of health care research suggests research that is experimental rather than correlational-descriptive; that focuses, because of its naturalistic thrust, on external validity more than internal validity; that incorporates as independent design variables the environmental context in which health behaviors occur; and that allows single-subject as well as multiple-group designs as research strategy. Finally, in terms of dependent variables, the research design requires a clear identification of the observable characteristics of the target health behaviors under consideration. In summary, health research geared toward professional goals appears to profit significantly from an ecological-behavioral approach which provides a model of high explication, specificity, and objectivity for knowledge generation and immediate application.

Behavior Therapy↗

PubMed2005

A two-stage design for bridging studies.

The ICH E5 guideline defines a bridging study as a supplementary study conducted in the new region to provide pharmacodynamic or clinical data on efficacy, safety, dosage, and dose regimen to allow extrapolation of the foreign clinical data to the population of the new region. Therefore, a bridging study is usually conducted in the new region only after the test product has been approved for commercial marketing in the original region based on its proven efficacy and safety. One of the current issues for evaluation of bridging studies is a cross-study comparison. Therefore, bias occurs when the study is not internally valid. A two-stage approach is proposed to overcome the issue of internal validity and at the same time to meet the objective of minimizing unnecessary duplication of clinical data required by the ICH E5 guideline. Under the framework of the proposed two-stage design, the bridging study of the new region is a second-stage substudy of the whole trial, and the patients for the bridging substudy are enrolled only after the data obtained in the original region demonstrate a statistically significantly positive treatment effect. Methods for the determination of the sample size for each region and the critical values at each stage are also proposed.

Clinical Trials as Topic↗

PubMed2001

Development and validation of a clinical prediction rule for major adverse outcomes in coronary bypass grafting.

In this study, we develop and internally validate a clinical prediction rule for in-hospital major adverse outcomes, defined as death, renal failure, reinfarction, cardiac arrest, cerebrovascular accident, or coma, in patients who underwent coronary artery bypass grafting (CABG). All adult patients (n = 9,498) who underwent a CABG and no other concomitant surgery at 12 academic medical centers from August 1993 to October 1995 were included in the study. We assessed in-hospital major adverse outcomes and their predictors using information on admission, coronary angiography, and postoperative hospital course. Predictor variables were limited to information available before the procedure, and outcome variables were represented only by events that occurred postoperatively. We developed and internally validated a clinical prediction rule for any major adverse outcome after CABG. The rule's ability to discriminate outcomes and its calibration were assessed using receiver-operating characteristic analysis and the Hosmer-Lemeshow goodness-of-fit statistic, respectively. A major adverse outcome occurred in 6.5% of patients in the derivation set and 7.2% in the validation set. Death occurred in 2.5% of patients in the derivation set and 2.2% in the validation set. Sixteen variables were independently correlated with major adverse outcomes, with the risk score value attributed to each risk factor ranging from 2 to 12 points. The rule stratified patients into 6 levels of risk based on the total risk score. The spread in probability between the lowest and highest risk groups of having a major adverse outcome was 1.7% to 32.3% in the derivation set and 2.2% to 22.3% in the validation set. The prediction model performed well in both outcome discrimination and calibration. Thus, this clinical prediction rule allows accurate stratification of potential CABG candidates before surgery according to the risk of experiencing a major adverse outcome postoperatively.

Aged↗