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At least 649 records · Page 36Linked to original sources

PubMed2002

Programmed electrical stimulation in Brugada syndrome: how reproducible are the results?

INTRODUCTION: Inducibility of ventricular arrhythmias at programmed electrical stimulation (PES) ranges between 50% and 80% of patients with Brugada syndrome. However, the variety of PES protocols and the lack of data relative to a control group or to ventricular arrhythmia reproducibility contribute to a still undefined interpretation of PES outcome in Brugada syndrome. METHODS AND RESULTS: Twenty-one patients with Brugada syndrome (18 men and 3 women; mean age 34 years; 9/21 symptomatic; 8/21 with SCN5A gene mutation) underwent a PES protocol from two right ventricular sites. The endpoint was PES protocol completion or induction of sustained or reproducible (>6 consecutive inductions) nonsustained (>6 beats) fast ventricular arrhythmia. In 17 of 21 patients with Brugada syndrome, PES was repeated 2 months later to test ventricular arrhythmia reproducibility. Twenty-five healthy patients (17 men; mean age 36 years) formed the control group. In patients with Brugada syndrome, ventricular arrhythmia inducibility rate at PES was high (18/21 patients [85%]) and increased with protocol aggressiveness, independent of clinical presentation. In control subjects, no ventricular arrhythmias were induced. Among patients with Brugada syndrome, 14 (82%) of 17 patients remained inducible at a second PES. CONCLUSION: In our experience, ventricular arrhythmia inducibility in patients with Brugada syndrome, at variance with healthy controls, is high and does not correlate with clinical presentation. PES inducibility is deeply influenced by the protocol used. PES outcome is reproducible at a mid-term follow-up mainly if a categorical endpoint (inducible vs noninducible) is used. The need to assess the predictive value of specific PES protocols in targeted studies is widely emerging and is confirmed by our results.

Adult↗

PubMed1999

In vitro analysis of coronary atheromatous lesions by intravascular ultrasound; reproducibility and histological correlation of lesion morphology.

AIM: To determine the reproducibility and histological correlation of qualitative intravascular ultrasound imaging of atheromatous coronary arteries using the recently proposed European Society of Cardiology classification of plaque composition in conditions approximating the clinical setting. METHODS: Atheromatous lesions (n=21), identified from 30 post-mortem human coronary arteries, were imaged using intravascular ultrasound in a pulsatile flow system which simulates coronary flow. Fifty sites (21 x minimum lumen area and 29 x distal reference sites) were selected independently by two observers from continuous video recordings. Atheromatous plaque was classified as echodense, echolucent, heterogeneous or calcified by each observer and by one observer on separate occasions. Arterial specimens were histologically sectioned at these sites and similarly analysed by a third observer blinded to the intravascular ultrasound appearances. RESULTS: Overall inter- and intra-observer reproducibility for plaque-type (Kappa 0.87[0.80-0.94] and 0.89[0. 85-0.93 respectively]) and focal calcification (0.78[0.74-0.82] and 0.88[0.84-0.92]) was high. Differences in site selection significantly influenced reproducibility particularly at reference sites. Agreement for overall plaque type between intravascular ultrasound and histology occurred in 89% of sites (Kappa 0.73[0.69-0. 77]). Specificity and positive predictive values for individual plaque types were greater than 90%. CONCLUSION: Using modern intravascular ultrasound technology in an in vitro system which approximates the clinical setting the proposed ESC classification of plaque composition by intravascular ultrasound is reproducible and correlates well with histology. It should therefore perform reliably in diagnostic intravascular ultrasound examinations and in the guidance of percutaneous coronary interventions.

Aged↗

PubMed2002

Intra- and inter-observer reproducibility of transthoracic pulmonary venous Doppler flow indices after acute myocardial infarction.

AIMS: To examine the intra- and inter-observer reproducibility of pulmonary venous flow indices in patients with acute myocardial infarction. METHODS: Two investigators, blinded to the results of the other examination, each examined 28 clinically stable post infarction patients in sinus rhythm. The two stored digital Doppler recordings from each patient were analysed in a blinded manner by both investigators to obtain the intra- and inter-observer reproducibility including both a new recording and new measurements. RESULTS: The intra- and inter-observer coefficients of variation for the different variables ranged between 5-15% and 8-23% respectively. For some of the indices there was a difference in means between the observers, and the indices were influenced in different degree by a new measurement and new recording. The degree of variability found in this study indicates wide relative limits of agreement, ranging from +/-10% to +/-45%. CONCLUSION: The reproducibility of pulmonary venous flow indices was only moderate with relatively wide limits of agreement. The reproducibility was, however, comparable to other echocardiographic measurements of left ventricular dimensions and function.

Adult↗

PubMed2005

Reproducibility of the new indicator test for sudomotor function (Neuropad) in patients with type 2 diabetes mellitus: short communication.

UNLABELLED: The aim of this study was to examine the reproducibility of the new indicator test for sudomotor function (Neuropad) in type 2 diabetic patients. The study included 142 type 2 diabetic patients (70 men) with a mean age of 67.3 +/- 7.6 years and a mean diabetes duration of 14.2 +/- 6.3 years. Sudomotor function was assessed by means of colour change in the indicator test. Each patient was examined twice. Moreover, inter-observer variability was assessed in 60 patients (35 patients with sudomotor dysfunction, 25 patients without sudomotor dysfunction). In the right foot, a highly significant (r = 0.91, p = 0.001) correlation was observed between time until complete colour change of the test on the first (910.7 +/- 431.6 seconds) and second examination (935.8 +/- 440.1 seconds). In the left foot, a highly significant (r = 0.89, p = 0.001) correlation was observed between time until complete colour change of the test on the first (911.6 +/- 430.3 seconds) and second examination (940.5 +/- 441.2 seconds). Reproducibility was excellent both in patients with sudomotor dysfunction (p = 0.001) and in those without sudomotor dysfunction (p = 0.001). Agreement in diagnosis of sudomotor dysfunction between the two examinations was 98 %. Inter-observer reproducibility was excellent (p = 0.001), both in patients with sudomotor dysfunction and in those without sudomotor dysfunction. Intra- and interobserver Coefficient of Variance ranged between 4.1 % and 5.1 %. CONCLUSIONS: These results indicate that reproducibility of the new indicator test for sudomotor function is excellent in type 2 diabetic patients with or without sudomotor impairment.

Aged↗

PubMed1999

Ventilatory, lactate-derived and catecholamine thresholds during incremental treadmill running: relationship and reproducibility.

Anaerobic threshold as a basic criterion of training recommendation can be estimated by various parameters. The purpose of this study was to investigate the relationship and the reproducibility of ventilatory, lactate-derived and catecholamine thresholds of an incremental treadmill exercise. Therefore, 11 male subjects underwent two incremental treadmill tests within 7 days. The lactate threshold (LT) was determined at the lowest value of the lactate-equivalent (ratio lactate/performance). The individual anaerobic threshold (IAT) was calculated at LT+1.5 mmol/L lactate. The ventilatory thresholds, using mass-spectrometry, were defined by the V-slope method (AT) and at the deflection point of end-tidal CO2 (ET-CO2) concentration (RCP). The thresholds of epinephrine (TE) and norepinephrine (TNE) were calculated in the manner of LT. The running velocities were highly reproducible at LT (test-retest correlation coefficient r=0.90), IAT (r=0.97), AT (r=0.88) and RCP (r=0.95). By contrast TE (r=0.49) and TNE (r=0.46) showed a poor reproducibility. TE and TNE occurred 5-11% below LT and AT with a low correlation to LT and AT. LT was found 4% below AT, both were correlated with r=0.70 (p<0.01, test 1) and r=0.95 (p<0.01, test 2). IAT occurred 7-8% above RCP, in both tests a close correlation was found between IAT and RCP of r=0.97 (p<0.01). In summary, the ventilatory and lactate-derived thresholds show a high and similar reproducibility, but the catecholamine threshold does not. In the present exercise protocol, there are systematic differences between the lactate-derived and ventilatory thresholds, in spite of a close relationship, and these must be taken into account in recommendations derived for training.

Adult↗

PubMed1998

Reproducibility of self-paced treadmill performance of trained endurance runners.

The reproducibility of performance in a laboratory test impacts on the statistical power of that test to detect changes of performance in experiments. The purpose of this study was to determine the reproducibility of performance of distance runners completing a 60 min time trial (TT) on a motor-driven treadmill. Eight trained distance runners (age 27 +/- 7yrs, peak oxygen consumption [VO2peak] 66 +/- 5 ml x min(-1) x kg(-1), mean +/- SD) performed the TT on three occasions separated by 7-10 days. Throughout each TT the runners controlled the speed of the treadmill and could view current speed and elapsed time, but they did not know the elapsed or final distance. On the basis of heart-rate, it is estimated that the subjects ran at an average intensity equivalent to 80-83% of VO2peak. The distance run in 1 h did not vary substantially between trials (16.2 +/- 1.4 km, 15.9 +/- 1.4 km, and 16.1 +/- 1.2 km for TTs 1-3 respectively, p = 0.5). The coefficient of variation (CV) for individual runners was 2.7% (95% Cl = 1.8-4.0%) and the test-retest reliability expressed as an intraclass correlation coefficient was 0.90 (95% Cl = 0.72-0.98). Reproducibility of performance in this test was therefore acceptable. However, higher reproducibility is required for experimental studies aimed at detecting the smallest worthwhile changes in performance with realistic sample sizes.

Adult↗

PubMed1999

Normal ranges and reproducibility of statistical, geometric, frequency domain, and non-linear measures of 24-hour heart rate variability.

Diabetic cardiovascular autonomic neuropathy (CAN) carries an increased risk of mortality. The early detection and characterization of CAN has traditionally been based on the results of autonomic reflex tests (AFTs). A variety of different measures to quantify 24-hour heart rate variability (HRV) have recently been introduced, but their normal ranges, reliability, and validity in patients with CAN have not been adequately studied. We established the normal ranges of statistical (SDNN index, CV, SNN50, RMSSD), geometric (triangular index (TI), triangular interpolation (TINN), top angle index [TAI]), frequency domain (spectral power in the VLF, LF, and HF bands, LF/HF ratio, LF in normalized units [NU]), and non-linear measures (CV1 and CV2 of the Poincaré plot) of 24-hour HRV in 94 healthy control subjects. Day-to-day reproducibility was evaluated on two occasions in 17 healthy subjects and 9 diabetic patients. The parameters of HRV were computed over time periods representing the day (6:00-24:00 hours), night (00:00-6:00 hours), and 24 hours in total. The results of all indexes, except for the LF/HF ratio and LF-NU, declined significantly with increasing age (p<0.05), but were independent of sex and BMI. The statistical, geometric, and non-linear measures (p<0.05), but not the frequency-domain parameters decreased significantly with increasing heart rate. Since the HRV data showed log normal distribution, log transformation was used to define the age-related lower limits of normal at the 2.5th centile. Intraindividual reproducibility was highest for the geometric measures. The nonlinear and statistical parameters also showed high reliability, except for the SNN50. The repeatability of the frequency domain measures was somewhat lower but still satisfactory. Reproducibility was lower in the diabetic than in the control group, higher during the day than during the night, and better than that reported previously for the AFTs. In conclusion, in healthy subjects the measures of 24-h HRV are not related to sex or BMI, but strongly dependent on age and heart rate, the latter except for the frequency domain measures. The majority of the HRV measures, in particular the geometric parameters, show a relatively high intraindividual reproducibility which underlines their suitability for the use in prospective studies.

Adult↗

PubMed2001

PrimeScreen, a brief dietary screening tool: reproducibility and comparability with both a longer food frequency questionnaire and biomarkers.

OBJECTIVE: Diet is an important determinant of health outcomes, but physicians have few ways to identify persons with suboptimal diets. The purposes of this study were to examine the reproducibility of a short dietary assessment questionnaire (PrimeScreen) and to compare its results with those of a longer food frequency questionnaire and with plasma levels of selected nutrients. DESIGN: Each subject completed two PrimeScreen questionnaires at an interval of 2 weeks and one full length, 131-item, semiquantitative food frequency questionnaire (SFFQ), and had a sample of blood drawn. We compared the PrimeScreen with two reference standards, the SFFQ and plasma levels of selected nutrients. SETTING: A large managed care organization in New England. SUBJECTS: A total of 160 men and women, aged 19-65 years, participated. RESULTS: For foods and food groups, the mean correlation coefficient (r) was 0.70 for reproducibility and 0.61 for comparability with the SFFQ. For nutrients, the mean r was 0.74 for reproducibility and 0.60 for comparability with the SFFQ. No substantial differences were evident by sex, race, body mass index, occupation or education. Correlation coefficients for the comparison of vitamin E, beta-carotene and lutein/zeaxanthin intakes from the PrimeScreen with plasma levels were 0.33, 0.43 and 0.43, respectively. These values were similar to those comparing the SFFQ with plasma levels. The median time to complete PrimeScreen was 5 min; 87% of participants required fewer than 10 min. CONCLUSIONS: A quick way to assess quality of diet among adults, PrimeScreen has adequate reproducibility and its results compare well with a longer food frequency questionnaire and biomarkers.

Adult↗

PubMed2003

Reproducibility and validity of a food-frequency questionnaire for use among low-income Brazilian workers.

OBJECTIVES: To assess the reproducibility and validity a 127-item, habitual intake, food-frequency questionnaire (FFQ), developed for low-income and low-literacy Brazilian workers, by comparison with a 24-hour dietary recall (24-HDR). DESIGN: The FFQ and 24-HDR were interviewer-administered at the local workplace to each subject twice, with a period of 6 months between estimates; and four 24-HDRs were conducted during the 4-month period between the two FFQs (FFQ1 and FFQ2). Reproducibility was tested by comparing mean nutrient intakes from the two FFQs. Validity was determined by comparing the mean nutrient intakes from the FFQs with the corresponding averages of the six 24-HDRs (reference method). SETTING: Goiânia City, in Central West Brazil. SUBJECTS: The study was based on 104 (62 women and 42 men) subjects, aged 18 to 60 years, who were randomly selected. RESULTS: Dietary intake from the FFQ was higher than from the 24-HDR. Reproducibility was assessed by Pearson correlation coefficients for nutrients from FFQ1 and FFQ2, and ranged from 0.23 for retinol to 0.69 for total energy (mean 0.52). Intra-class coefficients for nutrients averaged by the 24-HDRs ranged from 0.29 for vitamin C to 0.76 for total energy; retinol was not significant. In the validation study, correlation between the FFQ and the 24-HDR ranged between 0.21 for vitamin C and 0.70 for total energy (mean 0.50). Adjusting for total energy lowered the coefficients, except for calcium, retinol and vitamin C. Coefficients increased with attenuation, ranging from 0.35 for carbohydrate to 0.65 for calcium. CONCLUSIONS: Results indicate that this questionnaire had satisfactory reproducibility and reasonable validity.

Adult↗

PubMed1996

A reproducible assay of polymerase chain reaction to detect trinucleotide repeat expansion of Huntington's disease and senile chorea.

A simple and reproducible method of polymerase chain reaction (PCR) assay was established to detect trinucleotide repeat expansion for Huntington's disease (HD) using a new DNA polymerase and buffer system. The system consists of an extremely heat stable DNA polymerase (Pfu), and a buffer supplemented with ammonium sulfate and dimethyl sulfoxide. Previous methods to amplify expanded alleles for HD have been very complex in PCR conditions, but the reproducibility was sometimes very low because of repetitive sequences around the primer sequences. With the present method, strong bands for the disease alleles were reproducibly visible in a conventional agarose gel stained with ethidium bromide without using isotopes. Three cases with sporadic HD and a case with senile chorea showed expanded alleles for HD with smaller sizes of the expansion than cases with typical HD. These results showed that the present method provides a simple and reproducible way to detect HD allele, and some cases with sporadic HD and senile chorea had expanded HD alleles.

Adult↗

PubMed1990

Reproducibility of a diet history in older men in Hawaii.

A diet history method was tested for reproducibility among 106 older men from the five major ethnic groups (Japanese, Caucasian, Hawaiian, Filipino, and Chinese) of Hawaii. The questionnaire, administered by trained interviewers, was designed to estimate the dietary intakes of total and saturated fat, cholesterol, vitamin A, beta-carotene, vitamin C, and zinc. Subjects were asked to recall their usual frequencies and amounts of consumption during a usual month of more than 100 food items, along with the intake of seasonal foods with a high vitamin A content. A second interview was conducted 1-14 months later to obtain a diet history covering the same time period as the first interview. The same questionnaire was utilized in both interviews. The effects of ethnicity, age, and recall interval (period between the diet reference date and initial interview) on the reproducibility of nutrient intakes were examined. The intraclass correlation coefficient (rI) and the weighted kappa statistic (Kw) were used to assess agreement. The overall levels of reproducibility were relatively good. Neither ethnicity, age, nor length of recall period had a major effect on reproducibility. The data suggested that this diet history method is an appropriate instrument for estimating the usual dietary intakes of a healthy heterogeneous group of older men in Hawaii.

Age Factors↗

PubMed1996

Diagnostic value and reproducibility of fine-needle aspiration cytology in canine malignant lymphoma.

Cytological examination of biopsy samples obtained by fine-needle aspiration appears to be an accurate and reliable basis for the classification of canine non-Hodgkin's lymphoma (NHL). Intra- and inter-observer reproducibility of both the original and the updated Kiel classification were assessed blindly on two occasions by two experienced cytologists who examined biopsy specimens from 78 dogs with NHL. Analysis by kappa statistics showed moderate to good intra-observer reproducibility and poor to moderate inter-observer reproducibility for the original Kiel classification. In the updated Kiel classification both intra- and inter-observer reproducibilities were good, probably due in part to the additional information provided by the immunotyping. The consensus cytological classifications were compared with those based on histology, and the association constant (Cramér's V) was 0.65 for the original Kiel classification and 0.70 for the updated Kiel classification. The results suggest that the updated Kiel classification in particular is suited to cytological classification of canine NHL.

Animals↗

PubMed1993

Spirometry--acceptability and reproducibility in spinal cord injured subjects.

The American Thoracic Society (ATS) has formulated guidelines for spirometry. We hypothesized that individuals with SCI (SCI), as a result of weak respiratory muscles, would exhibit poor test acceptability and reproducibility. Seventy-eight SCI subjects (39 with complete SCI) answered a respiratory questionnaire and performed spirometry. Of those with complete SCI, the proportion of subjects which met ATS criteria decreased with higher levels of injury. Poor test performance was not associated with age, respiratory symptoms or muscle fatigue. The most common reason for failing to meet ATS criteria for acceptability was excessive back extrapolated volumes (EBEV). Individuals with efforts that were acceptable except for EBEV and/or for exhalation of less than six seconds had values for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) that were reproducible. If ATS criteria for acceptable spirometry were used in studying subjects with SCI, individuals producing otherwise reproducible values for FVC and FEV1 would be excluded. We found reproducibility similar to what has been reported in other cohorts and conclude that longitudinal study of respiratory function in SCI is feasible.

Adult↗

PubMed1996

Reproducibility of relative dose response (RDR) test and serum retinol and retinyl ester concentrations in children after a 2-week interval.

OBJECTIVE: Reproducibility of the relative dose response test (RDR), a test designed to measure vitamin A status, was tested in 23 Belizean children, 5-8 years after 2-week interval during which no treatment was given. METHODS: As required for the RDR test, serum retinol concentrations were determined before and 5 hours after an oral dose of vitamin A. An RDR score > 14% was used as the criterion of inadequate vitamin A status. The HPLC method used to measure serum retinol concentrations also determined the concentrations of four retinyl esters. RESULTS: The RDR test was reproducible for 17 of 23 subjects: 3 scored > 14% on both tests; 14, < 14% on both. Six subjects scored > 14% on only one test. The concordance correlation coefficient (rc) for the percent change in the two tests was 0.24; for fasting serum retinol concentration, rc = 0.81. For retinyl palmitate and stearate, the esters present in highest concentrations at 5 hours, concordance correlation coefficients were 0.75 and 0.59, respectively. CONCLUSION: The failure of the RDR test to classify 26% of the subjects reproducibly reduces the usefulness of the test. In addition, the reproducibility of the retinyl ester concentrations in serum 5 hours after the retinyl palmitate dose and the relatively high concentrations in some subjects suggests that some individuals may not metabolize sufficient retinol in 5 hours to cause a maximal increase in serum retinol, resulting in an underestimation of deficiency in a population in which the RDR test is used.

Anticarcinogenic Agents↗

PubMed1999

Reproducibility of a survey questionnaire for the investigation of low back problems in adolescents.

A test-retest design was used to investigate the reproducibility of the results obtained using a survey questionnaire for low back problems in adolescents. A 1-wk interval between test and retest was chosen. Participants were recruited from four schools. Selection of schools was based on geographic location, size of the school and educational level. Sixty-seven adolescents (mean age = 16.62 y; SD = 0.57; range = 16-18) suffering from low back problems agreed to participate. A questionnaire on perceived characteristics of back problems and functional limitations was designed. Item completion rate and the reproducibility of results were investigated by means of percentage agreement and (weighted) kappa. High levels of reproducibility were found for items that evaluated perceived characteristics of back problems and functional limitations (Kw = 0.70-0.93). Results suggest that the questionnaire used in the present study provided reproducible information. Detailed information on low back problems in adolescents could be obtained using this questionnaire.

Adolescent↗

PubMed2004

Reproducibility of blood pressure variability, white-coat effect and dipping pattern in untreated, uncomplicated and newly diagnosed essential hypertension.

OBJECTIVE: To investigate the reproducibility of blood pressure (BP) variability, white-coat effect (WCE) and nocturnal dipping pattern in untreated patients with uncomplicated essential hypertension using 24-hour ambulatory BP monitoring (ABPM). METHODS: Seventy-five newly diagnosed, untreated essential hypertensive subjects (54 men, 21 women 47.6 +/- 9.3 years) were recruited for the study based on conventional measured BP from a total of 180 patients referred for ABPM. Of these, 65 patients underwent repeated ABPM after 4 weeks observation without treatment. Reproducibility of BP, nocturnal dipping pattern, WCE and BP variability were assessed using different methods. RESULTS: The average 24-hour BP (140.8 +/- 11.9/91.8 +/- 6.4 vs. 140.5 +/- 14.5/90.7 +/- 7.6 mmHg, ns) or PP (49.6 +/- 10.8 vs. 49.8 +/- 9.8 mmHg, ns) did not change, nor did daytime BP or PP. The WCE diminished significantly during the observation period (reduction in SBP WCE delta8.2 +/- 12.5 mmHg, p < 0.0001, in DBP WCE, delta3.3 +/- 9.2 mmHg, p = 0.008 and in PP WCE delta4.8 +/- 11.2 mmHg, p = 0.002). Variability in SBP, DBP and PP decreased consistently and significantly during the observation period. The nocturnal dipping pattern was unchanged in 82% of the patients. In 12% non-dipping pattern was converted to dipping pattern after repeated measurement. CONCLUSION: Average ABPs are highly reproducible in patients with uncomplicated essential hypertension of limited duration. Similarly, nocturnal dipping pattern reproduced satisfactorily. These measures have important clinical applicability. The white-coat effect as well as variability are greatly attenuated during repeated measurements, and these measures may thus be of less utility in clinical practice.

Adult↗

PubMed2005

Reproducibility and inter-observer variability of dobutamine stress CMR in patients with severe coronary disease: implications for clinical research.

PURPOSE: The purpose of this study was to analyze reproducibility and inter-observer variability of dobutamine stress cardiac magnetic resonance imaging (dobutamine CMR) and its implications on serial studies. METHODS: Nineteen consecutive patients underwent two dobutamine CMR each (median 12 days apart), as part of eligibility criteria for phase I/II stem cell therapy trial. These patients had Canadian Cardiovascular Society Class III/IV angina despite maximal therapy. The two studies were compared for reproducibility of stress response. To assess inter-observer variability, 29 randomly selected dobutamine CMR studies were analyzed by three experienced observers and Kappa values were computed to measure the agreement. RESULTS: Dobutamine CMR studies were completed without any major complications. The left ventricular function, dobutamine and atropine dose, hemodynamic response, symptomatic response and the results of wall motion and perfusion abnormalities were highly reproducible between the two studies (p = .91). Sample size calculations suggested that a clinical trial using dobutamine CMR to detect an endpoint of resolution of two ischemic segments would require a sample size of 20 subjects and to detect an improvement in perfusion of two segments would require a sample size of 8 subjects. Inter-observer variability between individual and consensus interpretation of dobutamine CMR was good to very good (kappa = 0.81 for wall motion and 0.70 for perfusion). CONCLUSION: Dobutamine CMR is a highly reproducible technique with very good inter-observer variability and could be used as a specific endpoint in a relatively small clinical trial.

Adrenergic beta-Agonists↗

PubMed2000

Statistical validation of reproducibility of HPLC peptide mapping for the identity of an investigational drug compound based on principal component analysis.

Peptide mapping is a key analytical method for studying the primary structure of proteins. The sensitivity of the peptide map to even the smallest change in the covalent structure of the protein makes it a valuable "fingerprint" for identity testing and process monitoring. We recently conducted a full method validation study of an optimized reverse-phase high-performance liquid chromatography (RP-HPLC) tryptic map of a therapeutic anti-CD4 monoclonal antibody. We have used this method routinely for over a year to test production lots for clinical trials and to support bioprocess development. One of the difficulties in the validation of the peptide mapping method is the lack of proper quantitative measures of its reproducibility. A reproducibility study may include method and system precision study, ruggedness study, and robustness study. In this paper, we discuss the use of principal component analysis (PCA) to quantitate peptide maps properly using its projected scores on the reduced dimensions. This approach allowed us not only to summarize the reproducibility study properly, but also to use the method as a diagnostic tool to investigate any troubles in the reproducibility validation process.

Antibodies, Monoclonal↗