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Results for “Surrogate variables analysis”

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PubMed1994

No improvement in survival from melanoma diagnosed from 1973 to 1984.

BACKGROUND: While the incidence and mortality of melanoma has increased dramatically during the last few decades, survival rates, based on the case-fatality ratio, have apparently improved. Efforts at early detection have probably been effective in the discovery of lesions at a curable stage. However, the effects of lead-time bias need to be accounted for in order to understand the contribution of early detection to the increased incidence. This can best be done by appropriately controlling for depth of the tumour or a surrogate of depth, at diagnosis. METHODS: A survival analysis was conducted for 3197 Connecticut residents newly diagnosed with invasive melanoma between 1973 and 1984. Five prognostic variables were evaluated: sex, age at diagnosis, anatomical site, histological type, and year of diagnosis. RESULTS: As expected, women and the young had better survival than men and the elderly. Melanomas located on the trunk had poorer prognosis than those on other sites. The survival experience by histological type was significantly different; lentigo maligna melanoma and superficial spreading melanoma had the best survival and nodular melanomas the poorest, while 'other' and unclassifiable melanomas had intermediate survival. When survival by period of diagnosis was controlled by other variables, which included surrogates for disease stage, there was no improvement in survival over time. CONCLUSION: These data do not imply that early diagnosis and treatment are ineffective; rather, that within stages of disease, survival improvements did not occur during the period 1973-1984.

Adolescent↗

PubMed2006

Lipoprotein lipase mRNA expression in whole blood is a prognostic marker in B cell chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is characterized by high individual variability in clinical course and the need for therapy. Differentiation of prognostic subgroups is based primarily on the mutation status of the genes for the variable region of the immunoglobulin heavy chain (IGHV). The time- and labor-intensive nature of this analysis necessitates the use of easily applicable surrogate markers. METHODS: We developed a quantitative PCR (qPCR) method for determining lipoprotein lipase (LPL) mRNA expression and analyzed samples of lysed whole blood and CD19-selected cells from 50 CLL patients. Associations of LPL and ZAP70 [zeta-chain (TCR) associated protein kinase 70 kDa] expression with IGHV mutation status, overall survival (OS), and treatment-free survival (TFS) were investigated. RESULTS: Lysed samples of whole blood and CD19-selected cells were similar with respect to LPL expression (R = 0.88; P <0.0001). LPL expression was significantly associated with IGHV mutation status [chi(2)(1) = 15.3; P <0.0001] and showed an 89.3% specificity, a 68.2% sensitivity, an 83.3% positive predictive value, and a 78.1% negative predictive value for IGHV mutation status. LPL expression was significantly associated with both OS and TFS in log-rank tests (both P values = 0.002). LPL-positive patients had a significantly shorter median TFS time (23 months) than LPL-negative patients (88 months) (P = 0.002). CONCLUSIONS: LPL mRNA expression is a valuable prognostic marker in CLL. The method does not require cell purification, and its applicability with archived samples facilitates its use in the clinical routine and other studies.

Adult↗

PubMed1992

Logical and analytic issues in dental/oral product comparison research.

Possible meanings of "superiority" and "equivalence" in comparative dental studies are considered. A proposed refinement of vocabulary is introduced to precisely distinguish between these meanings. Implications for data analysis of different interpretations of "superiority" and "equivalence" are explored, as are implications for study design where design and analytic considerations are inseparable. Conceptual problems of equivalence studies are stressed. Choice of analytic unit(s), scaling of dependent variables, use of surrogate variables, and validity checking are discussed as they pertain to comparative studies. Analytic methods for correlated responses and categorized responses are briefly surveyed, particularly with reference to periodontal research.

Analysis of Variance↗

PubMed2000

Development of a schedule-dependent population pharmacodynamic model for rhizoxin without quantitation of plasma concentrations.

In previous phase I reports of short bolus infusion of rhizoxin, problems in assay sensitivity prevented the description of pharmacokinetic-pharmacodynamic relationships, and a pharmacologically guided approach to dose escalation was deemed not feasible. In this report, we describe a mathematical model, which explains the schedule-dependent interpatient pharmacodynamic variability of rhizoxin administered on a continuous infusion schedule. Using patient demographic and toxicity data from 45 patients treated in a phase I dose and duration escalation study of rhizoxin, we sought to model the nadir neutrophil count. We hypothesized that a surrogate derived variable based on dose and duration would reflect a pharmacokinetic parameter that would be a significant covariate. Multiple linear regression analysis was carried out to determine the other significant covariates. Dose/m2 x Log(DUR/ALB) was significantly correlated with the LogANCnadir (Log10 neutrophil nadir; r = 0.56, P < 0.001). Other significant covariates included baseline performance status (PS), baseline serum bilirubin (BIL), and Log10 baseline neutrophil count (LogANCbaseline). Model bias and precision were assessed using the mean prediction error (MPE) and the root mean square error (RMSE) of the ANCnadir, respectively. We constructed 1-4 covariate models. The variability of ANCnadir was modeled with good precision and accuracy with a 4-covariate model (MPE and RMSE 0.113 +/- 0.182 x 10(3) cells/microl and 1.22 x 10(3) cells/microl, respectively). This model should be validated and improved on with further clinical data. We believe that such pharmacodynamic modeling should be explored further to determine its performance and clinical relevance compared with modeling using pharmacokinetic parameters.

Adult↗

PubMed2005

A gender-based score system predicts the clinical outcome of patients with early B-cell chronic lymphocytic leukemia.

To facilitate the development of a prognostic model for early B-cell chronic lymphocytic leukemia (CLL), the Gruppo Italiano Malattie EMatologiche Maligne dell'Adulto (GIMEMA) proposes its multi-institutional effort as a working model. In total, 1138 newly diagnosed Binet stage A patients managed over the last 10 years outside the setting of clinical trials according to a "wait and see" policy form the basis of the present study aimed at investigating prognostic variables affecting disease progression, a surrogate endpoint for overall survival. A 3-stage risk system, simply obtained by summing the variables that proved significant in the multivariate analysis (i.e. short lymphocyte doubling time, advanced Rai substage, high peripheral blood lymphocytosis), is proposed. Clear-cut differences in the 10 year progression-free survival (PFS) were observed among patients scoring 0 (low risk), 1 (intermediate risk), 2-3 (high risk): 67.8, 41.0 and 24.8%, respectively (P<0.0001). The results of the Medical Research Council (MRC) suggesting a better clinical outcome for females prompted us to verify such a gender-related difference within our prognostic categories. Because changes in PFS only reflected gender for patients scoring 0 (P=0.04), the following prognostic subgroups are proposed: (1) females scoring 0; (2) males scoring 0; (3) patients scoring 1-3 whatever gender (10 year PFS: 76.2, 61.4 and 37.8%; P<0.00001). Our long-term database provides an adequate patient sample to generate a generalized risk stratification model based on clinical data. The indolent clinical outcome of women with early CLL is also supported by the higher frequency of the immunoglobulin heavy-chain variable (IgVH) mutational status and lower proportion of 17p and 11q deletions found in such a patient subset in the MRC CLL4 trial.

Adult↗

PubMed1995

Multivariate models for predicting progression to AIDS and survival in human immunodeficiency virus-infected persons.

Nine hundred thirty persons enrolled in the US Air Force Human Immunodeficiency Virus (HIV) Natural History Study were evaluated with a standard battery of 30 potential surrogate markers of disease progression. A risk score for predicting progression to AIDS was then calculated for each patient in the cohort by using the four highest-ranking variables from multivariate analysis: percentage of CD4 CD29 cells, anergy status, age, and hemoglobin. For predicting survival, beta 2-microglobulin replaced age in the Cox model. Stratification according to the risk score demonstrated that rates of progression to AIDS and survival were significantly different between risk groups (P < .0001). The novel combination of these markers results in extremely accurate risk scores, which may serve as the basis for the development of true surrogate markers of disease progression.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Calcaneal osteopenia is a new marker for arterial stiffness in chronic hemodialysis patients.

BACKGROUND: A high frequency of simultaneous low estimated bone mineral density (BMD) and atherosclerotic vascular disease is found in chronic dialysis patients. The degree of BMD may be closely related to the severity of atherosclerosis in dialysis patients. The purpose of this study was to determine the association of estimated BMD with severity of atherosclerosis using popular economical non-invasive strategies in chronic dialysis patients. METHODS: This cross-sectional design study included 58 subjects receiving maintenance hemodialysis (HD) therapy. The mean age was 68 +/- 12 years (range 39-93), 22 subjects were female, and 26 subjects (45%) had diabetic nephropathy. The brachial-ankle pulse wave velocity (baPWV) and estimated BMD, using calcaneal quantitative ultrasound measurements of the osteo-sono index (OSI) were measured in all of the subjects. RESULTS: The mean levels of OSI and baPWV were 2.3 +/- 0.3 and 21 +/- 5 m/s, respectively. Based on single variable regression analysis, the C-reactive protein concentration correlated with baPWV (r = 0.272, p = 0.039), and the serum albumin concentration was inversely correlated with baPWV (r = -0.318, p = 0.015). In addition, OSI had a strong negative correlation with baPWV (r = -0.470, p = 0.0002). To identify the independent factors correlating with baPWV, multivariate regression analysis was performed using confounding variables which had significant association in univariate analysis. OSI and diabetic nephropathy were found to be significant independent parameters. CONCLUSION: Calcaneal OSI, a surrogate marker for estimated BMD, has a strong ability to predict the severity of arterial stiffness independent of classical risk factors and markers of inflammation and malnutrition.

Aged↗

PubMed2003

Experimental injury study of children seated behind collapsing front seats in rear impacts.

In the mid 1990's the U.S. Department of Transportation made recommendations to place children and infants into the rear seating areas of motor vehicles to avoid front seat airbag induced injuries and fatalities. In most rear-impacts, however, the adult occupied front seats will collapse into the rear occupant area and pose another potentially serious injury hazard to the rear-seated children. Since rear-impacts involve a wide range of speeds, impact severity, and various sizes of adults in collapsing front seats, a multi-variable experimental method was employed in conjunction with a multi-level "factorial analysis" technique to study injury potential of rear-seated children. Various sizes of Hybrid III adult surrogates, seated in a "typical" average strength collapsing type of front seat, and a three-year-old Hybrid III child surrogate, seated on a built-in booster seat located directly behind the front adult occupant, were tested at various impact severity levels in a popular "minivan" sled-buck test set up. A total of five test configurations were utilized in this study. Three levels of velocity changes ranging from 22.5 to 42.5 kph were used. The average of peak accelerations on the sled-buck tests ranged from approximately 8.2 G's up to about 11.1 G's, with absolute peak values of just over 14 G's at the higher velocity change. The parameters of the test configuration enabled the experimental data to be combined into a polynomial "injury" function of the two primary independent variables (i.e. front seat adult occupant weight and velocity change) so that the "likelihood" of rear child "injury potential" could be determined over a wide range of the key parameters. The experimentally derived head injury data was used to obtain a preliminary HIC (Head Injury Criteria) polynomial fit at the 900 level for the rear-seated child. Several actual accident cases were compared with the preliminary polynomial fit. This study provides a test efficient, multi-variable, method to compare the injury biomechanical data with actual accident cases.

Accidents, Traffic↗

PubMed1993

Variability of physiologically based pharmacokinetic (PBPK) model parameters and their effects on PBPK model predictions in a risk assessment for perchloroethylene (PCE).

When used in the risk assessment process, the output from physiologically based pharmacokinetic (PBPK) models has usually been considered as an exact estimate of dose, ignoring uncertainties in the parameter values used in the model and their impact on model predictions. We have collected experimental data on the variability of key parameters in a PBPK model for tetrachloroethylene (PCE) and have used Monte Carlo analysis to estimate the resulting variability in the model predictions. Blood/air and tissue/blood partition coefficients and the interanimal variability of these data were determined for tetrachloroethylene (PCE). The mean values and variability for these and other published model parameters were incorporated into a PBPK model for PCE and a Monte Carlo analysis (n = 600) was performed to determine the effect on model predicted dose surrogates for a PCE risk assessment. For a typical dose surrogate, area under the blood time curve for metabolite in the liver (AUCLM), the coefficient of variation was 25% and the mean value for AUCLM was within a factor of two of the maximum and minimum values generated in the 600 simulations. These calculations demonstrate that parameter uncertainty is not a significant potential source of variability in the use of PBPK models in risk assessment. However, we did not in this study consider uncertainties as to metabolic pathways, mechanism of carcinogenicity, or appropriateness of dose surrogates.

Administration, Inhalation↗

PubMed1998

Some useful statistical methods for model validation.

Although formal hypothesis tests provide a convenient framework for displaying the statistical results of empirical comparisons, standard tests should not be used without consideration of underlying measurement error structure. As part of the validation process, predictions of individual blood lead concentrations from models with site-specific input parameters are often compared with blood lead concentrations measured in field studies that also report lead concentrations in environmental media (soil, dust, water, paint) as surrogates for exposure. Measurements of these environmental media are subject to several sources of variability, including temporal and spatial sampling, sample preparation and chemical analysis, and data entry or recording. Adjustments for measurement error must be made before statistical tests can be used to empirically compare environmental data with model predictions. This report illustrates the effect of measurement error correction using a real dataset of child blood lead concentrations for an undisclosed midwestern community. We illustrate both the apparent failure of some standard regression tests and the success of adjustment of such tests for measurement error using the SIMEX (simulation-extrapolation) procedure. This procedure adds simulated measurement error to model predictions and then subtracts the total measurement error, analogous to the method of standard additions used by analytical chemists.

Animals↗

PubMed1996

Rejection of the 'filtered noise' hypothesis to explain the variability of transcranial Doppler signals: a comparison of original TCD data with Gaussian-scaled phase randomized surrogate data sets.

Until the last few years the correlation dimension (D2) or the Lyapunow exponent were the two dominant mathematical methods which were applied to identify possible chaotic behavior in biological systems. Detection of deterministic chaos is important, because it suggests that a relatively simple nonlinear model might explain the data. It was however discovered that these methods could give rise to an erroneous detection of chaos. For this reason a new method was proposed in which the originally measured data set was directly compared with a computer generated 'surrogate' data set with exactly the same linear correlations as the original. The basic idea is then to compute a nonlinear statistic for the original data and for each of the surrogate data sets. In principle any statistic can be used. We used the correlation dimension (D2), which measures the complexity of a time series. In this study we applied this surrogate method to estimate whether the variability of the transcranial Doppler (TCD) waveforms is the result of nonlinearity or not. From 10 healthy volunteers, left middle cerebral artery (MCA) blood flow velocities were measured by TCD examinations. An artifact free epoch of each TCD was used for analysis. From each original data set 50 surrogate data sets were constructed using the Gaussian-scaled phase-randomized Fourier transform. For both the original and the surrogate data sets the D2 was measured. The D2 values of the original TCD waveforms differed significantly from the mean D2 of the surrogate data sets. Therefore the null hypothesis, which stated that the original TCD time series arise from filtered noise, is rejected and nonlinearity is detected. The clinical significance and implications are discussed.

Adult↗

PubMed1999

Methods for assessing the public health impact of outflows from combined sewer systems.

OBJECTIVES: Approximately 1,100 communities in the United States have combined sewer and stormwater systems whose capacity may be exceeded during moderate or heavy rainfall. Outflows may occur that can deposit water with varying concentrations of the components of sewage onto public areas, where contact with residents or workers is possible, potentially resulting in a range of adverse health effects. This study proposes and applies three analytic methods to evaluate the impact of such outflows on public health. METHODS: The work attendance records of 449 U.S Postal Service letter carriers in Sacramento, CA, were reviewed to determine the frequency of sick leave use (as a surrogate measure of illness) in relationship to rainfall and potential exposure to sewage-contaminated outflows in two distinct groups of letter carriers from October 1, 1992, through April 30, 1993. Rainfall was a surrogate measure of outflows from the combined sewer and stormwater system because no information existed about the extent of exposure of these (or any other) workers. One group of letter carriers delivered mail exclusively within an area served by the combined sewer and stormwater collection system; the second group delivered mail exclusively outside this area where sewage and stormwater collection are separated. The first approach to the assessment of the data was a description of the temporal relationship between rainfall patterns and absentee rates in the two groups of workers. The second approach used logistic regression modelling with varying lags between rainfall and sick leave usage. The third approach used Poisson regression analysis of the entire study period to examine the differential impact of rainfall on the two groups. RESULTS: The descriptive analyses detected no relationship between rainfall and sick leave use. The logistic regression analyses detected evidence (as measured by the interaction coefficient in logistic models) of an increased use of sick leave by the letter carriers within the Combined System area at lag periods of one, four, and five days after rainfall. These estimates were not, however, statistically significant (p > 0.05). The Poisson regression analysis showed no evidence of a differential impact of rainfall on the two groups (incidence rate ratio = 1.19 in both groups for periods of rain versus no rain). CONCLUSIONS: These three methods can be used to investigate the public health impact of combined system outflows. Ideally, however, these approaches would be applied to prospectively collected surveillance data that would rely upon direct measurements of exposure and illness, rather than surrogate variables.

Female↗

PubMed2002

A non-invasively determined surrogate of cardiac power ('circulatory power') at peak exercise is a powerful prognostic factor in chronic heart failure.

OBJECTIVES: This study was designed to assess the prognostic value of a new variable derived from a cardiopulmonary exercise test, the circulatory power, a surrogate of cardiac power, at peak exercise, in patients with chronic heart failure. BACKGROUND: Peak exercise cardiac power and stroke work are invasive parameters with recently proven prognostic value. It is unclear whether these variables have better prognostic value than peak oxygen uptake (VO(2)). METHODS: The study population comprised 175 patients with chronic heart failure (ejection fraction <45%) who underwent a cardiopulmonary exercise test. Circulatory power and circulatory stroke work were defined as the product of systolic arterial pressure and VO(2) and oxygen pulse, respectively. Prognostic value was assessed by survival curves (Kaplan-Meier method) and uni- and multivariate Cox analyses. RESULTS: With a mean follow-up of 25+/-10 months, ejection fraction, heart rate, systolic arterial pressure, peak VO(2), VCO(2), the anaerobic threshold, minute ventilation, the ventilatory equivalents of oxygen and carbon dioxide, the half times of VO(2) and VCO(2) recoveries, and the circulatory stroke work and power predicted outcome. Multivariate analysis demonstrated that the peak circulatory power (chi-square=19.9, P<0.001) (but not peak circulatory stroke work) was the only variable predictive of prognosis. CONCLUSION: The prognostic value of cardiopulmonary exercise tests in heart failure patients can be improved by assessing a new variable, the circulatory power - a surrogate of cardiac power - at peak exercise.

Adult↗

PubMed2005

Early adult-onset POAG linked to 15q11-13 using ordered subset analysis.

PURPOSE: Primary open-angle glaucoma (POAG) is a complex inherited disorder. It has been demonstrated in other complex disorders that phenotypic heterogeneity may be the result of genetic heterogeneity and that stratification analysis can be used to increase the power of detection. Ordered subset analysis (OSA) is a recently described method that utilizes the variability of phenotypic traits to determine underlying genetic heterogeneity. METHODS: Eighty-six multiplex families with POAG were clinically ascertained for genetic analysis. Age at diagnosis (AAD) was used as a surrogate for age of onset in affected family members. Nine genetic markers within the 15q11-13 interval on chromosome 15 were used for OSA analysis. RESULTS: An 11-cM linkage interval with a peak LOD score of 3.24 centered at the GABRB3 locus (P = 0.013 by permutation test) was identified in a subset of 15 families, which represents 17% of the total dataset (15/86 families). The mean AAD for the affected OSA families was 44.1 +/- 9.1 years (SD). The mean AAD for the complementary group was 61.3 +/- 10.4 years. African-American and white families were well represented in the OSA subset. CONCLUSIONS: Linkage was identified for POAG to an 11-cM region on chromosome 15, designated GLC1I. This result provides further evidence that AAD and other phenotypic traits can be used as stratification variables to identify genes in complex disorders such as POAG and suggests that the 15q11-13 locus is one of the largest genetic contributors to POAG identified to date.

Adult↗

PubMed2006

The risk of developing metastatic disease in colorectal cancer is related to CD105-positive vessel count.

BACKGROUND AND OBJECTIVES: Angiogenesis is a complex multistep process that involves extracellular matrix remodeling, migration and proliferation of endothelial cells, and morphogenesis of microvessels. CD105 (endoglin), a co-receptor of the TGF-beta superfamily, was proposed as a marker of neovascularization in solid malignancies. The aim of this study was to evaluate retrospectively the effect of CD105-assessed angiogenesis on the risk of developing metastatic disease in colorectal cancer (CRC). METHODS: One hundred and twenty-five paraffin-embedded samples were analyzed by immunohistochemical methods using a CD105 monoclonal antibody. The median follow-up was 70.8 months. Survivals were calculated from actuarial estimates, and logistic regression predicted the risk of developing metastatic disease. RESULTS: The CD105-vessel count was strongly correlated with the occurrence of metastatic disease. The median CD105-positive vessels in patients with and without metastatic disease were 24.7 and 13.2 vessels/mm(2), respectively (P < 0.001). For each one microvessel increase in the vessels count per 400x field, there was a 1.42-fold increase in the risk of metastatic disease (P < 0.001). CONCLUSIONS: The assessment of tumor angiogenesis with anti-CD105 was not sufficient for its use as a surrogate end point for survival because of the amount of survival variability explained was only 8% in absence of metastatic disease. In contrast, multivariate logistic regression analysis revealed that CD105-vessels count can identify patients at high risk of metastatic disease.

Adenocarcinoma↗

PubMed2002

Automated analysis of brachial ultrasound image sequences: early detection of cardiovascular disease via surrogates of endothelial function.

Early detection of cardiovascular disease would allow timely institution of preventive measures. Arterial endothelium play a primary role in processes leading to the development of atherosclerotic plaque and cardiovascular disease in general. Determination of flow-mediated dilatation (FMD) of brachial arteries from B-mode ultrasound image sequences offers a noninvasive surrogate index of endothelial function. A highly automated method for analysis of brachial ultrasound image sequences is reported and its performance assessed. The method overcomes the variability of brachial ultrasound images across subjects by incorporating machine learning and quality control steps. The automated method outperformed conventional manual analysis by providing a decreased analysis bias, increased reproducibility, and improved measurement accuracy. Consequently, it decreases inter- and intraobserver as well interinstitution variability. The method has been employed in a number of population studies with thousands of subjects analyzed.

Arterial Occlusive Diseases↗

PubMed1995

Assessment of GH status in acromegaly using serum growth hormone, serum insulin-like growth factor-1 and urinary growth hormone excretion.

OBJECTIVE: It is still not clear what is the most suitable method for monitoring progress of acromegaly. The aim of this study was to assess the relative merits of serum GH, serum IGF-I and urinary GH (uGH) excretion in the follow-up of acromegalic subjects. SUBJECTS AND METHODS: Thirty-six acromegalic patients each had a GH day series performed consisting of five serum GH measurements, together with an estimate of serum IGF-I and uGH. The first sample taken for serum GH was fasting (basal) whilst the third (1430h) was arbitrarily chosen as a random value. uGH was measured from two overnight collections and the mean value used for subsequent data analysis. MEASUREMENTS: Serum GH and IGF-I were measured by radioimmunoassay whilst uGH was estimated by an immunoradiometric assay using commercially available reagents. RESULTS: There is a highly significant linear correlation between serum GH and IGF-I following log transformation of these two variables (r = 0.85; P < 0.0001). Analysis of the raw data shows that the relation is in fact curvilinear rendering IGF-I less useful as a surrogate for integrated GH secretion at high levels of serum GH. There is a strong linear correlation between both a singleton basal serum GH and uGH (r = 0.78; P < 0.001) and the mean of five measurements (day series) and uGH (r = 0.81; P < 0.0001). Both uGH and IGF-I are excellent predictors of those patients with persistent elevation of serum GH, identifying 95 and 96% respectively with serum GH > 5mU/l. We have identified a number of patients, however, with persistent elevation of IGF-I in the presence of serum GH < 5mU/l and normal uGH. Until the significance of these findings with respect to long-term outcome is known, serum GH should continue to be used in the follow-up of these patients. An alternative, which reflects integrated overnight GH secretion, is uGH which is convenient and easy to collect as an outpatient and correlates strongly with serum GH. CONCLUSION: Acromegalic patients can be conveniently followed on an outpatient basis using a combination of uGH and serum IGF-I. Measurements of serum GH can be reserved for those with discrepant results.

Acromegaly↗

PubMed1986

Ethnic differences in Australian fertility.

Historically, immigration has played an important role in the demographic evolution of the modern Australian society. In order to measure the demographic impact of immigration, it is necessary to study the fertility behaviour of various immigrant groups in Australia. In this paper, ethnic differences in Australian fertility have been analysed, using country of birth as a surrogate variable for ethnicity. Main sources of data used are the population censuses and the birth registers. Most of the data presented refer to 1981, as analysis of data pertaining to 1971 and 1976 was reported in earlier papers. The study has shown that fertility of most of the European immigrants (except the Dutch and the Maltese), has been converging towards the Australian norm. The non-European immigrants have lower fertility, with the exception of the newly arrived refugee groups from Asia and the Middle East.

Adolescent↗