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Biomedical subjects

Les Irwig

Publications and source records attributed to Les Irwig.

At least 19 recordsLinked to original sources
PubMed2006

When is measuring sensitivity and specificity sufficient to evaluate a diagnostic test, and when do we need randomized trials?

The clinical value of using a new diagnostic test depends on whether it improves patient outcomes beyond the outcomes achieved using an old diagnostic test. When can studies of diagnostic test accuracy provide sufficient information to infer clinical value, and when do clinicians need to wait for results from randomized trials? The authors argue that accuracy studies suffice if a new diagnostic test is safer or more specific than, but of similar sensitivity to, an old test. However, if a new test is more sensitive than an old test, it leads to the detection of extra cases of disease. Results from treatment trials that enrolled only patients detected by the old test may not apply to these extra cases. Clinicians need to wait for results from randomized trials assessing treatment efficacy in cases detected by the new diagnostic test, unless they can be satisfied that the new test detects the same spectrum and subtype of disease as the old test or that treatment response is similar across the spectrum of disease.

Diagnostic Techniques and Procedures↗
PubMed2006

Effect of study design and quality on unsatisfactory rates, cytology classifications, and accuracy in liquid-based versus conventional cervical cytology: a systematic review.

BACKGROUND: Liquid-based cytology is reported to increase the sensitivity of cervical cytology and the proportion of slides that are satisfactory for assessment, in comparison with conventional cytology. Although some countries have changed to liquid-based cytology for cervical screening, controversy remains. We reviewed the published work to assess the performance of liquid-based cytology relative to conventional cytology in primary studies assessed to be of low, medium, or high methodological quality. METHODS: 56 primary studies were reviewed and assessed with strict methodological criteria. Liquid-based cytology and conventional cytology were compared in terms of the percentage of slides classified as unsatisfactory, the percentage of slides classified in each cytology category, and the accuracy of detection of high-grade disease. Data were examined for studies overall and in strata to examine the effect of study quality on results. FINDINGS: The median difference in the percentage of unsatisfactory slides between liquid-based cytology and conventional cytology was 0.17%. Only one small study was a randomised controlled trial. The classification of high-grade squamous epithelial lesion varied according to study quality (p=0.04), with conventional cytology classifying more slides in this category than did liquid-based cytology in high-quality studies (n=3) only. In medium-quality (n=30) and high-quality studies, liquid-based cytology classified more slides as atypical squamous cells of unknown significance than did conventional cytology when compared with low-quality studies (n=17; p=0.05). Only four studies provided sufficient verified data to allow estimation of sensitivity and specificity and comparison of test accuracy. INTERPRETATION: We saw no evidence that liquid-based cytology reduced the proportion of unsatisfactory slides, or detected more high-grade lesions in high-quality studies, than conventional cytology. This review does not lend support to claims of better performance by liquid-based cytology. Large randomised controlled trials are needed.

Cytological Techniques↗
PubMed2006

New methods give better estimates of changes in diagnostic accuracy when prior information is provided.

OBJECTIVE: Whether tests such as imaging should be read with or without access to prior clinical information is controversial. Naïve comparisons may suggest that the provision of prior information improves test accuracy, whereas in fact the opposite may be true. This is because provision of clinical background may actually bias test readers to over- or underinterpret relevant test findings, and they may suboptimally integrate the previous and current evidence. We propose comparing the combined accuracy of prior information and a test read (i) with or (ii) without knowledge of prior information. Analysis methods include simple decision rules and logistic regression. STUDY DESIGN AND SETTING: A study of cancer detection in women presenting with breast symptoms, in whom ultrasound could be read with or without reviewing prior mammography. RESULTS: Naïve analysis gave an area under the receiver operating characteristics curve (AUC) for ultrasound read with mammography on view that was 4.6% higher (P < .01) than without mammography on view. Our approach, comparing the combined accuracy of mammography and ultrasound read i) with and ii) without knowledge of mammographic findings, showed much smaller differences. CONCLUSION: Our approach is more appropriate than naïve analyses. The particular choice of analytic method depends on the study size and the diagnostic accuracy of combinations of the prior information and the test reading.

Adult↗
PubMed2006

Intraocular lens power in bilateral cataract surgery: whether adjusting for error of predicted refraction in the first eye improves prediction in the second eye.

PURPOSE: To assess whether the retrospectively calculated intraocular lens (IOL) position value in the first eye reduces the error of predicted refraction in the second. SETTING: Prince of Wales Hospital, Sydney, Australia. METHODS: One hundred twenty-one consecutive patients who had bilateral cataract surgery with the same IOL (SI-30NB, Advanced Medical Optics) were identified. The case-derived A-constant in the first eye was calculated from the postoperative refraction. This value was used to calculate the adjusted error of predicted refraction in the second eye and compared against the unadjusted error in that eye (calculated using manufacturer's A-constant). RESULTS: Axial length (r = 0.97), corneal power (r = 0.97), and IOL power (r = 0.90) were strongly correlated between eyes with no statistically significant mean interocular difference. Although there was no significant interocular difference in the mean error of predicted refraction (SRK/T), there was only a moderate correlation between eyes (r = 0.40). Using the axial length vergence formula, the mean adjusted error of predicted refraction in the second eye (-0.66 diopter [D]) was significantly larger than the mean unadjusted error (-0.47 D) (P = .029). The standard deviation of the adjusted error of predicted refraction (SRK/T) in the second eye (0.85 D) was greater than the standard deviation of the unadjusted error (0.79). Similarly, the adjusted mean absolute error of predicted refraction (0.65 D) was greater than the unadjusted error (0.63 D). CONCLUSION: Adjusting the IOL power in the second eye by the amount of overprediction or underprediction in the first eye did not improve prediction accuracy because the error of predicted refraction varied independently between the 2 eyes of an individual.

Cataract Extraction↗
PubMed2006

Radiological surveillance of interval breast cancers in screening programmes.

Interval breast cancers-those diagnosed after a negative mammographic screen and before the next scheduled screen-are an important indicator of the potential effectiveness of population screening for breast cancer. Although the incidence of interval cancers is usually monitored, radiological surveillance is not undertaken routinely in most screening programmes. Here, we describe radiological surveillance of interval breast cancers and discuss methodological difficulties in the radiological review process and in the categorisation of interval cancers as false-negative, true, or occult. Furthermore, we identify methods that affect whether an interval cancer is classified as a false-negative (missed) or a true interval cancer. For all radiological categories of interval cancers, we outline possible changes to screening programmes that might improve cancer detection. Standardised radiological surveillance of interval cancers might allow within-programme comparisons and has the potential to guide practice and improve quality.

Breast Neoplasms↗
PubMed2006

Lack of sphygmomanometer calibration causes over- and under-detection of hypertension: a computer simulation study.

OBJECTIVE: To estimate the contribution of inadequate sphygmomanometer calibration to over- and under-detection of hypertension. DESIGN: Monte Carlo simulation of the measurement of blood pressure (BP) of a population with calibrated and uncalibrated sphygmomanometers. Simulated BP measurements included systematic sphygmomanometer error and random variability. MAIN OUTCOME MEASURES: The percentage of hypertensive adults (BP > 140/90 mmHg) not detected and the percentage of adults incorrectly classified hypertensive due to sphygmomanometer error. The percentage of the false positives and false negatives attributable to sphygmomanometer error. The number of additional visits patients need to make to obtain the same improvement in hypertension detection as is obtained by sphygmomanometer calibration. RESULTS: After three visits, uncalibrated sphygmomanometer error causes 20 and 28% of all undetected adult systolic and diastolic hypertension, respectively, and 15 and 31% of all falsely detected adult systolic and diastolic hypertension. In some groups, under-detection is worse; for example, sphygmomanometer error causes 27% of all missed systolic hypertension in 35-44-year-old females. In some age groups, over-detection is worse; for example, after three visits, sphygmomanometer error causes 63 and 50% of falsely detected systolic and diastolic hypertension in 18-24-year-old females, respectively. In-service sphygmomanometer calibration achieves the same or greater improvement in hypertension detection as an additional two visits. CONCLUSIONS: Uncalibrated sphygmomanometers are a preventable cause of clinically significant over- and under-detection of hypertension. Sphygmomanometers should be calibrated regularly by accredited organizations or technicians. Standards and guidelines governing sphygmomanometers in service should be revised. Sphygmomanometer calibration is a cost-effective way of improving hypertension detection.

Adolescent↗
PubMed2005

Model of outcomes of screening mammography: information to support informed choices.

OBJECTIVE: To provide easy to use estimates of the benefits and harms of biennial screening mammography for women aged 40, 50, 60, and 70 years. DESIGN: Markov process model, with data from BreastScreen Australia, the Australian Institute of Health and Welfare, and the Australian Bureau of Statistics. MAIN OUTCOME MEASURE: Age specific outcomes expressed per 1000 women over 10 years. RESULTS: For every 1000 women screened over 10 years, 167-251 (depending on age) receive an abnormal result; 56-64 of these women undergo at least one biopsy, 9-26 have an invasive cancer detected by screening, and 3-6 have ductal carcinoma in situ (DCIS) detected by screening. More breast cancers (both invasive and DCIS) are diagnosed among screened than unscreened women. For example, among 1000 women aged 50 who have five biennial screens, 33 breast cancers are diagnosed: 28 invasive cancers (18 detected at screening and 10 interval cancers) and five DCIS (all detected at screening). By comparison, among 1000 women aged 50 who decline screening, 20 cancers are diagnosed over 10 years. There are about 0.5, 2, 3, and 2 fewer deaths from breast cancer over 10 years per 1000 women aged 40, 50, 60, and 70, respectively, who choose to be screened compared with women who decline screening at times determined by relevant policy. CONCLUSION: Benefits and harms of screening mammography are relatively finely balanced. Quantitative estimates such as these can be used to support individual informed choices about screening.

Adult↗
PubMed2005

The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed.

BACKGROUND AND OBJECTIVE: Publication bias and other sample size effects are issues for meta-analyses of test accuracy, as for randomized trials. We investigate limitations of standard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods. METHODS: Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy. RESULTS: Type I error rates for the Begg, Egger, and Macaskill tests are inflated for typical diagnostic odds ratios (DOR), when disease prevalence differs from 50% and when thresholds favor sensitivity over specificity or vice versa. Regression and correlation tests based on functions of effective sample size are valid, if occasionally conservative, tests for sample size effects. Empirical evidence suggests that they have adequate power to be useful tests. When DORs are heterogeneous, however, all tests of funnel plot asymmetry have low power. CONCLUSION: Existing tests that use standard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy. The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects.

Diagnostic Errors↗
PubMed2005

Review of complex breast cysts: implications for cancer detection and clinical practice.

The use of ultrasound in breast diagnosis has resulted in the increasing identification of incidental benign-appearing lesions, of which complex (or atypical) breast cysts are frequently reported. Complex breast cysts were estimated to be reported in approximately 5% of breast ultrasound examinations. A systematic review of the literature on sonographically detected complex breast cysts was carried out. The quality of primary studies and extracted data on cancer detection was assessed. Very few studies have examined complex breast cysts and quantified the associated cancer detection rate. In most of these studies, subjects have been selected on the basis of progress to intervention, which would overestimate the likelihood of malignancy. The only study to examine complex cysts from all consecutive ultrasounds reported one case of non-invasive cancer from 308 lesions--0.3% (95% confidence interval, 0.01-1.84). Ultrasound features associated with a higher risk of the lesion being a cancer are: thickened walls, thick internal septations, a mix of cystic and solid components, and an imaging classification of indeterminate. Using the information from the present review, complex breast cysts were categorized on the basis of associated risk of malignancy, and an approach to the management of these lesions to assist clinical decision-making was suggested. Provided adequate information is given to the patient, complex breast cysts with a very low risk of malignancy do not always require image-guided biopsy.

Algorithms↗
PubMed2005

High participation rates are not necessary for cost-effective colorectal cancer screening.

BACKGROUND: In many countries high participation is an explicit target in screening programmes. The desire for high participation often appears to drive screening policy, although it is increasingly recognized that encouraging high participation may impinge upon the rights of an individual to make an informed choice. One argument offered in support of high participation is that it improves the cost-effectiveness of screening. This is questionable on theoretical grounds, and empirically there are conflicting results. Two recent cost-effectiveness models of faecal occult blood test (FOBT) screening for colorectal cancer (CRC) showed that cost-effectiveness was improved, another showed that cost-effectiveness was worsened and a fourth indicated that cost-effectiveness was unaffected by increasing the participation rate. METHODS: We assessed the extent to which different levels and patterns of participation affect cost-effectiveness, using decision modelling of three CRC screening with FOBT scenarios. We estimate the incremental cost-effectiveness (value for money) ratios for each scenario. RESULTS: The way in which participation is modelled, particularly assumptions made about the subsequent screening behaviour of non-participants ("if" and "when" a non-participant attends for subsequent screening), affects the cost-effectiveness estimates for FOBT screening programmes. 100% participation in all screening rounds gives a cost per life year saved (LYS) of USD 9705. Cost-effectiveness is worst when people who do not take part in one screening round (initial or subsequent) never take part in any future rounds of screening. Under this scenario, a participation rate of 20% in second and subsequent rounds gives a cost per LYS of USD 29,500. Under more realistic assumptions, for example the attendance of even a small proportion of non-participants in subsequent rounds, cost-effectiveness is more favourable and similar to that achieved for full participation: the scenario with a random participation rate of 20% in second and subsequent rounds for both participants and non-participants has a cost per LYS of USD 11,270. CONCLUSIONS: Contrary to a commonly held view, high participation in screening programmes is not necessary to achieve cost-effectiveness. Setting high target participation rates in screening programmes does not guarantee cost-effectiveness and may in certain circumstances reduce the cost-effectiveness.

Colorectal Neoplasms↗
PubMed2005

Australian women's needs and preferences for information about human papillomavirus in cervical screening.

OBJECTIVE: The role of human papillomavirus (HPV) in cervical cancer and developments in medical technology to prevent cervical cancer has changed information needs for women participating in cervical screening. DESIGN: Qualitative face-to-face interviews were conducted with 19 women diagnosed with HPV infection on their Pap smear following routine cervical screening. SETTING: Family planning clinics, general practice and specialist gynaecologist practices in Sydney and the surrounding area, Australia. MAIN OUTCOME MEASURES: Women's information needs, preferences and experiences of HPV diagnosis. RESULTS: Women wanted further information on different HPV viral types, transmission, implications for sexual partners, prevalence, latency and regression of HPV, their management options and the implications of infection for cancer risk and fertility. Uncertainty about the key aspects of HPV, the style in which the clinician communicated the result and the mode of delivering the result (letter, telephone or consultation) influenced women's psychological response to the diagnosis of HPV. The delivery of results by letter alone was linked to considerable anxiety among the women interviewed. Women's experience of searching the Internet for further information about HPV was reported as difficult, anxiety provoking and contributing to the stigma of the infection because information was often located in the context of other sexually transmitted infections, with multiple sexual partners highlighted as a risk factor for infection. CONCLUSION: Women participating in cervical screening need high-quality information about HPV and its role in cervical cancer prior to screening rather than afterwards, when they face an abnormal result. The clinician potentially plays an important role in moderating the effects of diagnosis through the manner and mode in which an HPV diagnosis is delivered. Revision of cervical screening policy and practice in light of the changes in the understanding of HPV is recommended.

Adult↗
PubMed2004

Accuracy of diagnostic tests read with and without clinical information: a systematic review.

CONTEXT: Although it is common practice to read tests with clinical information, whether this improves or decreases the accuracy of test reading is uncertain. OBJECTIVE: To determine whether diagnostic tests are more accurate when read with clinical information or without it. DATA SOURCES: MEDLINE search (1966-December 2003) extended by search of reference lists and articles citing the articles retrieved (Web of Science, 1985-December 2003). STUDY SELECTION: All articles comparing the accuracy of tests read twice by the same readers, once without and once with clinical information, but otherwise under identical conditions. Only articles that reported sensitivity and specificity or receiver operating characteristic (ROC) curves were included. DATA EXTRACTION: Data were extracted by one author and reviewed independently by the other. When the data were difficult to interpret, differences were resolved by discussion. DATA SYNTHESIS: Sixteen articles met the inclusion criteria. Eleven articles compared areas under ROC curves for tests read with and without clinical information, and 5 compared only sensitivity and specificity. Ten articles used actual clinical information; 6 used constructed clinical information that was plausible. Overall, clinical information improved test reading accuracy although the effect was smaller in the articles using actual clinical information when compared with those using constructed clinical information. There were no instances in which clinical information resulted in significant reduction in test reading accuracy. In some instances, improved test reading accuracy came from improved sensitivity without loss of specificity. CONCLUSIONS: At least for the tests examined, the common practice of reading diagnostic tests with clinical information seems justified. Future studies should be designed to investigate the best way of providing clinical information. These studies should also give an estimate of the accuracy of clinical information used, display ROC curves with identified data points, and include a wider range of diagnostic tests.

Diagnostic Techniques and Procedures↗
PubMed2004

Adjustment for baseline measurement error in randomized controlled trials induces bias.

When estimating the treatment effect in a randomized controlled trial, it is common to have a continuous outcome which is also observed at baseline. These observations are often prone to measurement error, for example due to within-patient variability. Controversy exists in the literature about whether baseline measurement error should be adjusted for in this context. Computer simulations were used to compare the biases in the estimated treatment effect, with and without adjusting for measurement error, and for different levels of observed baseline imbalance. The impacts of sample size (30 per group and 300 per group) and reliability coefficient (0.6, 0.8 and 1) were also assessed. The results show that in randomized controlled trials, the ordinary least squares (OLS) estimator without adjusting for measurement error is unbiased. On the contrary, adjusting for measurement error leads to bias, especially when sample sizes are small and/or measurement error is large. The treatment effect adjusting for measurement error is on average overestimated when the baseline mean of the control group is larger than that of the treated group. It is underestimated when the control group has a smaller baseline mean.

Analysis of Variance↗