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Background: Pathologists sometimes disagree over the histopathologic diagnosis of melanoma. 'Over‐calling' and 'under‐calling' of melanoma may harm individuals and healthcare systems. Objectives: To estimate the extent of 'over‐calling' and 'under‐calling' of melanoma for a population undergoing one excision per person and to model the impact of potential solutions. Methods: In this epidemiological modelling study, we undertook simulations using published data on the prevalence and diagnostic accuracy of melanocytic histopathology in the U.S. population. We simulated results for 10 000 patients each undergoing excision of one melanocytic lesion, interpreted by one community pathologist. We repeated the simulation using a hypothetical intervention that improves diagnostic agreement between community pathologist and a specialist dermatopathologist. We then evaluated four scenarios for how melanocytic lesions judged to be neither clearly benign (post‐test probability of melanoma < 5%), nor clearly malignant (post‐test probability of melanoma > 90%) might be handled, before sending for expert dermatopathologist review to decide the final diagnosis. These were (1) no intervention before expert review, (2) formal second community pathologist review, (3) intervention to increase diagnostic agreement and (4) both the intervention and formal second community pathologist review. The main outcomes were the probability of 'over‐calling' and 'under‐calling' melanoma, and number of lesions requiring expert referral for each scenario. Results: For 10 000 individuals undergoing excision of one melanocytic lesion, interpreted by a community pathologist, a hypothetical intervention to improve histopathology agreement reduced the number of benign lesions 'over‐called' as melanoma from 308 to 164 and the number of melanomas 'under‐called' from 289 to 240. If all uncertain diagnoses were sent for expert review, the number of referrals would decrease from 1500 to 737 cases if formal second community pathologist review was used, and to 701 cases if the hypothetical intervention was additionally used. Conclusions: Interventions to improve histopathology agreement may reduce melanoma 'over‐calling' and 'under‐calling'. [ABSTRACT FROM AUTHOR]

Decisions about health care should be informed by systematic review of valid research evidence on the effects of interventions on health outcomes that matter. If systematic review suggests it is likely that a health care intervention does more good than harm in some settings, questions must be addressed about the local applicability of the intervention, its cost-effectiveness, and feasibility of implementation. If systematic review suggests that it is unlikely that an intervention does more good than harm in any setting, its use should be discouraged, while existing interventions are improved or alternative interventions developed. If it is uncertain whether an intervention does more good than harm, further analysis of existing data or new controlled trials are required. The article contains a flow diagram, which provides a structure for making such decisions., Introduction In poor and rich countries alike, planners and providers of health services and health research face the challenge of deciding how to make effective use of limited or contracting [...]

The treatments under comparison in a randomised trial should ideally have equal value and acceptability - a position of equipoise - to study participants. However, it is unlikely that true equipoise exists in practice, because at least some participants may have preferences for one treatment or the other, for a variety of reasons. These preferences may be related to study outcomes, and hence affect the estimation of the treatment effect. Furthermore, the effects of preferences can sometimes be substantial, and may even be larger than the direct effect of treatment. Preference effects are of interest in their own right, but they cannot be assessed in the standard parallel group design for a randomised trial. In this paper, we describe a model to represent the impact of preferences on trial outcomes, in addition to the usual treatment effect. In particular, we describe how outcomes might differ between participants who would choose one treatment or the other, if they were free to do so. Additionally, we investigate the difference in outcomes depending on whether or not a participant receives his or her preferred treatment, which we characterise through a so-called preference effect. We then discuss several study designs that have been proposed to measure and exploit data on preferences, and which constitute alternatives to the conventional parallel group design. Based on the model framework, we determine which of the various preference effects can or cannot be estimated with each design. We also illustrate these ideas with some examples of preference designs from the literature. [ABSTRACT FROM AUTHOR]

Background:Magnetic resonance imaging (MRI) has been proposed to guide breast cancer surgery by measuring residual tumour after neoadjuvant chemotherapy. This study-level meta-analysis examines MRI's agreement with pathology, compares MRI with alternative tests and investigates consistency between different measures of agreement.Methods:A systematic literature search was undertaken. Mean differences (MDs) in tumour size between MRI or comparator tests and pathology were pooled by assuming a fixed effect. Limits of agreement (LOA) were estimated from a pooled variance by assuming equal variance of the differences across studies.Results:Data were extracted from 19 studies (958 patients). The pooled MD between MRI and pathology from six studies was 0.1 cm (95% LOA: −4.2 to 4.4 cm). Similar overestimation for MRI (MD: 0.1 cm) and ultrasound (US) (MD: 0.1 cm) was observed, with comparable LOA (two studies). Overestimation was lower for MRI (MD: 0.1 cm) than mammography (MD: 0.4 cm; two studies). Overestimation by MRI (MD: 0.1 cm) was smaller than underestimation by clinical examination (MD: −0.3 cm). The LOA for mammography and clinical examination were wider than that for MRI. Percentage agreement between MRI and pathology was greater than that of comparator tests (six studies). The range of Pearson's/Spearman's correlations was wide (0.21-0.92; 16 studies). Inconsistencies between MDs, percentage agreement and correlations were common.Conclusion:Magnetic resonance imaging appears to slightly overestimate pathologic size, but measurement errors may be large enough to be clinically significant. Comparable performance by US was observed, but agreement with pathology was poorer for mammography and clinical examination. Percentage agreement can provide supplementary information to MDs and LOA, but Pearson's/Spearman's correlation does not provide evidence of agreement and should be avoided. Further comparisons of MRI and other tests using the recommended methods are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Background: Little is known about the value of long-term follow-up for localised cutaneous melanoma from the patients'' perspective. This study aimed to explore the benefits and potential downsides of follow-up; feelings about changes to frequency of follow-up, and patient-centred recommendations for improving follow-up care. Methods: Qualitative analysis of 29 in-depth interviews conducted with Australian patients undergoing long-term follow-up after surgical treatment of stage I/II melanoma. Results: Patient-perceived benefits of follow-up included reassurance, early detection of new melanomas and non-melanoma skin cancers, education about skin self-examination, the opportunity to ask questions, and reinforcement of ‘sunsafe’ behaviours. Downsides included anxiety leading up to and during follow-up visits; inconvenience of travel to attend visits; and lost work time. Patients varied in their engagement with skin self-examination, and their views on multiple skin excisions, but highly valued access to specialists for unscheduled visits. Most patients felt their follow-up intervals could be extended to 12 months if recommended by their clinician. Conclusion: The benefits and potential downsides of follow-up should be discussed with patients when deciding on a melanoma follow-up plan to achieve a balance between inducing additional patient anxiety and providing reassurance. Follow-up intervals of 12 months appear to be acceptable to patients. [Copyright &y& Elsevier]

Outcomes in clinical trials may be affected by the choice of treatment that participants might make, if they were indeed allowed to choose (a so-called selection effect), and by whether they actually receive their preferred treatment (a preference effect). Selection and preference effects can be important, but they cannot be estimated in the conventional trial design. An alternative approach is the two-stage randomised trial, in which participants are first randomly divided into two subgroups. In one subgroup, participants are randomly assigned to treatments, while in the other, participants are allowed to choose their own treatment. This approach yields estimates of the direct treatment effect, and of the preference and selection effects. The latter two provide insight that goes considerably beyond what is possible in the standard randomised trial. In this paper, we determine the optimal proportion of participants who should be allocated to the choice subgroup. The precision of the estimated selection, preference and treatment effects are functions of: the total sample size; the proportion of participants allocated to choose their treatment; the variances of the outcome; the proportions of participants who select each treatment in the choice group; and the selection, preference and treatment effects themselves. We develop general expressions for the optimum proportion of participants in the choice group, depending on which effects are of primary interest. We illustrate the results with trial data comparing alternative clinical management strategies for women with abnormal results on cervical screening. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

When no gold standard is available to evaluate a diagnostic or screening test, as is often the case, an imperfect reference standard test must be used instead. Furthermore, the errors of the test and its reference standard may not be independent. Some authors have opined that positively dependent errors will lead to overestimation of test performance. Although positive dependence does increase agreement between the test and the reference standard, it is not clear if test accuracy will necessarily be overestimated in this situation, and the case of negatively associated test errors is even less clear. To examine this issue in more detail, we derive the apparent sensitivity, specificity, and overall accuracy of a test relative to an imperfect reference standard and the bias in these parameters. We demonstrate that either positive or negative bias can occur if the reference standard is imperfect. The type and magnitude of bias depend on several components: the disease prevalence, the true test sensitivity and specificity, the covariance between the false-negative test errors among the true disease cases, and the covariance between the false-positive test errors among the true noncases. If, for example, sensitivity and specificity are 0.8 for both the test and reference standard and the errors have a moderate positive dependence, test sensitivity is then underestimated at low prevalence but overestimated at high prevalence, while the opposite occurs for specificity. We illustrate these ideas through general numerical calculations and an empirical example of screening for breast cancer with magnetic resonance imaging and mammography. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine women's informed preference for the management of a mildly abnormal Pap smear and the impact of a decision aid. METHODS: Women (n=106) were given a choice of management supported by a decision aid and surveyed before, and after decision making to evaluate predictors of choice and decision aid impact. RESULTS: HPV triage was preferred by most women (65%) although a substantial minority selected repeat Pap testing (35%). Women who chose HPV triage were more likely to have had children, have had a previous abnormal Pap smear and were more distressed than women who chose a repeat Pap test. In total, 68% of women made an informed choice. Rapid timing of follow-up was important for women choosing HPV testing. The lower chance of colposcopy and greater opportunity for regression, were rated as important by women choosing Pap testing. Decisional conflict was lower among women who chose HPV triage. No other differences in short-term psychological outcomes were found. CONCLUSION: The decision aid supported informed choice among the majority of women. Women tailored their choice to their practical, health and psychological needs. PRACTICE IMPLICATIONS: Offering women an informed choice for a mildly abnormal Pap smear may enable women to select the management that best suits their circumstances. [ABSTRACT FROM AUTHOR]

Background: Cholesterol level monitoring is a common clinical activity, but the optimal monitoring interval is unknown and practice varies.Objective: To estimate, in patients receiving cholesterol-lowering medication, the variation in initial response to treatment, the long-term drift from initial response, and the detectability of long-term changes in on-treatment cholesterol level ("signal") given short-term, within-person variation ("noise").Design: Analysis of cholesterol measurement data in the LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) study.Setting: Randomized, placebo-controlled trial in Australia and New Zealand (June 1990 to May 1997).Patients: 9014 patients with past coronary heart disease who were randomly assigned to receive pravastatin or placebo.Measurements: Serial cholesterol concentrations at randomization, 6 months, and 12 months, and then annually to 5 years.Results: Both the placebo and pravastatin groups showed small increases in within-person variability over time. The estimated within-person SD increased from 0.40 mmol/L (15 mg/dL) (coefficient of variation, 7%) to 0.60 mmol/L (23 mg/dL) (coefficient of variation, 11%), but it took almost 4 years for the long-term variation to exceed the short-term variation. This slow increase in variation and the modest increase in mean cholesterol level, about 2% per year, suggest that most of the variation in the study is due to short-term biological and analytic variability. Our calculations suggest that, for patients with levels that are 0.5 mmol/L or more (> or =19 mg/dL) under target, monitoring is likely to detect many more false-positive results than true-positive results for at least the first 3 years after treatment has commenced.Limitations: Patients may respond differently to agents other than pravastatin. Future values for nonadherent patients were imputed.Conclusion: The signal-noise ratio in cholesterol level monitoring is weak. The signal of a small increase in cholesterol level is difficult to detect against the background of a short-term variability of 7%. In annual rechecks in adherent patients, many apparent increases in cholesterol level may be false positive. Independent of the office visit schedule, the interval for monitoring patients who are receiving stable cholesterol-lowering treatment could be lengthened. [ABSTRACT FROM AUTHOR]

Decision aids (DAs) are tools to support patients make informed health decisions with their practitioner. They aim to improve patient knowledge of options, incorporate patient preferences and values, and increase patient involvement in health decision making. Increasingly, the debate about DAs concerns how they should be implemented in practice, with the view that DAs are superior to usual clinical care in facilitating health decisions. The authors challenge this view and suggest that DA research has focused on measures of decision process, leaving the effects on the outcome of the decision relatively unknown. It is still unclear in which conditions DAs are better for patient health and well-being than clinician-led decisions. The authors present a new randomized design to examine the effects of DA-supported patient choice on patient-centered outcomes to identify where DAs are best implemented in clinical practice. In this design, patients are randomized to 1 of 4 arms: intervention A, intervention B, choice of either intervention supported by a clinician, or choice of either intervention supported by a decision aid. Health and quality of life measured over the long term are presented as the primary outcomes. The authors propose that this design will allow the proper assessment of different modes of decision making. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Breast ultrasound is generally interpreted with knowledge of the mammographic examination. This study examined the influence of knowledge of mammography findings on the accuracy of ultrasound in women with breast symptoms. Subjects were sampled from all women 25-55 years of age consecutively attending a breast clinic. This included all 240 women shown to have breast cancer and 240 age-matched women shown not to have cancer. Ultrasound films were prospectively reviewed and reported by two radiologists independent of each other and in a blinded manner. A two-phase design was used. In the first phase, the radiologists provided an opinion on the ultrasound films. In the second phase, the ultrasound films were reread with consideration of the corresponding mammographic examination. The accuracy of reading the ultrasound with and without knowledge of the findings on mammography was compared using sensitivity and specificity, and receiver operating characteristics (ROC) curves. Reporting the ultrasound with knowledge of mammography (compared to without mammography) improved sensitivity and reduced specificity for both radiologists. For one reader, sensitivity increased from 77.5% to 86.7% (p = 0.0002) and specificity decreased from 89.7% to 85.4% (p = 0.04). For the other reader, sensitivity increased from 81.3% to 87.5% (p = 0.0023) and specificity decreased from 87.1% to 85.0% (p = 0.27). ROC curves for both radiologists showed that reporting ultrasound with knowledge of mammography resulted in small (about 3%), but significant improvement in the area under the ROC curve. Our study indicates that knowledge of the findings of mammography improves the interpretation of breast ultrasound in symptomatic women. [ABSTRACT FROM AUTHOR]

We systematically reviewed the literature on the accuracy of new technologies proposed for breast cancer screening. Four potential tests were identified (ultrasound, magnetic resonance imaging (MRI), full-field digital mammography (FFDM), and computer-aided detection (CAD)) for which primary studies met quality and applicability criteria and provided adequate data on test accuracy. These technologies have been assessed in cross-sectional studies of test accuracy where the new test is compared to mammography. Ultrasound, used as an adjunct to mammography in women with radiologically dense breasts, detects additional cancers and causes additional false positives. Magnetic resonance imaging may have a better sensitivity (but lower specificity) than mammography in selected high-risk women, but studies of this technology included small number of cancers. Computer-aided detection may enhance the sensitivity of mammography and warrants further evaluation in large prospective trials. One study of FFDM suggests that it may identify some cancers not identified on conventional mammography and may result in a lower recall rate. The evidence is currently insufficient to support the use of any of these new technologies in population screening, but would support further evaluation.British Journal of Cancer (2004) 90, 2118-2122. doi:10.1038/sj.bjc.6601836 www.bjcancer.com Published online 27 April 2004 [ABSTRACT FROM AUTHOR]

To make an informed choice about whether to be screened, people need information that allows them to weigh up the benefits and harms of screening. To understand their screening test results they require even more information. Yet currently, people attending a screening programme or considering a screening test may only be told that the test can detect disease or risk factors for disease, and that early intervention improves outcomes. When given their test results, people are generally only told the test was abnormal (“positive”) or normal (“negative”). We believe that information given before and after the screening test can, and should, be improved. This will probably require information that includes both the benefits and harms of screening and is probabilistic. Indeed, we believe the traditional dichotomisation of screening test results into positive and negative is problematic, and could be replaced by standard use of risks or probabilistic data before and after screening. The relevant risk data could be explained in a range of ways, for example, quantitatively, qualitatively, and/or by “anchoring” to everyday experiences. In this paper we explore why dichotomisation of screening test results is problematic and look at the adverse consequences of presenting test results in terms of true and false, positive and negative. We present some ideas on alternative ways of providing information on screening programmes and screening test results. Our aim is to stimulate debate about these issues and to provide some starting points which could be further developed and evaluated in a wide range of screening programmes. [ABSTRACT FROM AUTHOR]

SummaryAims Screening for asymptomatic Type 2 diabetes mellitus has been advocated on the grounds that diabetes is a common condition associated with increased morbidity and mortality, but uncertainty remains about the impact of early treatment. This study aimed to determine whether the potential benefits of screening are likely to outweigh the potential harm and to explore which variables significantly influence the balance of benefit and harm resulting from screening. Methods A decision analysis comparing the relative impact of using a single fasting blood glucose screening test, between the ages of 45 and 60 years, with the impact of not screening. The model weighs the increase in quality adjusted life years (QALYs) from reduction in microvascular and cardiovascular complications against the potential decrease in QALYs associated with earlier diagnosis and treatment in an asymptomatic population. Results The baseline model suggests a saving of 10 QALYs for every 10 000 individuals screened: a gain of four from postponed microvascular complications and 17 from avoided cardiovascular complications, as opposed to a loss of 11 as a result of earlier diagnosis in screening detected cases. The balance of benefit and harm is sensitive to baseline cardiovascular risk, the effectiveness of cardiovascular interventions and the relative disutility assigned to early diagnosis and treatment for an individual without symptoms. Conclusions The immediate disutility of earlier diagnosis and additional treatment may be greater than the potential long-term benefit from postponing microvascular complications. Screening decisions should therefore be based largely on consideration of cardiovascular risk and the availability of evidence based interventions to reduce cardiovascular risk. [ABSTRACT FROM AUTHOR]