Estimating the potential impact of interventions to reduce over-calling and under-calling of melanoma.

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'.

Beyond the treatment effect: Evaluating the effects of patient preferences in randomised trials.

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.

Meta-analysis of agreement between MRI and pathologic breast tumour size after neoadjuvant chemotherapy.

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.

Patients' perspectives of long-term follow-up for localised cutaneous melanoma.

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.

Early prediction of pathologic response to neoadjuvant therapy in breast cancer: systematic review of the accuracy of MRI.

Magnetic resonance imaging (MRI) has been proposed to have a role in predicting final pathologic response when undertaken early during neoadjuvant chemotherapy (NAC) in breast cancer. This paper examines the evidence for MRI's accuracy in early response prediction. A systematic literature search (to February 2011) was performed to identify studies reporting the accuracy of MRI during NAC in predicting pathologic response, including searches of MEDLINE, PREMEDLINE, EMBASE, and Cochrane databases. 13 studies were eligible (total 605 subjects, range 16-188). Dynamic contrast-enhanced (DCE) MRI was typically performed after 1-2 cycles of anthracycline-based or anthracycline/taxane-based NAC, and compared to a pre-NAC baseline scan. MRI parameters measured included changes in uni- or bidimensional tumour size, three-dimensional volume, quantitative dynamic contrast measurements (volume transfer constant [Ktrans], exchange rate constant [k(ep)], early contrast uptake [ECU]), and descriptive patterns of tumour reduction. Thresholds for identifying response varied across studies. Definitions of response included pathologic complete response (pCR), near-pCR, and residual tumour with evidence of NAC effect (range of response 0-58%). Heterogeneity across MRI parameters and the outcome definition precluded statistical meta-analysis. Based on descriptive presentation of the data, sensitivity/specificity pairs for prediction of pathologic response were highest in studies measuring reductions in Ktrans (near-pCR), ECU (pCR, but not near-pCR) and tumour volume (pCR or near-pCR), at high thresholds (typically >50%); lower sensitivity/specificity pairs were evident in studies measuring reductions in uni- or bidimensional tumour size. However, limitations in study methodology and data reporting preclude definitive conclusions. Methods proposed to address these limitations include: statistical comparison between MRI parameters, and MRI vs other tests (particularly ultrasound and clinical examination); standardising MRI thresholds and pCR definitions; and reporting changes in NAC based on test results. Further studies adopting these methods are warranted.

Optimal allocation of participants for the estimation of selection, preference and treatment effects in the two-stage randomised trial design.

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.

Effect of dependent errors in the assessment of diagnostic or screening test accuracy when the reference standard is imperfect.

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.

Who needs colonoscopy to identify colorectal cancer? Bowel symptoms do not add substantially to age and other medical history.

BACKGROUND: Many bodies advise that people with bowel symptoms undergo colonoscopy to detect colorectal cancer. AIM: To determine which bowel symptoms predict cancer on colonoscopy. METHODS: Information was collected on symptoms, demographics and medical history from patients subsequently undergoing colonoscopy. Multiple logistic regression modelling was used to identify predictors of colorectal cancer. An ROC curve was estimated for each model, and the area under the curve (AUC) was computed. RESULTS: Cancer was found in 159 patients and no cancer or adenoma in 7577 patients. Bowel symptoms that predicted cancer were rectal bleeding, change in bowel habit and rectal mucus. Prediction was the strongest in patients who had symptoms at least weekly and commencing within the previous 12 months; abdominal pain was predictive only in such patients. The odds ratios never exceeded 4.27. A model based on age, gender, and medical history was highly predictive (AUC = 0.79). Adding symptoms to this model increased the AUC to 0.85. CONCLUSIONS: This model predicts patients in whom colonoscopy will have the highest yield. Conversely, colonoscopy can be avoided in people at low risk: in our study, 95% of cancers could have been detected by doing only 60% of the colonoscopies.

Screening for colorectal cancer using the faecal occult blood test, Hemoccult.

BACKGROUND: Colorectal cancer is a leading cause of morbidity and mortality, especially in the Western world. The human and financial costs of this disease have prompted considerable research efforts to evaluate the ability of screening tests to detect the cancer at an early curable stage. Tests that have been considered for population screening include variants of the faecal occult blood test, flexible sigmoidoscopy and colonoscopy. Reducing mortality from colorectal cancer (CRC) may be achieved by the introduction of population-based screening programmes. OBJECTIVES: To determine whether screening for colorectal cancer using the faecal occult blood test (guaiac or immunochemical) reduces colorectal cancer mortality and to consider the benefits, harms and potential consequences of screening. SEARCH STRATEGY: Published and unpublished data for this review were identified by: Reviewing studies included in the previous Cochrane review; Searching several electronic databases (Cochrane Library, Medline, Embase, CINAHL, PsychInfo, Amed, SIGLE, HMIC); and Writing to the principal investigators of potentially eligible trials. SELECTION CRITERIA: We included in this review all randomised trials of screening for colorectal cancer that compared faecal occult blood test (guaiac or immunochemical) on more than one occasion with no screening and reported colorectal cancer mortality. DATA COLLECTION AND ANALYSIS: Data from the eligible trials were independently extracted by two reviewers. The primary data analysis was performed using the group participants were originally randomised to ('intention to screen'), whether or not they attended screening; a secondary analysis adjusted for non-attendence. We calculated the relative risks and risk differences for each trial, and then overall, using fixed and random effects models (including testing for heterogeneity of effects). We identified nine articles concerning four randomised controlled trials and two controlled trials involving over 320,000 participants with follow-up ranging from 8 to 18 years. MAIN RESULTS: Combined results from the 4 eligible randomised controlled trials shows that participants allocated to screening had a 16% reduction in the relative risk of colorectal cancer mortality (RR 0.84, CI: 0.78-0.90). In the 3 studies that used biennial screening (Funen, Minnesota, Nottingham) there was a 15% relative risk reduction (RR 0.85, CI: 0.78-0.92) in colorectal cancer mortality. When adjusted for screening attendance in the individual studies, there was a 25% relative risk reduction (RR 0.75, CI: 0.66 - 0.84) for those attending at least one round of screening using the faecal occult blood test. AUTHORS' CONCLUSIONS: Benefits of screening include a modest reduction in colorectal cancer mortality, a possible reduction in cancer incidence through the detection and removal of colorectal adenomas, and potentially, the less invasive surgery that earlier treatment of colorectal cancers may involve. Harmful effects of screening include the psycho-social consequences of receiving a false-positive result, the potentially significant complications of colonoscopy or a false-negative result, the possibility of overdiagnosis (leading to unnecessary investigations or treatment) and the complications associated with treatment.

Impact of privacy legislation on the number and characteristics of people who are recruited for research: a randomised controlled trial.

BACKGROUND: Privacy laws have recently created restrictions on how researchers can approach study participants. METHOD: In a randomised trial of 152 patients, 50-74 years old, in a family practice, 60 were randomly selected to opt-out and 92 to opt-in methods. Patients were sent an introductory letter by their doctor in two phases, opt-out before and opt-in after introduction of the new Privacy Legislation in December 2001. Opt-out patients were contacted by researchers. Opt-in patients were contacted if patients responded by email, free telephone number or a reply-paid card. RESULTS: Opt-in recruited fewer patients (47%; 43/92) after invitation compared with opt-out (67%; 40/60); (-20%; [-4% to -36%]). No proportional difference in recruitment was found between opt-in and opt-out groups varied by age, sex or socioeconomic status. The opt-in group had significantly more people in active decision-making roles (+30%; [10% to 50%]; p = 0.003). Non-significant trends were observed towards opt-in being less likely to include people with lower education (-11.8%; [-30% to 6.4%]; p = 0.13) and people who were not screened (-19.1%; [-40.1% to 1.9%]; p = 0.08). Opt-in was more likely to recruit people with a family history of colorectal cancer (+12.7%; [-2.8%, 28.2%]; p = 0.12). CONCLUSIONS: The number of participants required to be approached was markedly increased in opt-in recruitment. Existing participants (eg, screening attendees) with a vested interest such as increased risk, and those preferring an active role in health decision making and with less education were likely to be recruited in opt-in. Research costs and generalisability are affected by implementing privacy legislation.

Meta-analysis of sentinel node imprint cytology in breast cancer.

BACKGROUND: Intraoperative diagnosis of breast cancer metastases in axillary sentinel nodes is desirable to avoid a second operation for lymphadenectomy. Imprint or touch-preparation cytology is a popular technique that has high specificity and a wide range of sensitivity. METHODS: A systematic search of electronic databases was performed. Included articles were assessed for methodological and reporting quality. Random-effects model pooled estimates of sensitivity and specificity were calculated. Single-variable and multivariable meta-regression analyses were performed for predictors of sensitivity. RESULTS: Thirty-one studies were included; all were of good methodological quality but reporting quality varied. Pooled sensitivity of imprint cytology was 63 (95 per cent confidence interval (c.i.) 57 to 69) per cent and specificity was 99 (95 per cent c.i. 98 to 99) per cent. Pooled sensitivity for macrometastases was 81 per cent and that for micrometastases 22 per cent. Mean or median primary tumour size (P = 0.004), the prevalence of metastases (P = 0.103) and the proportion of micrometastases (P = 0.022) were significant risk factors in single-variable meta-regression analysis. Only the proportion of micrometastases remained significant in multivariable analysis. Frozen sectioning had better sensitivity than imprint cytology in three of four direct comparisons. CONCLUSION: Imprint cytology is simple and rapid, and has good sensitivity for macrometastases. The significance of poor sensitivity for micrometastases will be determined by trials investigating their natural history.

Florence-Sydney Breast Biopsy Study: sensitivity of ultrasound-guided versus freehand fine needle biopsy of palpable breast cancer.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is widely used in the diagnosis of breast cancer. It is unknown whether, for palpable cancers, ultrasound-guided FNAB is more accurate than freehand FNAB, and practice varies between physicians, services and countries. METHODS: From consecutive women attending a major cancer centre in Florence, we prospectively recruited subjects who had a definitely palpable lump which was solid on ultrasound and suspicious of malignancy (n = 102). All subjects were investigated using both ultrasound-guided and freehand FNAB (one aspirate with each method). Radiologists skilled in both sampling techniques performed all clinical examinations and aspirations, and for each subject the same radiologist obtained both FNAB samples. Sequence of aspiration method was randomised. Cytological interpretation was blinded to method of sampling. Comparative sensitivity (and insufficiency) for FNAB using the two methods was calculated in all cancers (n = 97). RESULTS: Ultrasound-guided FNAB resulted in 13.6% (5-22%) less insufficient aspirates than freehand FNAB (chi2 = 7.58; p = 0.006). When insufficient aspirates are included and considered as negative, ultrasound-guided FNAB has a 14.6% (5.8-23%) or a 16.5% (7.6-25.4%) significantly better sensitivity than freehand FNAB (for cytology 3-5 positive or cytology 4-5 positive respectively). When insufficient aspirates are excluded from the analysis, ultrasound-guided FNAB has a 1.4% (-1.2 to 3.9%) or a 2.6% (-2.5 to 7.8%) higher sensitivity than freehand FNAB (for cytology 3-5 positive or cytology 4-5 positive respectively) but this difference in the sensitivity of the two methods is not statistically significant. CONCLUSION: Our data suggest that ultrasound-guided FNAB has better sensitivity than freehand FNAB in palpable breast cancer, which is predominantly an effect of a significant reduction in insufficient aspirates, but in part an effect of 'upgrading' cytological classification of cancers.

Exfoliative cytology as a diagnostic test for basal cell carcinoma: a meta-analysis.

BACKGROUND: Exfoliative cytology is only occasionally used in clinical practice to diagnose basal cell carcinoma (BCC). OBJECTIVES: To systematically review the literature examining exfoliative cytology as a diagnostic tool for BCC and to meta-analytically summarize the accuracy of this test. METHODS: Diagnostic test meta-analysis. A computerized database search was made of MEDLINE (1966-2000) and EMBASE (1950-2000) using appropriately indexed terms. Hand searches of relevant journals were made. Bibliographies of relevant articles were further explored. Histopathology was used as the reference standard. A summary receiver-operating characteristic curve analysis was performed using the statistical package Meta-Test version 0.6 (J. Lau, New England Medical Center, Boston, MA, U.S.A., 1997). RESULTS: Eight primary studies (seven English language and one Italian language) fulfilled the inclusion criteria. The pooled sample included 1261 BCCs. These studies varied greatly in methodological quality and were, in general, poor. A meta-analysis showed the pooled sensitivity to be high at 97%[95% confidence interval (CI) 94-99]. Consequently, only 3% of BCCs included were misdiagnosed as non-BCC by cytology. The corresponding pooled specificity was 86% (95% CI 80-91). CONCLUSIONS: Exfoliative cytology probably has a high diagnostic accuracy for BCC. However, large, better designed and better reported studies are needed to ascertain the true accuracy of this technique. In the interim, this test should be considered in specific subgroups of patients in whom even a 2-mm punch biopsy may be considered inappropriate, e.g. a cosmetically sensitive site in a young person. Similarly, it should be considered when a BCC is to be treated without a diagnostic biopsy being taken, e.g. with cryotherapy.

New technologies in screening for breast cancer: a systematic review of their accuracy.

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.

The contribution of work-up or additional views to the accuracy of diagnostic mammography.

This study examines the influence of work-up on the accuracy of diagnostic mammography in symptomatic women. Subjects were sampled from all women consecutively attending a symptomatic breast clinic and aged 25-55 years (240 women shown to have breast cancer and 240 age-matched women shown not to have cancer). Mammography films were prospectively reported by two radiologists independently of each other and in a blinded manner using two phases of film reading: initially only baseline films were read, then mammography was re-read with work-up films. The accuracy of reporting mammography with and without work-up was compared using sensitivity and specificity, likelihood ratios, and receiver operating characteristic (ROC) curves. Reporting the mammogram with work-up (compared to without any work-up films) improved sensitivity (75.3% vs 69.0%, P=0.059) for one radiologist, with a non-significant gain in specificity (84.5% vs 79.4%, P=0.38). For the other radiologist, it resulted in a non-significant decrease in sensitivity (79.5% vs 83.7%, P=0.14) with a significant increase in specificity (85.6% vs 61.9%, P=0.00001). ROC curves for both radiologists showed that reporting mammography with work-up resulted in significant improvement (4.5% for R1, 6.8% for R2) in overall test accuracy. Our findings support the use of work-up mammography in the diagnostic setting.

Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative.

AIM: To improve the accuracy and completeness of reporting of studies of diagnostic accuracy in order to allow readers to assess the potential for bias in a study and to evaluate the general isability of its results. METHODS: The standards for reporting of diagnostic accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, and members of professional organisations shortened this list during a 2 day consensus meeting with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy. RESULTS: The search for published guidelines about diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. At the consensus meeting, participants shortened the list to a 25-item checklist, by using evidence whenever available. A prototype of a flow diagram provides information about the method of recruitment of patients, the order of test execution and the numbers of patients undergoing the test under evaluation, the reference standard, or both. CONCLUSIONS: Evaluation of research depends on complete and accurate reporting. If medical journals adopt the checklist and the flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of clinicians, researchers, reviewers, journals, and the public.

[Reporting studies of diagnostic accuracy according to a standard method; the Standards for Reporting of Diagnostic Accuracy (STARD)]. / Verslaglegging van diagnostisch evaluatieonderzoek volgens een standaardmethode; de 'standards for reporting of diagnostic accuracy' (STARD).

The objective of the 'Standards for Reporting of Diagnostic Accuracy' (STARD) initiative is to improve the reporting of studies of diagnostic accuracy, so as to allow readers to assess the potential for bias in a study and to evaluate the generalibility of its results. The group searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies. This was used to draw up a list of potential items. During a consensus meeting, a group of researchers, medical journal editors, and members of professional organisations reduced this list to a usable checklist. Wherever possible, evidence from the literature was used to justify the decisions made. The search for published guidelines about diagnostic research yielded 33 previously published checklists, from which a list of 75 potential items was extracted. At the consensus meeting, participants shortened the list to a 25-item checklist. A generic flow diagram was drawn up to provide guidance on the method for including patients, the order in which tests were to be conducted and the number of patients to undergo the test being evaluated, the reference standard, or both. A scientific publication can only be assessed when the reporting is both correct and complete. Use of the checklist and flow diagram will improve the quality of reports produced, to the advantage of clinicians, researchers, reviewers, journal editors and other interested parties.

Cancer screening.

"Screening is the systematic application of a test or inquiry, to identify individuals at sufficient risk of a specific disorder to benefit from further investigation or direct preventive action, among persons who have not sought medical attention on account of symptoms of that disorder."