Dataset Information

Assessing agreement between malaria slide density readings.

ABSTRACT:

Background

Several criteria have been used to assess agreement between replicate slide readings of malaria parasite density. Such criteria may be based on percent difference, or absolute difference, or a combination. Neither the rationale for choosing between these types of criteria, nor that for choosing the magnitude of difference which defines acceptable agreement, are clear. The current paper seeks a procedure which avoids the disadvantages of these current options and whose parameter values are more clearly justified.

Methods and results

Variation of parasite density within a slide is expected, even when it has been prepared from a homogeneous sample. This places lower limits on sensitivity and observer agreement, quantified by the Poisson distribution. This means that, if a criterion of fixed percent difference criterion is used for satisfactory agreement, the number of discrepant readings is over-estimated at low parasite densities. With a criterion of fixed absolute difference, the same happens at high parasite densities. For an ideal slide, following the Poisson distribution, a criterion based on a constant difference in square root counts would apply for all densities. This can be back-transformed to a difference in absolute counts, which, as expected, gives a wider range of acceptable agreement at higher average densities. In an example dataset from Tanzania, observed differences in square root counts correspond to a 95% limits of agreement of -2,800 and +2,500 parasites/microl at average density of 2,000 parasites/microl, and -6,200 and +5,700 parasites/microl at 10,000 parasites/microl. However, there were more outliers beyond those ranges at higher densities, meaning that actual coverage of these ranges was not a constant 95%, but decreased with density. In a second study, a trial of microscopist training, the corresponding ranges of agreement are wider and asymmetrical: -8,600 to +5,200/microl, and -19,200 to +11,700/microl, respectively. By comparison, the optimal limits of agreement, corresponding to Poisson variation, are +/- 780 and +/- 1,800 parasites/microl, respectively. The focus of this approach on the volume of blood read leads to other conclusions. For example, no matter how large a volume of blood is read, some densities are too low to be reliably detected, which in turn means that disagreements on slide positivity may simply result from within-slide variation, rather than reading errors.

Conclusions

The proposed method defines limits of acceptable agreement in a way which allows for the natural increase in variability with parasite density. This includes defining the levels of between-reader variability, which are consistent with random variation: disagreements within these limits should not trigger additional readings. This approach merits investigation in other settings, in order to determine both the extent of its applicability, and appropriate numerical values for limits of agreement.

SUBMITTER: Alexander N

PROVIDER: S-EPMC2817705 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Publications

Assessing agreement between malaria slide density readings.

Alexander Neal N Schellenberg David D Ngasala Billy B Petzold Max M Drakeley Chris C Sutherland Colin C

Malaria journal 20100104

<h4>Background</h4>Several criteria have been used to assess agreement between replicate slide readings of malaria parasite density. Such criteria may be based on percent difference, or absolute difference, or a combination. Neither the rationale for choosing between these types of criteria, nor that for choosing the magnitude of difference which defines acceptable agreement, are clear. The current paper seeks a procedure which avoids the disadvantages of these current options and whose paramete ...[more]

PMID: 20047679

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Project description:BackgroundRecent developments in diagnostic techniques for malaria, particularly DNA probes and sero-immunology, have raised questions as to how these techniques might be used to facilitate malaria diagnosis at the most peripheral levels of the primary health care system. At present, malaria diagnosis is based on the standard microscopic examination of blood films in most field epidemiologic studies and is likely to remain so in the immediate future in Africa. The objective of this study was to assess inter-observer agreement for the examination of Giemsa-stained slides for Plasmodium falciparum parasites.MethodsChildren aged 0 to 10 years were enrolled yearly in Bancoumana village (West Africa), mainly during the transmission season (June to October). The blood smears obtained from the persistently negative children in June 1996, August 1996, October 1996 and March 1997 were systematically re-examined. A stratified random sample (10%) proportional to the following parasite density classes 1-100, 101-5000, and 5001 and over was taken from the slides collected. The kappa statistics and the intra-class correlation were used as measures of agreement the first and the second slide examinations.ResultsThe weighted kappa statistic, widely used as a chance-corrected measure for nominal agreement, showed excellent inter-observer agreement (?(w)=0.7926; 95% CI [0.7588, 0.8263]; p=0.01). The intra-class correlation co-efficient had the same value of 0.7926 confirming the appropriateness of the weighted kappa statistic. Inter-observer agreement for slides read as negative by one observer, or as containing more than 100 parasites per ?l, was excellent: 97% (493/506) and 92% (145/158), respectively. In contrast, the inter-observer agreement for slides read by one observer as containing 1-100 parasites/?l was poor, 36% (96/268).ConclusionsIn field conditions in Mali, there was a high reproducibility for slides reported as negative or as having more than 100 parasites per ?l. However, smears with readings of 1-100 parasites per ?l were less reproducible and should be re-examined carefully.

Project description:Validating digital pathology as substitute for conventional microscopy in diagnosis remains a priority to assure effectiveness. Intermodality concordance studies typically focus on achieving the same diagnosis by digital display of whole slide images and conventional microscopy. Assessment of discrete histological features in whole slide images, such as mitotic figures, has not been thoroughly evaluated in diagnostic practice. To further gauge the interchangeability of conventional microscopy with digital display for primary diagnosis, 12 pathologists examined 113 canine naturally occurring mucosal melanomas exhibiting a wide range of mitotic activity. Design reflected diverse diagnostic settings and investigated independent location, interpretation, and enumeration of mitotic figures. Intermodality agreement was assessed employing conventional microscopy (CM40×), and whole slide image specimens scanned at 20× (WSI20×) and at 40× (WSI40×) objective magnifications. An aggregate 1647 mitotic figure count observations were available from conventional microscopy and whole slide images for comparison. The intraobserver concordance rate of paired observations was 0.785 to 0.801; interobserver rate was 0.784 to 0.794. Correlation coefficients between the 2 digital modes, and as compared to conventional microscopy, were similar and suggest noninferiority among modalities, including whole slide image acquired at lower 20× resolution. As mitotic figure counts serve for prognostic grading of several tumor types, including melanoma, 6 of 8 pathologists retrospectively predicted survival prognosis using whole slide images, compared to 9 of 10 by conventional microscopy, a first evaluation of whole slide image for mitotic figure prognostic grading. This study demonstrated agreement of replicate reads obtained across conventional microscopy and whole slide images. Hence, quantifying mitotic figures served as surrogate histological feature with which to further credential the interchangeability of whole slide images for primary diagnosis.

Project description:ObjectivesTo examine inter- and intra-observer agreement for four simple hepatobiliary phase (HBP)-based scores on gadoxetic acid (GA)-enhanced MRI and their correlation with liver function in patients with mixed chronic liver disease (CLD).MethodsThis single-center, retrospective study included 287 patients (62% male, 38% female, mean age 53.5 ± 13.7 years) with mixed CLD (20.9% hepatitis C, 19.2% alcoholic liver disease, 8% hepatitis B) who underwent GA-enhanced MRI of the liver for clinical care between 2010 and 2015. Relative liver enhancement (RLE), contrast uptake index (CUI), hepatic uptake index (HUI), and liver-to-spleen contrast index (LSI) were calculated by two radiologists independently using unenhanced and GA-enhanced HPB (obtained 20 min after GA administration) images; 50 patients selected at random were reviewed twice by one reader to assess intra-observer reliability. Agreement was assessed by intraclass correlation coefficient (ICC). The albumin-bilirubin (ALBI) score, the model of end-stage liver disease (MELD), and the Child-Turcotte-Pugh (CTP) score were calculated as standards of reference for hepatic function.ResultsIntra-observer ICCs ranged from 0.814 (0.668-0.896) for CUI to 0.969 (0.945-0.983) for RLE. Inter-observer ICCs ranged from 0.777 (0.605-0.874) for HUI to 0.979 (0.963-0.988) for RLE. All HBP-based scores correlated significantly (all p < 0.001) with the ALBI, MELD, and CTP scores and were able to discriminate patients with a MELD score ≥ 15 versus ≤ 14, with area under the curve values ranging from 0.760 for RLE to 0.782 for HUI.ConclusionGA-enhanced, MRI-derived, HBP-based parameters showed excellent inter- and intra-observer agreement. All HBP-based parameters correlated with clinical and laboratory scores of hepatic dysfunction, with no significant differences between each other.Key points• Radiological parameters that quantify the hepatic uptake of gadoxetic acid are highly reproducible. • These parameters can be used interchangeably because they correlate with each other and with scores of hepatic dysfunction. • Assessment of these parameters may be helpful in monitoring disease progression.

Project description:BackgroundWe consider the problem of assessing inter-rater agreement when there are missing data and a large number of raters. Previous studies have shown only 'moderate' agreement between pathologists in grading breast cancer tumour specimens. We analyse a large but incomplete data-set consisting of 24,177 grades, on a discrete 1-3 scale, provided by 732 pathologists for 52 samples.Methodology/principal findingsWe review existing methods for analysing inter-rater agreement for multiple raters and demonstrate two further methods. Firstly, we examine a simple non-chance-corrected agreement score based on the observed proportion of agreements with the consensus for each sample, which makes no allowance for missing data. Secondly, treating grades as lying on a continuous scale representing tumour severity, we use a Bayesian latent trait method to model cumulative probabilities of assigning grade values as functions of the severity and clarity of the tumour and of rater-specific parameters representing boundaries between grades 1-2 and 2-3. We simulate from the fitted model to estimate, for each rater, the probability of agreement with the majority. Both methods suggest that there are differences between raters in terms of rating behaviour, most often caused by consistent over- or under-estimation of the grade boundaries, and also considerable variability in the distribution of grades assigned to many individual samples. The Bayesian model addresses the tendency of the agreement score to be biased upwards for raters who, by chance, see a relatively 'easy' set of samples.Conclusions/significanceLatent trait models can be adapted to provide novel information about the nature of inter-rater agreement when the number of raters is large and there are missing data. In this large study there is substantial variability between pathologists and uncertainty in the identity of the 'true' grade of many of the breast cancer tumours, a fact often ignored in clinical studies.

Dataset Information

Assessing agreement between malaria slide density readings.

Background

Methods and results

Conclusions

Publications

Assessing agreement between malaria slide density readings.

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