Cells that count. The standardizing of Cells that count. The standardizing of diagnostic tests for bovine mastitisdiagnostic tests for bovine mastitis

Bert Nederbragt

Descartes Centre for the History and Philosophy of the Sciences and the Humanities and

Faculty of Veterinary Medicine

epidemiology clinical trial

diagnosis

therapy development

pathogenesis

epistemology (and social framing)

of a diagnostic test

accuracy of the test defined as sensitivity and specificity

gold standard

a reference test that is supposed to determine a target condition or disease state unambiguously

sensitivity = probability of a positive test

among patients with disease

specificity = probability of a negative test

among individuals without disease

sensitivity and specificity are never 1.0 false negatives and false positives may

occur

consider alleged disease state as hypothesis/theory

consider test result as evidence for the theory

because of a probability of false positives or false negatives

underdetermination

new test: gold standard as reference test

sensitivity and specificity of new test will always be less than those of the GS, although it may be a better test

undercalibration

new test: cut-off point

below what point do we consider individuals normal, above which point ill or affected?

changing cut-off points changes specificity and sensitivity of the test specificity and sensitivity undercalibrated

>> cut-off point not decisive

underdiscrimination

epistemology of the diagnostic test

bovine mastitis

epistemology of the diagnostic test

decreased milk quality

bovine mastitis:

inflammation of the udder by bacteria

clinical mastitis

redness, pain, nodes in tissue diagnosis: palpation

subclinical mastitis

predicts clinical mastitis decreased milkproduction

diagnosis: somatic cell count (SCC)

somatic cell count gold standard

for subclinical mastitis

what to do in case of underdetermination? (i.e. that testresults may be false positives or negatives)

diagnosis

multiple derivability

multiple derivability

the strategy to infer a theory from evidence obtained by two or more independent methods that differ in the background

knowledge and technical principles on which they are based

Mastitis streptococci and leukocytes (from Zschokke/Kitt 1908)

mastitis diagnosis and underdetermination

somatic cell count of milk: false positive or false negative

(underdetermination)

bacteriological investigation: presence of bacteria without disease is possible

(underdetermination)

both tests positive >> mastitis

mastitis diagnosis and undercalibration

electrical conductivity (EC) against SCC and bacteriological culturing (BC)

EC cheap and easy in robot milking

meta analysis of sensitivity and specificity of EC for mastitis detection, using different gold standards

SSC sens 0.57 spec 0.94 BC sens 0.75 spec 0.95 SSC and BC sens 0.60 spec 0.91

Mirjam Nielen, thesis 1994, Utrecht University

mastitis diagnosis and undercalibration

what to do in case of undercalibration? (i.e. that test results may be more or less probable than those of the reference test)

diagnosis

weighing evidence against context

weighing evidence against context

epistemological context: background knowledge

social context: consequences of decision

bovine mastitis weighing evidence against context

evidence: positive EC signal in milk of cow

social context: former mastitis problems on farm age of cow

stage of lactation

underdiscrimination

frequency distributions, threshold values, sensitivity and specificity

mastitis diagnosis and underdiscrimination

threshold values of somatic cell count (cells/ml milk)

going up and down by negotiation

Europe: 400,000 USA: 700,000

1950: 500,000 1970: 200,000 2009: 400,000

individual cow: 200,000 bulk tank milk: 400,000

International Dairy Federation 1967

"It will be economically justified to fix the threshold value for cells in bulk farm milk in such a way, that not more than 10 % of the production of the milk

must be declared abnormal or mastitic and therefore be rejected for delivery to the market."

diagnostic network

in which shifting of balances takes place

biomedical factors: SCC and immune system

technological factors: robot milking

commercial factors: milk quality

examples of factors that require re-framing of the network: