1. DIAGNOSIS

2. Diagnosis A diagnostic test is ordinarily understood to mean a test
Performed in laboratory ,but the principles discussed
apply equally well to clinical information obtained from
History, physical examination ,and imaging procedures.
They also apply when a constellation of findings serves as a
diagnostic test.

3. Simplifying data
clinicians generally reduce the data to simpler from to make them useful in practice. Example :heart murmurs
More often. Complex data are reduced to a simple dichotomy(for example. Present/absent, abnormal/normal, or diseased/well)
Exampel :blood pressure

4. the accuracy of a test result
The doctor’s certnainty or uncertainty about a diagnosis has been expressed by using terms such as rule out or possible before a clinical diagnosis
A simple way of looking at the relationships between a test’s resulst and true diagnosis is shown in next figure

5. The accuracy of a test result
The doctor’s certnainty or uncertainty about a diagnosis has been expressed by using terms such as rule out or possible before a clinical diagnosis

6. the gold standard
More often, one must turn to relatively elaborate, expensive, or risky tests to be certain whether the disease is present or absent
Sometimes the standard of accuracy is itself a relaltively simple and inexpensive test such as a throat culture for group A streptococus

7. For disease that are not-limited and ordinarily become overt in matter of few years after they are first suspected,the resulsts of follow up can serve as a gold standard such as cansrs and coronic diseases
Clinicians and patients prefer simpler tests to the rigorous gold standard

8. Lack of information on negative test
The goal of all clinical studies
Most information about the value of a diagnostic test is obtained from clinical,and not reaserch
Data on the number of true negative versus false negetives generated by a test tend to be much less complete in the medical literature than data collected about positive test resultes

9. Lack of objective standards for disease
For some conditions,there are simply no hard and fast criteria for diagnosis : angina pectoris
The validity of laboratory test is established by comparing its results to a clinical diagnosis based on a careful history of symptoms and a physical examination

10. Consequences of imperfect standards
physician must choose as their standard of validity another test that admittedly is imperfect,but is considered the best avalible
If a new test is compaired with an old standard test,the new test may seem worse even thought it is actually better

11. Sensitivivity and specifity

13. Definition
Sensitivity is defined as the proportion of people with the disease who have a positive test for the disease.A sensitive test will rarely miss people with the disease
Specificity is the proportion of people without the diseases who have negative test. A specificity test will rarely misclassify people as having the disease when they do not.

14. Use of sensitive test
when there is an important penalty for missing a disease such as TB, syphilis; hodgkin’disease
when a great many possibilities are being considered; to reduce the number of possibilities.
A highly sensitive test is most helpful to the clinician when the test result is negative.

15. Use of specific test
Spesific test useful to confirm for rule out diagnosis that has been suggested by other data
Before patients are subjected to cancer chemotherapy
In sum, a highly specific test is most helpful when the test result is positive

16. Trade_off between sensitivity and specificity…

17. The ROC curve
Another way to express the relationship between sensitivity and specificity for a given test is to construct a curve, called receiver operator characteristic(ROC) curve
The ROC curve shows how severe the trade-of between sesitivity and spesitivity is for a test and can be used to help decide where the best cutoff point should be
ROC curves are particularly valuable ways of comparing alternative tests for the same diagnosis.
The overall accuracy of a test can be described as the area under the ROC curve

20. Establishing sensitivity and specificity
At the crudest level, Sensitivity and specificity may be inaccurately because an improper gold standard has be chosen .
Two other issue related to the selection of diseased and nondiseased patients can profoundly affect the determination of sensitivity and specificity
Spectrum/bias

21. Spectrum of patient
Difficulties may arise when the patients used to describe the test’properties are somehow different from those to whom the test will be applied in clinical practice
Example: CEA in diagnosing colorectal cancer
The sensitivity and specificity of test are independent of the prevalence of diseased(in theory)
Several characteristics of patient,such as stage and severity of disease may be related to the sensitivity and specificity of a test and to the prevalence(in practice)

23. Bias
The sensitivity and specificity of a test should be established independently of the means by which the true diagnosis is established
All the biases discussed tend to increase the agreement between the test and the gold standard. That is, they tend to make the test seem more useful than it actually is

24. Chance
Values for sensitivity and specificity are usually estimated from observations on relatively small samples of people of peaple with and without the disease of interest
Reported value for sensitivity and specifity shoud not be taken too literally if a small number of patients is studied

26. Definitions
The probability of disease,given the results of a test is called the predictive value of the test
Positive predictive value is the probability of disease in a patient with a positive test
Negative predictive value is the probability of not having the disease when the test result is negative
Predictive value : “if my patient’ test result is positive,what are the chance that my patient does have the diseases?

27. Determinants of predictive value
The predictive value of a test is not a property of the test alone
It is determined by the sensitivity and specificity of the test and the prevalence of disease in the population being tested

28. The more sensitive a test is, the better will be its negative predictive value (the more confident the clinician can be that a negative test result rule out the disease being sought)
The more specific the test is the better will be its positive predictive value

29. Positive results even for a very specific test,when applied to patients with a low likelhood of having the disease will be largely false positive.similarly,negative results
Therefore as the prevalence of disease in a population approaches zero,the positive predictive value of a test also approaches zero

30. As prevalence approache 100% negative predictive value approaches zero

31. Estimating prevalence
Because prevalence is such a powerful determinant of how useful a diagnostic test will be, clinicians must consider the probability of diseases before ordering a test
Although the resulting estimate of prevalence are not likely to be very precise,using them to be more accurate than implicit judgment

32. Increasing the prevalence of disease before testing
Diagnostic tests are most helpful when the presence of disease is neither very likely nor very unlikely
There are several ways in which the probablity of a disease can be increased before using a diagnosis test

33. Referral process
Referral to teaching hospital wards,clinics, and emergency departments increases the chance that significant disease will underlie patient’complains
…Diagnostic evaluations may need to be adjusted to suit the specific situation

34. Selected demographic groups
Physician can increase the yield of diagnostic tests by applying them to demographic group known to be at higher risk for a disease
a sickle cell test in african american

35. Specifics of the clinical sitution
They are clearly the strongest influence on the order tests .
Symptoms,signs,disease risk factors all raise or lower the probability of finding a disease
The value of applying diagnostic tests to persons more likely to have a particular illness is intuitively obvious to most doctors
The less selective the approach,the lower the prevalence of the disease is likely to be and the lower will be the positive predictive value of the test

36. Implication for interpreting the medical literature
Published description of diagnostic tests often in clude,in addition to sensitivity and specificity,some conclusion about predictive value
The data for these publications are often gathered in university teaching hospitals where the prevalence of serious disease is relatively high
Statements about predictive value in medical literature may be misleading when the test is applied in less highly selected settings

37. Likelihood ratio
Likehood ratios are an alternative way of describing the performance of a diagnostic test that can be used to calculate the probability of diesease after a positive or negative test

38. odds
Probability used to express sensitivity, specifity and predictive valuertion
It is the proportion of people in whom a particular characteristic
Odd is the ratio of two probabilities

39. Definitions
The likelihood ratio for a particular value of a diagnostic test is defined as the probability of that test result in people with the disease divided by probability of the result in people without disease
If a test yields dichotomous results two types of likelihood ratio describe its ability to discriminate between disease and no diseased people

40. It can accommodate the common clinical practice of putting more weight on extremely high test results than on borderline ones when estimating the probability that particular disease is present
It is particularly well suited for describing the overall odds of disease when a series of diagnostic tests is used

41. Use of likelihood ratios
Pretest odds contain the same information as prior the same as sensitivity/specifity and post test odds the same as positive predictive value
The main advantage of likelihood ratio is possible to go beyond the simple and clumsy classification of a test result as either abnormal or normal

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45. Multiple tests
Because clinicians commonly use imperfect diagnostic tests with less than 100% sensitivity and specificity ,a single test results in probability of disease that is neither vary high nor vary low
The physician is ordinarily bound to raise or lower the probability of disease substantially in such situations
When multiple different test are performed and all are positive or all are negative ,the interpretation is straighforward

46. Multiple diagnostic tests can be applied in two basic ways
Multiple diagnostic can be used in parallel testing and a positive result of any test is considered evidence for disease
They can be done in serial testing with the decision to the next test it based on the previous test and diagnostic process is stopped with a negative result

48. Parallel testing
Multiple tests in parallel generally increase the sensitivity and negative predictive value above of each individual test
By using the tests in parallel the net effect is a more sensitive diagnostic strategy

50. Clinical prediction rules
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51. Serial testing
Physician most often use serial testing strategies where rapid assessment of patient is not required
When some of tests are expensive or risky
It leads to less laboratory use than parallel testing
Maximizes specificity and positive predictive value but lowers sensitivity and negative predictive value

52. Serial likelihood ratios
As reach test done, the posttest odds of one became the pretest odds for the next in the end a new probability of disease is found that takes into account the information contributed by all the tests in the series