Interpretation of Laboratory Tests
We have already encountered difficulties with interpretation of laboratory test results above. Interpretation of test results can be simple but on occasion can very challenging and require an in-depth knowledge of haematology, microbiology, biochemistry or immunology. Histopathology (looking at tissue samples under the microscope) is unique in that there are no simple YES/NO or POSITIVE/NEGATIVE divisions and interpretation of tissue pathology or cytology (cell smear) slides requires many years of training.
All people are subtly different and so is their physiology. This is why we have “normal ranges” (sometimes called reference ranges) for laboratory tests. These ranges theoretically encompass 95% of the healthy population. Because of this 1 in 20, (5%) of results from healthy people may fall outside the “normal” range. Usually these “abnormal” results in healthy people are only just outside the range of “normal” and if there are no clinical findings to suggest disease in the person the healthcare professional can either ignore the result or note it for recheck in the future if there are any concerns. Statistics tell us that if we do a large number of tests then there will almost certainly be some mild deviations from what has been defined as normal.
Other difficulties arise because tests in general are not 100% sensitive or 100% specific although they are often close to these figures. Test results need to be interpreted in the context in which they are performed. Let us go back to the example we used previously of the healthy middle-aged woman having a tumour marker test. Let us assume that the test is 97% sensitive (if we perform it on 100 people with that particular cancer it will correctly identify 97 of them) and it is 99% specific (if we do it on 100 healthy people 1 will receive false-positive results).
We now perform this test on two different people. One is our healthy middle-aged person who we estimate has a 1 in 2000 (0.05%) chance of having this cancer. We also do the test on another middle-aged person who has had this cancer in the past and been treated with surgery and chemotherapy and has come back one year later feeling unwell and with abdominal pain. We estimate their chance of having cancer as 1 in 2 (50%).
Somewhat surprisingly, the same result of the same test on these two different people means quite different things. Let us suppose they both get exactly the same modestly elevated test result. In the healthy person the positive predictive value (PPV) of the test i.e. the probability they have cancer given that they have a positive test result is less than 5%. In the previously treated cancer patient the PPV or probability they have recurrent cancer is nearly 99%.
Conversely if the test result had come back negative or normal the negative predictive value (NPV) or probability the healthy person does not have cancer is almost 100% and is 97% in the previously treated cancer patient. There is nothing mysterious about this. What it means is that a healthcare professional requesting a test needs to aware of how likely it is that the person having the test has the disease being sought and some feeling for the sensitivity and specificity of the test being used. They also need to take into consideration how abnormal the test result is, since a more abnormal result is more likely to be a true positive than a mildly abnormal one and this of course affects the calculations above which do not take degree of abnormality into account. When doctors or laboratory personnel interpret test results they take all these factors into account, not like a computer, but using knowledge and experience to make an approximate calculation.
There are a number of other things that need to be considered when interpreting laboratory test results. There is a very small probability that the result could be wrong for a variety of reasons. Mislabelling and taking the blood from the wrong patient are vanishingly rare due to the strict quality control measures that accredited medical laboratories have in place. However if the sample was collected at a distant location there is the small possibility that it has been subjected to adverse conditions during transport, for example being allowed to get too hot or cold despite all precautions being taken. More common but still rare, are interferences in the test. Examples of these are antibodies in the blood of the patient that interfere with some types of assay procedures and interferences by drugs. Laboratory scientists conducting the tests are very well trained and experienced operators can often identify the abnormalities caused by interferences and prevent the affected tests being reported. However if the interference is of a new type or relatively mild, then it may not be identified in the lab and an incorrect result reported. If the result does not accord with the clinical findings it is the responsibility of the healthcare professional to be suspicious and communicate with the laboratory and perhaps arrange repeat testing, sometimes using a different test method.
This is just a brief overview of some aspects of laboratory testing. Lab test results often do not give simple YES/NO answers and many factors may have to be taken into account to use laboratory testing services wisely.