When working in a medical laboratory there are a variety of different ranges against which different classes of test results are assessed. It can be confusing, but understanding how each range is derived and why it is applied to a particular type of result is essential. This article provides a basic explanation of the various ranges, limits and intervals that you may encounter. It is recommended that you are familiar with the concepts details in the introduction to statistics article prior to reading this one.

1 Critical Intervals

All patient test results are assessed against ‘critical intervals’, which you may also hear referred to as alert limits. If a result falls within these ranges it has generally been defined as abnormal in some way, and could potentially be life threatening unless there is prompt medical intervention.

Visualisation of a critical interval
Example of how critical intervals may apply to INR test results. In this instance any result that falls in the range 0 – 1 or 4 – 8 will trigger an alert for the individual performing the test, to let them know the result is deemed critical.

Whilst it’s not necessary to establish a critical interval for every analyte, to responsibly serve the users of the laboratory they should be defined for any tests deemed necessary, where particular results may indicate a medically threatening issue (e.g. INR, Hb etc…).

When an analyser reports a result it should be cross checked against ranges that have been set by the laboratory. If the result is found to be critical it must be communicated to a clinician urgently, which is the reason why pathology labs sometimes phone results through to GP’s.

Naturally thorough documentation and maintaining a clear audit trail of the actions that were taken should be undertaken in accordance with a facilities policies and procedures.

2 Reference Intervals

Reference intervals are reported alongside laboratory test results and provide a ‘reference’ for clinicians to determine where normal patient results should fall. In the example lab report shown below the reference interval is reported alongside the test result in brackets.

Pathology test report
Example of a patholgoy test report showing the reference interval in brackets alongside the test result.

Reference intervals typically quantify the variation of a measurement in 95 % of healthy individuals (i.e. 2 standard deviations from the mean). Reference intervals between different laboratories are not all the same because different measurement measurement methods will exhibit bias (a consistent difference) from one another, or the local populations who have been measured may differ for biological reasons (e.g. ethnicity).

Naturally, over time, if there are measurable changes in the labs test method, it may be necessary to adjust the ranges again.

3 Allowable Limits of Performance

Allowable Limits of Performance (ALP) specify the cut-off points within which comparison test results must fall. Practically there are two cases when the results from one test system are compared to those of another.

The first is when participating in a Quality Assurance Program, where target results are often assigned by an external and independant worldwide reference laboratory.

The second occasion is when conducting a lab comparison test locally for quality assurance purposes (inter-laboratory comparison), or when verifying the performance of a new test against another laboratory or test method.

In both these cases it may be appropriate to adopt the Allowable Limits of Performance set by the RCPA QAP, which may be found on their website.

When comparing results it’s important to understand that if a test result falls outside of the range set by the allowable limits, it doesn’t necessarily mean there is an issue with your test system. Consider the example shown below; because there is bias present some of the results appear to be below the lower ALP value, but it can clearly be seen that these results fall within 1 unit if the average (0 point) is moved.

Graph of normalised results from an inter-laboratory comparison
Lab comparison results from the mLabs system with visible bias.

With the hindsight of historical data it’s plain to see, but if the results were to be adjusted for bias there would be no question of systemic issues.

It’s important to take bias into consideration when comparing results that appear to be out of the allowed range.

4 Quality Control (QC) Limits

QC results are used to validate whether the instrument is operating within pre-defined specifications, inferring that patient test results are reliable. Once the test system is validated, patient results can then be used for diagnosis, prognosis, or treatment planning.

When conducting QC tests results may initially be assessed against batch specific limits which are set by the manufacturers of QC material and defined on product literature.

However, in a laboratory setting, after sufficient QC testing has been conducted it is then possible to set limits in-house, which will reflect the inter-batch variability and your own analysers performance.

 

QC limits are typically set 2 and 3 standard deviations from the mean of the data. What to do when results fall outside of these limits depends on the number of Westgard rules that are broken. It is strongly encouraged that you read and gain an understanding of the rules, which explain how to identify and categorise discrepant QC results and decide if there is an issue that may prevent patient testing.