Quality control (QC) in clinical chemistry is a systematic and concise process designed to maintain and enhance the precision and accuracy of laboratory tests.
It starts with patient preparation to results interpretation. This ultimately ensures optimal patient care.
There are two types of quality control in clinical chemistry.
They are:
- Internal Quality Control (IQC). IQCs are performed every day by medical laboratory scientists or personnel. This evaluates primarily the precision (repeatability or reproducibility) of methods used in the laboratory.
- External Quality Control (EQC). EQC is carried out periodically. The frequency of the EQC tests varies. It could be monthly, every two months, 4 times a year, etc. EQC is done to evaluate the accuracy of the laboratory’s analytical methods.
EQC is done through an EQAS program, External Quality Assessment Services, in which a lab must register to participate.
This article will focus on and explain the comprehensive approach to IQC in clinical chemistry laboratories based on three critical phases of laboratory testing: preanalytical, analytical, and post-analytical.
Table of Contents
PREANALYTICAL QUALITY CONTROL
This phase focuses on all the steps before a patient sample, like blood or urine, reaches the chemistry laboratory.
This includes ordering a test, patient preparation, sample collection, transportation, sample accession, and sorting. Any error or mistake here has already affected the result in advance.
So, let us look at each item above one by one.
Patient preparation:
Some tests require certain preparations by the patient. For instance, in a fasting blood sugar test, a patient is required to fast overnight(between 8 and 12 hours) before his or her blood is collected. No food or drinks are allowed within this period except water.
Some other tests require patients to refrain from certain drugs or activities before sample collection.
For instance, a patient should avoid any stress or exercise immediately before going for sample collection for a prolactin test.
Hence, patients need to be aware of what is expected of them per test. Otherwise, the accuracy of the result will be compromised if the patient fails to follow the preparation instructions or procedure.
Sample collection:
The responsibility to ensure quality here lies with the sample collector, usually the phlebotomist.
Phlebotomists understand how important it is to accurately and clearly label samples with patient details(full name, date of birth, hospital number, etc.), test(s) ordered, sample type, time of collection, etc.
So, they usually have standardized procedures for different sample collections, which should always be engaged for consistency.
For instance, a haemolysed sample for a potassium test has adversely altered the accuracy of the result, and oftentimes, the lab rejects this kind of sample if sent to the lab.
Also, there are different types of sample containers for clinical chemistry tests, and any sample collected in the wrong tube will affect the results. Again, a blood sample collected in an EDTA tube cannot be used for potassium estimation because it will give a false high value.
Phlebotomists are trained professionals who ensure quality with regard to sample collection. If you are performing the duty of a phlebotomist, make sure you have the skills, knowledge and training to do so.
Sample transportation:
Maintaining sample integrity is very important in quality management. The condition between sample collection and analysis largely determines the reliability of the test result.
For instance, the blood sample for an ammonia test is sent to the lab immediately after collection. However, where delays are anticipated, the blood is centrifuged, separated, and the plasma frozen.
The plasma can then be sent to the lab frozen on an ice pack or dry ice.
Sample accession and sorting:
Most hospitals have ‘sample reception’. Here, laboratory specimens are received, sorted, and registered in a laboratory physical document or Laboratory Information System(LIS).
Laboratory aides or technicians are often trained to work in this section of the laboratory. They ensure that samples are sorted correctly and promptly before being sent to the main laboratory for processing.
Ordering a test:
Physicians should consider a test’s relevance to a patient before ordering it. Ordering the wrong test for a given patient will negatively impact the patient in terms of time and cost.
Patient identification:
In the lab, a patient has two forms of identification: the sample container and the request form.
The laboratory request form must be filled out completely and with accurate information. This should include details like gender, age, full name, hospital number and the different tests to be done.
Any mismatch between the information on the request form and that on the sample container can lead to sample rejection in the lab, which wastes patient samples and time.
ANALYTICAL QUALITY CONTROL
This phase involves the actual testing process within the clinical chemistry laboratory. Some clinical chemistry labs are automated, while some are manual.
However, some have a combination of automation and manual methods of testing patient samples.
Whether manual or automated lab, the most important thing is that quality control has to be done.
The QC (IQC & EQA) done in a given chemistry lab depends on the types and number of tests run. It also depends on the method or instrumentation used.
On a daily basis, the following is done in a chemistry lab:
Daily Maintenance:
This involves cleaning the outer part of a machine or an analyser using the right cleaning fluid, which can be water, depending on the manufacturer’s instructions.
The next maintenance may involve cleaning the inner parts of the machine, such as probes, or checking the optical systems. This, however, usually involves giving the machine a command(through pressing a button), so this process is usually automated.
However, laboratory staff must check the reagent or fluid the analyser needs to clean itself (probes, etc.) to ensure it is enough by volume.
If an analyser requires 200ml of cleaning fluid, the cleaning fluid container must contain at least 201ml of fluid before the lab staff gives the machine the command to self-clean.
Regular maintenance of the equipment is very important in maintaining high performance and accuracy of results.
It also reduces repair costs and analysis interruptions due to breakdowns.
A good maintenance system should be adhered to, including routine checks and prompt address of any malfunctions.
This will help prevent unexpected errors and increase the reliability of test results.
After maintenance, the next thing is
Daily calibration:
Once you are done with daily maintenance, the next is to calibrate the analyser you use for testing patient samples.
You will use a solution or reagent called Calibrators. Calibrators are solutions with known concentrations of specific analytes, such as potassium and calcium.
What the calibrators do is to set a reference point for the instrument. According to CLSI, ‘Calibration is a process of testing and adjusting an instrument or test system to establish a correlation between the measurement response and the concentration or amount of the substance that is being measured by the test procedure’.
So, the medical scientist basically runs the Calibrator like he would run a patient sample.
Once the analyser is calibrated (which could involve adjustment), the next step is Daily IQC.
Daily IQC:
Internal Quality Control is run three times a day in a busy chemistry laboratory; some run it every three hours in a very busy lab.
The first IQC is done by 8 a.m., the second is done in the afternoon by 1:00 p.m., and the last one is run by 4:00 p.m. before the on-call scientists take over for the night shift.
And the process repeats itself the next day.
The times mentioned here may be different in some labs. Some labs could run their IQC by 9 a.m., 2 p.m., and 5 p.m.
However, less busy labs may run their IQC twice daily: morning and afternoon or even once daily in the morning.
For instance, a lab that receives 1000 samples for glucose tests daily may decide to run IQC 3 times daily. The one that receives 5oo may run IQC 2 times daily, while the one that receives 200 can run IQC once a day.
The choice of time intervals is because if the next IQC run fails, the previous run samples may need to be repeated.
For instance, if you run IQC by 8 a.m. and it passes, and you run it again by 1 p.m. and it fails, what happens to the patient samples run between 8 and 1 p.m.?
What if 1000 samples were run between 8 and 1 p.m.? The problem is that you don’t know which time the machine had issues between 8 and 1 p.m.
So, the problem is that the quality of those 1000 samples tested between 8 a.m. and 1 p.m. cannot be trusted or guaranteed to accurately reflect patient status.
Weekly IQC:
Some tests may require IQC once a week. The lab does not usually receive such requests often, so a weekly IQC may be adequate.
The other quality control parts include laboratory room temperature and reagent storage temperature.
Most manufacturers of laboratory reagents and consumables state the temperature storage conditions that must be followed.
So, proper storage and handling of reagents should be ensured to avoid compromising their integrity.
Some chemistry analysers give audible alarms when room temperature conditions are outside the specification.
The implication is that the patient sample MUST not be run when the machine’s temperature is outside the specified ranges.
A temperature of 0 degrees may be too cold, or 30 degrees may be too hot for a particular machine or analyser.
Other aspects of analytical quality control may not be discussed here. These include quality control sample levels(1,2 & 3), Levey-Jennings charts and Westgard rules, Validation, verification, Calibration verification, etc.
POSTANALYTICAL QUALITY CONTROL
The post-analytical phase includes all activities following the completion of the analysis, focusing on the interpretation, reporting, and utilization of test results.
This is the stage where doctors who specialize in laboratory medicine come in.
The steps could include:
Result verification and validation:
Some advanced laboratory has a system that does this automatically, where there is no apparent issue with the result.
The system usually flags a particular value if it is high, low, or inconsistent with the previous test on the system.
This flag is part of what we call Delta checks.
By definition, A delta check in a chemistry analyzer is a quality control process used to detect discrepancies in patient test results by comparing current values to previous ones. This helps identify potential errors before results are reported.
Some labs or systems do not have built-in checks, so senior medical scientists must manually perform verification before results are released.
Some tests require a consultant chemical pathologist review before they are released.
This review at this stage involves checking for accuracy and consistency in context with the patient’s history and other clinical information.
Result reporting and time:
Some test results need to be reported urgently. Samples designated “STAT “must be reported immediately, like high potassium results. Failure to do so may lead to patient death or harm.
Time is the most important part of a quality management system.
Laboratories should ensure that reports are comprehensible to both clinicians and patients and include all relevant information(like normal ranges ) needed for clinical decision-making.
Result interpretation:
Result interpretation should be clear and concise to support clinical decision-making. Doctors and nurses usually play the roles of interpreting the results to patients.
In conclusion, the overview provided here is a general framework for QC in clinical chemistry. Specific QC requirements may vary depending on the laboratory’s complexity and the tests performed. Adherence to relevant regulatory standards (e.g., ISO 15189) is very important.
By implementing a comprehensive QC program, clinical chemistry laboratories can significantly improve the accuracy and reliability of their test results, contributing to better patient care.
Just like I mentioned earlier, our focus here is not on EQA. However, you can read the following by clicking through the links provided. They are still part of Quality controls in the Clinical chemistry laboratory.
External quality assessment (EQA)
Proficiency testing
Standard operating procedures (SOPs)
Employee training
Internal audits
References:
- Westgard, Q. C., & Westgard, J. H. (2007). Quality control in clinical chemistry. Washington, DC: AACC Press.
- Henry’s Clinical Diagnosis and Management by Laboratory Methods.
- Clinical and Laboratory Standards Institute (CLSI) guidelines.
- Levey S, Jennings E. The use of control charts in the clinical laboratory. Am J Clin [21] Patho. 1950;20(11):1059-66.
- https://iris.who.int/rest/bitstreams/911202/retrieve
