What is the standardization of clinical testing?

Figure 1  Standardization will produce uniform test results

Clinical tests are tests for the purpose of medical diagnosis and treatment, like the health checkups we are all familiar with. But many of you have had the experience of receiving an abnormal test result in a health checkup only to be given the all-clear in a follow-up test. This may be because you happened to be unwell on the day of the checkup, but it could be due to an error in the result. The fact is that test results can vary depending on the testing facility. Even if the same blood is tested multiple times at the same facility on the same day, the same results are not guaranteed every time. This may result in one hospital diagnosing a patient as ill while another diagnoses the same patient as healthy. Efforts are therefore being made to make sure that tests produce the same result no matter where they are conducted, and these efforts are called "standardization" (Figure 1). Standardization is all around us: for example, the fact that toilet paper fits on the toilet paper holder no matter what brand we buy is the result of standardization to determine the size of the toilet paper and the thickness of the toilet paper tube.

 

What is the current state of HIV infection?

Do you know what HIV is? HIV is the Human Immunodeficiency Virus. When people are infected with HIV, their resistance to illness (immunity) gradually weakens, and they become susceptible to illnesses that healthy people are resistant to, leading to a state known as AIDS. So, what do you think of when you hear the word HIV? Most people probably think, "I haven't heard about it much recently, so it must have been eliminated", or "It has nothing to do with me", or "There are good medications now so it's not a problem", as though it were a disease affecting a far-away country that they need not worry about. HIV was discovered in 1983, and because there were no treatments available, it was considered a fatal illness at the time. In Japan, due to irresponsible reporting and ignorance, it became a word associated with discrimination and victimization. Public interest in the disease has since lessened over time, but the number of people infected has actually increased rather than decreased, and nearly 1,500 new cases are being confirmed every year.

 

What is your objective?

At present, HIV-infected patients can lead relatively normal lives through the use of medication. However, some strains of HIV may become unsusceptible to the medication during the course of treatment (drug-resistant HIV). Drug-resistant HIV is not only a resistant to treatment, but is also a problem because it leads to new transmission of the virus. Currently, the effectiveness of a medication can be determined by testing the HIV genome sequence using a test known as the HIV drug resistance test. But the results of this test can vary from facility to facility. This means that, depending on the hospital where the patient is tested, different drugs may be prescribed. The aim of my research is to standardize the test so that the results will be the same no matter where the patient is tested and every HIV-infected patient can receive the optimal treatment (Figure 1).

 

What sort of research are you doing for standardization?

Figure 2  Testing environment
Extraction of nucleic acids and preparation of reagents are
carried out in a clean bench

Figure 3 Machines for gene analysis
DNA sequencer (left), thermal cycler (right)

Why is a ruler the same length no matter where you are in the world? It is because every ruler is made according to a universal "basic ruler" known as the meter standard. Standardized tests use "basic rulers" called reference materials, and the results of measuring with such materials should be the same at every facility. However, there are no commercially available reference materials for the HIV drug resistance test. The patient's blood is therefore used as the reference material, but a large amount of blood is needed, which causes the patient a great deal of strain. So, one of the themes of my research is to develop a reference material. One simple material consists of HIV genes synthesized in a test tube; to make this more like actual HIV, we are experimenting with procedures to create a different virus integrating the HIV genes for use as the reference material. This carries no risk of infection and would produce a reference material constantly available in large quantities. My research involves periodically distributing these reference materials to facilities for use in tests, and then evaluating the quality of the tests across the whole of Japan. In my research, I employ mainly molecular biological methods, using a thermal cycler to amplify genes and a machine called a DNA sequencer to study genetic sequencing (Figs. 2, 3).

 

What sort of results can we look forward to?

This research will allow all patients being treated for HIV infection or starting treatment to receive high-quality testing. Also, it has recently become possible to analyze all the base sequences of the human genome in a matter of days. When such breaking technology is incorporated into clinical testing, standardization will become an absolute necessity. Hopefully, the reference materials developed in my research and the associated development process will be used for the standardization of numerous genetic tests.