Harmonization and standardization are the need of the hour

Clinical chemistry and immunoassay tests form a very important set of tests in a pathology laboratory – a tool that clinicians and patients alike depend on, to pin down the symptoms for treatment and relief.

However, it is these very sets of tests that have come in question. First, what is the normal and acceptable range (upper andlower limits) of different clinical chemistry and immunoassay biomarkers in a particular population has been debated in different scientific fora. This is because the level of markers can change in relation to other biochemicals, biomolecules, and hormones, which themselves vary considerably with race, gender, age, different physiological conditions (like pregnancy, and new-born), and other illnesses and interfering substances like Heterophilic Antibodies (human anti-mouse Ab, HAMA) and biotin interference etc.

Therefore, harmonization of procedures is the need of the hour, since a major problem clinicians and diagnosticians have to grapple with is the variability of test results; even a broadly similar set of instruments and methods can provide different results, even as much as 40 percent more or less, for example, in case of TSH values. It is then a real challenge to the physician to decide whether the patient is suffering from a disease or is it something else, since other factors can also cause changes in test levels.

Due to the lack of proper reference intervals and sometimes standardized measurement procedures, standardization and harmonization of clinical chemistry and immunoassay testing still remains a formidable challenge.

We have done reference interval verification study for most of the clinical chemistry and immunoassay tests. I would like to give you an example of one of most common routine tests, TSH. Ethnicity-specific cut-off of TSH is important for accurate test reports. I am also the Corresponding Member, IFCC Committee for Reference Interval & Decision Limit (IFCC C-RIDL) and was associated with IFCC Committee on Standardization and Harmonization of Thyroid Functions Tests (C-STFT). In Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute (KDAH), India, we have established reference interval for TSH and FT4 in the Indian population.

The reference interval (90 percent confidence interval) for TSH by non-parametric procedure (bootstrap) is 0.48–4.52, and by parametric one (after transformation of the data), it is 0.45–4.27 for the adult population, which is a little different from the manufacturer’s guidelines.

Furthermore, we at KDAH sought to investigate the opportunity to move from an overall Upper reference limit (URL) of High Sensitive Troponin I (hs-cTn I) of 26 ng/L to sex-specific URLs of 16 ng/L for women and 35 ng/L for men based on their URL verification study in 2804 patients (1670 Male & 1134 Female) for accurate diagnosis of acute myocardial infarction and improved outcomes. The difference in females undetected without gender specific cut-off was 14 percent.

Being a part of India section of IFCC Scientific Division and American Association of Clinical Chemistry, we are discussing with IVD industry, kit manufacturers, clinicians, hospitals, and laboratories to formulate guidelines for assisting in correct measurement, diagnosis, and management of diseases.

Let me give one example. There has been a continuous challenge in the healthcare system in the US, Europe, and other countries to standardize and harmonize the HbA1c reporting – the decision on what to report in NGSP (%) and/or IFCC (mmol/mol) units along with eAG (in either mmol/L or mg/dL). This globalization places a responsibility on us to reduce the current variability in patient results, which arises from differences between units, methods, and laboratory practices. With the standardization efforts of IFCC, NGSP and AACC, the quality of HbA1c reporting has increased dramatically. ii)

The roadmap for laboratory medicine, therefore, will involve strategies for harmonizing, communicating, and integrating with all stakeholders, such as clinicians, diagnosticians, and IVD industry, in order to formulate guidelines for assisting in correct measurement, diagnosis, and management of diseases.