Molecular diagnostics is one of the major driving forces of the incredible transformation currently sweeping the medical landscape. Thanks to the wealth of disruptive, personalized innovations that this state-of-the-art field has made possible—including early cancer detection, liquid biopsies, next-generation sequencing, and direct-to-consumer testing—our whole approach to health care and medicine is changing dramatically. Read on for a closer look inside this fascinating, complex, and rapidly growing world.
What exactly is molecular diagnostics?
As its name suggests, molecular diagnostics is the process of applying molecular biology to the field of medical testing; in other words, molecular diagnostics seeks to examine and diagnose disease at the level of an individual’s genetic code. Thanks to rapid advances in both technology and our understanding and knowledge of DNA and genetics, we have developed a sophisticated, and ever-increasing, set of tests and techniques that allow clinicians to look for and examine particular biomarkers found in a person’s genetic material. These biomarkers can provide valuable and detailed information about the health condition of the person they come from, and thus help physicians and other health professionals decide on the preventive measures or therapies that will best suit the needs of the individual patient. (This kind of tailored diagnosis and treatment based on genetic information is known as personalized medicine.)
What kinds of tests are used in molecular diagnostics?
At present, an astonishing number and range of genetic testing products are available for a variety of clinical uses. There are well over 60,000 different genetic testing products on the market, and industry experts estimate that eight to 10 new products are added to the market every single day.
Currently, genetic tests are grouped into two main categories: singles and panels. Singles are tests that examine just one gene at a time. Until recently, virtually all genetic tests were singles. Tests for the genetic risk of cancer, for example, traditionally involved starting with the most common candidate genes for mutation, and sequencing them on a gene-by-gene basis.
However, a new category of test has been introduced in the last few years. Known as next-generation sequencing, multigene panel testing, or simply panels, this type of test can examine a number of different genes at the same time, thus giving clinicians quicker access to a much broader range of health information. While this technology was very expensive when it was first introduced, it is much more cost-effective today, and its use is consequently becoming much more widespread, compared with traditional single testing; current cancer gene panel tests, for example, can involve anywhere from two genes to more than 50. However, because this type of testing is still quite new, clinical guidelines for use are still being established, and there remain many technical questions about performance and interpretation of multigene panels.
How are molecular diagnostics tests conducted and interpreted?
In order to establish the value of molecular diagnostics testing in determining optimal treatment and therapeutic strategies, clinicians consider the test in terms of its analytical and clinical validity as well as its clinical utility—these characteristics provide a helpful framework for interpreting the accuracy and usefulness of the information the test generates.
Analytical validity: This criterion is based on how effectively a particular diagnostic test measures the biomarker characteristics that it is designed to measure; in other words, analytical validity is all about how well the test does its job or fulfills its function.
Two factors govern analytical validity. The first is sensitivity, or how frequently a test correctly identifies a biomarker’s presence. When a test accurately identifies a biomarker that is present, the result is called a “true-positive”; conversely, when a test identifies a biomarker that is actually present as absent, the result is called a “false-negative.” A test’s sensitivity rating therefore indicates its capacity to achieve a true-positive result; for example, if a test has 95 percent sensitivity, this means that 95 percent of the time it correctly identifies people who are carriers of the biomarker the test is looking for.
The second factor governing analytical validity is specificity, or how frequently a test correctly identifies a biomarker’s absence. A correctly identified absence is called a “true-negative,” while an incorrectly identified absence is called a “false-positive.” Similar to the scenario described above, a test with 95 percent specificity will correctly identify people without the biomarker 95 percent of the time.
Clinical validity: This criterion describes the value of a test for accurately predicting the relationship between an analytic endpoint and a clinical outcome; in other words, can the test effectively indicate that a person with a positive molecular diagnostics test will indeed develop cancer?
Clinical utility: This final criterion describes the likelihood that a patient will experience an improved health outcome thanks to the intervention prompted by the result of molecular diagnostic testing. Clinical utility is based on safety, or the ability to reduce harmful effects of treatment; efficacy, or the ability to positively impact health outcomes; and effectiveness, or the likelihood that these improved health outcomes will happen.