In today's world, globally all business are striving hard to maintain the balance between the day-to-day work issues and adjusting to changing times. Healthcare and diagnostic business are also going through the similar phase of transition. Particularly in diagnostic industry, the need for sustaining competitive edge is especially pronounced because of the advent of molecular diagnostics. The pace of developments in this field is really amazing and is much faster than many realized. With the ongoing changes and more to come, it is imperative for all the major players in this field, including diagnostic research companies, diagnostic technology provider, pharmaceutical companies, clinical research organizations, clinical laboratories, clinicians and healthcare policy makers, to understand the current trends and the future projections in molecular diagnostics.
Global molecular diagnostics market:
Molecular diagnostics is the fastest-growing segment of the in-vitro diagnostic market (IVD). The US market provides the better pulse of molecular diagnostic growth and its impact in different parts of the world. In 2002, 30-40 million molecular tests were performed in US alone. In 2005, the molecular diagnostics industry took a significant leap forward, marked by a number of major events and several companies experiencing record growth. For the first time, FDA approved two highly multiplexed molecular IVDs: the Tag-It cystic fibrosis kit by TM Bioscience (Toronto) and the AmpliChip CYP450 test by Roche Molecular Diagnostics (Pleasanton, CA). The US molecular diagnostic testing market is estimated to exceed $2.5 billion by the end of 2007. By 2010, revenue from the molecular diagnostics market is expected to reach $3.7 billion, representing an annual growth rate in excess of 20 per cent. Further, the current growth in this field is strongly reflected from the impressive sales figures provided by leading technology providers globally.
Fuelling factors
Since its invention in 1986, the polymerase chain reaction (PCR) has been a cornerstone of molecular biology, underpinning many of the field's most significant discoveries. Series of breakthroughs such as the identification of genes responsible for many genetic diseases, successful completion of human genome project and elucidation of nucleotide sequence of numerous important organisms have actually paved way for development of wide range of diagnostic, prognostic and monitoring applications in the field of clinical diagnostics.
Molecular diagnostic tests have been used primarily to diagnose infectious diseases. For example, amplified nucleic acid assays that screen for HIV-1, hepatitis B and C were the first to appear on the scene. These tests detect viral RNA or DNA directly, rather than the body's immune response to an infection. Further modifications in these tests in terms of quantitation, have enabled physicians not only to diagnose but also to monitor disease progression, among these patients. HIV infection can now be managed as a chronic condition, thanks in part to viral-load tests that guide decisions about when to modify therapeutic regimens. With the success of these tests, wide range of PCR tests for a host of bacterial, viral and parasitic infections like tuberculosis, syphilis, chlamydia, neisseria, pneumonia, dengue, malaria and meningitis are now available for rapid screening, diagnosis and monitoring. Among these, the most popular of all is the tuberculosis PCR.
In high burden countries like Africa, India, China, Pakistan, Thailand and Malaysia availability of TB PCR has helped the physicians immensely for early diagnosis and monitoring the diseases. It has helped for initiating early therapeutic interventions with successful implications. Apart from infectious diseases, molecular diagnostics has unprecedented effect in other challenging fields of diagnostics, including cancer and genetic disorders. Before molecular diagnostics, clinicians categorized cancer cells according to their pathology, that is, according to heir appearance under a microscope. Apart from benefit of rapidity and sensitivity, compared to the conventional method, molecular tests help to track molecular changes that take place at the earliest stages of cancer. Hence, today molecular diagnostics are increasingly seen as the standard of care when diagnosing many cancers.
During the initial periods, the molecular diagnostic assays were restricted to major diagnostic laboratories having expertise, experience as well as infrastructure capability. However, considering the underlying benefits of molecular tests, the diagnostic technology providers worldwide have changed their focus to molecular assays of from immunoassay. With the availability of commercial kits and automated systems the scenario has changed. Today, any medium sized laboratory can have access to these kits and systems and can offer the molecular services. Thus, the change in focus has further increased the accessibility of molecular diagnostic testing in different parts of the world. The best example for this is development and commercializing of real time PCR platform. In recent years, real time polymerase chain reaction (PCR) has emerged as a robust and widely used methodology for quantification of specific nucleic acid sequences in the given specimen. Compared to conventional diagnostic technologies, real time PCR offers substantial time saving with benefit of explicit sensitivity and specificity, mainly for quantification of pathogens in clinical specimens. It is the method of choice for quantitative estimation of either viral or bacterial loads in any molecular diagnostic laboratories.
Emerging trends
Despite significant advances in molecular diagnostics, it is believed that the full potential benefits of the molecular diagnostic technologies are still to be exploited. Already molecular experts worldwide have initiated their work in this direction. Basing on the research and the breakthroughs obtained so far, two areas i.e, pharmacogenomics and genetic predisposition are projected to be the potential growth areas in the near future.
Pharmocogenomics
As the molecular mechanisms of pharmacologic effects, genetic determinants of disease pathogenesis, and polymorphisms in genes that govern drug metabolism and disposition are better understood, the polygenic determinants becomes more traceable. Pharmacogenomics promises to be the next revolutionary change in healthcare, reshaping the pharmaceutical industry and expanding opportunities for biotechnology and biopharmaceutical companies. The good news is that few pharmacogenic tests are either under development or are already available, which can benefit patients with serious conditions such as Cancer, Autoimmune Disorders, Multiple Sclerosis and Asthma. The most successful example of the same is FDA approved AmpliChip CYP450 test from Roche Diagnostics.
This test detects mutations in two genes that contribute to the metabolism of about a quarter of all prescription drugs. According to Roche, the test is "intended to be an aid for physicians in individualizing treatment doses for patients on therapeutics metabolized through these genes." Similarly, an article in the New England Journal of Medicine found that variations in a gene called VKORC1 can determine patients' responses to Warfarin, a drug that is commonly prescribed to prevent blood clots, but is difficult to dose correctly. Apart from these TPMT gene mutations in cancer patients undergoing Thiopurine drug treatment and DPD gene mutations among the patients undergoing 5-Fluorouracil therapy are offered globally for predicting the response as well as adjusting the therapy among these patients.
The ongoing extensive research in this field is expected to increase the list of pharmacogenomic tests in near future. Moreover the $1.35 billion joint initiative of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) to identify the range of genetic mutations responsible for causing all types of human cancer: The Cancer Genome Atlas (TCGA) is expected to pave the way for a new generation of more-targeted cancer diagnostics and therapies.
Genetic predisposition
With the completion of the human genome project, attention is now rapidly shifting towards the study of individual genetic variation. The most abundant source of genetic variation in the human genome is represented by single nucleotide polymorphisms (SNPs), which can account for heritable inter-individual differences in complex phenotypes. Identification of SNPs that contribute to susceptibility to common diseases will provide highly accurate diagnostic information that will facilitate early diagnosis, prevention, and treatment of human diseases. Molecular genetic tests detecting these SNPs, provide the foundation for more effective, timely, and customized preventive strategies based on each patient's unique genetic predisposition. In US already few of the clinical laboratories like Athena Diagnostics are offering these genetic tests for predisposition of metabolic disorders such as Diabetes, CVD, Osteoporosis along with other health concerns such as Stress, Aging, Chronic fatigue syndrome. However globally there is a concern over offering these as screening or diagnostics mainly considering the variability in the interpretation pertaining to different ethnic population.
Expected challenges
Based on the upcoming trends in oncology, pharmacogenomics, and many other areas, the future is bright for molecular diagnostics and better patient care. However, with such great opportunities come great challenges for the molecular diagnostic industry. Two of the most important challenges are the cost-effectiveness of these new markers and establishing the true clinical relevance through awareness building. Clinical leaders will require solid evidence that these test results are clinically relevant and show efficacy., whereas the Technology leaders need to work on the commercial aspect which will make these tests more affordable and thereby making it accessible to all.
Thus as new therapies, new diagnostic platforms, and a better understanding of the molecular world emerge, the potential of the molecular diagnostic industry is practically limitless. The clinical laboratories and the technology providers should look forward to the challenges of making molecular diagnostics a more integral part of better, more cost-effective medical care for patients around the world.
(The author is with Research and Development Division, SRL Ranbaxy Limited, Mumbai.)