Consolidation is happening quickly now that manufacturers have created open channels to allow automated laboratory-developed tests and are developing molecular instruments that almost anyone can use with test results in 20–30 minutes.
In recent years, the clinical laboratory community has vigorously debated the merits of microbiology tests versus their newer molecular counterparts for infectious disease cases. But today, several trends in the field are increasingly shifting labs toward molecular diagnostics and away from the highly laborious microbiology tests, even those long considered to be the gold standard for a specific pathogen. Microbiology will always play a key role in the clinical lab, but molecular diagnostics has been making a cogent case that it will be a staple of laboratory science as well, and in some cases will supplant the older technologies. Demand for molecular alternatives is being driven in large part by the need for faster results. As molecular tests have improved, their turnaround time has been significantly reduced – but microbiology tests by their nature simply cannot be run any more quickly. It is now possible to generate clinically actionable results from molecular diagnostics in as little as one to a few hours. Related to the interest in shorter turnaround, the antibiotic resistance crisis has made it essential to identify potential resistance markers as soon as possible to avoid prolonged exposure to empiric broad spectrum antibiotics for infectious disease patients. While microbiology methods typically require several days to generate this kind of information, molecular tests allow clinical lab teams to deliver this data within the first day.
Yet another driver for the shift to rapid molecular diagnostics stems from the antibiotic resistance crisis. Treating patients with broad-spectrum antibiotics is no longer the optimal approach because it is more likely to trigger resistance. Ideally, pathogen identification and analysis of resistance markers should happen fast enough to get the patient on a targeted antibiotic to control the infection without compounding the resistance problem. Microbiology tests cannot meet this time pressure, but molecular tests can. In addition to antibiotic resistance, the increasing recognition of the dangers of co-infections has also put more focus on molecular testing for infectious disease recently. Unlike microbiology tests, which typically lead to a single result, panel-based molecular diagnostics that test for a number of different organisms or closely related strains can identify cases where patients have more than one infection.
Significant advances are being witnessed in the development of highly sensitive, quantitative, and multiplex assays. Some of the new technologies include rapid amplicon detection at point-of-care (PoC) settings and low-cost polymerase chain reaction (PCR) devices and come in the form of disposable paper, plastic, or a combination of the two. Consolidation is happening quickly now that manufacturers have created open channels to allow automated laboratory-developed tests and new features such as random-access testing. Companies are now developing molecular instruments that almost anyone can use and offer test results in 20–30 minutes; and are also creating automation solutions with clever features and add-on requests. Molecular automation is improving satisfaction for patients, doctors, and laboratory professionals and will only continue to advance in the near future.
Presence of a huge target population, and high unmet clinical needs along with the rising prevalence of infectious diseases and hospital-acquired infections in India are expected to drive the market growth. The rising government initiatives to improve the healthcare infrastructure in the country will further drive the market growth. However, lack of a well-defined regulatory framework and guidelines for the diagnostic sector will negatively impact the growth of the molecular diagnostic market irrespective of the presence of a large population. Leading companies have been largely focusing on widening their product portfolios and tactical mergers and acquisitions to stay ahead of the competition.
Major players – an update, 2017-18
Abbott Laboratories has recently been awarded an order by NACO India in the vicinity of Rs. 500 crore, to be executed over a span of seven years. This will go a long way in NACO realizing its commitment to eliminate AIDS by 2030. Its strategy is of a massive scale-up viral load testing for all 12 lakh PLHIV on treatment, and labs are being set up for this. 64 VL testing machines in medical colleges have been delivered and once fully operationalized NACO will have one of the largest VL testing programs in the world. This is in the backdrop of CD4 testing, which continues. Currently, PLHIV on first-line ART are monitored by six monthly CD4 count testing to ascertain the treatment response. Those with immunological failure along with other supportive clinical criteria undergo targeted viral load testing for switching over to second-line ART. Now, NACO has introduced routine viral load monitoring of all patients on ART in a phased manner. The public private partnership model by engaging Metropolis has commenced in a phased manner and 5449 tests had been done till March, 2018. Approximately, 210,000 tests are to be conducted in one year through this mode.
F. Hoffmann-La Roche AG. In June 2018, Roche and Foundation Medicine, Inc. entered into a definitive merger agreement for Roche to acquire the outstanding shares of FMI’s common stock not already owned by Roche and its affiliate with the transaction corresponding to a total value of USD 2.4 billion on a fully diluted basis, and a total company value of USD 5.3 billion on a fully diluted basis. Earlier in July 2017, Roche had announced the CE-IVD launch of the cobas MRSA/SA nucleic acid test for use on the cobas Liat System for the qualitative detection and differentiation of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (SA) at the PoC.
Qiagen N.V. In April 2018, Qiagen announced the launch of QIAstat-Dxâ in Europe, providing a one-step, fully integrated molecular analysis of common syndromes as tested for in syndromes in infections, oncology, and other diseases. QIAstat-Dx (formerly Stat-Dx DiagCORE) represents the next-generation in multiplex molecular diagnostic systems that enable fast, cost-effective, and flexible syndromic testing with novel sample to insight solutions powered by Qiagen chemistries. Earlier in January 2018, Qiagen had entered into an agreement to acquire STAT-Dx, a privately-held company developing the next generation of multiplex diagnostics for one-step, fully integrated molecular analysis of common syndromes using a novel system based on real-time PCR technology and proven Qiagen chemistries.
The global molecular diagnostics market is estimated to be valued at USD 8623.2 million in 2017 and is expected to witness a robust CAGR of 11.5 percent from 2018 to 2025, estimates Coherent Market Insights. Advancements in molecular diagnostics have enabled detection of various diseases that could possibly result in severe social and economic burden. Increasing incidence and prevalence of infectious disease and cancer is expected to be a major factor for growth of the market. Molecular diagnostics also helps in providing precision medicine, due to capability of detecting specific disease. Therefore, various governments are focusing on initiatives in precision medicine, which is expected to foster growth of the molecular diagnostics market in the near future. Technological advancements in molecular diagnostics are expected to significantly drive the market as they enable greater accuracy, portability, and cost-effectiveness. The introduction of MinION, a portable and affordable sequencer by Nanopore Technologies, catering to users in PoC facilities and small peripheral laboratories, is expected to boost the growth of the global market.
Application of biomarkers in molecular diagnostic is increasing, due to advantages of biomarkers such as aiding in early detection of specific diseases. For instance, biomarkers are used in detection of ABO hemolytic diseases in newborns, Huntington’s disease and hereditary haemochromatosis, and cystic fibrosis. Biomarkers are also used in detection of disorders related to chromosome structure such as Turner syndrome, Down syndrome, Patau syndrome, and Edwards’s syndrome. Furthermore, biomarkers also have wide application in therapeutic areas, which includes neurological diseases, metabolic disorders, immune deregulation, and oncology. Increasing research and development for identification of biomarkers have led to development of new molecular diagnostic tests, which is expected to foster growth of the molecular diagnostics market. For instance, in February 2018, FDA granted marketing authorization to Banyan Biomarkers, Inc. for the first diagnostic blood test, for traumatic brain injury, Banyan BTI. Such innovation for various disease indications is expected to drive the growth of the molecular diagnostics market in the near future.
North America accounts for the largest share in the global market and this is attributed to increasing adoption of precision medicine and growing prevalence of cancer. According to a National Cancer Institute, 2016, an estimated 16.8 million new cases of cancer were diagnosed in the United States of America, with around 595,690 deaths from the disease. The number of people with cancer is expected to rise to 19 million by 2024, in turn increasing the demand of the molecular diagnostics market in the near future. Furthermore, the US government, in 2015, launched the Precision Medicine Initiative that aimed to revolutionize the treatment to improve health, as precision medicine provides an innovative approach that takes into account an individual’s differences in genes and offers tailored treatment. The Precision Medicine Initiative has led to the development of novel products and several new treatments are tailored for specific characteristic such as a person’s genetic makeup or genetic profile of an individual tumor that helps to transform the treatment. The Precision Medicine Initiative was valued at USD 215 million in 2016 and could accelerate biomedical research by providing clinicians with new tools to select innovative therapies tailored according to individual needs which, in turn favors, growth of the molecular diagnostics market.
The revenue growth of the global molecular diagnostics market has been prognosticated to be hampered by prolonged approvals required from the FDA and other regulatory authorities. This has created a dearth of sophisticated molecular diagnostics tools for clinicians to treat chronic diseases and infections. Moreover, lack of promising reimbursement policies has been projected to discourage the adoption of molecular diagnostics. However, the demand for molecular diagnostics has been prophesied to gain strength on the back of the rising prominence of personalized therapies in several developed countries. Additionally, the surging requirement of customized healthcare in developed regions could increase the demand in the coming years. The uptake of molecular diagnostics platforms in PoC settings could help expose lucrative avenues in the near future. Industry players are focusing their efforts toward developing new cost-effective, highly accurate, and easy operative molecular diagnostic products to satisfy increasing consumer demand and consolidate their market position. Strategic partnership, alliances, mergers, and acquisitions are major strategies followed by market players. Other key players in the global molecular diagnostics market include Hologic, Grifols, Abbott Laboratories, Qiagen, Bio-Rad Laboratories, F. Hoffmann-La Roche, Siemens Healthineers, Becton, Dickinson and Company, Alere, Bayer, and Beckman Coulter.
What to expect in 2018-19
It is just the right time to look ahead and consider what to expect in the molecular diagnostics field. Based on what is seen, flexibility and smart testing will play a major role in the coming year. On the economic front, reimbursement issues will continue to be the biggest storyline in 2018. Lab professionals are being asked to make a business case for the use of panels – and while it is simple to show the positive impact for reducing labor and time in the lab, it is more challenging to demonstrate the clinical utility for broad patient populations. It seems likely that targeted tests will remain the first choice for typical patients, while panel tests will be acceptable for cases such as immunocompromised, elderly, and other high-risk patients. In this environment, it will be more important than ever for clinical labs to have flexible solutions, with both targeted and syndromic tests available, as well as flexible testing options to keep costs in check.
Looking at the clinical realm, antibiotic resistance is a major aspect that will have a long-term impact in the molecular diagnostics space. There is now consensus that the optimal way to address this public health crisis involves an integrated approach of rapid testing, antimicrobial stewardship programs, and clear actions based on results. Without all three elements, medical teams are unable to make a real difference. Ongoing debate around whether more rapid susceptibility testing should be phenotypic or genotypic has led to the idea that there is a place for both. Rapid genotypic tests that produce positive results for a resistance marker offer fast, actionable information to improve patient care. Phenotypic tests will remain important for determining susceptibility and when resistance to a particular antimicrobial agent may be caused by multiple mechanisms.
Finally, in operational considerations, it is expected that the twin trends of centralization and decentralization will continue to reshape molecular diagnostic testing. Already, some tests are moving from local clinical labs to large reference labs for the economies of scale they can offer. Meanwhile, in many cases, rapid tests have been moving toward the point of impact, so results get to medical teams faster. The major shift here is that instead of running tests where the equipment and expertise dictate, we are now seeing tests deployed where they make the most sense for patient care. Ultimately, this means that physicians will receive results more quickly when it is important, and costs can be reduced for tests that are not as time-sensitive. The trend has largely been driven by the increased availability of automated, easy-to-run diagnostics platforms, and rapid molecular assays that are flexible enough to be run as stat or batch tests.
As demand for rapid molecular testing rises, technology trends have made these platforms stronger alternatives to microbiology tests. Initially, molecular tests were frequently classified as high-complexity, limiting the number of clinical labs or laboratorians qualified to use them. As the technology behind these tests has evolved, however, their ease of use has improved substantially. It is common today to find sample-to-answer molecular diagnostics platforms for which operation is as simple as loading samples into a cassette, inserting the cassette in an instrument, and pushing a button to start the reaction. Since these systems require minimal hands-on time or technical expertise, they are now suitable options for almost any clinical lab and can even make it easier to design new laboratory-developed tests.
PCR. The invention of PCR brought a great revolution. Since the discovery of standard PCR, a large number of changes have been developed in its procedure. Some of these changes have expanded the utility and diagnostics capability of PCR in many biological and medical fields. Conventional PCR methods give only amplification of targeted DNA that is not enough for rapid disease diagnosis. In last few years, a new technique, RT-PCR has been introduced. This technique is an improved form of conventional PCR in which the DNA can be quantified along with the amplification. Digital PCR (dPCR) is an increasingly popular manifestation of PCR that offers a number of distinctive advantages when applied to preclinical research. As is common with many new research methods, the application of dPCR to potential clinical scenarios is also being increasingly described.
PoC diagnostics. There is an enduring appeal to the concept of PoC or near-PoC diagnostic methods. Advances in miniaturization, nanotechnology, and microfluidics, along with developments in cloud-connected PoC diagnostics technologies are pushing the frontiers of POC devices toward low-cost, user-friendly, and enhanced sensitivity molecular-level diagnostics. The combination of various bio-sensing platforms within smartphone-integrated electronic readers provides accurate on-site and on-time diagnostics based on various types of chemical and biological targets. Further, 3D printing technology shows a huge potential toward fabrication and improving the performance of POC devices. Integration of skin-like flexible sensors with wireless communication technology creates a unique opportunity for continuous, real-time monitoring of patients for both preventative healthcare and during disease outbreaks.
Image-based rapid diagnostic system. It provides a method for quickly determining which bacterial species are present in a patient sample and the susceptibility of those bacterial species to different antibiotics. Currently, it takes 48–72 hours or longer to get a specific diagnosis of a suspected bacterial infection and a clarity about which drugs are appropriate to treat the infection. However, with the image-based rapid diagnostic system, that information can be gained in just 4–6 hours! And, when a patient is septic, every hour counts.
Molecular automation. Automation has come very far; in fact, it is poised to disrupt the very structure of molecular diagnostics laboratories. New molecular automation systems are capable of connecting directly to clinical chemistry and immunoassay lines, potentially moving high-volume testing out of molecular diagnostics entirely. Manufacturers now have a vision to allow customers to move routine molecular testing to the most high-production environment and that is in the core laboratory. Moving nucleic acid testing out of molecular laboratories presents a unique challenge, not just in automation but also in controlling the risk for contamination. A little bit of hepatitis C virus (HCV) RNA carried from one specimen to another will not make a difference in an immunoanalyzer, but would be a problem with molecular tests because their sensitivity is so high. Therefore, the onus is on IVD manufacturers to consider and to engineer their systems to prevent all forms of possible contamination.
NGS. Undoubtedly, the most exciting and promising DNA diagnostic method for discovery and patient care is next-generation sequencing. This method has already made a significant impact on the diagnosis and management of patients with inherited disorders, and those afflicted with rare but deadly infectious agents. NGS has also uncovered the mechanism behind the development of drug resistance, an inevitability in a disease as complex as cancer. The ongoing rapid advances in NGS technologies and capabilities have been to reduce the sequencing and patient diagnosis time, since in the case of patient care, where time is critical, rapid infection identification and diagnosis is imperative. On the other hand, when compared to existing molecular diagnostic assays that can take a few minutes to a few hours, NGS tests are relatively slow, though recent advances are proving that the par is reducible.
Appearing early in the healthcare cascade, diagnostics influence more than 70 percent of healthcare expenditures. Healthcare agencies, funding bodies, and governments are realizing that increasing the number of medical professionals and hospital facilities are not the only measures of success in healthcare anymore. Medical care is expensive and preventing people from requiring acute medical care by means of disease screening programs, early diagnosis, and effective outpatient treatment can help in reducing hospital admissions (and minimizing hospital acquired infections), bringing medical costs down. With the advent of personalized medicine practice, the role of molecular diagnostics is becoming absolutely
critical. There are a number of successful stories of personalized medicine in cancer diagnosis and management, riding on the back of molecular diagnostic technologies. With newfound ability to visualize in great detail, the complex plethora of chemicals and bio-molecules that constitute the human body, one can now pick apart single molecules and can tell whether there are any signs of disease without the need for invasive tests.
The benefits inherent in moving the accuracy and power of molecular diagnostic closer to the patient, in small hospitals or rural settings, will continue to drive the development of portable simple use technology for a range of clinical applications. Although molecular diagnostics technologies have grown extensively over the last couple of decades, there is still a long way to go in the development and application of molecular diagnostics to assist the diagnosticians. Molecular diagnostic technologies used in diagnostic clinics need to be robust, reliable, inexpensive, and easy to use so that they can compete with, and complement traditional technologies. The challenge now remains with researchers to develop practical technologies used for diagnostic settings.