Evolution of Molecular Diagnostics Market - An Expert's Perspective (#1) (Focus: India)
Wishing all of our readers a great start to the year 2020!
We are kick-starting this year's 'Interview with an Expert' series with an insightful discussion with Dr. Ravi Gaur on the evolution and the dynamics of the cancer molecular diagnostics testing space in India.
Dr. Ravi Gaur is the Chief Operating Officer of Oncquest Labs and has more than 20 years of experience in the field of diagnostics. His stated goal is to make advanced diagnostics available at an affordable price and at doorstep of the customer.
Click on 'Read More' to learn about his views on how cancer molecular diagnostic testing space has evolved over the years and the key emerging trends and challenges in this segment.
Dr. Ravi Gaur AM, MBBS, MD, MS Chief Operating Officer (COO),Oncquest Labs Ltd., New Delhi, India
Dr. Ravi Gaur is part of Verifothesis, our in-house research panel. Join Verifothesis to contribute to the evolution of the healthcare paradigm.
What sort of qualitative changes you have observed in the field of cancer molecular diagnostics in the last 5 years?
Dr. Ravi: Many important changes have taken place in the last few years. Rapidly evolving advanced technology for better diagnosis, lowering of price, better turnaround time, more relevant information and much more. In the last five years, our approach to cancer diagnosis has changed rapidly. From tissue biopsy to molecular, and getting more deeper into molecular testing to get maximum possible information about mutations is the trend. The fast-growing genomic technology has rapidly expanded to detect specific driver mutations. The understanding and acceptance about sequencing and genomics has vastly improved.
While IHC, FISH ,PCR testing have been standard-of-care, but now automated PCR, multiplex PCR ,digital droplet PCR, Sangers sequencing has evolved rapidly. Today, new tech like DNA Microarray and High-throughput Next Generation Sequencing (NGS) with new updated software, defined, refined finer processes are increasingly replacing older technologies.
In addition, the finding that circulating tumor cells (CTCs) and circulating DNA in blood can also have diagnostic value in metastatic cancers allowing clinicians to use them as the latent endpoints . Liquid biopsy is gaining ground given its convenience. Diagnostic tests based on such information enable “real time” biopsies of cancer progression and response to therapy. These new molecular and cellular technologies bring more precise and objective decision-making.
Cost of assays has come down while the range of assays has grown up substantially. For example, BRCA screening for breast cancer was priced at around Rs 60,000 just couple of years back, but now costs around Rs 25,000. Not only the cost, the report is now available in a week time against 3-4 weeks time earlier.
Similarly, entire tumour profiling used to take about 4 weeks and now it can be done in 7 days. Though the assays are still a bit expensive for the common man, but I expect the costs will come down further with time.
Not only the turnaround time and cost, but also the information derived out of these assays is getting better and more relevant. These changes can be definitely attributed to advancements in technology and growing demand.
Cost of assays has come down while the range of assays has grown up substantially. For example, BRCA screening for breast cancer was priced at around Rs 60,000 just couple of years back, but now costs around Rs 25,000. Not only the cost, the report is now available in a weeks time against 3-4 weeks’ time earlier.
Does your lab receive test requests from prescribers (doctors) OR are there cases of individuals coming to you on their own as they suspect them to be a carrier or at a high-risk?
Dr. Ravi: The advent of molecular technologies has revealed a wealth of information about signalling pathways and gene regulation in cancer. New biomarkers and methods for classification of cancer subtypes, diagnosis, prognosis and prediction of response to therapy have been emerging.
The term “ Molecular diagnostic’ covers three separate categories of test:
Diagnostic test - inform characteristics, indications and diagnosis of a disease
Prognostic test - provide information about the likely future path and outcome of a disease
Predictive test – provide information on the likely response of a patient to a drug or therapy.
Each of these tests contribute something different to our understanding, the sum of the parts helping to build a more complete picture of the patient’s status.
Our lab receives both type of patients. Majority of the patients are referred by doctors for finer diagnosis, but a few who come for predictive assays or prognostic assays do come directly. Generally, people who feel that they are at a high risk but are not suffering visit our facility directly. The later trend is increasing because of the increased awareness, lowering of cost, reduced turnaround time, better & relevant information and high quality pre & post assay counselling.
Talking about personalized therapies, do you see an increase in this trend among Indian physicians?
Dr. Ravi: Definitely. For almost all cancers, be it solid or haematological, clinicians have moved toward personalized therapies and it is now a routine medical practice in almost all private and bigger centres. Every clinician prefers to get molecular testing done to understand the nature & behaviour of the tumour and treat it accordingly. It adds to the cost, but it directs to final diagnosis and in defining the therapy . Without this information, we would just be giving broad-spectrum drugs.
In current medical practice, especially for the important tumours – breast, lung, prostate, pancreatic, oral , GIT cancers, lymphomas ,leukaemia, myelomas etc personalized medicine is already well-defined and is on practice . Definitely, advancement in molecular technology in this new era of precision medicine have led to the parallel development of companion diagnostics and novel tumour inhibitors.
As mentioned earlier, cost, turnaround time, skill and quality of reporting is an important aspect to be looked into. A delayed report which comes in 8 weeks probably won’t help!
Are there any key challenges in prescription of personalized medicine in India?
Dr. Ravi:One of the key challenges is to demonstrate the clinical value of a diagnostic test. It takes fairly a long time taken before a doctor starts prescribing assays, based on these new technologies. It involves validation, education and creating awareness. In the fast growing technology space, by the time, all this happens and doctor start prescribing these assays ,a better technology driven assay arrives. Efforts wasted and the cycle restarts!
Over the last 5 years, molecular testing has seen many ups and down, due to the so many rapid changes. Of late, there is some stabilisation. Doctors are now aware of the assays, various technologies, their clinical benefits and are now balancing out the use of conventional technologies vs the modern ones. Future is all set for Molecular biology or rather Molecular Pathology.
As mentioned earlier, cost, turnaround time, skill and quality of reporting is an important aspect to be looked into. A delayed report which comes in 8 weeks probably won’t help! It is only when the tumour is resistant to the treatment and there is no easy option that patient will utilise molecular test. All new technologies are trying to overcome all such challenges.
Most insurance companies and government insurance schemes are sceptical of molecular tests and are not reimbursing. This is another important roadblock in the growth of molecular testing.
Could you comment on how easy it is to take samples for molecular tests? Also, how soon can patients expect to get their results?
Dr. Ravi:Genetic testing has now become very simple and easy. It is not just that the less amount of sample is required, but technology allows us to use multiple types of samples for molecular testing, like tumour cells or tissue, blood or plasma, oral swab, cervical swab ,bone marrow ,body fluids etc. The main advantages of these procedures are that they are not invasive and with one sample, multiple tests can be done. Results can be expected as early as within 5 days at times.
Fine needle aspirate or needle biopsy can take out the tumour cells or tissue which can be easily used for cancer molecular assay. Such Tru-Cut biopsy can be done under local anaesthesia and no general anaesthesia is required. It has become a simple OPD procedure. Most procedures are very small walk-in, walk-out ones.
For cancers which are unapproachable for surgery ,specially lung cancer, liquid biopsy is being used .This allows us to check for mutation using blood itself. Improvement in technology has led to these tests becoming easier and simpler.
The practice of targeted therapy will become more and more refined. It will be like “cafeteria approach”, where for each type of mutation, a specific drug therapy will be available.
What are the key future trends in the cancer molecular diagnostics area? How is the whole sector going to evolve?
Dr. Ravi:As we go forward, I think cancer diagnosis will become a strong mix of surgical pathology, molecular pathology and radiology. The practice of targeted therapy will become more and more refined. It will be like “cafeteria approach”, where for each type of mutation, a specific drug therapy will be available. Furthermore, bioinformatics and AI together will play important role, wherein data regarding cancer-related mutations and patient information will be used to create better algorithms and personalised therapy. With basic genomic and other details, we will be able to know which drug will work with a patient’s tumour and how tumour progression will behave in a few years from now.
As we know, cancer development is not restricted to genetic alterations but can also be traced to epigenetic changes and protein expression levels. Studies of alterations in genetic, epigenetic and expression processes can help establish diagnostic biomarkers of tumours and classification of tumours based on recognition of complex molecular profiles or unique molecular alterations that occur in the specific tumour types.
However, it’s very difficult to achieve such objectives in practice for several reasons. The criss cross of different cancer-related pathways complicates the understanding of cancer biology. There is considerable heterogeneity in the tumour and functions of the genes among individuals with the same types of cancers. The treatment targets are not absolutely specific to cancer cells .The effectiveness of the treatments is limited because the targets are affected by other factors and the functions of the targets may change over time and produce resistance to the treatment. When so much is not known about a disease like cancer, there is a strong requirement of new biomarkers which determine the cause of the disease or susceptibility. High-throughput molecular discovery tools like next-generation sequencing will definitely take the diagnosis to next level and better understanding of disease development and progression,
The question remains as to whether the biomarker and the technology can become a clinically and economically feasible clinical tool. To answer the question requires a time and resource intensive development process.
Lastly ,the advent of Molecular Radiology is taking molecular testing to different level. It is currently in experimental stage. It involves replacement of frozen section by smart knives. Who knows the molecular radiology diagnosis the will tell us about the tumour mutations and progression. Future is still to be seen, but I am sure it’s on card!
As ever, the skill set will always be a big challenge, though automation and AI will help but one can’t deny the utility and importance of ‘Real Brains’ !
These new tests will impact not only the business of diagnostics from a low margin, single measurement science to a high value, information intensive science, but also, with acceptance by clinicians, the way medicine is practiced in the future.
Thank you Dr. Ravi for this insightful discussion! Dr. Ravi:Thank you as well!