India in the Era of Precision Medicine

India in the Era of Precision Medicine

Often it has been noted that common medications like beta-blockers and antidepressants work differently or don’t work at all on different patients, though they present with similar symptoms. Up until now, observations like these were confined to literature, since our knowledge about the underlying mechanisms was limited.

The advent of advanced genomic technologies are offering new answers to many such observations and dilemmas of healthcare providers.

About a decade ago, healthcare began to witness a paradigm shift when people started questioning the one-drug-fits-all approach to medicine. With this, the idea of personalised medicine has emerged, making large strides supported by high throughput technologies and advancements in bioinformatics platforms.

Possibly, we have already moved closer to an era where genome sequencing is a regular practice for clinicians and pharmacogenomics is an integral part of medicine, paving the way for precision treatment.

Thanks to the fast-improving genomic platforms over the last decade, precision medicine is becoming increasingly affordable and is expanding rapidly to all branches of healthcare.

Where is India standing in this healthcare revolution?

A series of interviews with industry professionals and healthcare workers, tells me that the rate of adoption of precision medicine in India revolves around three major factors: affordability, education, and specificity of the tests.

Let’s start by going back in time. Ten years ago, if you wanted to get your whole genome sequenced, it would’ve costed you around INR 70 lakhs (USD 95,000) whereas today, the most it would cost is about INR 1 lakh (USD 1,350). In fact, some labs claim that they can offer it for INR 45,000 (USD 600)!

To complement this example of increasing affordability is the nation-wide acceptance of NIPT (Non-Invasive Prenatal Testing). NIPT is a diagnostic tool that uses genomic methods including sequencing to check for genetic abnormalities in the fetus. According to a regional sales manager of a multinational diagnostics company, which is also a leading player in the field of NGS (Next Generation Sequencing), there has been a 200-300% growth in the demand for NIPT in the city of Mumbai in India. This growing demand has been a major contributing factor in its price falling from Rs 35,000 (USD 475) to Rs 10,000 (USD 135). In some states in India, the prices have dropped to as low as Rs 4,000 (USD 55).

Over time, prices have been falling due to the advancements in technology as well, in addition to the rising demand. However, there are still segments that are too expensive for the Indian market. For example, a myeloid panel using NGS technology costs Rs. 60-70,000 (USD 815-USD 950) for the patient. Moreover, it doesn’t help that neither private nor public insurance companies offer reimbursement for NGS-based testing, leading to large out-of-pocket expenses.

There is hope, though. During an interview with a senior professional from a leading NGS supplier company in India, it was mentioned that bringing in insurance reimbursement for NGS-based testing is in the works, albeit at a premium price. The price could be almost triple the cost of regular health insurance, and one would probably have to ask specifically for it. Though a small step forward, this is still a promising step forward.

To make precision medicine an affordable diagnostic tool, it is imperative that it is used on a wider scale. This brings into the picture the education gap in the clinical setting. To quote a national sales manager of a biotechnology multinational firm in India, “There is insufficient manpower for NGS because there is insufficient education for the same.”

Dr. Sudhakar Bailur who has been a General Practitioner in Mumbai for over 40 years, mentioned that back when he graduated, genetics was not offered as a separate subject in the syllabus. Fast forward half a century, and shockingly, this is still the case. A 2020 survey of MBBS graduates tell us that genetics is only offered as a basic chapter on genetic disorders, with little to no mention of genomic diagnostic tools!

NGS has the capability of removing the “gut feeling” that we so heavily depend on doctors for. For example, a patient presents with fever, a sore throat, and rigor. An experienced doctor will tell you to get tested for typhoid, malaria, dengue, and now, even COVID. But what happens when the tests do not lead to a specific diagnosis? Even worse, if a wrong diagnosis leads to wrong medical intervention and precious time is lost in saving the life of the patient? Moreover, there can be severe consequences in cases of drug-resistant infections that are not easy to diagnose.

Probably, genomic tools would offer solutions for many such medical dilemmas. For instance, some of the above mentioned medical situations can be easily curbed by introducing NGS into the clinical setting. Massive parallel sequencing can help to identify the pathogen quickly, without having to do blood cultures which could take days. Another beauty of NGS, unlike cheaper genomics platforms such as PCR, is that it can identify the biomarkers related to a series of pathogens in one experiment. This makes it especially beneficial in the infectious disease setting, where mutants and new diseases are presented.

Achieving such levels of a fast and accurate diagnosis is not easy, though. A sales professional for NGS products in India indicated that affordability is not the only market restraint for NGS in India. “Most clinicians are in a bubble where they believe NGS is difficult because the sequencers give huge amounts of output data, which is difficult to analyze. To filter out that data, they need skilled bioinformaticians, who can add value to the patient’s diagnosis.” – he says.

This statement points out that data analysis and interpretation are crucial factors to be addressed to speed up the adoption of NGS in clinical settings. India is currently facing a serious gap in the data analysis field due to the lack of skilled bioinformaticians who can effectively handle the huge amount of data being generated by NGS. To address this skill gap in the industry, some changes in the education system may be necessary. Why not consider adding bioinformatics to IT curriculums? Maybe they can be offered as electives. Similarly, genomics courses could perhaps be added to the MBBS curriculum as well.

Issues with data analysis are slowly getting addressed, though, thanks to the rising awareness about the potential of NGS-based assays in oncology, reproductive health, genetic disorders, etc. Several personalised healthcare companies like Mapmygenome India, 4baseCare, and Lifecode Technologies have been established in India over the last decade. These new players in the NGS market of India could likely play a critical role in addressing these issues. Hopefully, that will catalyse the growth of adoption of NGS into clinical settings.

Population-Scale Sequencing Initiatives

It is worrisome to consider that NGS-based disease diagnosis depends heavily on reference databases, which need to be relevant for the genetic makeup of the specific population for arriving at accurate conclusions. Though some assays developed in Indian labs do exist that are claimed to be validated against genomes from different communities in India, most of these are developed using hardly a few hundred samples for validation. The fact remains that most NGS assays being carried out in India are matched against western genomic databases.

How can a country with over 4000 communities and several thousand endogamous groups (according to the Indian Genome Variation database) be compared to an almost entirely Caucasian reference genome? India has a large proportion of consanguineous marriages, which is bound to give rise to a very conserved genome. Due to this, there will be certain subgroups of populations, for which certain diseases will be prevalent. If we continue to use western-based assays or assays that represent a very small portion of the population, we will not be able to generate accurate diagnoses for the different subgroups in India.

This gap is now being addressed through various nation-wide initiatives. The Genome India Project is an example of one such initiative, which can help us to move closer than ever to address the problem of non-specificity of our assays. On February 10th, 2019, the Indian Ministry of Science and Technology’s Department of Biotechnology initiated the Genome India Project or GIP. This project targets to sequence 20,000 whole Indian genomes.

10,000 genomes of GIP will be sequenced to create a reference genome, and another 10,000 will be genomes sequenced from patients, suffering from mental illnesses, cancer, and non-communicable diseases like diabetes. This will help to understand the genetic predispositions and the nature of diseases and traits that affect the diverse Indian population, thereby enabling the creation of more accurate screening processes for NGS-based diagnostic tools in India.

A sub-project of the Genome India Project is the IndiGen program, funded by the CSIR (Council of Scientific and Industrial Research). Just six months after its initiation in April 2019, the team reported completion of the sequencing of a total of 1008 Indian genomes.

Simultaneously, the Institute of Genomics and Integrative Biology (IGIB) under CSIR is leading two separate programs- GOMED (‘Genomics and Other Omics Tools for Enabling Medical Decision’) and GUaRDIAN (‘Genomics for Understanding Rare Diseases India Alliance Network’).

The GOMED program ensures that the genome database and genetic screening will lead to the development of cost-effective diagnostic tools and tests that can be licensed out to private and public healthcare institutions. The GUaRDIAN program, on the other hand, specifically focuses on identifying rare diseases in different communities in India. Instead of carrying out whole genome sequencing (WGS) that can cost up to INR 1 lakh (USD 1,350) per person, IGIB will create assays that specifically screen for that genetic mutation, for just INR 2,000 (USD 27). As of mid-2020, they have created about 180 different assays, for 180 genes. These assays are given to many private diagnostic labs in India such as Dr. Lal PathLabs, Medgenome Labs, and Lifecell International, who will offer the diagnostics services to patients in an affordable manner.

The Future of Genomic Medicine in India

With these large-scale genomic sequencing initiatives, India is able to keep pace with the evolving ecosystems for precision medicine, also known as genomic medicine, recognising the role of genomic platforms in achieving this goal. The optimism is shared by various stakeholders in the industry. A forward-looking statement made by a senior professional of a multinational corporation is worth mentioning in this context.

He says, “[I am] very optimistic, that with India’s skilled workforce and its rapid rate of digitalisation and modernisation, the Indian NGS market size will more than double or even triple by 2026-27. Based on discussions with other APAC representatives, India is foreseeably set to become a superpower in terms of technology and science-based fields.”

Precision medicine gives us the potential to figure out problems at the level of our DNA, by moving past our physical symptoms, beyond what the human eye can see. It is exciting to witness the fast developments in the NGS field facilitating this possibility. The rising need for the integration of computer-based technologies with biological sciences can offer significant opportunities for Indian youth with the right pool of skill sets in the coming years. Though there is still a long way to go, I believe that India has already stepped foot into this new era of precision medicine, and I’m excited to see what will happen next!


Aditi Doshi- InternBy Aditi Doshi, Market Research Analyst (Intern)

Biotechnology undergraduate student, final year, DY Patil University, India

January 02, 2021

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