Genomics

Genomics and Personalised Medicine in India

Status Check
ince my article in my column A Dose of IT last year (19 September, 2011) titled Genome on an iPad (http://www.slideshare. net/XKAPS/your-genome-on-anipad-9318207) and serving as the Vice Chairman for Personalised Healthcare and Genomics at FICCI this year, Indian market is witnessing very fast development in launch of a slew of genetic and molecular diagnostic tests of various kinds.

These include: During the last count, earlier this year, around 900-odd tests are being offered by various players in India. These tests are offered through the doctors, directly to the consumers/patients. As competition intensifies and newer next generation gene sequencing machines hit the Indian shores, we would definitely see the costs of these tests reducing drastically with the affordability of the common man.

Recent Positive Global Developments

When the human genome was mapped the first time in 2000, it cost around $3000 million and it wasnt actually the genome of a single individual but a composite everyman DNA of

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Test type Diagnosis of genetic disease Newborn screening Carrier tests Examples Testing of patient, following indicative clinical findings, to confirm genetic diagnosis Testing of newborn to identify conditions that require immediate initiation of treatment to prevent death or disability Testing to identify an asymptomatic adult who is a carrier for autosomal-recessive or X-linked recessive conditions. Testing is usually initiated on the basis of family history or because the genetic condition is common among individuals of the patients ethnicity Testing to identify a fetus with a genetic condition. Testing is usually initiated on the basis of maternal factors or family history that indicate increased risk. Some prenatal genetic tests are offered routinely; for example, maternal serum screening to identify increased risk of neural-tube defects or Down syndrome Testing of asymptomatic young adults to identify a genetic condition that will occur later in life Testing to identify an increased risk of future health problems, such as heart disease or diabetes

Prenatal tests

Adult onset of conditions Assessment of genetic risk for common complex diseases Tests to predict drug response Courts-mandated test

Testing to identify an individual with less likelihood of response, or increased risk of adverse reaction, to a particular medication Testing to private individuals, law enforcement and legal representatives to resolve paternity disputes, establish child custody, assist with immigration claims, identify rightful heirs, assist with the adoption process Test Initial application Localization of ACTH in pituitary gland Tissue-specific antigens in cancer Motherson inheritance of ocular malformation Assignment of human genes to chromosomes DNA sequencing of human chromosomes Differential gene expression at DNA level Expression of drug targets in human disease Pharmacogenomic drugtest co development Mutation analysis in CharcotMarieTooth Syndrome

Year 1951 1963 1964 1972 1976 1995 1996 2005 2010

Market Opportunity
The discovery of a gene disease association lays the groundwork for the development of a genetic test. We have successfully discovered the Indian Genome by CSIR. While all agree that the large Indian population with a genetically diverse gene pool and chronic diseases is a huge opportunity. These opportunities in creating genomic tests and treatment of diseases and will encompass: Diagnostics BioIT and Informatics Genetic counseling Clinical trials and development Others-direct to consumer products and services Core delivery of healthcare practices. An optimistic estimate as worked by us pegs this around INR 50,000 million by 2020. The size of this market will have a derived impact on the lab equipment, production of diagnostic kits, chips and ancillary services in India. This could be to the tune of INR 105,000 million by 2020. While various expert committees and
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Immunofluorescence Immunohistochemistry Cytogenetics In situ hybridization Gene sequencing Microarray gene expression Pharmacogenetics Companion diagnostics Whole-genome sequencing

Moores Law of Genomics: different technologies over the years for Genetic Testing

several volunteers. The costs of genome sequencing have fallen by over 100,000 fold in the last 12 years. As per this trend (called the Moores Law of Genomics), the costs of carrying out full genome sequencing would be less than $1000. As a result the affordability and accessibility to such genetic by patients is possible in the near future. Here are a few positive developments in this direction: The UK Prime Minister has recently launched a national DNA database of upto 100,000 patients with cancer and rare diseases. 23andMe, based in Mountain View, California, tests peoples
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genes and gives them data about their ancestry and genealogy based on those tests. It has raised $ 50 million from a powerful Russian billionaire. Including the new funding, 23andMe has raised about $102 million in capital to date. The more people who take part in testing, the better the data gets. The company says the new investment will go toward boosting its user base of 180,000 customers to one million people. To get to its goal of one million users, the company is lowering the cost of its Personal Genome Service to $99.

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Statutory Regulation
Pre-Market Review & Regulatory Oversight Several countries have now implemented regulations to manage this sector and also protect the individual citizens of their countries for any adverse fall out due to the introduction of genetic tests. Some countries have provided regulatory moratoriums for 5 years to watch how the sector is shaping up before regulating it. There is a need to benchmark some of the regulatory best practices and experiences of countries that are step ahead of India in framing the regulations. Quality Assurance Regulations and Protocols for Labs for the Tests A lot of work has been done by several countries in OECD to adopt a common quality assurance framework for genetic testing in their countries. While a few protocols are available for clinical trials there is a need for an elaborate protocols in India for these tests. What also needs to be understood now is whether the labs that provide these tests need to come under Indias white papers are being prepared by various industry groups to ensure viability and growth of this segment, it is still early on how the issues & regulation of this sector pans out. However, some of the Indian and global experts that I spoke to seem to be skeptic that Indian market may even be half as big.

Framework to Enable Genomics & Personalised Healthcare in India

While several scientific and research agencies in India have conducted research in this space over the last decade. It is time that it is exploited widely in the treatment
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of diseases in healthcare. The following framework would help in guiding the discussions forward. A large part of my discussions with relate to statutory regulation and healthcare delivery.

NABL accreditation or a separate independent regulatory body under the lines of TRAI or IRDA needs to be formed to ensure speed clearances.
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Anti-Discrimination Measures US (Genetic Information Nondiscrimination Act) and European countries have introduced laws that limit employers and/or health insurers use of genetic information to a varying degree. These laws indicate a consensus against the use of genetic susceptibility information in access to health services & employment. Whether genetic information is likely to be used for this purpose is not yet clear, and the optimal regulatory strategy remains uncertain. There are no such regulations in India that enable consumer protection. Protection for Offshore Tests Currently over 75% of the tests conducted in India are through the labs in the US, Europe and Singapore. Regulation of testing done in laboratories in other countries is limited. Direct-toConsumer DNA genetic tests that are offered and conducted by overseas-based laboratories are not regulated in India. There are no protections applicable to Indians against overseas based laboratories. This could leave Indian consumers at risk should problems arise. Marketing & Direct-toConsumer (DTC) Testing Today, several genetic tests are being advertised and sold directly to the consumers, both through the websites of the labs and service providers and through their agents in India. There are not enough consumer protection guidelines being issued to protect the Indian consumers. Some of the key executives at the Consumer Genomics Companies from the US that I spoke to believe that the Indian regulatory environment is not yet mature for DTC genomics testing.
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Direct-to-consumer (DTC)
The purpose of the test A general description of the testing process A description of the diseases or conditions tested for, including their ranges of severity The risks and benefits of, and alternatives to, the predictive genetic test Confidentiality issues, including confidentiality protections, the circumstances under which results of tests may be disclosed without the patients consent, and the names of persons and/ or organizations to whom the patient has consented to disclose the results Protections against adverse uses of genetic information The chances of false positive and false negative results The meaning of both positive and negative results The ability, or lack thereof, of the test to predict a diseases severity and age of onset The possibility that no additional risk information will be obtained at the completion of the test Available medical surveillance, treatment, and/or reproductive options following testing A statement that, prior to providing informed consent to genetic testing and after receiving the results, the individual may wish to obtain professional genetic counseling. The risks of transmitting the relevant mutation to children and that the mutation may be present in other blood relatives A statement that no tests other than those authorized will be performed on the biological sample and that the sample will be destroyed at the end of the testing process, or not more than a specific period of time after the sample was taken, unless the subject consents to a longer period of storage That the test is voluntary An offer to answer inquiries The fees charged for the laboratory tests and preand posttest counseling. Departments would play an important role in educating the public about genetics generally and about particular genetics services that are available to the public. They also should support production and dissemination of genetics educational materials to health care providers. In this context the Ministry of Health and Family Welfare would be required to issue guidelines to enable this. There are also needs for upgrading the labs with the latest next gen sequencing equipment at the Public Health Labs in India.
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Healthcare Delivery
Public Health Allocation in Genomics & Personalised Healthcare Globally, public health assessment activities in the genetic context include population surveillance and molecular genetic epidemiology research. Policy development activities include the translation of scientific and medical discoveries about genetics into guidelines, regulations, and legislation to promote the publics health. Public Health

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New Practice Guidelines and Treatment Protocols for Treatment My discussions with the personalized healthcare and genomics experts reveal new practice guidelines need to be developed, which can better integrate biological information for a complete picture of health & disease at a personalized level. The three areas where they are required areDiagnostic medicine: Identify whether an individual has a certain genetic disease. This type of test commonly detects a specific gene alteration but is often not able to determine disease severity or age of onset. It is estimated that there are >4000 diseases caused by a mutation in a single gene. Examples of diseases that can be diagnosed by genetic testing includes cystic fibrosis. Predictive medicine: Determine whether an individual has an increased risk for a particular disease. Results from this type of test are usually expressed in terms of probability & are therefore less definitive since disease susceptibility may also be influenced by other genetic & nongenetic (e.g. environmental, lifestyle) factors. Examples of diseases that use genetic testing to identify individuals with increased risk include certain forms of breast cancer (BRCA) & colorectal cancer. Pharmacogenomics: Classifies subtle variations in an individuals genetic makeup to determine whether a drug is suitable for a particular patient, & if so, what would be the safest & most effective dose. Given that the costs of conducting wholegenome sequencing could come down to a few thousand rupees, these tests can be done not once,
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but potentially in a routine fashion multiple times over the course of disease. However, at this point in time, the decision to conduct these tests are best left to the clinical team treating the patient. In a few years, it may be possible to conduct a prenatal and new born tests on all children born in India and be linked to their UIDs!

Education of healthcare providers

While there is consensus amongst the labs and pharma about the need to educate the doctors about the benefits of this new science, the task at hand of reaching out top 300,000 doctors across the length and breadth of India is huge. Different medical and physician associations welcome the need for conducting continuing medical education (CME) programs, there are issue of logistics to be worked out. On the other hand, some of the wellknown medical colleges in India are also considering introducing modules in their PG and super specialisation programs. There is need for the apex medical bodies in India to issue proactive guidelines to enable this.

reinsurers and insurers in India on various scenarios, that the country may take, provide a very grim outlook. While many of the CPT and ICD codes associated with these tests are available in the US and other countries globally, they are yet to touch the Indian shores. While some of the insurance experts believe that these tests would not be covered by health insurance policies in India as there are no riders available. On the other hand the industry is awaiting guidance from the Health Insurance Regulator, IRDA on this issue. Health insurance coverage for these tests would be one of the key enable for genomics and personalized healthcare in India.

Conclusion
By building public trust, a future reality can be envisaged in which genomic testing can identify clinically relevant abnormalities early in the disease course, and guide effective intervention in a timely fashion. The fundamental concept of a future business model in India is that genomically informed medicine will cost less and deliver better care across the longitudinal span of patient health in the near future. Mitigating against this optimistic future reality are a host of uncertainties, as outlined.

Health Insurance Coverage for Genomics and Personalised Healthcare in India

My discussions with the health

Kapil Khandelwal

Kapil Khandelwal, recognised as an expert in health sciences, education, agri and information communications and technology (ICT) serves several company boards and industry advisory committees in these sectors. His expertise positions him as one of the thought leaders in India, Asia Pacific and Emerging Markets. Kapil runs his own investment banking and advisory services company, Equnev Capital. He has carried out over 30 transactions including cross-border and played an influencing role with the Governments in India and abroad. He has Chaired FICCIs Personalised Healthcare and Genomics Committee and provided thought leadership and direction to policies and regulation in this area.

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