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EMERGING CLINICAL RESEARCH OPPORTUNITIES IN INDIA: A NEW SOURCE OF PATIENTS FOR COMPETITIVE CLINICAL TRIALS EMERGING CLINICAL RESEARCH OPPORTUNITIES IN INDIA: WHITEPAPER A NEW SOURCE OF PATIENTS FOR COMPETITIVE CLINICAL TRIALS
Given India’s past regulatory environment, biopharma The Emerging Clinical Research companies have been reticent to conduct clinical Opportunities in India trials in this country over the last few years. That is A vast population and growing economy changing, however. With its vast population, growing economy, major disease burdens, improved regulatory India’s population of more than 1.3 billion people, 2 environment, and strong research infrastructure, or 17.75% of the total world population, is growing. the Indian market is now emerging as an ideal According to UN estimates, it is expected to overtake destination for clinical research. An especially China’s by 2025 to become the world’s most populous 3 important fact for sponsors seeking a less competitive nation. According to the 2011 Census data, India landscape for study candidates is that only 1.4% is home to 104 million elderly people (aged 60 years of all global trials are currently conducted in India.1 and above), 53 million women and 51 million men. However, the opportunities do not come without It is also a well-educated population with a workforce challenges. A successful entree into this market is that has better English language skills than many best accomplished by using partners with extensive Eastern European markets. There are more university country, state and local experience. This includes graduates with degrees in India than there are people a provider dedicated to the recruitment of patients in South Africa or Poland. and sites for clinical trials in India. This significant population makes India the world’s third largest economy in purchasing power parity terms. The Search for Hard-to-Find Clinical Its recent economic growth (7.0% GDP) has been Trial Patients a significant achievement, driving rapid urbanization and an increasingly large new middle-class.4 For sponsors of clinical trials in highly competitive therapeutic areas, such as Inflammatory Bowel and Cardiovascular Disease, finding enough study subjects in the United States and Western Europe has become a major challenge. When multiple companies are researching similar compounds, + the number of patients in active research sites 1,300,000,000 PEOPLE is limited, there are not enough investigators, and/or existing research sites are full, the result is a backlog of trials and high costs for recruited patients. In order to accelerate research and 17.75% development in crowded therapeutic areas, sponsors OF TOTAL WORLD POPULATION need to find new sources of patients. 7.0% GDP
16.28% CAGR IN HEALTHCARE SECTOR
2 EMERGING CLINICAL RESEARCH OPPORTUNITIES IN INDIA: WHITEPAPER A NEW SOURCE OF PATIENTS FOR COMPETITIVE CLINICAL TRIALS
A rapidly growing healthcare industry Once known as exporters of bulk Active Specifically, healthcare has become one of India’s Pharmaceutical Ingredients (APIs), Indian generic largest sectors, both in terms of revenue and drug makers have managed to gain a foothold in employment. During 2008-2022, the market is regulated markets such as the U.S. and Europe. expected to record a Compound Annual Growth Rate (CAGR) of 16.28%, with the total industry size expected to reach $372 billion by 2022.5 3 27 25 ______ 2 4 372 5 35 ______ 5 4 3 ______2 25 ______4 6 2 4 2 4 2 ______ 6 generic dosages by volume in annualized growth rate of total sales 5 ______the U.S. that are manufactured for Indian generic drug companies 4 ______ by Indian companies from 2004 to 2014 6 6 73 5 ______45 52
Source: www.nasdaq.com 2008 2008 2010 2011 2012 2014 2015 2016 2017F 2020F 2022F
Notes: F - Forecast. CAGR - Compound Annual Growth Rate This augurs well for Indian companies, which are also Source: Frost and Sullivan, LSI Financial Services, Deloitte. Aranca Research experiencing growth momentum in their domestic market.7 It is opined that clinical research will follow This growth is being driven by several factors: this success, with India eventually becoming one • Dual disease burden (infectious and of the dominant research destinations. non-communicable) A significantly improved regulatory environment • Rising healthcare awareness In an effort to put India back on the global clinical • Increasing levels of disposable income research map, the Indian government has taken • Growing population and urbanisation great steps forward to speed up approvals, remove Another significant accomplishment for India intermediaries and provide more transparency. The has been the growth of its pharmaceutical Central Drugs Standard Control Organization manufacturing. Currently, India has the highest (CDSCO), whose main objective is to standardize number of FDA-approved manufacturing plants clinical research and bring safer drugs to the Indian 6 market, has made its vision clear: “To Protect and outside the U.S. It is also a leader in the field 8 of generic manufacturing, with products registered Promote Public Health in India”. and taken all over the world. Over the past decade, the regulatory climate in India has fluctuated wildly, creating an uncertain research climate for biopharma companies. After 2 2 4 2 4 5 7 7 2 4 2 4 2 finally becoming fully TRIPS compliant in 2005, 2 4 7 6 65 India emerged as a favourable destination for the 4 6 2 conduct of clinical trials. With its timely completion 55 of trials, large patient pool, highly skilled medical 5 6 investigators and related professionals, India’s share 4 45 2 of the global clinical trial market subsequently grew 4 9 2 4 2 5 2 6 2 7 2 2 2 2 2 2 2 3 2 4 from 0.9% in 2008 to more than 5% in 2012.
Source: PhramaBiz
3 EMERGING CLINICAL RESEARCH OPPORTUNITIES IN INDIA: WHITEPAPER A NEW SOURCE OF PATIENTS FOR COMPETITIVE CLINICAL TRIALS
However, legacy infrastructure challenges and Since the introduction of the regulatory reforms, sometimes less efficient regulations resulted in India is well positioned for growth in the clinical many unfortunate complications on clinical trials. research arena. There has been a rapid increase in During late 2011 and early 2012, the existing the number of clinical research projects approved regulatory framework and patient safety guidelines in India: 84 in 2016 and 59 in the first six months were challenged. This led to sweeping changes, of 2017. Importantly, sponsors, CROs, sites and the introduction of an onerous and restrictive investigators all share a sense of optimism regarding 10 three-tier approval process, and new regulations. the changes and increased activity. Unfortunately, the unintended consequences were excessive timelines, as well as a significant increase A population in urgent need of medical treatment in cost and effort to adhere to the new regulations. Although India continues to struggle with the This led to many research institutions and burden of communicable diseases associated investigators discontinuing clinical trials in India. with a developing country, every state now has To reverse this situation, The Ministry of Health a higher burden from non-communicable diseases convened an Advisory Council in 2015 to formulate and injuries than from infectious diseases. The more practical policies related to the approval of contribution of non-communicable diseases clinical trials and new drugs. Following extensive to health loss — fueled by unhealthy diets, high input from various stakeholders – sponsors, CROs, blood pressure, and hyperglycemia — has doubled investigators and the pharmaceutical industry in India over the past two decades.11 – the committee recommended changes to the Cardiovascular diseases have now become the regulatory framework with an objective to revive leading cause of mortality in India, with a quarter the industry, while ensuring that trials are based of all mortality attributable to CVD. Ischemic heart on sound science and the highest ethical standards. disease and stroke are the predominant causes and Of significant importance for sponsors of clinical are responsible for >80% of CVD deaths.12 trials, they initiated:
• The CTA review timeline of 180 days maximum, as compared with unspecified timelines before. • A pre-trial checklist provided by the Regulatory High Income (GBD 2010) Authority to help sponsors ensure that their CTA Global dossier meets all the information requirements (GBD 2010) from the outset, avoiding potential delays. US (GBD 2010) • The ability to include an application for an India import and export “No Objection Certificate” (GBD 2010) (NOC) license in the CT. Previously this was not Mumbai, India applied for until after CTA approval. (2010) Kerala, India • Removal of the requirement to apply for “Export (2010) No Objection Certificate” from the CDSCO in Andhra Pradesh, India order to export clinical trial biological samples (2006)
from India. 0 5 10 15 20 25 30 35 40 45
• Online submission of regulatory application and Women Men monitoring of the status of an application. https://www.ahajournals.org/doi/10.1161/ CIRCULATIONAHA.114.008729I I I I I I I I I I
4 EMERGING CLINICAL RESEARCH OPPORTUNITIES IN INDIA: WHITEPAPER A NEW SOURCE OF PATIENTS FOR COMPETITIVE CLINICAL TRIALS
Eight years ago, the overall estimated IBD population in India was 1.4 million, which was the second highest number after the USA (with 1.64 million) and one of the largest across the globe.13
1.8 ______ 64 1.6 ______ 4 1.4 ______
1.2 ______
1.0 ______
0.8 ______
0.6 ______ 55
0.4 ______0.2 3 5 3 0 ______
Source: karger.com
Although public healthcare in India has achieved who are potentially ready and willing to gain access several important milestones, the vast majority to better healthcare and new therapies by participating of India’s population are treatment naïve or in clinical research studies. inadequately treated. Access to care remains limited by a number of factors such as a shortage of healthcare infrastructure, the number of trained Tapping the Clinical Research providers relative to the vast population, and Opportunities in India limited health financing options. Currently, only Arguably, India offers great potential for sponsors 15% of the population is covered by government seeking new sources of study subjects, but it also health insurance companies and 2% by private represents significant challenges for the uninitiated. health insurance. Moreover, health awareness and The use of knowledgable partners is essential, education, accurate and timely diagnosis, adherence including a provider dedicated to the recruitment to and completion of doctor prescribed treatment 14 of both patients and sites for clinical trials in India. are still neglected, even today. In order to help a sponsor successfully maneuver All of this leads to an increase on the demand side through this uncharted territory, a provider must of healthcare while the supply side remains relatively possess a range of experience and capabilities. constrained. It also points to a vast number of patients
5 EMERGING CLINICAL RESEARCH OPPORTUNITIES IN INDIA: WHITEPAPER A NEW SOURCE OF PATIENTS FOR COMPETITIVE CLINICAL TRIALS
2
4 33 7 722 2 34
4 366 24 4
Familiarity with all three categories of healthcare Strong relationships and access to existing delivery in the public sector infrastructure It is imperative to have a partner that understands Successful site and patient selection requires how all levels need to work together in a cohesive a provider that has strong relationships that manner to effectively deliver care to the majority it can leverage with both hospital management of the population. and investigators in hospitals across all three major • Government Hospitals run by state government categories of institutions where clinical trials or central government: The majority of the Indian usually take place. population access these hospitals for general and speciality consultations. Because they are run by government, a minimum fee is charged for services. Many of the government hospitals are also teaching institutions that provide undergraduate and post-graduate education. • Private Hospitals run by corporations, individuals or groups of clinicians: Many corporate hospital chains exist in India, such as Fortis, Apollo, Max, Escort, and Columbia Asia, to name a few. These hospitals are usually expensive and primarily used by upper middle to high income classes. • Trust Hospitals: They have subsidized rates for patient treatment and are utilized by large populations.
6 EMERGING CLINICAL RESEARCH OPPORTUNITIES IN INDIA: WHITEPAPER A NEW SOURCE OF PATIENTS FOR COMPETITIVE CLINICAL TRIALS
The ability to mitigate sponsor concerns about access to 35 sites across the major Indian cities and India’s regulatory process cover the whole spectrum of Civil (public sector), Trust and Private/Specialty hospitals. Although there are a lot of similarities to the Western standards of clinical research, there are With staff strategically positioned at hubs within also grey areas that often raise unfounded concerns sites across the country, as well as experience across among sponsors. The right partner in India will have a broad range of therapeutic areas, the teams provide the deep knowledge and experience to eliminate any management and project support onsite, effectively misconceptions that may still linger from the earlier managing the relationship between sites and sponsor 15 regulatory environment , such as: and/or CRO, and streamlining the research experience Liability risk for the sites, investigators and patients. Misconception: India’s liability risk is out of sync These established relationships allow access to wards, with other countries. This persists from the post- outpatient clinics, and importantly, the principal 2012 regulation requiring compensation for any investigators across a broad range of therapeutic areas. patient injured on a trial, irrespective of whether These investigators typically have an undergraduate or not the investigational product was responsible degree from an Indian university with specialization for the injury. and fellowships from international (USA / European) Fact: This has been corrected in the new regulations universities. Many sit on global advisory boards for and are now in line with other countries. multinational biopharma companies and are frequent contributors at international meetings and congresses. Lagging IP framework Misconception: Running a trial in India is somehow Synexus/S4 are also fully versed and experienced at higher risk of intellectual property theft. By not in India’s regulatory process, as well as the practical running projects in India, sponsors think they can issues of conducting a clinical trial such as investigator somehow prevent their IP from being reverse- selection, language and culteral nuances. engineered by the generic pharmaceutical industry. Finally, as a testament to their track record of Fact: India is TRIPS compliant and enjoys IP enrollment and data certainty, Synexus/S4’s current protection. list of research clients is extensive, with 33 studies ongoing at 14 sites across India. A solid track record of success Sponsors need to know that a partner can commit to reasonable timelines for study approval and start, 2 deliver on committed patient numbers, and provide confidence of data quality and integrity. Clearly, for any sponsor that wants to take advantage of the emerging clinical trial opportunities in India, 7 an experienced, knowledgeable, and well-connected 4 partner such as Synexus is essential. Synexus and its 4 4 Indian affiliate, S4, offer sponsors the ideal entree into the market. Together, these two independent 2 companies combine the experience of the leading site management organization with S4’s local market knowledge in India to support pharmaceutical 2 companies and CROs in their mission to take advantage of the patient recruitment potential and cost-saving opportunities in India. Synexus/S4 have 7 EMERGING CLINICAL RESEARCH OPPORTUNITIES IN INDIA: WHITEPAPER A NEW SOURCE OF PATIENTS FOR COMPETITIVE CLINICAL TRIALS
Conclusion
In their competitive races to market with new compounds, the companies that know how to tap the emerging potential of the Indian clinical trial market by leveraging the appropriate and knowledgable partners stand to reap huge gains. When this happens, everybody wins – sponsors, patients, as well as the Indian healthcare system and economy.
References: 1 Bagchi Law. 2017. Clinical Trials in India (Part 1) – The early years of regulation. [https://libguides.lub.lu.se/c. php?g=297505&p=1984175]. Accessed August 2018. 2 Worldometers. 2017. India Population. (Live).http://www.worldometers.info/world-population/india-population/. Accessed August 2018. 3 The Times of India. 2017. India’s population to surpass that of China around 2024:UN. [https://timesofindia.indiatimes.com/india/ indias-population-to-surpass-that-of-chinas-around-2024-un/articleshow/59257045.cms]. Access August 2018 4 The World Bank. 2017. India-at-a-Glance. [http://www.worldbank.org/en/country/india]. Accessed August 2018. 5 IBEF. 2018. Healthcare Industry in India. [https://www.ibef.org/industry/healthcare-india.aspx]. Access August 2018. 6 Clinical Leader. 2017. Conducting Clinical Trials in India: Opportunties and Challenges. [https://www.clinicalleader.com/doc/ conducting-clinical-trials-in-india-opportunities-and-challenges-0001], Accessed August 2018. 7 Nasdaq. 2016. India’s Generic Drug Manufacturers: Poised for Continued Growth. [https://www.nasdaq.com/article/indias- generic-drug-manufacturers-poised-for-continued-growth-cm586029]. Accessed August 2018. 8 Central Drugs Standard Control Organization. Vision. [http://www.cdsco.nic.in/Forms/contentpage1.aspx?lid=2114]. Accessed August 2018. 9 PHARMABIZ.com. 2017. Clinical Trials in India- Changing regulatory environment. [http://www.pharmabiz.com/NewsDetails. aspx?aid=100125&sid=9]. Accessed 2018. 10 EPS International. 2017. India’s regulatory reforms for clinical trials. [https://epsi-global.com/locations/india/article01.html]. Accessed August 2018. 11 The Hindu. 2017. Burden of disease shifts to non-communicable ailments. [https://www.thehindu.com/sci-tech/health/burden-of- disease-shifts-to-non-communicable-ailments/article20445793.ece]. Accessed August 2018. 12 Circulation. 2016. Cardiovascular Disease in India: Current Epidemiology and Future Directions. [https://www.ahajournals.org/ doi/abs/10.1161/circulationaha.114.008729]. 13 KARGER. 2017. Epidemiology of Inflammatory Bowel Disease in India: The Great Shift East. [https://www.karger.com/Article/ FullText/465522]. Accessed August 2018. 14 KPMG. 2016. Report on healthcare access initiatives. [https://assets.kpmg.com/content/dam/kpmg/in/pdf/2016/08/Report-on- healthcare-access-initiatives.pdf ]. Accessed August 2018. 15 Bagchi Law. 2017. Clinical Trials in India (Part 2) – Risks and how to minimize them. [http://bagchilaw.com/clinical-trials-india- part-2-risks-minimize/]. Accessed August 2018]
Synexus is a world class Site Network Organization with global expertise spanning patient recruitment, trial planning, management and patient retention. We recruit and retain more engaged patients, at fewer sites, and in less time than traditional centers, enhancing the quality and efficiency of our customers’ drug www.synexus.com development programs. Our success is based on a simple, but crucial, principle: we place the patient at the heart of everything we do.