Outsourced clinical trials and ethical implications: India the most preferred global clinical trial hub

Persis Naumann
Duquesne University, Pittsburg, Pennsylvania (Spring 2017)

 

Introduction

Pharmaceutical research is a complex social enterprise. With the proliferation of corporate globalization in the healthcare industry, pharmaceutical companies from western developed countries have increasingly offshored and outsourced global biopharmaceutical clinical trials to developing countries. The power of global pharmaceutical industries is extensive. It is important to understand the structure of the pharmaceutical industry, the consolidation of the top companies in recent decades, and the dominance of western companies and markets before exploring the implications of a global pharmaceutical industry.[i]

 

The globalization of clinical trials in healthcare

India, the most preferred global
clinical trial hub (Public Domain)

The pharmaceutical industry plays a major role in the worldwide economy. Its global sales amount to around US$1 trillion in 2014, surpassing the gross national product of several low-income countries.[ii] A small group of large multinational companies such as Novartis, Pfizer, Sanofi, Roche, Merck & Co., Johnson & Johnson, AstraZeneca, and GlaxoSmithKline, Teva, and Gilead Sciences dominate the market. They are among the top ten pharmaceutical companies in sales value as of 2014. Of these nine are USA or Europe based, Teva being a recent entrant based in Israel.[iii] With the proliferation of corporate globalization in the healthcare industry, drug companies from western developed countries have increasingly outsourced the production of medicines and commercial clinical trials to developing countries.[iv] Contract Research Organizations (CROs) support  pharmaceutical companies by providing outsourced research services such as product development; formulation and manufacturing; clinical trial management; clinical, medical and safety monitoring; preclinical, toxicology, and clinical laboratory services for processing trial samples; management, biostatistics, and medical writing services for  FDA New Drug Application (NDA) and  Abbreviated New Drug Application (ANDA); regulatory affairs support; and many other complementary services.[v] The CROs have become essential to the pharmaceutical, medical technology, and biotechnology companies, supporting drug and medical device research and their development. Owing to greater outsourcing of work, including patent expiration, the proliferation of generic medications, and technological innovations such as mobile health and big data influence to CROs, the global market earned revenues of $27 billion in 2014 and is estimated to cross $32 billion in 2017.[vi] The CRO market value in India, according to Frost and Sullivan analysis, reached $485 million in 2010-2011 and is expected to exceed $1 billion in 2016.[vii] The participants operating in India are multinational CROs, Indian CROs, and multinational or Indian pharmaceutical companies. The multinational CROs still dominate the nation’s market.[viii] Until 1990 India was not a preferred destination for the global pharmaceutical companies, but a steep rise in the demand for world class clinical trial management capacity and productivity has now made India the preferred site for the time-consuming and expressive affair of drug discovery and development.[ix] Proponents of outsourcing have pointed that this offers advantages such as a large treatment naive patient base; a wide spectrum of diseases; ethnic variability; English speaking professionals; sound medical and IT infrastructure; adoption of Good Clinical Practice (GCP) and bioethics guidelines; high patient enrollment rates; good quality data; low salaries for professionals; low payments to trial participants; and insurance premiums.[x] All of these  operate at costs of 40-60% less than in developed countries. Furthermore, major reforms in the area of jurisprudence, with the restructuring of the Patents Act 1970 and the Indian Drugs and Cosmetics Act 1940, as well as the adoption of “product patents” on the lines of Trade Related Intellectual Property Rights (TRIPs) in 2005, guarantee data protection, data exclusivity, and incentives granted on the part of the government of India. These incentives include the exemption of import duty and service tax on the testing and analysis of new drugs, vaccines, and herbal remedies on human participants by a Clinical Reference Group (approved by the Drugs Controller General of India to conduct clinical trials). All of these encourage more and more foreign investment in the Indian Clinical Research Industry, and clinical research outsourcing has thus become a lucrative business.[xi]

 

The irregularities that impact patient care

Community health worker assisting India’s poor and illiterate (Public Domain)

Despite the increase in health research activity in India and the obvious economic benefit, only limited work has been done to address ethical issues. Clinical trials form an integral part of drug development worldwide.  They are essential to ensure the safety and efficacy of a new drug in the market, and therefore human subjects are used in these health related interventions to study or evaluate the effects on health outcomes. The offshoring and outsourcing of biopharmaceutical clinical trials to India, however, has prompted several new and specific ethical concerns.[xii] Furthermore, ethical violations in clinical trials in India have exposed gaping holes in the country’s regulatory system, which has struggled to oversee the booming industry. It is the interjection of profit motivation into drug research that creates the greatest ethical challenges, leading to exploitative and unethical practices such as subject coercion, lack of voluntary and informed participation, inadequately informed consent, and the systematic exploitation of  poor and non-literate people.[xiii] Outsourcing clinical trials to India may expedite the research process, which in turn expedites the approval of new medicines, but often presents ethical problems because of inadequate enforcement of regulations and human subject protection.[xiv] Targeting vulnerable people as research subjects has become a problem, and recruiting them without informed consent or post trial benefits has exposed the exploitation of these people.[xv] Since India’s most illiterate and poor tend to be more vulnerable to manipulation, they are often signed up without their knowledge, especially since they are desperate for medical care that would otherwise be unavailable and unaffordable.[xvi] They are often unaware of the benefits and risks, as they are not always able to differentiate between treatment and research. Extracting benefits from individuals by taking advantage of their vulnerability is intuitively considered morally wrong.[xvii] It is the responsibility of the regulatory agencies to ensure the ethical integrity in clinical trials, but the lack of regulation has enabled dubious trials in India and exposed ethical irregularities.[xviii] Regulatory agencies are less equipped to deal with the large number of clinical trials. With the prevailing corruption, enforcement of existing regulations in clinical trials is relatively weak in India and increasingly so with the proliferation of foreign trials.[xix] 

 

Conclusion

Because of these factors, trials of new drugs have been halted and amendments to clinical trial regulations were made by the Supreme Court of India.[xx] Despite the traditional bioethical problems existing locally, ethical paradoxes arise when countries with relatively high levels of economic development initiate, design, or fund research conducted in countries that are relatively less developed. Global concerns remain about the notion of double standards in research ethics, the higher and more restricted standards in developed countries, and the lower and less stringent standards in developing countries.

 

References

  1. Hanefeld, Johanna. Globalisation and Health. Berkshire: McGraw-Hill Education, 2015. eBook Collection (EBSCOhost), EBSCOhost (accessed December 4, 2016). 127.
  2. “Top-Line Market Data.” IMS Health. 2016. Accessed December 06, 2016. http://www.imshealth.com/en/about-us/news/top-line-market-data.
  3. “Top-Line Market Data.” IMS Health. 2016. Accessed December 06, 2016. http://www.imshealth.com/en/about-us/news/top-line-market-data.
  4. Emanuel, Ezekiel J. Ethical and Regulatory Aspects of Clinical Research: Readings and
    1. Baltimore: Johns Hopkins University Press, 2003. 25-28.
  5. Drabu, Sushma, Alka Gupta, and Anupama Bhadauria. “Emerging trends in contract research industry in India.” Contemporary clinical trials 31, no. 5 2010: 419-422.
  6. ProClinical. “Top 10 Contract Research Organisations (CROs) to Watch in 2016.” Top 10 Contract Research Organisations (CROs) to Watch in 2016. Accessed December 06, 2016. http://blog.proclinical.com/top10-contract-research-organisations-to-watch.
  7. “India CRO Market to Earn $1B by 2016, Says Frost & Sullivan – CenterWatch News Online.” Center Watch News Online. 2012. Accessed December 06, 2016. http://www.centerwatch.com/news-online/2012/08/20/india-cro-market-to-earn-1b-by-2016-says-frost-sullivan/.
  8. “India CRO Market to Earn $1B by 2016, Says Frost & Sullivan – CenterWatch News Online.” Center Watch News Online. 2012. Accessed December 06, 2016. http://www.centerwatch.com/news-online/2012/08/20/india-cro-market-to-earn-1b-by-2016-says-frost-sullivan/.
  9. Maiti, Rituparna, and M. Raghavendra. “Clinical trials in India.” Pharmacological Research 56, no.1. 2007. 1-10.
  10. Drabu, Sushma, Alka Gupta, and Anupama Bhadauria. “Emerging trends in contract research industry in India.” Contemporary clinical trials 31, no. 5 2010: 419-422.
  11. Drabu, Sushma, Alka Gupta, and Anupama Bhadauria. “Emerging trends in contract research industry in India.” Contemporary clinical trials 31, no. 5 2010: 419-422.
  12. Kamat, V.R. “Fast, cheap, and out of control? Speculations and ethical concerns in the conduct of outsourced clinical trials in India.” Social Science And Medicine 104, (March 1, 2014): 48-55. Scopus®, EBSCOhost (accessed December 6, 2016).
  13. Kamat, V.R. “Fast, cheap, and out of control? Speculations and ethical concerns in the conduct of outsourced clinical trials in India.” Social Science And Medicine 104, (March 1, 2014): 48-55. Scopus®, EBSCOhost (accessed December 6, 2016).
  14. Yee, A. “Regulation failing to keep up with India’s trials boom.” The Lancet 379, no. 9814 (February 4, 2012): 397-398. Scopus®, EBSCOhost (accessed December 6, 2016).
  15. Henk, ten Have. Vulnerability Challenging Bioethics. Routledge: London, 2016. 7-9
  16. Yee, A. “Regulation failing to keep up with India’s trials boom.” The Lancet 379, no. 9814 (February 4, 2012): 397-398. Scopus®, EBSCOhost (accessed December 6, 2016).
  17. Henk, ten Have. Vulnerability Challenging Bioethics. Routledge: London, 2016. 11-17.
  18. Yee, A. “Regulation failing to keep up with India’s trials boom.” The Lancet 379, no. 9814 (February 4, 2012): 397-398. Scopus®, EBSCOhost (accessed December 6, 2016).
  19. Sharav, Vera. “India Supreme Court Orders End to Illegal Clinical Trials.” Alliance for Human Research Protection. January 6, 2016. Accessed September 9, 2016. http://ahrp.org/india-supreme-court-orders-end-to-illegal-clinical-trials/.
  20. Yee, A. “Regulation failing to keep up with India’s trials boom.” The Lancet 379, no. 9814 (February 4, 2012): 397-398. Scopus®, EBSCOhost (accessed December 6, 2016).

 


 

PERSIS NAUMANN, is a Ph.D student in Healthcare Ethics and a graduate research assistant at Duqesne University, Pittsburgh, Pennsylvania.

Follow Hektoen International via social media to see more featured content.