Update

Forum: Science & Society

India’s growing participation in global clinical trials

Yogendra K. Gupta1 and Biswa M. Padhy2

1 Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India2 Department of Pharmacology, Hamdard Institute of Medical Sciences and Research, New Delhi 110062, India

Lower operational costs, recent regulatory reforms andseveral logistic advantages make India an attractivedestination for conducting clinical trials. Efforts formaintaining stringent ethical standards and the launchof Pharmacovigilance Program of India are expected tomaximize the potential of the country for clinical re-search.

IntroductionWith mounting pressure on R&D costs across the pharma-ceutical industry in developed markets, there is increasingfocus on reducing the cost of clinical development. Emerg-ing countries such as India, which have lower operationalcosts, have become preferred destinations for multination-al pharmaceutical companies. The number of global clini-cal trial applications received by the Indian drug regulatorthe Central Drugs Standard Control Organization(CDSCO) has increased several fold over the last few years.In 2005 the CDSCO received 100 applications; this numberrose to 300 in 2007 and peaked at 350 in 2008. However, in2009 the number of applications decreased to 262, possiblyreflecting the global economic recession. Nevertheless, 180applications received by July 2010 indicates a revival of thetrend [Drugs Controller General, India – DCG(I); personalcommunication]. An analysis of trials with Indian sitesregistered in the USA clinical trials registry (www.clini-caltrials.gov) also illustrates the uptrend. This reported 79registrations (drug trials - 65, other trials - 14)) in 2004which increased to 225 (drug trials - 173, other trials - 52)in 2008 [1]. Furthermore, the clinical trial outsourcingmarket in India is forecast to grow at a compounded annualgrowth rate of over 30% during 2010–2012 and to be worth600 million USD by 2012, exponentially up from the 50million USD at the start of millennium (Ernst &Young/Federation of Indian Chambers of Commerce and Industry(2009); Jayasheel, B.G. (2010); Box 1).

The strategic advantages offered by India (referred to asthe ‘Advantage India’) include a large treatment-naı̈vepatient base, a wide spectrum of diseases, ethnic variabili-ty, English-speaking healthcare professionals, sound med-ical and IT infrastructure, adoption of Good ClinicalPractice (GCP) and bioethics guidelines, faster recruit-ment and good quality data, at nearly half the operationalcosts than in developed countries (Ernst &Young/Federa-tion of Indian Chambers of Commerce and Industry (2009);Box 1) [2]. However, despite these factors, only 1.2% of allglobal trials are conducted in India. In addition the countryfaces stiff competition from other emerging R&Dhubs such

Corresponding author: Gupta, Y.K. (yk.ykgupta@gmail.com).

as Singapore, China and Israel [3]. To realize the fullpotential of the country, industry, regulators, scientificorganizations and academia are currently working in syn-ergy to build capacity and improvethe overall clinicalresearch environment.

The evolving regulatory landscapeThe regulatory review of clinical trial applications andsubsequent approval by the CDSCO has been criticizedfor its protracted course. However, following the recruit-ment of more staff and a host of other changes under thecurrent DCG(I), the median review period has reducedfrom 16 weeks to 10 weeks (Jayasheel, B.G. (2010); Box1). The new timeline for approval of clinical trials by theCDSCO is targeted at 45 days (Central Drugs StandardControl Organization (2010a); Box 1). Recently, draft guid-ance for new drug applications has also been issued to actas a format for sponsors and to guide submission of rele-vant information in their applications. Additionally, the e-governance initiatives of the CDSCO (such as the file-tracking system and daily dispatch reports) are also aimedat bringing transparency and accountability (CentralDrugs Standard Control Organization (2010b); Box 1).The regulator is also aiming for ‘single-window’ clearancefor export of biological samples of clinical trials, in collabo-ration with the Directorate General of Foreign Trade(personal communication). To regulate the clinical re-search organization (CRO) sector, the CDSCO has issueddraft rules for registration of CROs. India is the firstcountry in the world to put in place such registrationcriteria. Under the draft rule, to be included in the Drugsand Cosmetics Act 1945 (Schedule Y-1), a CRO can carryout its activities only if it is duly registered. The validity ofregistration has been fixed for a period of five years fromthe date of issue (Babu, G. (2009); Box 1).

The Clinical Trial Registry–India (CTRI) is an onlineregister of clinical trials conducted in India, and more than1000 studies are currently registered. It was started by theIndian Council of Medical Research (ICMR) in 2007 withtechnical support from the World Health Organization(WHO). Since the 15th June 2009, sponsors have beenmandated to register all trials with the CTRI before studyinitiation. Before this it was only recommended that clini-cal trials should be registered before patient enrollmentbegan. The impact was immediate, with �100 studiesregistering within a span of one month after enforcementof the order (compared with 137 studies registered duringentire of period of 2008) and within six months the numberof registered studies increased to 689 [4]. A recent study ontrials registered in the CTRI (425 in 2009, and 245 untilmid-2010) revealed that a large number were Phase III

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Box 1. Web sources on clinical research in India

� Babu, G. (2009) Centre releases draft rule for Schedule Y-1

mandating registration of CROs. (http://www.pharmabiz.com/

article/detnews.asp?articleid=50653)

� Central Drugs Standard Control Organization (2010a) Targeted

Timelines for Approvals of Complete Applications by DCG (I)

Office. (http://www.cdsco.nic.in/revised_new_timelines.pdf)

� Central Drugs Standard Control Organization (2010b) Daily

Dispatch Details. (http://cdsco.nic.in/daily-letters.htm)

� Central Drugs Standard Control Organization (2010c) Guidance on

Clinical Trial Inspection. (http://cdsco.nic.in/CLINICAL%20TRIAL

%20INSPECTION%20PROGRAMME%20OF%20INDIA.pdf)

� Ernst &Young/Federation of Indian Chambers of Commerce and

Industry (2009) The Glorious Metamorphosis: Compelling Rea-

sons for Doing Clinical Research in India, September 2009. (http://

www.ficci.com/publication-page.asp?spid=20026)

� Gupta, Y.K. (2010) Pharmacovigilance Programme for India.

(http://www.pharmabiz.com/article/detnews.asp?articleid=

56487&sectionid=46)

� Jayasheel, B.G. (2010) Carrying out Clinical Trials in India. (http://

www.acunovalife.com/pdf/whitepapers/RAJ_Pharma%20Ju-

ne%202010_Jayasheel%20final.pdf)

Update Trends in Pharmacological Sciences June 2011, Vol. 32, No. 6

trials (200 in 2009, and 111 in 2010) sponsored by privatepharmaceutical companies (350 in 2009, and 191 in 2010).The majority of the trials were for drugs or biologicals (285and 79 respectively in 2009, and 132 and 78 respectively in2010). These focused predominantly on the five therapeuticareas of oncology, cardiovascular diseases, neuropsychia-try, endocrine disorders and infections. The study alsohighlighted the abundance of sites in Western and South-ern cities such as Mumbai, Pune, Ahmedabad, Hyderabad,Bangalore and Chennai [5]. The exponential increase inthe number of trials has brought into focus the need ofregulatory oversight to uphold the quality of the trials.Clinical trial inspections by the CDSCO started in late2008, and fully fledged onsite inspections by US-FDA-trained Indian inspectors and regulatory experts (usingupdated audit checklists) were initiated in July 2010.Recently, the CDSCO has also released a guidance docu-ment for clinical trial inspections (Central Drugs StandardControl Organization (2010c); Box 1).

Recognizing the need for monitoring of adverse drugreactions (ADR), the Government of India launched thePharmacovigilance Program of India (PvPI) in July 2010.The first phase was introduced in mid 2010, aiming toinduct ADR monitoring centers (AMC) in 40 medical col-leges by the first quarter of 2011; 60 more medical collegeswill be added by early 2012, and 100 more by 2013. Theentire healthcare system will be covered by 2014. All theAMCs are provided with operational and logistic supportby the CDSCO offices of their respective zones which areunder the direct administrative control of CDSCO head-quarters in New Delhi. The National Coordinating Center(NCC) of PvPI is located at the Department of Pharmacol-ogy, All India Institute of Medical Sciences (AIIMS), NewDelhi, and provides technical support to the CDSCO head-quarters. ADR reports collected at the AMCs are trans-mitted to the coordinating center, which conducts causalityassessment and incorporates this into the national phar-macovigilance database. The ADRs from all other sources(including the pharmaceutical industry, health care pro-fessionals, and the national immunization program) will

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eventually be incorporated in the database at the NCC. Inaddition, the center also implements and integrates phar-macovigilance activities into public health programs in-volving mass usage of drugs such as anti-malarials, anti-tuberculars and anti-retrovirals. The reports will then beuploaded into the WHO–Uppsala Monitoring center ADRdatabase (Vigibase) for comparison with data from othercountries (Gupta, Y.K. (2010); Box 1). To foster the cultureof ADR reporting, all medical colleges in India have beenmandated by the Medical Council of India to establishPharmacovigilance units, making it a first-of-its-kind ini-tiative in the world.

Future challengesIt is estimated that there are only 1500 GCP-trainedphysicians in India, and engaging adequately trainedinvestigators is increasingly difficult. In addition, thereis an acute scarcity of biostatisticians and pharmacoepi-demiologists available for clinical data analysis. Moreover,in the absence of government-recognized clinical researchtraining institutes, private players offering a variety ofcourses have mushroomed (from three in 2006 to 25 in2010), often employing self-styled curricula and inade-quately experienced trainers. In view of this, in 2009 theDepartment of Biotechnology, Government of India, incollaboration with AIIMS, established six clinical researchtraining centers to train potential young medical investi-gators and to increase the outreach of clinical research inthe country. However, its actual impact has yet to beascertained [2,6].

With increasing numbers of trials there are rising con-cerns about ethics in clinical research. In the past, trans-gressions such as a lack of informed consent inerythromycin– contraceptive trials and in the letrozoletrials for infertility had dampened public confidence inthe clinical research enterprise [7]. Fortunately, with in-creasing awareness and newer safeguards such as manda-tory trial registration, ethics-committee review andregulatory inspections, such incidents are becoming rarer.Admittedly, institutional and independent ethics commit-tees with adequately trained members are predominantlylocated in large cities of India. However, such committeesare gradually increasing in medical institutions across thecountry, as is apparent from the formation of Forum forEthics Review Committees of India (FERCI), but theirexact number (estimated to be about 40 in 2008) cannotbe quantified due to the absence of systematic studies [3,8].Therefore, to increase accountability, mechanisms for reg-istration/accreditation of ethics committees, training ofethics-committee members, and provisions for stringentpenalty and criminal prosecution for fraud and scientificmisconduct are under consideration.

Efforts at boosting ‘Advantage India’ might be per-ceived as favoritism towards multinational pharmaceuti-cal companies if global trials conducted in the countrymerely focus on lifestyle diseases and ignore indigenoustropical diseases [7]. Therefore, strategic partnershipsbetween all stakeholders will be crucial for creating anequitable research environment and in leveraging theposition of India as a dominant player in the clinicalresearch arena.

Update Trends in Pharmacological Sciences June 2011, Vol. 32, No. 6

AcknowledgementThe authors are thankful to the DCG(I), Dr. Surinder Singh for hisvaluable inputs in the manuscript.

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doi:10.1016/j.tips.2011.02.017 Trends in Pharmacological Sciences, June 2011, Vol. 32, No. 6

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