India: Future Of Clinical Trials In India

Introduction: "Clinical Trials" and debates associated with it have been in headlines since past few months pursuant to the strict view taken by the apex court on the matter. The number of deaths in India resulting from clinical trials has increased to an unendurable figure of 2,868 during the period 2005-20121. If on the one hand this figure relating to number of deaths resulting from clinical trials is fearful, on the other hand the decline in the number of clinical trials and approval given for conducting such trials in last few months is equally shocking. Till April 2013, only 12 (twelve) clinical trials have been approved by the authority as compared to almost a three digit figure in last year2. This certainly raises a concern for the future of clinical trials in India- country which once was perceived as a fertile place for growth of clinical trials by most of the multi-national corporations. Currently estimated at USD 500 million, India's clinical research market was projected to more than double and cross USD one billion mark by 2016 driven by favorable factors like diverse and accessible population, availability of low cost and effective resources3.

The controversies relating to clinical trials are not something which can be decided in black and white. Rather it's an interface of elements like law, ethics, scientific development, human rights and social good. As these scientific tests and trials involve application of advanced technologies, there is a need for well framed rules and laws for the conduct of these tests and trials. Certainly it's not easy to set an order of priority or precedence among these elements.

This Article is an attempt to analyze the current controversy revolving around the clinical trials in India and to come out with feasible suggestions to ensure the ethical conduct of such clinical trials without undermining the need of scientific research and development and its benefits to society. However before proceeding further, it is necessary to understand in nutshell what does "clinical trial" actually means and how are they regulated in India.

What are "Clinical Trials"? Clinical trials in layman's language mean any investigation on human subjects carried out by pharmaceutical experts in order to discover or verify the clinical and pharmacological effects of any investigational medicinal product(s) and/or to identify any adverse reactions of such medicinal products(s) and/or to study such investigational medicinal product(s) with the object of ascertaining its safety and/or efficacy. Like any standard scientific and research activity, clinical trials are carried out with a definite aim through well- defined procedure and under closed conditions.

Applicable laws and regulatory framework: Clinical trials, in addition to national laws, are governed by well established guidelines and directives at international level like EU regulations and directives, ICH- Good Clinical Practices (GCP) guidelines, recommendations of World Medical Association Declaration of Helsinki, Guidelines for Good Pharmacoepidemiology Practices and ICMR guidelines. These guidelines, recommendations and opinions are considered as "soft law" and are not legally binding but play an important role in regulating these clinical trials. Most of the multi -national corporations carrying out clinical trials worldwide voluntarily and as a good practice follow these guidelines and recommendations. These guidelines and directives primarily aim at protecting the subject from taking undue risk in participating in a clinical trial; enforce both voluntary consent to research and the continual assessment of risk and benefit. In India, Central Drugs Standard Control Organization (CDSCO) (headed by Director Control General of India) is the primary authority and "Drugs and Cosmetics Act, 1940" (along with the rules framed there under) is the principal legislation for the regulation of clinical trials. Schedule Y of the Drugs and Cosmetics Rules, 1945 ("Rules") provides for the detailed conditions, and compliances relating to clinical trials in India.

Recent amendment to Schedule Y of Drugs and Cosmetics Rules, 1945: Recently on 30th January 20134, Government of India came out with certain amendments to Schedule Y of the Rules with a view to tighten the norms relating to the conduct of clinical trials especially in terms of taking informed consents from the trial subjects and providing them or their legal representatives (as the case may be) compensation in case of any trial related injury or death. The amendment has imposed complete and ultimate liability on the sponsor of the clinical trial to reimburse any cost incurred by the trial subjects for the medical treatment of "any injury" suffered by the trial subjects as well as financial compensation for such injury or death. Further in case the sponsor fails to provide the proper medical treatment and/ or the financial compensation as per the orders of the licensing authority to the trial subjects (or their representatives as the case may be), then the authority may cancel or suspend the license of the sponsor to carry out the clinical trials and may even debar it from carrying any clinical trial in future in India. The amendment also mandates GCP compliance and adverse event reporting. The amendment has certainly acted as a deterrent on the multi-national corporations and is a negative catalytic agent to the prospects of clinical trials in India.

Ins and outs of the amendment: The aforesaid amendments to Schedule Y of the Rules came as a response to demands from the apex court, which were outraged by the lack of supervision and regulation of these clinical trials in India. As per the law existing prior to the said amendment, sponsors of the clinical trials were required to pay compensation "for deaths that results from clinical trials". Further there was no prescribed formula or minimum amount for determining such compensation and the time lines for making such payments by the sponsor in the Rules. Consequently only 45 out of 2,868 were reported to receive the compensation by the sponsors in last 7 years5. Additionally, there were no minimum clinical standards for trials prescribed under the law, for instance the requirement of registrations of the entities/ clinical research organizations conducting such trials, defined conditions and ethical standards to be complied with while conducting such trials.

After instances of unethical trials and unpaid compensations reached the courts and CDSCO early this year, CDSCO as a measure to bring about a planned change to the law relating to clinical trials in India decided to bring on table the amendments to schedule Y of Rules.

Also as a response to the public interest litigation(s) filed by few NGOs working for the human rights of the vulnerable sections, the apex court has acknowledged the lack of proper standard of care adopted by the clinical research organizations, lacunas in the existing legal framework and has shown serious concerns over the use of Indian subjects as "guinea pigs" in the conduct of clinical trials by the multi- national giants. This further triggered the CDSCO and Ministry of Health and Welfare to tighten the norms relating to the conduct of clinical trials and also the approval mechanism for such clinical trials.

While the human rights activists and NGOs are supporting the amendments to Schedule Y of the Rules, the pharmaceutical industry, sponsor pharmaceutical companies and clinical research organizations are certainly not unanimous with respect to supporting these amendments. As a result of stricter compliances and uncertain approval process, the number of clinical trials coming to India has decreased significantly in the recent past. One of the reasons for the decrease is due to the unpredictable nature of the regulatory timelines for clinical trial approval and the unreasonable demands of the authorities like protocol amendments, site selection etc. which in turn further increases the unpredictability and timelines associated with regulatory approvals. There are some who argue that this will just increase the cost of doing clinical trial in India, eventually pricing out local drug manufacturers and making India affordable only for multinational corporations. However it cannot be overlooked that as a result of aforesaid amendments and uncertain approval mechanism, the multi-national corporations would prefer other locations for carrying out the clinical trials like China, South Korea and Russia which provide a comparatively flexible and less strict regulatory atmosphere for carrying out clinical trials.

Not only the sponsors are affected by the change in regulatory scenario but also the doctors and investigators involved in the clinical trials are facing the consequences of these amendments. For example, as per the amended Schedule Y of the Rules, the investigators have an obligation to report any serious adverse effect of the drug under investigation within 24 hours of the "occurrence of such effect". Also sponsor has a responsibility to forward such reports within 10 days of the occurrence of such serious adverse event. However it is not practically possible to do so in most of the cases. Since such effects are not always physical or visible, it can be reported by the investigators only once they themselves became aware about the adverse effects of the drug through the subject or its representatives. Reporting of adverse effects and serious adverse effects are important since the same are directly related to the clinical trial injury and payment of financial compensation by the sponsors and hence the ambiguity in the amended language needs to be clarified by the authorities soon to avoid any ambiguity.

Striking out a balance between need for strict regulatory regime and the growth of clinical trials in India: Clinical trials not only contribute to the scientific research and development but also ensure better patient care than normal clinical practice and in long run is a boon for the society as it eventually leads to the development of new generic drugs and medicines. It is unfortunate that India is losing out the opportunity to other nations because of the uncertainties in the regulatory framework and approval mechanism.

Without undermining the need of amending the existing regulations relating to the clinical trials thereby making the clinical trials safer and preventing the exploitation of vulnerable subjects participating in such trials, it is necessary to appreciate that we as a developing economy with the conditions so suitable for clinical trials like diverse population, cost effective facilities and resources, presence of reputed pharmaceutical companies including subsidiaries of such multinational corporations willing to act as a sponsor and trained investigators, should not restrict the growth of clinical trials and instead try to promote a strong culture of research and development in the health sector in India.

No company or institution desires to be get publicized negatively or defend itself over ethical issues like violation of human rights or unethical treatment of patients, for any reason whatsoever. In today's diverse and competitive business environment, one must acknowledge that law often embodies ethical principles, but law and ethics are far from co-extensive. Regulators have to and should take into account other elements like social utility, economic growth etc. also while framing laws and hence it is not necessary that law would always prohibit something which is considered as unethical and the vice versa holds good.

There is a strong requirement for liberalizing the regulatory environment in favor of the sponsors conducting such trials and at the same time balancing the interest of the subjects involved in such trials. Further the approval mechanism needs to be more transparent and time efficient. Concerns raised by the human rights activist and NGOs are genuine, but rejecting or delaying the approval to the applications for conducting clinical trials is in no way a solution to the problem. Law should be for the "regulation" of the clinical trials and not for "restricting" the clinical trials. Instead of dismissing clinical trials or delaying the approval process, what is required is to identify and fix the loopholes in the regulatory framework and implement existing laws effectively to ensure that clinical trials are conducted with utmost transparency and diligence. Otherwise we would end up losing the prospects of growth of clinical research activities in India, which would certainly be a huge loss to our health care sector.

Way Forward: Following are some of the changes suggested in the existing law, which can go a long way to strike a balance between the interest of the subjects and the growth of clinical trials in India:

  1. Informed consent: Improvement in the system of obtaining informed consent from the subjects. Audio/ visual techniques of recording should be used while explaining the subjects about the process, the likely side effects and taking their consent. Further, subjects should be clearly informed about the past records of such clinical trials and number of adverse effects/deaths reported due to such clinical trials. Merely poverty and free treatment should not be the basis of engaging subjects in the clinical trials. Investigators and sponsor should be morally responsible in this regard.
  2. Restricting the liability of sponsors: Restricting the liability of the sponsors to the injury or death of the subject which are resulting directly or sufficiently attributable to the participation of the subjects in the clinical trials. With as many as 2,868 deaths during clinical trials from 2005 to 2012, only 89 have been attributed directly to such trials6. The timelines for payment of compensation should be liberalized depending upon the case to case basis. A fixed timeline in all type of adverse events and claims may not serve the purpose. Further the amount of financial compensation (over and above the cost of medical treatment) should be quantified or objective criteria to determine the same should be ascertained. For example, a terminally ill patient who chooses to be the subject of a clinical trial need not be given the same compensation as a healthy individual who has opted to become the subject for clinical trial. It should not be left at the sole discretion of the licensing authority or ethics committee.
  3. Institutionalization and registrations: Independent research and trials should be restricted and only institutionalized clinical trials to be carried out. It is commonly seen that investigators and doctors at individual level carry out unregulated clinical research in private clinics and hospitals. This is required to be checked by the authorities. Registration of clinical trials with Clinical Trials Registry India and registration of clinical research organizations should be mandatory. This is already in place, however the effective implementation of the same should be ensured.
  4. Approval mechanism: Fast and time efficient approval mechanism is required. Objective criteria for accepting or rejecting the applications, transparency in the entire process and the decisions for rejection or pending applications should be supported with the appropriate reasons. It is to be noted that the approval time for initiating drug trials in India typically runs from six to eight months, compared to 28 days in Europe and Canada.7
  5. Transparency: Transparency from the side of investigators and institutions is also very important. It is one of the core guiding principles in the ICMR Ethics Guidelines. Institutions and investigators should be open to public about regarding kind of investigation, standard of care taken, subjects involved, etc.
  6. Inspection and auditing: Officials of the CDSCO or licensing authority carrying out the inspection of the site should be of the same field with adequate knowledge and expertise on the subject. Also the use of CCTV camera at the trial site to administer the whole procedure of trial should be implemented. Further, involvement of the experts from the industry and legal field in the ethics committee and more emphasis on institutionalization of the ethics committee is also necessary. These would help the ethics committee and regulatory authority to investigate the matter more efficiently.
  7. Applicability of stringent laws: Multi-national corporations which are voluntarily following the internationally recognized guidelines and directives or are governed by laws of other home countries which are materially equivalent strict in terms of following the good clinical standards and protecting the interest of the subjects, should not be made to comply with more procedural compliances and practices and should be provided a conducive regulatory atmosphere for coming to India and carrying out clinical trials.
  8. Drugs with serious side effects: It is seen that most of the deaths occurred in the past few years is due to some specific drugs which were time and again put to investigation and every time resulted in the severe adverse effects. Special care should be taken in approving the clinical trials of such drugs and only in exceptional cases and depending upon the utility of such drug the permission should be given.
  9. Role of media: Negative publicity of clinical trials and multi- national corporations involved in such trials should be avoided and discouraged. Media should be responsible in spreading any critical report relating to the clinical trials and same should be approved by the licensing authority in advance. In past it is seen that out of the 2,868 deaths reported only 89 of them were taken place due to clinical trials8. Rest were either remotely related to the trial or were in regular course due to the disease of the subjects. Such negative publicity discourages the sponsor and creates uncertainties in the mind of the subjects. Rather media should emphasize on spreading awareness about such clinical trials targeting the vulnerable sections who mostly get involved in trials as subjects.
  10. Pending actions from the side of Government: The proposal of Ministry of Health and Family Welfare with respect to forming a committee comprising of science and regulatory experts that would formulate policy on drug approvals, clinical trials and drug bans should be implemented promptly. Also the draft bill on Biomedical Research on Human Participants (Promotion and Regulation) prepared by the Indian Council of Medical Research should be tabled in the parliament on priority basis. It would be beneficial if the comments and suggestions of the experts from the industry are taken.
  11. Clarification: Removing the loopholes in the language of the amended schedule Y (for instance as mentioned above the time period with respect to the reporting of serious adverse events) and bringing clarity to the same.

The ethical concerns of the clinical trials cannot be removed completely. But the above suggestions, if implemented, can certainly give bright prospect to the growth of clinical trials and research in the health care sector in India and would help in regaining the lost confidence of the multi-national corporations interested in carrying out clinical trials in India. At the cost of repetition, I would like to reiterate: Law should be for the "regulation" of the clinical trials and not for "restricting" the clinical trials!

Footnotes

1 Please see : http://www.business-standard.com/article/pti-stories/only-45-of-2-868-clinical-trial-deaths-compensated-since-2005-113030500403_1.htm l; last visited on June 21, 2013

2 Please see : http://www.thehindu.com/sci-tech/health/policy-and-issues/post-stringent-norms-clinical-trials-in-india-plummet/article4639976.ece ; last visited on June 21, 2013

3 Frost & Sullivan report, please see http://www.thehindubusinessline.com/industry-and-economy/clinical-trial-market-to-reach-1-billion-by-2016-report/article3877317.ece ., last visited on June 21, 2013

4 Notification GSR 53(E) dated January 30, 2013 For more details please see: http://www.cdsco.nic.in/GSR%2053(E)%20dated%2030.01.2013.pdf , last visited in June 21, 2013

5 Supra foot note no. 1

6 Supra foot note no. 1

7 Please see http://www.pharmalive.com/india-losing-its-edge-clinical-trials , last visited on June 21, 2013.

8 Supra foot note no. 1

© 2013, Vaish Associates, Advocates,
All rights reserved with Vaish Associates, Advocates, 10, Hailey Road, Flat No. 5-7, New Delhi-110001, India.

The content of this article is intended to provide a general guide to the subject matter. Specialist professional advice should be sought about your specific circumstances. The views expressed in this article are solely of the authors of this article.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Authors
Priyesh Sharma, Vaish Associates Advocates Delhi, India
Similar Articles
Relevancy Powered by MondaqAI
 
In association with
Related Topics
 
Similar Articles
Relevancy Powered by MondaqAI
Related Articles
 
Related Video
Up-coming Events Search
Tools
Print
Font Size:
Translation
Channels
Mondaq on Twitter
 
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
 
Email Address
Company Name
Password
Confirm Password
Position
Mondaq Topics -- Select your Interests
 Accounting
 Anti-trust
 Commercial
 Compliance
 Consumer
 Criminal
 Employment
 Energy
 Environment
 Family
 Finance
 Government
 Healthcare
 Immigration
 Insolvency
 Insurance
 International
 IP
 Law Performance
 Law Practice
 Litigation
 Media & IT
 Privacy
 Real Estate
 Strategy
 Tax
 Technology
 Transport
 Wealth Mgt
Regions
Africa
Asia
Asia Pacific
Australasia
Canada
Caribbean
Europe
European Union
Latin America
Middle East
U.K.
United States
Worldwide Updates
Registration (you must scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.

Disclaimer

The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.

General

Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions