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| MISCELLANEOUS - HEART TO HEART |
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| Year : 2015 | Volume
: 1
| Issue : 3 | Page : 294-296 |
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Ethics of clinical trials in India: The ring of gyges
Sundeep Mishra
Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| Date of Web Publication | 23-Feb-2016 |
Correspondence Address:
Sundeep Mishra
Department of Cardiology, All India Institute of Medical Sciences, New Delhi
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2395-5414.177312
India is poised to take center stage in global pharmaceutical research. There is a need to strengthen the regulatory apparatus to conduct human trials. It is important for clinicians, regulators, healthcare industry, and most importantly, patients work together to ensure conduct of clinically meaningful research. Keywords: Benefits of participating in a clinical trial, ethics of clinical trials, regulatory apparatus
How to cite this article:
Mishra S. Ethics of clinical trials in India: The ring of gyges. J Pract Cardiovasc Sci 2015;1:294-6 |
| Introduction | |  |
The South Asian subcontinent including India is all set to become one of the world's preferred destinations for clinical trials. India may be the preferred destination because it has a technically competent workforce (skilled English-speaking medical personnel), patient availability (the largest pool of patients suffering from cancer, diabetes, cardiovascular disease, and other maladies), low costs (about 60%), and a friendly drug-control system. While it is a good news for India's economy, it is also a cause for concern because India in the past has been in the news for clinical trials which did not follow the principles of good clinical practice (GCP), though the regulatory system in India is gradually strengthening itself to make the atmosphere more conducive to conduct trials as per GCP guidelines.
| Ethics of Clinical Trials | | |
Clinical enquiry is an observation of differences, indeed the basis of any science. [1] However, despite the objectivity, there are several nondiscursive elements and even a degree of subjectivity in the discourse. Thus, there is a need to have certain ethics in the conduction of science. In the context of a clinical trial, ethics generally involves three issues. Is the question being asked relevant to the needs of humanity in general and to the population being studied in particular. In other words, is it the felt need of society or is it just a case of invention in search of a need? second, is the methodology proposed able to answer the question asked or is it under-powered or worse designed in a way to provide the intended answer one-way or the other. However, the most contentious issues are the rights and ethics concerning patients. The aim of the health-care industry is to provide a better and a more effective cure for the humanity which will not be possible unless new drugs/therapies/devices are developed and tested on human subjects. However, it is the responsibility of the medical profession to ensure that all the possible beneficial therapies are employed before an investigation therapy is offered. Thus, an experimental therapy can/should always be offered as a last resort, thus restricting its use almost to no-option, end-stage patients, thus restricting the numbers to a minor fraction of the total population. Further, the first rule of medical ethics is "do no harm," thus, restricting to those therapies which are relatively safe. [2],[3] At the same time, a huge potential exists to cure the patient with a new therapy. Thus, the crux of the matter is "risk/benefit" ratio. In other words, relative advantages and relative risks of a particular therapy in a given patient population have to be carefully considered before taking a decision to include/not include the patient in a clinical trial. Further, this risk/benefit discussion cannot be conducted in an intellectual domain, but should be communicated with the patient accurately so that he/she can make an informed consent.
| Are Indians Being Used as Guinea Pigs in Clinical Trials? | | |
Historically, it has been difficult to find subjects in a trial where the side effects of a given therapy could be high (and efficacy low or uncertain). Thus, mentally unstable and incarcerated individuals were the favorite subjects for such human experiments as conducted by Nazi's. [4] Thus, the possibility of using poor, illiterate Indians in un-ethical clinical trials is very real. In an affidavit, submitted to the honorable Supreme Court of India, the Centre had admitted 2644 people died during clinical trials of 475 new drugs. [5] Further, it stated that "Around 11,972 serious adverse events (excluding death) were reported during the period from January 1, 2005 to June 30, 2012, out of which 506 events were found to be related to clinical trials," It is not surprising that a number of commentators, in India and abroad, have alluded to the participation of Indians in clinical trials as the "guinea pig syndrome." The reason why Indian patients are possibly subjected to this syndrome could be manifest/subtle coercion of the subject to participate based on out-right monetary compensation to lure of free drugs and therapies to the reluctance on the part of patients to go against the wishes of their treating physicians (will he bear a grudge against me for saying no to participation?). It could also be a lack of understanding on the part of the patient or inability to really understand the choices available to him/her.
| The Benefits of Participating in a Clinical Trial | | |
With all this background, there arises a question: Are trials at all necessary, or what are the benefits of participating in a trial? Over the last century, clinical research has added much to the body of knowledge in the healthcare community. As a society, it is important for clinicians, regulators, healthcare industry, and most importantly, patients work together to ensure conduct of clinically meaningful research, so as to provide solutions to our ever-increasing medical problems. Conducting and participating in this clinical research is thus a credible, even desirable goal for any state aspiring overall betterment for its citizens. In addition to the philosophical goals, there are several practical advantages of participating in research. For one, the outcomes of a trial with local participants are likely to be directly applicable to the local needs. Often, we talk of research being done elsewhere not being applicable to Indian patients. Moreover, it may bring state-of-art healthcare facilities and systems not only to the patients but also the local physicians, hospitals (new diagnostic equipment and new treatment algorithms), contributing to the over-all elevations of healthcare delivery in a given community. It can even serve as an economic boost for health-related industry of the region, ultimately subsidizing the healthcare costs to the patients. Further, as a part of the study, Indian patients are not treated differently than patients in Australia or Europe or North America and many patients actually receive a better care than other patients (not participating in the trial). [6] Finally, despite all the recent buzz of increasing clinical trials in India, the number of Indian patients participating in clinical trials remains a tiny fraction of those in other countries (<5% of clinical trial patients globally). [7]
| So What is the Way Out? | | |
The only solution to this dilemma seems to be to strengthen the regulatory apparatus (both external and self-regulation) and law enforcement. Several steps in the direction of better regulation can be undertaken. Accreditation of healthcare facilities and personnel, establishing guidelines for conducting research, central registration and monitoring trials, independent audit of trial at all levels, adjudication of safety and efficacy endpoints are some of the ways to achieve this. [8] However, establishing a robust and independent Ethics Committee is perhaps the most important step. They should have a right to review, advise, suggest a course correction, with-hold further participation, and even terminate a trial, if required. [9] Another important component addressing the right of the patient is obtaining an informed consent. Clinical trials in India include a large proportion of literate and illiterate patients, reflecting the reality of our society. There may be a myth that patients in India are not capable of understanding the choices available to them. However, to understand these choices, one does not need to be literate. It may indeed be preposterous to suggest that an Indian patient cannot understand that he is being asked to enroll in an experiment, that he has options available to him, and that there are potential risks and benefits of all options. Similarly, while conducting an informed consent under ever increasing scrutiny may be at present the only realistic step, but may underscore our inability to trust our own physicians/scientists. It may raise the anxieties and uncertainties and even Paranoia among the physician-researchers: "The Big Brother is Watching Syndrome." A good informed consent takes time, patience, and effective articulation on the part of the consenting physician culminating in an effective communication. But once this is done, Indian patients are as capable (and free to) exercise choices as citizens as in any other country. It is important to appreciate that informed consent can be taken ethically, and if it is not, then that is an aberration that can and must be addressed. Thus, an exemplary, speedy, and predictive delivery of justice can be used to tackle all kinds of scientific misconduct, mala fide, and research fraud carried out by physician-investigators. A model of society so well enshrined in the West, where law breakers are dealt so swiftly, predictably, and even harshly that nobody dares break the rules. Other potent deterrents are the democratic institutions, the freedom of the press, and the availability of open platforms where these misconducts can be openly discussed putting professional reputation of scientist-doctor at stake.
| Responsibilities of an Intellectual | | |
Despite all these steps, the best discipline is self-discipline and a regulation, self-imposed may be the best and most cost-effective way to address this problem. At the same time, notification of scientific misadventure by a colleague, senior, employee, or an even an employer (whistle blowing) is indeed being one of the responsibilities of any scientist.
| Conclusions | | |
India is poised to take center stage in the collaborative global pharmaceutical research. However, the possibility of poor and illiterate Indian subjects being taken as fodder for these expensive multi-national trials is real and ever-present. There is a need to strengthen the regulatory apparatus to conduct human trials in the country. Particularly, the Ethics Committees and the way informed consents are taken need to be strengthened. Talking openly about the clinical trial process and measures to strengthen those can only serve to further strengthen the foundations of our research infrastructure and mindset. Making research un-necessarily difficult and costly may be counterproductive to our national interest. This problem can be correctly addressed by increasing awareness among the scientific medical community, making them understand their responsibilities as an intellectual and strict enforcement of rules and sound and predictable punishment of misconduct.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Mishra S. What ails the practice of medicine: The Atlas has shrugged. Indian Heart J 2015;67:1-7.  |
| 2. | Finlay I. ′First do no harm′ - A clear line in law and medical ethics. J R Soc Med 2006;99:214-5. |
| 3. | Hippocratic Oath. Available from: https://www.en.wikipedia.org/wiki/Hippocratic_Oath. [Last accessed on 2015 Dec 30]. |
| 4. | Nazi Human Experimentation. Available from: https://www.en.wikipedia.org/wiki/Nazi_human_experimentation. [Last accessed on 2015 Dec 30]. |
| 5. | |
| 6. | |
| 7. | Poongothai S, Unnikrishnan R, Balasubramanian J, Nair MD, Mohan V. Why are clinical trials necessary in India? Perspect Clin Res 2014;5:55-9. [ PUBMED]  |
| 8. | |
| 9. | Gandhi P, Gandhi R, Shekhawat S, Shah J, Kabara M, Khinchi MP. Clinical Trials in India. Innovare J Med Sci 2013;1:19-32. |
Editor's Note
The story of the Ring of Gyges:
The ring of Gyges makes you invisible: Basically, an old story asking whether an intelligent person would be moral if he did not
have to fear being caught and punished for doing injustices. In this tale, a shepherd finds a magical ring of invisibility. Using the
power of the ring, he seduces the queen and, with her help, murders the king and takes control of the realm. It is suggested that
if identical rings were given to a just man and an unjust man, then both men would act unjustly. It is postulated that people act
justly only under compulsion. By nature, all living beings desire more than what they are actually due. Despite this, someone
might decline to use the ring to perform misdeeds.
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