India Ethical Clinical

Project Description

Trials and Errors! Clinical Research in India; Ethical issues and Challenges!

India has become a strong hub for Clinical Research in recent years. This trend is quite strong and evident in the past few years and estimates show that the trend will continue in an even stronger manner with many more pharmaceuticals firms and Contract Research Organizations (CROs) setting up their bases and labs in India. There are many reasons for this phenomenon. These include

conducting trials at a fraction of the cost incurred in North America and Europe

Large patient pool for all the disease conditions the trials are done because of the 1.1 billion population.

Ease of patient recruitment at a much higher rate than in the developed world.

Regulatory laws and enforcements are less stringent than in the developed world.

Availability of English speaking and qualified personnel in all sectors and Phases of Clinical Research.

Quicker trial completion which again means that drugs can be marketed faster with less time lag.

However to become a global hub of Clinical Research, quite a few important ethical factors are also very important, which are not given that much importance and focus at the moment. These include the fact that

India lacks Investigators and personnel trained in Good Clinical Practices, which is essential for the Ethical conduct of Clinical Trials. Only less than 1000 investigators are trained and with current need is anything between 3000 and 6000.(1)This shows that at least 66% to 84% of trials are handled by Investigators who are not trained in Good Clinical Practice, a major bioethical issue. Most of clinical research can also be a nanoethical issue as many drugs studies involve the use of materials in the nanoparticle range.

Another important ethical issue is the practice of GCP by Investigators who are trained. Unfortunately quite a few of the trained investigators do not comply with Good Clinical Practices which have resulted in problems and controversies and also a major ethical issue for ongoing and future clinical trials.

Above mentioned are just the ethical issues with Good Clinical Practices for Investigators. There are also ethical issues with Informed Consent Processes,

Ethical Committees, Pharmaceutical Firms, Regulatory Authorities and subjects taking part in a Clinical Trial.

One of the major issues here is the Informed Consent Form or Informed Consent Document (ICF or ICD).The ICH GCP guidelines state in detail about the Informed Consent Form and Process. Most ICF are in accordance with the guidelines. But the problem lies with the consent process. Many patients who are enrolled in clinical trials in India are illiterate. There are many, though literate, with limited knowledge of the study that they are taking part in, though they have gone through the Informed Consent Form and signed it. In most cases even, the literate representative of the patient will not understand what the study is about, (though the ICF is supposed to be in a language understandable to laymen) and will ask the doctor to take a decision on their behalf.

There are also instances where trials are done without a copy ICFs being given to the patient. As per ICH GCP guidelines a signed copy of the ICF should be given to the patient for his information and reference. This is not done in many cases resulting in doubt and confusion in patients. The reason for some investigators in doing this is to avoid giving patient any supportive treatment if there is any side effect or reaction due to experimental treatment and to deny legal rights of the patient. In many trials and situations patients (obviously less educated or illiterate) were enrolled in clinical trials

Telling them that this is a “scheme” where you get free treatment if you sign a form

the (ICF) and give some blood or urine samples regularly for a certain period.

There are instances of “healthy competition” between investigators in recruiting patients the above mentioned way. In many cases the Pharmaceutical Firm or CRO running the trial are aware of this factor, but chose to turn a blind eye towards it. Their aim is unhindered and quick recruitment and completion of the trial and in the end marketing the approved products. There was even an incident when John Hopkins University was in hot water due to unethical conduct of Clinical Trials in India.(2) Patients also take undue advantage of investigators and firms at times for all their treatment needs (including their family) and if not obliged, withdrawing from trial. At times, investigators with recruitment targets will oblige to these unreasonable demands.

It is mentioned the in ICF that the patient can withdraw voluntarily at any stage of the Clinical trial without effecting the nature of care that the patient is receiving. But in usual practice, neither withdrawing voluntarily nor getting the same kind of care afterwards is possible. There are few Clinical Studies that were prematurely terminated as the data had shown no significant benefit from an earlier phase the trial. Then the all the patients included in the trial (including the one in the controlled arm getting approved drugs) will be deprived of treatment and drugs with almost immediate effect. Mostly this will be in such a way that the patients are stopped halfway in the course of treatment. The fact that the study has been terminated will be notified to the Ethics Committee as and regulatory authorities. These are some things common with many clinical trials and I had quite many experiences in this regard while I was handling Clinical Trials .Also I have noted that quite some clauses can be ambiguous and different pharmaceutical firms defining it to suit their advantage.

Ethical issues are there to be dealt with in the case of Ethics Committees also. In many cases the Ethics Committee will just accept and file the notification of termination (or in cases study closure) and will not be asking to cover the patient’s treatment till a particular cycle or course of treatment is completed. This inaction of the Ethics Committees is also an Ethical Issue. In most of the hospitals where clinical trials are conducted there is no regular Ethics Committee. There are many instances where the hospital or institutional purchase committee passes off for Ethics Committee. The principal investigator or co investigator being part of the Ethics Committee which approved the study is also a common occurrence (which is prohibited by ICH GCP guidelines.)

I am a Pharmacist with training and specialization in Clinical Pharmacy .I am also trained and certified in Advanced Ethics and GCP guidelines by GCP Alliance-Europe, Indian Council of Medical Research (ICMR), South Asian Cochrane Network and Fogarty International. I had worked with Cancer Clinical trials for 3 years as a Research Coordinator and Pharmacist in one of the leading hospitals in South Asia (Christian Medical College, Vellore www.cmcvellore.ac.in ).This was an opportunity to work in a non profit organization involved in the healing ministry in the spirit of Christ. I was involved with the conduct of clinical trials and also as the primary source for the flow of information between the Ethics Committee, Principal Investigator ,Regulatory authorities and Pharmaceutical firm or Contract Research Organization running the trial. I was also the responsible person for reporting the side effects (both serious and non serious and routine ones) to Ethics Committee and the Pharmaceutical firm running the trial. This had given me an insider knowledge and experience of clinical trials, both from the point of view of corporate, investigator, hospital, patient and Ethics Committee. I am now specializing in International Health. So my education, training and experience are relevant for my research on Ethical issues and challenges for clinical trials in India. The research topic is quite relevant as there is no study done in this field that I had come across. I plan to get new information and proof of the above mentioned issues and challenges which are mostly lacking now. My career interest is in Ethical Clinical Research and this topic is the right arena for me to use my knowledge, expertise and training. This, I believe will help in addressing Ethical Clinical Research which will be beneficial in better and safer treatment options in the future.

The initial thing will be collecting information from various sources like medical and bioethical, clinical research and business journals, databases, newspaper articles, portals of pharmaceutical firms, CROs, regulatory bodies, clinical trial registries etc. Primary information will be obtained by interviews and questionnaires from various people involved in all aspects of clinical trial. These include Principal and Co investigators, Ethics Committee members, Clinical Research Monitors from Pharmaceutical firms, CROs, Central labs etc, Research coordinators working in the hospital ,patients enrolled in a trial, about to be enrolled and formerly part of a trial and their relatives, journalists who had come across and reported and brought to light unethical clinical trial practices. Interviews and discussions will also be done with chaplains and pastors who are involved in the healing ministry and also in Ethics Committee. All category of members will be interviewed ,viz medical doctor, lawyer, chaplain, statistician, scientist, social worker, psychologist etc. Interviewees will be from my acquaintances and their colleagues and acquaintances from the above mentioned categories. Investigators and patients will be from various hospitals in India with varying facilities so that a cross sectional data is obtained. In this regard I plan to include hospitals and research facilities which are rated to be in the top, middle and lower sector in the country.

Reviews and analysis will be done by software tools like Review Manager and Statistical Package for the Social Sciences (SPSS).Data collection through interviews and questionnaires will approximately require six months in India. Before this the questionnaire and details of the interview will be finalized after discussion with my guide/supervisor allotted by the University.

By this study I plan to come across solid proof for some of the grave ethical issues and challenges. I also plan to come with some suggestions based on study findings. There may or may not be new ethical issues unearthed during my research. I am not expecting results of any particular kind, which will be a bias and hampering the quality of research.

Hence I plan to do the research with an open mind closed to bias!

Since this research project deals with the Ethical issues and challenges of Clinical Trials,the relevance will be to the Centre of Bioethics and Nanoethics. As the issue is about drugs, both bioethics and nanoethics will have a role. A time period of about six months will be needed for data collection in India. The exact details will be finalized after discussion with my guide/supervisor assigned.