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Acts and omissions: What should we do about human research in India?

Gagandeep Kang,


Quite frankly, I was horrified when I read in The Hindu that in castigating the government regarding its approval and oversight of clinical trials in India earlier this year, one of the Supreme Court justices had made a remark along of the lines of “Show me what will happen if I stop all clinical trials in India now, nothing will change”.

Of course, the Court was correct in pointing out that clinical trials need to be ethical and conducted to the highest standards, ensuring the rights and well-being of study participants—a responsibility that we are repeatedly informed is overlooked by multi-national companies and contract research organizations. Of course, we have a moral obligation to protect the vulnerable and to exclude those who can not make an informed and considered decision to participate, to deny no one the best standard of care, to maximize risk and minimize harm.

But the fact that the highest bench in the land, considering a matter that is so fundamental to the advancement of human health, could make such a comment, set me thinking.

Most ethicists think that we have a greater moral responsibility for the things we do than for the things we fail to do; i.e. that it is morally worse to do harm by doing something than to do harm by not doing something. Acts are more important than omissions.

For example: we think that the person who deliberately pushes a person in front of a car has done something much more wrong than the person who refuses to pull a poorly sighted person away from walking across a busy road.

In the human experiment context, if the experiment takes place, it is possible that the experimenter will carry out actions that harm the humans involved.

If the experiment does not take place the experimenter will not have done anything. This may cause harm to human beings because they will not benefit from a cure for their disease because the cure will not be developed.

The Supreme Court appears to believe the acts and omissions argument. But is this appropriate?

There are several points to consider related to this issue. For example, is it fair for Indians to reap the benefits of drugs that have been evaluated and proven to be effective in other populations elsewhere in the world, if we are not willing ourselves to be ‘guinea pigs’ for new drugs?

If experimentation on humans is not allowed, then can no doctor ever tweak a dose for a specific patient, because the recommended dose has been defined by a drug company? Will no new surgical technique ever be developed? No new or improved devices? Pacemakers or painless injections?

Experimenting on humans is not to be taken lightly, but civil society, regulators and the judiciary do more harm than good when they tar investigator-initiated research with the same brush that they use for big pharma.

Medical investigators in India, of which there are a handful, aim at addressing questions of local importance first, even when sited in a global context. Whether the research is observational, to describe a phenomenon or develop a hypothesis or experimental, to test an intervention, the goal always is to improve the lives of Indians by finding better/cheaper/less toxic ways to prevent or cure disease.

 

I spent ten years following 400 children from before they were born (we recruited the mothers) until they reached three years of age, making sure that we captured every illness in every child and collecting almost 45,000 stool samples and thousands of blood samples (never more than 2 ml), in order to understand what happened in Indian children with rotavirus infection. Rotavirus causes severe diarrhea in children. Oral vaccines were being developed and working wonderfully in America and Europe. Based on what we were finding (took us 3 years to analyse the samples), we knew that the vaccines were not going to be as good in India, but we knew that even with a lower efficacy the vaccines could have a huge effect on disease because our burden of diarrhoeal disease is so high.

Based on what we had found it was a natural next step to participate as one of three sites in a phase III vaccine trial for an Indian vaccine, a truly remarkable Indian led partnership where a vaccine based on a Indian strain was taken through early development through a strong Indo-US partnership and then tested in phase I, Phase II and Phase III in India as a public-private partnership. Children in the study were intensively monitored, had 24 hour access to study physicians and to transport to referral facilities. This was to the extent that we then became just a little worried that we not be able to measure the effect of the vaccine because the children would not get sick since our obsessive-compulsive research team was making sure the children were referred and seen and not because of the vaccine intended to prevent disease!

Nonetheless, we were committed to making sure that children were looked after--we gave them direct medical benefits, resulting in family savings and in much lower rates of death than background rates in young children in the same localities and this intensive collaborative effort resulted in an affordable indigenously manufactured product.

In one sense, the children who participated in our study, were guinea pigs, but no child died or was harmed by participation in the trial and we have a product that has the potential to save 40,000 Indian children’s lives annually. Should we not have done this?

Where does our responsibility lie? Would it have been ethical not to do anything about this? Is it ethical to promote products in India when we do not know whether they work here? And I mean really work…not a ‘bridging’ study that measures a surrogate marker.

 

There is much subjectivity in physician management of disease as widely practiced today. As academic medical professionals it is our responsibility to base treatment and prevention on clear evidence of efficacy. Human beings are so heterogenous in their responses to drugs and treatments that testing in one or a limited number of groups of people is not sufficient to prove that one product will work equally well in everyone.

For India, it is our responsibility to support innovation and generate the evidence we need to advance medical science. In human research, we need action, not omission.

Gagandeep Kang

GK is a professor in the Department of Gastrointestinal Sciences at the Christian Medical College (CMC) in Vellore, India. Dr. Kang’s research focuses on enteric infections in children. She has worked to determine modes of transmission and assess immune responses to design effective interventions for addressing enteric infections in children.

 

Professor Kang does not agree that we have a greater moral

Professor Kang does not agree that we have a greater moral responsibility for the things we do than for the things we fail to do.

He feels that  the person who does not pull a poorly sighted person away from walking across a busy road is as guilty as one who pushes a poorly sighted person in front of an oncoming car. This logic is impossible for ordinary men like me to fathom.

There is more: He asks "is it fair for Indians to reap the benefits of drugs that have been evaluated and proven to be effective in other populations elsewhere in the world, if we are not willing ourselves to be ‘guinea pigs’ for new drugs?"

Please note that this is a medical researcher speaking. He feels Indians must become his guinea pigs, before he extends to them the benefits of what has been researched overseas. The courts have found that numerous 'guinea pigs' in India were made to participate in trials without their consent and when they died of horrific adverse events, they received no compensation nor even medical care. The consent process for the trial of HPV on tribal girls is a documented example of how these trials are done.

From there, Professor Kang goes on to defend the rotavirus trial. But he lets his team down with two very revealing sentences.

The first admits that the vaccine has very poor efficacy in India. I quote him below

"Based on what we were finding (took us 3 years to analyse the samples), we knew that the vaccines were not going to be as good in India"

The second

"Children in the study were intensively monitored, had 24 hour access to study physicians and to transport to referral facilities. This was to the extent that we then became just a little worried that we not be able to measure the effect of the vaccine because the children would not get sick since our obsessive-compulsive research team was making sure the children were referred and seen and not because of the vaccine intended to prevent disease"

It is to be remembered that this is a blinded placebo controlled trial. The measured end point was rotavirus diarrhea. If any child has diarrhea the stool is tested and the child referred. So why was the Professor worried that the effect of the vaccine would not be measurable "because the children would not get sick since our obsessive-compulsive research team was making sure the children were referred"?

This is indeed a very interesting commentary on our researchers. With such researchers around, I am happy the courts have taken the side of the ‘guinea pigs’.

 




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