Thursday, August 23, 2012

Up to January, 2061 Clinical Trial Deaths

Clinical trials, or clinical errors?

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Compensation for adverse impacts should not be positively linked to income levels. — M.A. Sriram
Compensation for adverse impacts should not be positively linked to income levels. — M.A. Sriram
The proposed compensation norms for clinical trial mishaps are topsy-turvy.
Over the last 20 years, India has become a leading supplier of finished formulations and bulk drugs to countries across the world, including the US. India concomitantly has become a destination for clinical trials. Doing clinical trials for others is now seen as a “business opportunity”.
How much business this really brings, or how much research capability in India it promotes are valid questions. But concerns have risen by the actions of middlemen and contract research organisations (CROs), and persons, such as medical-college faculties, who conduct the research on behalf of big pharma. There are issues of accountability here. And these come to the surface when things go awry.
An RTI petition has revealed that during the 49-month period ending January, there were 2,061 clinical trial-related deaths. And only 22 were compensated. As it is official data, one can safely assume the number of deaths is a conservative figure.
One does not know about the figures for long-term damages caused to trial participants who continue to live, or their conditions thereafter — especially when the trial participants are poor, illiterate and/or tribal, which is usually the case. What should be the compensation given to such participants?


After much pressure from public health experts and concerned citizens including members of Parliament, the Central Drugs Standard Control Organisation has come out with draft guidelines for comments (“Guidelines for determining quantum of financial compensation to be paid in case of clinical trial related injury or death” dated August 3). The positive aspect of these draft guidelines is that the Government appears to have acknowledged that the affected participants and their families deserve some compensation; this is over and above any expenses incurred in the medical treatment of the participant. But unfortunately, the positive aspects end here.
We point out a few problems with the guidelines below.
Para 5 says: “In case of clinical trial related injury the trial subject shall be entitled for financial compensation as per the recommendations of the Ethics Committee.” This is problematic, as ethics committees are known to have conflicts of interest. In all cases, however, affected persons need to have access to appeal to a statutorily constituted authority, in case they disagree with the ethics committee.
For assessing compensation in the case of trial-related injury or death, the draft guidelines propose three parameters to be taken into consideration: age of the deceased; income of the deceased; and seriousness and severity of the disease of the subjects at the time of the trial. And it then goes on to give a formula.


In the formula, the first factor is Factor A, which is to be 50-60 per cent of the income of the affected person — which means the better-off get more compensation than the poor.
This is to be multiplied by a factor B — given in a separate annexure. This multiplier starts with 228.4 for age 16 years and decreases to 99.37 for 65 years and more. This second factor has the effect of awarding more compensation to younger persons; and those whose life is disrupted by the clinical trial — say age 40 years with two children — will get less than a 16-year old youth. Factor A times B determines the compensation for healthy subjects in rupees.
For a 16-year old healthy person earning, say, Rs 5,000 a month, if he dies his dependents will get a maximum of Rs 5.71 lakh and if he lives he will get Rs 6.85 lakh — that is if you survive, you will get more.
There is nothing specified in the guidelines as to how compensation will be calculated if the affected are children and/or unpaid working women who are also homemakers. If women are poor, they are likely to be doing a greater amount of unpaid productive labour than, say, middle-class women.
If one such woman dies, her family will get nothing for the disruption to their lives. Also, compensation in the case of the trial affecting pregnancy and/or in utero children, or children of subsequent generations, is not even discussed. Nor is one clear what happens to persons below 16 years — will they get nothing or the same as a 16-year-old?


Further, there is a multiplier in the formula for compensation for the diseased — a risk factor F which is zero for healthy persons and 100 for fatality. The actual multiplier is (1-F/100) and the compensation for the diseased will be A times B times (1-F/100).
The last factor is one minus one hundredth of the risk factor F. So this means healthy persons get more compensation and if my risk factor is 50, my compensation will be half of the healthy person. There is also nothing specified in the guidelines how the risk factor will be calculated, except that the risk factor will be determined by the investigator — to reiterate, not even the ethics committee, but the kindness and objectivity of the investigator of the trial!
Nor do the guidelines stop there. If there is a disability as a result of the trial, the above compensation formula will be now A times B times (1-F/100) times D/100, where D is the “disability percentage”.
For people who are not challenged by algebra, this should mean that the greater the disability, the greater the factor D, and that means a 50 per cent disability person should get less compensation than a 50 per cent-at-risk diseased person, and who in turn should get less than a healthy person affected by the trial. One would think in a sane world, it ought to be the other way around.


The algebra confounds common sense. We would like to believe it was a genuine mistake in drafting the guidelines and not a deliberate intent to discount the tribulations caused to trial participants. We would suggest that a base figure of Rs 10-15 lakh compensation should be given to anybody affected, irrespective of productive capacity; and compensation should be paid regardless of the participant’s ability to prove that the medicine being researched, or the researcher’s negligence, caused the damage (like in Australian guidelines).
Compensation should be least for the healthy participant with minor adverse effects. It should be more for the diseased, and most for the diseased and/or completely disabled, and the dead. Women whose productive/reproductive capacity is affected should be clearly compensated as also children who willy-nilly are made participants, as also children of the coming generation (think of the DES babies and the thalidomide children).
These guidelines give the impression of being hastily put together. They need more application of thought --- and heart.
(The author is associated with Locost, Vadodara, and All India Drug Action Network.)
(This article was published on August 22, 2012)

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