Questionable ethics and confused regulation

Citalopram, an anti-depressant, was administered by Sun Pharma, on daily labourers as part of bioequivalence studies demanded by an importer. Some patients developed complications; one of them developed gangrene as well as renal complications.

Bioequivalence studies are done establish the therapeutic equivalence of a branded product and its generic (non-branded) version. In India there are no guidelines for bioequivalence studies. Guidelines of the WHO, USFDA and National Institutes of Health say that such studies should involve, in principle, adult, healthy volunteers. To what extent underfed volunteers can be called healthy is a moot question. Worse, it is not clear if they were adequately informed about what they were getting into.

A monograph on Citalopram says, “The possibility of a suicide attempt is inherent in depression and may persist until remission occurs. Therefore, high-risk patients should be closely supervised throughout therapy with Citalopram hydrobromide and consideration should be given to the possible need for hospitalisation. In order to minimise the opportunity for overdose, prescription for Citalopram should be written for the smallest quantity of drug consistent with good patient management.” Clearly giving Citalopram to ‘healthy’ people seems to present a risk. Giving it to underfed, poor people, seems to be an even worse choice.

The Sun Pharma company says the trial was part of Phase IV post-marketing surveillance (PMS). However, PMS is done on patients who have been prescribed the drug for the said condition.

The same monograph on Citalopram says that, “to date, no information is available on the pharmacokinetic or pharmacodynamic effects of citalopram in patients with severely reduced renal function.” Did the patients have a history of renal dysfunction? Did the company check?

A WHO guideline on bioequivalence studies reads, “Health monitoring, before, during and after the study must be carried out under the supervision of a qualified medical practitioner licensed in the jurisdiction in which the study is conducted.” The Sun Pharma medical director is quoted in the papers as saying ‘How can we be held responsible?’

The researchers claim to have taken informed consent. This is meaningless when the research subject is non-literate, poor and otherwise weak in bargaining power.

Sun Pharma claims to be subjecting every batch or export consignment to bioequivalence studies, albeit at the insistence of the importer. The guidelines do not mention such a practice which is both absurd and fraught with dangers.

Soon after this controversy, Sun Pharma advertised in the newspapers asking for volunteers for trials. Is the public entitled to know what these trials are for and which ethical guidelines are followed? If they are for bioequivalence will the Drug Controller explain why we need bioequivalence studies for every export consignment? If Parliament could pass a law for the right to information in public affairs for the country, what about the right of the public at large to know what kind of trials are going on, on whom and for what purpose?

The recent post-liberalisation hype is to project India as a favored destination for clinical trials. But our very advantages – a large population, genetic diversity and low costs – are compounded by poor or no regulatory laws and ignorance on research ethics and law among the public and even health professionals.

The application fee for phase I clinical trials will be Rs 50,000 and the fees for both phase II and phase III trials are just Rs 25,000 each. Many companies will of course get ‘informed consent’ from illiterate poor people who will be targeted with drugs known and unknown. Citalopram is just an indicator.