Bulletin of the World Health Organization

Clinical trials without ethical review under the spotlight

26 March 2004

A recent series of unethical, and in some cases illegal, clinical trials in India is fuelling concern over the incidence of clinical trials conducted without ethical approval in other countries where legislation may be either inadequate or not implemented.

In a series of articles last year, Dr Chandra Gulhati, editor of an independent pharmaceuticals journal, the Monthly Index of Medical Specialities in India, shed light on the illegal trials and illegal promotion of the anti-cancer drug, Letrozole, as a fertility drug in India.

More than 400 women, who had been trying in vain to conceive, were enrolled without their knowledge or consent to take part in clinical trials across India to see if the drug induced ovulation.

The drug was a copy of a patented Novartis product, Letrozole by Mumbaibased generics firm, Sun Pharmaceuticals. The women were under the impression they were receiving expensive fertility treatment.

Letrozole has been approved globally for the treatment of breast cancer in post-menopausal women, but it is not approved for any other use in any country, including India.

Since then, India has seen a huge public outcry over the regulatory authorities’ failure to crack down on a recent series of illegal and legal, but unethical clinical trials.

A Delhi-based nongovernmental organization is filing a complaint about the Letrozole case to India’s Supreme Court and last month, the Indian Government pledged to push through tougher, more effective legislation to tackle the problem this year.

Dr Gulhati contends that although the company and doctors who carried out the tests broke the law no one has been put under criminal investigation by the Indian authorities.

The Letrozole trials are a shocking example of a widespread global phenomenon. A recent survey of more than 200 health researchers concluded that a quarter of clinical trials conducted in developing countries do not undergo ethical review. The survey was commissioned by the former US National Bioethics Advisory Commission and published in February’s edition of the Journal of Medical Ethics (Journal of Medical Ethics 2004;30:68-72).

John Williams, director of the ethics section of the World Medical Association in Paris, said drug approval agencies in developed countries such as the US Food and Drug Administration and EMEA (European Agency for the Evaluation of Medicinal Products) require ethics committee approval of trials for the sale and distribution of any drug.

“These are strong incentives to seek such approval,” Professor Williams said, adding that editors of major journals also require such approval for studies submitted for publication.