E-DRUG: Illegal drug trials in India
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The following editorial has appeared in the latest
issue of MIMS INDIA (Vol. 23, Number 12; December
2003)
Illegal trials on letrozole:
Hundreds of Women Used as Guinea Pigs
Over 430 unsuspecting young women have been used as
guinea pigs by self-styled researchers in India to
test if an anti-cancer drug Letrozole can be used to
induce ovulation. The clinical trials have been
conducted illegally without permission from the Drugs
Controller General, India (DCGI) predominantly at
private clinics not recognized as research centres. At
least one �investigator� with just a diploma in
gynaecology could hardly claim to be qualified or
competent enough to try untested drugs.
Curiously enough, based on documents submitted by
the innovator of the drug Novartis, both the U. S.
Food and Drug Administration (USFDA) and the British
Medicines and Healthcare products Regulatory Authority
(MHRA) have labelled Letrozole as embryotoxic,
fetotoxic and teratogenic at minuscule doses of
one-tenth to one-hundredth of human dose. The drug is
contraindicated for use in pre-menopausal women, the
sole candidates for infertility treatment. Its other
serious side effects include: ovarian tumours, liver
cancer, angina, myocardial infarction,
life-threatening pulmonary embolism, hemiparesis, loss
of libido and stroke.
Being an anti-cancer drug, letrozole belongs to
Schedule G of the Drugs and Cosmetics Rules and
therefore can only be sold against prescriptions from
cancer specialists. This warning is clearly printed on
every strip of the medicine. In violation of this
rule, unauthorised practitioners have been prescribing
and retailers selling the drug.
It may sound incredible but animals subjected to
experiments in the United States enjoy more protection
than human subjects in India. Any trial done on any
animal without permission from the Ethics Committee
carries a mandatory fine of Rs. 120,000 (US$ 2,500)
under Animal Welfare Act. In India, hundreds of young
women have been treated worse than animals in America.
When contacted, the �researchers� claimed that a
Mumbai-based company marketing letrozole had requested
them to undertake clinical trials. Unlawful trials
were conducted at the following places:
� Dr. Anoopkumar Gupta, at a private clinic called
�Delhi IVF Centre�. Number of women in the trial: 35
� Dr. Sadhna Patwardhan and Dr. Mangala Ketkar, at a
private clinic called �Nagpur Test Tube Baby Centre."
Number of women in the trial: 10.
� Dr. B. N. Chakrabarty at the Institute of
Reproductive Medicine, Kolkata. Number of women in the
trial: 45.
* Dr. Vandana Batra and Dr. Sanjay Makwana at a
private clinic called �Vasundhara Hospital & Fertility
Research Centre�, Jodhpur. Number of women in the
trial: 60.
� Dr. S. S. Chawla at District Hospital, Ajnala
(Amritsar Dist.). Number of women in the trial: 40.
� Dr. G. Padmasiri, at a private clinic called
Hyderabad Fertility and Research Centre. Number of
women in the trial: 111.
� Dr. Mandakini Parihar. Number of women in the trial:
not disclosed.
� Dr. Konkan Mitra, Dr. B.K.Mitra. Number of women in
the trial: 75.
� Dr. S. Krishna Kumar. Number of women in the trial:
59.
(Source: Booklet of Sun Pharmaceutical Industries Ltd,
Mumbai).
The "results" of these illicit trials have been
extensively used by pharmaceutical manufacturers to
illegally promote letrozole for ovulation induction.
As per ORG-MARG data, the annual sale of letrozole
exceeds Rs. 6 crores with a growth rate of 430 per
cent in the case of just one company alone.
Such illegal trials are conducted without any fear
because regulatory authorities, either by design or
default, fail to take suitable action. A couple of
years ago, totally untested new chemical entities
(NCEs) called M4N and G4N discovered in the United
States were unlawfully tested on 26 oral cancer
patients at the Regional Cancer Centre (RCC) in
Thiruvananthapuram. Under unrelenting pressure from
the media and NGOs, an unwilling Government was
literally dragged to take action. Instead of
penalizing the guilty, further research on untested
substances was temporarily suspended for six months.
The law provides for three months imprisonment for the
guilty.
All clinical trials in India require prior
permission from DCGI and approval by the concerned
Hospitals� Ethics Committees. Drug trials can only be
conducted at recognized centres by duly qualified and
experienced investigators
As per Section 122 (E) of the Drugs and Cosmetics
Rules, all drugs are considered new if they are to be
tested for an unapproved indication. Clinical trial of
�New Drugs� is governed by Schedule Y of the D&C
Rules. There are a large number of pre-conditions but
important ones are: submission of Protocol,
Investigator�s Brochure, Case Report Forms (CRFs),
draft of Informed Consent documents in English and
local language by the sponsor to DCGI to obtain
approval. Insurance or similar arrangement have to be
made to compensate patients in case of trial-related
injury including loss of wages and income.
Once DCGI approval is received, an application has
to be made to the Ethics Committee of the recognized
research hospital. Trials can begin only after the
Ethics Committee's permission is received. Patients
have to be specifically informed that they are being
subjected to a trial and there could be risks
involved. Their written consent is legally mandatory.
Progress reports on all clinical trials have to be
submitted periodically to the Ethics Committee and
finally to the DCGI.
Most of the clinical trials in India are conducted
without any arrangement for compensation in case of
study-related injury, disability or even death. Indian
Council of Medical Research (ICMR) Guidelines
specifically require that each research �shall include
in-built mechanism for compensation for the human
subjects�to cover all foreseeable and unforeseeable
risks.�
The investigators for clinical trials, particularly
when drugs are to be tested, are chosen by sponsoring
companies. Naturally, all manufacturers want that
their products should be found to be safe and
effective. There cannot be a better way to ensure
positive results than to select friendly, obliging and
ever willing investigators to do the bidding. Many
investigators that conduct clinical trials are, or
have been, beneficiaries of largesse from the
pharmaceutical manufacturers. The financial ties
include paid speaking engagements, shares of the
sponsoring companies, expensive gifts such as cars,
refrigerators, air conditioners, medical equipment,
attendance at sponsored scientific conferences, paid
consultancy work, authoring �ghostwritten� scientific
articles and travel grants for domestic and foreign
travel. Last year a Mumbai-based foreign company
marketing erythropoietin had obliged some 300 senior
most nephrologists to visit Singapore on an expense
paid jamboree, an effective strategy not only to
garner more prescriptions but ensure positive results
of future clinical trials.
Neither the regulatory authorities nor the Ethics
Committees seek conflict of interest information from
investigators.
Unless laws are fairly and firmly implemented, the
current unsupervised, unethical and often illegal
trials will pave the way for similar tests in gene
therapy that may leave many Indians diseased, deformed
or even dead.