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 For two years, Prakash participated in trials of drugs being tested
to treat HIV/AIDS and other diseases for contract research
organizations (CROs) hired by global pharmaceutical companies. The
drugs tested at Indian CROs have been key in getting several hundred
medicines approved for sale around the world.
Yet, Prakash did not follow international guidelines for testing –
and the CROs that hired him didn’t require him to. He says that to
earn more money he would participate in back-to-back trials on
different drugs with gaps of only a few weeks or even a few days,
instead of waiting the 90 days that the World Health Organization
recommends.
Half of more than a dozen volunteers interviewed by Reuters across
four cities - Chennai, Hyderabad, Bengaluru, and New Delhi - also
said they waited much less than 90 days between trials. In the past
three-to-four years, they said they spent several months at a time
in different cities so that they could participate in as many
studies as possible.
Prakash provided documentation proving he underwent trials with
short gaps at Apotex Research Pvt Ltd, owned by Canadian drugmaker
Apotex Inc; Lotus Labs, owned by U.S. generics giant Actavis; Ethics
Bio Lab, owned since last year by U.S. drugmaker Par Pharmaceutical
Inc; and India’s Semler Research Center Pvt Ltd, among others.
Ethics Bio and Apotex did not respond to requests for comment. Lotus
Labs and Semler said they had systems in place to check for
cross-participation by trial volunteers.
The guidelines of the WHO, which decides on approvals for drugs sold
in several countries dependent on United Nations programs for basic
medicines, are not legally-binding for the CROs. While India has
guidelines on clinical trials, they don’t specify the length of time
participants should take between trials.
Still, the serial testing of some volunteers is raising new
questions about the level of oversight of India’s generic drug
trials industry, after some CROs came under recent international
regulatory scrutiny. Last year, the European Medicines Agency banned
about 700 medicines across Europe after an investigation revealed
data tampering in some trials of generic drugs in India.
International medical experts said that undergoing back-to-back
trials endangers the health of patients participating. It can also
compromise clinical data gathered through these trials, on the basis
of which drugmakers seek approval to sell generic medicines around
the world.
“The time gap between participation in two different trials should
be 90 days minimum,” said Stephanie Croft, a lead inspector at the
WHO. “When [data] is incomplete or incorrect it could pose a serious
risk to patients.”
Gyanendra Nath Singh, head of India’s national drug watchdog, the
Central Drugs Standard Control Organization (CDSCO), said that it
has been trying to inspect more CROs in the past two years. The
watchdog is also considering the introduction of a track-and-trace
system through which patients can be tracked across CROs, he told
Reuters.
“We are emphasizing on good regulatory practices … some reports have
shown that the CROs have deviated from (the) system,” said Singh.
India's Health Ministry did not respond to requests for comment.
GLOBAL REACH
Several large international drugmakers, including Teva
Pharmaceutical Industries Ltd and Mylan NV, rely on CROs in India to
carry out tests on cheaper versions of branded drugs. The aim of
these so-called “bioequivalence” studies is to gauge whether
non-branded drugs are equally safe and effective. The faster the
trials are undertaken, the faster the drugs can come to market.
In some major markets, such as the United States, being the first to
launch a generic guarantees market exclusivity for a period of time,
which can reap millions more in sales.
International and local regulators have struggled to keep its
oversight in line with the growth of an industry that expanded
rapidly in the 2000s, as drugmakers shipped clinical trial work to
India to save money. The market is estimated to have crossed $1
billion in 2016, according to consultants Frost and Sullivan.
Over the past two years, international regulators have suspended or
banned medicines tested by four major Indian CROs after finding
manipulation of clinical trial data and other violations.
Issues found at Indian CROs are "a big problem that is gaining more
and more attention from all sorts of agencies," said Anders Fuglsang,
a consultant and former regulator long involved in audits and
inspections of CROs around the world on behalf of international
regulatory agencies and companies.
Last year, the European Union banned about 700 medicines that had
been approved based on clinical trial data provided by GVK
Biosciences, then India’s largest CRO. European regulators said they
found GVK had manipulated data concerning the heart readings of
patients taking part in the study. GVK denied any violation, but
several large drugmakers that had won drug approvals based on GVK’s
data were asked to re-apply for approval with fresh evidence.
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Such re-testing is a headache for drugmakers, as it is expensive,
and delays lead to a loss in sales, said Nilesh Gupta, managing
director of India’s Lupin Ltd, which was one of the companies to be
affected by a U.S. ban on trials by Semler earlier this year.
GVK, part of the Indian conglomerate GVK Group, has since limited
its business interests in the generic drugs testing business, said
Shankar Chelluri, a spokesman for the company. Overall, sentiment
toward the generic drug trials business is weak, Chelluri said.
Another CRO, Quest Life Sciences, was found last year to have
manipulated clinical data on certain trials, according to inspection
reports from the WHO and the UK’s medicines authority. The Spanish
and German regulators had also found problems with Quest’s trials,
and the WHO said it found Quest had falsified data on drugs
including the antibiotic doxycycline hyclate and HIV/AIDS drugs
lamivudine, zidovudine and nevirapine.
Quest managing director T.S. Jaishankar said his CRO, which has
conducted dozens of generic drug trials for companies including
India's top drugmaker Sun Pharmaceutical Industries, has since
invested heavily in improving its systems and been cleared by all
international regulators. In a response to Reuters, a spokeswoman
for the European Medicines Agency said they were “closely
monitoring” the involvement of Quest in the drug approval
applications they receive.
India, like other countries, has ethics committees - groups of
independent experts - meant to approve the design and conduct of
clinical trials. Their stamp of approval is required by foreign
regulators considering allowing a generic drug to be sold. However,
these committees depend on the CROs for reimbursement in exchange
for reviewing trials. Three members of different committees Reuters
spoke to said national guidelines did not clearly define their roles
and responsibilities.
In the wake of trial data manipulation scandals at CROs in the past
three years, many large drugmakers including Swiss firm Novartis,
have been shifting more critical trials back to the United States
and Europe, according to consultants and industry executives.
Novartis is also ramping up its own checks of Indian CROs, said Bodo
Lutz, a data integrity officer at the Swiss firm. Speaking on the
sidelines of a conference in Hyderabad in July, he said: "We can't
rely on the regulators ... we're increasing our own audits."
VOLUNTEERING "LIKE AN ADDICTION"
Prakash, the former mechanic, said he was never asked by CROs, and
their ‘agents’ who approached him for studies, about whether he had
recently taken part in another trial.
"Everybody does it. Once you start getting the money, it's very hard
to quit. It's like an addiction," said Prakash.
He said after the first study, he began to regularly receive
messages on his phone and Facebook, often from agents working on
behalf of CROs, informing him about ongoing clinical trials where
volunteers were required. Such messages included three key things:
the city where the trial was being conducted, the total pay offered,
and the “blood loss”, or the amount of blood the volunteer will need
to provide.
Venkatesh, from the southern city of Tirupathi, described traveling
from Chennai to Hyderabad and then to Bangalore and Mangaluru for
different trials.
"I know of several people who participate in three or four trials in
the same month," said Venkatesh, who stopped volunteering two months
ago and has since married. He did not want to be referred to by his
full name.
Prakash said he was paid 10,000-30,000 rupees ($147-$441) per trial,
depending on the duration and type. He stopped participating after
his health began to deteriorate last year at age 25.
He now works at a call center earning 20,000 rupees a month, but,
despite knowing the risks, entered two more trials recently to raise
cash.
"I needed some money desperately so I did it, but I won't do it
again," he said.
(Additional reporting by Aditya Kalra in New Delhi; Editing by
Martin Howell)
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