Corrupt drug trials in India-- 42 trials, 49 deaths-- article

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Corrupt drug trials in India-- 42 trials, 49 deaths-- article

Exerpt: Asked whether India today offers a safer environment for

clinical drug studies, the lawyer leaned back and smiled. " Are you

talking about safety for the patient or the corporation? " he

asked. " For the corporation, it's 100 percent safe.

From: VERACARE <veracare@...>

Subject: Riveting Investigative Report: Drug Trials in India_Tampa Bay Times

" Infomail1@... " <Infomail1@...>

Date: Thursday, December 18, 2008, 10:01 AM

ALLIANCE FOR HUMAN RESEARCH PROTECTION

Promoting Openness, Full Disclosure, and Accountability

http://www.ahrp.org and http://ahrp.blogspot.com

FYI

For those who thought The Constant Gardener was a sensational work of

fiction....take a deep breath before reading a riveting investigative report by

Kris Hundley of the Tampa Bay Times, whose focus is clinical trials in India.

Quintiles, the world's largest contract research organization (CRO),

boasts of enrolling 50 patients with diabetes in one month in India

and 204 infants for a vaccine study in three days, far faster than

possible in the States. In a brochure, Quintiles sums up India's

allure: " It's practically a paradise for conducting clinical trials. "

The lure of India for pharmaceutical companies and the for-profit

CROs India is ideal because Life is cheap. Everybody wants a piece of an

industry estimated to top $1-billion by 2010. Thousands of English-speaking

doctors and millions of people suffering everything from exotic diseases to

ailments common in the West - diabetes,

cancer, heart disease. With two-thirds of the nation living on less

than $2 a day and health insurance rare, these patients are often

" treatment-naive, " presenting a clean slate to pharmaceutical

companies. An added bonus: suing doctors is almost unheard of in

India.

The testing milieu:

" Two hours after opening, the pediatric waiting room at All India

Institute of Medical Sciences is like the anteroom to hell. Families, anxious,

restless, sweaty in the soupy air, cram into plastic chairs,crouch in corners,

crowd doorways, clog up aisles. Cries jangle off the ceiling. Feces litter the

floor. Signs in the corridor attempt to impose order on the chaos: Don't spit.

Don't feed the monkeys. Don't pay bribes. "

It was revealed that since the beginning of 2006, the pediatric

department at the All India Institute had conducted 42 trials,

involving 4,142 children. Number of deaths: 49. News of the deaths

triggered unease about a drug-testing phenomenon, propelled by

mountains of money.

Dr. C.M. Gulhati, editor of an Indian medical journal, Monthly Index

of Medical Specialties, said authorities cannot cope with the tsunami of trials.

" India's drugs controller general's office is both understaffed and incompetent,

'' he said, citing a case where the agency claimed it reviewed an 800-page trial

protocol in just five days. " How is that even possible? "

Does it matter that the trials didn't meet scientific or ethical

standards? Does it matter that the data is likely corrupted?

Fraudulent clinical trial data is harder to detect off-shore-

particularly when that country has a reputation for cutting corners.

In India, cops execute suspected criminals in so called " encounters. "

Laws against selectively aborting female fetuses are ignored,

and " everyone pays bribes. "

Indeed, Dr. Arun Bhatt is president of Clininvent, a contract research

organization in Mumbai that is running 11 trials involving 1,000 patients. He

worries that Indian doctors ignore patients' reactions to experimental

medicines, missing critical clues about a drug's safety. " Most sites are not

used to recognizing serious adverse events, so they are underreported, '' said

with an attitude of resignation. " Either they don't recognize, don't realize or

are

afraid to report this information. "

In the past three years, FDA inspected exactly eight sites out of

thousands operating in India.

Americans are not entirely home free because FDA approval of

dangerous drugs tested under dubious uncontrolled conditions, where

no one can vouch for the integrity of the data, has resulted in the

marketing of lethal drugs that killed thousands of Americans.

" In the burgeoning clinical trial business, says Amar Jesani, a

doctor and medical ethicist in Mumbai, every layer of oversight is

compromised by cash, and independent monitoring is nonexistent. He

has resigned from supposedly independent ethics committees that

rubber-stamp drug companies' proposals and overrule any objections.

" We're sitting on a time bomb that may explode at any time. "

A lawyer who represented a victim of a cancer experiment conducted 8

years ago by a researcher from s Hopkins University, Asked

whether India today offers a safer environment for clinical drug

studies, the lawyer leaned back and smiled. " Are you talking about

safety for the patient or the corporation? " he asked. " For the

corporation, it's 100 percent safe. For the patient, that is a matter for study

and investigation. It's a sad situation here. "

See the video: http://www.tampabay.com/specials/2008/reports/india/

See: 49 Deaths raise questions in Indian hospital

http://www.tampabay.com/news/business/article934633.ece

Part II, OUR DRUGS, THEIR BODIES, will follow

Contact: Vera Hassner Sharav veracare@... 212-595-8974

http://www.tampabay.com/news/business/article934677.ece

TAMPA BAY TIMES

The latest industry being outsourced to India: clinical drug trials

By Kris Hundley, Times Staff Writer

Published Thursday, December 11, 2008 5:07 PM

NEW DELHI

Two hours after opening, the pediatric waiting room at All India Institute of

Medical Sciences is like the anteroom to hell. Families, anxious, restless,

sweaty in the soupy air, cram into plastic chairs, crouch in corners, crowd

doorways, clog up aisles. Cries jangle off the ceiling. Feces litter the floor.

Signs in the corridor attempt to impose order on the chaos:

Don't spit.

Don't feed the monkeys.

Don't pay bribes.

This overstretched government hospital and medical college treats about

4-million people a year. It's also one of a growing number of Indian hospitals

that use their patients to gather data on experimental drugs destined for

Western markets. It recently was revealed that 49 children have died during

clinical trials at the institute. Though the hospital blamed the deaths on

underlying illnesses, the news triggered unease about a drug-testing phenomenon,

propelled by mountains of money, that has swept India with little publicity. As

the world flattens, India is not just answering our tech calls. Global drug

companies are tapping its population of nearly 1.2-billion to test the safety

and effectiveness of compounds that, if approved, will end up in medicine

cabinets in the United States. The upshot: the distance has been compressed

between a patient trying a new diabetes drug in New Delhi and the retiree who

will buy that prescription in St. sburg.

" All the ingredients are there for a huge problem,'' said Dr. Ross, a

former FDA medical officer.

" First of all the data must be applicable to the U.S., where the population may

differ in clinically significant ways, " he said. " And the FDA has to have the

capacity to go over and inspect the data. If not, you're asking for trouble. "

In the past three years, the FDA has inspected just eight of the thousands of

trial sites in India.

Poor oversight invites problems in an overseas drug pipeline, as Americans

learned after deaths from Chinese-made blood thinners this year. In a rare

proactive move, the FDA slammed the door on 30 generic drugs from one of India's

biggest drug makers in September after finding problems at its factories.

K. Pendergast, a former FDA deputy commissioner, said identifying a

dangerous product is difficult enough. It's considerably trickier to find

fraudulent clinical trial data, which could lead to the approval of dangerous

drugs years later.

" It's much more time-consuming and extraordinarily tedious,'' said Pendergast,

who plowed through such data when she was prosecuting doctors doing drug studies

in the United States. " It's especially hard if the trial is taking place in a

different country. "

Particularly when that country has a reputation for cutting corners. In India,

cops execute suspected criminals in so-called " encounters. " Laws against

selectively aborting female fetuses are ignored. And those " No bribes " signs in

public hospitals? Bhupali Magare, whose uncle was recently hospitalized in

Mumbai, just shrugged.

" Everybody pays bribes, " she said.

In the burgeoning clinical trial business, says Amar Jesani, a doctor and

medical ethicist in Mumbai, every layer of oversight is compromised by cash, and

independent monitoring is nonexistent. He has resigned from supposedly

independent ethics committees that rubber-stamp drug companies' proposals and

overrule any objections.

Said Jesani: " We're sitting on a time bomb that may explode at any time. "

• • •

Drug makers spend hundreds of millions of dollars bringing a promising compound

to the stage where it can be tested on humans — only to be stymied when subjects

in developed countries are slow to sign up.

So the companies have moved offshore in search of subjects, and now nearly half

of all studies are conducted outside the United States. Brazil, Russia and China

have been popular trial locales, but India is moving up fast, aggressively

courting the drug study business.

Its pitch? Thousands of English-speaking doctors and millions of people

suffering everything from exotic diseases to ailments common in the West —

diabetes, cancer, heart disease. With two-thirds of the nation living on less

than $2 a day and health insurance rare, these patients are often

" treatment-naive, " presenting a clean slate to pharmaceutical companies. An

added bonus: suing doctors is almost unheard of in India.

Asif Iqbal brought his 61-year-old father from Kolkata (Calcutta) to Mumbai to

be treated for brain cancer. When the doctor said his father might live longer

if he enrolled in a clinical trial, Iqbal signed the forms though they were in

English, a language he does not understand.

" I surrendered to the doctor,'' Iqbal, 30, said through an interpreter, as he

pulled the unintelligible papers from a worn plastic bag. " I said, 'I am a lay

person, you are god to me.' ''

To accommodate pharmaceutical companies' needs, a cottage industry of site

managers and trial monitors has sprung up so rapidly no one can keep count of

the players.

Contract research organizations keep tabs on trials with regular audits. Site

management organizations put an extra set of eyes in the doctor's office. Both

entities dangle promises of FDA-ready studies in half the time, at 30 to 60

percent the cost in the United States. The secret? Cheap help and fast patient

recruiting.

Quintiles, the world's largest contract research organization, boasts of

enrolling 50 patients with diabetes in one month in India and 204 infants for a

vaccine study in three days, far faster than possible in the States. In a

brochure, Quintiles sums up India's allure: " It's practically a paradise for

conducting clinical trials. "

Everybody wants a piece of an industry estimated to top $1-billion by 2010. But

as a gold-rush mentality grips India's booming clinical trial business, even its

proponents are having second thoughts.

Dr. Arun Bhatt is president of Clininvent, a contract research organization in

Mumbai that is running 11 trials involving 1,000 patients. He worries that

Indian doctors ignore patients' reactions to experimental medicines, missing

critical clues about a drug's safety.

" Most sites are not used to recognizing serious adverse events, so they are

underreported,'' he said with an attitude of resignation. " Either they don't

recognize, don't realize or are afraid to report this information. "

Dr. Nandini Kumar retired in June as deputy director general of the Indian

Council of Medical Research, the equivalent of the U.S. National Institutes of

Health. She now works as a consultant for the agency in New Delhi, teaching

doctors how to run ethical trials. Kumar is stunned by their ignorance of

internationally recognized standards for conducting drug studies.

Asked what aspect of good clinical practice most surprised her students, the

gray-haired, sari-clad Kumar snapped, " Everything. "

" There are efforts to put rules in place, but at the same time there are people

who just want to get the extra dollars or perks like trips abroad from doing

drug trials,'' Kumar said as monsoon rains pounded outside her cramped office

and the power kept winking off. " My work is like a drop in the ocean. "

• • •

Though demand has far outstripped the country's supply of researchers and

monitors — a shortfall of up to 50,000 trained clinicians according to one

government report — that hasn't slowed the surge.

The number of registered clinical trials being conducted in India has nearly

doubled in the past year, to more than 800 ongoing or completed, according to

www.clinicaltrials.gov.

These studies are being conducted at massive public hospitals, like the All

India Institute of Medical Studies in Delhi, where doctors take on the extra

work despite a waiting room overrun with patients.

Trials are a lucrative sideline for private oncologists like Dr. Chiraq Desai,

who shares a modern office with five other doctors in the dusty northwestern

city of Ahmedabad. A year ago, Desai made a presentation to Pfizer executives in

New Jersey, touting a patient population in India that is " willing and

compliant. " Today he's running 20 trials on 67 subjects.

Dr. S.P. Kalantri has conducted trials for global pharma at the government

hospital in Sevagram, a small town in central India. But he said he has pulled

back from doing the studies.

" It's difficult to explain the complexities of trials to study participants,''

Kalantri said of the hospital's mostly poor, illiterate patients. " I think many

investigators tend to take their patients for a ride. And there's an abysmal

lack of know-how about clinical research among investigators. "

• • •

On the ground in India, it is impossible to find anyone running, monitoring or

auditing clinical trials who is not on the payroll of the drug makers.

Doctors are paid according to the number of patients they enroll. Local ethics

boards, set up to ensure patient safety, are often comprised of colleagues who

approve each others' projects and blackball naysayers.

C.J. Shishoo, former dean of India's oldest pharmacy college, runs an

independent ethics committee in Ahmedabad. He lost the business of two big

clients when he objected to how they were running their studies.

" They just went elsewhere,'' Shishoo said of the drug companies he alienated.

" I'm very much concerned. Life here is a little cheap. "

Shishoo was not surprised to hear of the offer made to Afsar Khan, a motorcycle

mechanic in Mumbai. Khan and his uncle were told that a new drug from America

could cure their diabetes, but it would cost them each 100,000 rupees (about

$2,000). Unable to pay, the men walked away. A few weeks later they got a much

different offer: Try the drug and we'll pay you 25,000 rupees ($500).

" That made us suspicious, so we backed away,'' said Khan, who makes about 6,000

rupees ($120) a month. Unable to afford Western drugs for his diabetes, Khan,

46, is now treated by a hakim, a practitioner of traditional Islamic medicine,

at his mosque. " I have blackouts and pain in my knees, " he said. " But I can live

with it. "

Government regulators on both sides of the globe are supposed to be the final

backstop on the safety of clinical trials. But that hasn't happened in India.

Despite being stung by controversies involving the testing behind drugs like

Vioxx, Avandia and popular antidepressants, the FDA inspects fewer than 1

percent of all drug trials in the United States. Its record overseas is even

worse.

DiFrancesco, an FDA spokesman, said the agency puts no cap on the

percent of patient data that can be submitted for drug approval from a single

country, despite its inability to keep an eye on the process. The FDA hopes to

open offices in New Delhi and perhaps Mumbai by year-end, he said.

India's top drug regulator, Dr. Surinder Singh, said the FDA is training 24

Indian officials to conduct random audits of trial sites, to begin as soon as

this month. His predecessors made similar promises of imminent inspections,

which went unfulfilled, in 2006 and again in 2007.

Singh, India's drugs controller general, has rolled out the welcome mat for

foreign drug companies, promising to review applications in two to six weeks and

push his ossified operation, as he put it, " from the Stone Age to the Clone

Age. "

As proof of his commitment, Singh said recently he will remove restrictions

prohibiting foreign companies from conducting Phase I, or first-in-human,

studies in India. That announcement caused pause even among those who could

profit from the business.

" We are not ready to do Phase I trials of global quality yet,'' said

Clininvent's Bhatt. " They are very risky. We should not rush into them. "

Dr. C.M. Gulhati, editor of an Indian medical journal, Monthly Index of Medical

Specialties, said authorities cannot cope with the tsunami of trials.

" India's drugs controller general's office is both understaffed and

incompetent,'' he said, citing a case where the agency claimed it reviewed an

800-page trial protocol in just five days. " How is that even possible? "

Gulhati, who fights unbridled drug testing from a dim and cluttered office above

a busy Delhi shopping plaza, reeled off a litany of troubled trials:

In 2003 in Hyderabad, an unregistered study of a heart attack drug that resulted

in six deaths.

In 2004 in Delhi, a first-in-human trial of a new suturing device on 13 patients

without regulators' approval.

Last year, India's decision to become the only nation to allow domestic drug

maker Sun Pharmaceutical Industries to market the anticancer drug Letrozole for

infertility in women despite the drug's originator, Novartis, warning that it

may cause fetal harm and should be used only in postmenopausal women.

And in October in Bangalore, the death of a baby during the testing of a new

Wyeth vaccine.

" It's a total farce, " said Gulhati, who could not think of a single case of an

Indian doctor disciplined for mishandling a trial. " When I complain people have

broken the law, they ask 'What harm have I done?' "

• • •

One well-known scandal occurred about eight years ago, when a s Hopkins

University researcher injected an untested chemical in 27 patients at a public

cancer hospital in the southern state of Kerala.

Lawyer Panikangulara represented an illiterate coolie laborer with

throat cancer who unknowingly enrolled in the trial after signing a form in a

language he did not understand. India's court dismissed his claim of a human

rights violation, citing a statute of limitations of one year from the time of

the injection. By the time the court ruled, the patient was dead.

" There was an institutional commitment to protect other institutions at the

expense of the rights of individuals, " Panikangulara said. " The question of

human rights violation was never even on the agenda. "

Asked whether India today offers a safer environment for clinical drug studies,

the lawyer leaned back and smiled.

" Are you talking about safety for the patient or the corporation? " he asked.

" For the corporation, it's 100 percent safe. For the patient, that is a matter

for study and investigation. It's a sad situation here. "

Kris Hundley can be reached at hundley@... or (727) 892-2996.