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

[Guest guest]

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.

Subject: Riveting Investigative Report: Drug Trials in India_Tampa

Bay Times

To: " Infomail1ahrp (DOT) org "

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@...

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 .

About these stories

Times staff writer Kris Hundley spent three weeks this fall in India

on a

World Affairs Journalism Fellowship administered by the International

Center

for Journalists. The fellowship is sponsored by the Ethics and

Excellence in

Journalism Foundation. Hundley was one of eight journalists from

around the

country to be awarded a 2008 World Affairs Fellowship.

Her proposal to research drug testing in India stemmed from several

stories

she wrote on U.S. clinical trials in the St. sburg Times in

2007. For

more information on that series, written with Times staff writer Rob

Farley,

see links.tampabay.com.

What they're saying:

Dr. Nandini Kumar, former deputy director general of the Indian

Council of

Medical Research in New Delhi: " I am not very confident right now

about

how

ethically it (a trial) would be conducted. "

Dr. Chirag Desai, oncologist in Ahmedabad, who is conducting 20

trials:

" There is pressure from the pharma industry for doing things. Until

Indian

regulators, investigators and ethics committees mature, possibly the

patients are vulnerable. "

Dr. Vinod K. , head of pediatrics at All India Institute of

Medical

Sciences, New Delhi: " There is money-driven research, with private

doctors

who receive 100,000 rupees ($2,000) for each patient they get. "

Y.K. Sapru, retired executive director of & Ltd.

(India),

now chief executive of non-profit Cancer Patients Aid Association:

" Despite

all the credos which are written down in pharmaceutical company's

worldwide:

'We stick to honesty, we are all for god.' All that is bull----. The

manager

who follows that will lose his job ... and his bonus. "

Dr. S.P. Kalantri, a public hospital physician in Sevagram, a small

village

in central India: " We see 200 patients with snake bites every year and

lose

10 percent of them. We see 300 to 400 pesticide poisonings (attempted

suicides) and we lose 20 percent of them. The drugs and treatments

for both

are fairly expensive. But no one seems interested in these problems. "

Veena Jaguste, director of development operations in Mumbai for

Amgen, which

is conducting nine trials in India with 300 patients: " For a well-

managed

study (the data is) as good or in some cases maybe even better (than

from

U.S. studies). "

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