#India – Cost of cancer treatment could drop to Rs 1,000 a month #goodnews #Health



Author(s):
Akshay Deshmane
Issue Date:
2013-6-7

Tata Memorial Hospital’s preliminary studies of combination therapy prove successful; clinical trials to begin soon

Treatment for cancer may become far more affordable and cost less than Rs 1,000 per month in coming years, if an ongoing research project at the Tata Memorial Hospital in Mumbai is successful. The treatment currently being researched combines low dosage metronomic therapy—administration of chemotherapy at low, minimally toxic doses every day –with drug repositioning, which is the use of low cost drugs usually administered for ailments other than cancer.

The treatment of the commonest form of cancer in India – head and neck cancer– usually costs between Rs. 15,000-20,000 a month. With the new form of drug therapy, a patient’s cost of treatment could be reduced to as low as Rs 500 per month, or even Rs 250 per month if the treatment is carried out at the Tata Memorial Hospital.

Testing efficacy

A review of the preliminary studies of the method which proved successful was published in the May issue of British medical journal Lancet. Researchers are now set to begin randomised clinical trials of the combined approach of treatment on patients with head and neck cancers from next month. Confirming the development, Shripad Banavali, head of medical oncology department at Tata Memorial Hospital, said the institutional review board of the hospital has recently given clearance to begin randomised trials on patients suffering from head and neck cancer.

“More than 400 patients suffering from head and neck cancer will undergo randomised trials over three years at the hospital, beginning next month. We are starting with this (type of cancer) as it is the commonest cancer in India. Once we conduct these trials, we will have conclusive evidence about the effectiveness of the therapy,” said Banavali.

The drugs Celicoxib and Methotrexate, usually used as anti-inflammatory drugs, are also considered useful in treating head and neck cancer. Low chemotherapy doses of these drugs will be administered on patients and their effects studied closely to gauge efficacy.

Drug repositioning

The current method of treatment of cancer is called maximum tolerated dose therapy. This involves administering heavy doses which target the tumour every three or four weeks. A gap between two doses is maintained to ensure that the patient has enough time to recover from the overwhelming effects of the treatment. This treatment, however, is very expensive and not widely available. In metronomic therapy, daily low doses are administered not only on the patient’s tumour but also in areas surrounding the tumour; the blood supply is cut off and resistance power of the body is increased.

The drug discovery system followed in the West involves making new inventions and discoveries for the treatment of ailments. However, this method does not solve the problem of affordability and access to treatment in most of those suffering from ailments. In our context, we need to follow drug re-positioning method, says Banavali.

“We use drugs which are already there in the market for treatment. Also, our effort is to ensure that the drugs are among those included in the World Health Organisation’s Essential Drugs list as they are not only cheap but affordable and available the world over,” adds Banavali.


 

#India – Clinical drug trials in Rajasthan claim 95 lives


STAFF REPORTER, tHE hINDU

291 cases of serious adverse events reported

Drug trials on humans in Rajasthan over the last eight years have claimed 95 lives, while 291 persons experienced serious adverse events, according to the State government’s latest deposition before the Supreme Court in an ongoing public interest litigation.

While informing the apex court of the figures, the Rajasthan government has sought to be made part of the overall monitoring and regulatory framework regarding clinical trials in order to protect the health of its citizens, deal with rogue trials and expedite the compensation process.

The 95 deaths include those caused due to the trials, besides deaths due to the natural history of the disease and other unrelated health events.

Four cases of death were deemed fit for compensation by sponsor companies out of which two had been compensated, while the process of compensating the other two was on.

This information was revealed in an affidavit submitted earlier this year by Rajasthan Chief Secretary C.K.Matthew to the Supreme Court, hearing a public interest litigation petition. A committee appointed by the state government came up with these figures after collecting data from 60 principal investigators regarding 213 clinical trials, conducted between 2005-2012.

However, the total number of deaths could be much higher as a total of 326 trials were conducted in Rajasthan during this period.

Some of the drugs for which trials were conducted include Talactoferril, Kremezin, Aliskirel, SU011248 (code name), Prasugrel and Clopidogrel.

In line with responses from other State governments in the case, the Rajasthan government too, has argued for higher powers to the States in the overall monitoring and regulatory framework regarding clinical trials.

“Certainly, the State government needs to be part of the whole process or else how are we to know what steps are to be taken [to deal with rogue trials],” Mr. Matthew told The Hindu .

In its deposition, a copy of which is with The Hindu , the Rajasthan government argued that while the Drugs and Cosmetic Act 1945 was a Central legislation, the State government was primarily responsible for the health of its citizens.

“The data would clearly reveal that sometimes clinical trials have significant adverse impact on the health of patients…existing rules need to be amended accordingly, especially with regard to immediate care for persons suffering SAEs and…with respect to compensation [in case of mortality],” the State government has argued.

It has also called for the strengthening of the existing framework “with sufficient safeguards…with penalties as well as adequate compensation”.

The government argued in favour of an online monitoring system for persons undergoing trials and a proper accreditation system for the selection of principal investigators in which the State government should have a role to play.

Since almost all Ethics Committees overseeing the propriety of the trial process are in-house bodies of sponsor hospitals of which Principal Investigators are also members, the government has called for Ethics Committees to be detached from trial sponsoring sites/institutes.

According to information submitted to the court by the Union Health Secretary in the case, a total of 2,644 deaths and 11,972 SAEs were reported during clinical trials in India between January 2005 and June 2012.

 


  • State government seeks higher powers in overall monitoring, regulatory framework
  • Government argues in favour of online monitoring system

 

MPs panel raps ministry for clearing 33 drugs without trials


New Delhi | Sunday, 2013 6:06:00 PM IST

Clinical Trials (journal)
Thirty-three new drugs were granted approval by the health ministry without clinical trials on Indian patients between January 2008 and October 2010, a parliamentary panel has found.

It a report tabled in parliament last week, the panel headed by parliament member Brajesh Pathak said: “This is yet another instance where the ministry, inspite of appreciating the serious problem the continued marketing of these 33 drugs may pose to Indian patients, has chosen to take no action to resolve it”.

The panel criticised the union health ministry for its “inaction” on certain alleged irregularities in clinical trials of drugs before their introduction in the country.

It also charged the officials involved in granting approval to these drugs with violation of law and “an intention to save the guilty”.

“The committee is shocked to note this dilly-dallying by the ministry on the matter, which could be affecting lives of lakhs of people in the country, who are consuming these drugs,” it said.

“The ministry agrees with the committee’s viewpoint about review of approvals to ensure safety of patients, fair play, transparency and accountability but instead of taking strict and immediate action in all proven cases of delinquency and omission and commission, it still continues to be in a state of profound procrastination,” the parliamentary standing committee on health and family welfare said in its 66th report.

It said that even after a lapse of more than seven months the three-member expert panel looking into this contentious matter has come out with “virtually nothing concrete” and observed that the government “intends to delay a decision by referring it to yet another committee”.

“These tactics have been, as stated at several places in this report, resorted to by the government to delay indefinitely the decisions and consequent actions that would be required to be taken against several officials and non-officials who have indulged in rampant acts of omission and commission while approving these drugs in gross violation of the law of the land.”

The committee has taken strong objections to these “dilatory tactics” and recommended immediate decision on these “proven gross violations, lest the health of the people is compromised irrevocably.”

Indo-Asian News Service spc/ros/vt

#India- Clinical Trials offer no security to clinical trial participants


 


Trial and error

Author(s):
Kundan Pandey
Issue Date:
2013-4-15

Recent notifications offer no security to clinical trial participants

Trial and errorVICTORIn the past eight years, 2,868 deaths have occurred during clinical drug trials across India. But only 89 have been attributed to such trials and compensation has been paid in 45 cases, said the Union health minister on March 5 in Parliament. Considering the Supreme Court’s recent observation that uncontrolled clinical trials “are causing havoc to human life”, Ghulam Nabi Azad’s speech only highlights the poor state of regulations for clinical drug trials.

To tighten guidelines for conducting these trials, the health minstry had amended the Drugs and Cosmetics Rules by passing three not ifications between January and Febr uary. The notifications specify procedures for compensation and functioning of the ethics committee, which is constituted by an institution conducting the trial.

Health activists say the notifications are rife with loopholes. The first one deals with compensation in case of injury or death during clinical trial but the onus of deciding the injury continues to be with those carrying out the trial. S Srinivasan of All India Drug Action Network says, “The notification does not define injury. How does one  prove that an injury is related to the trial? Who is the appellate body in case the compensation is not satisfactory?” Amar Jesani, editor of Indian Journal of Medical Ethics, says it is important that arbitration boards are created at local and regional levels to arbitrate on the quantum of compensation a provision that was present in the draft but is missing in the notification.

Claiming compensation continues to be difficult. As per the first notification, the Drugs Controller Gen eral of India (DCGI) will be the final authority to determine cause of injury and compensation amo unt. There is a provision that the victim, if not satisfied with the compensation decision, can approach the Centre. How ever, it is not clear which Central body should be approached. In the abs ence of an appellate body, the final auth ority should have been a neutral body, say activists.

The first notification ensures that compensation is received within six months. But what if the pharma company does not agree with DCGI’s decision? If it approaches a lower court, the decision could get prolonged indefinitely.

sordid<br />
tale” src=”<a href=http://www.downtoearth.org.in/dte/userfiles/images/20130415_21-table.jpg&#8221; width=”237″ height=”257″ align=”left” border=”1″ hspace=”5″ vspace=”5″ />Activists say since the majority of the participants in clinical trials are poor, there should be provision that the aggrieved party can promptly approach the resp ective high court. This will fast track the case.

In view of the complications in obtaining compensation, activists have long been demanding that in case a participant starts showing signs of an adverse effect he or she be immediately paid half of the compensation. Although the draft had met this demand, the final version makes no such mention. Srinivasan says the compensation model needs clarity (see http://www.downtoearth.org.in/content/clinical-trialsillogical-compensat… [1]).

Another sphere where government efforts have fallen short is in defining the role of ethics and expert committees in the third notification. Jesani, who has participated in many ethics committees, informs, “The notification on ethics committees is in response to the criticism that they are not registered with public authorities and there is no supervision over them.” The notification, however, does not satisfy on two counts. First, there is no information on how the Central Drugs Standard Control Organisation, which oversees pharma companies and clinical trials, will manage since it is short of staff and low on funds, says Jesani. Secondly, he says, unless all ethics committees adopt a uniform procedure for monitoring trials, their decisions would become arbitrary. “They also need to be independent of their institution’s interests.” Similarly, the third notification does not define the constitution of the expert committee, which is tasked to recommend quantum of compensation to DCGI in case of death. “On what basis will the expert committee recommend has also not been defined,” says Jesani.

 


 

#India 436 deaths recorded during clinical trials last year


 

New Delhi |  March 12, 2013 5:06:02 PM IST

 

A total of 436 deaths were recorded during clinical trials in India in 2012, parliament was told Tuesday.

While 438 deaths took place during clinical trials in 2011, 668 people died during 2010, Health Minister Ghulam Nabi Azad said told the Rajya Sabha in reply to a question.

Out of the 436 deaths in 2012, 16 were caused due to the clinical trials, he said. Rest of the deaths might have been disease-related in the cases of terminally ill patients suffering from cancer, cardio-vascular diseases and AIDS or due to side effects of drugs administered during the trial.

Azad said compensation is paid in cases of deaths and injury which are attributable to clinical trials.

The Drugs and Cosmetics Rules, 1945 have been amended specifying the procedures to analyse the reports of serious adverse events occurring during clinical trials and procedures for payment of compensation in case of trial related injury or death as per prescribed timelines, he added.

Indo-Asian News Service spc/vd/dg

 

 

 

Have #India’s poor become human guinea pigs? #clinicaltrials


By Sue Lloyd-RobertsBBC Newsnight

Narayan Survaiya and family
Narayan Survaiya’s mother Tizuja Bai died several weeks after being given new drugs

Drug companies are facing mounting pressure to investigate reports that new medicines are being tested on some of the poorest people in India without their knowledge.

“We were surprised,” Nitu Sodey recalls about taking her mother-in-law Chandrakala Bai to Maharaja Yeshwantrao Hospital in Indore in May 2009.

“We are low caste people and normally when we go to the hospital we are given a five rupee voucher, but the doctor said he would give us a foreign drug costing 125,000 rupees (£1,400).”

The pair had gone to the hospital, located in the biggest city in Madhya Pradesh, an impoverished province in central India, because Bai was experiencing chest pains.

Their status as Dalits – the bottom of the Hindu caste system, once known as Untouchables – meant that they were both accustomed to going to the back of the queue when they arrived and waiting many hours before seeing a doctor.


Nitu Sodey

This was really expensive treatment for the likes of us”

Nitu Sodey

But this time it was different and they were seen immediately.

“The doctor took the five rupee voucher given to BLPs [Below the Poverty Line] like us and said the rest would be paid for by a special government fund for poor people,” Sodey explains. “This was really expensive treatment for the likes of us.”

What Sodey says she did not know was that her mother-in-law was being enrolled in a drugs trial for the drug Tonapofylline, which was being tested by Biogen Idec. Neither could read and Sodey says she does not remember signing a consent form.

Bai suffered heart abnormalities after being given the trial drug. She was taken off it and discharged after a few days. Less than a month later, she suffered a cardiac arrest and died at the age of 45.

The trial, which was registered in the UK by Biogen Idec, was later halted due, say the company, to the number of seizures recorded. The company also says Bai’s death was not reported to them.

Her case is not an isolated incident.

In a different trial with a different company, Narayan Survaiya says neither he nor his late mother Tizuja Bai were asked if she wanted to participate, or even told that she was taking part in one, when she sought treatment for problems with her legs. And, like Sodey, he claims the family were told that a charity was footing the bill for the care.

A few weeks after taking the drug, Survaiya says his mother’s health deteriorated and she was left unable to walk.

“I told the doctor, but he said don’t stop the doses. It is a temporary paralysis and the drug will make it better.”


Please don’t do these trials on poor people – rich people can overcome these problems but if I can’t work the whole family suffers”

Ramadhar Shrivastav

His mother died a few weeks later.

In all, 53 people were test subjects in that trial, which was sponsored by British and German drug companies, and eight died. There is no hard evidence that the drug was the cause of death, but nor were there any autopsies to enable a full investigation.

Over the past seven years, some 73 clinical trials on 3,300 patients – 1,833 of whom were children – have taken place at Indore’s Maharaja Yeshwantrao Hospital. Dozens of patients have died during the trials, however no compensation has been paid to the families left behind.

Internal hospital documents seen by Newsnight reveal that since 2005, 80 cases of severe adverse events in trials have been recorded in Indore. One patient listed on the severe adverse events document is Naresh Jatev, who is now four.

His father, Ashish Jatav, says that his son was a healthy three-day-old baby when doctors said he needed a polio vaccine.

Naresh Jatev and familyNaresh Jatev – in the white shirt – with his family

The family says that they had no idea that the drug Naresh was given was a trial one, and that the hospital forms which they signed had been written in English “so we couldn’t understand anything”.

According to an investigation by the hospital, the healthy baby boy had a seizure shortly after receiving the drug and suffered an attack of bronchitis.

Drug trials in India

  • Almost 2,000 trials in past seven years
  • Tests include drugs made by well-known companies such as Biogen Idec, Astra Zeneca and Glaxo Smith Kline
  • 288 deaths in 2008
  • 637 deaths in 2009
  • 668 deaths in 2010
  • 438 deaths in 2011

He now has breathing and eating problems, although the family have been assured that this is nothing to do with the trial vaccine. They say they no longer know what to believe.

Time after time in Indore, I heard a depressingly familiar tale of poor, often uneducated people saying how flattered and privileged they were made to feel as they were suddenly offered the chance to receive medicines usually out of their reach. All of them claim that, contrary to Indian laws governing drugs trials, there was no informed consent.

I also repeatedly heard patients’ relatives say that the treatment they received at Maharaja Yeshwantrao Hospital was overseen by Dr Anil Bharani.

Bharani has since been charged by the state government for receiving illegal payments and foreign trips from drug companies, and for carrying out drugs trials without patients’ consent.

He refused to speak to Newsnight, even when I approached him in person in his office at the hospital. He called security and I was marched out of the hospital by an armed guard. But two days later, Bharani was himself transferred from the hospital after more than 30 years service.

Bharani is just one of a number of doctors at the hospital who have been already been fined for irregularities during drugs trials. None of the problems might have ever come to light if it had not been for another doctor, Dr Arnand Rai, who had an office on the same floor of the hospital.

Dr Arnand Rai with Sue Lloyd RobertsDr Rai says he was fired for raising concerns

Rai says he became concerned when he saw poor people being ushered in to the best consulting rooms. He says he was sacked from his job because of his questioning, but that he has been researching the hospital trials ever since.

“They choose only poor people,” he says, even though drug trial protocols demand that they should be carried out on all sections of society. “They chose poor, illiterate people who do not understand the meaning of clinical drug trials.”

Dr KD Bhargava, head of the ethics committee at Maharaja Yeshwantrao Hospital, admits that the hospital’s oversight of the trials has been flawed. “Suddenly lots of money got involved and there was too much going on. And, yes, maybe we may have lost control,” he says.

But the issue goes well beyond one hospital.

Since India relaxed its laws governing drugs trials in 2005, foreign drug companies have been keen to take advantage of the country’s pool of educated, English-speaking doctors and the huge population from which to choose trial subjects.

The Bhopal disaster

A rally in memory of the Bhopal victims
  • Considered the world’s worst industrial disaster
  • On night of 2 December 1984, Union Carbide’s pesticide plant leaked tonnes of lethal chemicals over Bhopal
  • At least 3,000 people died in first 24 hours
  • And thousands more from after-affects

In the past seven years, nearly 2,000 trials have taken place in the country and the number of deaths increased from 288 in 2008 to 637 in 2009 to 668 in 2010, before falling to 438 deaths in 2011, the latest figures available.

The provincial capital of Madhya Pradesh is Bhopal – a city whose name will for ever be linked with the world’s worst industrial accident. An explosion at the Union Carbide plant caused a gas leak that killed an estimated 25,000 people, campaigners say.

The only good thing to come out of the disaster was the Bhopal Memorial Hospital, built as part of a compensation agreement with Union Carbide to help care for some half a million locals affected by the disaster.

Little did they know that when they came for treatment, some would be used for clinical drug trials.

Ramadhar Shrivastav was one such person. As he makes his way uncertainly to the door of his house to greet me, he says he was lucky, having got off comparatively lightly in the 1984 disaster – only his sight was affected.

Five years ago, he suffered a heart attack and went to the Bhopal Memorial Hospital. He does not read English, and it was a journalist who last year noted that his discharge paper showed that he was part of a trial by the British company Astra Zeneca on a drug being tested for patients with ACS (acute coronary syndrome).

Shrivastav claims the drug has affected him badly and he now cannot work.

Ramadhar Shrivastav and family
Ramadhar Shrivastav had previously been caught up in the Bhopal leak

When he learned we were from Britain, he asked us to pass on a message to Astra Zeneca.

“Please don’t do these trials on poor people. Rich people can overcome these problems but if I can’t work the whole family suffers. Why did they choose us? They should have tested it on themselves.”

Professor NP Mishra

It’s not being tried out to harm them” Professor NP Mishra

Astra Zeneca admit there were problems with consent with a few patients on the trial identified through there routine monitoring during the trial and the issues were quickly rectified. They say that Shrivastav was not one of those affected.

From a medical point of view, doctors agree that the long-term effects of exposure to the Bhopal gas, methyl isocyanate, are still not known so why use the victims for drug trials? I put this question a doctor involved in setting up the Bhopal Memorial Hospital and who once served on the ethics committee there, Professor NP Mishra.

He says trials are carried out for the long-term benefit of patients. “It’s not being tried out to harm them.”

But haven’t these people suffered enough? Is it right to put them at further risk in a clinical drug trial? “The way you talk, medicines would never be developed.”

I ask again, why choose gas victims? “That I cannot comment on,” he says. “It was not my job to find out.”

Sue Lloyd-Roberts reports from the poverty-stricken state of Madhya Pradesh

The problem, I found while working on this subject, is finding anyone who is prepared to be held responsible.

I found Tarjun Prajapati supervising a construction site in a new suburb of Bhopal. He is joint owner of a building company. His father was a gas victim who, four years ago, suffered a heart attack. He was given drug called Fondaparinux at the Memorial Hospital. When he ran out of the medication, his son found it easier to nip out to the shops rather than cross town to pick up more from the hospital for his father.

“I went to the market to buy them but couldn’t,” he remembers. “I was told they were only available from the hospital and only then did I realise he was on a trial drug. I feel very bad that my Dad died because of those medicines.”

This claim is impossible to verify because, once again, there was no autopsy.

On the trial documents, it says that the British company Glaxo Smith Kline are the sponsors of the drug, are responsible for the trial and are the investigators of the drug.

But GSK says they bought the rights to the drug while the trial was being carried out by the French company Sanofi, which is named as a collaborator on the document. When we contacted Sanofi, they told us the trial was in fact “conducted through an Indian research organisation called Quintiles”.

Lawyer Satnam  Singh BainsSatnam Singh Bains, a British barrister in Indore, is looking into the complaints

There is no doubt that the drugs trial set-up can be complicated. A couple of drug companies might team up and then delegate the actual work of the trial to what in India are called Clinical Research Outsourcing Organisations. In the past, when there have charges of malpractice, drug companies have tended to blame these local companies.

Which leaves those who believe they have a just grievance against the drug companies somewhat bewildered.

Lawyers are now looking at whether there is a case to answer in the UK. Satnam Singh Bains, a British barrister in Indore, is looking into a couple of cases.

He shows me a recently published report by the Indian Parliamentary Committee on Health and Family Welfare that looks into what is happening around the country. The report is damning.

It confirms that the set-up for regulating trials in India is, in Singh Bains’ words, “not fit for purpose”. There are too few inspectors at the regulatory agency, coping with too many demands, including having to supply data on 700 parliamentary questions and 150 court cases in one year.

“Still worse,” the report says, “there is adequate documentary evidence to come to the conclusion that many opinions [during the drug trials] were actually written by the invisible hand of drug manufacturers and experts [the doctors] merely obliged by putting their signatures.”

Singh Bains says there are real concerns. “About, at the very least, collusion between experts and the drug manufacturers or, at worse, there is a suggestion that there is a fraud taking place – that these reports are being signed off without any independent, clinical scrutiny of their findings in the way that conclusions are expressed.”

He adds that this could have global implications about “whether the findings of these clinical trials can be safely relied upon”.

The dark underbelly of India’s clinical trials business- #medical ethics #humanrights


Incidents at Bhopal and Indore highlight irregularities and ethical violations in some trials

First Published: Wed, Oct 10 2012. , at Live Mint

Protesters outside the Bhopal Memorial Hospital and Research Centre. Photo: Sayeed Farooqui/Mint
Updated: Thu, Oct 11 2012. 12 20 AM IST
New Delhi: In 2004, doctors at the Bhopal Memorial Hospital and Research Centre (BMHRC), established exclusively for treating the victims of the 1984 gas leak, recruited unsuspecting survivors for clinical trials without their knowledge or consent; 14 participants died during the course of the trials.
Together with the episode in Indore’s Maharaja Yashwantrao Hospital (that Mint reported on 10 October), where 32 people have died in clinical trials between 2005 and 2010, this incident highlights irregularities and ethical violations in some trials conducted by clinical research firms and pharma companies—the dark underbelly of the booming clinical trial business in India.
In 2005, India introduced patent protection laws. Since then, it has become a global hub for clinical trials, drawing companies because of its ethnically diverse pool of potential test subjects, while bringing down research and development (R&D) costs by nearly 60% in phase II and III trials, according to lobby group Confederation of Indian Industry.
A phase II trial establishes the protocol for testing and a phase III one is the final testing prior to approval.
Regulatory failures have marred the clinical trial business in India, experts said, pointing to lapses in the functioning of so-called ethical committees that are required by law for each trial, contract research organizations (CROs) and the Central Drug Standard Control Organization (CDSCO).
A parliamentary panel in May found CDSCO to be in collusion with drug companies and doctors, and approving at least one drug every month without conducting clinical trials or seeking expert medical opinion. Concerns over the conduct of clinical trials prompted the same panel to look into the rapidly growing industry, and the international and domestic pharmaceutical companies sponsoring them.

“Many issues have been raised in Parliament—people being treated as guinea pigs, lack of informed consent and unattributed deaths during trials,” said Sanjay Jaiswal, a Lok Sabha member and a physician himself. “We are not against clinical trials. The issue is about how these trials are being done. Rules need to be followed.”

A report on this will be presented to Parliament in the winter session, he said.
Medical ethicists are concerned that the rapid growth— without trained manpower or a clear-cut regulatory framework —could be a “race to the bottom”, with global ramifications and not just confined to one country.
“What the media doesn’t get straight is that drug companies aren’t using poor Indians as guinea pigs for Americans,” said Arthur Caplan, a bioethicist at the New York University Langone Medical Center. “The more common thing is that say Vietnam competes with India to see if the companies will come and bring in their studies, bring in the doctors, bring some relief if the drug or vaccine works—maybe spend some money in these places, give a bribe or two to the local health ministry to recruit in the local mental hospital. So, if India tightens regulation, companies will just go to Vietnam. This is not just an India problem—it’s a global issue.”
A globalized market
International boundaries blurred substantially when the US food and drug administration (FDA) relaxed regulations allowing drug companies to submit results of foreign trials in applications for new drugs to be marketed in the US.
Between 1990 and 2008, the number of clinical trials conducted largely by US companies shot up about 24 times to 6,465 from 271, according to a 2011 article in Vanity Fair. The 20 largest US-based drug makers conduct about one-third of their phase III clinical trials outside the country, and a majority of their study sites also are elsewhere, according to American Medical News.
A large genetic pool, high-quality hospitals, English-speaking staff and low costs make India an attractive destination for pharma firms looking to conduct clinical trials.
According to CDSCO, there are an estimated 150,000 people enrolled in clinical trials in India. According to a 2011 Associated Chambers of Commerce and Industry of India (Assocham) report, nearly 100 domestic and multinational pharmaceutical companies are conducting trials in the country and the business is worth Rs.8,000 crore.
Trials in countries such as India are cheaper to run: According to a 2008 Harvard Business Reviewarticle, tracking Indian test subjects costs between $1,500 and $2,000, (Rs.79,500 and Rs.1.06 lakh today), while in the US, it would cost $20,000.
When clinical trials are conducted ethically, India’s poor also stand to gain. With only 20% of India’s 1.2 billion people covered by health insurance and 35% living below the poverty line, the bulk of the population pays from the pocket for healthcare, according to health industry data provided by Assocham.
“A lot of patients don’t have access to healthcare otherwise,” said Irene Schipper, a researcher at the Netherlands-based Centre for Research on Multinational Corporations (SOMO). “But the problem, of course, is that when the clinical trial is over, they don’t have access anymore.”
Many clinical trials aren’t conducted ethically.
Schipper is concerned that tight regulatory policies in the US and the European Union (EU) appear to be driving high-risk trials to developing countries such as India, where rules or their enforcement may be lax. In 2008, SOMO released a report, Ethics for drug testing in low and middle-income countries, cataloguing a trend of offshoring risky clinical trials to developing countries that would be prohibited by ethics committees in the EU.
In one case, AstraZaneca Plc sponsored large, multi-centred placebo-controlled trials for Seroquel XR, an anti-psychotic drug for the treatment of patients with schizophrenia. The drug was tested against a placebo, which meant that roughly half the participants—all diagnosed schizophrenics—went without any treatment for the duration of the trial.
Due to the worsening of their conditions, 8.3% of the patients receiving the placebo required hospitalization. After 173 days of placebo treatment, one 25-year-old man committed suicide. “The consequences of this practice are serious,” Schipper said in the report. “According to the Declaration of Helsinki, this type of trial can never justify the use of a placebo because it involves withholding treatment from seriously ill patients risking irreversible harm. Nevertheless, the Dutch Medicines Evaluation Board approved Seroquel XR for the EU market.”
The multi-centre trials were conducted in India, Bulgaria, Poland, Russia and the Ukraine. While companies also continue to conduct such clinical trials elsewhere, “these days you’re seeing a lot more of these sorts of trials in India”, she said.
“At AstraZeneca, we take very seriously our responsibility towards the patients participating in our studies and our responsibility to deliver consistently high standards of ethical practice and scientific conduct in all our trials wherever they take place,” Andrew Higgins, a spokesperson for AstraZeneca, said in a statement.
“A placebo treatment does not imply a deficient standard of care. In accordance with the Good Clinical Practice rules, all patients in our clinical trials are provided with the same amount of care and are strictly monitored with the option to switch to another therapy or to be discontinued from the study where it becomes necessary,” he said.
Offshoring responsibility
Central to the growth of off-shoring clinical trials is the role of CROs—independent companies hired by sponsors to undertake clinical trials. Nearly 90% of trials in India are conducted by CROs, favoured by sponsors for their ability to form partnerships with local research organizations, recruit large numbers of participants and quickly conduct trials.
But medical ethicists worry this comes with a dark side. “To put it in a somewhat less polite way, the big company outsources the responsibility to the CRO. If something goes wrong, they say the CRO is completely responsible for this,” bioethicist Caplan said.
In 2011, CDSCO suspended the licence of Hyderabad-based CRO Axis Clinicals Ltd for recruiting illiterate women for a trial without obtaining proper consent. Following the incident, DCGI ordered an investigation into the operation of all 10 CROs in Andhra Pradesh.
Axis failed to respond to Mint’s repeated requests for comment.
“The problem with outsourcing to CROs is that oversight can be problematic,” said Schipper. Many CROs will divide tasks, such as administration, recruitment and research among various other CROs, making monitoring the process difficult for sponsors who are often based overseas, she said. “In our research, we’ve interviewed sponsors who have stopped using CROs entirely because they found that the cost of effectively monitoring them was greater than the money saved by hiring them.”
Caplan further worries that market incentives can drive CROs to complete trials at any cost. “There’s a conflict of interest when you hire a CRO, to act as a scientific and an ethical committee in India,” he said. “The sponsor wants the data—and wants it fast, and every day a study goes past its predicted date of completion, because they don’t have subjects enrolled, costs millions and millions of dollars—perhaps then they don’t continue to pay as much attention to informed consent or eligibility criteria.”
No functional regulatory system
Axis is not the first CRO in India to be facing hard questions: Quintiles, one of the largest global companies in the segment and based out of North Carolina, received a polite warning letter from DCGI for the clinical trials on Bhopal gas victims. “It should be noted that the studies conducted at BMHRC were approved by the Institutional Ethics Committee that was completely aware of the medical status of the patients visiting the hospital and participating in these trials,” Quintiles wrote in response to Mint’s inquiries.
Doctors, activists and researchers note that Indian ethics committees are often flawed. “Ethics committees are the front line regulators for clinical trials. If they were functional, they would be a major factor in preventing unethical trials,” said Amar Jasani, a researcher and trainer in the field of bioethics and public health. “The problem is the ethics committees are completely controlled by the institutions—they are not at all independent, the people on the committees are not trained, nor do they have the resources or independence to do their job.”
According to Jasani, Indian law allows for commercial ethics committees to be hired by the very CROs they are meant to monitor. “There’s a double conflict-of-interest,” he said. “They are governed by the CROs or the pharma companies. At the same time they are profit making—so they are more motivated by financial interest than (the safety of participants).”
While international standards governing clinical trials do exist, most are voluntary and lack regulatory teeth. The Delcaration of Helsinki, of which India is a signatory, says that potential research subjects need to be informed of the risks involved prior to participation, and reserve the right to refuse to participate.
Foreign drug authorities, such as FDA, have also made efforts to curtail unethical trials, by requiring that drug companies abide by certain guidelines. But their reach is limited. A 2010 report by the US Government Accountability Office found that FDA inspects fewer than 1% of clinical trials abroad, and that in many cases, it isn’t aware where clinical trials are being conducted until drug companies submit applications to market the new drug.
“There is no registry or international database—so I don’t think anyone knows what percentage of clinical trials are happening in the developing world. How many participants are men or women, old or young is also hard to know,” said Caplan. “We don’t have good information about what is really going on there, until there is a scandal, a problem or a death—but the overall picture is tough to know, because no one is responsible for monitoring it.”
The impact, though, is widespread: Nearly 80% of drug applications to FDA for marketing approval include tests done on foreign soil. With an FDA stamp of approval, many of the drugs end up being sold all over the world. “Seeing this as Americans exploiting Indians is not accurate,” said Caplan. “Drug companies are equally happy to sell to wealthy Indians. Drugs tested in these trials are eventually sold everywhere—studies in poor nations affect everyone.”

 

#India- Clinical trials: Regulating chaos #Medical ethics #Humanrights


-Vidya Krishnan and Malia Politzer

First Published: Wed, Oct 10 2012.  Live Mint

Lata Mehra’s experience exposes the gaps in both regulation and enforcement in clinical trials, which, in some instances, have caused deaths, in addition to violating fundamental human rights. Photo: Akhil Hardia/ Mint
A hospital in Indore has been able to get away with unethical medical trials in which 32 people have died over five years, according to the state government. This despite several investigations, a state government ban and Supreme Court strictures—a classic example of the lawless nature of the clinical trial business in India.
Lata Mehra, who works in a government-run healthcare centre, was desperate when doctors told her in 2009 that she would be on medication for the rest of her life after a heart attack. The monthly medical bill, a little less than half her salary of Rs.1,000 per month, would leave her with enough to just cover food and rent.
Then, Anil Bharani, a professor of medicine at the state-run Maharaja Yashwantrao Hospital in Indore, offered the 47-year-old a dream deal that he called a “company plan”. The Rs.1,300 a month plan would pay for the drugs and also reimburse Mehra for transportation.
What Mehra did not know was that the “company plan” was part of an unauthorized drug trial of anticoagulants. Nor was she aware that Bharani and some of his colleagues were already being investigated by the state government over allegations of misconduct in clinical trials, an investigation that eventually led to the banning of the trial by the Madhya Pradesh government in October 2010.
Regardless, Bharani continued the trials despite the ban, and Mehra unknowingly became a test case for the drugs.
photo

Lata Mehra. Photo: Akhil Hardia/Mint

The ban was imposed after it was uncovered that informed consent was not taken, and the patients subjected to clinical trials included newborns, children, pregnant women and mentally challenged persons.

The state followed up with more action, and in January barred Bharani and another doctor from conducting trials, and pulled up 12 other doctors at Maharaja Yashwantrao Hospital and 78 other private doctors for refusing to cooperate in the investigation.
That too hasn’t stopped the trials.
Bharani and officials at the hospital declined comment.
The Indore case highlights glaring gaps in regulation and enforcement in India’s rapidly growing clinical trial industry. A 2011 Associated Chambers of Commerce and Industry of India report put the value of the business at Rs.8,000 crore, or $1.8 billion.
On Monday, the Supreme Court turned the spotlight on the business of clinical trials, when it threatened to impose a blanket ban on clinical trials across the country if the Union government didn’t act. The court has given the Union health ministry a month to provide the apex court with information on deaths, compensation and general practices when new drugs are tested on Indians.
“We can even issue a one-line direction that all these clinical trials which affect many people must stop forthwith,” justices R.M. Lodha and A.R. Dave said, hearing public interest cases dealing with the incidents at the Indore hospital.
The court’s order has once again drawn attention to India’s inadequate regime to regulate such trials. Not all clinical trials run in India violate norms, yet, Mehra’s experience exposes the gaps in both regulation and enforcement in clinical trials, which, in some instances, have caused deaths, in addition to violating fundamental human rights.
Government apathy
Mehra was more than happy with the “company plan” until her neighbour Mangilal Shreevas died suddenly, in early 2012.
“He was also a heart patient covered under the same ‘company plan’ at the same hospital and under the same doctor,” said the healthcare worker. “We took the same pills and we went to the hospital together for check-ups. After Mangilal’s death, his wife wanted his medical case sheets to lodge a complaint, but the hospital refused. I was disturbed by this and wanted a different doctor to have a look at my case sheet.”
The rest of her story is similar to that of several such participants in unauthorized clinical trials who express reservations. The doctors refused to hand over the medical file, saying it was “hospital property” and took Mehra off the “plan”. The reimbursements were discontinued.
Meanwhile, in January this year, the state government gave two doctors, Bharani and Ashish Patel, a rap on the knuckles, telling them to refrain from conducting clinical trials for six months; it also fined 12 doctors Rs.5,000 each for not cooperating with investigators.
The fines have not yet been paid, and despite the ban, the trials continue, according to petitioners Swasthya Adhikar Manch, an activist group and Dr Anand Rai, a whistle-blower who filed two separate public interest litigations (PILs) in February 2012 bringing the subject to the court’s attention.
So far, 32 people enrolled in various trials at Maharaja Yashwantrao Hospital have died between 2005 and 2010; the state government has attributed the deaths directly to the testing.
Bharani and Maharaja Yashwantrao Hospital are the targets of both a central probe by a parliamentary committee looking into irregularities in clinical trials across the country, as well as a state level investigation of ethical violations in 94 clinical trials conducted at the hospital.
Judicial activism
Mounting evidence prompted the Supreme Court to step in. Hearing the PILs on the Indore trials, the same two-judge bench of the Supreme Court came down hard on the government and said on 17 July: “There has to be some sense of responsibility (on the part of the government). Human beings are being treated as guinea pigs. This is unfortunate.”
Meanwhile, the ethical committees that were supposed to have overseen the trials continue to function, said Amulya Nidhi, an Indore-based public health activist belonging to the Swasthya Adhikar Manch.
Complaints made to the Human Rights Commission—both state and national—are yet to yield results. In 2011, the joint director of health, Indore division, constituted a four-member committee that recommended the state impose a lifetime medical practice ban on each guilty doctor at Maharaja Yashwantrao Hospital and cancel registrations. That has had no impact.
Powerless government
As disturbing as the trials is the government’s apparent inability to do anything to regulate them.
In June 2011, the Madhya Pradesh economic offences wing (EOW) submitted a report on clinical trials at Maharaja Yashwantrao Hospital that established a conflict of interest, pointing out that pharmaceutical companies had sent principal investigators in several trials on “foreign trips and money was received (by doctors)”. Mint has reviewed a copy of the report.
The same month, a joint director in the state government submitted a second report advising the state government to initiate criminal proceedings against doctors for ignoring protocol.
The EOW report stated that 81 “serious adverse events” were reported in various clinical trials at Maharaja Yashwantrao Hospital.
Besides these cases, 1,833 children from the Chacha Nehru Bal Chikitsalaya (the paediatric hospital affiliated with MGM Medical College) and 233 mentally ill patients had been enrolled in clinical trials without any consent, according to documents submitted to the Supreme Court.
“As per government rules, guardians of mentally ill patients and children have to give an informed consent before they can enrol in trials,” said Nidhi of Swasthya Adhikar Manch, referring to the report.
In total, 12 doctors were named in the two reports. The EOW investigation listed Bharani (medicine), Salil Bhargava (superintendent), Ashoka Vajpayee (former superintendent), Pushpa Verma (dean), Hemant Jain (paediatrician) and Apoorv Puranik (neurologist), recommending that the Medical Council of India (MCI) initiate disciplinary action against them under Indian Council of Medical Research rules. Except for Verma, who maintained she was not involved in the drug trial controversy, none of the doctors were available for comment.
The “disciplinary measures”, including the Rs.5,000 fine, have to be compared with the Rs.5 crore that doctors earned for the trials, according to Swasthya Adhikar Manch’s PIL. Mint couldn’t independently verify this figure.
All but one of the doctors continue to practice medicine. Verma was promoted to the office of dean in January.
Over the past two years, victims and activists claim to have registered complaints at various forums, including the Central Vigilance Commission, EOW, the state police, the National Human Rights Commission, the medical education department, MCI, the Enforcement Directorate and the Central Drug Standard Control Organization. None of them seem to have had much effect.
Sarat Pandit, the joint director who submitted the 2011 report that recommends criminal proceedings against the doctors involved, blamed the delays on red tape and the involvement of too many government departments.
Victims languish
“Our mandate was to investigate the goings-on in Maharaja Yashwantrao Hospital and we did just that. Several irregularities in protocol and ethics were clearly established and we recommended action,” said Pandit. “The report is now lying with the government and it is up to them to act on it. The matter has now become sub judice. While several agencies are investigating the case, nothing is being done for the safety of people exposed to these doctors.”
There have been attempts to rally support for the victims. In January, Communist Party of India (Marxist) leader Brinda Karat sent a memorandum to then drug controller general of India, V.G. Somani, seeking action against the doctors.
“Families are upset and angry, and there is a clear groundswell. It is outrageous that Indians are being used as guinea pigs,” Karat said.
Mint has seen a copy of the letter.
The Madhya Pradesh state assembly has seen about 40 questions being asked in the past two years about trials, according to whistle-blower Rai.
“When RTI (Right to Information) replies were vague, we approached local politicians to raise the issue in the state assembly,” added Rai, who worked at Maharaja Yashwantrao Hospital and first exposed the trials. “Most of the information I have was collected by this route.”
The Union government has been trying to pursue the issue without much success.
“What happened in Indore was truly horrendous,” said Keshav Desiraju, additional secretary in the health ministry, who has been trying to get more information from the state government. “They have not responded to my queries.”
The parliamentary committee, which recently exposed the alleged nexus involving the drug regulator’s office, pharmaceutical companies and doctors, is to visit Indore to investigate the matter. Its report is expected to be tabled in the winter session of Parliament.
According to the health ministry, more than 1,500 people have died in clinical trials since 2008, a figure that’s contested by public health activists. According to documents presented in the Rajya Sabha, 2,163 people have died in India due to clinical trials since 2007.
“In Indore alone, trial subjects have died as recently as February, and this does not reflect in the government investigations. The whole subject is technical, and even when deaths occur during the trial, it is very difficult to attribute it directly to the drug tested. Several committees have pointed out that doctors do not maintain proper records of severe drug events,” added Nidhi of Swasthya Adhikar Manch.
No one has been compensated yet.
And what about those like Mehra, who participated in the clinical trial to obtain critical medication and then chose to be the whistle-blower?
“This is the cost of speaking up against doctors,” she said. “They have taken me off the company plan.”

India -Supreme Court warns it can ban clinical trials


Published: Tuesday, Oct 9, 2012, 8:24 IST
By Rakesh Bhatnagar | Place: New Delhi | Agency: DNA

 

Distressed at the rampant misuse of the practice of clinical trials by negligent doctors and drug companies that have killed 1,954 patients since 2009 in the country, the Supreme Court has asked the Centre and various states governments to reveal the truth behind such gruesome tragedies.

Expressing anguish at the sordid affairs in the private and government hospitals including mental hospitals, a bench of justice RM Lodha and justice AR Dave on Monday also asked Union government to inform about the side effects of these trials and whether the close relatives of victims had been adequately compensated.

During the inconclusive hearing in a PIL filed by an NGO Swasthya Adhikar Manch alleging large scale clinical drug trials across the country by various pharmaceutical firms using Indian citizens as guinea pigs, the court said “we are very serious about this matter’’.

“We can even issue a one-line direction that all these clinical trials which affect many people must stop forthwith. It must suffice, we are very serious about it,” judges told additional solicitor general Siddharth Luthra.

Responding to an earlier direction, the Madhya Pradesh government sought to put the record straight and said charge sheets have been filed against several private and government doctors who had been performing these tests illegally.

It has admitted that both private clinics and government hospitals had been indulging in the tests illegally.

However, it also drew the court’s attention towards Union health minister Ghulam Nabi Azad’s statement in parliament confirming deaths of 1,954 persons from 2009 till June 2012 due to “serious adverse events of death” in clinical trials. Azad also told the House that these deaths could be attributed to various reasons and the side effects of the drugs not ruled out.
Seeking blanket ban on clinical trials that were engineered by various pharmaceutical firms from India and abroad, petitioner’s counsel Sanjay Parikh contended that permission for trials were granted by the Central government without consulting the states.
However, MP’s lawyer Dushyant Dave said the states cannot be faulted for the tests.

But the judges pointed out that the clinical trials were conducted in state governments hospitals whose employees and doctors are under the control of the respective state governments.

Judges said there are reports about deaths due to clinical trials saying “one person is dying every day. Human beings are treated as guinea pigs. We do not know personally but we believe a responsible statement is made before the court’’.

In the public interest litigation, Parikh had said over 3,300 patients were used for the tests in Madhya Pradesh.

 

United States Private-Sector Physicians and Pharmaceutical Contract Research


 

Clinical trials 06

Background

There have been dramatic increases over the past 20 years in the number of nonacademic, private-sector physicians who serve as principal investigators on US clinical trials sponsored by the pharmaceutical industry. However, there has been little research on the implications of these investigators’ role in clinical investigation. Our objective was to study private-sector clinics involved in US pharmaceutical clinical trials to understand the contract research arrangements supporting drug development, and specifically how private-sector physicians engaged in contract research describe their professional identities.

Methods and Findings

We conducted a qualitative study in 2003–2004 combining observation at 25 private-sector research organizations in the southwestern United States and 63 semi-structured interviews with physicians, research staff, and research participants at those clinics. We used grounded theory to analyze and interpret our data. The 11 private-sector physicians who participated in our study reported becoming principal investigators on industry clinical trials primarily because contract research provides an additional revenue stream. The physicians reported that they saw themselves as trial practitioners and as businesspeople rather than as scientists or researchers.

Conclusions

Our findings suggest that in addition to having financial motivation to participate in contract research, these US private-sector physicians have a professional identity aligned with an industry-based approach to research ethics. The generalizability of these findings and whether they have changed in the intervening years should be addressed in future studies.

Please see later in the article for the Editors‘ Summary.

 

Citation: Fisher JA, Kalbaugh CA (2012) United States Priv

Read full study here