gardasill trial

Aman Dhawan, 16, from Indore, lost weight and strength after being enrolled in the trial, which he didn't know he had signed up for either
Children as young as nine suffered side-effects after being used as unwitting human guinea pigs for a new multi-billion pound anti-cervical cancer drug, it has been claimed.

The new anti-cancer drug has just been approved for use in the United States and is due to be released in Britain this year.

But MailOnline has learned that several of the children used as 'guinea pigs' for the drug trial in India reported suffering problems including weight loss, fatigue, dizziness and menstrual problems.

They and their parents claim they had no idea they were being used to test out Gardasil 9, which was then an untried drug.

The claims have sparked a furious row with the mother of reality TV star Jade Goody, one of the most high profile recent victims of cervical cancer, telling MailOnline: 'It is not right.'

Jackiey Budden said she would not have wanted her daughter - who died aged 27 in 2010 - to have been vaccinated with a drug that had been tested on children who did not know what was happening to them.

'Vaccination is a good idea but it shouldn't be tested on kids,' she said.

'It is difficult because you want to save lives but it is not right to do it on children that young. They should be able to make up their own minds if they want to test it out.'

Drug firms are already facing claims that they exploited children in the developing world to develop the vaccine.

Merck, which makes Gardasil 9, faces a hearing in India's Supreme Court tomorrow over the alleged use of young girls from poor tribal communities in trials of an earlier anti-cervical cancer drug.

It also involves the Cervarix vaccine produced by GlaxoSmithKline, along with US-based health non-profit organisation PATH, which organised the trials with the backing of the Bill and Melinda Gates Foundation.

Seven girls died before the trials were halted, although those involved deny the deaths were linked to the vaccines.

An Indian government committee which investigated those trials concluded that they amounted to a serious breach of trust and medical ethics amounting to child abuse and 'a clear cut violation of the human rights of these girl children and adolescents'.

Now Merck is facing fresh claims that it put children at risk to satisfy the demand for a new vaccine.

Cervical cancer is the second most common type of cancer in women worldwide and kills more than 265,000 people every year, according to Cancer Research UK.

In the UK alone there were 920 deaths in 2012, the latest figures available.

Both America and Britain advise girls to be inoculated against the deadly disease while in adolescence - and the vaccination programme is worth huge sums of money to the pharmaceutical industry.

Merck's new drug, Gardasil 9, is designed to protect against the strains of Human Papillomavirus responsible for 90 per cent of cervical cancers.

Its effectiveness is not disputed: Merck's clinical trial data shows impressive results, with 99.5 of participants testing positive for antibodies after completing the trials.

But as the Indian test subjects discovered - and Merck's own published research confirms - some recipients of the vaccine do suffer side effects, known as systemic adverse reactions.

The most frequently reported side effects were headache, pyrexia [fever], nausea, dizziness and fatigue.
Dr Hemant Jain

Dr Hemant Jain faces accusations that he ran drugs trials for international pharmaceutical firms without the consent of patients. The latest case to emerge involves Merckís new Gardasil 9 drug, which Dr Jain administered to 44 children
In one trial more than 1,000 out of 7,071 subjects reported suffering headaches, with more than 200 reporting dizziness up to 15 days after the vaccination.

According to Merck, 305 people reported 'serious adverse events' and 321 reported new medical conditions 'potentially indicative of systemic autoimmune disorders'.

Its own report warns that the similarities between the new drug and its predecessor mean that when Gardasil 9 becomes more widely available, some users may also suffer problems reported during the use of Gardasil - including deep vein thrombosis, immune system disorders, gastrointestinal disorders and nervous system disorders such as Guillain-Barré syndrome - known as locked-in syndrome - and motor neuron disease.

Claims of such side effects have made the original Gardasil the subject of some controversy in the US, where some campaigners have questioned its safety.

But last month, after studying the results from trials on at least 13,234 people [Merck also uses the figure of 13,236 in its published research] the US Food and Drug Administration concluded that the vaccine was safe and approved the vaccine for use on children aged nine and upwards. It is now expected to become one of the most widely used anti-cancer drugs in the world.

For Merck - which has cut 8,500 jobs in the last two years in an attempt to save £1.5billion a year - the stakes could not be higher: industry analysts estimate that Gardasil 9 could be worth more than £1.2billion a year to the company in sales.

But those forecast sales may have been on the back of trials conducted on children in the Indian city of Indore that, according to an affidavit lodged with the Supreme Court, were both illegal and unethical.
whistleblower pharma drug trials

Kalpana Mehta highlighted a series of drug trials on young girls in India which resulted in at least seven deaths. A public interest litigation she brought with two others left Indiaís Supreme Court to request a government investigation into the trials and ultimately led to the court halting drug trials in India
The affidavit, submitted to the court as part of the public interest litigation over the earlier drug trials, claimed that:
  • None of those involved were told that they were taking part in a drug trial
  • Middlemen acted as touts to recruit patients
  • Parents were lied to and told their children would be getting a successful foreign medicine
  • Those involved targeted the poor and vulnerable
  • Children who suffered health problems received no health care or compensation
Documents lodged with India's Clinical Trials Registry [CTR] reveal that trials of the drug - which during testing was known as V503 - also took place in the UK and 25 other countries.

In India the work was allotted to seven investigators and involved 225 boys and girls aged from nine to 15. Those involved received a series of three injections. No details have been published of the outcomes on the CTR documents.

But MailOnline has seen the list of 44 participants who took part in the study run by Dr Hemant Jain at the MGM Medical College in Indore. The documents bear his stamp and signature. They are the subject of the affidavit submitted to the Supreme Court.

In addition to the affidavit, MailOnline has spoken to families whose children were used as 'guinea pigs' for the drug.

Among them is Aman Dhawan, 16, who lives with his family in the Pancham Ki Phel slum in Indore in Madhya Pradesh state in the heart of India.

Until 2010 he was a healthy young boy with an aspiration to be be a dancer.

The invitation to receive the vaccinations had come from a neighbour. Other parents were doing it, she said, and not only were their children getting a fantastic new Western 'cure-all', they were getting money for going too - as much as Rs 1,000 [£10] - a large sum in a country where more than 300 million people live on less than the official poverty rate of Rs 47 a day. What was there to lose?

'The doctor said "Don't worry, the vaccine is very good, it will take care of all your diseases",' he says.

'My mum told me this would cure me from several diseases including malaria.

'I wasn't afraid of the injection. But after taking the medicines I saw there were things taking place in my body.'

He began to lose weight and strength, he says.

'Whenever I was eating I wanted less. I was losing my taste for food so that now I don't like to eat a meal in the evening.I was unable to do the things I used to do earlier.'

He shrugs the shoulders of his slight frame.

'I was a very good athlete. At school I won many prizes, but now when I try to run as fast as I used I feel pain in my body and my stomach aches.'

His family do not know what is wrong with him: they say they have received no follow up care after the trial and are too poor to be able to afford to pay for tests of their own.

'I think it may be because of the injections. I can't do the things I used to be able to do. I wanted to be a famous dancer. But I can't be a dancer now. My body is too weak. I don't have the strength. So now, I don't know. Maybe I will open a shop.

Dr Jain has stamped his name onto this paperwork relating to the drug trial, which was released as a result of questions asked in the Madhya Pradesh state assembly

The first couple of times he attended for the injections, the family was given Rs 200 [£2] 'because they said"'you've come a long way and couldn't work today",' says his mother Seema. The last time he went they were given Rs 1,000 [£10].

'Until now we didn't realise that these drugs were being tested on our children,' she says.

'He was okay initially but then lately he was ill. Earlier he had a good physique but gradually he has lost his weight and he has lost his health.

'Because of our poor and illiterate background we were taken for a ride. If we knew that they were doing this we would never have allowed our children to take these tests.'

Whether by accident or design, many of those who agreed to let their children take part in the trial were poor and illiterate.

Some, like the Dhawans, also noticed changes in their children - late periods, dizziness and weakness. They had something else in common too: they say they had no idea they were taking part in a trial of a new anti-cervical cancer vaccine.

Muskan and Akash Hansari both had the injections, but their father told researchers working for the group behind the Supreme Court case that he was led to believe that it would prevent all sicknesses and illness in general.

'[He has] no idea as to what cervical cancer is. Doesn't know what a uterus is let alone where it is located,' the researchers noted in a report compiled to support the Supreme Court affidavit.

The family was, however, warned that there could be side effects like fever and stomach ache and were given a thermometer to take home and, like all the other trial participants, they were called in later for blood tests.

Muskan, 15, said she was about 11 at the time of the vaccination. She said she 'did not understand anything about the vaccine because nothing was explained to her.'

'Muskan took the vaccine because her father told her to and she trusted him and her father trusted the government doctor,' the report notes.

Mazhar Ansari, 18, and sisters Sana, 17 and Aasiya, 17, were signed up after a cousin heard about the injections from Dr Jain, the man running the trial.

No details have been published on how much Dr Jain was paid to conduct the trial, but published rates for other trials in Indore suggest that an investigator might expect to be paid up to £5,000 for such a trial. Rates vary widely though.

But it is alleged youngsters like Aman are being used as guinea pigs without their knowledge to ensure the drugs are safe for children in the UK and US

'It should not have been done. It is completely wrong,' says their father Mohammed Umar Ansari.

The family was told that the vaccine was for cervical cancer, but Ansari said he had no idea what that was. Like the Dhawan family, they were paid for their time. Both girls say they have experienced problems with their periods, which have become late and irregular.

This echoes accounts from the US, where some girls vaccinated with the original Gardasil have reported problems with missed periods.

Shaurya Mishra's father told the researchers the family felt 'short changed and cheated' by the doctors after the 14-year-old was signed up for the trials. He was told the vaccine would prevent cervical cancer but confessed he did not know what this was.

'He felt bad that American companies try their vaccines out on Indians and then those same vaccines are given to the Americans to benefit them while the Indians are just used as guinea pigs.'

Shruti and Leena Pardeshi's mother was also convinced that the vaccine would be good for her girls. She was warned that they could get a light fever and stomach ache, and was given a thermometer to take home.

Instead, Shruti had felt dizzy and weak and doctors had been unable to get blood from her on the blood tests. Both girls started to experience late periods.

The activists behind the court challenge include veteran women's campaigner Kalpanna Mehta and Dr Anand Rai, a doctor who has campaigned for years against drug trials.
Dr. Anand Rai

Whistleblower Dr Anand Rai, 37, lifted the lid on the scandal of illegal drugs trials in the city and now has been given an armed guard to protect him
Mehta shuffles a sheaf of documents released by the state health department in response to a request from a member of the state assembly. This is where the list of the trial participants came from.

'The trials are extremely faulty,' she says.

She says her researchers have interviewed 14 of the children and their families and recorded a range of problems suffered since the vaccinations.

'One girl had serious mood swings and depression. Another developed serious anaemia. One boy lost a lot of weight, one girl has stomach ache, four have menstrual abnormalities and one has stopped her periods.'

But many patients do not realise they have rights, she says.

'Even when they know it is wrong they don't want to fight. We still live in a country were they think doctors are gods. There are no risks [for the drug companies] here.'

But there are risks for the campaigners. Last year Dr Rai was given a bodyguard in response to death threats made against him because of his campaigning.

He sits in the canteen of the MY Hospital in Indore, watching his bodyguard clean a double-barrelled shotgun.

'Some people are unhappy with me,' he says. He says he has been threatened by other doctors and told he will not get work because of his efforts to expose the way some drug trials are run in the city.

'They chose poor groups, weaker groups, illiterate groups, those who needed medicine at any cost. They are poor. They have to rely on these doctors, they have to rely on government hospitals because they don't have any option.

'International companies use Indians as guinea pigs.'

A detailed report prepared by Dr Rai and colleagues - upon which the affidavit submitted to the Supreme Court was based - is highly critical of the Gardasil 9 trials.

It noted side effects among children including dizziness, weakness, weight loss, mood swings, depression and suicidal tendencies.

'Not a single family knew it was a clinical trial and were all duped into believing that this vaccine had proven to be effective in other parts of the world,' it says.

The report does not, however, allocate blame for who was responsible for this failure.

'These families have been duped into taking the HPV vaccine and their right to give informed consent was violated. Many of them took the vaccine in good faith and were unsuspectingly used as guinea pigs for yet another clinical trial in India.'

The man behind the trials, Dr Jain, refused to meet face to face, but issued a staunch defence of his work, claiming that the allegations about the trials were the work of 'vested interests' chasing compensation.

Dr Jain, a paediatrician, criticised the 'hue and cry' around his trials. He said his centre had World Health Organisation approval for conducting vaccine trials and that many of the children involved in the Gardasil 9 trials were middle class or the children of colleagues.

'All the trial participants and their parents were adequately informed about the whole process of the trial and their queries if any were suitably answered at the time of signing the consent form,' he said in a written response.

It is not the first time he has had to issue a denial over his drug trial work. An earlier report by the State Bureau of Investigation of Economic Offences criticised him after 18 people suffered serious adverse events during drug trials he conducted. The report notes that he received several large payments for the trials, including Rs 2 million (£20,000) for a World Health Organisation sponsored trial on 400 children. Dr Jain said that none of the adverse events were related to the trials.

Previously India's National Commission for Protection of Child Rights also registered a case against Dr Jain following a complaint by the parents of an 11-year-old girl, who claimed she had been the subject of a vaccine trial without their consent and which had led to serious side effects.

In 2012, Dr Jain was the subject of an undercover television investigation by India's Headlines Today station, which filmed him talking about the profit margins from drug trials. He was shown explaining that there was an 18-20 per cent margin.

The news channel accused him of signing up patients to trials without informing them that they were participating. He denied any wrongdoing.

In a statement Merck - which trades in India as MSD Pharmaceuticals Pvt Ltd - said: 'Merck conducts clinical trials worldwide to evaluate the safety and efficacy of its therapeutic candidates. These trials are fundamental to the development of innovative medicines and vaccines that help treat or prevent illness in humans.

'It is Merck policy that all investigational studies in human subjects must be conducted in a manner consistent with laws, regulations and guidelines for the protection of human subjects, including International Conference on Harmonization-Good Clinical Practices (ICH-GCP) standards.

'Individual country regulations and guidelines are an important source of specific requirements for the conduct of medical research.'

A spokeswoman for Merck argued that while the additional affidavit on the Gardasil 9 trials had been submitted to the Supreme Court, it was not included in a subsequent list of issues the judges were considering.

The campaigners say that it was submitted and remains part of the case launched two years ago by Mehta and her colleagues.

The court's record of proceedings from last August shows that the judges are primarily concerned about whether those taking part in the original trials of Gardasil and GSK's anti-cervical cancer drug Cervarix gave their informed consent and whether they had been the subject of clinical experimentation. They cited at length the report of a hugely-critical government report into the original trials.

The whole matter was 'fishy,' according to the 72nd report of the parliamentary standing committee on health and family welfare. Everything pointed to a 'well planned scheme to commercially exploit a situation.'

The committee noted that a large number of participants were illiterate and had apparently consented by placing a thumb print on forms they could not read.

It concluded that the trial operators 'violated all laws and regulations laid down for clinical trials by the government.'

Their sole aim had been to promote the commercial interests of the manufacturers who 'would have reaped windfall profits' if the drug had been approved for use in India.

'This is a serious breach of trust by any entity as the project involved life and safety of girl children and adolescents who were mostly unaware of the implications of vaccination,' it wrote. 'The violation is also a serious breach of medical ethics...It also deems it an established case of child abuse.'

That report led the Supreme Court to temporarily suspend clinical trials across the country until new safeguards could be put in place, including new independent ethics committees, registration of all trials and audio-visual recording of consent.

'Foreign companies are treating India as a heaven for clinical trials, but it is proving hell for India,' the judges stated at the time.

Over the past decade, drug trials have become a £300 million a year business in India. In 2003, there were fewer than 50 clinical trials running in India, but the number increased rapidly as pharmaceutical firms realised that costs were up to 60 per cent lower in India than in the US. By 2011, there were 1,852 trials registered with the government, involving an estimated 150,000 patients.

In March 2013 India's health minister Ghulam Nabi Azad revealed that 2,868 people had died since 2005 in government-approved drug trials.

GSK argues that the Supreme Court case does not involve the company and is targeted only at those who conducted the tests, although it is named as a respondent in court papers.

In a written statement GSK said: 'GSK has not been named in the ongoing case and therefore it would be inappropriate for GSK to comment on the matter further.

'Cervarix is already licensed for use in India. GSK submitted the required clinical trial data demonstrating the safety profile and efficacy of Cervarix to the regulators in accordance with the applicable regulations. It is now registered in 130 countries worldwide and has been used in national vaccination programmes to protect women from cervical cancer in many countries, including the Netherlands, Panama and regional programmes across Italy, Poland, Spain and Mexico.'

In a statement PATH said it had cooperated fully in the inquiry into its use of the vaccines and was committed to meeting the highest scientific, ethical and legal standards.