A 27-YEAR-OLD man has died in a government-funded medical trial, in which at
least two other patients were given overdoses.
Gary Foster, a graphic designer who was planning to get married this month,
was on seven occasions given double the amount of chemotherapy he should
have been prescribed. His mother, Colleen Foster, said: “Gary was slowly
poisoned to death.”
The mistakes raise questions about the safety of medical trials in Britain two
years after the notorious “elephant man” trial, which was supposed to have
led to tighter supervision. Six men nearly died after their bodies swelled
horrifically after taking the experimental drug TGN1412.
University College London Hospitals NHS Trust (UCLH), one of Britain’s largest
trusts, has been forced to suspend the trial although it is continuing at
other UK hospitals.
Foster’s death was due to a fundamental error in the setting-up of the trial
on the hospital computer system. A second UCLH patient was affected by the
same error, but survived.
Another patient, who died at a different hospital, and whose name has not been
disclosed, also received an overdose of the drug bleomycin. In that case,
the overdose was due to an error by a nurse or doctor rather than a basic
flaw in the setting-up of the trial. According to the Medical Research
Council (MRC), the government-funded organisation which ran the trial, the
drug was not the direct cause of his death.
When the MRC suspected that patients had been given overdoses, instead of
calling UCLH immediately, it posted a letter on October 3, 2007. An inquest
into Foster’s death heard that a nurse failed to open the letter until
October 16, two days after his death.
The family concede that by October 3 it was too late to save Foster because he
was already dying of organ failure caused by the overdoses.
Foster, from Waltham Abbey, Essex, was eager to join the medical trial in June
2007. He had just been diagnosed with testicular cancer, and he had a 60%
chance of survival. The disease has a survival rate of about 95% if caught
early. Doctors told Foster that, if he was accepted for the trial, his
chances of survival would increase.
Colleen Foster said: “The trial sister said: ‘Good news, Gary, you have been
selected for the trial.’ At UCLH they said, ‘Don’t worry, testicular cancer
is curable. We will monitor Gary for 10 years – you don’t have to worry.’
They made us feel so confident.”
His fiancée, Paula Collins, 35, added: “When Gary became involved in the
trial, we thought it was fantastic news because we thought Gary’s chance of
survival would be greater and the care would be better.”
The trial, called TE23, was testing whether a combination of five existing
chemotherapy drugs was better at treating testicular cancer than the
standard treatment of three drugs. Foster was in the group receiving the new
therapy.
From June until mid-Septem-ber 2007 he made regular trips to UCLH in central
London, to receive the drugs. On seven occasions between July and September
last year, he received 30,000 units of one of the drugs, bleomycin, instead
of 15,000.
Foster and his family had no idea the drugs they believed were saving his life
were killing him. Colleen Foster said: “We just thought Gary was getting
tired because of the chemotherapy.”
Eventually Foster developed a dry cough, a symptom of lung damage, caused by
an overdose of bleomycin. An inquest heard that the cough should have been
recognised by doctors and nurses as a warning sign that the bleomycin was
damaging his lungs. Despite the cough, Foster was given a final dose.
The coroner ruled that Foster died as a result of lung damage caused by an
overdose of bleomycin. The coroner also found that the instructions for the
trial had been wrongly set up on the electronic prescribing system at UCLH.
Colleen Foster said: “An overdose gives the impression that it was a one-off.
It was seven times. Every week my poor Gary was going into hospital, we
thought he was getting better but, actually, he was being slowly poisoned
and poisoned to death.”
Eventually he became so ill that he was transferred to intensive care and put
on a ventilator, but attempts to save him were in vain. Foster’s family
blame his death on a trial they say was set up in a hurried and piecemeal
manner.
Collins said: “Checks should have been carried out. It is incomprehensible
that they were dealing with the most dangerous medicines and they were so
blasé. It was so slapdash.
“We had dreams and lots of plans together,” she said. “Gary also had his own
ambitions. We were supposed to be getting married on Saturday September 6,
instead, on the Tuesday before, we were at the inquest. He was such a lovely
person. He was so well liked and had so many friends.”
“We do need trials but there need to be more controls,” Collins added. “I
would encourage other people thinking about taking part in trials to proceed
with caution. I would hate to think of anyone else going through what we
have gone through.”
The family’s solicitor, Mark Bowman of Field Fisher Water-house, said: “This
case high-lights the potential dangers involved in any form of clinical
trial. Such trials need to be set up, regulated, monitored and administered
with the utmost scrutiny, to avoid others suffering the fatal consequences
that befell Mr Foster.”
As well as suspending the trial, UCLH says it has introduced measures to make
the tests safer. These include instructing pharmacists and senior
consultants to double-check all medical trial instructions on the hospital’s
computer prescription system. Nurses will be required to carry out
additional checks of whether a drug has caused any damage before giving
further doses.
A statement issued by UCLH said: “The trust has met Mr Foster’s family on four
occasions to discuss their concerns and to share the lessons we feel can be
learnt from his treatment. We would like to reiterate our deepest sympathy
and condolences to the family and friends of Mr Foster.”
The MRC said it had reviewed its trial procedures as a result of the tragedy
and introduced additional checks. It said it followed its normal procedures
by posting its concerns rather than making an emergency phone call.
“During the processing of the forms for the UCLH patients, a possible dosing
error for these two patients was spotted. A query form was then returned to
the hospital.”
Dr Stephen Harland, who was in charge of the trial at UCLH and supervised
Foster’s care, declined to comment.
The ‘Elephant man’ case
Six men were gravely injured in March 2006 when a trial of the experimental
drug TGN1412 at a research unit run by the company Parexel went disastrously
wrong.
The men, who were healthy, were each paid £2,000 to receive the drug. All of
the volunteers suffered multiple organ failure, including Ryan Wilson, left,
who had to have his toes and the tips of his fingers removed.
After the so-called ‘elephant man’ trial, a group of experts set up by the
government made 22 recommendations designed to ensure that danger signs were
not overlooked again. TeGenero, the German company behind TGN1412, has since
been declared insolvent.
The rules of testing
Before a new drug, or combination of drugs, can be approved for use, it must
go through an extensive set of trials to assess both safety and
effectiveness.
After animal studies have been carried out, there are three main stages of
human trials.
Phase one tests the safety of a treatment and studies any side effects. These
trials involve only a small number of people, who may be healthy volunteers.
Drug companies often pay them, with rates typically from £100 a day.
Phase two tests the efficacy of a treatment. Trials are conducted on a larger
group, who usually have the disease for which the treatment is to be used.
Usually a few hundred people take part in this stage.
Gary Foster was involved in a phase two clinical trial for a new combination
of existing chemotherapy drugs rather than a unique medicine. Fifty-six
patients were taking part in the trial.
Phase three tests the new treatment in a larger group of people and compares
it with what is currently on offer or with a placebo. These trials typically
last a year or more and involve several thousand patients.
While healthy volunteers are often paid to test new drugs in phase one trials,
phase three trials are generally unpaid because the volunteers are usually
patients trying to find an effective new treatment for their illness.
In almost all cases, the European Medicines Agency is responsible for
licensing drugs across the European Union. The Medicines and Healthcare
Products Regulatory Agency (MHRA) oversees clinical trials in Britain.
