On Monday night this week, six men aged between 18 and 45 went from paragons of healthfulness to suffering severe organ and respiratory failure within a matter of hours. These men had voluntarily offered themselves as human ‘guinea pigs’ for a drugs trial involving a Phase 1 antibody-based product, designed to treat ‘chronic inflammatory conditions and leukaemia’ at the Parexel medical unit in Northwick Park Hospital, north-west London.
Many people quite rightly feel compassion for these unfortunate men and their families as it appears that their fate may have, in some part (pending investigation), been due to human error or negligence. As a freelance journalist it is essential to one’s integrity to remain as stoic and objective as possible at all times. Yet, in this instance I afford myself a selfishly high level of gratitude because it could so easily have been me in Intensive Care right now.
Only a few weeks ago I considered the option of screening for the very same trial (a ‘screening’ is the initial full medical examination that takes place in order to determine who may or may not participate on a medical trial. Exclusions include smokers, recreational drug users and those that do not adhere to the strict dietary and physical activity restrictions). Thanks to an unforeseen extension on my current work contract, I was forced to postpone signing up for the trial, leaving me now with a feeling akin to witnessing a car accident.
On the surface, this may appear to be my about-face considering the article I wrote last year regaling the idea of medical trials as ‘Money for Nothing’ (see link below). I have, for many years, unscrupulously accepted many a place on many a medical trial with the constant chime of sterling ringing my ears and rolling my eyes. In fact, I was once even paid by The Mirror newspaper for an interview regarding my experiences on drug trials.
Truth be told, though, I still believe drug trials to be a safe and lucrative environment for travellers, students, creatives and small business owners to sow the seeds of their unorthodox lifestyle practices. In the 10-15 trials I have completed in the 8 years since I first started, I have only once felt any significant side effects from a drug. It was on an occasion when the effects were actually predetermined and deliberately instigated. I was injected in the stomach with a small dosage of scopolamine to replicate the effects of Alzheimer’s. This was then eradicated with the trial drug a few hours later. I was monitored by nurses throughout the whole procedure.
The most frightening experience I have had in connection with a medical trial was during a screening process last year. A small Walkman-sized monitor was fixed to my upper body with wires for a period of 24 hours whilst I continued my daily patterns. However, this was during the weeks directly after the shooting of Jean-Charles De Menezes at Stockwell station, so it easy to understand why I was nervous wearing the contraption on the tube (this practice has now been discontinued by the Parexel unit).
As with most men on the trials (limited number of trials open to female volunteers) the lure of easy money is strong and the last trial you did is never just that – the last. Despite volunteers only being allowed to take part in one trial every 3-4 months, the addictive and simple nature of the process stays with you like a vacation. It is a quick break from the outside world, a chance to relax and read the papers, watch the Commonwealth Games, meet interesting like-minded, usually Antipodean, free spirits such as yourself. Very rarely does anything remotely dramatic happen in the wards.
I spoke with three friends, A, B and C, who chose to remain anonymous for fear of being hounded by the press. They are acquaintances of mine through previous trials at the Parexel unit. I was particularly interested to hear their version of the events that took place on Monday as all three of them were present when these incidents occurred. They had been part of another trial taking place at the same time. For Friend A this was trial #10 at the Parexel unit. For Friend B, it was #3. Friend C was on his 2nd outing.
All, like me, have NEVER experienced any incidents anywhere near the magnitude of this (mild headaches and fatigue being the most regularly-mentioned symptoms previously).
On the ward
Upon arriving on Monday morning my Friends encountered a mood that was very different from the subdued atmosphere one usually expects on Day 1 of a trial. Friend A told me how, “The air amongst the staff was noticeably anxious. When I arrived at 11am, which would have been around 3 hours after the guys [taken ill] had been dosed, there were 3 ‘suits’ looking very tense, pacing up and down the corridor. These later proved to be German visitors from TeGenero, the company responsible for the drug trial.”
By 2pm a senior nurse had gathered the group together and told them to move all their belongings out of Ward 1, the ward nearest the exit, and into the common area. At 2.30pm, Friend A went back into Ward 1 to collect a towel that he had left behind.
“I saw that one volunteer was on a respirator and a second had all the curtains fully drawn around his bed with a flotilla of staff revolving around him. During the course of the afternoon I observed nurses systematically taking all of the oxygen tanks from each of the wards to use in Ward 1, and at some point in the early evening I overheard a conversation between several staff saying that they had now used up all of the oxygen in the whole Parexel unit – which I guess would be a minimum of 14 cylinders.”
According to information that was overheard or filtered from other volunteers, my Friends discovered that within 45 minutes of having the drug administered (by I.V.) the 6 men had pulse rates of up to 160 and their blood pressure was crashing. In addition, they had been alternately burning hot with sweats and dropping to ice cold temperatures within minutes. This was concurrent with erratic periods of convulsing and vomiting.
Two of the 8 men taking part on the TeGenero trial were given placebos. Friend C described how one of them felt about the situation: “The look on the faces of the men taking the placebos was something to witness. I have no idea how I would have felt, but I remember a not-particularly notable chap sitting in the corner minding his own business, and after we had been discussing what was happening for a few minutes, he finally piped up and said he was the placebo. I could see he was in a kind of surreal state. I don’t think he even realised the seriousness of the events at that point, but you could see he wasn’t sure if he was supposed to be happy that it wasn’t him in that ward, or if he should feel genuinely sorry for the other six. As someone had mentioned before, it was like a game of Russian roulette, and his number hadn’t come up.”
Everyone was then moved away from the scene in Ward 1 toward the other end of the unit. When asked, the staff said it wasn’t serious and that it was just that they were feeling a ‘bit sick’, according to Friend B.
Evidently, the Parexel staff asked the 6 men if they would like to eat, and only two of them said yes. They were then individually brought to the dining area in wheelchairs, where all three of my Friends observed their condition.
“When the two guys appeared in the doorway a part of me wanted to get up and receive them as heroes. I could tell these two guys were putting on their happy faces and trying to keep their spirits up, but it didn’t take long before their conditions worsened again,” Friend C noted.
Friend B spoke about how, “They tried to eat some dinner, but one guy couldn’t even lift the fork and the other was so out of it that he had flopped down with his head flat on the table and his arms hanging down. The nurses stood by nervously asking if they were ok. Stupid question I know. One of them, with dribble coming from his mouth, said, ‘Yeah I feel better now’.”
Friend A noticed how, “The first guy was drenched in sweat and his face was swollen and white, but with dark red blotches and wide, heavily bloodshot eyes. He was clearly in agony, and spoke of searing pains shooting through his whole body. He said that whichever way he moved or turned in bed more pain seemed to ensue. I asked him if he felt better than he had been. He replied that he was definitely better and that he was slowly recovering. He even joked a little about what he had been through, and about what bad luck it was since this was his first medical trial. The second volunteer was brought out. He sat with his head on the table and was convulsing quite severely. Various staff attended to him and asked if he wanted to return to bed but he remained where he was for 15 to 20 minutes until they finally took him back in the wheelchair, his meal untouched. I remember thinking that these were the sickest looking people I’d ever seen, and yet these were the two who had recovered the most. I wondered what the condition of the remaining four must be like in comparison.”
As is the usual routine on these trials, a ‘lights out’ call comes promptly at midnight, yet unusually, no such action was taken on Monday night. As no news had been officially passed back to my three Friends, they approached some of the senior nurses themselves about an update. According to Friend A, “She said that in 16 years of working with medical trials she’d never seen, or even heard of, anything like this before. We asked her if she thought the guys would be OK. She replied they’d almost certainly be fine by the morning, by which time things would have flushed from their systems. She said that nausea is a terrible thing to have.”
When they awoke the next morning, well passed the scheduled time of resumption for their own trial, a doctor told them that only one of the sick men had gone to the Intensive Care Unit, as a precaution procedure, and that the others were fine.
Friend A confirmed that, “We were told that a couple of them were ‘holding their own’. That didn’t seem hopeful, to say the least, and I thought that even when they do recover they would surely have suffered organ damage from the toxin that their kidneys and liver were trying to remove. It didn’t even occur to me that some of them might never recover at all. There was a sense of disorganisation about the place which I’d not encountered before. It felt like there was lots of staff there but no-one really knew what to do in the circumstance.”
They were then told that their trial was to be put on hold (due to staff working with the ill patients) and told to go home. The trial has since been extended by one week and a further ?500 compensation has been given to the participants. Friend C told me that he had, “Heard of trials being cancelled early, but that one trial should affect all others had to mean something more ominous.”
So how could a drug that had been tested on animals without any significant drawbacks have such a severe adverse reaction in healthy humans? Was the dosage too high? Was there any human error involved? Was there a problem with storage of the drug? Was there unforeseen affects that occurred which would not have been proved through animal testing? Or was it down to inexperience?
According to Parexel, the staff acted completely within regulatory, medical and clinical research guidelines when administering the appropriate dosage to the volunteers. A protocol had been designed by TeGenero and had been approved by the ethics committee and the MHRA (the Medicines and Healthcare products Regulatory Agency).
TeGenero, a privately-owned German biotechnology company with only 15 members of staff, was founded as recently as June of 2000 by a group of immunologists. It was specifically created to exploit the commercial potential of their discovery, the TGN1412 antibody. It would seem that this is the first time TeGenero has ever tested on humans.
What does this awful incident tell us about medical trials and what can we learn? Friend A gave me his perspective on the matter: “Compare TeGeneros meagre finances to the $millions and huge human resources that it costs to bring most other drugs to human testing stage. I think you can see the potential for shortcuts and speedups in the effort to make a saleable product! It’s interesting how this major incident has brought into focus (for the wider population) the exact nature of the tests. The necessity of human testing doesn’t seem to be something that most people have any previous awareness of. The other thing that this drug has highlighted is the potential fallibility of animal testing. If we assume that this drug was administered properly, and was not contaminated, then it can only be the case that a molecule that was heavily tested on animals over several years, and was subsequently passed as safe by an independent ethics committee, has had a totally different impact in human subjects. Either that or the early testing was improperly done.”
Friend B has, “No problem with human medical trials, as they are an essential part of medical research. People should stop pissing themselves over this incident because that’s the point of human medical trials, to see if they are safe in man. This one obviously isn’t. The issue is whether the sponsor fucked up the dosing or ingredients of the drug.”
A thorough investigation, including branches of Scotland Yard, is currently in operation.
As the nation awaits the outcome of the six men involved, I, and others like me, begin to wonder whether we should continue to take part in trials after witnessing these terrible situations.
Friend C has decided to call it a day on completion of his current trial:
“I’m going to finish this trial, because I’ve already had the first dose and know it doesn’t do anything, but I don’t think Parexel will be hearing from me again any time soon. I’ll bank my money while I’m still up!”
Both Friend A and Friend B, however, told me that they would definitely do another trial, Friend A in particular stating that if he were to do another trial in the future he, “Would probably do far more research into the background of the compound and sponsor than I have done in the past. In that sense, I think that this incident has highlighted the importance of my personal responsibility for my actions.”
Personally, I choose to await the publicity of the investigative findings before making a decision on whether to take part in another trial. I also follow closely any news on the condition of the 6 men still in Intensive Care which, as I write, remains at 4 showing slight signs of recovery and 2 still very critical. My thoughts go out to them with the hope that our medical professionals can capably bring them safely out of this terrifying ordeal.
Perhaps I should put my trust in Professor Herman Scholtz, head of international clinical pharmacology for Parexel, when he says: “Such an adverse drug reaction occurs extremely rarely and this is an unfortunate and unusual situation.”