Seriously ill volunteers after clinical trial treatment

[Humphreys]

I'm just waiting for the PETA people to start gloating that "animal testing doesn't work." I suspect that volunteers will still come forward - students will do anything for a bit of spare cash.

Apparently, the demand has actually increased since this event!

Maybe people think it can't possibly happen again, or more likely, people who never even knew you could get money for being a guinea pig now do, and fancy getting their heads popped.

 

[Capsid]

Ethical review bodies include a non-scientist lay person on the committee to question the "holy methods of modern science".

 

[Abooga]

"So the market economy clashes with making good drugs does it? How many major drugs ever came out of the communist bloc? Go on, name one."
I have no idea.
What I´m saying is that the market economy allows for making good drugs that dont´s kill too many people. And that morality calls for those deaths to be avoided. Or at least to try to avoid them. See the clash? it´s a bit subtle perhaps.
I´m not a commie as in Comunist, I just don´t dig neoliberal ideology.

Ok Elaedith, let me rephrase that "Let the pharmaceutical professionals to it, they know best". Happy now?

I´m off till Monday so don´t expect me to answer till then. This has been my first day in this forum and I´ve enjoyed it greatly. Thank you. Adios!

 

[Asolepius]

Ethical review bodies include a non-scientist lay person on the committee to question the "holy methods of modern science".

In my experience the lay members are not the ones to question the science. They just question the ethics. The scientists question the science. But of course they are not divisible - an unscientific trial is unethical because it exposes subjects to risk for no good reason.

Ethics review is not by any means optimal but we would be lost without it.

 

[Deetee]

The British Medical Journal this wek has a review of this new book by Jacky Law: "Big Pharma: How the World's Biggest Drug Companies Control Illness"
The editor of the Drugs and Therapeutics Bulletin says: (Selected extracts)

The pharmaceutical industry is a business. This banal and obvious fact needs emphasising because it is often forgotten or overlooked by both supporters and critics of the industry's ethos and activities. And the industry itself is happy to downplay its true motivations where this suits the circumstances. It can, for example, pose instead as educator, charity supporter, health service provider, and even patient advocate.

While such roles hardly mask the underlying commercial imperative, observers may be reluctant to consider them primarily in business terms. This would be a mistake, not least because, when viewed in this way, there is much to admire about the pharmaceutical industry. Other industries could perhaps learn from its energy, professionalism, flexibility, and ability to ensure that its interests are well represented wherever key healthcare decisions are taken. What is more, a focus on the pharmaceutical industry as a business need not deny the great advances the industry has provided and continues to offer, or the good intentions of many who work in it.

Indeed, the difference between the interests of industry and the public good is not necessarily a problem. Where medicines are affordable and scrupulously regulated, and offer genuine therapeutic benefits, the overlap between public health and the legitimate business interests of industry can be self evident. There is a danger, however, in taking such overlap for granted. Multinational pharmaceutical companies grew big through producing and promoting innovative medicines for major diseases. But it becomes ever more difficult and expensive to repeat such successes. Increasingly, therefore, the companies stay big by identifying and promoting diseases for their major medicines and refashioning and repackaging old products as "innovations." Also, they commonly operate under regulatory and other statutory arrangements that appear to assume that what industry produces is inevitably worth having—an approach that is more patent focused than patient focused. In this environment, assuming or pretending that there is a direct relationship between industry's efforts and improvements in public health is, at best, naive.

later....

The author is clearly no great fan of the industry. But, refreshingly, she avoids the sort of lazy polemic that casts major pharmaceutical companies as an evil empire that continually foists its products on unwilling and unsuspecting healthcare professionals and patients. Nor does she shy away from criticising those outside the pharmaceutical industry—government, regulators, doctors and patients—who have encouraged or acquiesced in the industry's way of doing things.

Food for thought and perhaps worth a read.

 

[Moochie]

Seems to me that many have rushed to their keyboards knowing few facts.

I prefer to wait and see.

M.

 

[Soapy Sam]

I have recent personal experience with the German drug testing firm Parexel...
(snip)...I certainly would never again volunteer for any drug trial that involved Parexel.

I find this disturbing. All of the information was available before the poster left home. The entire wasted trip was avoidable with a minute's thought by the company.
It certainly does not suggest a high degree of organisation.

I had supposed that drug companies did their own testing- at least in the non clinical situation. (Using the definition of clinical which I take from Rolfe's and Asolepius' posts).
It seems not.

Is there a legal requirement for this separation of function?

 

[Asolepius]

I find this disturbing. All of the information was available before the poster left home. The entire wasted trip was avoidable with a minute's thought by the company.
It certainly does not suggest a high degree of organisation.

I had supposed that drug companies did their own testing- at least in the non clinical situation. (Using the definition of clinical which I take from Rolfe's and Asolepius' posts).
It seems not.

Is there a legal requirement for this separation of function?

OK, let's get some facts straight:

1. This was a clinical trial. Clinical in this context means humans, pre-clinical (or more accurately non-clinical) means in vitro or in vivo lab work.

2. Parexel is a large contract research organisation (CRO). Drug companies contract out all sorts of work, just like other industries. There is nothing sinister or questionable about this. Many drug companies contract out all their R & D, or even their manufacturing. It's perfectly normal.

3. CROs like Parexel are so large that the experience of a single individual study subject is a very poor guide to the company as a whole. Does one medical error damn the entire National Health Service? I work with CROs day in day out, and they are just like any other type of organisation - imperfect.

4. There is no need to assume automatically that the adverse events were in any way related to negligence. They could be, but they could also be just a previously unknown effect. The problem as I see it is that people are looking for someone to blame, rather than finding out the truth.

5. The volunteers in this study will be covered by a no-fault compensation scheme. This is a requirement before the study gets ethics approval. This means that victims don't have to prove negligence to get compensation. This will cover their medical treatment. I have heard people complaining (elsewhere) that the NHS has to pay for the treatment. Not so. In any case the phase I unit was in an NHS hospital and for a good reason - so that full medical support was immediately available. Again this is normal practice. The NHS does quite well by renting out facilities for CROs.

6. I just read (BBC again) that the dose levels were checked and found to be correct. There is no evidence so far of any error or negligence. But the MHRA will audit everything and that's out of the hands of either TeGenero or Parexel. Believe me, you don't mess with the MHRA. I know.

So nothing is perfect, there is always risk, and conspiracy theorists can sleep easy in their beds. The important thing is the lesson learned from this - and we don't fully know that yet.

 

[Soapy Sam]

OK, let's get some facts straight:

1. This was a clinical trial. Clinical in this context means humans, pre-clinical (or more accurately non-clinical) means in vitro or in vivo lab work.

-You mean DoubtingStephen's case or the London one? There were people involved in both, but patients only in the former. DS was actually suffering the illness in question, so it's clearly later in the test process. That one's clinical, yes?

2. Parexel is a large contract research organisation (CRO). Drug companies contract out all sorts of work, just like other industries. There is nothing sinister or questionable about this. Many drug companies contract out all their R & D, or even their manufacturing. It's perfectly normal.
New datum for many of us I suspect. I'm not implying anything sinister. I was just surprised.

3. CROs like Parexel are so large ...
Like I say, this is a revelation to me. I never heard of CROs before. I had the impression (and can't really explain how'I got it) that the London study was done by a small outfit. Live & Learn.

4. There is no need to assume automatically that the adverse events were in any way related to negligence...
What limited news I've seen (all internet stuff) suggests the protocols were followed properly , but that they may be revised as a result of the London incident.

5. ... The NHS does quite well by renting out facilities for CROs.
The NHS as a whole, or just selected Trusts ?

.

So nothing is perfect, there is always risk, and conspiracy theorists can sleep easy in their beds... (I wonder if they do?) The important thing is the lesson learned from this - and we don't fully know that yet.

Do you think we will? I mean from the incident itself? Or will it require a whole slew more testing? Or is it just too early to say?

 

[Mojo]

Originally Posted by richardm:
I'm just waiting for the PETA people to start gloating that "animal testing doesn't work." I suspect that volunteers will still come forward - students will do anything for a bit of spare cash.

I would say, if anything, this calls for more animal testing.

Presumably without animal testing we'd be seeing this sort of thing a lot more often.

 

[scotth]

Presumably without animal testing we'd be seeing this sort of thing a lot more often.

It is a very logical conclusion. As flawed as the animal model is, it is the best thing we have. We are starting to understand how drugs work at the molecular level. But, we aren't that great at it yet. We need much more practice. And I expect our ability to simulate the effects of a drug accurately in a computer will become a reality some day. But for now, it would be very hazzardous to rely soley on our analytic modeling. We can pretty well understand how a potential drug will function on its target molecule. But, there are huge numbers of molecules that we don't model at all in the body. If the drug reacts to molecules other than the intended target, it can completely alter how it functions. We are many times more likely to catch dangerous unintended consequences with animal testing than computer modeling, today.

The continuing trend of ever more powerful computers being available to researchers may be our biggest asset to bring the costs of new drugs back into a reasonable range. I hope so.

 

[Asolepius]

It is a very logical conclusion. As flawed as the animal model is, it is the best thing we have. We are starting to understand how drugs work at the molecular level. But, we aren't that great at it yet. We need much more practice. And I expect our ability to simulate the effects of a drug accurately in a computer will become a reality some day. But for now, it would be very hazzardous to rely soley on our analytic modeling. We can pretty well understand how a potential drug will function on its target molecule. But, there are huge numbers of molecules that we don't model at all in the body. If the drug reacts to molecules other than the intended target, it can completely alter how it functions. We are many times more likely to catch dangerous unintended consequences with animal testing than computer modeling, today.

The continuing trend of ever more powerful computers being available to researchers may be our biggest asset to bring the costs of new drugs back into a reasonable range. I hope so.

Good sense here, but the key problem is that we can only program the computer with what we know. We simply don't know anything like enough to do a reliable simulation of the human body.

 

[scotth]

Good sense here, but the key problem is that we can only program the computer with what we know. We simply don't know anything like enough to do a reliable simulation of the human body.

Quite true. The reason we don't model most of the molecules in the human body is because we don't know of them at all, or we don't know enough about them to model them in a computer.

 

[Rolfe]

1. This was a clinical trial. Clinical in this context means humans, pre-clinical (or more accurately non-clinical) means in vitro or in vivo lab work.

Ok, OK! That wasn't how I had understood the terminology to be used, but I'll happily bow to your superior (and more recent!) knowledge of the matter.

Rolfe.

 

[Asolepius]

Do you think we will? I mean from the incident itself? Or will it require a whole slew more testing? Or is it just too early to say?

I'll answer your embedded questions first.

1. All the drug regulatory authorities label all human studies as clinical trials, whether healthy volunteers or patients with the disease under study. Phase I studies are usually in volunteers (looking at safety, pharmacokinetics, but now sometimes biomarkers of efficacy). Phase II firstly tries to prove (or disprove) the concept, by seeing what happens in a small number of patients with the disease. Next, usually called phase IIb, we give a range of doses and hopefully identify the therapeutic range. If all goes well, in phase III we carry out large scale trials, which generate the data required for a product licence application. Trials continue after marketing, in phase IV, to gain further knowledge of real-world use of the drug.

2-4 - not really questions so nothing I can add

5. I'm not aware of any top level business dealings by the NHS with industry. Individual trusts set up all sorts of collaborations. There are lots of phase I units sited in NHS hospitals, eg Guy's, and St George's (both in London).

WRT lessons learned, my experience is that the bigger my mistake the more I learn. But then this could be a very small mistake with very big consequences. Undoubtedly practices will change as a result of this. About 20 years ago nobody screened phase I volunteers for drugs of abuse, until the son of the British ambassador in Dublin died because he had not told anyone he was on opiates.

 

[Mojo]

Undoubtedly practices will change as a result of this.

I've seen it suggested that one of the problems was that they didn't follow the usual current practice, in that they gave an experimantal drug to eight subjects simultaneously. If they had been done one at a time we might at least have been looking at only one man in hospital instead of six.

 

[MRC_Hans]

There's no question that these men were healthy.

.

Actually, you both have a point. Now, as Rolfe correctly explains (when is she ever wrong?), a phase 1 trial is conducted on healthy volunteers, period.

However, new drugs are occasionally tried as a last resort on seriously ill patients. This can be new, yet untried, drugs, or it can be drugs that are already registered, but for a different indication. The legality of this is through the fact that a physician can prescribe whatever he/she deems to be right for a patient. Of course under full responsibility. With modern risk of ruining lawsuits, this practice is vaning, but many pioneer drugs were introduced this way (penicillin and insulin come to mind). Various speculative teatments for AIDS have also been (so far unsuccessfully) tries on terminal AIDS patients. A couple of years ago, NovoNordisk's Novoseven(tm) anticoagulant, which is originally developed for hemophiles, was given to an Israeli soldier who was hemorrhaging from bullet wounds, faster than they could infude new blood. He survived, and opened up a whole new indication for that drug.

Hans

 

[Rolfe]

I've seen it suggested that one of the problems was that they didn't follow the usual current practice, in that they gave an experimantal drug to eight subjects simultaneously. If they had been done one at a time we might at least have been looking at only one man in hospital instead of six.

I may be wrong here , but I don't believe that staggering the drug administration is "usual current practice". There was one commentator vocally suggesting that this should be done, and given what happened this time maybe it will in future, but I don't think anybody really anticipated anything quite as dramatic as this happening, and so soon.

The suggestion, that volunteers be given the drug at two-day intervals, sound like a logistical nightmare.

In any case, I suspect that two is the absolute minimum number to start with, to exclude some wild coincidence. Until last week, I suspect that restricting the risk to six people was considered to be precaution enough.

Rolfe.

 

[Rolfe]

.... a phase 1 trial is conducted on healthy volunteers, period.

However, new drugs are occasionally tried as a last resort on seriously ill patients. ....

I believe that phase 1 trials are very occasionally done on sick individuals, for example where the drug (perhaps something very cytotoxic) is considered too poisonous to subject a healthy person to. It may be that with hindsight the drug in question may turn out to be in that category. It may be one of those things which is relatively safe if the patient has the abnormality it is designed to correct, but dangerous to a normal person - perhaps someome with a normally functioning immune system in this case.

Rolfe.

 

[NeilC]

I suspect the drug would not have been tested on non-human primates before this stage. Sad though it is to say, I wonder if more primate testing might have prevented something like this.

Rolfe.

They did test it on monkeys and it gave them swollen lymph glands, apparantly,