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Research Ethics

This will hurt a bit

11 Apr, 14 | by David Hunter

In a piece titled in a fashion to simultaneously win the internet and cause every male reader to wince, Michelle Meyer asks “Whose Business Is It If You Want a Bee To Sting Your Penis? Should IRBs Be Policing Self-Experimentation?

In this piece she describes the case of a Cornell graduate student who carried out a piece of self-experimentation without IRB approval (based on the mistaken belief it wasn’t required) which aimed to assess which part of the body was worst to be stung by a bee on and involved:  ”five stings a day, always between 9 and 10am, and always starting and ending with “test stings” on his forearm to calibrate the ratings. He kept this up for 38 days, stinging himself three times each on 25 different body parts.”

While IRB approval was required and not sought in this case, Meyer argues that this isn’t problematic effectively because in her view regulating researcher self experimentation constitutes an unacceptable level of paternalism:  ”The question isn’t whether or not to try to deter unduly risky behavior by scientists who self-experiment; it’s whether this goal requires subjecting every instance of self-experimentation, no matter how risky, to mandatory, prospective review by a committee. It’s one thing to require a neutral third party to examine a protocol when there are information asymmetries between investigator and subject, and when the protocol’s risks are externalized onto subjects who may not share much or any of the expected benefits. Mandatory review of self-experimentation takes IRB paternalism to a whole other level.”

Perhaps this is just my inherent lack of a distaste for relatively benign paternalism but I don’t quite see this objection to regulating self experimentation working for three reasons.

Firstly the distinction Meyer draws between self and other experimentation assumes a high level of understanding of the risks and benefits on the behalf of the researcher in a way that negates the need for the normal consent process. This is probably right most of the time and so we can assume consent is present. Does this negate the need for external review? I am not sure it does since the researchers understanding is not perfect and they may be self deceiving in regards to the magnitude and level of risk. Meyer notes for example that this project originally involved stings to the eye, until the supervisor of this student pointed out that this risked blindness. So review by external experts regarding risks and benefits of research can and does reduce the levels of risks in research. In Research Exceptionalism James Wilson and I argue that this is a general justification for external research regulation – the ethics and risks and harms of research are complex and unpredictable and hence external regulation helps clarify these risks and ethical issues to enable researchers to fulfil their moral duties. This is of course paternalistic in the case of self-experimentation, but I presume that the student in this case is grateful to his supervisor for saving his vision, so I think it is the kind of paternalism we ought to endorse, since it is in regards to a risk that the person wouldn’t want to run.

Secondly valid consent, doesn’t just consist of having information, it also requires competency and particularly in these types of cases an absence of coercion. This is a graduate student who is to be frank in a vulnerable institutional position (like many of us in academia…) – if they want to improve their standing and move to the next level they need to keep their superiors happy. This makes them vulnerable to self exploitation and risk taking, which external regulation can reduce and remove.

Finally I suspect that what is going on here is a kind of reverse research exceptionalism where the regulation of research is seen as somehow more problematic than the regulation of other aspects of our lives. It is commonplace for health and safety to require us in the course of our employment to to act and not act in particular ways. This is both paternalistic insofar as it protects us, but it is also not paternalistic insofar as it protects both others and the instution we work at. In this case, this student is working in a lab in an institutional context and if something had gone wrong for the student or others in the course of this research then the institution could well have been held liable for damages arising from this. As such it seems perfectly within their rights to me to decide how to regulate these risks to them, and to decide to regulate these via prospective review.

Now as Meyer notes this is an external requirement rather than a choice that Cornell has made, but I don’t think this changes the justification for the regulation – given that we know in markets competition tends to drive towards failures to protect workers and others, there is nothing inappropriate with the state correcting the market failure here via legislation.

 

 

 

 

 

An Attack of the What-Ifs

25 Oct, 13 | by Iain Brassington

Among the comments to the last post, there’s this from Parmenion59:

So…if a cure for lung cancer is found, and the study has been funded through money from a tobacco company…the BMJ won’t publish said study?
Way to go BMJ.

Hmmm.  At least on the face of it, this looks like an important point – one that deserves a bit of unpacking.  We can begin by distinguishing between responses to this particular point, and responses to the general idea behind it.  First things first.

I’m willing to bite the bullet and admit without worrying too much that the policy of not accepting papers funded by the tobacco industry may mean that some research is not publicised.  There’s a small handful of reasons why I’m willing to do that.  One of them – admittedly the weakest of the lot – is based on the idea that it’s not wholly clear that much tobacco money really is directed at finding a cure for lung cancer, rather than firefighting other research about the detrimental properties of tobacco.  But that, as I say, is weak, based on suspicion rather than anything enormously substantial; and even if the hunch is correct, it’s merely empirical rather than anything conceptual.  Still, even if the hunch is wrong, it shouldn’t matter, because there’re stronger reasons.

One is based around the idea that there’s a special providence in the fall of a pipette – or, put another way, you can’t keep a good truth down.  If something is there to be discovered and is worth the effort, then it’ll be discovered sooner or later; if not by Smith, then by Jones.  And, because scientific progress is invariably a matter of the accretion of the work of several teams, all working independently and making minor discoveries, rather than one heroic person who would be solely responsible for The Cure For Cancer ™, the loss of one paper here and there probably won’t make all that much of a difference in the grand scheme of things. If that’s correct, then the idea that we might lose the cure for cancer is not all that compelling – not one about which we should worry too much.

A final reason is that, as I’ve said before elsewhere, I’m not persuaded that research is obligatory: it’s admirable, but not required by duty.  There’s a range of second-order arguments one might present here, but most relevant has to do with the benefits that research might generate.   more…

Smoking out Tobacco Industry-Supported Research

18 Oct, 13 | by Iain Brassington

BMJ Open, along with a couple of other journals, published a statement a couple of days ago saying that they’d no longer accept papers based on research wholly or partially funded by the tobacco industry.  The gloss on the statement is damning:

The tobacco industry, far from advancing knowledge, has used research to deliberately produce ignorance and to advance its ultimate goal of selling its deadly products while shoring up its damaged legitimacy.  We now know, from extensive research drawing on the tobacco industry’s own internal documents, that for decades the industry sought to create both scientific and popular ignorance or “doubt.”  At first this doubt related to the fact that smoking caused lung cancer; later, it related to the harmful effects of secondhand smoke on non-smokers and the true effects of using so called light or reduced tar cigarettes on smokers’ health.  Journals unwittingly played a role in producing and sustaining this ignorance.

Some who work within public health and who buy the notion of “harm reduction” argue that the companies that now produce modified cigarette products and non-cigarette tobacco products, including electronic nicotine delivery devices (e-cigarettes), are different from the tobacco industry of old, or that the tobacco industry has changed. For “hardened” cigarette smokers who can’t or won’t quit cigarettes, the argument goes, new tobacco products could represent potential public health gains, and company sponsored research may be the first to identify those gains.

But one fact remains unassailably true: the same few multinational tobacco companies continue to dominate the market globally and, as smaller companies develop promising products, they are quickly acquired by the larger ones. However promising any other products might be, tobacco companies are still in the business of marketing cigarettes. As US federal court judge Gladys Kessler pointed out in her judgment in the case of US Department of Justice versus Philip Morris et al, the egregious behaviour of these companies is continuing and is likely to continue into the future.  And just this summer documents leaked from one company showed a concerted campaign to “ensure that PP [plain packaging of tobacco products, bearing health warnings but only minimal branding] is not adopted in the UK.”  The tobacco industry has not changed in any fundamental way, and the cigarette—the single most deadly consumer product ever made—remains widely available and aggressively marketed.

What should we make of the policy?

A bad argument against the ban – yeah, I know that that misses some linguistic subtlety, but it’s close enough – is that it’s a violation of free speech: it really is no such thing, for the simple reason that noone is trying to stop the tobacco industry making its case – a right to free speech doesn’t imply a right to a platform.  Of course, if every reputable publisher denies the industry a platform, than this might be a de facto rather than de jure curb on free speech – but that’s just the way it goes: just as noone gets to insist that a particular person gives them a platform, they don’t get to insist that they be provided with one at all.  (Also – though it doesn’t apply in this case – merely to splutter “B…b.. but free speech!” isn’t an argument anyway.)

Still, I guess I am uneasy about a ban. more…

Research Ethics and Ethical Problems

16 Aug, 13 | by Iain Brassington

Noted on Ben Goldacre’s twitter feed a couple of weeks ago was this article in Slate about the recruitment of pregnant women into drug trials.

Essentially, there’s a situation in which there’s a dearth of information about the impact of drugs during pregnancy.  According to the article,

[p]harmaceutical companies are not willing to navigate the legal and ethical minefield of testing drugs on pregnant women, especially because pregnancy lasts only nine months, a short window in which the tests could pay off in additional sales.  As a result, drugs are often prescribed to this population off-label, meaning that they haven’t been specifically approved for pregnant women.

Of course, that doesn’t explain why testing is an ethicco-legal “minefield” to begin with.  Still, it’s not all that hard to come up with at least a skeletal explanation: the whole point of trials is that the effect of a drug is unknown, and this might mean that it’s not safe.  When we’re talking about a volunteer, then it’s important that they know the risks before enrolling; but when a woman is pregnant, another dimension is added: she’s effectively volunteering her unborn child as well.  And it might be problematic to expose another human – even a foetus – to an unknown risk.

But this leaves us with a paradox: more…

Safety First? How the Current Drug Approval System Lets Some Patients Down

15 Aug, 13 | by BMJ

Post by Julian Savulescu

Cross-posted from the Practical Ethics blog, and relating to this paper in the JME.

Andrew Culliford, whose story is featured in the Daily Mail, is one of the estimated 7 in 100,000 people living with Motor Neuron disease, a progressive degenerative disease which attacks muscles, leaving those affected eventually unable even to breathe unassisted. For Andrew, a young father who has a severe form of the disease, it means a two to five year life expectancy.

Like Les Halpin and Jenn McNary, the mother of twins afflicted with a similar rare disease, he has a simple request: earlier access to medicines that might help improve or extend his life.

The US introduced a mandatory pre-approval process for pharmaceutical drugs after over 100 people were killed by an untested drug formulation. Today, each drug must go through a series of strictly controlled trials, including Phase 1 tests on healthy volunteers, followed by Phases 2 and 3 which test the drug and dosages on smaller and then larger patient groups. The process is estimated to cost $500 million per drug and to take 8 – 12 years.

The process is designed to ensure the efficacy of drugs has been scientifically demonstrated to a very degree of confidence, and to ensure that patient safety is sufficiently protected. In many ways it has been a triumph of science and regulation.

But it has been a failure for one small group of patients: those with rare, imminently lethal diseases, for whom there are no existing good treatments. more…

The Value of Role Reversal

20 Jun, 13 | by BMJ

Guest Post by Rebecca Dresser, Washington University in St. Louis

Not so long ago, medical researchers had a habit of using themselves as guinea pigs.  Many scientists saw self-experimentation as the most ethical way to try out their ideas.  By going first, researchers could test their hypotheses and see how novel interventions affected human beings.

Today we rely on a more systematic process to decide when to begin human testing, with experts and ethicists evaluating when a trial is justified.  But a modified version of self-experimentation still makes sense.

People who conduct human research, as well as those serving on research ethics boards, can learn a lot from volunteering for studies.  Just as doctors learn from personal experience as patients, scientists and ethicists learn from personal experience as subjects.

Looking at study requirements and the consent process from the subject’s point of view can be quite educational.  I discovered this myself when I was given the option of enrolling in a cancer treatment trial.  I had never before realized that enrolling in a trial can delay the start of treatment, because of the extra appointments and procedures research enrollment can require.  Nor had I realized that because cancer trials take years to finish, subjects in those trials may lose an opportunity to receive new drugs that emerge during that time.  I’ve spent three decades writing about research ethics and serving on research review boards, but I learned new things once I had to decide whether to become a subject myself.

No one should be forced to participate in research, of course.  But I encourage research professionals to consider becoming subjects themselves (not necessarily in their own trials, but in studies conducted by others).  This modern version of self-experimentation might give researchers and ethicists a better sense of what people need to know before enrolling in a study.  It might also give scientists and review committees a deeper understanding of the risks, inconveniences, and benefits that subjects experience in research.

Rebecca’s paper “Personal Knowledge and Study Participation” is now available online first here.

X-rays, aslyum seekers and research ethics/governance

12 Apr, 12 | by David Hunter

There is an interesting story here: in the Guardian about a research trial being carried out by the UK border agency using dental x-rays to try and identify the age of young asylum seekers.

more…

Of Tusks and Tuskegee: A Problem in Research Ethics

1 Mar, 12 | by Iain Brassington

Xtaldave, by his own admission, has the horn.  Well, if you’re being accurate about it, he has the tusk.  But what’s important is that he has a whopping great piece of ivory to play with.

Dave works in the labs here in Manchester, doing clever things with chemicals and science and crystalography and that sort of thing.  The ivory has been confiscated by customs; it found its way into his lab because the dentine in a great big tooth is a useful medium on which to carry out research that may generate significant benefits.  In his words, the tusk is

an acceptable substitute for human bone in the sorts of assays that our lab does to test the effect of various substances on cells called Osteoclasts that are responsible for bone resorption (basically bone destruction).  During growth and development of the skeleton, bone is formed (by Osteoblasts) and broken down (by Osteoclasts) – it is thought that the bone disease Osteoporosis is caused by an imbalance of bone formation and destruction – i.e. too much Osteoclast activity.

If we can find a therapeutic agent that inhibits Osteoclast activity, we might be able to halt or slow the progression of Osteoporosis.  The upshot of all this is that our lab has obtained a section of Elephant horn that has been confiscated by the UKBA.  We will recycle this and use the dentine in our bone resorption assays.

Why’s this of interest here?  Well, the ivory trade is (a) illegal, and (b) deeply morally problematic.  The fact that it’s illegal means that the UK Border Agency confiscates ivory as it’s imported into the country in most cases.  (There are situations in which importation is legal, but they’re rare, and needn’t concern us here.)  And this confiscation means that the Agency ends up with a load of ivory on its hands.

One option might be to sell it; but that’s ruled out by the same considerations that make importation illegal to begin with.  Another is simply do destroy the lot.  A third is to allow labs like Dave’s to make use of it.  This is where the moral claims come in.  It would be, he says, immoral (as well as legally problematic) to sell the ivory, and

if someone has already killed the elephant and removed the Ivory, better that we use it to further medical research and perhaps save or improve some lives, than turn it into a bauble that sits on a shelf gathering dust.

Or, to put it another way: that the elephant has been killed is bad; but we can at least salvage something from the moral wreckage.

Is this correct?  Well, the structure of the argument seems to follow quite closely that which is sometimes presented in relation to the use of – for example – data derived from the morally repugnant experiments of the past.  If there is, in Stan Godlovich’s words, “demonstrably important and beneficial information gathered methodically through means completely unacceptable to us”, what should we do with it? more…

Is Bird Flu Research a Security Risk?

21 Dec, 11 | by Iain Brassington

A story that has had a little airtime on the news over the last 24 hours or so concerns requests by US officials that details of research into a bird flu variant be held back from publication on the grounds that it might be of use to terrorists:

The National Science Advisory Board for Biosecurity recommended that the “general conclusions” be published but that final manuscripts not include details that “could enable replication of the experiments by those who would seek to do harm”.

The BBC’s health news blog reports that

Professor John Oxford from Barts and the London School of Medicine [says], “They should definitely publish. The biggest risk with bird flu is from the virus itself. We should forget about bio terrorism and concentrate on Mother Nature.”  [He and Prof Wendy Barclay from Imperial College London] agree that the influenza virus would make a pretty poor bioterrorist weapon, unless your aim was to spread the infection across the world. Influenza has no respect for borders, so introducing a virus in one country would inevitably spread it globally.

But Michael Parker, Professor of Bioethics and Director of the Ethox Centre at the University of Oxford, disagrees.  ”The position that everything should be published is not tenable. There must be some scientific information which contains an immediate threat to public safety if it fell into the wrong hands.”

Parker’s worries reflect those articulated by Tom Douglas and Julian Savulescu in the JME a little while ago; they argued that synthetic biology raises significant new ethical problems, not least because of the potential for “dual use”.

I have to admit that I have yet to be convinced by the biosecurity worries.   more…

Fighting Fire with a Different Kind of Fire?

16 Aug, 11 | by Iain Brassington

How much would I love to have been on the ethics committee that was faced with this?

Researchers at the University of Pennsylvania were interested in a method of treatment for leukaemia that made use of modified versions of white blood cells.  Cells were taken from leukaemia patients and genetically modified in two ways: first, they were adapted to target the cancer cells; second, they were adapted to reproduce like crazy.  This second modification is important, because attempts to make use of the first have hitherto fizzled out as the modified cells died off.  Or, in slightly more scientific language, the New England Journal of Medicine explains that

[f]irst-generation chimeric antigen receptors had limited clinical activity, primarily because in vivo activation of the chimeric antigen receptor T cells induced only transient cell division and suboptimal cytokine production, which failed to produce prolonged T-cell expansion and sustained antitumor effects. These deficiencies were overcome by the addition of a costimulatory signaling domain in second-generation chimeric antigen receptors, which enhanced the proliferation, survival, and development of memory cells — features that appeared to be the hallmarks of successful therapy with EBV-specific T cells and tumor-infiltrating lymphocytes.

And this approach, based on preliminary results, seems to be very promising, having exceeded expectations.  The paper reporting the experiment is available here.

But how do you get the modification into the cells to begin with?  The team

used HIV-derived lentiviral vectors for cancer therapy, an approach that may have some advantages over the use of retroviral vectors.

And that, of course, is where things get interesting. more…

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