Two interesting news articles on different sorts of conflicts of interest in research can be found here in the New York Times:
Doctor Accused of Leak to Drug Maker
Financial Ties Are Cited as Issue in Spine Study
The first piece describes how, Steven M. Haffner of the University of Texas Health Science Center in San Antonio, leaked an article critical of Avandia to GlaxoSmithKline after agreeing peer-review it for the New England Journal of MedicineA key member of the Senate said Wednesday that a prominent diabetes expert leaked an unpublished and confidential medical journal article to GlaxoSmithKline last year, tipping the company to the imminent publication of safety questions involving the company’s diabetes drug Avandia.
The second piece describes a potential conflict of interest in the study of an artificial spinal disc.“As a surgeon, it is gratifying to see patients recover function more quickly than after fusion and return to their normal activities more easily,” Dr. Jack E. Zigler, a well-known spine specialist and one of the study’s lead researchers, said in a 2006 news release announcing the latest results of the Prodisc clinical trial.
As it turns out, Dr. Zigler had more than a medical interest in the outcome. So did doctors at about half of the 17 research centers involved in the study. They stood to profit financially if the Prodisc succeeded, according to confidential information from a patient’s lawsuit settled last year.
Thursday, January 31, 2008
Conflicts of interest in big business research
Monday, January 14, 2008
Facebook and Research Ethics
This is a juxtaposition of two things I noticed recently associating social networks and various issues in research ethics.
The first is this thoughtful piece from the PredictER blog: Biomedical Research Ethics 2.0: MySpace and Pediatrics which explores some of the issues that might emerge as more and more medical information is shared by users on these sites.
The second where the delightful picture above was drawn from is an application on Facebook called "I'm a Guinea Pig!" and is described as:
Do you wish to help furthering medicine, while benefiting from state-of-the-art medical care and possibly from a remuneration ? Become a "guinea pig" for medical research!
The spectrum of experiments is very large and includes psychological tests, medical imaging studies, medical equipement testing, genetic tests, drug trials, and evaluation of the safety and efficacy of cosmetics.
Feel free to add Volterys's application and fill your profile in our database. You'll be able to browse offers from research labs. Your contacting details will only be communicated to a researcher upon your approval. At any time will you be able to decline an offer, withdraw your application for a research or unsubscribe from Volterys.
You can see the app for yourself here: Guinea Pig though only if you have a facebook account of your own.
Presently only usable in the EU, while I admire the company's inventiveness obviously it has to be questioned whether this is the best place to be recruited for medical research...
Friday, August 24, 2007
Ethics & Pesticide Research
Brandon Keim has a series of posts over at Wired Science on ethical issues in pesticide research which are worth the read.
Dow: Our Unethical Tests Show That Nerve Poison is Safe
Why Testing Pesticides on People is Wrong, Part One: Unwitting College Students
Why Testing Pesticides on People is Wrong, Part Two: Devilish Details and the Greater Good
Human Pesticide Testing's Greatest Hits
Wednesday, August 15, 2007
Communicating bad trial results to the media
An interesting article on SciDevNet called Trial practitioners must become media savvy drew my attention to this paper: South Africa's Experience of the Closure of the Cellulose Sulphate Microbicide Trial
In PLoS Medicine.
It is an interesting paper about the media reporting after the ceasing of a trial of a microbicide as a preventative measure for HIV in South Africa. Despite what looks like some fairly good efforts by the researchers to control the story, it escaped them and they report became overblown & misconstrued.
They given an excellent list of suggestions for the future of communication in these sorts of events:
* Emphasise community education.
* Explain and emphasise to the community that HIV seroconversion is the only way to measure effectiveness of new prevention technologies including microbicides (i.e., there are no surrogate markers of infection that can be used in trials).
* Educate the media and community about clinical trials, including regulatory procedures and good clinical practice guidelines followed by clinical trialists.
* Develop early drafts of press releases of all possible DSMC outcomes—positive, negative, and no effect—in partnership with local researchers and community representatives.
* Inform local ethics committees, drug regulatory authorities, and health authorities of trial outcome prior to press release.
* In drafting press releases, be sure to include the contribution of in-country investigators, community advisory boards, and other relevant bodies.
* Issue the press release in developing countries where the research is conducted. At the press conference, it is valuable to include the local principal investigator and representatives of the trial sponsor, ethics committee, and the local health authority.
Monday, August 13, 2007
NHS Scale research testing
Ben Goldacre appears to be running a series on how pharmaceutical corporations contribute to the high cost of health care in the Guardian: Evil ways of the drug companies Spectacularly expensive cost of trial and error
In this post I will discuss the second article where he makes an interesting argument for whole scale medical testing in the NHS to reduce medical costs:Imagine there are two drugs called Sixofone and Halfadozen. Nobody knows which one is better for treating sickitis. The drug companies periodically do trials, but funnily their own drug always seems to come out the best.
In our clinic, the doctor sees 200 patients in a month with sickitis. If she gives Sixofone or Halfadozen to her patients at random, on a whim, as a reflection of her own indecisiveness, then the regulation is the same as for any prescription: give reasonable verbal information about risks and benefits, thus obtaining informed consent, and so on.
But let's say the same doctor, in a spirit of inquiry, recognises that there is massive clinical uncertainty - nobody knows which of these drugs is better after all - and she wants to test her hunches, rather than simply act on them. Then she's in trouble.
She could run a speculative little trial, giving 100 patients Sixofone, and compare them with the others on Halfadozen. But she'd be struck off, unless she went through so much red tape that the idea becomes unmanageable.
After passing through the endless obstructive and bureaucratic hoops of the ethics committees, from each and every patient she would need to obtain elaborate written consent, and give huge amounts of information. Remember, nobody knows which is best, and if she wanted to hand over the same drugs, entirely at whim, outside of her "trial", there'd be no problem. This is a huge double standard, and it costs us knowledge.
But if we ever had a scientist in charge of health, instead of tinkering with payments to big pharma, they would do one simple thing: move hell and high water to collect and collate the best and cheapest evidence on healthcare. First you would give huge amounts of money to the Cochrane Collaboration, which collects and collates data independently on all healthcare interventions, and is quietly one of the most subversive organisations ever to be created, because it blows the lid on false commercial claims.
Doctors waste money by irrational prescribing decisions, so give them clean, clear, accessible information, and that will stop.
But more than that, we are in a unique position to generate data: we have inherited an extraordinary information resource, in this vast monolith of the NHS.
Nobody knows what the best treatment for stroke is, but if we randomised every single new stroke patient in the UK, over one week, into a rough trial, we'd have our answers in a couple of years.
Part of the target of his article is research ethics committees, who he claims are in effect complicit in a huge double standard, namely that doctors can prescribe according to their whims in practice, but not in research... Of course in practice this only applies when we have two reasonably equal treatments. I'm happy to agree there are sometimes biases built into the system of review, for example there is a huge bias towards the existing standard of treatment, regardless of how weak the evidence base is for that treatment. But I think this issue here is a non-starter. If we have two treatments for a condition which appear to be equally valuable, then almost certainly through out the country physicians will already be prescribing both of these. Why go through the unnecessary cost and hassle of a clinical trial, when we could get similar results, just by consulting already existing patients notes. Research ethics committee permission would still need to be obtained of course, but this is much less of a hassle than constructing a clinical trial.
There is of course also a presumption built into the article, namely that there is such a thing as a best treatment for a specific condition. But it is unclear that this is the case, it is likely instead that things are more complex than this, and what will suit one patient will not suit others. At best we can establish something less grand, namely the medicine most likely to be best.
Thursday, August 09, 2007
Snapshots of Research Ethics around the world and around the web
Research ethics is an interesting field because although most countries seem to support similar sounding values in our research ethics systems these systems are often radically different from each other. Likewise different disciplines approach ethics differently. In this post, I'm going to present four snapshots of research ethics from 3 different countries and 4 different disciplines.
First up is this excellent post: An inside-outsider’s view of Human Research Ethics Review From Greg Downey, a member of the Department of Anthropology at Macquarie University, Sydney, Australia. In it he discusses the ethics review of ethnography, both as a researcher and as a member of the University's research ethics committee. He responds to an article: Katz, Jack. 2006. Ethical Escape Routes for Underground Ethnographers. American Ethnologist 33(4):499-506.
Secondly there is this post: e-Research Ethics: A Note from Mallory Wober by William H. Dutton, Director of the Oxford Internet Institute , Professor of Internet Studies, University of Oxford. It is a fascinating post of a discussion of some of the ethical issues involved in online research.
Thirdly there is this post: IRBs vs. Departmental Review by Zachary M. Schrag, Assistant Professor of History, George Mason University, USA. Which contains a discussion between myself and Zach about the best form of oversight for oral history projects.
Finally there is my own post here: Research Ethics in the UK: The present "system" which summarises the current state of play in regards to ethics review in the UK.
If you are interested in cross cultural comparisons of the ethics review that is carried out in universities, this is probably not a bad starting point.
Monday, August 06, 2007
Irregularities in Recruitment in Potential Gene Therapy Research Death
Last week I linked to an emerging story about a woman who has died while being involved in gene therapy for arthritis: Not a good day for research. While it is not yet confirmed whether the woman's death was due to the gene therapy it does appear that there were some irregularities in process of recruitment that lead her to be involved. The Washington Post has a very comprehensive article: Death Points to Risks in Research
Key points are:
B"It was presented to her like this is going to make her knee better," said Robb Mohr, an agronomist who lived with his wife of nine years in a modest vinyl-sided ranch home near Springfield, Ill. "It was supposed to be just a simple thing."
A two-sentence paragraph halfway through a 15-page consent document that Jolee Mohr signed warns of the possibility of "unknown side effects," including, "in rare circumstances, death."
Further in, after long descriptions of how the product may help, a single sentence states: "We do not expect you to receive any direct medical benefits from participation in this study."
Mohr was in an early-phase study, the prime goal of which was to see whether the treatment was safe, not to provide a therapeutic benefit. If the drug passed muster, other studies would determine whether it was an effective treatment.
So first things first, a 15 page consent document is worse than useless, few people will read this much material in detail. Especially if, as later emerges in the article, they are not given the document to take away and study. And while the disclaimers are there by the sounds of things, they are hidden by the context, it isn't appropriate to talk about the potential benefits of a treatment, at great length, in what is effectively a safety study.
It then gets worse, since her rheumatologist gets payments from the company involved for each person they recruit onto the study. So we have direct therapeutic recruitment, which is bound to cause therapeutic confusion coupled with a conflict of interest.
The sad thing is that it is unlikely that this is an isolated case of poor practice, instead this is likely to be only the tip of the iceberg, revealed by a tragic death.
Friday, August 03, 2007
Research Ethics in the UK: The present "system"
This post is inspired in part because of the discussion I am having with James on this post: Distinguishing Audit from Research But it is also inspired by a discussion that I am having over at the Institutional Review Blog an excellent blog by Zachary M. Schrag, Assistant Professor of History, George Mason University focused on the American research ethics system. The particular discussion is whether more general ethics review ought to be preferred to departmental review. As part of this, I have said I would give a general description of the research ethics
"system" (insofar as that is a fair description) here in the UK. I'm also doing this because I want to suggest and discuss a few problems the present system in the UK has, and to do this, first we have to know what the system is. As such this will be a series of posts, like the series on the Human Tissue Act.
Currently much of the research carried out in the UK is unregulated, barring either common law or regulations on specific types of research. Most professional bodies have codes which usually indicate how their members ought to conduct research, but it is up to individual members to follow these.
There are a variety of systems for ethics review in place, ranging from the highly regulated, and well constituted NHS research ethics committees to the unregulated university research ethics sector to private research which often avoids any independent scrutiny. I will now briefly describe each system, then move on to detailing what research requires what review in the next post in this series.
The most rigorous system for review is that in the NHS, which has a national framework detailing operating procedures, REC membership and a common form: Standard Operating Procedures for Research Ethics Committees in the United Kingdom General details can be found here: National Research Ethics Service Presently all applications are reviewed by a full committee, although a system of proportional review is presently being trialled for "low risk" research. Reaching this point of a common system and form has been long and (particularly for researchers) somewhat painful, but it is hard to argue that what we have now isn't considerably better than the mishmash that the UK had 16 years ago.
In contrast what is present in UK universities is a multiplicity of different systems of ethical review, a real mishmash.
Many universities have set up research ethics systems, both due to internal reasons and because of outside drivers such as journals requiring evidence of ethics review and in particular the Economic and Social Research Council requiring that universities funded conform to their Research Ethics Framework
The most comprehensive review of the different systems is University Research Ethics Committees: Their role, remit and conduct a report published in 2004 by Anthea Tinkler and Vera Coomber.
There are basically three broad systems in operation in UK universities.
The first system is a system of review by a central research ethics committee for the university. In principle these will look at all research, but in practice this seems unlikely. According to the report half of the universities with just central committees, reported reviewing between 1-50 pieces of research a year. It would be surprising if this was all that was carried out at these research institutions.
The main alternative is a decentralised model by some School or Faculty based committee. This will often involve particularly ethically complex or worrisome research being reviewed by a higher or central committee.
The third model of ethical scrutiny is some other form of ethical scrutiny which takes a more hands off approach and either includes ethical review as a part of peer review or perhaps by providing ethical training for individual researchers and then trusting the researchers to abide by the principles which they have learned.
In the next post in this series I will indicate when there is regulatory requirements for ethical review and what these entail.
Thursday, August 02, 2007
Drug approval: what is safe enough
I mentioned recently the safety concerns in regards to Avandia a diabetes medication manufactured by GlaxoSmithKline. Wired has an excellent article disambiguating why this drug would stay on the market despite the safety concerns and how potentially still unsafe drugs reach the market.
It is a good clear article, well worth the read: FDA Drug Standards: What's Safe Enough?
Wednesday, August 01, 2007
India Research Ethics Scandal: Students made guinea pigs in sex study
A research ethics scandal appears to be breaking in India in regards to research carried out with adolescents within a school without parental consent. (Hat tip to Nita)
While the school principal claimed that this was just part of routine practice this seems to be false, as it is part of a study being carried out by the Health Care and Research Association for Adolescents. Furthermore despite the innocuous sounding name a committee came to the conclusion that the privacy of the participants was violated, and worse still it was done for commercial purposes.
Apparently this research involved genital examinations and a number of probing personal questions, about for example, underwear size and menstrual periods. The researchers claim that they presumed the school had handled consent.
It will be interesting to see what measures the Indian government takes to deal with this.
Postscript while we would all like to think this sort of thing won't happen here (wherever here is) posts like this: Drug study on kids won't require consent should suggest that we should not relax too much.
Saturday, July 28, 2007
Distinguishing Audit from Research
In the latest issue of Theoretical Medicine and Bioethics there is an interesting paper on the difficulties of distinguishing audit from research in a rigorous fashion by E. Cave and C. Nichols called: Clinical Audit and Reform of the UK Research Ethics Review System. The paper is worth reading just for the overview of different research ethics systems around the world, but also hones in on a difficult issue for research ethics.
This issue is that while many research ethics system make a strong distinction between research and audit, in practice it is difficult to see what justifies this difference such that 'research' requires ethical review whereas 'audit' does not. Part of the difficulty stems from the difficulty in identifying what research is, but the larger problem is that however we define these activities some instances of each will have low risks of ethical issues and other instances will have high risks. As such it seems odd to treat them differently. However submitting every audit to full REC consideration will be very time consuming and may stretch the present system beyond breaking point. They suggest instead establishing committees which look at quality issues in audit, much the same as R&D now looks at quality in research. The role in part of these committees will be to identify those audits that need full ethical review.
While I think this is a sensible compromise position, I am hesitant to support it primarily because I would be concerned whether the audit committees would be well suited to identifying audits that needed ethical review. It is difficult to see a system that would be more robust than requiring full ethical review. This may of course mean there will be less research, but that may well be a price worth paying to protect research participants.
Friday, July 27, 2007
Not a good day for research
Today appears to be a bit of a black Friday for research and publication since there are three different stories all of which touch on the conduct, regulation and publication of medical science.
First the Washington Post reports on the as yet scanty information released by Targeted Genetics in regards to a patient who may have died because of the novel gene therapy for arthritis they were undertaking. If this turns out to be the case it will be another set back for a field littered with potential promise and actual setbacks.
The New York Times discusses a report into safety concerns regarding Avandia a diabetes medication manufactured by GlaxoSmithKline and is broadly critical of the FDA's ongoing handling of this affair.
Finally The Scientist discusses the recent withdrawal of a paper on stem cells from Science on the grounds of research misconduct, and expresses some surprise that this paper got through the peer review system, especially given the Hwang case.
Thursday, July 19, 2007
Ethics of Deception in Research & FreudPops!
Advances in the History of Psychology have an excellent post giving a Bibliography of The Use of Deception in Research
It is a fairly comprehensive list, and roams far outside the usual ethics journals. You might be wondering why is there a picture of Freud as a lollipop in this post? Well Advances in the History of Psychology also introduced me to the fact that Archie McPhee are now selling Freud Headpops just mildly disturbing...
Saturday, July 07, 2007
Human Tissue Act: Tissue Banks
This post continues the series of posts on the Human Tissue Act. Thus far I have examined when individual applications to use human tissue without consent should and shouldn't be approved. In this post I am going to look at a different issue, the issue around granting approval to a human tissue bank.
A human tissue bank is a store of human tissue that will be used for further, perhaps at this point unknown, research purposes. Classically these were common resources that many universities and hospitals in the UK gathered and human tissue was routinely retained for research purposes, often without explicit consent. To a large degree this and the outcry following the Alder Hey's scandal was what prompted the Human Tissue Act in the UK. However, the government didn't want to simply ban tissue banks since they rightly recognised that this would prevent worthwhile research. So instead the act regulates these tissue banks, ensuring that they meet good practice standards, in particular in regards to storage conditions and consent. This is primarily done by requiring a license from the Human Tissue Authority. However a tissue bank can also voluntarily seek approval of their practices from a National Health Service Research Ethics Committee. While this not a legal requirement, it could be seen as part of good practice. There may also be a bonus for research groups in that it is possible to request ethical approval such that research projects associated with the bank do not need to seek further ethical approval if they are only using tissue from that bank. This can only be granted by a limited number of RECs and in a later post in this series I will explore when RECs ought to approve these applications.
Wednesday, June 27, 2007
The Human Tissue Act: When should applications to not require consent be approved?
This is a continuation of a series of posts on the Human Tissue Act in the UK. It is primarily aimed at trying to work out what the practical implications of the HTA are for members of National Health Service Research Ethics Committees (RECs) and especially highlight the responsibilities it places upon them.
In this post: Human Tissue Act: Intro I noted that the HTA had placed RECs in the potentially difficult position of having to decide when research on human tissue can take place without consent. In this post: HTA Reject I discussed which applications to use human tissue should be rejected. In this post I am going to discuss what sorts of research should be approved to not need consent for the use of human tissue. I should note though that there is definitely still a grey area here, and often whether a project is genuinely justifiable will rely in part on the good it might do.
Some reasonably clear cases:
1. Where there was prior consent to use this tissue for generic research purposes.
While this is arguably a form of consent, given the lack of information the consenter had, it is hard to see how this is informed consent. Nonetheless presuming the research is of worth, this seems straightforwardly the sort of project that could be approved under these provisions.
2. Where consent cannot now be obtained.
This may be because the tissue is a left over diagnostic sample from a person who is now dead. Or it could be that the tissue is old and contacting the person is nearly impossible. Or finally the tissue may have been anonymised so there is no link to the original owner of the tissue. In these cases again presuming the research is of some merit, it seems the REC should give consent.
Some grey areas:
1. Where contacting the donor would be possible but costly or tricky.
This is a grey area because it will depend on how much funding the project has, the merits of the project and how costly or difficult it will be to contact donors.
2. Distressed Proxy consent
These are case where the originator of the tissue cannot now consent for themselves, but another can who may be very distressed by the request. Take for example the parent of a child who has been admitted with acute septicaemia. While you could ask them for consent for their child’s left over blood samples to be used in a research project the quality of this consent would be likely to be poor given the stress they are under. Likewise the very request might cause great distress. It could be argued that this distress should be taken to outweigh the need for consent.
None of this should be taken as definitive, it is instead explorative.
I will explore these issues further in later posts in this series.
Wednesday, June 13, 2007
Human Tissue Act: When shouldn't a request to not require consent be granted
In this post: The Human Tissue Act An open question for Research Ethics Committees Part 1 I introduced a series of posts that I intend to make regarding the Human Tissue Act (In the UK) and it's implications for Research Ethics Committees. I noted that the Human Tissue Act gave RECs the responsibility of deciding when human tissue may be used without seeking consent from the research subject. In this post I'm going to explore some of the cases where I think a request to not require consent shouldn't be granted.
The first and most obvious case would be one where the gathering of consent is easy. Take for example a piece of prospective research intending to use the left over waste blood samples taken from diabetics who have come in for a routine clinic as soon as these samples are gathered. It really adds minimal cost or hassle to get properly informed consent in this scenario, so an application to waive the need for informed consent ought not be approved.
Harder cases are when there is some hassle or cost involved in getting informed consent, where for example the patient is not competent, or the sample is older and the patient needs to be contacted via mail. Nonetheless I am inclined to think that in many of these cases if the collection of the sample is routine rather than urgent, or if the patient is contactable then RECs should be reluctant to not require informed consent.
Do you have any other cases to suggest?
In the next part of this series I will discuss when these applications should be approved.
Saturday, May 26, 2007
The Human Tissue Act An open question for Research Ethics Committees Part 1
The Human Tissue Act, aside from the existence of Research Ethics Committees themselves is perhaps the most complained about thing currently in the UK research environment. It is easy to see why, it is an extremely complicated act, covering many different areas, not just research. In this series of posts I want to explore some of the implications of the HTA for research and for National Health Service Research Ethics Committees (RECS).
In this particular post I want to explore something that the Human Tissue Act explicitly thrusts onto RECS. This is deciding when researchers do not need to get consent to use human tissue for research purposes. The act makes it lawful to use (note not collect, this is governed by common law) human tissue for research purposes if it is properly anonymised, and if it is approved of by a recognised research ethics committee. This like many items in the act is presumably intended to play a balancing role between the need to foster good quality research on one hand and on the other to respect people's rights to control their body and material derived from their body.
However this leaves a REC in the uncomfortable position of deciding when they ought to allow research to proceed, and when they ought to require explicit consent. It could be the case that RECs should simply allow all such research since it would be lawful, but this misses the point of requiring REC approval, if it was just a rubber stamp then why require it legislatively?
Surprisingly there has been no guidance issued by the National Research Ethics Service and there is little in the literature specifically about this. (Although there is much which indirectly bears on it.)
The next entry in this series will speculate on some cases when a REC should permit this, and some cases when it should reject this.
Friday, May 25, 2007
Drug study on kids won't require consent
An interesting article from USA TODAY
As with the polyheme trial this takes advantage of the federal rule that allows researchers to test on human subjects without consent in emergencies. Unlike the polyheme trial this is aimed at children rather than adults.
The study assesses how two reasonably well tested drugs work in children whose seizures last over 30 minutes. While these drugs are in common use with adults they are not currently validated for usage with children.
While I can understand why the researchers want to carry out this trial, I am unclear why it is required to be done without consent? Could they not identify a population likely to seize, get prior consent from their families and then treat if/when they come in. This would of course be more expensive, but it would seem more ethical.
Thursday, May 24, 2007
Polyheme
Interesting news about the Polyheme trial here: Secret test gave patients a substitute for blood
As you can tell by the title the article takes the approach of questioning whether this research can ever be ethical if it is done without consent. While it is argued that this is the only way the research can be done, I'm not so sure, why not testing with conscious patients who are going to need blood transfusion in the future.
Saturday, April 28, 2007
Full time Research Participants
Another fascinating article on research ethics is available in Wired. This time it is about the small subset of research participants who might be called full time research participants, people who effectively just become enrolled in more and more research studies for money.
While there are concerns about the risks these people are taking, but they are autonomous individuals who at least eventually are probably well aware of the risks. The real worry here I think is the hash that these people are making of the science by lying to get on the research. Its interesting that the reporter themselves are swiftly lying to the researcher to avoid an unpleasant change of diet...
