Plagiarism and the scientific paper

According to the Science Insider, the recent highly-publicized paper demonstrating how sperm could be made from human embryonic cells, published in Stem Cells and Development , has been retracted by the journal after charges of plagiarism were made against the paper's corresponding author (who is also, I'm assuming, the principal investigator), Karim Nayernia of Newcastle University (UK).

Here is the story: Journal Editor Retracts Paper on Sperm Made From Stem Cells

Graham Parker, editor-in-chief of Stem Cells and Development, told ScienceInsider that he received an email on 10 July from the editors of another journal, Biology of Reproduction, claiming that two paragraphs from Nayernia paper’s introduction were copied without attribution from a 2007 review article by Makoto Nagano of McGill University in Montreal, Canada, that was published in their journal. Surprisingly, Parker says, those introductory paragraphs describe previous work done by the authors of the new paper, raising questions about why such a passage would be plagiarized. Parker emailed Nayernia and the other paper’s authors asking for an explanation. “My hope was that a genuine mistake had occurred,” Parker said in an email to ScienceInsider.

Parker says Nayernia told him the offending text was inserted by a postdoctoral fellow. But Parker says the explanation he received was not consistent with an innocent mistake. “Once I had established that the suggested reason for the text's inclusion was not being substantiated I decided to retract the paper” on 21 July, Parker says.

Many principal investigators in the context of science labs/large research teams likely face the same problem: large numbers of persons involved in an actual research project as well as the writing of a paper. Papers may result from contributions by a number of persons who are permanent parts of the team as well as more transient lab staff like grad students and post docs. But ultimately, the responsibility for the integrity of a published paper has to lie with someone on the team — and that should be the principal investigator (PI). As the editor of the journal notes, trying to explain the insertion of plagiarised material in a published paper by claiming a postdoctoral fellow inserted it isn't an acceptable rationale or excuse. Clearly, it's problematic to have a corresponding author/PI who claims to not have had ultimate control over the writing of a paper — no matter how many people were involved in the process. It's hard not to wonder, in a case like this, how much control and monitoring was exerted over the actual research, in order to ensure not only scientific rigor but also ethical soundness.

India "Ramping Up" for Clinical Trials

Ethical issues in research in developing nations (which, when done on behalf of Western drug companies, is called "outsourcing") is a hot topic right now. (We've blogged about it here, here and here.) I think one of the best ways for ethicists and members of ethics review boards to get a grip on this topic is actually to read some non-Western sources once in a while. This is 2009, after all, and the internet brings a wealth of non-Western views right to your computer screen. Here's a good example:

From The Hindu Business Line:

The clinical trials market is booming. The number of clinical trials being conducted in India has doubled from 170 in 2006 to 350 at the end of 2008, according to the Central Drug Standard Control Organisation.

And going by the indications in the first six months of 2009, the number of registered clinical trials in the country is likely to touch a new high....

The article notes that ethics plays an important role in this ramping-up:

The drug regulator is also ramping up its system and infrastructure to bring more transparency and ethics into clinical trials.

Apart from making it compulsory for all Clinical Research Organisations to register themselves and the trials being undertaken on behalf of any pharmaceutical company, a system is also being set up to track the volunteers who participate in these trials.

The regulator is putting in place a finger printing technology for the volunteers, which will make sure that the same persons are not involved in two different trials at the same time....

Notice that last bit: is anyone in North America using such sophisticated technology? Is anyone ensuring participants aren't enrolled in multiple trials (rather than just asking trial participants)?
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p.s. just to be clear: I'm not cheering for the use of finger-printing technology...just pointing out that it's interestingly.

Sacha Baron Cohen's "Bruno" and the Erosion of Informed Consent

Bear with me. I promise this isn't a movie review. There are no plot spoilers below. This really is about research ethics — in particular, the ethics of informed consent.

But it starts out what seems like worlds away, in the world of cinema. Check out this article, from Forbes, about a high-profile movie currently in theatres: Bruno's Legal Precipice

Experts say Sacha Baron Cohen's latest mockumentary has pushed business ethics over the edge.

Baron Cohen and his film's distributor, Universal Pictures, have meanwhile been impervious to a flood of lawsuits that have emerged from angry individuals who appeared in the film thanks to a team of legal heavyweights, a carefully constructed legal framework and a rule that all people who appeared in the film sign consent forms.

But legal experts not involved the case are still concerned about the ethics of Bruno's tactics....

Now, a film is not a Randomized Controlled Trial, and consenting to be shown on-screen is not the same as consenting to have something injected into your veins. But still, those of us interested in research ethics should be interested in this story, and not just because there's a sense in which Baron Cohen's movies (both Bruno and Borat) are highly-publicized "experiments", designed to determine how people will react in a range of socially-awkward scenarios.

Three points:

1) This story is a good reminder of why, in Research Ethics (and in Clinical Ethics) we repeat over and over again the mantra: "Consent...is...not...a...form. Consent...is...a...process." The goal of well-intentioned consent-seeking is not legal reassurance, but actual consent — we want the individual receiving treatment or participating in research really to understand and agree to what they're getting into. The makers of Bruno only cared about legal coverage. Researchers presumably want to hold themselves to a higher standard.

2) Let's grant that consenting to be in a movie is very different, in many ways, from consenting to participate in research. Still, there might well be reason for those of us interested in Research Ethics to worry about the shenanigans required to make this movie. Because arguably what this kind of film-making does is erode standards regarding, and public confidence in, the very notion of informed consent.

3) If you think consenting to be in a movie really is quite different from consenting to participate in an RCT, it's worth thinking about just why it's so different. Does the difference lie in the goal? Movies are entertainment; research is an attempt to contribute to our shared body of knowledge. Well, the social benefit of research might arguably imply a more relaxed standard for consent, not a higher one. Is it the history of the 2 enterprises? Modern standards for Research Ethics grew in part out of a reaction against unethical research of the past. The film industry doesn't have (as far as I can think) its own version of Nazi human experimentation or the Tuskegee syphilis study. Or is the difference a matter of institutional setting? Research (at least the kind regulated by institutional ethics review) is, well, institutional. It's typically done by people at large, well-funded organizations, ones with avowed obligations to promote the public good. Or is the difference something else entirely?

Sometimes we really can learn a lot from movies; just not necessarily by seeing them.

Context counts when assessing the social value of research

In the most recent issue of the American Journal of Psychiatry, editor Franklin Miller comments on the work of Zeanah and colleagues who conducted a randomized controlled trial (RCT) on orphaned and abandoned children in institutions in Romania. Institutionalized children were randomized to either continue in institutional care or sent to family foster care. After a period of time, pyschiatric outcomes between the two groups were compared.

Here is Miller's editorial: The Randomized Controlled Trial as a Demonstration Project: An Ethical Perspective

It might be argued that this research is deficient, and hence unethical, on grounds of both social value and risk/benefit ratio. Do not we already know that institutional care is deleterious and inferior to foster family care, especially for very young children? Indeed, in their opening paragraph the authors list features characteristic of institutional care "which all contribute to an adverse caregiving and social environment." Although this is the first randomized trial comparing outcomes for children who remain within institutional care versus those who receive foster care, randomized trials are not the only source of reliable knowledge. For example, we know that heart transplants and dialysis save lives despite the absence of randomized trials. Critics might contend that since the answer to the research question was already known, based on prior observational research and the extensive experience of child welfare agencies, there is no social value in conducting the research...

At first glance, I was very surprised that this RCT was deemed ethically sound and allowed to be conducted. After all, don't we already know that foster care is preferable to institutional care for vulnerable children? Aren't we therefore exposing children who are randomized to continue living in an institution to what we know to be a "worse-off" condition? My intial concerns were twofold: I wasn't sure that there was clear clinical equipoise and I wasn't entirely clear that the risk/benefit balance was favourable. Overall, I wasn't clear on the social value of this project - what would the researchers have found out that we likely didn't already know?

Miller's editorial touched on my own concerns and raised further interesting questions for consideration. Here's what I found most thought provoking:

Context counts. While there may be agreement that foster care is preferable to institutionalized care in North America (the researchers clearly agree on this in the introductory remarks of the article), this was not the case in Romania — prior to this study. The predominant belief was that institutionalization was, in fact, the preferred way of raising abandoned or orphaned children. With no foster care in Romania, the researchers knew that they had to have some very compelling evidence in order to open up the discussion with policy-makers to establish a foster care system in their country. An RCT seemed to be the way to demonstrate that foster care resulted in improved psychiatric outcomes and thus provide demonstrable evidence for policy-makers favouring foster care. As Miller reiterates, while RCTs are not the only way we can "know" things, it's clear that policy-makers still look to this "gold standard" in order to influence their decisions.

My first gut reaction was to question the social value of this RCT based on the fact that the question I assumed the researchers wanted to ask had already been answered, i.e. is family foster care better for children than institutional care? However Miller notes that we must look carefully to determine what the research question really is before we decide on a project's social value or lack thereof. This point is a very important one for anyone assessing the ethical soundness of research to remember. In this case, the researchers were specifically aiming to determine whether children who were initially institutionalized had better outcomes after a shift to foster care. That specific question had not been answered before the researchers set out to do this study.

I think that there are two good take-away messages here for those who review research from an ethical perspective. The first is that the specific research question must be clarified before making an assumption regarding the social value of a research project. Too often, we assume that research questions are already answered without first considering two things. First, we often don't look as carefully as we should at what the researchers really want to achieve, explore or uncover with their study. Second, we often neglect to thoughtfully consider context or to even question our own assumptions on what is the "norm", especially in research projects like this one that involve other countries or jurisdictions in which markedly different sociocultural, economic and political forces shape norms and values that are also, in turn, quite different. In his discussion of research projects that involve more than one country with different norms, Miller asks, "Whose equipoise counts?" Not an easily answered question. However it is one that must be, at the very least, asked and reflected upon.

International Research Standards: Xenotransplantation

For practical purposes, ethical standards in research are set on a national basis. There are, of course, important international documents like the Declaration of Helsinki and the Nuremberg Code. But for most purposes, ethics standards are "local" — both because to a certain extent local conditions and national values differ, and because ethical standards are most effective when they have the force of law and regulation behind them. But in some cases, there's a particularly good argument for international standards. Here's one.

From Australian Life Scientist: Xenotransplantation trial to commence in NZ

New Zealand biotechnology company, Living Cell Technologies (LCT), has announced today that it has gained approval from the New Zealand government to begin clinical trials of its DiabeCell treatment for insulin-dependent diabetes.

DiabeCell are pig cells that produce insulin and when implanted into the abdomen have been shown to lead to near-normal blood glucose levels in patients, reducing or eliminating the need for insulin injections.

Here's the interesting part:

Trials in Australia are currently banned as a result of a moratorium in place by the Australian Government on xenotransplantation.

The Australian Government imposed a five year moratorium on xenotransplantation in 2004, prohibiting the transplantation of organs or cells from animals to humans until more information is available about possible health risks.

Now, from what I understand, the key health risk in xenotransplantation is zoonosis — roughly the trans-specific spread of contagious disease. There may be diseases carried by, say, pigs, that are neither very contagious nor very serious to pigs, but which, if they made the leap to humans (say via having pig parts transplanted into humans) could turn out to be deadly, or contagious, or both. And if we're talking about contagious diseases, the risk is not simply a risk to the health of the individual patient/research subject. It's to the population. So presumably Australia's ban exists because of the fear (justified or not) that xenotransplantation poses a public health risk.

So: New Zealand's standards for research ethics permit xenotransplantation. Australian standards forbid it. The problem is that zoonosis (if it happened) would be a problem highly unlikely to respect international borders. Now, admittedly, NZ is an island. But there are flights between countries these days. If ever there were a case that calls for international harmonization of standards, wouldn't this be it?