The Research Ethics Blog

Excluding Gays and Lesbians From Clinical Research

2010-03-18T13:11:00.008-04:00

A recent story from CBC news has uncovered that in the US, clinical trials are being done from which potential participants who identify as gay or lesbian are being excluded. This trend was uncovered by a biostatistician who was gathering data on enrollment into cancer studies and found that, in a couple of studies he came across, sexual orientation was used as a screening tool and, ultimately, an exclusion criteria. After reviewing exclusion and inclusion criteria on more than 80,000 studies on ClinicalTrials.gov, a registry of clinical trials in the USA, he and his colleagues found that it wasn't just a fluke he had uncovered in one or two studies, but a noticeable trend in a percentage of clinical trials.

Here's the story: Gays, lesbians excluded from U.S. trials: MDs

The letter in Thursday's New England Journal of Medicine includes examples of 37 studies out of 243 searched or 15 per cent that had explicit exclusionary language, such as requiring participants to be "in a reciprocal relationship with a person of the opposite sex." Some trials are restricted to heterosexual patients because of the nature of the study, such as how HIV spreads between heterosexual partners. But the researchers also found trials where there is no clear need to exclude lesbians and gay men, including a clinical trial of attention deficit-hyperactivity disorder.

While some might say, well, that isn't a huge number of studies in which this discriminatory and seemingly irrational practice has been employed, so why is this so worrisome? Here's why. Clinical research has a long history of trying to do one thing: prove that a hypothesis is correct. Best case scenario? Proving, through a randomized controlled trial — still considered the gold standard of scientific evidence — that x does in fact directly cause y. And the one thing that scientists don't like when trying to clearly demonstrate a correlation or cause? Confounding factors, i.e. things other than x, that might be causing y. So for many years in many studies, care was taken only to include participants who made up a relatively homogeneous group in order to minimize confounding factors. The result? We learned a lot about older, white males because they were the most dominant and powerful group. We learned about how heart disease affects older, white males. What a heart attack looks like in an older white male. How medications to treat chronic hypertension work in older, white males. You get the idea. Meanwhile a whole bunch of black men were dying from hypertension. Little to nothing was known about the disease, how to prevent it or treat it, in black men.

If we look back at clinical research, we see that many already-marginalized groups and those felt to be more vulnerable have been purposefully excluded from research. Non-whites, children, women, pregnant women, persons with mental illnesses, Aboriginal persons, the elderly, etc. While sometimes these exclusions have been for well-intentioned reasons, they often aren't scientifically justified. What happens is that, as a clinical community, we end up knowing very little about the health, illnesses and medication tolerances of these excluded groups — and like the case of hypertension in older men, there may be some significantly different effect or tolerance that clinicians should and must know about.

Sometimes it makes sense to exclude particular groups. If you're conducting a study on the effect of certain hormonal medications on peri-menopausal women, then it makes sense to exclude men. But does it make sense to exclude non-white women, gay or bisexual women? Since menopause is a reality for all women, it really doesn't make sense. If you're conducting a clinical trial to find the ideal dose of a medication to treat SARS, it doesn't make much sense to conduct trials that might exclude women or children. SARS certainly isn't selective about who to infect. Knowing little to nothing about what is considered a safe dosage or medication for a pregnant woman or a child presenting in an emergency room with SARS can directly result in serious negative outcomes, and even death.

The exclusion of gays and lesbians, without one good scientifically sound reason, shouldn't be tolerated by the clinical community for two reasons. First, it's blatant discrimination, and without clear scientific rationale, seems simply like someone's political agenda making its way into scientific exclusionary criteria. Second, it seems clear that allowing this on any level implies we might well look the other way when faced with discriminatory clinical or research practices like this which have already been clearly shown, through history, to be far from beneficial.

Here's the letter that the biostatistician along with other colleagues, wrote to the New England Journal of Medicine, uncovering their findings on this practice:Clinical Trials That Explicitly Exclude Gay and Lesbian Patients

p.s. Thanks to Desiree (teh_skeptic on Twitter) for the story!

Neanderthal Research Subjects?

2010-02-22T11:54:00.002-05:00

If we could clone Neanderthals, should we? Why or why not? What would the ethical pitfalls be? Would the consequences of doing of it be the problem, or would the research leading to the cloning be problematic in its own right?

Here's the article inspiring the questions, by Zach Zorich, in Archaeology, Should We Clone Neanderthals?

If Neanderthals ever walk the earth again, the primordial ooze from which they will rise is an emulsion of oil, water, and DNA capture beads engineered in the laboratory of 454 Life Sciences in Branford, Connecticut. Over the past 4 years those beads have been gathering tiny fragments of DNA from samples of dissolved organic materials, including pieces of Neanderthal bone....

There are still technical obstacles, but soon it could be possible to use that long-extinct genome to safely create a healthy, living Neanderthal clone. Should it be done?....

Two main thoughts occurred to me, reading this article.

1) Do (or would) Neanderthals fall, as a matter of jurisdiction, into the domain of regulations established to protect human research subjects? Whether Neanderthals ought to count as human is controversial among scientists (according to the Wikipedia page on Neanderthals, "Neanderthals are either classified as a subspecies of humans (Homo sapiens neanderthalensis) or as a separate species (Homo neanderthalensis)." Given such scientific controversy, it's at least not obvious that laws & guidelines set up to protect specifically human research subjects would apply. Research on non-human research subjects is covered by the laws & guidelines for animal research.

Now, the article has some interesting stuff about human rights law, which suggests that interpretation of the term "human" in that regard might be broad enough to include Neanderthals. But then, it might not — depending on the jurisdiction and the decision-maker. Also, it's not clear that the standard applied under human rights law would automatically be the standard taken up by those who administer the rules of research ethics. And even if it were, that leaves open interesting questions about just how far from homo sapiens you have to stray before you leave the domain of "human" research, for either ethical or regulatory purposes.

2) The article points to a number of technical obstacles to cloning a Neanderthal. It points out, for example, that getting Neanderthal DNA isn't enough — the DNA needs to be formed into chromosomes and situated inside an egg, for starters. But the article leaves out one other, ethically crucial part of the equation: Mom. To create a living, breathing Neanderthal, you'd need not just an egg loaded with Neanderthal DNA, you need to implant that egg in the uterus of a female of a closely-related species. In other words, a woman. So, even setting aside the question of whether a genetically-Neanderthal fetus would be a "human fetus", such an experiment would still clearly fall into the category of research on human subjects. Would an ethics board approve it?

Fitter, Faster and Stronger: Olympics Athletes as Research Subjects

2010-02-11T08:49:00.009-05:00

While the Olympics don't officially start until tomorrow, the "anti-doping" investigation clinics are open and working well before the games begin. But this year, those who test athletes for "doping" are faced with another possible way for athletes to enhance performance: gene therapy.

Here is a link to the story, from CBC news: Gene Doping Risky for Athletes

"Some athletes and coaches will be tempted, prematurely and unwisely, to take advantage of results packaged by some as performance-enhancement 'breakthroughs,' even if they are untested in humans and the only 'breakthrough' is faster or stronger mice," the researchers wrote. The article says gene therapy has complicated international competitions like the Olympics. Online marketing campaigns target athletes with ads focusing on how treatments can "alter muscle genes … activating your genetic machinery."

Already, scientists doing experiments in lab animals have been approached by athletes volunteering themselves as human test subjects. The athletes want to be like the "Schwarzenegger mice" that have an extra copy of a gene that led the critters to become 30 per cent stronger.

Gene therapy isn't new. It's been used in a number of therapeutic ways, but in many contexts, it remains highly experimental. As a performance-enhancing agent, gene therapy has been used in animal experiments with baboons and the famous "Schwarzenegger mice" but has yet to be safely or thoroughly tested on humans.

The risk to athletes is considered potentially deadly. One of the most interesting aspects of this kind of performance-enhancing gene therapy is also the most lethal: the kinds of physiological processes that are "turned on" when this kind of gene product is injected into a person can't be simply turned off. This lack of control over the physiological processes can lead to deadly consequences, clearly demonstrated in animal studies.

A few thoughts:

In terms of gene therapy, science is moving quickly. However, not quickly enough, it seems. The vision and hope for the science are racing ahead of even the most efficient research. And this clearly can lead to unethical and, in this case, potentially deadly consequences as athletes are being used as research subjects exposed to very high-risk experimentation.

The potential for profit creates even more pressure to use the products of scientific inquiry prematurely. The interest in using experimental gene-based enhancements on athletes is quickly growing. As noted in the CBC report, an article that will appear in Science on Feb 12 will cite an Associated Press report that gene therapy products were being surreptitiously offered to athletes at the 2008 Beijing Olympics.

One of the take-away messages here is that potential profit and great hope for a product of research creates pressure to advance the science as quickly as possible, often, much too quickly. Earlier this month, we blogged about the
Wakefield case. While this is very different, there is one similarity. The strong desire for a quick answer to the question What causes autism? and the possibility for profit from such an answer meant that unethical and unsafe science was advanced overzealously, resulting in significant harm to many. In this case, the hope to make athletes as fit, fast and strong as possible (and the subsequent potential for profit from their achievements) is driving the science of gene therapy much faster than any safe, ethical lab or researcher.

[Chris has also written about this over on the Biotech Ethics Blog
- I highly recommend reading his analysis as well]

The Tragedy of the Wakefield Case

2010-02-02T15:33:00.000-05:00

Here's an update to a troubling story I published here almost a year ago. Dr. Andrew Wakefield was a senior lecturer in the Departments of Medicine and Histopathology at The Royal Free Hospital (a teaching hospital in London) and a consultant in experimental Gastroenterology. Last year, when I published the original blog entry, Dr. Wakefield was in the midst of being investigated for medical misconduct, in a "fitness to practice" panel hearing of The General Medical Council in the UK. The hearing was centered around a Feb 1998 Lancet article in which Wakefield made various claims about autism, the MMR vaccine and inflammatory bowel diseases. Since the publication of that Lancet article (which, as of today, has been retracted by the journal), vaccination rates in the UK have plummeted and Wakefield has been viewed as the scientist "poster-boy" of sorts for the supposed link between autism and vaccination. You can read more about it in my initial blog entry here.

The longest medical misconduct inquiry ever conducted by the General Medical Council has now come to an end, and as Brian Deer of the Sunday Times reports, they confirmed more than 30 charges against Wakefield.

Here is a link to the Sunday Times story: ‘Callous, unethical and dishonest’: Dr Andrew Wakefield

The panel’s findings were astounding, both in their number and substance. More than 30 charges were found proven against Wakefield. For him alone they ran across 52 pages. Embracing four counts of dishonesty — including money, research and public statements — they painted a picture of a man not to be trusted. Other proven charges included nine of mistreating developmentally challenged children: causing invasive “high-risk” research to be carried out without ethical approval and against their best clinical interests.

The panel ruled that Wakefield caused three children to undergo lumbar punctures without clinical reason. Three more rulings said he had breached his employment contract at the hospital’s medical school which forbade him from involvement in patient care. He was also found to have shown “a callous disregard” for the “distress and pain” of children to whom he paid £5 in return for blood samples at his son’s fifth birthday party.

This is arguably one of the "worst case scenarios" we imagine in the field of research ethics. While we're appropriately concerned with a myriad of ethical problems such as ghostwriting, undeclared conflicts of interest, breaches of confidentiality and the like, conducting research on vulnerable children without ethics approval is clearly one of the worst and most tragic cases we can think of. The resultant harm in this case, however, is not limited to the children and families Wakefield used in his "research". I'm thinking of two additional harms that may well have resulted, surely in part, from the Wakefield case.

First, there is the societal effect that the condemned research has had. Vaccination rates in the UK (and other countries) have significantly decreased. The lack of clarity about this issue has polarized communities of parents with autistic children, creating "us" and "them" camps of parents and families. Serious misunderstandings abound, both about autism and about vaccination. As I said in my original posting last year, it's difficult to hold Wakefield solely responsible for these problems. However, in part, his research spearheaded this movement for many (especially in the UK) and he has continued to promote his findings, despite considerable objections and serious questions from the scientific community.

The second kind of harm I'm thinking of is harm to the research community in general. It's challenging enough for highly trained researchers and clinicians to sort through the vast collection of research articles and findings on this topic, that range from high-quality, valid, reliable and trustworthy to questionable, unreliable, invalid and simply untrue. For a lay person or concerned parent to try to sort through this topic and figure out what constitutes "good" versus "bad" data is beyond challenging. Now, this case may result in discredit and distrust of researchers, thus further "muddying the waters" for lay persons trying to figure out whose data to trust and whose to dismiss.

Privacy of Data is an Ongoing Concern

2010-01-17T19:03:00.000-05:00

This week, just outside of Toronto, an unencrypted USB key was lost that contained the names, government-issued ID numbers and personal health information of more than 80,000 patients who visited a local H1N1 vaccine clinic.

Here's the story from CBC News:
Ont. privacy commissioner orders 'strong encryption' of health records

In December the Durham health authority, which is responsible for a large area east of Toronto, announced it had lost the medical records of thousands people after a nurse misplaced a USB key at Durham region's headquarters in Whitby, Ont. The information on the USB key, also known as a memory stick, was not encrypted. The device contained data collected from more than 83,000 patients during H1N1 flu vaccination clinics in the region between Oct. 23 and Dec. 15.

On Thursday, Ontario privacy commissioner Ann Cavoukian said Durham must ensure the safety of patient records and ordered it "to immediately implement procedures to ensure that any personal health information stored on any mobile devices [laptops, memory sticks, etc] is strongly encrypted." Cavoukian made clear in her report that she expects every health authority in the province — not just Durham — to follow suit.

As Cavoukian notes, personal health information must be kept confidential. This includes (although Cavoukian doesn't explicitly say this) personal health information that is part of research data. The safeguard that she is urging all health authorities to implement (encryption) is something that ethics review boards should be urging researchers to use in order to protect the confidentiality of research data. And this, of course, doesn't just apply to personal health information, but any research data about which a promise has been made to maintain confidentiality. We have become much more sensitive to the careful protection of health information (although this story indicates otherwise!) but there is a great deal of research that has nothing to do with health in which careful consideration must be taken to protecting confidential data or identities, as promised in many processes of consent.

Simply advising researchers to encrypt electronic data isn't enough. Granted, it's better than just protecting your data with a password. But there are more things that researchers who use electronic data must be thinking about.

There are two questions related to electronic data storage and security that ethics review boards must ask researchers to also think about if they haven't already. collection.

The first question is, where are the data being stored? Best case scenario is always to store data locally, i.e. on secure servers that never requires the data to be "moved" anywhere. Many hospitals and academic centres now have these and issue staff passwords and "space" on the servers so that data can be stored locally. Once you transport data electronically even just to a non-local server, you increase the risk of that data being lost, manipulated, leaked or corrupted. This is something that is particularly worth keeping in mind when research projects involve electronic surveys. Many electronic survey tools store data remotely, even outside of the country where the research is being conducted. Case in point: Survey Monkey. Survey Monkey has long been the choice of many researchers to collect information easily using an electronic survey. However, the fact data are stored on servers within the USA and are therefore subject to the USA PATRIOT Act means that many non-USA researchers are now choosing Canadian-based, local survey tools.

The second question is how are the data being stored? If the data are stored on a local server accessible only to the researcher and research team via a password-protected desktop computer in a securely locked office, that's a very good start. The data doesn't have to be "transported" anywhere so it's difficult to lose it and it's reasonably inaccessible to others. If, however, the data is being stored on any kind of portable device such as a laptop or memory key — as data often are — then the data must be encrypted.

It's very easy to now buy a USB key that uses encryption to store data. If you happen to lose it, the data is virtually useless to others. They're much cheaper now and hold large amounts of data.

One final strategy is to always require that researchers store identifiable information separately from other kinds of data. Coding lists, consent forms and raw data should always be stored securely and separately.

Hopefully none of these safeguards is news to most researchers and ethics review board members. They are, for the most part, not burdensome or time-consuming for the researcher. However, clearly, as the above story demonstrates, many are not paying attention to these quite easy-to-implement safeguards, resulting in deleterious effects: loss of trust, breaking promises of confidentiality, and the potential for significant harm.

Journal Editors and Conflicts of Interest

2010-01-09T11:48:00.000-05:00

A recent story in the Milwaukee-Wisconsin Journal Sentinel points to what seems like a new kind of potential conflict of interest in medicine. We've published various stories on conflicts of interest in medicine and research before more than once — stories about ghostwriting, asking authors to declare potential conflicts of interest, about med schools tightening up their conflict of interest policies, a story on how personal relationships between drug reps and physicians and most recently, a story the appointment of a Pfizer VP to CIHR's Governing Council. But this time, the story focuses on someone in a different role with a clear conflict of interest — a journal editor.

Thomas Zdeblick, a University of Wisconsin orthopedic surgeon, took over as editor-in-chief of The Journal of Spinal Disorders and Techniques in 2002 while he was working with Medtronic (which he continued to do) in developing, researching and patenting spinal implants. And making millions of dollars in royalties for the patented spinal implants that he then wrote about and published in a number of articles over the last seven years, all published in his own journal.

Here's a link to the story, in the Milwaukee Sentinel: Journal editor gets royalties as articles favor devices

It would be the beginning of a beautiful friendship.

In the years to come, Zdeblick would receive more than $20 million in patent royalties from Medtronic for spinal implants sold by the company. And the medical journal he edited would become a conduit for positive research articles involving Medtronic spinal products, a Journal Sentinel analysis found.

Dozens of studies that mentioned Medtronic products have been published while Zdeblick has been editor. But in issue after issue, readers of the journal were not told that he was receiving millions of dollars in royalty payments from Medtronic at the same time.

Most of the time the articles, including some co-authored by Zdeblick himself about devices for which he gets royalties, had good things to say about the Medtronic products. Only on a small number of occasions did the articles find major problems with Medtronic devices.

It's clear that Zdeblick had a conflict of interest and that he was not forthright with readers about this conflict, both in his role as author and his role as editor — according to the article, his relationship with Medtronic was not disclosed in any articles or editorials. Certainly, journals do and should ask authors to declare any potential conflict of interest. And it's obvious that having a vested financial interest in the success of a device should put up a red flag for anyone assessing the author's ability to be objective about such a device. But that role — assessing the author's objectivity and asking questions about relationships — is really the role of an editor along with an editorial board and assigned reviewers. But according to the Sentinel, Zdeblick never declared his relationship with Medtronic and it seems, until now, no one asked.

While there has been plenty of discussion over potential conflicts of interest for authors and researchers, little attention has been paid to editors of journals who have a great deal of control over what research gets published. The representative for Wolters Kluwer (who publishes the journal) and the rep for Medtronic, both cited in the article, feel that there is no need for concern though. Their reassurance, however, is based on the claim that the journal is "independent and peer reviewed" through "strict processes". Processes which are controlled by the editor-in-chief, who also happens to have co-authored a number of the articles, etc. etc.

Unfortunately, it seems like it's hardly news anymore when a conflict like this is revealed. In this case, while it seems unique as we're highlighting a journal editor instead of say, a researcher or an author, it's the same theme time and time again. Lack of transparency and accountability. No one asking the obvious questions. In this case, one is left wondering about the roles of the editorial board and the reviewers who would have encountered and reviewed article after article, co-authored by the editor-in-chief, about Medtronic spinal implants. It seems like no one had any backbone, until now, to ask questions about this.

As of today, Zdeblick is still listed as editor-in-chief of the journal. We'll keep you updated on this story as it develops.

Conflict of Interest at Med Schools (podcast)

2009-12-15T12:26:00.003-05:00

A couple of weeks ago, I was interviewed on Yoni Freedhoff's excellent Weighty Matters blog. The blog entry and podcast are here: Milk, conflicts of interest, and med-school profs.

Here's a bit from the blog, setting up the issue:

...should University professors disclose their potential conflicts of interest before lecturing students? I certainly don't remember any professors disclosing their ties to anyone during my medical school days at the University of Toronto yet it's an obligatory practice for those same professors to do so at conferences and in journal articles.

To me this seems like a dangerous double standard as one might argue that students are far more vulnerable than full fledged physicians and researchers in critically appraising data. Given the incredible power differential between professor and student and the intrinsic trust one places in the purveyors of their education I wondered about the ethics of such a lack of disclosure and so I contacted Dr. Chris MacDonald to chat about this further....

The direct link to the audio podcast is here: MacDonald on Conflict of Interest.

(We've blogged before about this issue. See: Harvard Med School Students Push for Stricter Conflict of Interest Policy.)

Should Pfizer VP Sit on CIHR's Governing Council?

2009-11-28T21:00:00.007-05:00

Controversy has arisen over the appointment of one of Pfizer's VPs to the governing council of the Canadian Institutes of Health Research (CIHR). (For those who don't know, CIHR is the Canadian government's main agency for funding research in the area of health.)

Here's the story, as reported by the CBC: Appointment of Pfizer exec to health funding body criticized

Prominent bioethicists have expressed alarm at the recent appointment of a senior pharmaceutical executive to the Canadian Institutes of Health Research (CIHR), the government's funding arm for medical research.

They hope to have their concerns about the three-year appointment of Dr. Bernard Prigent, vice-president and medical director of Pfizer Canada, to the governing council of the CIHR addressed at a parliamentary meeting Monday....

The CBC story also refers to a petition recently begun, in opposition to Prigent's appointment. Here it is: Petition Against the Appointment of the VP of Pfizer Canada to CIHR Governing Council.

The main worry here is conflict of interest. Perception plays a big role in conflict of interest. In this regard, both the government and their critics are wrong. It's not a matter of whether Prigent will be able to avoid letting his obligations to his shareholders affect his obligations as a member of the Council. The problem is whether his job at Pfizer will jeopardize the reputation of CIHR (and more particularly its governing council) by rendering its judgment suspect. I don't know anything about Dr. Prigent & he may well be an individual of outstanding integrity. The point is, that doesn't matter. Even if he does exercise his best, publicly-minded judgment on behalf of CIHR, his presence could still render the governing council's judgment suspect.

It's also worth noting that opposition to this appointment involves 2 separable issues. One is the appointment of someone from the pharmaceutical industry to CIHR's governing council. The other is the appointment of someone from Pfizer, in particular.

So one issue is Pfizer's less-than-stellar reputation. As the CBC story notes, Pfizer recently paid a record-breaking $2.3 billion fraud settlement. And I've also blogged about just a handful of the many cases of wrongdoing at Pfizer, including here and here and here. And because of Pfizer's poor reputation, I think the petition-writers are right that Prigent is a bad choice to be on CIHR's governing council. Pfizer's reputation is not good, and so many people will justifiably be suspicious of the intentions and judgment of its senior executives. That's crucial to the worry about conflict of interest.

The other issue is whether anyone from the pharmaceutical industry could ever be on CIHR's governing council, and that I think is a harder issue, one on which the writers of the petition have overreached. I for one would need to know much more about the governing council, its mandate, and its operations, to know whether an executive from a small or mid-sized pharmaceutical company with a good reputation could be valuable in that role. "Divergence of interests" between a company's shareholders and the public isn't sufficient reason to exclude executives from that company. Nobody's interests are perfectly aligned with the public's. What matters is whether the divergence is sufficient to render an individual's advice suspect in a way that cannot be remedied through standard mechanisms used to mitigate the effects of conflict of interest (mechanisms such as disclosure and recusal). So simply working for industry doesn't strike me as an insurmountable flaw, particularly if (if!) the governing council's role makes an intimate understanding of the drug industry useful.

But the main point remains: it's very hard to support the inclusion of an executive from this pharmaceutical company on the governing council of Canada's most important health-research-funding organization.

The Newest Place to Connect On-Line: The Participant Pool!

2009-11-12T09:57:00.006-05:00

It was with some surprise that I happened across this website. It's called ResearchMatch and it's described as a "National (US) Research Study Recruitment Registry". The press release that led me to the ResearchMatch website was one announcing that Rockefeller University was now joining the registry.

Here's the press release: Rockefeller joins first national research study recruitment registry

“The Rockefeller University Center for Clinical and Translational Science is proud to be a founding collaborating institution of ResearchMatch,” says Barry S. Coller, vice president for medical affairs and codirector of Rockefeller’s CCTS. “ResearchMatch is an important initiative in speeding both the discovery of new knowledge and the translation of that knowledge into improved health. It incorporates a number of confidentiality and privacy protections and has been approved by a human subjects ethics committee.”

ResearchMatch, at first glance, appears to be almost as appealing as any other social networking site. The taglines and catch phrases include (wildly out of context) inspirational quotations by Carl Sagan and Jane Goodall alongside pictures of very happy, very interesting, diverse persons who we assume are potential research participants. People who, according to Barbara Alving, director of the National Center for Research Resources (a part of the National Institutes of Health) are contributing "to advancing new treatments.”

Participant pools have been around in clinical research for quite a while. Usually situated in academic centres, and quite often in psychology departments, they often include only students who are enrolled in first year clinical courses, such as pscychology or medicine. They're typically students who are also learning how to conduct research themselves, and taking part in research is a necessary aspect of this learning. This is, in essence, just another very large participant pool, isn't it? Well, yes, it is. However, a few things worry me about this site.

First, it's very slick. Nothing wrong with that, but it makes you want to join just to see who you'll meet! (It is, after all, called ResearchMatch!) There are options on the site to "share with friends!" Visitors to the site are encouraged to "Join today! It only takes a few minutes!" and "Create your profile now! It's free and and everyone can join!" I found the kinds of motivational statements that are flashed across the website to inspire participation most interesting. One famous quote from Jane Goodall ("Every individual matters. Everyone has a role to play. Every individual makes a difference") seems to be referring to participation in studies through ResearchMatch. This quotation, in fact, does not refer to research at all, according to The Jane Goodall Institute of Canada. Rather it refers to our individual obligation to protect the environment, ensure animal welfare and try to better understand of relationships between humanity, the animal world and the natural environment. Now, there isn't anything wrong with taking a good inspirational quote out of context if it applies to the situation. And there isn't anything wrong with using slick and attractive lifestyle advertising to get people's attention. However, I'd recommend against doing any of that in the context of recruitment. Most ethics boards strongly and appropriately discourage "slick" recruitment processes. Transparency and clear information are a key part of any recruitment process, including a process to recruit into a participant pool.

My biggest concern with this service comes out of the following statement on the website: "You may either register yourself or someone else as their parent, guardian or caretaker." This statement is repeated on the profile creation page, accompanied by a picture of a young handsome dad in front of his laptop in the backyard with his toddler son in his lap, apparently signing the boy up for participation in research studies. With 52 institutions taking part in this initiative, and countless trials and studies coming out of those institutions, it's unclear who is overseeing it and who would ensure that the best interests of those who are not signing up for themselves would be protected. The website refers to the activities of ResearchMatch as being overseen by "an" Institutional Review Board but the provided link simply takes you to the US Office of Human Research Protection. Are they overseeing it? Again, it's unclear. Awfully worrying is the fact that while it's emphasized that if you sign up, you always "have a choice" to participate or not in research studies, there are no clearly stated safeguards in place for those who are signed up by others.

It's clear that human participants are needed in order to advance research. Of course. I'm just not sure that what appears to be pretty slick lifestyle advertising without clarity of information is the best way to do it.

Sex-Toy Research: Nothing Wrong With a Little Controversy

2009-11-07T12:10:00.008-05:00

Conducting research with all due attention to regulations and ethical standards doesn't automatically insulate it from criticism and controversy. Nor, for that matter, should adherence to rules & regs necessarily imply that one's research cannot be the subject of ethical scrutiny. Even when researchers are careful not to cross those lines, there's often still plenty of room for disagreement about what is ethically better and ethically best, and about what research is minimally useful versus what research really makes a significant contribution. And as we've blogged about here before, research on sex is liable to garner more that its share of critical attention.

Now, according to the Associated Press, Sex-toy study at Duke raises some eyebrows:

DURHAM, N.C. — A campus religious leader is unhappy about a study at Duke University that invites female students to attend parties where they can buy sex toys.
The News & Observer of Raleigh reported Friday that the director of the Duke Catholic Center has lodged a complaint with researchers. The Rev. Joe Vetter says the study doesn't promote relationships.

Here's a longer version of the story, from The News & Observer of Raleigh: Sex toy research causes a stir at Duke.

(Note: I'm not a fully disinterested commentator, here. The principal investigator in the study under discussion is a Fellow at Duke's Kenan Institute for Ethics, where I'm also a Fellow.)

The first thing to note is that the criticism is off-target. University-based research studies are not typically aimed at promoting relationships, or promoting anything at all; they're about generating generalizable knowledge. Of course, the job of the ethics board that approved the Duke study is to make sure that the risks to which participants are exposed are reasonable, and that those participants understand those risks prior to participation. But, to the best of my knowledge, no one seriously argues that ethics boards should be contemplating whether the conducting of a study in itself contributes to the social good, independent of the knowledge it is likely to generate. (Then again, to his credit, Rev. Vetter isn't complaining to the ethics board; he's complaining directly to the researchers.)

The other thing to note is the (rightly) timid tone of the headlines above. There's no implication of scandal here. This is about a study that is causing "a stir" and raising "some eyebrows." Those things are in fact healthy. If university researchers never caused a stir or raise eyebrows, it might just be that, collectively, they're not doing their job.

Michael Schoenfeld, Duke's VP for public affairs, quoted here, gets it right:

"Not all research will make people comfortable. In fact, there's a lot of things, there are a lot of questions, there are a lot of issues that are studied at a university that make people uncomfortable," Schoenfeld said. "That's how we get an understanding of things like ethics (and) behavior."

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p.s. here's a useful blog entry over at Science Blogs that tells a bit more about the controversy, as well as about the scholarly reputation of the study's P.I.: Response to Dan Ariely's Duke Sex Toy Study

Getting to the heart of the matter at Columbia?

2009-10-29T13:19:00.000-04:00

A recent story from the Huffington Post, as reported by Jeanne Lenzer and Shannon Brownlee, highlights a story about a cardiac surgery trial at Columbia that began in ~ 1999.

The story reports that the Office of Human Research Protections (OHRP) in the US has requested that Columbia University notify participants enrolled in the trial entitled "Effect of different intravenous fluids on thromboelastography during cardiac surgery” that they may “have suffered harms that were a function of the design and procedures of [a] study” (quote from OHRP as reported in HuffPo) conducted a decade ago. According to the story, some of the patients in the trial had severe adverse reactions to a blood-expanding fluid used in surgery. The main goal of the trial was, in fact, to test different kinds and doses of blood-expanding fluids in surgery (used to replace lost blood volume). In high doses, some of these fluids had previously been shown to cause serious bleeding. According to the story, a number of participants received excessively high doses (higher than recommended safe maximum amounts) of the fluids. Two patients in the trial died and many more required transfusions as a result of serious bleeding.

Here is the story as reported in the Huffington Post: Government Orders Columbia to Tell Patients 'True Nature' of Drug Study

The main criticisms of the trial include the claim that participants were not fully informed of the goals of the study and potential risks of trial participation, including the potential risk of serious bleeding. Additionally, the authors claim that there may have been some misconduct in the recruitment of patients who were Spanish-speaking only, socio-economically disadvantaged or considered to be more vulnerable.

This story has been reported all over the Internet by sources such as The Indiana University Center for Bioethics (IUCB),the Google group on progressive activism, The Alliance for Human Research Protection, Cardiobrief, and finally, the law firm of Weitz & Luxenberg who are asking that patients of the trial contact them as part of a "lawsuit review".

Here's what worries me. This seems, at first glance, to be an extremely serious potential breach of research ethics. It also is a pretty monumental medical story — a clinical trial resulting in deaths and serious morbidity. Yet I haven't been able to find any sources, other than HuffPo, that have corroborated this story. The blogs and newsgroups I note above each cite the HuffPo story only. The story has not been picked up by mainstream media. Documents supporting the story, such as the letter to Columbia from OHRP, are not publicly available. The Huffington Post has had its share of criticism over their coverage of science, medicine and health-related reporting. It may not be the most reliable source for science and medicine stories. And yet it's still the only one for "this" story.

Why are there no corroborating sources? Why, when you search for more information on what appears to be a "breaking news" clinical trial story, do you simply end up back at the original Huffington Post report? With a story as potentially serious as this, with lives lost, with people hurt and with even more lives and careers at stake, I'd feel much better about this story if someone else were asking these questions. And getting some answers from more than one place.

HIV vaccine trial: a "shot in the arm"?

2009-10-15T08:21:00.001-04:00

Last month, it was announced that an HIV vaccine trial carried out in Thailand showed hope for further progress towards use of a vaccine for HIV. This was not a small trial — it was carried out on more than 16000 Thai volunteers, costing $105 million USD. The initial press release which was heralded, blogged, tweeted and retweeted reported that the data from the trial showed a decrease in the risk of HIV infection by 31% compared to a placebo. Characterized as a veritable "shot in the arm" for those engaged in HIV vaccine research (so called by the Principal Investigator of the study, Dr. Scott Hammer) this trial seemed to be the most positive and hopeful news in this area to date.

But is it?

New reports shows that the initial data (demonstrating the "moderate" 31% decrease in infection rates) included a subgroup of participants who did not follow the trial protocol. According to the Scientist's most recent report, if that subgroup is excluded, the data, when analyzed, still shows a moderate decrease in infection rates but the result is no longer statistically significant.

Here's the most recent update, from The Scientist: Hubbub brews for HIV vax data

Although both sets of data were available to the researchers at the time of the original announcement, they chose not to report them alongside the initial analysis, Jerome Kim, a US Army scientist who was involved in the study, told the Wall Street Journal. "We thought very hard about how to provide the clearest, most honest message," Kim said. "We stand by the fact that this is a vaccine with a modest protective effect." But some AIDS researchers (who preferred to remain anonymous) have suggested that the study leaders were dishonest and put a positive spin on a study with, at best, inconclusive results.

For those of you who haven't been in a stats class recently, statistical significance is not a trivial matter. It's the measure by which you can state that a particular finding isn't simply due to chance, that it can be reproduced, that it is a reliable finding. In this case, it's the justification that would have allowed researchers to claim that the decrease in infection rates was really due to the vaccine, and not something else. If in fact a number of participants did not follow the protocol, it's very difficult to say that confounding factors (things other than the vaccine that might well be responsible for some of the decrease in rates of infection) were adequately controlled.

We've talked about the responsibility of researchers and the media in reporting research stories to the public ( here, here, and here) and this story serves to remind us, yet again, of the responsibility when presenting data to the public in a non-scientific, easy-to-understand way (at the time of the update, the data had not been presented at a scientific meeting or in a publication). While it's important to be clear and honest — and the researchers have said repeatedly that they were aiming to be as clear and honest as possible — researchers also have an ethical obligation to ensure that the data, disseminated in any context, are not misleading, are scientifically sound, and are presented in a complete way. Especially with an issue like this one, an issue in which many are actively looking for a glimmer of hope.

It may well be that the data support a conclusion that does provide hope — a decrease in infection rates that is really due to the vaccine. But with this current confusion and doubt, the burden of proof rests now with the researchers to present all the data to both the public (again) and the scientific community, in ways that everyone can clearly understand.

Trust in Pharma?

2009-10-08T16:46:00.005-04:00

Should we trust Big Pharma? Plenty of people don't, and for good reasons familiar to readers of this blog.

Over at the Business Ethics Blog, I just posted a longish item about reasons for, and against, trusting Big Pharma — or rather, trusting particular companies on particular issues on particular days.

The "against" side is easy: pursuit of profits has clearly driven a pattern of disreputable behaviour within the industry.

The "for" side is more complex. I'll just list 5 factors briefly (see my other blog entry for greater detail) and then make an additional comment about Research Ethics & the role of Ethics Boards.

1) Individual Ethics — Pharma, despite being a troubled industry, is full of normal people with normal ethics. Most of them are likely to be honest most of the time.

2) Regulations — The industry is highly regulated. Enforcement isn't always great, but generally there are serious penalties for clear wrongs.

3) Peer Review — The basis for all pharma product claims is open to public, and especially expert, scrutiny. A good but imperfect system.

4) Scientific Overlap — Pharma may have too much influence in some parts of Medicine, but not all physicians are on the payroll, and nor are most of the biologists, chemists, statisticians, etc., who also get to see and critique published medical research.

5) Competition — Pharma is intensely competitive, as are medical researchers. Collusion and conspiracy are the exception, not the rule.

In the list above, I left out the role of Ethics Boards and scholars in research ethics. Ethics Boards are, in a sense, the public's first line of defence, making sure that the clinical trials that get conducted are conducted ethically — and as it happens, good ethics in research overlaps very considerably with good science. On the scholarship side, you've got people like Charles Weijer, working to make sure that the principles according to which biomedical research gets done are the best ones. (Charles has argued, for example, that for ethical and scientific reasons, in almost all cases new drugs ought to be tested against the best drugs currently available, rather than against placebos.) To the extent that good scholarship influences policy, it helps ensure that drugs that make it to market really do deserve to be there.

The pharmaceutical industry has, alas, seemingly worked very hard at gaining its own lousy reputation. Trust Big Pharma, full stop? Clearly not. But we should be careful not to throw the baby out with the bathwater. We need instead to think clearly about the social and institutional mechanisms that help keep Pharma in line, and about how we can make those mechanisms better.

Being Excited About Research: Is it Still Possible?

2009-10-01T11:53:00.003-04:00

This isn't a research ethics story per se - but a fascinating story about some exciting research that highlights a few important things that researchers, research ethics board members and the public often forget.

Here's the story, from the New York Times: A Race in Cardiology

A race is on to develop the potentially next big thing in heart surgery: a replacement valve that can be implanted through thin tubes known as catheters rather than by traditional open-heart surgery.

The contest pits two major companies, Edwards Lifesciences and Medtronic. Analysts estimate a market for the product that could exceed $1.5 billion within six years. But if the valves catch on, their benefits for the nation’s aging population could be substantial — even if the impact on the nation’s health care bill may be hard to calculate.

The new valves — which make it possible to repair the heart without the rigors of chest-opening surgery — have been available in Europe for about 18 months, with sales of about $100 million split about evenly last year between the two companies. While doctors say that the early results have been promising, they add that it is too early to gauge the technology’s long-term benefits.

In the United States, the devices are currently being tested in older, critically ill patients in clinical trials. Many medical experts and financial analysts predict that if the devices live up to their makers’ claims, they could revolutionize valve replacement, a common heart operation, and extend the lives of thousands of frail patients who are not now considered candidates for surgery.

In addition to my own fascination with cardiac medicine and surgery from my previous career as a cardiac surgery nurse, I found that this story reminded me, as I said above, about a few things we tend to forget about.

First, industry isn't all bad. It's awfully trendy to, in a knee-jerk way, resent big corporations. Yet here is an example (and there are many) of multi-billion dollar corporations who are the only ones who can and will fund research like this. Of course, I'm not naïve — I do realize that there are huge potential future profits for whichever company perfects the valve that allows for minimally invasive cardiac valve replacement. But it's important to realize that while corporations must aim for profit, they can and sometimes do so through support of technologies like this one, that offers hope to many and helps to revolutionize health care. Without collaborative relationships between corporations, research ethics boards, clinicians and researchers, this kind of research simply wouldn't be possible.

Second, it's necessary to respond to changing technology in health care and the only way to do so is through research — sound, ethical research. It's up to us, as research ethics boards, to recognize potential benefits and the possible fecundity of those benefits. It's also up to researchers to clearly articulate potential benefits alongside risks. As research ethics board members, we tend to focus on risks. We do (and must) attend to potential benefits, but often not on their own. We need to always view benefits as they are weighed against potential risks. However, when reading a story like this, it does make one pause for a moment. Making minimally invasive cardiac valve replacement surgery an option really does mean that the procedure could be available for many patients who would otherwise be deemed inoperable. It would open the doors for more and more minimally invasive procedures (coronary bypass surgeries and angioplasties can be done in a minimally invasive manner) that reduce risks of surgery and allow surgery to be carried out on more potential patients than ever before. Don't get me wrong — I'm certainly not saying here that research like this shouldn't be very carefully reviewed and monitored with a thorough risk-benefit analysis but it's also okay to sometimes say, "Wow, wouldn't this be great if it really did live up to its potential!" Having read probably thousands of research ethics protocols by now, I'd like to think I could still get excited about possibilities like this — despite all the skeptics waving red flags at me about big corporations and profit and ompetition and risk.

As research ethics board members, we tend to be inundated with negative stories that are often fraught with problems, wrongdoing and concerns. Realistically, it is our job to look at research with a critical eye. Nevertheless, this story reminds me of the excitement, the possibility, and promise of research, and why it's so satisfying to be a collaborative and integral part of the facilitation of research.

Survey on Personal Genomics, Privacy & Consent

2009-09-27T13:41:00.003-04:00

Here's an announcement for a new "interactive" or "deliberative" survey that we are running, on Personal Genomics, Privacy & Consent. Anyone can participate. (We refer to the survey as "interactive" or "deliberative" because participants get to see each other's answers, and respond to them, while taking the survey.)

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Our research group (at University of British Columbia, Saint Mary’s University, & Ryerson University) has created an online, interactive survey to better understand values & attitudes related to Personal Genomics. We’d like to include input from readers of this blog because they represent important perspectives on ethical issues related to Personal Genomics.

The survey will take about 10-20 minutes.

To take the survey you will need to register. This requires entering your email address. This is so that we can make the survey safe from spammers & hackers. We will not be able to link your e-mail address with your answers, & we won’t give your details to any third party.

If you have questions or concerns, email us at chris.macdonald@smu.ca or nwalton@ryerson.ca.

You can access the ‘Personal Genomics & Privacy’ survey via this link: http://www.yourviews.ubc.ca.

Thank you. We value your input.

Chris MacDonald PhD. & Nancy Walton, Ph.D.

Moving Ethics Review Out of the institution: Are We Throwing Caution to the Wind?

2009-09-22T13:08:00.002-04:00

There is a debate out there in the research ethics world about "outsourcing" research ethics review responsibilities. In other words, taking the (Research Ethics Board) REB from the University or hospital and situating it outside of the institution. For those of you not familiar with Canadian research ethics review processes, we use a fairly common "local model of review" standard as articulated in our federal guidelines, found in the Tri Council Policy Statement for the Ethical Conduct for Research Involving Humans (TCPS). The model of local review implies that research must be reviewed by multidisciplinary, independent local ethics review boards who apply both the national norms or guidelines (as outlined in the TCPS) and local interpretations of the guidelines as outlined in institutional ethical standards for research. Boiled down, this means that Universities and hospitals, along with other kinds of research-generating institutions, have local ethics review boards to review research conducted at their institution and by those affiliated with their institution. The current question is whether or not to take these ethics review boards out of the institution and create a different kind of ethics review model.

It's an interesting debate and one that, I'm sure, we have not heard or seen the end of quite yet.

Why even suggest taking the ethics review board outside of the institution?

Well, there are a few reasons. First, there is a claim that it would create a kind of "arms-length" board that can fulfill the need for ethics review for research without, presumably, the worry over potential conflicts of interest, special treatment of certain researchers or bias against others. Of course, this is a pretty difficult claim to make. The world of research and research ethics is much smaller than you'd think. The act of situating an ethics review board outside of an institution doesn't necessarily take away the worry that board members might be faced with a potential conflict of interest.

Second, ethics review boards that are not situated directly within an institution might well be better able to coordinate ethics review for multi-centre research projects. Without a clear institutional affiliation, such a Board may be able to approve a project that could be carried out at a number of institutions right away, instead of what happens now. Currently, researchers must apply to every local review board within institutions where the research may be conducted (as well as any institution with which they are affiliated). For many researchers involved in multi-centre projects, this can be burdensome and frustrating. Case in point: Recently, for my own low-risk research, I had to apply to 17 separate Ontario Research Ethics Boards. Each had different local norms and requirements for recruitment and consent, thus requiring me to "reinvent the wheel" with almost every application. Some Research Ethics Boards did not allow an expedited review (typical for already-approved low risk research) even when the project had clearly been previously approved by 15 other Boards. With outsourcing, some institutions might agree to regional reviews or something of the like — where a "regional" external ethics review Board could approve a study once for a number of local institutions.

Third, getting faculty members, students and clinicians to serve as Board members is a notoriously difficult task. It's not like some committee work at Universities that involves simply attending an occasional meeting with no "homework". Compared to most committee work (required by most higher educational institutions as part of the service requirements for tenure-track faculty), it's a great deal more work and effort. However, it's clearly not a priority for many institutions who don't recognize or promote the importance of these kinds of processes nor are those involved in the work rewarded or supported as well as they should be. Old news.

Outsourcing that work to an external Board would eliminate, to some degree, the need to recruit busy professors and clinicians from within the institution. However it would likely involve increased costs. Currently, many ethics review board Chairs and members essentially "work for free". They might perhaps be provided with a course release or a merit increment in pay for their ethics review work. Outsourcing ethics review responsibilities would mean direct costs for institutions, who would have to pay for external Board members and their work.

Which leads us to the clear downsides of a move to outsource research ethics review. But, really, shouldn't we just be glad to offload this work?

Well, the model of local review works — at the very least, it helps ethics review boards with their primary mandate of protecting participants. A local board, situated within an institution or community, has special knowledge of that community, the populations, etc. That "insider" knowledge not only helps to maintain the protection of potential participants from within the community but also it helps researchers. At the end of the day, knowledge of community-held local norms and offering advice on such communities can help researchers to gain appropriate access into certain institutions and participants.

Local norms help protect institutions with "special" populations or considerations. Here's how. A pediatric hospital or a community mental health centre may have very different local norms for ethics review than a large academic acute care hospital. In turn, a small arts college may have much different norms than those of a large University with emphases on biomedical research programs. These kinds of local norms are, for the most part, based on local interpretations of the federal guidelines for the ethical conduct of research. These kinds of variations in, for example, approaches to recruitment or requirements for a consent form, are vitally important in helping to protect participants, especially those "special" populations that may be more vulnerable.

Additionally, the issues of responsibility and liability are unclear when a Board that is external to the institution approves a study. Detailed agreements would need to be in place and would require ongoing revision, almost on a case-by-case basis for large centres with highly varied research being carried out. Again, the issue of the competing priorities of academic research centres comes up. It would require a great deal of dedicated vigilance to work with an external body to ensure that local standards for the ethical conduct of research are being upheld. If the support for research ethics work isn't in place now, how will support for that dedicated vigilance and ongoing coordination, required with an external board, ever become a reality?

This isn't an easy question to answer. It also isn't one that will be answered by a "one size fits all" kind of solution. Clearly, the model of local review has particular attributes that are situated in important values and principles for how the Canadian community feels that research participants should be protected. Whether those values and principles can be upheld by taking the REB completely out of the institution remains to be seen.

Here's an older, but still very interesting article on this issue, which also puts forth some suggestions for alternative models:
Debate Over Institutional Review Boards Continues as Alternative Options Emerge

Finally, Some Good News in Research Ethics

2009-09-11T23:45:00.001-04:00

Call it effect of the "Back to School" time of year, filled with hope for new beginnings, but I am compelled to write a blog entry about something positive in research ethics. I have found the last few months replete with discouraging stories about deception and bad behaviour in the conduct of research. I was more than ready for something inspiring when I happened upon the website for this UK-based program.

R4D (Research for Development) is a web "portal" for the funded research of the DFID (The Department for International Development) in the UK. The DFID, as part of its mandate, funds research in the developing world and R4D is the mechanism by which the rest of the world can learn about the research that is underway.

Here's a bit about DFID from their website:

The UK government believes it is in all our interests to help poor people build a better life for themselves. So in 1997 it created a separate government department - the Department for International Development (DFID) - to meet the many challenges of tackling world poverty. It is DFID’s job to make sure every pound of British aid works its hardest to help the world’s poor.

We work in 150 countries and have 2,600 staff, half of whom work abroad. We have headquarters in London and East Kilbride, near Glasgow, and 64 offices overseas.

The R4D website is essentially a repository of information about the kinds of research the DFID funds. It has case studies, a database of information from previous studies, information about the 6 research priorities for DFID (Growth, Sustainable Agriculture, Climate Change, Health, Governance in Challenging Environments, Future Challenges and Opportunities) and published papers from DFID-funded projects.

One such project is the Young Lives project. Young Lives is a long-term international project documenting the changing nature of child poverty in four developing countries: Ethiopia, Peru, India and Vietnam. Following 12 000 children, the investigators on this project are aiming to facilitate the implementation of more relevant policies to aid the world's poor, especially children and youth. It's a very worthwhile project and the methods are outlined in incredible detail on the website.

But something else drew me to this project, aside from the obviously meritorious objectives. On their website, they have a section called "Research Ethics". Here they address the kinds of research ethics issues they have faced in their project and articulate their approaches to these issues, e.g. informed consent, anonymity and compensation. They also include a guidelines paper on the use of photography in research on children. They even provide a link to a working paper by a Young Lives Co-Investigator, Virginia Morrow on The Ethics of Social Research with Children and Families in Young Lives: Practical Experiences

Why is this so positive? Well, it demonstrates that the investigators on the project don't consider research ethics to be merely a bureaucratic or administrative process to be completed before research can begin or to fulfill the requirements of funding agencies or federal guidelines. Rather, it shows that they consider research ethics to be an important, dynamic and consistent part of conducting research. And while I'm a little hesitant to use the buzzword "transparent" to describe their approach, the fact that anyone can visit their website to read their consent forms or learn more about photography of children in their project, is laudable. It's clear that novice researchers, graduate students and research assistants on this project are getting valuable and relevant education on how to conduct research with integrity. And to see this approach taken on a project involving such a vulnerable population — poor children — is more than encouraging.

It's clear that, at least in the eyes of these researchers, research ethics is more than simply an application or stamp of approval. It's an integral part of a project, from beginning to end. And while that isn't necessarily a newsflash to most of us, to see research ethics presented as an intrinsic part of the research process is very good news.

CIA Physicians and Research on Torture

2009-09-03T23:21:00.004-04:00

As reported by The Guardian:

Doctors and psychologists the CIA employed to monitor its "enhanced interrogation" of terror suspects came close to, and may even have committed, unlawful human experimentation, a medical ethics watchdog has alleged.

Physicians for Human Rights (PHR), a not-for-profit group that has investigated the role of medical personnel in alleged incidents of torture at Guantánamo, Abu Ghraib, Bagram and other US detention sites, accuses doctors of being far more involved than hitherto understood.

PHR says health professionals participated at every stage in the development, implementation and legal justification of what it calls the CIA's secret "torture programme...."

It's important to note that (at least as reported by the Guardian) what's at issue, here, is not the simple presence of physicians and psychologists at interrogation sessions; it's the notion that they were there doing research. According to the PHR's press release...

The [CIA Inspector General's] report details how the CIA relied on medical expertise to rationalize and carry out abusive and unlawful interrogations. It also refers to aggregate collection of data on detainees' reaction to interrogation methods. PHR is concerned that this data collection and analysis may amount to human experimentation and calls for more investigation on this point....

Now, on one hand, the fact that detainees were used as research subjects without their consent might be thought of as the worst of their problems. I suspect that when you're being waterboarded, the fact that the guy in the white coat standing in the corner didn't ask your permission to take notes isn't your foremost worry. But think of it this way: if there's anything worse than being tortured, it might just be being tortured with the additional knowledge that your torturers are using you as a way of learning how to torture others more effectively.

Interestingly, notwithstanding the focus on consent in the Guardian and in the PHR's press release, the PHR's full report barely mentions consent as an issue, or research more generally for that matter. This raises the question of whether the research ethics angle, here, is considered an important one by PHR, or whether research ethics rules are being used (rightly or wrongly) as a tool to achieve other objectives.
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p.s., back in May, Nancy posted this related item: Research on torture: Should we put limits on what topics researchers can study?

PLoS Ghostwriting Archive

2009-08-21T12:57:00.006-04:00

Two weeks ago we blogged about a ghostwriting case involving Wyeth. So we were interested to see that PLoS Medicine has now put an entire archive of documents related to Wyeth's sophisticated ghostwriting system.

See also this editorial accompanying the archive, from PLoS Medicine's Chief Editor, Ginny Barbour: Ghostwriting: The Dirty Little Secret of Medical Publishing That Just Got Bigger. The editorial reads, in part:

If you are an editor, author, reviewer, or reader of medical journals, or if you depend on your doctor or health care provider getting unbiased information from medical journals, then the 1,500 documents now hosted on the PLoS Medicine Web site should make you very concerned and angry [1]. Because, quite simply, the story told in these documents amounts to one of the most compelling expositions ever seen of the systematic manipulation and abuse of scholarly publishing by the pharmaceutical industry and its commercial partners in their attempt to influence the health care decisions of physicians and the general public....

To Barbour's list of people-who-should-be-concerned, I'd add Ethics Board members as well as university administrators. In particular, with access to this kind of evidence about ethical standards at Wyeth, don't you think it at least possible that Ethics Boards are going to be scrutinizing research protocols extra-carefully, when those protocols are sponsored by that company? And in turn, wouldn't any researcher who knows Wyeth's now-tarnished reputation have misgivings about associating themselves with that company's name?

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Tip of the hat to Sheril Kirshenbaum, who blogs at Discover.

The persistence of the therapeutic misconception

2009-08-14T08:49:00.001-04:00

A recent paper in BMC Medical Ethics shows that, in a small sample, a majority of research participants expressed a therapeutic misconception about the research in which they were involved. This isn't necessarily news. The notion of therapeutic misconception has been around for a long time and Applebaum et al, in 1982, finally gave a name to it. Much has been written on therapeutic misconception since that time and interestingly, it seems to have become a pitfall of human participant research that many comment on.

Here's the story: Expression of therapeutic misconception amongst Egyptians: a qualitative pilot study

There are two major ethical concerns with the TM. First, failure to appreciate correctly the risks and benefits of research participation raises concerns regarding the validity of informed consent. Indeed, understanding is an important requirement of informed consent, which itself is fundamental to ethical clinical research. Second, the presence of TM reflects the very real possibility that research participants will see themselves as patients and trust researchers as if the investigator's role was that of the physician. The resulting concern is that patients will be susceptible to exploitation, as investigators might take advantage of such misplaced trust to enroll them in clinical research. The specific concern is that patients will view an invitation to enroll in research as a professional recommendation that is intended to serve their individual treatment interests.

Therapeutic misconception (TM), according to the authors of the BMC article, comes in two forms. In the first form, participants mistakenly believe that decisions regarding randomization in a study will be individualized to their needs and will "help" them and not cause potential harm, i.e. "The study doctor will make sure that I'll get the better drug!" The second form of TM occurs when participants overestimate the degree of individual benefit that will come from enrolling in a study, i.e. "My doctor wouldn't ask me to take part if she didn't think participating would help me!" The existence of an "already-standing" relationship, especially a therapeutic or trusting one (doctor-patient, therapist-patient) can contribute to TM in a significant way.

This is arguably one of the most serious problems in human participant research, both clinical and non-clinical (and I'll say later why the concept of TM is so important in non-clinical research as well). Why is this one of the most serious problems in research ethics? First of all, it's pervasive. While this article was nicely conceptualized and well-written, it wasn't saying anything new. More participants than not think that research, to some degree, may involve personal benefit and will certainly not cause them harm. Second of all, for a moment, just imagine the opposite case. Imagine if a patient coming in for surgery to bypass his diseased coronary arteries actually thought he was undergoing an intervention related to research, instead of a routine bypass surgery for therapy. The clinical team would, no doubt, work very hard to clarify the therapeutic value of the procedure and ensure that he demonstrated understanding that this wasn't a "research study" before allowing him to consent to the surgery. As researchers, do we work as hard to ensure that human participants in research actually understand that research does not equal therapy? I don't think so. I'm not sure why.

Most of the literature on therapeutic misconception addresses the phenomenon in the context of biomedical research. I think that the therapeutic misconception is just as pervasive in many other types of human participant research, from what I've seen and read. Students involved in educational research believe that their trusted professors wouldn't expose them to a useless learning or teaching intervention as part of an educational study. They may, in turn, also believe that participation in a study by their professor will augment their knowledge or help them be in a position of advantage in terms of learning. Participants involved in qualitative interviews may believe that it is a form of beneficial talk-therapy. Those who volunteer for psychology studies may well harbour false hope that the studies will offer them individualized help. While it's true that, in some cases, students involved in educational research may learn new skills that will help them in their academic life and those involved in qualitative interviews may feel empowered from telling their stories, research participants must be made to understand that research study involvement cannot guarantee personal or individualized benefit. How to ensure this? First, it must be more than simply a routine statement on a consent form. As I've said before, consent is much more than a form. It's a process that is merely represented, in many cases, by a form. Concepts like randomization, risk and benefit must be clearly explained during the research process and ideally, participants should be provided with understandable information about the goals and purposes of the study. Care must be taken in recruitment processes to avoid role confusion — the caring physician may not be the ideal person to recruit her own patients for a study and the engaged and passionate professor might be better to have a research assistant introduce a study to a classroom of students.

Each study and potential case of TM is different. Researchers must be aware of the kinds of messages that they explicitly (through consent forms) and implicitly (through "already-standing" therapeutic relationships) send to participants when discussing benefit and obtaining consent. Research ethics boards need to be vigilant about reading consent forms carefully, examining consent processes, identifying "already-standing" therapeutic relationships and engaging in discussions with researchers about these kinds of issues so that pitfalls, like TM, can be avoided.

Research Ethics in Space

2009-08-12T08:48:00.002-04:00

Yes, in space. We've blogged before about ethical issues related to research done overseas. But research ethics in space? That's a new one for us.

Check out this conversation with Paul Root Wolpe, from the New York Times: Scientist Tackles Ethical Questions of Space Travel

Q. AS NASA’S CHIEF BIOETHICIST, WHAT DOES YOUR WORK INVOLVE?

A. I’m an adviser to the chief medical officer for the agency. I don’t make decisions. Instead, I analyze situations and policies and offer bioethical perspectives on specific problems.

NASA does hundreds of research studies. Every astronaut who goes into space is, essentially, a human research subject. NASA’s looking at the effects of weightlessness, of G-forces and radiation on the human body. One of the things I do is look over the research protocols and make sure they are in compliance with earth-bound regulations about informed consent and health and safety. I also try to help solve some of the thorny ethical problems of medical care for astronauts in space....

A few quick thoughts:

1) My first thought is about the challenges such a unique research setting poses for Wolpe, who, from the sounds of it, essentially acts as a one-man ethics board for NASA. Nancy blogged back in June about the fact that research ethics boards typically learn, and improve, by a process of trial and error. The number of trips into space, and hence the number of space-based experiments, is tiny. That makes it hard for anyone to build up a base of expertise — assuming, as seems reasonable, that there are at least a few ethical peculiarities unique to doing research in space.

2) Nor is there going to be a body of literature to draw upon. There's no Journal of Space-Based Research Ethics. So there won't be any place to look to see how other people in the field have dealt with the same issues.

3) But of course, research in space isn't totally unique: it has parallels, though maybe not precise ones. NASA isn't technically military, but it seems reasonable to expect that research during a space mission would share some things in common with research on military personnel. And given that astronauts are basically trapped in a shuttle or space station, research on them would have something in common with research on institutionalized individuals, like prisoners.

4) Unlike most research, research on board a shuttle or space station probably blurs the line between researcher and subject. In many cases, everyone on board will play both roles. That's unavoidable, but it's also likely to require additional safe-guards.

5) Finally, to the extent that the military analogy is valid, the US Army is a pretty good organization to look to in terms of having well-worked-out policies to protect their personnel in research contexts. (For example, Army Regulation 70-25 [PDF here.] rightly forbids use of military-legal penalties against personnel who decline to participate in research.) I don't know much about how well the Army has done at applying those policies, but having such policies in place is a very good start. And if their policies are sound ones, then Wolpe isn't working entirely in a vacuum; he's not merely left to boldly go where no research ethicist has gone before.

Ghost-Writing and the Corruption of Research

2009-08-05T10:36:00.002-04:00

Earlier today I posted, over at the Business Ethics Blog, an item called Wyeth, 'Ghost-Writing' and Conflict of Interest. It was based on this article by Natasha Singer, writing for the NY Times: Medical Papers by Ghostwriters Pushed Therapy

Newly unveiled court documents show that ghostwriters paid by a pharmaceutical company played a major role in producing 26 scientific papers backing the use of hormone replacement therapy in women, suggesting that the level of hidden industry influence on medical literature is broader than previously known.

The articles, published in medical journals between 1998 and 2005, emphasized the benefits and de-emphasized the risks of taking hormones to protect against maladies like aging skin, heart disease and dementia. That supposed medical consensus benefited Wyeth, the pharmaceutical company that paid a medical communications firm to draft the papers, as sales of its hormone drugs, called Premarin and Prempro, soared to nearly $2 billion in 2001....

On the Business Ethics Blog, I focused on the fact that the company involved, Wyeth, completely missed the point in arguing that the articles it paid to have ghost-written were scientifically sound. Wyeth's argument misses the point, I said, because the problem with conflict of interest is not that it typically results in bad outcomes; the problem, rather, is that it shakes our confidence in the reliability of a decision-maker and possibly in an entire institution.

What I didn't touch on in that blog entry is the role of the physician-researchers whose names appeared on the ghost-written papers. Clearly, their cooperation in the charade is crucial. And some of them — maybe all of them — also fail to see the true problem with ghost-writing. Check out this quotation, from Dr. Gloria Bachmann, one of the medical professionals involved:

“There was a need for a review article and I said ‘Yes, I will review the draft and make sure it is accurate,’ ” Dr. Bachmann said in an interview Tuesday. “This is my work, this is what I believe, this is reflective of my view.”

Once again, this misses the point entirely. The problem is not whether the paper that resulted from the ghost-writing process was sound, or whether it represented a point of view that Dr. Bachmann could stand behind. The point is: how can we be sure? How do we know just how much, or how little, influence Wyeth, had on the paper that resulted? It's not that we don't trust Dr. Bachmann. I, for one, am willing to give her the benefit of the doubt. The problem is that the process used to generate the paper that bore her name was one highly likely to cast doubt upon the process of scientific publication. I wonder, if more researchers saw things that way, would they be more hesitant to participate in that process?

Plagiarism and the scientific paper

2009-07-29T12:25:00.004-04:00

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

2009-07-26T13:22:00.006-04:00

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

2009-07-22T17:04:00.001-04:00

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.