Paying to Participate in Genetic Research

How would it — how will it? — affect ethics review of research protocols if research subjects paid to participate? That is, what if research subjects — instead of either volunteering or being paid to participate — paid the researchers? How would that change things? Would that change the kinds of protections offered? Should it?

See this opinion piece from Nature.com: Personal genomes: Misdirected precaution

If anything, personal genomics has rendered this relationship [between modes of producing knowledge and producing economic value] even closer. 23andMe, for example, encourages customers to upload health, physical and lifestyle information, and to participate in genetic research. For the first time, we see research participants paying to be enrolled. (emphasis added)

(23andMe has appeared on this blog before: Want to find out what makes you "stand out from the crowd"? Consider signing up for a research study!)

So does this change anything, in terms of ethics review? Some will be quick to say it shouldn't: a research subject is a research subject, and all are equally deserving of protections. But I think that's too quick. Much of our thinking about the protection of human research subjects is rooted in clinical or quasi-clinical settings, in which researchers with a public-good agenda (or even just intellectual curiosity) seek out people to do their research on. In the kind of research being discussed in the Nature article above, it's the other way around: customers are seeking out 23andMe with their own wants, needs, and agendas.

Now that's not to say that research ethics in such contexts becomes a case of "buyer beware." Far from it. Even in the most nearly free markets, consumers deserve all kinds of protections (mostly to make up for very serious information asymmetries). But it's worth at least considering how research like this puts pressure on our assumptions, by pulling us between two different normative paradigms.

Ethics and autism research

In a story from September 2008, Harold LD (an east coast Canadian blogger) calls attention to a large multi million dollar study, headed by Dr. Stanley Greenspan, professor of psychiatry at George Washington University. Greenspan, a long time researcher and expert on emotional and development disorders, will identify infants at risk for either autism spectrum disorder or attention deficit disorder, provide half of them with intensive behavioural intervention (IBI therapy — also sometimes referred to as ABA therapy) while the other half will have no therapy. All the children will be followed through to age 5.

Here's the story From Harold LD's blog: Autism Research Ethics - Is It Ethical to Deny ABA to Autistic Infants for Research Purposes?

It's been proven that two things are beneficial for kids diagnosed with autism. The first thing is early intervention. Early identification that a child is "at risk" is a good indicator of a possible diagnosis. Many parents spend months and years, going from generalist to specialist, trying to find a diagnosis for their child. By the time some kids are diagnosed with autism, the window for effective early intervention may be closing. The second thing is IBI. Now, IBI is not without its critics — based on principles of behavioural therapy, it is incredibly expensive, highly focused on outcomes and rewarded reinforcement and frankly, it's not a panacea for every kid diagnosed with some form of autism. However, there is clear evidence that this intensive therapy, when offered in various, individualized forms and delivery modes, can help many kids with autism to develop generalizable skills in areas of communication and socialization — two commonly affected areas in kids who are autistic.

The literature supports these two things as beneficial. Early intervention and at least a trial with IBI therapy is a good thing for most kids with autism, notwithstanding that if you have 20 kids with autism in a room, you'll have 20 very different kids. But it's pretty easy to say that, across the board, early intervention with effective therapy benefits these kids.

So, back to the question posed in the headline — is it ethical to deny some kids with autism or who are at risk of autism, access to IBI therapy? In medical trials, the principle of clinical equipoise is an important consideration. It is the ethical foundation of sound medical research projects that assign subjects to more than one arm. If it is evident that one arm or treatment is superior to another, the trial should not begin (if it hasn't been started) or should not continue (if it is already underway). The notion of clinical equipoise implies real uncertainty over the relative benefits of one arm of treatment over another. A trial, designed to meet the criterion of clinical equipoise should, at it's completion, be able to answer the question, "Which treatment is preferable?". In this case, I would posit that we already know the answer to that question...

In this case, we know that early intervention is beneficial to kids at risk of autism or diagnosed with autism. (Note — the study notes that these kids are "at risk" of autism — not necessarily kids diagnosed with autism. So at risk kids in this group who are never diagnosed with autism will arguably benefit from close observation by simply being enrolled in the trial, through to age 5.)

However, it is foreseeable that a good number of these kids likely will be diagnosed with autism somewhere along the way and hopefully well before age 5 (it would make sense that they would be diagnosed early if they are being observed so closely). Should the children who go from being identified as at-risk to then being diagnosed with autism be removed from the trial in order to receive the clearly documented benefits of early intervention and treatment....?

Updates on this story to follow.

To read more about autism and IBI, here's a good straightforward Q&A on autism and IBI therapy from the Sick Kids Hospital (Toronto, Canada) website.

To read more about clinical equipoise, here's a short, clear article from the BMJ by Weijer, Shapiro and Glass: Clinical equipoise and not the uncertainty principle is the moral underpinning of the randomised controlled trial.

Race & Physicial Referral to Clinical Trials

Here's an interesting study from the Journal of the National Medical Association: Factors Influencing Physician Referrals of Patients to Clinical Trials. [PDF file] Here's a brief, incomplete summary...

Rationale for the study:

Including minorities and particularly, elderly minorities, in medical research is particularly important in light of evidence of potential racial and ethnic differences in response to treatment. Yet a common barrier to the development of new knowledge for medical problems affecting racially and ethnically diverse populations is the ability to enroll diverse patients in research studies.

How they did it:

We surveyed 200 physicians from areas ...with ≥40% African Americans or Latinos. Physicians were asked about attitudes toward research, likelihood of referring patients to PD trials and past research participation, and administered the Trust in Medical Researchers Scale.

The authors' main conclusion:

Study results emphasize the importance of developing a trusting relationship with local physicians if investigators expect these physicians to refer their patients to clinical trials. The trust-related barriers for minority-serving physicians, regardless of their own race/ethnicity, seem to mirror the trust-related issues for their minority patients.

Research, ethics and the internet

As a relatively new blogger, I've become interested in lots of issues in digital media. One issue that comes up time and time again, in a variety of contexts is how we *allow* ourselves to be represented online through various formats of digital media (e.g. blogs, social-networking sites, Wikipedia, virtual worlds, etc.).

An recent article in Education Week online highlights a current project at the Harvard Graduate School of Education led by psychologist Howard Gardner, in which researchers are looking at the kinds of unique ethical issues faced by the pervasiveness of the digital world in the lives of most young people. Here is the story (you do need a subscription to get the full story, but a one week free subscription is available): Project probes digital media's effect on ethics.

Here are two noteworthy findings from the data collected so far:

First, many young people are not prepared to make decisions about how they are represented or how their own images are disseminated online. WIthout clear established norms about how one *should* treat images, statements about or representations of another person - how many people have posted pictures of others on their Facebook pages, tagging others without asking them first? - young people are making the ethical rules up as they go.

Second, the researchers state that we've gone from an age of "Walter Cronkite to Sarah Palin". In other words, the ways in which young people regard institutions have moved from ideas about authority and representing oneself in a way that would be considered objectively acceptable to a more modern ideological choice to present oneself as truly authentic and transparent, good or bad, without thoughtful consideration of the possible consequences of these kinds of choices. Furthermore, most youth interviewed by Gardner and his colleagues said that the idea of responsibility and "ethics" was considered as optional for young people today and was instead, something that one only had to worry about when older and more established.

This is a challenge for all of us involved in digital media, from casual Facebook or Wikipedia users to hardcore bloggers (I'm not putting myself in that category by any means, yet!). Ethics review boards are going to have to start thinking about this issue - or they should be already. The preliminary findings of this project demonstrate that young people today have unique ideas about what "ethics" is in terms of how one *should* interact with others and represent oneself, through digital mediums. Second, it shows a level of comfort that borders on nonchalance about the way in which their photos, ideas, images and opinions are shared online. With social networking sites, blogs and dedicated websites already being used to recruit participants, collect data and even disseminate results of research in creative and innovative ways, these finding are especially compelling. They will, for sure, create new ethical challenges for ethics review boards to consider in areas like consent, data management and security, privacy, confidentiality and sharing of research findings.

More reading:

FYI, The Social Sciences and Humanities Research Ethics Special Working Committee, a working committee of the Interagency Advisory Panel on Research Ethics (PRE) has a report entitled Extending the Spectrum: The TCPS and Ethical Issues in Internet-based Research

In memory of Jay Katz

Dr. Jay Katz, a scholar and major figure in the field of research ethics, died yesterday in New Haven at age 86. Katz, a physician and Yale law school professor, served on the Tuskegee Syphilis Study Ad Hoc Advisory Panel. Not only did the Panel publicly declare the study itself blatantly unethical, they contributed to the regulations and guidelines that are in place today to protect human participants in research.

Here's a link to the Centers for Disease Control and Prevention's website, noting the contribution of the Ad Hod Advisory Panel:

Research Implications from the Tuskegee Syphilis Study's Ad Hoc Advisory Panel

The Final Report of the Panel (1973) clearly notes the importance of 3 fundamental issues in research ethics: Oversight of governmental agencies conducting human participant research, informed consent and the establishment of ethical review boards to oversee the conduct of research. This document contributed to The Common Rule, which, in the USA, is a key policy for protection of human participants.

Katz also did fundamental (and at the time of publication, groundbreaking) work, examining and articulating the complexity of ethical issues within the traditional physician-patient relationship in his book,The Silent World of Doctor and Patient. This is a book every bioethicist and research ethicist, without a doubt, has on their bookshelf. Or should.

Here is more on Jay Katz, from the PRIMR website, from which he recieved a Lifetime Achievement Award in Ressearch Ethics: Jay Katz: In Memoriam

Other books by Jay Katz:

Experimentation with human beings: The authority of the investigator, subjects, professions and state in the human experimentation process

Research, Teaching, and Conflict of Interest

The topic of "research ethics" sometimes gets conflated with the sort of stuff that Ethics Boards oversee, including mainly the protection of human subjects and compliance with relevant regulations.

But research ethics is of course broader than that. Here's an interesting story about how the funding of a professor's research has implications for his or her relationship with students.

From The Harvard Crimson: Harvard Medical School Students Push to Codify Conflict of Interest Polices

Addressing a weekly clinic for “The Molecular and Cellular Basis of Medicine,” a required introductory course for first-year medical and dental students, Medical School professor Paul G. G. Richardson was accompanied by a patient diagnosed with myeloma, a potentially deadly blood cancer.

The patient was being successfully treated with a bortezomib-based therapy, a drug marketed as Velcade by the Cambridge-based Millennium Pharmaceuticals. Students said that during the clinic discussion, Richardson suggested bortezomib can now be used as a first-line treatment—meaning that physicians can prescribe use of the drug at diagnosis, rather than only as a second or third-line therapy when the disease has recurred.

Intrigued by his presentation, several students later looked up some of his peer-reviewed articles and found that Richardson was on Millennium’s advisory board—a potential conflict of interest that was not disclosed during the session with Richardson and his patient.

The story continues:

In response to the student concerns, the school’s curriculum committee revised the school’s student handbook last month to include a section of new policies mandating that faculty and students disclose all financial ties to pharmaceutical companies when discussing drugs developed by those companies.

It's food for thought...at least on a day when you're not busy either preparing, or reviewing, a proposal!

Four excellent books to recommend:

• Conflict of Interest in the Professions, edited by Michael Davis and Andrew Stark
  
• Ethics and the University, by Michael Davis
  
• Conflict of Interest in American Public Life, by Andrew Stark
  
• Conflicts of Interest: Challenges and Solutions in Business, Law, Medicine, and Public Policy, edited by Don A. Moore, Daylian M. Cain, George Loewenstein , and Max H. Bazerman (This book focuses on really intriguing work on COI coming out of experimental psychology and experimental economics.)
  

When anonymous isn't really anonymous

Some researchers -- particularly inexperienced ones -- find it hard to understand why Ethics Boards are sometimes so picky about data management and about the difference between "anonymous"and "confidential" data.

Here's an interesting story from an unlikely source that gives a partial explanation. From The Ottawa Business Journal: Private eyes are watching you...electronically

Khaled El Emam says he teaches his students not to trust
in anonymous data. The University of Ottawa professor, who holds positions at a trifecta
of local institutions, routinely has his students cross-reference whatare supposed to be anonymous land registries, real estate databases and the like with phone books and the Internet.

He says it usually doesn't take long before names start popping up – a lesson he bore in mind when developing a new medical record tool for the Children's Hospital of Eastern Ontario (CHEO).

In Canada, while there are provincial laws to protect personal health information, these protections do not apply to data that have been "anonymized". If, however, the data have not been adequately stripped of potential identifiers in the first place, this leaves nothing in place for protection. And that doesn't mean removing only names and birthdates from data sets. Even the first three letters in a postal code can help to potentially identify someone. This story highlights both how useful aggregated health-data can be to researchers, but also how easy it can be to de-anonymize data that hasn't been carefully anonymized in the first place.

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Relevant Books:

• Health Information Management: Principles and Organization for Health Information Services
  
• Understanding Privacy
• The Digital Person: Technology and Privacy in the
  Information Age
  
  

Indian Vaccine Trial Halted over Infant Death

Who's to blame if a useful medicine is delayed in getting to sick children because a trial had to be stopped due to a violation of ethics rules?

Here's a relevant story from LiveMint (the website for an Indian newspaper published by the Wall Street Journal)... Wyeth drug tests fall foul of watchdog. Here are the first bits:

New Delhi: Patient trials of an advanced pneumonia vaccine by the domestic unit of US drug giant Wyeth Inc. have been suspended by India’s drug quality regulator after the death of an infant on whom the vaccine was tested in a trial in Bangalore.

The child had a pre-existing cardiac disorder. Indian drug rules prohibit testing on human subjects with such conditions without the prior approval of the drugs controller general of India (DCGI), the drugs quality regulator.

Also worthy of note:

Though the Indian regulator has suspended several drug trials in the past, all of them have been over adverse reactions or efficacy issues, and not for violation of the rules themselves, according to drug regulation experts.

Just who is to blame is not yet clear:

It was not immediately clear at which link in the testing chain the mistake occurred. Wyeth Ltd, the Indian unit, said the tests were conducted by GVK Biosciences, contracted for the trials, LiveMint writes, although Singh [India's Drugs Controller General] says Wyeth had conducted the trials on its own.

So, some will say this is a regulator/bureaucrat slowing down research over a technicality. (Note that the trial was topped over a violation of the rules, not over the infant's death per se.) But the blame more properly sits with those conducting the trial: Wyeth, GVK, and the physicians actually on the front lines. How to apportion the blame is a harder question, the answering of which will have to await further information.

But it's another example of how bad ethics ends up also being bad science, and bad for the very people such research is designed to help.
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Hat tip to Pharmalot.

A revised Code of Ethics for anthropologists

The American Anthropological Association is in the midst of revising their Code of Ethics, which was originally created in 1971 as a reaction to the discovery that anthropologists had been conducting counterinsurgency research during the Vietnam War. Issues arising from military activities in post 9/11 Afghanistan and the Iraq War have pushed the Association to rethink the Code of Ethics and to call for a serious revision.

Here is the story, by Carolyn Fluehr-Lobban, an anthropologist, in the November 14 issue of the Chronicle of Higher Education (sorry, subscription or academic access required!): New Ethical Challenges for Anthropologists.

One of the things that the AAA is most concerned about right now is secret research. To some degree, this has arisen out of the use of anthropologists by the US military as part of the Human Terrain Teams in Iraq and Afghanistan — which has drawn comparisons, by some, to Project Camelot and The Phoenix Program, both counter-insurgency military/social science "research" programs conducted during the Vietnam War, and partial catalysts for the introduction of an AAA Code of Ethics.

The Human Terrain Teams (HTT) program is a US military-based effort that embeds anthropologists (as a type of “cultural advisor”) with active combat units to help those units understand local cultures, engage locals, and understand cultural traditions and histories with the goals of helping the locals set up governments, police departments and other protective agencies in order to control counter-insurgency and sustain political stability. The AAA is more than a little concerned, however: in 2007, it denounced the program, stating that it was potentially unethical, exploitive and potentially disgraceful to the profession in the long run. The AAA is justifiably concerned that all anthropologists might be seen as "mercenary anthropologists" using discipline-specific knowledge for political gain or for intelligence-gathering.

Either way, the program could easily paint anthropologists in a negative light, as they may be seen as mere puppets meeting the goals of larger, often covert politically or militarily-driven projects. In a world in which foreign trust in America has been damaged, the continued use of embedded social scientist researchers might do further irreparable harm. Certainly, the project may do some good. However the notion of embedded, somewhat secretive social scientist-researchers as active partners in military counter-insurgency units is hardly the image to boost positive relationships or to engender trust in the discipline. The AAA currently has a Commission on Engagement of Anthropology with the US Security Community (which deals with anthropological research/practice in military and intelligence activities), and since 2006, Fluehr-Loggan, who serves as part of this Commission, alongside her colleagues, has been grappling with revising and articulating ethical standards for such complex research activities. In light of a new political age in America, it will be interesting to see how this story progresses. I'll follow up with any new developments.
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Addendum:

Here's a relevant book:
Anthropological Intelligence: The Deployment and Neglect of American Anthropology in the Second World War, by David Price (Duke University Press 2008)

Here's a review of Anthropological Intelligence from the Times Higher Education Supplement.

73 Years Ago Today: First "Modern" Lobotomy. Would Your Ethics Board Approve?

The lobotomy is about as controversial as surgical interventions get. Nothing else stirs the popular imagination -- a bit of fascination, a bit of horror -- in just the same way. It is also a controversial procedure, in part because it does precisely what it promises to do: change behaviour. It is surely a procedure that has its victims; and just as surely, there are people it helped.

It is a truism that for every medical procedure, there is a first time. Today, as it happens, is the 73rd anniversary of one such innovation. From Wired.com: Nov. 12, 1935: You Should (Not) Have a Lobotomy

Nov. 12, 1935: The world's first modern frontal leukotomy is performed in a Lisbon hospital by Portuguese neurologist Antonio Egas Moniz.

Moniz's leukotomy (or leucotomy, from the Greek for "cutting white," in this case the brain's white matter) soon became popularly known as the lobotomy. It was not, however, the surgical procedure now generally associated with lobotomies. Rather, Moniz drilled two holes in the patient's skull and injected pure alcohol into the frontal lobes of the brain to destroy the tissue, in an effort to alter the patient's behavior.

Within a year of Moniz's procedure at Lisbon's Santa Marta Hospital, American neurosurgeons Walter Freeman and James Watts had performed the first prefrontal lobotomy in the United States. Their approach, which they would continue refining in subsequent surgeries, also involved drilling holes, but instead of using alcohol they surgically severed the nerves connecting the prefrontal cortex to the thalamus.

With various refinements, this became standard operating procedure for the prefrontal lobotomy.

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Two books providing very different perspectives on the practice, as popularized by Freeman:
My Lobotomy by Howard Dully and Charles Fleming
The Lobotomist: A Maverick Medical Genius and His Tragic Quest to Rid the World of Mental Illness, by Jack El-Hai

REB oversight of Embryonic Stem Cell Research in Ireland

Here is an interesting development in the debate over the use of stem cells in research. Last week in Ireland, one university, University College Cork (UCC), passed a policy to allow the use of embryonic stem cells in research.

Here's the story from the Irish Times: UCC gives go-ahead for embryonic stem-cell research

A point worth noting:

There is no current legislation in Ireland over the use of embryonic stem cells although certainly, with other Universities planning to also follow UCC's lead, pressure will be on the government to enact legislation. For now, oversight, policy development and monitoring will be the responsibility of the Research Ethics Board (REB) at the University.

The REB's responsibility, (as articulated in the article and passed by the Academic Council of UCC), includes not only the ethical review and ongoing monitoring of research involving embryonic stem cells, which in and of itself would certainly not be an unusual role for an REB, but it also includes advising on the "scientific merit of the research aims of the project". Most REBs require separate scientific review of proposed research, and while attentive to scientific merit, leave the evaluation to scientific review committees and discipline-specific peer review committees. In this case, in the absence of national policies or legislation regarding what is a very emotional and heated topic of debate, having the REB evaluate scientific merit could be seen as forcing the Board to act as gatekeepers, deciding what is either acceptable or not in terms of embryonic stem cell research. True, the UCC REB subcommittee will be made up of experts on the use of stem cells in research. However, this tremendous responsibility, which some might say is outside the standard purview of REBs, places the REB in what is, frankly, a potentially controversial and likely unenviable position.