These pages
describe some of the ethical principles in the conduct of research as well as
information on how an Institutional Review Board (IRB) or other research ethics
board evaluates research proposals. Articles are arranged by date with the most recent entries at the top. Also
see Category: Conflict of interest, Category: Fraud in research, Category: Privacy in research. You
can find outside resources at the bottom of
this page. Other entries about ethics in research can be found in the
ethics in research page at the
StATS website.
2008
- P.Mean: Ethics of research into
unscientific therapies (created 2008-11-15). What is a responsible
ethical position on research on complementary or alternative medicine that is
not based on "generally accepted" principles of science? For example,
redirecting energy fields in the body; or demonstrating the positive effects
of intercessory prayer (prayer on behalf of another person). It is one thing
for a scientist member to say "I don't think the proposed statistical
methodology is adequate to the task." It's quite another thing to say "I don't
believe that there is any scientific basis for the proposed research." What
then?
- P.Mean: IRB approval of studies with
less than adequate research integrity (created 2008-11-14). How should an
IRB view its job with respect to research approval if the study design is "less
than adequate" to provide valid results? Is the IRBs job only to assess for
patient risk? If a study's design is poor and will not yield useful results
should the IRB approve the study if there is minimal risk? Does it matter if the
study is minimal risk vs greater than minimal risk?
2002
- P.Mean: Getting IRB approval for your research
(created 2002-10-09, updated 2010-04-01). Dear Professor Mean: I am submitting a proposal to
our Institutional Review Board. Is there anything you can do to help me get
IRB approval? --Terrified Terri. This article is an update of an article
published at my old website:
www.childrensmercy.org/stats/plan/irb.asp.
Outside resources:
- Kevin P. Hill, Joseph S. Ross, David S. Egilman, Harlan M. Krumholz.
The ADVANTAGE Seeding Trial: A Review of Internal Documents. Annals of
Internal Medicine. 2008;149(4):251-258. Seeding trials, clinical studies
conducted by pharmaceutical companies that are designed to seem as if they
answer a scientific question but primarily fulfill marketing objectives, have
not been described in detail. To describe a known seeding trial, ADVANTAGE
(Assessment of Differences between Vioxx and Naproxen To Ascertain
Gastrointestinal Tolerability and Effectiveness), through documents of the
trial sponsor, Merck & Co. (Whitehouse Station, New Jersey). Merck internal
and external correspondence, reports, and presentations elicited to inform
legal proceedings of , and . The documents were created between 1998 and 2006.
An iterative case-study process of review, discussion, and re-review of
documents to identify themes relevant to the design and conduct of ADVANTAGE.
To supplement the case-study review, the authors did a systematic review of
the literature to identify published manuscripts focused on seeding trials and
their conduct. Review of the documents revealed 3 key themes: The trial was
designed by Merck's marketing division to fulfill a marketing objective;
Merck's marketing division handled both the scientific and the marketing data,
including collection, analysis, and dissemination; and Merck hid the marketing
nature of the trial from participants, physician investigators, and
institutional review board members. Although the systematic review of the
literature identified 6 articles that focused on the practice of seeding
trials, none provided documentary evidence of their existence or conduct. The
legal documents in these cases provide useful, but limited, information about
the practices of the pharmaceutical industry. This description of 1 company's
actions is incomplete and may have limited generalizability. Documentary
evidence shows that ADVANTAGE is an example of marketing framed as science.
The documents indicate that ADVANTAGE was a seeding trial developed by Merck's
marketing division to promote prescription of Vioxx (rofecoxib) when it became
available on the market in 1999. [Accessed July 17, 2010]. Available at:
http://www.annals.org/content/149/4/251.abstract.
- Sherman, Silverstein, Kohl, Rose & Podolsky, Attorneys at Law. New
Jersey Bioethics Litigation Lawyer :: Bioethics and Clinical Trials Litigation
:: Sayreville, New Jersey Medical Ethics Attorney. Description: This
webpage lists resources covering many controversial research experiments.
[Accessed July 17, 2010]. Available at:
http://www.sskrplaw.com/lawyer-attorney-1449361.html.
- Association of Academic Health Centers. Clinical Trials Administration.
Description: This product is quite expensive ($8,500) but the fact that an
organization can charge so much for this is an indication of how important it
is to get down all the details associated with compliance. [Accessed July
17, 2010]. Available at:
http://www.aahcdc.org/toolkit/.
- Anthony Costello. Debating how to do ethical research in developing
countries. The Lancet. 2007;370(9592):1025-1026. Description: This is a
review of the book Ethical Issues in International Biomedical Research: A
Casebook. James V Lavery, Christine Grady, Elizabeth R Wahl and Ezekiel J
Emanuel, eds. Oxford University Press, 2007. Pp 400. £32·99. ISBN
0-19-517922-4. This book contains 21 case studies of recently published
research. The review is mostly positive. Dr. Costello likes the fact that the
book raises more questions than answers, and characterizes the perspectives as
"self-reflection without dogma." [Accessed July 17, 2010]. Available at:
http://www.thelancet.com/journals/lancet/article/PIIS0140673607614615/fulltext.
- Office for Human Research Protections. Guidance on Engagement of
Institutions in Human Subjects Research. Excerpt: "This guidance
document applies to research involving human subjects that is conducted or
supported by the Department of Health and Human Services (HHS). When an
institution is engaged in non-exempt human subjects research that is conducted
or supported by HHS, it must satisfy HHS regulatory requirements related to
holding an assurance of compliance and certifying institutional review board (IRB)
review and approval. This guidance document describes: (1) scenarios that, in
general, would result in an institution being considered engaged in a human
subjects research project; (2) scenarios that would result in an institution
being considered not engaged in a human subjects research project; and (3) IRB
review considerations for cooperative research in which multiple institutions
are engaged in the same non-exempt human subjects research project."
[Accessed July 17, 2010]. Available at:
http://www.hhs.gov/ohrp/humansubjects/guidance/engage08.html.
- Mike Adams. The History of Human Medical Experimentation in the United
States. Description: This webpage provides a detailed and harshly
critical timeline of medical research. The author has an axe to grind against
traditional medicine and big drug companies, but the descriptions are still
valuable. Excerpt: "The United States claims to be the world leader in
medicine. But there's a dark side to western medicine that few want to
acknowledge: The horrifying medical experiments performed on impoverished
people and their children all in the name of scientific progress. Many of
these medical experiments were conducted on people without their knowledge,
and most were conducted as part of an effort to seek profits from newly
approved drugs or medical technologies. " [Accessed July 17, 2010].
Available at:
http://www.naturalhealthreport.com/USHME01.html.
- Anup Malani, Tomas J. Philipson. Push for more trials may hurt patients.
Washington Examiner. 2010. Excerpt: "U.S. pharmaceutical companies are
increasingly going abroad to conduct clinical trials required by the FDA.
Recently, the Department of Health and Human Services released a report
suggesting that the FDA lacks the resources to adequately monitor these
foreign trials. Four of every five new drugs sold in the U.S. are tested in
foreign trials, and the FDA inspects less than one in 10 of these. This is
half the rate of inspection for domestic trials." [Accessed July 27,
2010]. Available at:
http://www.washingtonexaminer.com/opinion/columns/Push-for-more-clinical-trials-may-hurt-patients-1002114-98875969.html.
- Erik Stokstad. Medicine. Stalled trial for autism highlights dilemma of
alternative treatments. Science. 2008;321(5887):326. Excerpt: "The
tension between parents desperate to help their sick children and researchers
who worry about quack medicine has long put public health agencies in a bind.
Last week, a long-simmering controversy boiled over when newspapers across the
country ran an Associated Press story claiming that "government researchers
are pushing to test an unproven treatment on autistic children, a move some
scientists see as an unethical experiment in voodoo medicine." In fact, a
trial of the controversial treatment was halted last year, and Thomas Insel,
director of the National Institute of Mental Health (NIMH) in Bethesda,
Maryland, says he's not pushing to restart it. The case, and the publicity
surrounding it, illustrates the difficulty of deciding whether to test these
questionable therapies, especially in children." [Accessed July 17, 2010].
Available at:
http://www.ncbi.nlm.nih.gov/pubmed/18635766.
- Physicians for Human Rights. The Torture Reports. Excerpt:
"Experiments in Torture is the first report to reveal evidence indicating that
CIA medical personnel allegedly engaged in the crime of illegal
experimentation after 9/11, in addition to the previously disclosed crime of
torture. In their attempt to justify the war crime of torture, the CIA appears
to have committed another alleged war crime—illegal experimentation on
prisoners." [Accessed June 10, 2010]. Available at:
http://phrtorturepapers.org/.
- Michael Goodyear. Unintended results of research. Harm Reduction
Journal. 6(5). Description: "This letter is a response to an article about
the epidemic of HIV/AIDS in Vancouver, British Columbia. The letter writer is
critical of the article and claims that research subjects in the study have
been 'harmed, stigmatised and quite probably subjected to increased levels of
violence'. He goes on to argue that the subjects did not provide informed
consent. 'When women gave permission to be tested for HIV they did not
anticipate that it would be used to stigmatise them, and presumably when they
gave consent for it to be used for research they were not informed of that.'"
Available at:
http://www.harmreductionjournal.com/content/6/1/5/comments#336610.
All of the material above this paragraph is licensed under a
Creative Commons Attribution 3.0 United States License. This page was written by
Steve Simon and was last modified on
2010-07-27. The material
below this paragraph links to my
old website, StATS. Although I wrote all of the material
listed below, my ex-employer, Children's Mercy Hospital, has claimed copyright
ownership of this material. The brief excerpts shown here are included under
the fair use provisions of U.S. Copyright laws.
2008
- Stats: Why we need case studies of
research ethics in graphic novel format (April 3, 2008). I was asked to
provide some justification for a project I am working on, case studies in
research ethics using a graphic novel format. Here is what I wrote.
2007
- Stats: Illustrations for a case
study of the TGN 1412 trial (October 12, 2007). I am working with a
graphic artist to produce some illustrations to help explain what happened
during the disastrous TGN1412 trial. The general structure of these
illustrations are not quite set in stone, but here are my initial thoughts.
- Stats: Conflict of interest in the
Wakefield MMR study (July 26, 2007). An interesting case study in
conflict of interest (perhaps a bit too complex to be described fairly in
this brief weblog entry) involves a controversial paper. The lead author of
this paper, Wakefield A; Murch S, Anthony A, Linnell J, Casson D, Malik M,
Berelowitz M, Dhillon A, Thomson M, Harvey P, Valentine A, Davies S,
Walker-Smith J (February 28 1998). Ileal-lymphoid-nodular hyperplasia,
non-specific colitis, and pervasive developmental disorder in children
637-641. The Lancet - Vol. 351, Issue 9103.
DOI:10.1016/S0140-6736(97)11096-0, is Andrew Wakefield. Dr. Wakefield has
alleged on the basis of twelve children referred to his clinic that there was
a link between the MMR vaccine and the development of autism.
- Stats: Illustrated case studies
of research ethics and research fraud (June 11, 2007). I've written a
fair number of case studies involving research ethics and research fraud for
the Chance Wiki. I want to take some of this material and produce some web
pages with nice illustrations that will bring these cases to life and make
them more memorable. This may eventually lead to a book, but that is quite a
way down the road.
- Stats: IRB review of studies with
methodological flaws (April 10, 2007). Someone (AK) wrote into the
IRBForum asking about how the IRB should do when they discover methodological
flaws in the proposed research. If everything else is in order (e.g.,
appropriate consent forms), is the IRB still justified in asking that the
flaw be fixed prior to approval of the research?
- Stats: IRB review of a pilot study
(March 26, 2007). Dear Professor Mean: I am the new chair of the IRB
at a county hospital. Many of the studies we review are pilot studies with
small samples. I have been trying to locate criteria for the scientific
review of pilot studies, but have not found a consensus in the literature
that I have seen. Is a pilot study merely a "dry run" of the procedures that
will be used in a later, larger-scale study? Or, is it reasonable for the IRB
to demand that the investigator provide specific criteria for determining
whether the pilot has been a success? And, should the IRB furthermore demand
that specific hypotheses be formulated? My impression is that many
investigators declare their studies to be pilots in order to avoid more
rigorous scrutiny of their proposals.
2006
- Stats: Academic freedom and the
Institutional Review Board (October 17, 2006). The American Association
of University Professors (AAUP) recently published a report, Research on
Human Subjects: Academic freedom and the Institutional Review Board. This
report is sharply critical of Institutional Review Boards (IRBs) and cites
several anecdotes of abuse and misuse of the review process by IRBs.
- Stats: Special issues for
research involving children (September 15, 2006). Research is difficult
enough, but it becomes more difficult when the research involves children.
The issues that you need to consider are physiologic, ethical, and
statistical.
- Stats: Questions a volunteer should
ask before participating in a clinical trial (July 18, 2006). A regular
contributor to the IRBForum (MG), wrote a nice list of questions that a
volunteer should ask before they decide to participate in a clinical trial.
- Stats: Ethics and the fiduciary
obligation (June 19, 2006). One of the regular contributors to the
IRBForum noted the publication of the following article: Miller PB, Weijer C.
Fiduciary obligation in clinical research. Journal of Law, Medicine &
Ethics 2006; 34(2): 424-440. which is too recently published for me to find a
good PubMed record. Another contributor pointed out a competing viewpoint:
Morreim EH. The clinical investigator as fiduciary: Discarding a misguided
idea. Journal of Law, Medicine & Ethics 2005; 33(3): 586-598. and E.
Haavi Morreim, Litigation in Clinical Research: Malpractice Doctrines
Versus Research Realities, 32 J.L. Med & Eth 474, 477 (2004). These
articles caught my eye because a lot of discussion about ethical practice
refers to the fiduciary duty of a physician for his/her patients.
- Stats: Waiver of informed consent
(March 3, 2006). Most prospective research studies require the informed
consent of the participants, so it is interesting to find exceptions to this
rule. I found a recent publication that has a common sense reason to bypass
informed consent: TREC-Rio trial: a randomised controlled trial for rapid
tranquillisation for agitated patients in emergency psychiatric rooms
[ISRCTN44153243]. G. Huf, E. S. Coutinho, C. E. Adams. BMC Psychiatry
2002: 2(1); 11..
2005
- Stats: Self experimentation
(September 13, 2005). Stephen Dubner and Steven D. Levitt, authors of the
hot selling book, Freakonomics: A Rogue Economist Explores the Hidden Side
of Everything, have a regular column in the New York Times Magazine. In
the September 11, 2005 issue, the article "Does the Truth Lie Within"
discusses self-experimentation.
- Stats: IRBs and scientific validity
(August 12, 2005). One of the regular posters on the edstat-l mailing
list shared a comment that is commonly held among many of the people I have
talked to. IRB's should NOT be in the business of trying to make studies
good. IRBs are not sufficiently experts in all the different kinds of
proposals that come across their desks. They are there to make sure that the
principles of informed consent and lack of coercion ... have been faithfully
taken care of. This comment is a reaction to the tendency of some IRBs to
nitpick. While I am somewhat sympathetic to overly intrusive reviews that we
all have to endure, it is important to remember the underlying rationale for
IRB review of scientific validity.
- Stats: Ethical principles for Complementary
and Alternative Medicine Research (January 24, 2005). The National
Academies Press, has a new publication available, Complementary and
Alternative Medicine in the United States. This publication was prepared by
the U.S. Institute of Medicine at the request of the National Institutes of
Health and the Agency for Healthcare Research and Quality. You have to
purchase the PDF files that constitute the book, but you can also browse
through the contents and view a free executive summary. One chapter title
that immediately caught my attention was "An Ethical Framework for CAM
Research, Practice, and Policy." The authors list five ethical principles
that provide the foundation for their recommendations.
- Stats: Monetary incentives (January
3, 2005). Someone on the IRBForum asked about monetary incentives in
research. This is a controversial area (see the OHRP website, Foy 1998,
Sugarman 2004, Young 2001), and especially controversial for studies
involving children (Fernhoff 2002) but monetary incentives do indeed help
improve recruitment, at least for a postal survey (Edwards 2002; Smeeth
2002).
2004
- Stats: Submitting a research protocol to the IRB
(July 29, 2004). I usually just watch and advise as others submit
research protocols to our Institutional Review Board (IRB). But now I might
end up having to submit one myself. I want to perform a secondary data
analysis on a data set that was collected several years ago. It should be an
educational experience. If I do learn anything valuable, I'll put it on this
weblog.
2003
- Stats: Why informed consent is so important
(May 2, 2003). To understand why researchers today must obtain informed
consent from their patients before they subject them to experiments, you need
to understand some of the previous abuses of medical research.
2002
-
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Creative
Commons Attribution 3.0 United States License. This page was written by
Steve Simon and was last modified on
2010-07-27.
