P.Mean >> Category >> Ethics in research (created 2007-08-06).

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.

2012

23. P.Mean: Arguing with the material in an ethics training program (created 2012-01-12). I'm taking one those web based ethics training programs that is required by the UMKC IRB. It's not a punishment for something bad I did. The IRB requires this from all researchers. I'm probably one of the worst people to take these programs because I disect every assertion and look for the data behind every claim. It takes me forever to finish these things. Anyway, here's an example of the type of thing that drives me crazy

2010

22. P.Mean: I won't serve on my IRB, but there is a way I can still help (created 2011-02-17). I had offered to help out our local IRB but was not careful to clarify how I could help. This resulted in me being appointed as an alternate member of the IRB. That's not a good role for me because of my conflict of interest. I work with a large number of clients through the Research and Statistical Consult Service (RSCS), and would have a hard time providing an impartial review of an IRB application that I had some role in developing. Also, for researchers who have not worked with the RSCS, if there protocols had major statistical flaws, I would be uncomfortable asking them to consult with the RSCS, as it might appear that I'm trying to artificially build demand for the RSCS. So I'll have to turn down this role. But there is another way I could help.

2008

21. 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?

20. 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

19. 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.

Journal article: Anja von der Ropp, Tony Tubman. Bioethics and Patent Law: The Cases of Moore and the Hagahai People WIPO Magazine. 2006. Excerpt: "This is the final article in the WIPO Magazine series on intellectual property and bioethics. It looks at questions raised by the Moore and the Hagahai cases, where patents resulting from research based on human genetic material were challenged because prior informed consent had not been sought from the donors." [Accessed on January 12, 2012]. http://www.wipo.int/wipo_magazine/en/2006/05/article_0008.html.

Webpage: Lisa Seidman, Jeanette Mowery. A Case Study relating to Pharmaceutical Regulations. Classroom Activity: Frances Kelsey and Thalidomide in the United States Excerpt: "This dramatic case study tells the story of Dr. Frances Kelsey of the Food and Drug Administration (FDA) and the drug thalidomide. This incident provides a good introduction to the processes by which drugs are approved and regulated in the United States, and the reasons for these processes. This is also a great story showing how the actions of individuals can be important." [Accessed on January 4, 2012]. http://biotech.matcmadison.edu/resources/methods/quality/caseStudy.htm.

Webpage: Theresa Bycroft. Competencies for Conducting Safe Human Subjects Research Excerpt: "The competencies needed to practice, teach, and monitor human subjects research are complex and have a specialized set of rules and ethics. Despite the importance of protecting the rights of participants in research, competencies researchers need to in order to conducting safe human subject research have not been identified. Therefore, the purpose of this study was to identify competencies researchers need in order to conduct safe, knowledgeable, and effective research while protecting the research participant's well being." [Accessed on June 2, 2011]. http://www.conti-creations.com/Research_Competencies.htm.

Journal article: Michael A. Rogawski, Howard J. Federoff. Disclosure of Clinical Trial Results When Product Development Is Abandoned Science Translational Medicine. 2011;3(102):102cm29. Abstract: "Currently, sponsors are not required to report the outcomes of clinical research on drugs or devices that do not lead to an approved product. Consequently, the public cannot benefit from scientific information derived from all failed or abandoned drugs and devices. Provisions in the U.S. Food and Drug Administration Amendments Act of 2007 provide an opportunity for the Department of Health and Human Services to rectify this situation. By reporting the results of clinical trials of abandoned products in a publicly accessible database and in the peer-reviewed journal literature, sponsors would satisfy a core ethical obligation of clinical research and enhance translational science." [Accessed on September 30, 2011].

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.

Charles Weijer, Jeremy Grimshaw, Monica Taljaard, Ariella Binik, Robert Boruch, Jamie Brehaut, Allan Donner, Martin Eccles, Antonio Gallo, et al. Ethical issues posed by cluster randomized trials in health research Trials. 2011;12(1):100. Abstract: "The cluster randomized trial (CRT) is used increasingly in knowledge translation research, quality improvement research, community based intervention studies, public health research, and research in developing countries. However, cluster trials raise difficult ethical issues that challenge researchers, research ethics committees, regulators, and sponsors as they seek to fulfill responsibly their respective roles. Our project will provide a systematic analysis of the ethics of cluster trials. Here we have outlined a series of six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation: 1. Who is a research subject? 2. From whom, how, and when must informed consent be obtained? 3. Does clinical equipoise apply to CRTs? 4. How do we determine if the benefits outweigh the risks of CRTs? 5. How ought vulnerable groups be protected in CRTs? 6. Who are gatekeepers and what are their responsibilities? Subsequent papers in this series will address each of these areas, clarifying the ethical issues at stake and, where possible, arguing for a preferred solution. Our hope is that these papers will serve as the basis for the creation of international ethical guidelines for the design and conduct of cluster randomized trials." [Accessed on April 26, 2011]. http://www.trialsjournal.com/content/12/1/100.

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.

Rebecca Skloot. The Immortal Life of Henrietta Lacks. First Edition. Crown; 2010. Description: I got this book out of a sense of obligation. It sounded like a book that would be a bore to read, but something important enough that it would be worth reading anyway. I was wrong. The story was quite compelling. There were four stories, actually. The first is the story about the life of Henrietta Lacks, a young woman and mother of five children who died at a young age from a very aggressive cervical cancer. The second is the story of a cell line derived from the biopsy of this woman's tumor (taken without her permission or knowledge. This cell line, known as HeLa, was the first immortal human cell line developed. The HeLa cells played a unique role in much of the work involving development of the polio vaccine and in many other scientific developments over the past five decades. The third story is about the people in the laboratory that developed the HeLa cell line and what they did differently from other scientists at the time that helped develop the HeLa cell line. The fourth story is about the surviving children of Henrietta Lacks, how they were abused and taken advantage of by the same scientists that took Henrietta Lack's tumor sample without her knowledge, and how they dealt with the anger over this abuse. The fifth story is about how the author, Rebecca Skloot, worked to gain the trust of the Lacks family, who were justifiably anxious about strangers showing up and asking lots of questions. These stories are all interwoven and are told with a masterful sense of their interdependence.

Gerald P. Koocher, Patricia Keith-Spiegel. Peers nip misconduct in the bud. Nature. 2010;466(7305):438-440. Excerpt: "What do researchers do when they suspect a colleague of cutting corners, not declaring a conflict of interest, neglecting proper oversight of research assistants or 'cooking' data? In one study1, almost all said that they would personally intervene if they viewed an act as unethical, especially if it seemed minor and the offender had no history of infractions." [Accessed August 14, 2010]. Available at: http://www.ethicsresearch.com/images/Nature_Opinion_-_Koocher_Keith-Spiegel.pdf.

Journal article: Gardiner Harris. The Public's Quiet Savior From Harmful Medicines The New York Times. 2010. Excerpt: "Dr. Frances Oldham Kelsey is 96 now, nearly deaf and barely mobile, as modest as her faded house in this Washington suburb. And though her story is nearly forgotten, she was once America's most admired civil servant — celebrated for her dual role in saving thousands of newborns from the perils of the drug thalidomide and in serving as midwife to modern pharmaceutical regulation. " [Accessed on January 4, 2012]. http://www.nytimes.com/2010/09/14/health/14kelsey.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.

Patricia Keith-Spiegel, Joan Sieber, Gerald P. Koocher. Responding to Research Wrongdoing : A User Friendly Guide. Excerpt: "Every once in awhile a product comes along that is destined to make a difference. This Guide is such a product. Informed by data generated through surveys and interviews involving more than 2,000 scientists, the Guide gives voice to those researchers willing, some with eagerness and others with relief, to share their stories publicly in their own words. There are stories from scientists who want to do the right thing, but are unsure how to go about it or concerned about negative consequences for them or their junior colleagues. There are accounts from researchers who took action, and are keen to share their successful strategies with others. On the flip side, there are those who hesitated and now lament not having guidance that might have altered the course of past events." [Accessed August 14, 2010]. Available at: http://www.ethicsresearch.com/images/RRW_7-17-10.pdf.

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.

Journal article: Nick Defiesta. When psychologists "go wrong" Yale Daily News. Excerpt: "This summer marked two important anniversaries for Yale's Psychology Department. The Stanford prison experiment, conducted by Yale graduate and former lecturer Philip Zimbardo GRD '59, took place 40 years ago, while the Milgram experiment, led by Yale professor Stanley Milgram on campus, marked its 50th anniversary this year. The experiments, both of which are considered landmark social psychology studies, are known for their controversial approach to ethics and for what they suggest about the nature of good and evil inside humans: that people are not as good as they think they are." [Accessed on September 29, 2011]. http://www.yaledailynews.com/news/2011/sep/28/when-psychologists-go-wrong/.

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 2011-01-03. 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

18. 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

17. 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.

16. 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.

15. 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.

14. 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?

13. 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

12. 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.

11. 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.

10. 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.

9. 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.

8. 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

7. 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.

6. 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.

5. 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.

4. 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

3. 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

2. 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

1. Stats: Getting IRB approval for your research (October 9, 2002). 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

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This work is licensed under a Creative Commons Attribution 3.0 United States License. This page was written by Steve Simon and was last modified on 2011-01-03.