Posts Tagged human studies ethics

CRISPR and the Ethics of Gene Editing


If you have not heard of CRISPR yet, you should have. This is a truly transformative technology that allows for cheap and easy gene editing. It makes a powerful technology easily accessible.

Powerful biological technology, like stem cells to give another example, always seem to provoke profound hope and fear. The ability to manipulate human biology comes with it the hope of treating horrible and currently untreatable diseases. At the same time such technology provokes fear that it will be abused, or that it will violate the sanctity of what it means to be human.

As the public debate over stem cells seems to be fading into the background a bit (like IVF before it), debates over CRISPR and gene editing are likely to come to the forefront.

What is CRISPR?


Posted in: Ethics

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Dr. Oz Doubles Down on Green Coffee Bean with a Made-for-TV Clinical Trial

“One of the most important discoveries I believe we’ve made that will help you burn fat – green coffee bean extract” – Dr. Oz, September 10, 2012, Episode “The Fat Burner that Works”

Dr. Mehmet Oz may be biggest purveyor of health pseudoscience on television today. How he came to earn this title is a bit baffling, if you look at his history. Oz is a bona fide heart surgeon,  (still operating 100 times per year), an academic, and a research scientist, with 300+ or 400+ (depending on the source) publications to his name. It’s an impressive CV, even before the television fame. He gained widespread recognition as the resident “health expert” on Oprah, and went on to launch his own show in 2009. Today “The Dr. Oz Show” is a worldwide hit, with distribution in 118 countries, a massive pulpit from which he offers daily health advice to over 3 million viewers in the USA alone. For proof of his power to motivate, just look at the “Transformation Nation Million Dollar You” program he launched in 2011, enrolling an amazing 1.25 million participants. Regrettably, what Oz chooses to do with this platform is often disappointing.  While he can offer some sensible, pragmatic health advice, his show’s content seems more focused on TV ratings than medical accuracy, and it’s a regular venue for questionable health advice (his own, or provided by guests) and poorly substantiated “quick fixes” for health issues. (And I won’t even touch Oz’s guests like psychic mediums.) One need only look at the number of times the term “miracle” is used on the show as a marker of the undeserved hyperbole. Just this week, Julia Belluz and Stephen J Hoffman, writing in Slate, itemized some of the dubious advice that Oz has offered on his show, with a reality check against what the scientific evidence says. It’s not pretty. (more…)

Posted in: Clinical Trials, Herbs & Supplements, Medical Ethics

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Evidence-Based Medicine, Human Studies Ethics, and the ‘Gonzalez Regimen’: a Disappointing Editorial in the Journal of Clinical Oncology Part 2

NB: If you haven’t yet read Part 1 of this blog, please do so now; Part 2 will not summarize it.

At the end of Part 1, I wrote:

We do not need formal statistics or a new, randomized trial with a larger sample size to justify dismissing the Gonzalez regimen.

In his editorial for the JCO, Mark Levine made a different argument:

Can it be concluded that [the] study proves that enzyme therapy is markedly inferior? On the basis of the study design, my answer is no. It is not possible to make a silk purse out of a sow’s ear.

That conclusion may be correct in the EBM sense, but it misses the crucial point of why the trial was (ostensibly) done: to determine, once and for all, whether there was anything to the near-miraculous claims that proponents had made for a highly implausible “detoxification” regimen for cancer of the pancreas. Gonzalez himself had admitted at the trial’s inception that nothing short of an outcome matching the hype would do:

DR. GONZALEZ: It’s set up as a survival study. We’re looking at survival.

SPEAKER: Do you have an idea of what you’re looking for?

DR. GONZALEZ: Well, Jeff [Jeffrey White, the director of the Office of Cancer Complementary and Alternative Medicine at the NCI—KA] and I were just talking a couple weeks ago. You know, to get any kind of data that would be beyond criticism is—-always be criticism, but at least three times.

You would want in the successful group to be three times — the median to be three times out from the lesser successful groups.

So, for example, if the average survival with chemo, which we suspect will be 5 months, you would want my therapy to be at least — the median survival to be at least 15, 16, 17 months, as it was in the pilot study.

We’re looking for a median survival three times out from the chemo group to be significant.

Recall that the median survival in the Gonzalez arm eventually turned out to be 4.3 months.


Posted in: Cancer, Clinical Trials, Health Fraud, Medical Academia, Medical Ethics, Politics and Regulation, Science and Medicine

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My NCCAM Wish List

For a number of reasons, well-argued many times here on SBM, it would be beneficial to American citizens if the National Center for Complementary and Alternative Medicine (NCCAM) were abolished. This does not seem to be in the cards anytime soon. Here, then, are my suggestions for making the Center less dangerous and less of a marketing tool for pseudomedicine than it has been since its inception. Some suggestions might even make the Center somewhat useful. They are listed in order of priority. The Center should:

1. Abandon all unethical trials, beginning with the Trial to Assess Chelation Therapy (TACT, which is under the joint auspices of the NHLBI). This should be done in a very public manner. The reasons for abandoning the TACT, in summary, are as follows.


Posted in: Medical Ethics, Politics and Regulation, Science and Medicine

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Human Subjects as Political Pawns

When it comes to “alternative medicine” trials, it seems that the NIH is willing to experiment on people in ways that would be unthinkable for real biomedical research. The federal Office for Human Research Protections (OHRP) has posted a preliminary determination letter, dated May 27, 2009, addressing some of the charges we had made against the politics-driven NIH Trial to Assess Chelation Therapy (TACT).

It is a remarkably damning statement, particularly regarding an NIH study. That is, it found—or the recipients admitted—that each of several charges was valid. Among these are misleading statements and unstated risks in the consent form, and the embarrassing backgrounds of TACT investigators. According to the determination letter,

…investigations revealed multiple instances of substandard practices, insurance fraud, and felony activity on the part of investigators.”


Posted in: Politics and Regulation, Science and Medicine

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“Chelation Therapy”: Another Unethical “CAM” Trial Sponsored by Taxpayers

Please forgive the promotion of our own work and the facile evasion of a full-length blog, but two of your faithful bloggers are co-authors of an article published this week:

Why the NIH Trial to Assess Chelation Therapy (TACT) Should Be Abandoned

Kimball C. Atwood IV, MD; Elizabeth Woeckner, AB, MA; Robert S. Baratz, MD, DDS, PhD; Wallace I. Sampson, MD

Medscape J Med.  2008;10(5):115.  ©2008 Medscape

Posted 05/13/2008

Available here.

You may be asked to “register”; don’t worry, it’s free. The article is very long, but the Introduction, Executive SummaryDiscussion, and Conclusion are reasonably succinct and make the important points. Readers who want to learn more details, who want to see more evidence for our assertions, or who are compelled by an odd fascination with crackpotism (my own weakness) will want to read more. Here is a small sample:


The National Institutes of Health (NIH) Trial to Assess Chelation Therapy (TACT) was begun in 2003 and is expected to be completed in 2009. It is a trial of office-based, intravenous disodium ethylene-diamine-tetra-acetic acid (Na2EDTA) as a treatment for coronary artery disease (CAD). A few case series in the 1950s and early 1960s had found Na2EDTA to be ineffective for CAD or peripheral vascular disease (PVD). Nevertheless, a few hundred physicians, almost all of whom advocate other dubious treatments, continued to peddle chelation as an office treatment. They claim that chelation dramatically improves symptoms and prolongs life in 80% to 90% of patients. In response, academics performed 4 controlled trials during the 1990s. None favored chelation, but chelationists repudiated those findings.

We have investigated the method and the trial. We present our findings in 4 parts: history, origin and nature of the TACT, state of the evidence, and risks. We present evidence that chelationists and their organization, the American College for Advancement in Medicine, used political connections to pressure the NIH to fund the TACT. The TACT protocols justified the trial by misrepresenting case series and by ignoring evidence of risks. The trial employs nearly 100 unfit co-investigators. It conflates disodium EDTA and another, somewhat safer drug. It lacks precautions necessary to minimize risks. The consent form reflects those shortcomings and fails to disclose apparent proprietary interests. The trial’s outcome will be unreliable and almost certainly equivocal, thus defeating its stated purpose.

We conclude that the TACT is unethical, dangerous, pointless, and wasteful. It should be abandoned.

Readers of my postings on SBM will find more discussion (and abundant evidence) of familiar material: ethical breaches resulting from political incursions into science; the pitfalls, both scientific and ethical, of ignoring prior probability; a Dirty Secret of the Extraordinary Popular Delusion that is “CAM,” that much of what masquerades as sober research or the practice of “integrative medicine” was spawned by Laetrile; and widespread dishonesty in “academic CAM.”

Medscape Journal of Medicine invites readers to post comments or to send private letters to the editor for potential publication (and replies by yours truly, in this case). If you are so moved, you might consider posting comments in duplicate, both there and here on SBM, for the benefit of our select readership.

Posted in: Clinical Trials, Health Fraud, Medical Ethics, Politics and Regulation

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The Ethics of “CAM” Trials: Gonzo (Part VI)

Part V of this Blog argued that the NCCAM-sponsored trial of the “Gonzalez regimen” for cancer of the pancreas is unethical by numerous criteria.† To provide an illustration, it quoted a case history of one of the trial’s subjects, who had died in 2002.¹ It had been written by the subject’s friend, mathematician Susan Gurney. A similar story was told on ABC 20/20 in 2000, albeit not about a trial subject. Each of these cases demonstrates the wide breadth of Gonzalez’s quackery, as did his brush with the New York medical board during the 1990s.

This entry addresses some aspects of how those in charge of the trial failed in their duty to protect human subjects. By implication, it suggests what is necessary to prevent similar travesties in the future. It also addresses, to the small extent that the information exists, what appear to be the final ethical violations: first, that the trial will never be completed, thus having “expose[d] subjects to risks or inconvenience to no purpose.” Second, that Columbia University and the responsible investigators have no intention of explaining why.


Posted in: Cancer, Clinical Trials, Medical Academia, Medical Ethics, Science and Medicine

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The Ethics of “CAM” Trials: Gonzo (Part V)

Part IV of this blog ended by observing that the NIH-funded trial of the “Gonzalez regimen” for cancer of the pancreas,† to have begun in March, 1999, was in trouble almost as soon as it started. As originally designed, it was to have been a randomized, controlled trial comparing gemcitabine, the standard chemotherapy, to the “Gonzalez regimen” of pancreatic enzymes, “supplements,” twice-daily coffee enemas, and other purported methods of “detoxification.” By June, 1999, according to Dr. John Chabot, the Columbia University surgeon acting as Principal Investigator (PI) of the trial, only 3 of the first 50 potential subjects had agreed to be randomized, and none of the three met the eligibility criteria. By January, 2000 it had become clear that the trial would not accrue a sufficient number of subjects if it remained randomized, because almost all of the potential subjects were intent on being in the “nutritional,” ie, the Gonzalez arm.

Trouble with Randomizing

The investigators at Columbia therefore decided to change the protocol to a “single-armed, non-randomized case-cohort study where patients will only be enrolled in what was the nutritional arm.” Paradoxically, PI John Chabot had recently explained, at the 1999 Comprehensive Cancer Care Conference of James Gordon’s Center for Mind-Body Medicine, why this would not be a scientifically sound design:


Posted in: Clinical Trials, Health Fraud, Medical Academia, Medical Ethics

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The Ethics of “CAM” Trials: Gonzo (Part II)

Laetrile and the Politics of NIH-Sponsored trials of “Alternative Cancer Treatments”

Part I of this blog ended by asking how, in light of the implausible and arduous nature of the “Gonzalez regimen” for cancer of the pancreas, and the unconvincing “best case series,” the NIH could ever have decided to fund a trial of it.† This entry will begin to answer that question. In so doing it may seem to veer from the original subject, but hold on to your seats: what you’ll find here is a piece of the treasure map that leads to the Mother Lode of Fool’s Gold that is government-sponsored “CAM” research.

All historical accounts of the encroachment of implausible claims into the research agenda of the NIH must begin with Laetrile. By that is meant all implausible claims, not merely those having to do with cancer. Elsewhere we have traced the history of “chelation therapy” for coronary artery disease, and have shown that its origins as a political movement, eventually leading to an unethical, $30 million, 2000 subject NIH trial, were intimately associated with people and organizations advocating Laetrile—the most lucrative health fraud ever perpetrated in the United States. In that essay we offer evidence that the creation of the NCCAM itself was at least partly attributable to the history of Laetrile and its advocates. Several good histories or partial histories of the Laetrile debacle are available online, including here, here, here, here, here, and here. The best,¹ but one that does not seem to be available online, is by the recently deceased dean of historians of American quackery, James Harvey Young. (more…)

Posted in: Cancer, Clinical Trials, Health Fraud, Medical Academia, Politics and Regulation

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The Ethics of “CAM” Trials: Gonzo (Part I)

Blogger’s note: This blog, which is rough going in places, will be presented in either 2 or 3 parts (I won’t know which until next week). I’ll post a part each week until it is complete, but due to overwhelming popular demand I promise to maintain the every-other-week posting of the far more amusing Weekly Waluation of the Weasel Words of Woo/2.


On Feb. 25, 2008, the federal Office for Human Research Protections (OHRP) cited Columbia University Medical Center (CUMC) for violating Title 45, Part 46 of the Code of Federal Regulations: Protection of Human Subjects (45CFR§46). The violations involved Columbia’s administration of the NIH-sponsored trial of the bizarre “Gonzalez Regimen” for treating cancer of the pancreas.† The OHRP’s determination letter to Steven Shea, MD, the Director of the Division of General Medicine and Senior Vice-Dean at CUMC, cited ethical problems of a serious kind:

We determine that the informed consent for the 40 of 62 subjects referenced by CUMC was not documented prior to the start of research activities, nor was the requirement for documentation waived by the CUMC IRB for subjects in this study.

It was the second time that the OHRP had cited Columbia for its dubious management of the “Gonzalez” trial. The first occurred in Dec. 2002, after investigators had determined that the trial’s consent form “did not list the risk of death from coffee enemas.” The OHRP listed several other violations at that time, but “redacted” them from the letter that it made available to the public. (more…)

Posted in: Cancer, Clinical Trials, Health Fraud, Medical Ethics, Politics and Regulation

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