Help Wanted, Part 2

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So, what are some of the intriguing ethical questions of Kolata’s August 2d article? Here is one: when researchers conduct studies and ethics committees review protocols, resource allocation is an important consideration. If, as Kolata alleges, mediocre trials siphon eligible patients away from good trials, then there is a case to be made that IRBs and investigators need to ponder carefully the effects proposed trials will have on other studies- even when proposed trials have a favorable direct benefit-risk balance for volunteers who enter them.


Second, if resource allocation is a key consideration in realms where patients are scarce, investigators (and IRBs) need reliable criteria for assessing the broader social value of study protocols. They further need some way of being able to compare one protocol against a body of others that are either underway or in the pipeline. The current system provides no straightforward way of doing this.

Third, if 50% of trials fail to recruit sufficient numbers to produce meaningful results, investigators, IRBs, DSMBs, and granting agencies are doing a lousy job ensuring high ethical standards in human research. It is well established that, for any study to redeem the burdens that volunteers endure on enrollment, it must produce valuable findings. It is disturbing, to say the least, that many volunteers enter studies that go nowhere, and that investigators, IRBs, and funding agencies are not realistically projecting recruitment.

Last, Kolata suggests that many cancer trials are merely aimed at “polishing a doctor’s résumé.” It would make a useful contribution to the field of cancer research- and bioethics- to measure the frequency of this practice. Meantime, this inability of IRBs to detect this kind of conduct, and stop it in its tracks, signals an important deficiency in human protections. Which leads me to my next post… (photo credit: ziggy fresh 2006)

BibTeX

@Manual{stream2009-88,
    title = {Help Wanted, Part 2},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2009,
    month = aug,
    day = 9,
    url = {http://www.translationalethics.com/2009/08/09/help-wanted-part-2/}
}

MLA

Jonathan Kimmelman. "Help Wanted, Part 2" Web blog post. STREAM research. 09 Aug 2009. Web. 21 Sep 2017. <http://www.translationalethics.com/2009/08/09/help-wanted-part-2/>

APA

Jonathan Kimmelman. (2009, Aug 09). Help Wanted, Part 2 [Web log post]. Retrieved from http://www.translationalethics.com/2009/08/09/help-wanted-part-2/


Red Tape: More IRB-bashing

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Slow news day, I guess, at the New York Times. In today’s paper, American Enterprise Institute scholar Sally Satel laments that “federal ethics regulations” have become “so stringent and unwieldy that the ethics oversight system often impedes the kind of careful research we should be promoting.” And the paperwork, according to Satel, is driving up costs and “‘…pricing large clinical trials out of reach.'”

I enjoy a good IRB bashing now and then. But notice how, in Satel’s analysis, dysfunctionality = driving up costs and “cutting into productivity.” Well yes- that’s what regulations do. Perhaps the IRB system is indeed dysfunctional. On the other hand, the dearth of major scandals in human protection over the last decade, and the trust that many volunteers seem to place in the system of clinical research, provide grounds for at least a little skepticism about the “dysfunctionality” claim.
As for the nature of that dysfunctionality: In my previous posting, I described an article by Gina Kolata that seems to offer an opposing analysis: that by being too permissive, IRBs are approving mediocre trials that siphon patients away from the good ones. (photo credit: McBeth 2005)

BibTeX

@Manual{stream2009-89,
    title = {Red Tape: More IRB-bashing},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2009,
    month = aug,
    day = 9,
    url = {http://www.translationalethics.com/2009/08/09/red-tape-more-irb-bashing/}
}

MLA

Jonathan Kimmelman. "Red Tape: More IRB-bashing" Web blog post. STREAM research. 09 Aug 2009. Web. 21 Sep 2017. <http://www.translationalethics.com/2009/08/09/red-tape-more-irb-bashing/>

APA

Jonathan Kimmelman. (2009, Aug 09). Red Tape: More IRB-bashing [Web log post]. Retrieved from http://www.translationalethics.com/2009/08/09/red-tape-more-irb-bashing/


Red Handed: An Independent Review of IRBs

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A decade or so ago, the Government Accounting Office published a series of reports faulting human protections at VA hospitals, raising concerns about HHS oversight of human research, and urging continued vigilance in human research


After a seeming pendulum swing toward protections bashing (witness the outpouring of condemnation after OHRP sanctioned a team of researchers investigating ways to cut infection rates in intensive care units, or the Tricouncil draft policy’s use of the phrase “over-protection”), a recent GAO report may show a revival of concerns about independent review operations.

In it, GAO reports the result of a “sting” operation in which a sham device study was presented to three private IRBs.  The IRBs were selected on the basis of having “less burdensome initial paperwork requirements.”  Two of the IRBs rejected the protocol, describing it as “awful” and “the riskiest thing I’ve ever seen on this board.”  But one– identified in a New York Times article as Coast Independent Review Board (whose webpage lists “speed” as the first selling point), unanimously approved the protocol, characterizing it as “probably very safe.” 

Congress, GAO, and press reports are framing this as evidence of flaws in private IRB review. I’m actually impressed that the glass is 2/3 full.  And without suggesting endorsement of the private IRB model, I actually wonder how well academic medical center IRBs– most of whose members are salaried by an institution with a significant financial and professional stake in seeing research protocols approved– would have performed.  (photo credit: laughing squid, 2008)

BibTeX

@Manual{stream2009-107,
    title = {Red Handed: An Independent Review of IRBs},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2009,
    month = mar,
    day = 28,
    url = {http://www.translationalethics.com/2009/03/28/red-handed-an-independent-review-of-irbs/}
}

MLA

Jonathan Kimmelman. "Red Handed: An Independent Review of IRBs" Web blog post. STREAM research. 28 Mar 2009. Web. 21 Sep 2017. <http://www.translationalethics.com/2009/03/28/red-handed-an-independent-review-of-irbs/>

APA

Jonathan Kimmelman. (2009, Mar 28). Red Handed: An Independent Review of IRBs [Web log post]. Retrieved from http://www.translationalethics.com/2009/03/28/red-handed-an-independent-review-of-irbs/


NOTES from the Underground

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Surgical innovation has always been a problem for medical ethics.  Surgeries are unregulated, and partly as a result, few are introduced to clinical practice having been validated in randomized controlled trials. Moreover, attempts at novel surgeries typically fly beneath the radar of ethical review, because they are viewed as innovative clinical practice rather than research. There are some good–and not so good– reasons for such “surgical exceptionalism.”


On Sunday, the Washington Post ran a story (“Scarless Surgery Uses Body’s Own Openings,” Rob Stein, Sept 21) on a new type of surgery, Natural Orifice Transluminal Endoscopy (NOTES), which avoids skin incisions by accessing organs through the mouth, anus, or vagina. Various teams are testing and/or using NOTES to remove gall bladder stones, to perform appendectomies and cholecystectomies, and to collect tumor tissue for cancer staging.

NOTES has the potential to reduce pain and scarring, and to hasten recovery. But the technique still requires validation in animal models. One major concern is infection: NOTES requires incisions through flora-rich environments like the rectum, stomach, or vagina.

Several U.S. and European medical societies have established initiatives aimed at guiding development of this technique. One example is NOSCAR (www.noscar.org), which maintains an outcome registry and identifies unmet research needs. The group also urges surgeons to seek independent ethics review before attempting NOTES in humans.

However, many first tries at NOTES have been performed outside traditional centers of medical innovation. For instance, the first team to perform a NOTES appendectomy is based in Hyderabad, India; several surgical teams in Brazil are also publishing a disproportionately large volume of human case reports (the prominence of Latin America and Asia is briefly NOTEd in the Washington Post story). One searches far and wide for any commentary on this phenomenon. Why are Brazil and India at the vanguard of surgical innovation? Is this simply one manifestation of the knowledge economy moving overseas? Or does it have something to do with laxer regulations and safety standards? Are there characteristics of NOTES that make it particularly attractive for surgeons working in resource-limited circumstances? (photo credit: photosan0, Pink Floyd album, 2006)

BibTeX

@Manual{stream2008-135,
    title = {NOTES from the Underground},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = sep,
    day = 22,
    url = {http://www.translationalethics.com/2008/09/22/notes-from-the-underground/}
}

MLA

Jonathan Kimmelman. "NOTES from the Underground" Web blog post. STREAM research. 22 Sep 2008. Web. 21 Sep 2017. <http://www.translationalethics.com/2008/09/22/notes-from-the-underground/>

APA

Jonathan Kimmelman. (2008, Sep 22). NOTES from the Underground [Web log post]. Retrieved from http://www.translationalethics.com/2008/09/22/notes-from-the-underground/


On Not Getting It…

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Here is the scenario: you have cancer, and your doctor has told you there is no way to treat it. But there is an experimental drug that is being offered in a phase 1 study. Your doctor asks if you’re interested.


You join the study because its your best shot. You know there are likely to be side effects–there always are with cancer drugs. You know the drug might not work–no cancer drug works all the time for all people.

If your doctor knew that entering the phase 1 study was unlikely to eradicate your cancer– or even extend your life– would you want to be told, or would you prefer that the doctor keep this information from you?

The question came up in a recent research ethics committee (IRB) meeting I attended, in which a phase 1 cancer study consent form contained language to the effect of “you may or may not benefit from joining this study.” I proposed that the language be changed to “this study is unlikely to significantly affect the course of your cancer.” My preference was based on the following reasons:

1- “may or may not benefit” does not contain any information about probability. Indeed, there is a subtle rhetorical partity, wherebt most readers view “may” as having equal weight as “may not” such that they view this as suggesting a 50% probability of benefit.

2- two recent, large mete-analyses showed that studies of the type reviewed here result in tumor shrinkage for about 10% of patients. There is no evidence that tumor shrinkage in these studies actually translates to longer life or improved comfort. So, in fact, we do have information about probability of benefit.

3- Patients enter these studies not because of a desire to further cancer research, but rather, because they are seeking cure. This has been shown in numerous surveys.

4- Patients who enter these studies significantly overestimate the probability that they will benefit clinically. Also shown in numerous surveys.

5- Informed consent requires, at a minimum, that volunteers be provided information that a reasonable person would consider material to their decision to enroll.

A reasonable, terminal cancer patient would probably want to have some information about the probability that a drug that is likely to have strong side effects is unlikely to work against their cancer.

Incredibily, most of the members of my IRB disagreed, saying (among other things) that it would discourage patients (hmmm. I thought medical paternalism went out with Buicks with tailfins); that nothing in the original language implied benefit was a sure thing (yes, the original language made it very clear that instead of 100% chance of benefit, chance of benefit was somewhere between 0 and 99.999%);  that no one would enroll in the study with my language (wow! I thought our job was to protect volunteers, not investigators); that we’ve never done that before (let me make sure I understand this.  It’s ok to withhold relevant information from volunteers, as long as you’ve done it before).

Yes, Virginia, the IRB system really is broken! (photo credit: Kenoir 2007)

BibTeX

@Manual{stream2008-146,
    title = {On Not Getting It…},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = jun,
    day = 27,
    url = {http://www.translationalethics.com/2008/06/27/on-not-getting-it/}
}

MLA

Jonathan Kimmelman. "On Not Getting It…" Web blog post. STREAM research. 27 Jun 2008. Web. 21 Sep 2017. <http://www.translationalethics.com/2008/06/27/on-not-getting-it/>

APA

Jonathan Kimmelman. (2008, Jun 27). On Not Getting It… [Web log post]. Retrieved from http://www.translationalethics.com/2008/06/27/on-not-getting-it/


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