Recently in Ethics Category
This morning, the FDA has finally stepped in and is warning healthcare professionals and MS patients alike about death and other injuries associated with the so-called "liberation procedure" (ugh), which amounts to either angioplasty or stenting of (typically) jugular veins. The procedure, which is ostensibly designed to promote the egress of blood flow from the brain, has no basis for use, because there is no confirmed link between chronic cerebrospinal venous insufficiency (CCSVI) and multiple sclerosis. For background on this ever-vexing issue, start here.The FDA has received reports of associated adverse events, which include "death, stroke, detachment and migration of the stents, damage to the treated vein, blood clots, cranial nerve damage and abdominal bleeding." In February, the agency sent a letter to a NY vascular surgeon, warning of "objectionable conditions" and the lack of regulatory protocol and oversight for what amounts to an investigational (ie, non-FDA-approved) procedure.
There may be no good guys in the questionable chain of international drug wholesalers that recently peddled fake Avastin. Yesterday the WSJ reported that the 2 managing directors of the Danish wholesaler ran afoul of local law in 2007 by illegally importing medicines into Denmark. Although the paper, citing the Danish National Board of Health, was not able to convey the particulars—eg, what medicine from what country.
Previous news reports imply that it was either the Danish wholesaler or the Swedish outfit that notified US authorities of the counterfeit Avastin, which then passed through a British wholesaler, River East Supplies, Ltd., before reaching the United States. Canadian Thomas Haughton reportedly manages a network of drug distributors, including River East Supplies, Ltd, as well as the US supplier of the fake drug, Montana Healthcare Solutions, which Haughton acquired in 2010 through a Barbados holding company. The Avastin-that-was-not-Avastin was then distributed by a Tennessee-based distributor to 19 medical practices, most of which are in California or Texas. It is unclear whether any cancer patient actually received the fake IV drug, which contained salt and starch (among other inactive ingredients).
The origin of the fake Avastin is also unclear. Named suspects include China, Egypt, and Turkey.
Previous news reports imply that it was either the Danish wholesaler or the Swedish outfit that notified US authorities of the counterfeit Avastin, which then passed through a British wholesaler, River East Supplies, Ltd., before reaching the United States. Canadian Thomas Haughton reportedly manages a network of drug distributors, including River East Supplies, Ltd, as well as the US supplier of the fake drug, Montana Healthcare Solutions, which Haughton acquired in 2010 through a Barbados holding company. The Avastin-that-was-not-Avastin was then distributed by a Tennessee-based distributor to 19 medical practices, most of which are in California or Texas. It is unclear whether any cancer patient actually received the fake IV drug, which contained salt and starch (among other inactive ingredients).
The origin of the fake Avastin is also unclear. Named suspects include China, Egypt, and Turkey.
The path of the fake Avastin that recently entered the United States is painfully complex and possibly a template for the terribly circuitous travel of questionable drugs throughout the globalized marketplace.
According to the latest coverage by the WSJ, the ersatz cancer drug—which possibly originated in China (where else, folks, where else?)—traveled through Turkey and Egypt before being sold by Swiss and/or Danish wholesalers to a UK-based wholesaler. From the UK, the phony vials were sold and imported into the US by a Canadian, Thomas Haughton, who lives in Barbados and manages a "network of drug distributors," including the UK wholesaler, River East Supplies, Ltd.
As well, Haughton owns or manages a Barbados-based holding company that acquired Montana Healthcare Solutions in 2010. Montana Healthcare Solutions, the reported contact for which is (or was) one Paul Bottomley in tiny Belgrade, sold the fake Avastin to 19 medical practices, most of which are in California. The drug was then shipped or distributed by the Tennessee-based Volunteer Distribution, the management of which is pretty damn sketchy.
The FDA is leading the necessarily complex federal investigation, but the US Attorney in Los Angeles is also issuing subpoenas to the California practices, writes the WSJ. The paper adds that Haughton had no idea that the Avastin was fake (despite the product's rock-bottom price). Furthermore Haughton "no longer does business with" the Tennessee distributor (although this end-of-the-line company, whatever it is, may be a mere scapegoat for the much-more globally connected Haughton).
Here's hoping that news sources like the WSJ stay on top of this developing story.
According to the latest coverage by the WSJ, the ersatz cancer drug—which possibly originated in China (where else, folks, where else?)—traveled through Turkey and Egypt before being sold by Swiss and/or Danish wholesalers to a UK-based wholesaler. From the UK, the phony vials were sold and imported into the US by a Canadian, Thomas Haughton, who lives in Barbados and manages a "network of drug distributors," including the UK wholesaler, River East Supplies, Ltd.
As well, Haughton owns or manages a Barbados-based holding company that acquired Montana Healthcare Solutions in 2010. Montana Healthcare Solutions, the reported contact for which is (or was) one Paul Bottomley in tiny Belgrade, sold the fake Avastin to 19 medical practices, most of which are in California. The drug was then shipped or distributed by the Tennessee-based Volunteer Distribution, the management of which is pretty damn sketchy.
The FDA is leading the necessarily complex federal investigation, but the US Attorney in Los Angeles is also issuing subpoenas to the California practices, writes the WSJ. The paper adds that Haughton had no idea that the Avastin was fake (despite the product's rock-bottom price). Furthermore Haughton "no longer does business with" the Tennessee distributor (although this end-of-the-line company, whatever it is, may be a mere scapegoat for the much-more globally connected Haughton).
Here's hoping that news sources like the WSJ stay on top of this developing story.
The most recent lots of counterfeit Avastin (Roche), which found their way to various oncology clinics in the United States (most of which are in California), originated in Egypt and were essentially a slurry of inactive ingredients, reports Fox News. The fake vials of the purported anticancer drug contained a hodgepodge of salt, starch, citrate, isopropyl alcohol, "propandiol" (probably propylene glycol), t-butanol, benzoic acid, difluroinated benzene, acetone, and phthalate—but no bevacizumab, the monoclonal antibody and active ingredient in Avastin that is intended to suppress angiogenesis and tumor growth.
The counterfeit vials were reportedly processed through legitimate distributors in Switzerland, Denmark, and Britain before entering the United States, where the fake drug was sold to 19 oncology clinics or physicians by Quality Specialty Products (aka Montana Health Care Solutions). A company with the terribly generic name of Volunteer Distribution,* located in Gainesboro, Tennessee distributed QSP's products, according to the FDA.
A web search reveals an address for Volunteer Distribution in Gainesboro: 101 W. Gore Ave. Google Maps provides this lovely screenshot for the Tennessee address, although the location is identified on the annotated street view as "Anderson & Haile Drug Co Phrm." A web search also reveals the listed phone number for Volunteer Distribution as 931-268-4506; that for Anderson & Haile is 931-268-0233.** Important update: Further searching of Google Maps and its street-view feature shows that Anderson & Haile is actually located in a commercial property at the corner of W. Gore Ave. and S. Union St. in Gainesboro, Tennessee.
Fake Avastin (or Lucentis) on the market is evidently an ongoing problem for Roche (and susceptible patients). Shanghai was the source for a bogus version in 2010, and Syria in 2009, says Fierce Pharma.
What vials of Avastin should contain are bevacizumab (the active ingredient), along with trehalose dihydrate, sodium phosphate (both monobasic monohydrate and dibasic), polysorbate 20, and water.
* I suppose that "Volunteer" must refer to Tennessee.
** And another web search provides these listed contacts for Anderson & Haile at 101 W. Gore Ave: Teneal Jenkins and Christie Banker. Yet another web search shows that Teneal Jenkins is "doing business as" Anderson and Haile Drug Company, a pharmacy and supplier of medical equipment and supplies. And yet another web search shows that Teneal Jenkins has a PharmD. A license lookup at the Tennessee Department of Health shows that Teneal Chaffin Jenkins of 101 W. Gore Ave in Gainesboro, Tennessee (Anderson and Haile Drug Co.) graduated with a PharmD in 2004 from the University of Tennessee (Memphis) and has sustained no disciplinary or significant liability claims.
And a clarification: I have no idea if Anderson & Haile Drug Company, located at 101 W. Gore Ave., in Gainesboro, TN, or pharmacist Teneal Jenkins and Volunteer Distribution, located at the same commercial building, have (or had) any connection whatsoever. Although it would be an unfortunate coincidence for Anderson & Haile and pharmacist Jenkins if they did not. FWIW, street images of the area, courtesy of Google Maps, show unreadable hanging shingles and ascending stairs to an entrance at the back of the building.
The counterfeit vials were reportedly processed through legitimate distributors in Switzerland, Denmark, and Britain before entering the United States, where the fake drug was sold to 19 oncology clinics or physicians by Quality Specialty Products (aka Montana Health Care Solutions). A company with the terribly generic name of Volunteer Distribution,* located in Gainesboro, Tennessee distributed QSP's products, according to the FDA.
A web search reveals an address for Volunteer Distribution in Gainesboro: 101 W. Gore Ave. Google Maps provides this lovely screenshot for the Tennessee address, although the location is identified on the annotated street view as "Anderson & Haile Drug Co Phrm." A web search also reveals the listed phone number for Volunteer Distribution as 931-268-4506; that for Anderson & Haile is 931-268-0233.** Important update: Further searching of Google Maps and its street-view feature shows that Anderson & Haile is actually located in a commercial property at the corner of W. Gore Ave. and S. Union St. in Gainesboro, Tennessee.
Fake Avastin (or Lucentis) on the market is evidently an ongoing problem for Roche (and susceptible patients). Shanghai was the source for a bogus version in 2010, and Syria in 2009, says Fierce Pharma.
What vials of Avastin should contain are bevacizumab (the active ingredient), along with trehalose dihydrate, sodium phosphate (both monobasic monohydrate and dibasic), polysorbate 20, and water.
* I suppose that "Volunteer" must refer to Tennessee.
** And another web search provides these listed contacts for Anderson & Haile at 101 W. Gore Ave: Teneal Jenkins and Christie Banker. Yet another web search shows that Teneal Jenkins is "doing business as" Anderson and Haile Drug Company, a pharmacy and supplier of medical equipment and supplies. And yet another web search shows that Teneal Jenkins has a PharmD. A license lookup at the Tennessee Department of Health shows that Teneal Chaffin Jenkins of 101 W. Gore Ave in Gainesboro, Tennessee (Anderson and Haile Drug Co.) graduated with a PharmD in 2004 from the University of Tennessee (Memphis) and has sustained no disciplinary or significant liability claims.
And a clarification: I have no idea if Anderson & Haile Drug Company, located at 101 W. Gore Ave., in Gainesboro, TN, or pharmacist Teneal Jenkins and Volunteer Distribution, located at the same commercial building, have (or had) any connection whatsoever. Although it would be an unfortunate coincidence for Anderson & Haile and pharmacist Jenkins if they did not. FWIW, street images of the area, courtesy of Google Maps, show unreadable hanging shingles and ascending stairs to an entrance at the back of the building.
And reasonably, I might add. Here's the video link. Notably the piece was done with the cooperation from higher-ups at Duke Med (ie, Robert Califf).
Potti is now an oncologist at South Carolina's The Coastal Cancer Center, the website for which advertises Potti's time at Duke University and (not surprisingly) makes no mention his colossal scientific fraud while there.
Potti is now an oncologist at South Carolina's The Coastal Cancer Center, the website for which advertises Potti's time at Duke University and (not surprisingly) makes no mention his colossal scientific fraud while there.
Continue reading 60 Minutes "Does" the Duke-Anil Potti Tragedy.
Sherley et al v Sebelius et al. The case that won't go away...to the chagrin of scientists who rely on government funding for research with human embryonic stem cells (hESCs).The Nature News Blog reports today that scientists James Sherley and Theresa Deisher, who choose to work with adult stem cells, are appealing Judge Royce Lamberth's reluctant decision in July to shoot down a permanent injunction against federal funding for hESC research. The scientists submitted their legal brief yesterday to the US Court of Appeals for the DC Circuit. The appeals court, which ruled against Sherley et al last April (with respect to their request for a preliminary injunction), will hear oral arguments on April 23rd in this new appeal to overturn Lamberth's ruling against a permanent injunction.
But a similar decision granting federal funds for hESC research by the appeals court is not a given. The randomly selected, 3-judge panel for the April hearing will be somewhat different than the one that ruled last year, the Nature News Blog reveals. The judges for the upcoming appeals hearing will be Republican appointees Chief Judge David Sentelle, Judge Janice Rogers Brown, and Judge Karen LeCraft Henderson. The lone, common panel member is Henderson, who dissented in the previous appeals hearing by calling the government's favorable interpretation of existing law (ie, the highly ambiguous Dickey-Wicker amendment) "linguistic jujitsu."
Image of undifferentiated hESCs from http://www.nih.gov/catalyst/2007/07.01.01/page1.html.
About one-third of cognitively normal elderly demonstrate an elevated load of beta-amyloid,* a pathologic hallmark of Alzheimer disease, in the brain, according to a newly published study from the Mayo Clinic. These data support previous observations, in which the PET-imaged brains of about a third of elderly, nondemented subjects will exhibit an abnormal accumulation of the AD-associated protein.However, the Mayo investigators went a bit further by examining the potential association between the load of beta-amyloid, as measured with an established radiolabeled tracer (Pittsburgh compound B, or PiB) on PET images, and cognitive performance on various memory, language, attention, and visuospatial tests. As well, a relationship among brain amyloid, cognitive performance, and APOEe4 status (a well-known genetic marker for AD) was examined. What the researchers found was that poorer cognitive performance was associated with greater amyloid deposition, and that this relationship was more robust in APOEe4 carriers. Conversely the association between amyloid load and relative cognitive impairment was much weaker (ie, only "modest") in subjects who did not carry an APOEe4 allele, suggesting (the authors concluded) "that APOE isoforms modulate the harmful effects of [beta-amyloid] on cognitive function."
What any of this information means practically is very murky, however. Will some of these cognitively normal subjects with heavier amyloid burdens (and who perform less well on cognitive tests) develop AD—that is, if they live long enough? Is AD more likely in these subjects if they're APOE e4 carriers? We don't know, and obviously further longitudinal work is necessary. The Mayo authors do imply that follow-up is ongoing.
In an accompanying editorial, Buchman and Bennett commended the Mayo investigators for the size of the study (a highly respectable 408 subjects [with a median age of about 80 years]) and their "important contribution to our understanding of AD, illustrating that even among persons without dementia or [mild cognitive impairment], amyloid deposition is associated with very mild symptoms, especially among carriers of the APOE e4 allele." But "[w]hether...amyloid imaging agents will have clinical utility remains to be determined," the editorialists appropriately caution. They advise about the lack of data concerning the prognostic value of amyloid retention (presumably in any subjects, whether demented or not) and how amyloid retention may change over time. And they add that the utility of amyloid-imaging agents "will remain low in the absence of an effective amyloid modulating agent." In other words, what's the point of knowing the amyloid burden if you can't do anything to lighten the load?
A related issue, however, not explored by the editorial authors, is whether even removing amyloid in the context of cognitive impairment, is beneficial or, in fact, does more harm. Existing AD trials suggest that amyloid-modulating agents (eg, bapineuzumab) can cause brain edema—presumably due to the removal of vascular amyloid—and that they do so without improving cognition to any substantial degree overall.
Intervening earlier with anti-amyloid drugs in less cognitively impaired subjects, as proposed by some industry investigators, is a tricky move: obviously primum non nocere in persons with only mild cognitive impairment and certainly in individuals with no practical cognitive problems (regardless of their amyloid burden).
PET = positron emission tomography.
* Defined by a "global cortical PiB retention ratio" of greater than 1.50.
Photograph: Atrophied brain from person with AD from National Institute on Alcohol Abuse and Alcoholism.
For those who are following the XMRV-CFS-Mikovits story, science blogger John Timmer at ars technica provides a decent synopsis of the crazy soap opera/Greek tragedy.
Specifically Timmer outlines a complicated narrative in reasonably comprehensible (but not outstanding*) prose. The salient points:
CFS = chronic fatigue syndrome; DHHS = Department of Health and Human Services; XMRV = xenotropic murine leukemia virus-related virus.
Specifically Timmer outlines a complicated narrative in reasonably comprehensible (but not outstanding*) prose. The salient points:
- the rise and fall of data linking XMRV with the dubious CFS;
- researcher Judy Mikovits's refusal to abandon the idea that XMRV is associated with CFS, despite others' data indicating XMRV contamination;
- the symbiotic nexus between Mikovits and individuals with CFS, some of whom reportedly tried to undermine any investigation debunking the link between XMRV with CFS;
- Mikovits's subsequent unethical, and possibly criminal, behavior; and
- the overall integrity of the collective, collaborative scientific process (including nods to the DHHS and the "publishing system").
CFS = chronic fatigue syndrome; DHHS = Department of Health and Human Services; XMRV = xenotropic murine leukemia virus-related virus.
And probably rightly so, given a number of issues.- The Harvard press release is terribly (and irresponsibly) overdramatic, emphasizing the "endocrine-disrupting" effect of bisphenol A (which is only documented in laboratory animals, to my knowledge) and the >1200% increase in urinary BPA after consuming canned soup (Progresso) for 5 days. There is no mention of absolute numbers in the attention-grabbing press release, just the astonishing percentage jump.
- The JAMA report, available here (courtesy of JunkScience.com), is actually published as a letter and not a more stringently peer-reviewed article.
- JunkScience.com takes the letter authors to task for not distinguishing between the urinary measurement of BPA (which is evidently not possible or very difficult) and that of a quickly produced metabolite. BPA is evidently rapidly processed in the body, and its "biologically inactive" metabolite (not BPA per se) was actually measured in urine, says JunkScience.com (the blog further claims that at least some of the authors should have known or do know this fact).
- While the percentage increase of mean urinary BPA values among canned-soup eaters is very impressive, we're talking about differences in MICROGRAMS PER LITER: 1.1 mcg/L after 5 days of fresh-soup consumption vs 20.8 mcg/L after 5 days of canned-soup consumption, for a difference of 19.7 mcg/L.*
- The urinary spike in BPA (or its metabolite) was probably transient, and the authors themselves acknowledge, "The effect of such intermittent elevations in urinary BPA concentration is unknown."
* In the updated National Health and Nutrition Examination Survey, levels of BPA were detected in all subjects older than 6 years of age. Geometric means were approximately 2 mcg/L, but levels rose to 20 mcg/L (or thereabouts) in the 95th-percentile groups.
Image of can of Progresso vegetable minestrone soup from progresso.com.
The Nature News Blog and Retraction Watch provide the ongoing, head-torquing narrative of Judy Mikovits, the dubious or embattled (depending on your viewpoint) XMRV-CFS researcher who was fired in September from the Whittemore Peterson Institute in Reno, Nevada. The latest news: Mikovits was arrested last Friday in California (as a fugitive from Nevada, from what I can tell) for allegedly stealing property—eg, laboratory notebooks—from the Institute.
And while the jig certainly appears to be up for Mikovits regarding the validity of her past scientific claims about XMRV and chronic fatigue syndrome or a future career in legitimate science, to hold her without bail (especially while, elsewhere, an alleged serial pedophile is allowed out on $100,000 and no monitoring) seems terribly draconian and patently unfair.
And while the jig certainly appears to be up for Mikovits regarding the validity of her past scientific claims about XMRV and chronic fatigue syndrome or a future career in legitimate science, to hold her without bail (especially while, elsewhere, an alleged serial pedophile is allowed out on $100,000 and no monitoring) seems terribly draconian and patently unfair.
