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Corporate pharma ethics and you

Although I’m one of the few non-clinicians writing here at SBM, I think about clinical trials a great deal – especially this week.

First, our colleague, Dr. David Gorski, had a superb analysis and highly-commented post on The Atlantic story by David H. Freedman about the work of John Ioannadis – more accurately, on Freedman’s misinterpretation of Ioannadis’s work and Dr. Gorski’s comments. While too rich to distill to one line, Dr. Gorski’s post struck me in that we who study the scientific basis of medicine actually change our minds when new data become available. That is a GoodThing – I want my physician to guide my care based on the latest data that challenges or proves incorrect previously held assumptions. However, this concept is not well-appreciated in a society that speaks in absolutes (broadly, not just with regard to medicine), expecting benefits with no assumption of risk or sacrifice in reaping those benefits. Indeed, the fact that we change our minds, evolving and refining disease prevention and treatment approaches, is how science and medicine move forward.

Then, I had the opportunity to hear an excellent talk on pharmaceutical bioethics by Ross E. McKinney, Jr., MD, Director of the Trent Center for Humanities, Bioethics, and History of Medicine at Duke University School of Medicine. McKinney is a pediatrics infectious disease specialist who led and published landmark Phase I and Phase II trials zidovudine (AZT) for pediatric AIDS patients. While he continues working in this realm, McKinney also studies clinical research ethics, conflicts of interest, and informed consent. I was absolutely fascinated and refreshed by hearing from an expert who while describing and citing major ethical lapses in our system of drug development is also willing to propose solutions and do the hard thinking required for us to maximize the benefits we derive from pharmaceuticals while minimizing unethical behavior.

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Posted in: Clinical Trials, Pharmaceuticals

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Yes, drug companies do pay attention to herbal medicine

I’m only a monthly contributor here but between being a SBM reader and having my own blogs, I often grow weary of the blind criticism that researchers and drug companies couldn’t care less about traditional folk medicines as drug products. My laboratory spends every single day working on natural product extracts in the search for compounds that may have selective effectiveness against cancer. So, this is a bit of a sore spot for me.

Two papers this week from Cancer Prevention Research on the potential anticancer effects of a diabetes drug (Nathan Seppa story here) remind me to tell the story of a Middle Ages European herbal medicine used to treat polyuria that gave rise to one of the most widely prescribed drugs in the world, metformin (Glucophage in the US). Metformin, known chemically as a biguanide, dimethylguanide to be precise, traces its roots to the plant Galega officinalis. Known as goat’s rue, French lilac, or professor weed, this plant was shown to be a rich source of guanidine and a less toxic compound later called galegin or galegine (isoamyline guanidine).

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Posted in: Herbs & Supplements, History, Pharmaceuticals

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Can it get any worse?: industrial bleach as cancer and HIV cure

On the heels of Scott Gavura’s superb post yesterday on dietary supplement regulation in the US and Canada, I bring you one of the most egregious and obscene product cases I have seen in 15 years of teaching on botanical and non-botanical products: Miracle Mineral Solution. Please accept my apologies in advance for not having a scholarly post for you today – this is just too unbelievable not to share with Science-Based Medicine readers.

On July 30, the FDA released this warning:


FDA NEWS RELEASE

For Immediate Release: July 30, 2010
Media Inquiries: Elaine Gansz Bobo, 301-796-7567, elaine.bobo@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA Warns Consumers of Serious Harm from Drinking Miracle Mineral Solution (MMS)
Product contains industrial strength bleach

The U.S. Food and Drug Administration is warning consumers not to take Miracle Mineral Solution, an oral liquid also known as “Miracle Mineral Supplement” or “MMS.”  The product, when used as directed, produces an industrial bleach that can cause serious harm to health.

The FDA has received several reports of health injuries from consumers using this product, including severe nausea, vomiting, and life-threatening low blood pressure from dehydration.

Consumers who have MMS should stop using it immediately and throw it away.

MMS is distributed on Internet sites and online auctions by multiple independent distributors. Although the products share the MMS name, the look of the labeling may vary.

The product instructs consumers to mix the 28 percent sodium chlorite solution with an acid such as citrus juice. This mixture produces chlorine dioxide, a potent bleach used for stripping textiles and industrial water treatment. High oral doses of this bleach, such as those recommended in the labeling, can cause nausea, vomiting, diarrhea, and symptoms of severe dehydration.

MMS claims to treat multiple unrelated diseases, including HIV, hepatitis, the H1N1 flu virus, common colds, acne, cancer, and other conditions. The FDA is not aware of any research that MMS is effective in treating any of these conditions. MMS also poses a significant health risk to consumers who may choose to use this product for self-treatment instead of seeking FDA-approved treatments for these conditions.

The FDA continues to investigate and may pursue civil or criminal enforcement actions as appropriate to protect the public from this potentially dangerous product.

The FDA advises consumers who have experienced any negative side effects from MMS to consult a health care professional as soon as possible and to discard the product. Consumers and health care professionals should report adverse events to the FDA’s MedWatch program at 800-FDA-1088 or online at www.fda.gov/medwatch/report.htm.


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Posted in: Cancer, Science and Medicine

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Natural is not innocuous: the case of Angel’s Trumpet and tropane alkaloid intoxication

With this post, I’m happy to return to Science-Based Medicine on a regular basis, at least monthly and perhaps more depending upon how often commentary is required on natural products, whether they be herbal medicines or single-agent pharmaceuticals derived from natural sources. Next week, I’ll be attending the 2010 Annual Meeting of the American Society of Pharmacognosy being held jointly with the Phytochemical Society of North America in St. Petersburg, Florida. I hope to bring back the latest on novel natural products in preclinical development.

But today, I bring recent news that revisits a timeworn folly of the young (and some older folks): recreational use of toxic plants for the purpose of hallucination.

Toxicity reports are re-emerging in southern California this week after a dozen hospitalizations of kids using teas made from a fragrant flowering plant called Angel’s Trumpet. The tea is used to produce hallucinations, but they can progress to extremely unpleasant experiences. Moreover, Angel’s Trumpet can be deadly, accelerating the heart rate and causing fatal cardiac rhythmic disturbances and bronchoconstriction that can trigger asthma attacks in sensitive individuals.

220px-Atropine.svg.pngAngel’s Trumpet is one of a series of plants in the Brugmansia genus that make a variety of muscarinic cholinergic antagonists such as atropine (dl-hyoscyamine, pictured to the right) and scopolamine (l-hyoscine). These compounds are also known chemically as tropane alkaloids or belladonna alkaloids, the latter derived from their classical isolation from Atropa belladonna. The belladonna name derives from the use of eye drops made from the plants that prevent constriction of the pupils (mydriasis), back when the size of a woman’s pupils was a sign of beauty and arousal.

The tropane alkaloids are ubiquitous in plants and fungi and act as classic hallucinogens when used in high doses. Their legend goes back to witches brews and beyond. A wonderfully colorful history of tropane alkaloids by Robert S. Holzman of Children’s Hospital and Harvard Medical School was offered in this free 1998 paper in the journal, Anesthesiology (1998; 89:241-249).

However, the aftermath of Angel’s Trumpet use is far from colorful. In cases like these, I like to turn to the Erowid site, a respected, user-supported site that offers non-judgmental information on plant-derived and synthetic psychoactive agents. The Erowid Experience Vault has several descriptions of the use of Angel’s Trumpet but this one is the most detailed and representative of the downsides of this plant. (Note that the colloquial term for Angel’s Trumpet in Australia is sometimes “Tree Datura,” although Brugmansia is a closely-related but distinct genus from Datura within the Solanaceae family.)

I also came across a poorly-documented 2003 news article cited a German teenager cutting off his penis and tongue with garden shears after using Angel’s Trumpet.

While I’m NOT a physician, emergency personnel stumbling upon this post would do well to note that physostigmine or pilocarpine are typical antidotes for anticholinergic poisonings with Angel’s Trumpet, Atropa, Datura, and other similar plants that cause dilated pupils with loss of accommodation, xerostomia (dry mouth), and tachycardia. Click on this paragraph to access the Medscape poisoning article with more details on when and where specific treatments should be employed.

From the eMedicine article linked to in the above paragraph:

Remember common signs and symptoms with the mnemonic, “red as a beet, dry as a bone, blind as a bat, mad as a hatter, and hot as a hare.” The mnemonic refers to the symptoms of flushing, dry skin and mucous membranes, mydriasis with loss of accommodation, altered mental status (AMS), and fever, respectively.

I encourage all clinicians to be vigilant about anticholinergic poisonings in the weeks to come. In some cases in the past, I have found that reports such as these from southern California will often give rise to attempts to use the hallucinatory plant elsewhere despite the risks detailed.

Posted in: Science and Medicine

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James Ray and testosterone replacement therapy (TRT)

For the last four years I have served in a volunteer capacity among a panel of pharmacotherapy experts queried regularly by the ABC News Medical Unit about breaking or upcoming news involving the efficacy and safety of drugs and supplements. Where appropriate, I provide background information that informs the story.

My incentive is largely to put my time where my mouth is when I say that scientists need to take a more active role in making sure medical stories are reported accurately. An additional dividend is paid to my students who then benefit from my presentation of the science behind timely medical developments.

On occasion, perhaps once or twice a year, I’ll be asked for an on-camera interview. Even when this occurs, the resulting story will contain no more than 15 seconds of the interview and some summary by the reporter of other issues we discussed. I take this responsibility very seriously and prepare as much as I can given the deadlines of the press and my daily education and research schedule.

But given airtime constraints, much of what I prepare would normally end up in the abyss of my files and come out in the classroom when I lecture about that particular topic. Blogging, however, now allows us to expand further on stories where we are consulted, giving us an opportunity to air, albeit to a smaller audience, the information we found important from our perspective. Authoring a blog, therefore, takes away the excuse some scientists and physicians have in not wanting to talk to the press: “There’s never enough airtime to tell the whole story the way I would tell it.”

This post was informed by one of those brief appearances, this time on ABC World News Sunday with Dan Harris. The interview was solicited last weekend following the release of information obtained during the execution of a search warrant in lodging occupied by the self-help guru, James Arthur Ray, who led an Arizona sweat lodge ceremony last October where three people ultimately died and almost two dozen were hospitalized. The segment was not archived to the World News website but some ABC affiliates subsequently aired truncated versions of the story.
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Posted in: Pharmaceuticals, Science and the Media

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Ontario naturopathic prescribing proposal is bad medicine

Two weeks ago, Canadian Skeptics United published on their Skeptic North site a piece by an Ontario pharmacist criticizing a proposal by the province to grant limited prescribing rights to naturopaths. The essay, which was reprinted in the National Post on Tuesday, outlines the intellectual and practical conundrum presented by allowing those with education that diverges from science-based practices to prescribe drugs.

The naturopath lobby came out in force and was relatively unopposed in the 54 comments that followed, primarily because the NP closes comments 24 hours after online posting. Therefore, those with a more rational and considered viewpoint based in facts were locked out from commenting. This is quite disappointing to me personally and professionally because of the wildly emotional appeals, strawman arguments, and smears and attacks on the author himself without, of course, addressing his well-founded criticism of the prescribing proposal before the provincial government.

At the Skeptic North post, the piece even drew a naturopath who equated the criticism of his/her field with the Nazis and Mussolini. However, you can’t write critiques of these practices without attracting attacks ad hominem, especially Godwin’s Law, that are the resort of those whose arguments are logically flawed.
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Posted in: Science and Medicine

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The effective wordsmithing of Amy Wallace

One of the most engaging and clearly-written pieces of science journalism over the last year or so was published in Wired magazine last week. Now in the midst of a firestorm of attention, Amy Wallace’s, “An Epidemic of Fear: How Panicked Parents Skipping Shots Endangers Us All,” is part interview with rotavirus vaccine developer, pediatric infectious disease physician and immunologist, Dr Paul Offit, and description of the anti-vaccination movement in the United States.

Wallace’s work is the centerpiece of a masterful collection of smaller articles providing science-based information about vaccination that also refuts common anti-vaccination myths including “How To Win An Argument About Vaccines” and “The Misinformants: Prominent Voices in the Anti-Vaccine Crusade”.

Wired’s follow-up discussion of the issue includes, “A Short History of Vaccine Panic,” for those of us who “have a day job” and not enough time to read Paul Offit’s 2008 book, “Autism’s False Prophets.”
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Posted in: Public Health, Science and the Media, Vaccines

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Commercial deception: undeclared drugs in herbs and other dietary supplements

Back in February, an acupuncturist in Key West, Florida, was arrested on charges of using a physician’s credentials to obtain controlled substances and other prescription drugs.  While some of these drugs were for the individual’s personal use, the Key West Citizen reported from arrest records that the acupuncturist had obtained other drugs for her patients, including anxiolytics, a muscle relaxant, and sedative sleep aids.

While it is not clear if the individual in question specifically mixed those drugs with herbal or homeopathic remedies available at her practice, the demographics of her clientele are likely to be inconsistent with the use of prescription drugs.

Why do I propose this hypothesis and where would a practitioner get the idea to mix prescription drugs with herbal products to make them appear effective?

Why, the dietary supplement industry, of course.
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Posted in: Health Fraud, Herbs & Supplements

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NCCAM is a victim of its own history

Let me begin with a story. An assistant professor submits a reasonable application to NCCAM to investigate the potential metabolic and pharmacodynamic interactions of St. Johns wort with conventional chemotherapy. This was the year or year-and-a-half before SJW was known to have significant CYP3A4 inductive activity due primarily to its component, hyperforin. Said investigator used this preliminary data, not explicitly required for theNIH funding mechanism (called an R21), to question whether St. John’s wort used by depressed cancer patients might interfere with chemotherapy. The original proposal earned a priority score of 228 (as with golf, the lower the better: the best is 100, the worst is 500.)

The major reviewer critique was that the assistant professor, Your Humble Pharmacologist, lacked, at the time, significant natural products chemistry expertise. YHP was then doing his sabbatical in the NC Research Triangle area and wisely sought the support and expertise of the now-late Dr. Monroe Wall and surviving Dr. Manuskh Wani. These gentlemen discovered and solved the structures of taxol from Taxus brevifolia and camptothecin from Camptotheca acuminata. Taxol itself became a blockbuster drug for Bristol-Myers Squibb while camptothecin required water-soluble modifications to foster topotecan (Hycamptin) and irinotecan (Camptosar) that collectively saved or prolonged the lives of thousands of men and women subjected to breast, ovarian, lung, and gastrointestinal tumors. In 2003, they received the designation of an American Chemical Society National Historic Chemical Landmark for their three decades of work in this area. (Sadly, they received none of the profits from these drugs as their discoveries pre-dated the Bayh-Dole Act that allowed NIH funded researchers to share in the revenues of intellectual property emerging from their work.).

Being a savvy young investigator, I sought and enlisted the assistance and support of Dr. Wall and colleagues to provide my team with world-class, natural products expertise. Stunningly, the subsequent application was awared a score of 345 (*much worse than the original) with the criticism from reviewers that all Dr. Wall did was to lend a drug development aspect to an otherwise “herbal” applicaton.

To this day, I cannot fathom who better I could have sought for natural products expertise on this grant application.

Since then, three of my colleagues and I have submitted 13 applications to NCCAM, including an application for a comprehensive Botanical Research Center grant. All 13 received unfundable scores. Among these was a 279-page application for a NCCAM Botanical Research Center – reviewed but not discussed by the evaluation panel.

Nonetheless, I have taken the approach that if NCCAM were to continue its existence, I would try to be part of the solution.  I have accepted several invitations to review research and training grants for NCCAM and I am pleased to say that one or two projects that I ranked highly ended up being very productive, specifically in the area of natural products and traditional herbal medicines.  I also have some friends and valued colleagues who contribute to the scientific integrity of NCCAM. However, my collective experiences lead me to believe that they are voices quenched by the vast wilderness of the promotion and advocacy of “integrative medicine” and CAM.
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Posted in: Basic Science, Herbs & Supplements, Politics and Regulation, Science and Medicine

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University of the Sciences in Philadelphia Justification for Scientific Honor of Homeopathic Leader, John A. Borneman, III

To update readers, I posted last week that my alma mater was to offer a Doctor(ate) of Science degree at our Founders’ Day celebration to Mr. John A. Borneman, III, pharmacist graduate (1952),  founder of the Board Member, Homeopathic Pharmacopoeia Convention of the United States, Southeastern, PA, and Chairman, Standard Homeopathic Company, Bryn Mawr, PA

The university, known prior to 1998 as the Philadelphia College of Pharmacy and Science (PCP&S), has been led by Dr. Philip Gerbino, a gentleman whom I hold in highest regard for his leadership and dedication to pharmacy practice. As I increasingly appreciate the time demands on a university administrator, I was grateful to receive a very prompt response from Dr. Gerbino following the public posting here of my letter of objection last week:

Dear Dr. Kroll,

I would like to thank you for e-mailing myself and our provost, Dr. Russell DiGate, on Jan. 26 with your concerns regarding our Founders’ Day honoree. We most certainly respect your opinion and thoughtful correspondence.

We had no intention of eroding the honorific nature of science with our selection of John A. Borneman, III, P’52, RPh. Instead our objective was to honor a man who is a founder, innovator, and successful entrepreneur.  His selection for the Honorary Doctorate of Science degree is not about the rigors of science, nor the appropriate applications of science to homeopathic and alternative medicines, but about a founder who possesses remarkable leadership qualities and who is willing to share some of those with our students.  

Mr. Borneman’s selection as our Founders’ Day degree recipient provided a source of considerable discussion internally. I can say that in the end, it was decided that since one of our missions is to provide our students with academic and personal development through intellectual, cultural, and ethical understanding and awareness, Mr. Borneman’s honor would ultimately benefit them on their own paths to becoming future leaders and innovators. As point of emphasis, and in this context, we honor founding, not the field of homeopathic medicine. We honor a founder with entrepreneurial spirit.

Again, we appreciate your interest and comments and value your opinion. This letter is not intended to change your mind. It is provided to offer a better understanding of our decision. A good criticism is healthy and often inspiring. While it is not always necessary that we all agree, the basis of academia is to provide an environment of inquiry, debate, and critical thought where all opinions are respected.

Sincerely.

Philip P. Gerbino, PharmD

President

Again, readers, please keep in mind that I hold Dr. Gerbino in my highest regard.  He has been a university leader since I conducted my very first research project at PCP&S in 1984. Knowing what I know of him personally, even considering the unrecognized challenges of being a lead university administrator, I am led to register an even stronger objection to this honor of Mr. Borneman.

At first, I thought it might be more appropriate to acknowledge Mr. Borneman with an honorary MBA from the university.  However, even this recognition would honor leadership and entrepreneurship in the absence of ethics by promoting the sale of products with no medicinal value under the guise of health remedies.

Not to be melodramatic, but if I were to collect lawn clippings from my yard and sell them as a cure for cancer with 30% of patients claiming they were helped, would I be worthy of an Honorary Doctorate of Science from my alma mater?

And I also submit that Mr. Borneman’s grandfather, John P. Borneman (1907) was a PCP graduate and promoter of both botanical medicines *and* homeopathics at a time when dose-response pharmacology was first being realized in the United States.

My most serious point is that one cannot, as Dr. Gerbino proposes, separate the business leadership and success of Mr. Borneman from the fact that the business is one of deceptive products marketed in the name of medicine.

Whatever Mr. Borneman offers to my alma mater in terms of business acumen and leadership training, I find his honor highly deficient in ethics and an affront to the principles of authenticity and scientific rigor put forth by the founders of the Philadelphia College of Pharmacy.

Unfortunately, my compatriots are graduates of a small college with a small alumni organization. I was graduate number 17,346 since 1821 and the school has only had between 900 and 2,500 students per year in the last 20 years. I doubt seriously that a significant public objection can be mounted against the honoring of Mr. Borneman.  I’m sure he is a fine gentleman personally, and I hope to meet him at some point to discuss these issues, but I am disgusted by the imprimatur about to be given to him by the same institution whose academic endorsement hangs above my desk.

 

Posted in: Homeopathy

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