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Addiction, FDA, Health Policy, In the News, Podcasts

E-cigarettes and the FDA: A conversation with a tobacco-marketing researcher

E-cigarettes and the FDA: A conversation with a tobacco-marketing researcher

The FDA announced today its plans to regulate e-cigarettes. The news comes as little surprise to many, including Robert Jackler, MD, chair of otolaryngology at Stanford Medicine, who studies the effects of tobacco advertising, marketing, and promotion through his center, the Stanford Research Into the Impact of Tobacco Advertising. I asked Jackler this morning what he thought of the FDA’s plan, and he had this to say:

While I welcome the FDA proposal to deem electronic cigarettes as tobacco products under their regulatory authority, I’m disappointed with the narrow scope of their proposal and the snail’s pace of the process. Given its importance, I’m particularly troubled by the FDA’s failure to address the the widespread mixing of nicotine with youth-oriented flavorings (e.g. gummy bears, cotton candy, chocolate, honey, peach schnapps) in electronic cigarettes products.  Overwhelming evidence implicates such flavors as a gateway to teen nicotine addiction [which] led the FDA to ban flavors (except for menthol – which is presently under review) for cigarettes in 2009.  Give the lethargic pace of adopting new regulations, a generation of American teens is being placed at risk of suffering the ravages of nicotine addiction.

In a podcast last month, Jackler spoke in-depth about the rise of, and problems with, e-cigarettes. If you haven’t yet listened, now is a great time to.

Previously: E-Cigarettes: The explosion of vaping is about to be regulated, Stanford chair of otolaryngology discusses federal court’s ruling on graphic cigarette labels and What’s being done about the way tobacco companies market and manufacture products

Applied Biotechnology, Clinical Trials, FDA, Public Health, Research, Stanford News

The best toxicology lab: a mouse with a human liver

The best toxicology lab: a mouse with a human liver

of mice and menA few years ago, Stanford pharmacogenomic expert Gary Peltz, MD, PhD, collaborating with researchers in Japan, developed a line of bioengineered mice whose livers were largely replaced with human liver cells that recapitulate the architecture and function of a human liver. Now, in a recent study published in PLoS Medicine, Peltz’s team has shown that routine use of this altered lab mouse in standard toxicology tests preceding clinical trials would save human lives.

Among the liver’s numerous other job responsibilities, one of the most important is chemically modifying drugs in various ways to make them easier for the body to get rid of. But some of those chemical products, or metabolites, can themselves be quite toxic if they reach high levels before they’ve been excreted.

The Food and Drug Administration requires that prior to human testing, a drug’s toxicological potential be assessed in at least two mammalian species. But we humans metabolize things differently from other mammals, because our livers are different. That can make for nasty surprises. All too often, drugs showing tremendous promise in preclinical animal assessments fail in human trials due to unforeseen liver toxicity, said Peltz, a former pharmaceutical executive who is intimately familiar with established preclinical testing procedures in the industry.

That’s what happened in 1993 when, after a short safety trial of a drug called FIAU concluded without incident, the comp0und was placed in a phase-2 clinical trial of a drug for hepatitis B. FIAU belongs to a class of drugs that can interfere with viral replication, so it was considered a great candidate for treating virally induced infections such as hepatitis B.

As I wrote in my release about the new study:

“FIAU was supposed to be a revolutionary drug,” Peltz said. “It looked very promising in preclinical tests. In phase 1, when the drug was administered to subjects for a short period of time, the human subjects seemed to do fairly well.” But the phase-2 trial was stopped after 13 weeks, when it became clear that FIAU was destroying patients’ livers.

In fact, nearly half the patients treated with FIAU in that trial died from complications of liver damage. Yet, before advancing to clinical trials FIAU had been tested for as long as six months in mice, rats, dogs and monkeys without any trace of toxicity. An investigation conducted by the National Academy of Sciences later determined that the drug had shown no signs of being dangerous during those rigorous preclinical toxicology tests.

In Peltz’s new study, though, FIAU caused unmistakable early signs of  severe liver toxicity in the bioengineered mice with human livers. This observation would have served as a bright red stop signal that would have prevented the drug from being administered to people.

Bonus item: Using bioengineered mice with human livers instead of mice with murine ones would no doubt result in the clinical and commercial success of some drugs that never got to the human-testing stage because they caused liver toxicity in mice.

Previously: Fortune teller: Mice with ‘humanized’ livers predict HCV drug candidate’s behavior in humans, Alchemy: From liposuction fluid to new liver cells and Immunology escapes from the mouse trap
Photo by erjkprunczyk

Addiction, FDA, Health Policy, Podcasts, Public Health

E-Cigarettes: The explosion of vaping is about to be regulated

E-Cigarettes: The explosion of vaping is about to be regulated

E-cigarettes are about to get zapped. To date, across the globe, they’ve been largely unregulated – and their growth since they first came on the scene in 2007 has been exponential. Now, in the first big regulatory action that is sure to spur similar responses across the pond, the European Parliament approved rules last week to ban e-cigarette advertising in the 28 EU member nations beginning in mid-2016.  The strong action also requires the products to carry graphic health warnings, be childproof and contain no more than 20 milligrams of nicotine per milliliter. It’s expected that the U.S. Food and Drug Administration will soon follow suit and the days of great independence for e-cigarettes will come to a crashing halt. A few U.S. cities, Los Angeles most recently, have banned e-cigarettes in public spaces.

e-cigUntil recently, I was completely ignorant about the whole phenomenon of e-cigarettes. What is the delivery system? Where are they manufactured? Are they a safe alternative to smoking? And how are they being marketed and to whom? Well here’s an eye opener: According to the Centers for Disease Control and Prevention, e-cigarette usage more than doubled among middle and high school students users from 2011 to 2012. Altogether, nearly 1.8 million middle and high school students nationwide use e-cigarettes.

Robert Jackler, MD, chair of otolaryngology at Stanford Medicine, has long studied the effects of tobacco advertising, marketing, and promotion through his center, SRITA (Stanford Research Into the Impact of Tobacco Advertising). After years of detailing how tobacco use became ubiquitous in the U.S. he’s now tracking the marketing of e-cigarettes, and what he’s found probably won’t surprise you. The same sales techniques that brought about the explosive growth of tobacco use are being deployed again to make e-cigarettes look sexy, cool and defiant.

While there are claims by the e-cigarette industry that e-cigarettes are important tools to help people kick the tobacco habit, there’s little evidence to date to back up that claim. And Jackler isn’t completely sold on the notion that e-cigarettes will bring about a great cessation of tobacco smoking; he sees them more as a continuity product. He told me:

What the industry would like to see you do is when you go to a place that you can’t smoke, that you pick up your e‑cigarette and you vape, and you get your nicotine dose in the airport when waiting, or when you’re in your workplace, or when you’re even in school, and that way, when you leave school or the workplace, you go back to the combustible tobacco products.

Sorry if I’m a bit cynical, but as an ex-smoker I find it hard to believe that Big Tobacco – which is increasingly getting into the e-cigarette business – doesn’t also see vaping as a way to continue to keep smokers smoking. Bubble gum flavors and packaging designed to resemble lipstick containers! Who’s really being targeted here?

After my 1:2:1 podcast (above) with Jackler, I’m convinced we’ve been down this road before and it wasn’t pretty health-wise. More than 16 million Americans suffer from a disease caused by smoking. Listen to the podcast and you be the  judge about the true intentions of those promoting e-cigarettes.

Previously: Stanford chair of otolaryngology discusses federal court’s ruling on graphic cigarette labelsWhat’s being done about the way tobacco companies market and manufacture products and Image of the Week: Vintage Christmas cigarette advertisement
Photo by lindsay-fox

FDA, Health Disparities, Sexual Health, Women's Health

Female sexual health expert responds to delay in approval for “Viagra for women”

Female sexual health expert responds to delay in approval for "Viagra for women"

As announced yesterday, Sprout Pharmaceuticals, manufacturer of flibanserin, dubbed a “female Viagra,” is appealing the Food and Drug Administration‘s decision requesting more information on the drug before approving it for use in the U.S. Leah Millheiser, MD, director of Stanford’s Female Sexual Medicine Program, writes an appeal of her own on her blog, DrLeahM.com, in response to the FDA’s delay.

From the post:

Many of us in the field of female sexual medicine felt that Flibanserin had the best shot at being the first FDA-approved “Viagra for Women” – the holy grail for women with persistent low sexual desire in whom other treatments have failed (relationship therapy, sex therapy, off-label medications,etc). With this latest rejection, I ask you to consider the following: 43% of women in the US compared to 31% of men suffer from a sexual function complaint. There are currently 2 drugs that are FDA-approved for female sexual dysfunction (both for the treatment of postmenopausal painful intercourse due to vaginal dryness) compared to over 10 FDA-approved treatments available to men.

Previously: Speaking up about female sexual dysfunctionYoung, single, dating – and a breast-cancer survivorAsk Stanford Med: Director of Female Sexual Medicine Program responds to questions on sexual health and Shining the spotlight on women’s sexual health

FDA, Parenting, Pediatrics

Be in the know when it comes to kids’ cold meds, FDA reminds parents

Be in the know when it comes to kids' cold meds, FDA reminds parents

Last week, my co-worker had to ask me if I was okay after hearing me sneeze and blow my nose every 15 minutes. I immediately chalked it up to allergies and took some antihistamines. The sneezing stopped, but for the next few days I still had a runny nose and developed a sore throat. So deciding it must be the sniffles and not seasonal allergies, I tried some cold meds this time around.

Because symptoms for a cold and allergies can be very similar, choosing which medication to take can be difficult and confusing. The U.S. Food and Drug Administration is stressing the importance of paying attention to the active ingredients in medications, especially when it comes to treating kids – as mixing drugs can cause adverse reactions or serious health complications. From an agency news release:

Many medicines have just one active ingredient. But combination medicines, such as those for allergy, cough, or fever and congestion, may have more than one.

Take antihistamines taken for allergies. “Too much antihistamine can cause sedation and—paradoxically—agitation. In rare cases, it can cause breathing problems, including decreased oxygen or increased carbon dioxide in the blood, Sachs says.

“We’re just starting allergy season,” says Sachs. “Many parents may be giving their children at least one product with an antihistamine in it.” Over-the-counter (OTC) antihistamines (with brand name examples) include diphenhydramine (Benadryl), chlorpheniramine (Chlor-Trimeton), clemastine (Tavist), fexofenadine (Allegra), loratadine (Claritin, Alavert), and cetirizine (Zyrtec).

But parents may also be treating their children for a separate ailment, such as a cough or cold. What they need to realize is that more than one combination medicine may be one too many.

“It’s important not to inadvertently give your child a double dose,” Sachs says.

Via HealthDay
Previously:
CDC launches campaign to reduce accidental drug overdoses among children and New ways to prevent drug overdoses in children
Photo by anjanettew

FDA, Public Health, Research

The importance of including risk information in ads for over-the-counter medications

Findings published today in the Journal of the American Medical Association show that when prescription medications become available over-the-counter, advertisements for the products are less likely to alert consumers to potential risks or side effects.

In the study (subscription required), Brigham and Women’s Hospital researcher Jeremy Greene, MD, PhD, and colleagues examined print and broadcast advertisements for four commonly used medications that were marketed to consumers as prescription drugs and later approved for over-the-counter sale. The advertisements ran for 24 months before and six months after the switch to over-the-counter. The researchers found that when drugs required a prescription, 70 percent of the advertisements mentioned potential risks and side effects. However, once drugs were available without a doctor’s signature, this figure dropped to 11 percent.

Greene discusses the findings in a Q&A on news@JAMA. He had the following to say about why risk information in advertisements is necessary for patients and how he hopes this study will be useful to physicians:

When the average consumer thinks about an OTC drug, they think this drug has to be safe or it wouldn’t be available without a prescription. But as any pharmacologist knows, there is no such thing as a safe drug. Our most potent cures can be poison if used improperly, and that is just as true for OTC drugs.

It is increasingly important to know all of the substances a patient is taking. We understand that the total amount of acetaminophen consumed can shift it from a safe medication to one of the leading causes of emergency department visits and liver failure. It’s important for us to know the landscape of promotion and how it influences consumers’ perceptions of medication risks.

Previously: Report shows over 60 percent of Americans don’t follow doctors’ orders in taking prescription meds and One label fits all? A universal schedule for prescription drugs
Photo by PinkMoose

FDA, In the News, Science Policy, Stem Cells

U.S. District Court rules that stem cells are drugs

Peter Aldhous from New Scientist reports today that the U.S. District Court in Washington, DC, has ruled that a person’s own cultured stem cells are drugs subject to regulation by the Food and Drug Administration.

This is a big deal, as it’s the cornerstone of an ongoing argument between the agency and Colorado-based Regenerative Sciences (The FDA Law Blog summarized the legal tussles nicely last October). It’s also germane to the issues surrounding Texas-based Celltex, which I’ve blogged about before.

According to Aldhous:

It’s official: stem cells are drugs. At least, that’s the opinion of the [court]… which has ruled that the Food and Drug Administration (FDA) has the authority to regulate clinics offering controversial stem cell therapies.

Treatments in which stem cells are harvested from bone marrow and injected straight back into the same patient are deemed part of routine medical practice – not regulated by the US government. But if the cells are subjected to more than “minimal manipulation”, the FDA maintains that the therapy becomes a “drug”, which must be specifically approved for use.

Aldhous also quotes Regenerative Sciences’ medical director Christopher Centeno, MD, vowing to appeal the ruling, as well as Stanford’s own Christopher Scott:

“I think it’s a good ruling, and I’m glad to see that that the FDA has exercised its muscle on the case,” says Christopher Scott, who heads the Program on Stem Cells in Society at Stanford University in California.

Scott hopes that the FDA will now step up its efforts to regulate other clinics offering unproven stem cell therapies. These include Celltex of Sugar Land, Texas, which rose to prominence after Texas governor Rick Perry was injected with stem cells supplied by the company to aid his recovery from back surgery.

This is obviously not the last of the story– we’ll keep you posted.

Previously: FDA audit of Texas stem cell clinic revealed by Houston Chronicle and Stanford’s Irving Weissman on the (lost?) promise of stem cells
Photo by sideonecincy

FDA, HIV/AIDS, In the News

Truvada: Not a magic bullet for preventing HIV

Truvada: Not a magic bullet for preventing HIV

As you may have heard, the U.S. Food and Drug Administration yesterday approved the drug Truvada as a preventative measure for HIV-negative individuals who are at high-risk for contracting the virus. The pill, which is already used in patients with HIV, has been shown to reduce the risk of infection.

A segment on KQED’s California Report today focused on some of the controversies surrounding Truvada’s approval, including concerns from doctors and researchers about how the drug could encourage users to forego safe sex practices. Andrew Zolopa, MD, director of the Stanford Positive Care Clinic, told reporter Joshua Johnson:

There’s no magic bullet here. It’s not just a pill by itself – it really does require careful prevention planning, safe sex education, the use of condoms… All of those things still are required as well as medical monitoring for the medication, because of course there are side effects to medications. All medications, even a medication as good as the one that’s just been approved for prevention, Truvada, do have side effects.

Previously: FDA panel recommends use of new cost-effective tool to curb AIDS epidemic, Preventing HIV with daily drug is costly but useful and Treat patients early to stop HIV spread, study finds

Cardiovascular Medicine, Clinical Trials, FDA, Stem Cells

Stem cell-based heart-attack therapy approved for clinical trials

Marking a first for the California Institute for Regenerative Medicine, the FDA has given the go-ahead for clinical trials on a stem-cell based approach to repairing damage caused by heart attack. CIRM provided funding to the Cedars-Sinai Heart Institute researchers who worked on the potential therapy; as noted in a press release, “this is the first time that research by a CIRM-funded Disease Team has resulted in an Investigational New Drug (IND) approval from the FDA.” More from the release:

The therapy, which will be taken forward by Los Angeles-based biotechnology company Capricor, uses Cardiosphere Derived Cells (CDCs) to reduce scarring and repair the damage caused to heart muscle by a heart attack. The cells are found in heart tissue and have the potential to change into a variety of different heart cell types. The CIRM funded work enabled development of an “off the shelf” product that has the potential to treat large numbers of patients and be available whenever a patient needs it.  The theory is that these cells will help support the heart’s own healing mechanisms.

In preliminary studies with a related product derived from the patient’s own cells (e.g., not an “off the shelf” product), giving patients these modified CDCs were shown by an imaging study to reduce the amount of scarring left by the heart attack.

FDA, In the News, Stem Cells

FDA audit of Texas stem cell clinic revealed by Houston Chronicle

I haven’t written much about it here, but I’ve been following carefully the ongoing drama between the Food and Drug Administration and a Texas stem cell clinic, Celltex. (Texas Governor Rick Perry underwent experimental injection of his own adult stem cells last year, and thrust Celltex into the spotlight.) Today the Houston Chronicle published portions of documents from an agency audit of the clinic in April, obtained through a Freedom of Information Act filed by University of Minnesota bioethicist Leigh Turner, PhD. According to the paper:

In a report one expert called a blow to the entire adult stem-cell industry, the FDA found that Celltex Therapeutics Corp. cannot guarantee the sterility, uniformity and integrity of stem cells it takes from people and then stores and grows for eventual therapeutic reinjection.

At issue is whether Celltex, or other similar companies, can remove adult stem cells from a patient, culture them in a lab and then reinject them into the same patient from which they were derived. U.C. Davis stem cell researcher Paul Knoepfler, PhD, included on his well-regarded stem cell blog a damning comment today from Turner:

Since February, many individuals have expressed both concern and outrage in response to Celltex’s involvement in processing mesenchymal stem cells, banking stem cells, and making these cells accessible to individuals with such illnesses as multiple sclerosis and Parkinson’s disease.  Among various issues raised by bioethicists, scientists, journalists, and other individuals who have investigated Celltex’s operation in Texas are fundamental questions about whether the stem cells Celltex provides to patients are safe and effective. Celltex has failed to make any attempt to demonstrate safety and efficacy and yet it charges patients with serious illnesses $20,000 to $30,000 for stem cell “infusions.” There is no reason to assume that these procedures are safe and effective.  To the contrary, by providing local physicians with clinically unproven stem cell interventions Celltex is putting patients at risk of harm.

The California Institute for Regenerative Medicine also weighed in today, no doubt trying to mitigate any overall negative fallout for the field of adult stem cell research, emphasizing how important it is for stem cell companies to work with regulators like the FDA to bring the best therapies to patients.

The as-yet-unresolved role of Celltex and other adult stem cell clinics in this country is one all stem cell researchers and reporters should be watching with interest. It pits patients, many of whom feel their own stem cells (and how they and their physicians choose to use them) should not be subject to government oversight, against regulators who argue that these cells (once removed from the body and grown in a laboratory) should at least be shown to be safe and effective before the technique is commercially marketed to patients.

Previously: Stanford’s Irving Weissman on the (lost?) promise of stem cells, Stem cell researchers challenge clinics’ questionable practices, and Bioethicist Arthur Caplan slams unproven stem cell clinics

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