As with so many other harmful drugs, the use of testosterone went off the rails when companies pushed the drug’s use for off-label purposes. Although testosterone replacement therapy was approved to treat just two specific conditions, companies eventually pushed their products to treat all kinds of other conditions, uses never approved by the FDA. According to the Third Amended Master Long-Form Complaint filed in the testosterone multi-district litigation (MDL 2545), it was this aggressive off-label marketing and label-expansion that led to many unnecessary injuries, suffering, and thousands of lawsuits.

FDA Approves Testosterone For Treatment of Two Conditions

In 1953 the FDA first approved a version of synthetic testosterone to treat two conditions: (1) primary hypogonadism and (2) hypogonadotropic hypogonadism. Since that time the FDA has not approved testosterone to treat any other diseases or conditions.

• Primary hypogonadism

This is a condition where the man’s testicles fail to function in certain important ways. Specifically, the man’s body fails to produce sufficient amounts of testosterone. Primary hypogonadism can occur in childhood or later in life. If it happens in childhood, the child may not fully develop sex organs, may not grow body hair, and may fail to move normally through puberty. If hypogonadism occurs in adulthood, the man may suffer from erectile dysfunction, infertility, decreased body hair and muscle mass, loss of bone mass or density, and other problems. The FDA noted that primary hypogonadism may be specifically caused by undescended testicles, rotated or twisted testicles, inflammation in the testicles (orchitis), surgical removal of a testicle, or vanishing testicles. (And yes, it pained me to write out that list.)

• Hypogonadotropic hypogonadism

This is a form of hypogonadism which is caused by a problem with the pituitary gland or the hypothalamus (a part of the brain that regulates the pituitary gland and other bodily functions). Basically, hypogonadotropic hypogonadism (let’s call it HH) occurs when a lack of hormones fails to activate the testicles, and thus little or no sex hormones are released. HH can be caused by damage to the pituitary gland or to the hypothalamus from injury, surgery, tumor, infection, or radiation. It can also be caused by genetic defects, chronic disease, drug abuse, nutrition problems, or even stress. The symptoms of HH are like those of primary hypogonadism.

Over the years the FDA approved many different testosterone products for use to treat these two conditions. But only these two conditions. The FDA never approved the use of testosterone for use to treat erectile dysfunction, low energy, depression, lack of sexual interest, “Low-T,” or any other condition unless it was a diagnosed symptom of the two types of hypogonadism discussed above.

The business problem for the companies selling these products is that the population of men suffering from hypogonadism is not significant. The population of men suffering from low sex drive, low energy, loss of muscle mass, or erectile dysfunction, however, is much, much larger. Find a way to sell to that larger group and these companies can make much more money.

Aggressive Off-Label Marketing and Label Expansion

According to the Master Complaint (MDL 2545), companies marketed testosterone for off-label use. In addition, the companies are alleged to have exploited ambiguities in the product labeling to expand the permitted uses for testosterone beyond treatment of hypogonadism.

According to the Complaint, drug manufacturers attempted to blur the lines between hypogonadism and a condition referred to as “Low-T.” Many people have heard of the term Low-T, but it does not actually appear to be a condition recognized by the scientific or medical community. The Master Complaint alleges that AbbVie, Inc., maker of the testosterone product “Androgel,” represented that Low-T was an “acquired form of hypogonadism.” Low-T (whatever it is) is not the same as hypogonadism, and therefore use of testosterone to treat Low-T is an off-label and unapproved use. Other testosterone makers–including Eli Lilly, Endo, Auxilium, Pfizer, and Actavis–also pushed off-label uses and blurred the lines between hypogonadism and other conditions. This effort by the drug companies was intended to expand the reach of the approved uses for testosterone. The companies used ambiguities in the drug label to advocate for treatment of other conditions and thus sell much more of the product than it would if it were only sold to those men actually suffering from hypogonadism.

Once these connections were made, the target population of testosterone users expanded rapidly, from one million to five million and eventually up to twenty million men. Let me be very clear: twenty million men do not suffer from hypogonadism. Rather, as the years marched along more men without a diagnosis of hypogonadism but who may have suffered from an isolated condition such as low energy or reduced sex drive may have been prescribed testosterone. This medication is very potent and comes with significant risks and potentially nasty side effects (such as heart attacks, stroke, and blood clots), and it should be taken only if there is a serious underlying condition such as hypogonadism.

If you have taken testosterone, or otherwise have interest in this subject, I encourage you to read the Amended Master Complaint in the testosterone MDL. If you have suffered an injury after taking testosterone, call me.

Note: This post was written after review of court filings and news reports. Please note that the makers of testosterone dispute some of the points made in the Master Complaint and in this article.

Just to recap, Androgel is a roll-on testosterone product. Jesse Mitchell began taking Androgel in 2007 after doctors ran blood tests and found that Mitchell’s testosterone levels were quite low. In 2012, at the age of 49, Jesse Mitchell had a massive heart attack. From what I’ve read, the heart attack almost killed him.

Mitchell and his wife sued AbbVie in 2014, claiming the company marketed and sold Androgel without properly warning men about the increased risk for heart attacks. During the trial an expert for the Mitchells testified that in his opinion there was a connection between Mitchell’s 2012 heart attack and his extended use of Androgel.

AbbVie’s defense was that the FDA did not see a serious problem with Androgel and did not require further testing, so the drug maker should not be to blame. In addition, the defense argued that Mitchell’s team simply did not establish “legal causation” between Mitchell’s use of Androgel and his heart attack. Among other things, AbbVie noted that Mitchell was obese, suffered from high blood pressure and bad cholesterol levels, and was a smoker. If this health description is accurate, these “bad facts” can derail an otherwise strong plaintiffs’ case.

The Verdict

The jury did not accept the argument that plaintiffs had proven the connection between Jesse Mitchell’s use of testosterone and his heart attack. Thus, the drug maker “won” on the claims of negligence. After the verdict an AbbVie spokesperson stated that the “jury found that Androgel did not cause any damage.” Let me stop here and note that this is not what the jury found. Finding, for example, that someone is “not guilty” is not the same thing as finding them “innocent.” Similarly, in a civil case against AbbVie, the verdict can be read only as indicating that the plaintiffs did not meet their burden of proof of establishing causation between the use of Androgel and Mitchell’s heart attack. It does not mean that the jury believed Androgel caused no damage. In any event, many observers of the trial believe that Mitchell’s poor health played a large part in preventing the jury from finding the connection between use of testosterone and the heart attack. It’s quite possible that a plaintiff with fewer health issues would have been able to establish the legal causation for the heart attack. We will certainly see in future bellwether trials.

Nevertheless, the jury did find that AbbVie was liable for fraudulent misrepresentation. Mitchell argued in this separate claim that AbbVie intentionally targeted middle-aged men with misleading marketing that claimed AndroGel could successfully treat a condition called “Low T” or low testosterone. Many medical experts agree that the symptoms of Low T are simply normal signs of the male aging process. It is undisputed that a healthy nineteen year old man will produce more testosterone than a healthy fifty year old man. Lower testosterone levels among middle-aged men–most doctors will say–do not require testosterone replacement therapy (TRT) with products like Androgel. Jesse Mitchell further argued that the FDA had never approved AndroGel for treatment of Low T.

The jury found that AbbVie had fraudulently misrepresented the use of the drug Androgel, then awarded the plaintiffs $150,000,000.00 in punitive damages. That is a really big number. Particularly coming as it does after the jury found that plaintiffs had not proven the connection between Androgel and the heart attack. Clearly, the jury did not like AbbVie’s aggressive marketing of Androgel for off-label uses.

The glaring problem with this verdict is that the punitive damages were awarded without any award of compensatory damages. In most states, there must be some compensatory damage award to permit an additional award of punitive damages. It goes like this: “we (the jury) find that you hurt the plaintiff–at least a little–and we also find that you should be punished for your really bad acts.” Sometimes when a jury decides that the defendant was a bad actor but they cannot agree on actual damages to the plaintiff, the jury will award nominal compensatory damages, such as a single dollar, to pave the way for a much larger punitive damages award. Even a damages award of $1.00 can shield a large punitive damages award post-trial attack. A punitive damages award alone, however, often will not stand.

So the chance that this punitive damages award is upheld in post-trial motions or on appeal is not great. It may well be that Jesse Mitchell and his family walk away with nothing.

Testosterone Multidistrict Litigation

The lawsuits against testosterone drug companies have grown in the past few years. Currently more than 6,000 men and families have filed suit. On June 6, 2014, the Judicial Panel on Multidistrict Litigation (JPML) created a multidistrict litigation (MDL) site to consolidate cases against testosterone manufacturers. The MDL is situated in the U.S. District Court for the Northern District of Illinois, with Judge Matthew Kennelly presiding. The MDL has been expanded to include suits against AbbVie, Inc. (Androgel), Eli Lilly & Co. (Axiron), and Endo Pharmaceuticals, Inc. (Fortesta, Delatestryl).

What is Testosterone?

Testosterone is a naturally occurring hormone which is important to the development of masculine characteristics and male growth. It is mainly produced in the testicles. Testosterone production increases during male puberty, and the hormone works to deepen the male voice and increase muscle mass; it also functions to increase facial and body hair, and to spark the sex drive. It’s the thing that helps the boy become the “man.” Testosterone can also be produced in laboratories. FDA-approved testosterone replacement therapy (TRT) products include a gel applied to the skin like Androgel, an injection, a patch (also applied to the skin), and another method of delivering testosterone through application to the upper gum or inner cheek. The FDA has approved these products for men who “who lack or have low testosterone levels in conjunction with an associated medical condition.” The problem is, several studies have shown an increased risk in heart attacks in men who use testosterone products.

On March 3, 2015, the FDA required testosterone label revisions to warn of the “possible increased risk of heart attacks and strokes associated with testosterone use.”

If you have been using prescription testosterone and have had heart issues or other health problems, I would advise that you see your doctor promptly, and if you think you may have a civil case against the drug maker, give me a call ((919) 830-5602) and we will figure it out.

The information in this post was gathered from the FDA and other media and news sources.

Zofran is an anti-nausea drug. It works to prevent nausea and vomiting by blocking the effects of serotonin, a chemical in the body that triggers nausea and vomiting. The drug was designed to help cancer patients dealing with the side effects of chemotherapy but it was also approved by the FDA for those suffering nausea due to radiation therapy, anesthesia and surgery. Nevertheless, GlaxoSmithKline (GSK) eventually pushed to market and sell Zofran to pregnant women. Women who are pregnant are often plagued by morning sickness, and some can suffer from extreme nausea. The problem is, the FDA never approved the use of Zofran for pregnant women; it’s an “unapproved” use of the drug. Unfortunately, “off-label drug use” is very common. I wrote about off-label drug use and its potential dangers here.

By 2013, 110,000 monthly prescriptions of Zofran were issued to pregnant women. If this were an approved use, we could rest easier, as an approved use means the drug has been thoroughly tested and evaluated, with the determination backed up by “strong scientific data.” For unapproved uses there is none of that. If a drug is approved for any use, a doctor can then use his best judgment to prescribe the drug for any other purpose.

more Does Zofran Cause Birth Defects?

In 2014 a study of Zofran was published by the American Journal of Obstetrics & Gynecology (AJOG). Among other findings, the study noted a two-fold increased risk of heart defects in infants whose mothers used Zofran during their pregnancies, which led to a 30% increased risk of major congenital malformations. Other birth defects potentially caused by the pregnant mother’s use of Zofran include cleft palate and cleft lip, skull deformities, and club foot. The AJOG study also noted that other anti-nausea drugs (doxylamine and pyridoxine) were approved for use in pregnant women, which means they were thoroughly tested for use by pregnant women. So why should pregnant women use Zofran, the study asked.

In 2016 a study published in Reproductive Toxicology indicated that researchers did not see a connection between use of the drug Zofran during pregnancy and birth defects. The study appeared to focus on “extreme morning sickness,” and concluded that extreme morning sickness could be worse for the health of the baby than being exposed to Zofran.

Studies on the connection between Zofran and birth defects are continuing.

Zofran Multidistrict Litigation (MDL 2657)

Still, many children born to mothers who used Zofran during pregnancy have been born with serious birth defects. Hundreds of these families have filed lawsuits against GSK. So far more than 400 lawsuits have been filed. A multidistrict litigation (MDL) court was established in 2015 in federal court in Massachusetts (In Re: Zofran (Ondansetron) Products Liability Litigation, Case No. 1:15-md-2657). Because thousands of women have been prescribed Zofran during their pregnancies, this number will likely increase dramatically over the next few years.

MDL Judge Allows Fraud Claims to Stay in Lawsuits

In April 2017, the judge presiding over the Zofran MDL denied GSK’s motion to dismiss all fraud claims from the litigation. Now fraud is a special kind of claim against a defendant, and it requires careful and detailed allegations in the lawsuit in order to survive a motion to dismiss. In a simple negligence action, for example, a plaintiff can simply lay out basic facts to support negligence (“the driver was negligent when he was speeding along the highway, and the driver’s speed caused the car crash”). But fraud is a different animal: it essentially alleges that the defendant was intentionally deceptive, misleading, or untruthful. Fraud claims are big, and if a plaintiff proves fraud in court, the defendant can be exposed to additional damages, including punitive damages, which can explode a trial verdict.

Because fraud claims can be very expensive and burdensome on defendants, the Rules of Civil Procedure require that plaintiffs “state with particularity the circumstances constituting fraud . . . .” In the Zofran MDL, GSK argued to the Court that the plaintiffs had failed to meet this pleading burden, and therefore that the fraud claims should be dismissed.

Judge Dennis Saylor disagreed, at least with regard to allegations of GSK’s misrepresentations in its Zofran labeling. He ruled in April that plaintiffs had satisfied Rule 9(b) of the Federal Rules of Civil Procedure.

The master complaints, according to Judge Saylor, “allege generally that plaintiffs and their physicians relied on the misrepresentation in the label in prescribing and ingesting Zofran and/or ondansetron. [citations omitted] In this context, at least, that is sufficient. Pharmaceutical product labeling is highly regulated, and its very purpose is to advise prescribing physicians, who may reasonably rely on the representations in such labeling.” Memorandum and Order, pp. 14-15.

So What Does All this Mean?

The fraud claims in the Zofran MDL can move forward against GlaxoSmithKline. This is a big court victory for the 400+ plaintiffs in the litigation. But there is still work to do. If the plaintiffs can win their fraud claims at trial, they stand to recover punitive damages, and these damages are extra damages meant to punish a “bad actor.” Punitive damages are intended to send a signal to a defendant found to have intentionally or recklessly harmed someone else, and these damages are intended to be large enough to change behavior. In a recent Depuy Pinnacle hip trial in Texas, a jury awarded one billion dollars in punitive damages to plaintiffs harmed by the bad actions of Depuy, Inc. A billion dollars can certainly change behavior, even in a huge company like Depuy or GSK.

Despite the plaintiffs’ recent win regarding the fraud claims in the Zofran MDL, GSK will still vigorously defend itself. At this point, GSK refuses to admit Zofran is unsafe. However, more lawsuits will be filed, bellwethers cases will soon be tried, and we will get a better sense of the strength of these cases in the coming months.

If you took Zofran during your pregnancy and your child was born with a birth defect, contact me or another product liability attorney to discuss your potential case against GlaxoSmithKline.

Let me state the obvious: companies sell you stuff with one purpose in mind, to make money. McDonald’s doesn’t sell you quarter pounders because the company believes what you need to live a better life is to eat more quarter pounders. The NRA doesn’t advocate gun ownership because it believes you need to own five Glock 9s (you don’t), but rather so the gun makers can sell more guns. Mercedes doesn’t make expensive cars because its board of directors hope to improve the world by selling you cars with heated leather seats. Every company sets out first to last to make money. And the more money the better.

So it goes with pharmaceutical companies. The general public may sleepwalk through the concept and lazily presume that the primary motivation for drug companies is to develop medications which cure diseases or which minimize the suffering from diseases. But in fact the motivation for pharmaceutical companies is to make money, and a lot of it. This is rather obvious and not a controversial point, and I’d like to believe that every “BigPharma” corporate board would agree with me. But it helps to keep this profit motive in mind when doing research on drugs you have been prescribed or which you are currently taking. And to be hyper-vigilant about assessing any new “wonder drugs” which hit the market.

“Off-Label” Drug Promotion

Recently, the pharmaceutical industry strenuously objected to new regulations implemented by the U.S. Food and Drug Administration (FDA) on off-label drug uses. Essentially, several advocacy groups supporting the pharmaceutical industry filed petitions opposing heightened restrictions on the marketing and sale of drugs for unapproved or “off-label” uses.

Let’s back up.

There are approved and unapproved uses for prescription drugs. For approved uses, the drug has been thoroughly tested and evaluated. The FDA has determined that the benefits and risks are acceptable and that this determination is backed by “strong scientific data.” Finally, for approved uses, the drugs have labels which set out clearly how to use the drug and for what specific purposes.

Then there are unapproved uses. Once the FDA approves any drug, your doctor is then allowed to prescribe the drug to treat another condition which is not listed as an approved use. Basically, once the FDA green-lights a drug, it relies on competent, unbiased physicians to make the best decisions for their patients in prescribing the drug, for whatever purpose.

Doctors may prescribe a drug for an unapproved use when the doctor believes the drug will help the patient in some way and there is no other drug available to help the patient. The FDA uses the example of a cancer drug approved for one type of cancer, but the oncologist prescribes it to treat a different form of cancer that does not have a similar medication available for treatment.

This sounds reasonably benign, even helpful, but drug companies can be aggressive in promoting off-label use. I have written about troubling off-label uses on this site. One off-label drug use nightmare occurred when doctors prescribed Risperdal for adolescent boys with certain behavior issues. Risperdal was originally approved solely to treat adult patients with schizophrenia. But Johnson & Johnson pressed for FDA permission to market the drug to treat other conditions, such as bipolar disorder and autism, and eventually to permit use in children. It was then expanded further to treat adults and children suffering from attention deficit disorder, anxiety and depression. As it turned out, Risperdal can promote the growth of female breast tissue (“gynecomastia”). Female breasts on adolescent boys is a terrible and traumatic disfigurement. And thousands of lawsuits have resulted from these injuries.

Thus, it is critically important that off-label drug use and off-label drug promotion are monitored carefully. You would think that the pharmaceutical industry would wholeheartedly agree, but . . .

BigPharma Objects to New FDA Off-Label Regulations

The FDA recently published its latest guidelines on regulating off-label drug use. The guidelines give the FDA new authority to police the selling of prescription drugs for unapproved uses. Specifically, the FDA focused on “intended use,” which is “the objective intent of the persons legally responsible for the labeling of drugs.” The goal is to make sure the companies promoting a drug are not pushing for it to be used in an unintended way. Intended use analysis is helpful to the FDA as it “helps the FDA gauge whether companies are intentionally marketing products for unapproved uses.” See FDA Website. The new rule was supposed to give more power to the FDA to hold manufacturers liable for promotion of off-label, unapproved uses of drugs.

The drug industry has objected, calling the new rule a “vague standard” with “no support in existing law.” At the end of the day, the drug companies simply do not want to be held liable for getting caught promoting drugs for off-label use. The industry’s position seems to be “get out of our way and let us make as much money as possible.”

They may get their wish. Recently, President Donald Trump has issued a “regulatory freeze” on all FDA rules and regulations. From what I’ve seen coming out of Washington lately, regulations on BigPharma are likely to get weakened, not strengthened, over the next four years. If you do not do your own research, you may be vulnerable to prescription drugs with unwelcome and harmful side effects.

What to Ask Your Doctor:

If your doctor prescribes a drug for an unapproved use, you should ask:

• What was the drug originally approved for?
• Why am I getting it for my condition?
• Are other drugs available that have been approved to treat my medical condition?
• Do studies support the use of this drug to treat my condition?
• Will this drug work better to treat my medical condition than using an approved treatment?
• What are the benefits and risks of treating my medical condition with this drug?

As always, be careful out there.

There is an unsettling criminal case being tried in Massachusetts federal court this week. Two executives of a company called Acclarent are being prosecuted for fraud in the marketing of a medical device known as “Stratus.” The Stratus was a device that was supposed to relieve symptoms of sinusitis using saline. It consisted of a tube with a balloon attached to a sharp pin. The device would be implanted in the patient’s sinus, where it would be left in place for two weeks. It was reported to work as similar devices which created space in the sinus area using saline, which allowed patients to breathe easier. But according to testimony in the criminal trial, Acclarent had other intentions for the Stratus. Instead of using saline, the Stratus was intended to deliver “Kenalog,” a steroid found in medications like Nasacourt.

But I should back up.

more Again, The Flawed 510(k) Medical Device Approval Process

The Stratus was first approved for sale by the FDA utilizing the 510(k) process. The Code of Federal Regulations allows a manufacturer to notify the FDA of its intent to market a device (like the Stratus). It then allows the company to apply for market approval without rigorous testing or clinical trials. The company must explain how a new device is “substantially equivalent” to an existing product that did undergo testing. Many of the medical devices that have led to thousands of lawsuits (metal-on-metal artificial hips, artificial knees, transvaginal mesh) reached the market under the 510(k) process. In the case of Stratus, Acclarent reported to the FDA that the device was similar to other devices on the market which utilized saline to open the sinus area and to relieve pressure in the sinus. On the basis of these representations, the FDA approved the Stratus for sale in 2006.

The Allegations Against Acclarent Executives

Federal prosecutors allege that two executives committed fraud by obtaining market approval from the FDA under false pretenses. The claim is that Acclarent represented the Stratus was much like devices on the market which used saline, but then intentionally marketed the Stratus instead to deliver the steroid Kenalog. There was virtually no testing of the Stratus and its safety and effectiveness in delivering Kenalog directly into the sinus of patients. Prosecutors state that this intentional misrepresentation defrauded the FDA, the doctors who prescribed the device, and Johnson & Johnson, which purchased Acclarent in 2010 for $800 million. J&J pulled the product in 2013.

Evidence From The Acclarent Criminal Trial

One surgeon testified that he was very concerned that Acclarent had not properly tested the Stratus as safe when using the drug Kenalog. Dr. Michael Armstrong testified that he believed the marketing jumped ahead of the research on the medical device. Although it got approval for the Stratus using saline, Acclarent gave presentations to doctors focusing on the device delivering the steroid. This was not the proper use the FDA approved. Training materials developed by Acclarent showed a white liquid which was not saline (and believed to be Kenalog).

Prosecutors also called to the stand a former sales rep of Acclarent. She testified that the major emphasis in her sales training was in promoting the off-label use of the device and the steroid Kenalog. Because sales reps are not allowed to suggest off-label uses of drugs, the sales reps at Acclarent joked that they wanted to make buttons stating: “Ask me about Kenalog.” The sales rep also testified that Acclarent representatives told her the device was approved only for use with saline, but that doctors would probably not use saline with the Stratus.

At least from this testimony, it seems clear that Acclarent wanted to press ahead (recklessly) to sell the Stratus as a device to deliver the steroid Kenalog, which was not approved by the FDA and which had not undergone sufficient testing. This does not mean the executives will be found guilty of criminal fraud. But it does suggest a rush to market and a dangerous promotion of an off-label use of a drug.

The Takeaway

As consumers, we cannot presume that companies will always act ethically and responsibly. We all need to be vigilant when obtaining products and services. If you are planning to hire an attorney or a home builder or an accountant, check client references. If you are undergoing surgery, do some research in advance on your physician, and check with other people who know the doctor in your community. Is he a good surgeon? Is he responsive? Does he explain the procedure in helpful ways? Does he have a decent bedside manner? And if you are undergoing a procedure where a medical device is being implanted, investigate before the surgery. Ask your doctor about the specific product being used. Get a second opinion from another physician if possible. Ask your doctor why she chose one medical device product over another. Check out the articles on the medical device at the FDA website. Do a check on pending lawsuits against the manufacturer of the device. I know it sounds paranoid, but you may find some useful information and avoid a bad result or even an injury. No one can eliminate all risk in this life (especially when surgery or medical care is involved) but we should never blindly trust doctors or medical device companies.

The criminal case is titled: United States v. Facteau et al, 1:15-cr-10076 (U.S.D.C. Massachusetts). I will let you know the results of the trial when the jury reaches a verdict.