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.

Smith & Nephew Artificial Hip Replacement

By way of background, the hip is a ball-and-socket joint, moving not just forward and back (like a knee joint) but also sideways. In a total hip replacement, part of the upper thigh bone and the ball portion of the hip joint are replaced with metal components. Part of the replacement includes a liner between the ball and the socket that allows the hip to rotate freely. Some patients have hip resurfacing surgery instead, where only the interface between the hip joint’s ball and its socket is replaced with a new surface.

The plaintiff in this case, Walter Shuker, received a total hip replacement using Smith & Nephew’s R3 Acetabular System. Although Smith & Nephew holds itself out as a “world leader in joint replacement systems,” the R3 hip replacement that Shuker received didn’t use a typical plastic liner.

Instead, the liner in Shuker’s replaced hip was an R3 metal liner designed for use in Smith & Nephew’s Birmingham Hip Resurfacing System. The R3 metal liner was neither designed nor approved for total hip replacement. In fact, its label states that it “must be replaced with an R3 poly[ethylene] liner” if used in a total hip replacement. Despite that label, Smith & Nephew marketed the R3 metal liner as an “option for its R3 Acetabular System” in its promotional materials.

Less than two years after having his hip replaced, Shuker developed hip pain that was severe enough to limit his activities. When his surgeon investigated, he found “metallic debris” indicating that the metal-on-metal joint in his hip was wearing away and had to be replaced. Shuker ended up needing multiple revision surgeries to correct the defective replaced hip.

Walter Shuker’s Case Against Smith & Nephew

Shuker brought three types of state law claims against Smith & Nephew: for its failure to warn patients about the dangers of the R3 metal liner, he claimed negligence, strict liability, and breach of implied warranty. Based on Smith & Nephew’s off-label promotion of the R3 metal liner, Shuker also claimed negligence, while his wife claimed loss of consortium. Finally, Shuker argued that Smith & Nephew engaged in fraud.

The trial court dismissed Shuker’s claims, finding that they were preempted by federal law.

Shuker appealed to the Third Circuit Court of Appeals, which recently issued its opinion. The appeals court agreed that the failure to warn claims should be dismissed due to federal preemption. However, it allowed Shuker’s off-label promotion claims to proceed.

So what does federal preemption actually mean, and how did it apply here?

Federal Preemption and Medical Device Lawsuits

The U.S. Constitution declares federal law to be the “supreme law of the land.” Therefore, when a state law conflicts with a federal law, the federal law controls and the state law is essentially voided. This concept is called preemption. Preemption may be express—where a federal law specifically says that it controls and that state laws can’t interfere—or it may be implied.

Medical devices are regulated under the 1976 Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act. That law expressly states that it preempts any state “safety or effectiveness” claims. Here, Shuker tried to claim that Smith & Nephew was negligent under state law even though it had passed the Food and Drug Administration’s safety regulations for medical devices. The Third Circuit held that Shuker’s state law negligence claim was preempted by federal law.

Why did Shuker attempt this argument? His lawyer argued that only the component that failed—the R3 metal liner—was regulated and governed by federal law. The system as a whole, the argument went, was not subject to the same strict federal regulation. It’s true that only the R3 metal liner was subject to a comprehensive testing and approval process. However, the appeals court held that a medical device is defined as any component within the device, not the entire system as a whole, preempting these claims.

Federal preemption is one of several powerful defenses available to negligent medical device manufacturers. Often people injured by the clear negligence of companies do not have a right to compensation because of the legal concept of preemption. (This is one reason it is critically important for federal agencies like the FDA to “get it right” when allowing products into the market.)

Fortunately for the Shukers, the appeals court also ruled that their off-label promotion claims—arguing that Smith & Nephew negligently marketed the R3 metal liner for an unsafe off-label use—were not expressly preempted by federal law. Those claims are still pending in the trial court.

What Does This Mean for Your Case?

As you’ve probably figured out, these cases can be complicated! Federal preemption often lurks to destroy what may seem to be a valid claim against a negligent manufacturer. If you’re having a problem with a medical device, you don’t have to try to fight the manufacturer alone. Give me a call today to discuss your specific injuries and your specific claims against the manufacturer (919.830.5602).

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.

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.

Communications between pharmaceutical companies and medical device manufacturers and physicians are highly regulated by the federal Food and Drug Administration (FDA), but the agency, as much as it may want to be, does not have the final say in all regulation. These companies have First Amendment commercial free speech rights (though they’re not as broad as the free speech rights individuals have) and there’s a tension between what the FDA wants companies to say, what these companies want to say, and what the courts say the companies can say.

The agency in late August published a notice of public hearing and request for comments concerning manufacturer communications regarding unapproved uses of approved or cleared medical products. The hearing will be held on November 9-10, 2016 in Silver Spring, Maryland, and in case you want to present information you must register by October 19. You could also send in written comments by January 9.

more Off-Label Drug Use

These are very hot button topics. Manufacturers can’t market their products for purposes that are not approved by the FDA (such as if a drug is approved to treat lung cancer only it can’t be marketed to treat malaria), but once approved by the FDA a physician can prescribe it for off label uses. There have been court rulings stating manufacturers can talk truthfully about unapproved uses of their products to physicians. It’s a fine line, and it can easily be abused.

To be approved for a particular use a drug manufacturer must go through a long and expensive process to show the FDA the drug is safe and effective. The danger to patients is that if they take a drug for an unapproved use it may not be safe or effective. It may be a waste of money, it may harm them directly, or the time wasted taking this ineffective drug may allow the disease or condition to worsen, possibly making treatment more difficult or impossible.

On the flip side patients may be suffering from a disease or condition that may be very difficult to treat or is untreatable. A drug approved for one purpose may show promise in clinical trials to battle this hard-to-treat or impossible-to-treat disease. Instead of potentially waiting years for formal approval, these patients may be able to benefit in the present instead of waiting to use it in the future (if they live that long).

FDA Public Hearing

The FDA poses a number of questions on which it would like input from a number of interested parties including manufacturers, health care providers, patient advocates, payors, academics and public interest groups. The topics generally cover:

• How off-label communications impact public health,
• How changes in the health care system result in data on new uses of approved products,
• How to preserve incentives for manufacturers to seek approval for new uses,
• Standards for truthful and non-misleading information provided by manufacturers,
• What the FDA should consider when it monitors and enforces the law on off-label communications by manufacturers, and
• Changes FDA should consider to regulations covering manufacturers’ communications about their products.

Can Congress Help?

Add Congress to the mix. In May the House Committee on Energy and Commerce sent a letter to Health and Human Services Secretary Sylvia Burwell:

• Showing concern that FDA hadn’t clarified its position on permissible manufacturer communications about uses of drugs and devices beyond their approved labeling; and
• Voicing displeasure that HHS apparently was stopping the FDA from issuing guidance or new regulations after a number of court victories for companies and individuals prosecuted for off-label communications about drug and medical devices.

First Amendment commercial speech protections have been interpreted by the courts to allow manufacturers’ truthful and non-misleading speech concerning their products even if that speech includes uses of their products that have not been approved by the FDA. Companies and groups impacted by the issue have encouraged FDA to issue new guidance or change its regulations so its oversight and enforcement actions reflect these court decisions. This announcement and these public hearings are a possible step in that direction.