A recent article in the LA times tells of a husband’s quest to find a treatment for his wife’s Alzheimer’s disease. This is a narrative that journalists know and love—the brave patient or loved-one who won’t accept the nihilism of the medical establishment, who finds a maverick doctor willing to buck the system.
The article itself at least was not gushing, it tended toward a neutral tone, but such articles do tend to instill in the public a very counterproductive attitude toward science and medicine. I would have preferred an exposé of a dubious clinic exploiting desperate patients by peddling false hope. That is a narrative in which journalists rarely engage.
The story revolves around Dr. Edward Tobinick and his practice of perispinal etanercept (Enbrel) for a long and apparently growing list of conditions. Enbrel is an FDA-approved drug for the treatment of severe rheumatoid arthritis. It works by inhibiting tumor necrosis factor (TNF), which is a group of cytokines that are part of the immune system and cause cell death. Enbrel, therefore, can be a powerful anti-inflammatory drug. Tobinick is using Enbrel for many off-label indications, one of which is Alzheimer’s disease (the focus of the LA Times story).
The Dubious Health Clinic
Before I go into the details of Tobinick’s claims, let’s review the typical features of what we commonly call the “quack clinic” or the dubious health clinic. I wrote about this in 2009, and listed the following features:
- The clinic often has an impressive name, such as “The Institute Of,” but lacks any formal affiliation with an established institution, like a university or hospital, and was founded and may even continue to be operated by one person.
- The clinic claims to treat or cure one or more diseases that is currently believed to be incurable. Their claims sound too good to be true.
- There is only one clinic in the world that can perform their special procedure or that uses their proprietary treatment. Sometimes the treatment offered is new and experimental.
- The clinic claims to cure a variety of diseases, all with different causes and pathophysiology, with a single treatment – the “one cure for all diseases” approach.
- The clinic is often located in a country with little or no regulation.
- The clinic claims that it is the victim of repression. Typically they will say that either Big Pharma, the medical establishment, the insurance industry – or some other convenient villain—is trying to suppress their revolutionary treatment. Alternatively, the “medical establishment” is simply closed-minded to their paradigm-shifting ideas.
- Testimonials are used to promote the treatments offered by the clinic, but they have not published appropriate research in legitimate peer-reviewed journals.
- When challenged by professional organizations, the clinic defends itself by appealing to politicians, using the testimonies of previous patients who believe they have been helped by the clinic and the accusation of a conspiracy of those trying to protect their monopoly.
The Institute of Neurological Recovery
Now let’s take a look at Tobinick’s clinic. It has an impressive name—a one-man institute.1 The website proclaims:
The Institute of Neurological Recovery (INR®) is pleased to provide this introduction to its pioneering medical concepts, research, and treatment programs. INR designates a group of separate medical practices that utilize innovative, patented, off-label medical treatments developed by Edward Tobinick M.D. These treatment methods are designed to target a number of neuroinflammatory conditions with unmet medical need.
Many of the features of a dubious clinic are right there—the impressive name, claim to treat many conditions with one treatment, emphasis on how innovative the treatments are. The website also claims that his treatments are patented.
This is an interesting side issue, worthy of its own post. There has been a surge in the US in recent years in medical procedure patents. However, the first (and I think only) infringement lawsuit lost its case. Medical procedure patents are generally opposed by medical organizations as counterproductive profiteering and are banned in 80 countries. They are still legal in the US but there has been a number of legislative effort recently to limit or ban them.
The patented procedure (even if not enforced) seems like just another way to market the uniqueness of the treatments offered by the dubious clinic.
The list of conditions for which Tobinick claims or even has patented use of Enbrel include Alzheimer’s, stroke, traumatic brain injury, Parkinson’s disease, carpal tunnel syndrome, brain tumor, spinal cord injury, and back pain. That quite impressive for a doctor who isn’t even a neurologist. Tobinick is an internist who, prior to curing a long list of neurological diseases, specialized in laser hair removal.
The LA Times reports:
But his claims about the back treatment led to an investigation by the California Medical Board, which placed him on probation for unprofessional conduct and made him take classes in prescribing practices and ethics.
Tobinick has since moved his practice to Florida,2 which is a very quack-friendly state.3 Its “health care freedom” law effectively shields dubious practitioners from pesky medical boards.
Plausibility and evidence
When considering just the notion that Enbrel, a TNF inhibitor, might have a broad range of applications, this is entirely plausible. It is common for immunosuppressive drugs to gain an FDA approved indication for one specific condition, such as transplant rejection or rheumatoid arthritis, and then to be used off-label for many other autoimmune conditions.
This is very tricky, however, as the immune system is complex. There are different components to the immune system, and different aspects of immunity are involved in different auto-immune conditions. Therefore there is no one immunosuppressant drug or treatment for all auto-immune conditions.
When a new immune-suppressing drug comes on the market it is common for it to be tried in a variety of conditions—but practice then follows evidence. Initially we might see some case reports, followed by a case series. If the drug shows promise, then a double-blind placebo-controlled trial would ultimately determine its effectiveness.
This is definitely a gray area of off-label use. How much evidence is necessary to justify an off-label use of a drug—and how far off label? Sometimes the popularity of a new off-label use of a drug gets ahead of the evidence. In most cases, however, eventually the research is done and practice conforms to the evidence.
The claims of Tobinick, however, are not in the gray area—they are leaps and bounds ahead of the evidence. Further, the conditions he claims to treat are not clearly immune-mediated diseases. It’s one thing to use an immune-suppressing drug to treat a disease that is known to be caused by immune activity, and probably the kind of immune activity suppressed by the drug.
Tobinick, however, is claiming that a wide range of neurological conditions not known to be immune mediated are treated by a specific immunosuppressant.
On his website he cites many studies, but none of them establish the effectiveness of Enbrel for any of the conditions he is treating. Most of them are simply identifying that TNF is increased in the condition. This is very weak evidence, however, as markers of immune activity are frequently increased in diseases that are not caused by immune activity. The immune system is very reactive — it reacts to disease with inflammation (often what we refer to as the cleanup crew). The inflammation is not causing the disease, it is simply the body’s reaction to it.
Tobinick has also started to publish case series — little more than retrospective case series reporting on his own patients. This is weak evidence even when coming from an established researcher within their own area of expertise. It is all but worthless coming from clinic like Tobinick’s.
This is where his lack of expertise is especially relevant. Such arguments are often portrayed as elitist, as if a mere internist cannot have a valuable insight into how to treat neurological disease. But medicine and research are complex and there are many pitfalls. Unless you have expertise dealing with strokes or dementia, including how to properly research these conditions, you are likely to fall for these pitfalls.
For example, in his recent case series he writes:
Significant improvement was noted irrespective of the length of time before treatment was initiated; there was evidence of a strong treatment effect even in the subgroup of patients treated more than 10 years after stroke and TBI.
This, if anything, is evidence that the observed treatment effect is mere placebo. It is very implausible that stroke or TBI deficits will be equally responsive to an anti-inflammatory treatment (or any treatment) regardless of time since the stroke or trauma.
Stroke researchers are also very familiar with what is known as the “cheerleader effect.” Take any patient with chronic deficits, give them any intervention and then encourage them to function better, and they will function better. This can result simply from trying harder, or even just the incidental physical therapy benefit of engaging in a treatment and being evaluated.
Unless all these factors are controlled for with proper blinding, no conclusions about the treatment effect are possible. Tobinick is providing the kind of evidence that is guaranteed to be positive, but not the kind of evidence that would determine if his treatments are effective or not.
If you strip away the gratuitous narrative in the LA Times story and just look at the facts presented, a very different narrative emerges. Ken Chiate brought his wife to Tobinick’s clinic for 165 injections of Enbrel over four years, at a cost of $800 each (that’s $132,000).4 During that time there were questionable subjective effects from the treatment, typical of placebo-only effects. Meanwhile his wife continued to relentlessly progress, as is typical of the disease, until she finally died in 2011.
According to the article, the treatments gave Chiate a sense of purpose and of hope — a false hope, it turned out. He still clings to the idea that Enbrel may be an effective treatment for Alzheimer’s disease — even though Tobinick himself has apparently moved on to treating stroke.
In my opinion, the story documents exploitation of a well-meaning and desperate husband at the hands of a dubious practitioner, practicing at the fringes of medical ethics and evidence, making bold claims without adequate justification. The story also documents the utter failure of the regulatory system to prevent (or even properly react to) such exploitation. Florida in particular appears to be a haven for such activity.
Update April 2, 2015
1 Dr. Tobinick objects to this characterization on the basis that his practice includes multiple staff and other physicians. I maintain that this characterization is appropriate because his “institute” is merely his private practice of which he is the only significant component. The “institute’s” websites are found at tobinick.com, strokebreakthrough.com, nrimed.com, painbreakthrough.com, and alzheimerbreakthrough.com. Despite having several websites, his is the only bio that appears on any of them (and he so testified in court). No other physicians are featured on the INR website, nor any of the “Institute”’s other websites.
2 Tobinick objects to the fact that the original text stated that he moved his clinic to Florida. However, the clinic did not move to Florida, Dr. Tobinick himself moved to Florida where he opened an additional clinic, where he now works, but kept his a California clinic open also.
3 Dr. Tobinick objects to my characterization of Florida as “Quack Friendly.” However, as I pointed out in the text, Florida has a healthcare freedom law that specifically shields practitioners from having action taken against their license simply because they are practicing below the standard of care. In fact I was involved in a case where the court concluded a neurologist was practicing below the standard of care, but they appealed based upon Florida’s health care freedom law and the claim that they could not be held to the standard of care, and they won on appeal.
4 Dr. Tobinick disputes this figure, claiming that the LA Times story is incorrect. He claims that he charged Chiate a total of $71,000 for the treatments. However, other news sources state that he charges thousands of dollars for the initial treatment.