Are Clinical Trials Safe? The Risks of 'Medical Research'.

The day before I wrote this, I read about a ‘research’ fiasco where 3 individual were blinded after receiving stem cell injections into their eyes.  This ‘research’ was done in a physician’s office and cost each patient $5,000.   What a tragic outcome.  At least two of these patients discovered that this treatment was available by clicking on ClinicalTrials.gov, a name that suggests government approval, which is not true.  Clearly, the name of this website is deceptive.  Neither the Food and Drug Administration (FDA) or the National Institutes of Health had any endorsement or sponsorship role here.  Moreover, press reporting indicates that these patients had scant medical evaluation prior to and following the medical procedure.

Note to readers:

• Legitimate clinical trials generally do not charge patients for participation.
• Legitimate clinical trials have intensive evaluation to screen patients for eligibility.  Many or most patients may be excluded because of specific requirements of the study.  Adhering to these requirements is what helps to make a medical study valid.
• Legitimate clinical trials have a rigorous informed consent procedure.
• Legitimate clinical trials have aggressive follow-up after the experimental procedure so that results and adverse reactions can be measured and recorded. 
• Legitimate clinical trials aim to publish their results in peer reviewed journals.

Ophthalmologists have commented that injecting both eyes with an experimental treatment on the same day is an obvious deviation from acceptable  research practice.  Think about it.  Wouldn’t you want to inject only one eye at a time for reasons that need not be explained?

The Human Eye - Handle with Care!

 Like every doctor, I prescribe medications and treatments that are not approved by the FDA, a practice which the FDA supports.  Much of my advice is based upon my knowledge and experience, and may not be supported by sound medical evidence.  This is not because I am a quack, but because we don’t always have medical evidence for a patient’s particular medical issue.    Should we tell such a patient to return in a decade or two when the supportive evidence is available, or should we use our medical knowledge and judgment as best we can to address the current issue?

However, if I am prescribing a medicine to you off label, meaning for a purpose not officially approved by the FDA, I won’t call it ‘research’ or refer to it as a ‘clinical trial’.  It’s simply an ordinary day in the practice of medicine.  

Who Should Get the Liver Transplant?

People with liver failure and cirrhosis die every year because there are not enough livers available.  Who should receive the treasured life-saving organ?  There is an organ allocation system in place, which has evolved over time, which ranks patients who need liver transplants.  Without such a system, there would be confusion and chaos.  How can we fairly determine who should receive the next available liver?  What criteria should move a candidate toward the head of the line?  Age?  Medical diagnoses? Insurance coverage? Employment status?  Worth to society?  Criminal record?

An artist's rendering of the liver from the 19th century.

Consider the following 6 hypothetical examples of patients who need a liver transplant to survive.   How would you rank them?  Would those toward the bottom of your list agree with your determination?

• A 50-yr-old unemployed poet is an alcoholic.  He has been sober for 1 year.  His physicians believe he will not survive another year without a transplant.
• A 62-yr-old prisoner has end stage liver disease from hepatitis C, contracted from prior intravenous drug use.  He has been showing serious medical deterioration and his physician is concerned that his demise approaches unless he undergoes a liver transplant.  He will be incarcerated for life.  He is taking college classes pursuing an undergraduate degree.
• A 45-yr-old piano teacher has a malignant liver lesion.   Her physicians have advised a liver transplant. Although the survival rate for a liver cancer transplant is reasonable, it is lower than for sober alcoholics or hepatitis C.   There are no other effective treatments available.  Her prognosis with standard medical treatment is dismal.
• A 40-yr-old has end stage liver disease of unclear cause.  Liver transplant would likely save his life.  He is self-employed and has no medical insurance. 
• A 60-yr-old hedge fund operator needs a new liver to survive.  He is concerned that according to medical criteria, he will not be given a liver soon enough.  In exchange for a liver, he offers to donate $5 million to the medical institution to fund cutting edge research in treating liver disease.  This research has the potential improve the lives of thousands of individuals.
• A 55-yr-old is trying to get a liver transplant for his child.  In exchange for preferential treatment, he will stipulate that several family members will agree to donate various organs upon death.

How should the ranking decision made?  What factors should be weighed?  Ability to pay?  Worth to society, assuming this could be calculated?   Probability of long term survival?

Every one of these 6 individuals has a right to receive a new liver, but some of them will be left aside because others will be judged to have a greater right to a transplant. When any decision is made that creates winners and losers, the system will be challenged and attacked by those who decry what they believe to be an unfair process and outcome.  It is for this reason that transplant policy be made primarily by those who are as free as possible from agonizing conflicts of interest. 

A conflict of interest understandably taints our views.  For example, we may be against paying ransom for kidnapped hostages, until our kid is taken hostage.

Opioid Deaths in Ohio - Hell in the Heartland

We are working hard to bend the curve of the opioid crisis here in Ohio.  The cause of the crisis is complex and so is the remedy.  Statistics examining the last several months have not yet been released, but the trend over the past several years is very troubling.  When I first learned that Ohio was the epicenter of opioidmania, I was quite shocked, as I wrongly thought that this plague would spare the heartland.  In contrast, it seems the heartland is ground zero.  While I have no specific expertise in addiction medicine or sociology, here are my speculations on some of the contributors to the current crisis.

• Aggressive marketing by pharmaceutical companies.
• Deceptive marketing by pharmaceutical companies claiming non-addictive potential of their products.
• Economic decline and hopelessness.
• Increasing expectation by the public of a pain free existence.
• Physicians prescribing opioids, rather than non-addictive alternatives, in response to a new prescribing culture for these agents.
• Physicians writing opioid prescriptions containing more pills than necessary.
• Increasing availability of affordable, illicit opioids.

 Ohio overdose deaths were 3613 in 2016 and 5232 for the 12 months prior to June 2017.

A popular bromide is to accuse the medical profession of spawning the crisis.  While my profession clearly bears responsibility here, I think the causes are multifactorial.  The reason it is so important to have a clear understanding of all the causes is that this is essential to successfully formulate a strategy to combat the epidemic. 

It is a much easier task to prevent addiction than it is to treat it.  While I support treatment efforts, experts have told me that the probability that an opioid addict can conquer the addiction is rather dismal.  We all have heard vignettes of addicts who are revived multiple times by paramedics with naloxone, who immediately afterwards return to their addiction.  If fact, some individuals have raised the question if there should be a limit on the number of times that an individual should be revived.  I am not supporting this effort, but merely reporting on it here.  However, city budgets have limited resources.   How might a city’s residents respond if someone died of a heart attack because the paramedics were treating an overdose victim for the 5^th time?  

This is going to be tough work, but I think it’s a battle we must wage.  Moreover, I truly believe that real progress is possible and is ahead.   If we are all pushing in the same direction, then we can start to bend the curve. 

A Rare Cause of Rectal Bleeding

‘I can’t stand the site of blood!’  We’ve all heard that adage.   Blood can provoke emotional reactions from even steely muscle-bound bodybuilders.  We gastroenterologists routinely receive fearful phone calls from patients who have observed even minor rectal bleeding.  Fortunately, in most of these cases, there is a benign explanation for the sanguinary seepage.

If blood repels you, then gastroenterology should not be on your short, or even long list of professions under consideration.  We confront blood every day.  Of course, blood is the elixir of life as it courses into every remote recess of our bodies.  But, when blood loses its bearings, takes a wrong turn, and emerges errantly from our gastrointestinal tract, then gastroenterologists - or G-men -are called in.   Indeed, searching out the site of blood leakage in patients is one of our primary diagnostic tasks.  You might say that blood is our ‘bread & butter’.

I recently evaluated a patient in my office that confounded me and my staff.  Collectively, we have seen thousands of cases of internal bleeding, and yet we had never seen such a case as this before.  Will our discovery be a game changer in my specialty?  Should I publish this case in a medical journal to alert other practitioners of our groundbreaking discovery?  Should I start out on the lecture circuit?

Here are the facts.

A young woman underwent a colonoscopy in my office to evaluate abdominal pain and other digestive complaints.  There was no rectal bleeding.  Yet, during the colonoscopy there was blood throughout her colon, an entirely unexpected finding.  Now, we physicians are trained to deal with unexpected eventualities, but we are as surprised as anyone when we confront an unanticipated situation. We like stuff to make sense.   Suddenly, I needed to add diagnostic considerations to explain this surprising finding.  I assiduously searched with my scope for the origin of the bleeding, but I could not identify any lesion.

At that moment, I realized what must have occurred.  This patient, against our instructions, must have mixed the laxative with a red beverage, which was now masquerading as blood.  I smugly shared this hypothesis with my staff and dispatched a nurse out to the waiting room to ask the mother about pertinent laxative details.  The nurse returned informing us that the patient mixed the laxative with a blue beverage.  My smugness evaporated.  What is happening here?

After the patient was recovering and awake, we inquired about any ingestions that she did not previously disclose.  At that moment, she offered a full confession.  At midnight, she reached for a snack that we will now add to the list of forbidden foods prior to undergoing a colonoscopy.  Mystery solved.

We considered having her wear a scarlet letter as penance for her culinary sin.

Warning! Coffee May Cause Cancer!

Are you getting a little tired of being warned that all kinds of stuff you do is unsafe?  I wrote a post recently about Warning Fatigue with regard to our office’s Electronic Medical Record which I fear will emit a flashing Red Alert if I prescribe a patient an aspirin.

Now, I start every morning with a steaming cup of coffee.  In fact, there is one beside me right now, as I peck about my Dell keyboard to create this post.  My inner circle of intimates and those with whom I share a high percentage of DNA, are aware that I add something to the java, which is a rather atypical additive.  Curious readers may inquire further, although I cannot pledge here that I will make a full disclosure.   Persuade me to disclose, and I will give your request due consideration..

Recently, a judge in California ruled that various coffee companies, including Starbucks, must issue a cancer warning regarding a component of coffee called acrylamide  Violators would be subject to a mere $2,500 daily fine until the establishment complied.  Should Starbucks file for bankruptcy?  Or, better yet, can we sue the coffee companies if we become ill?  What about the fear of becoming ill?  Shouldn't that be compensable?

You might think that this warning could discourage sales since most folks, including me, are against cancer.  But, most folks, including me, shrug off dire warnings on substances and activities that have become part of our daily lives for hundreds of years.  And, calling something a carcinogen – which sounds scary – does not mean it is truly toxic. It may in theory pose a risk that is simply too infinitesimal to take seriously.  For example, if some laboratory rodents (the most unlucky creatures on the planet) are given the equivalent of 500 cups of coffee a day for a year, and they develop tumors, should we humans be concerned because some element of the java may be a carcinogen?

Arsenic in Disguise?

More confusing is to consider all of the putative health benefits of coffee, which even a rudimentary Googler such as myself quickly uncovered.   There are claims, for instance, that coffee can protect us against diabetes, Parkinson’s disease, dementia, depression and liver disease.  Perhaps, we should increase our coffee intake to protect ourselves.  

If we avoided every substance that an organization claimed to be risky and injurious, we would have to live in a hermetically sealed chamber receiving specialized feedings through a tube.  Doesn’t that sound like fun?

What if some organization decided that oxygen was toxic and needed to be avoided?  How long can you hold your breath?

                                                                                                                                               

Why I Now Treat Hepatitis C Patients

In a prior post, I shared my heretofore reluctance to prescribe medications to my Hepatitis C (HCV) patients.  In summary, after consideration of the risks and benefits of the available options, I could not persuade myself – or my patients – to pull the trigger.  These patients were made aware of my conservative philosophy of medical practice. I offered every one of them an opportunity to consult with another specialist who had a different view on the value of HCV treatment.

I do believe that there is a medical industrial complex that is flowing across the country like hot steaming lava.  While I have evolved in many ways professionally over the years, I have remained steadfast that less medical care generally results in better outcomes. 

A Scouting Patrol of the Medical Indutrial Complex

There was an astonishing development in HCV treatment that caused me to reevaluate my calculus.  New treatment emerged that was extremely safe and amazingly effective.  Now, nearly all patients with HCV can be cured by taking pills – no injections – that only rarely cause side effects.  Over the past 2 years, I have had many successes treating patients who on my advice had declined prior treatment options.

If you now have HCV, how can you refuse a safe medicine that works superbly?

This has been a game changer and the pharmaceutical companies should be congratulated on these breakthroughs.  There are several outstanding drugs currently available.  Initially, a 12 week course of treatment cost about $1,000 a day, clearly a pricey option.  And, if you believe that every HCV patient in the country should be treated, which may be up to 5 million people, do a cost calculation which might crash your computer.

To those who demonize the pharmaceutical industry for sport, would such a monumental research effort have even been undertaken without the promise of a huge profit?  Would you take a huge risk in your business without the hope of realizing a robust profit?  It takes years and tens of millions of dollars to do drug development, and most of these efforts fail either along the way or after the drug has hit the market and safety concerns arise.  

I’m not suggesting that this industry is filled with Eagle Scouts.  We have all read about numerous excesses and even illegalities in the drug trade.  But, if we want real pharmaceutical breakthroughs, and not just another heartburn or hypertensive medicine, then we need to provide incentives for undertaking this research. 

Market forces have substantially lowered the cost of HCV treatment, but it is still expensive.

Patients come to my office already informed about current HCV treatment.  Many are referred to me by physicians expecting me to treat them.   The drugs are safe and effective and approved by the F.D.A.   Although I still feel we are overtreating, my arguments for holding back have been somewhat dismantled by the new pharmaceutical developments.  Am I now at the vanguard of the Medical Industrial Complex?

Avoiding Drug Interactions and Side Effects - Be Warned!

Eons ago, there was a television show where a non-human character would yell out, ‘Warning’, Warning’, when he sensed imminent danger.   The series was called Lost in Space where we were entertained by a set of quirky characters on a cheesy set.  We loved that stuff.  It’s hard to imagine today’s millennials and younger folks being transfixed, as we were, with the deep television dramas of our day.  Who could match the subtle allegory and nuance of shows such as Green Acres or Gomer Pyle?  Some superficial viewers regarded The Andy Griffith Show as a homespun, idyllic view of small town America.  In truth it was a biting satire on the excesses and abuses of law enforcement in the 1960’s.

Robot and Dr. Smith

I am overwhelmed with the warnings that I receive in my work and in my life.  It seems that warnings, caveats and disclaimers are so omnipresent that they have lost their impact.  As I write this, I am seated in McDonalds, sipping a cold beverage that does not quite qualify as a nutritive elixir.  Had I chosen a steaming hot ‘cup of joe’, I’m quite certain that the beverage’s container would warn me that it contains a hot beverage.  Such a warning, of course, is of great benefit to the consumer, who would behave entirely differently equipped with the knowledge that his hot coffee is actually hot. 

With some regularity, when I prescribe a medication using our office’s beloved electronic medical record (EMR), a red warning flashes indicating that there is a potentially severe interaction with one of the patient’s current medications.  The intensity of the warning would suggest that I was prescribing cyanide or rat poison.   Our EMR allows me to bypass the warning and prescribe anyway, leaving this action memorialized in the EMR and available to plaintiff attorneys who might be in a position to query me on this decision, should an adverse medical event ensue. 

Now, I take these warnings seriously and would never place a patient at risk, unless the medical circumstances justified it, and the patient was properly informed.  My point is that many of these electronic warnings are hyperbolic, if not spurious.  Many times when I call a pharmacist – a human drug professional – in the presence of the patient, I am advised that there is no material risk.  In fact, the last time I did this just a few weeks ago, the pharmacist assured me that there was NO risk of an interaction.  I always document these conversations in the record and hope that the truth would set me free, if necessary. 

I cannot explain why the EMR’s software is set so sensitively.  I suppose I could investigate raising the threshold for issuing an apocalyptic warning, but then I might miss some actual legitimate warnings.

Do you think that all of the warnings we read, hear and trip over are issued to protect us or the companies and organizations that issue them?