Friday, January 6, 2017

EMPATHY - a DOUBLE-EDGED SWORD?

Let us forge a question. Is empathy a true moral signpost? And a second question to follow that one…Is Empathy a Primal tool to manipulate?

Now I understand that both those questions have interlaced within them a stream of emotion-provoking, incendiary thoughts that raise the collective eyebrows. But for this exercise let us kick this can down the metal roof and see if the noise becomes over-bearing?



“Empathy is the capacity to understand or feel what another person is experiencing from within the other being's frame of reference.” This definition is the hallmark of all things good and just. So how can something so good have another edge to it? After all, feeling the distress of someone that evokes a desire of compassion is sacrosanct in the virtue of being human. Isn’t it? We all aspire to be good people. We all aspire to do good. We imagine ourselves to be virtuous, moral and compassionate human beings. What then?



Ok enough of Tantalus’s tentacles tugging at your sleeves. Let me get to the core of this duality issue.

True empathy evokes compassion, yes, that is true. But is too much of it just too much? That is the question worth looking into. Or putting it mildly is too much of a good thing bad? And the answer is a possibly yes!



Let us take the healthcare environment for just a minute. Evoking empathy has fueled the FDA into granting approvals of many biological medications that have minimal benefit but a moderate amount of risk. The approvals are based on petitions cramped with thousands of signatures signed willingly by the many, touched by a heart-rending story of one. 



This “Made to Stick” format is a harbinger of the empathic culture that does not want to be seen callous by not signing the petition. And by signing the petition he or she shows the virtuous self to all others who have and have not signed. Underneath it all is the serpent of risk that raises its ugly head when the drug is put towards human use. Yet those harrowing stories of complications and even death are waylaid by the goodness to fit in this comfortable skin of false virtue. Many Adverse Events (AE) later as the true signal of truth becomes obvious, the drug is quietly withdrawn from the market. Of course there are many a manager in the middle that see to it that the drug reaches its consumer for they reap enormous benefits under the guise of Pharmacy Business Managers or PBM…but that is another story for another time. Recently we were made aware by the policy wonks, who decided that “Pain” should be granted the designation as a “5th Vital Sign.” Since all physicians were lambasted as not “caring” by not adhering to “pain prevention” principles, they out of 'goodness" started writing opioids for the patients. Thus, began the “Opioid crisis!” Some individuals became addicted and used the “5th Vital Sign” to get what they craved. Fault and finger-pointing notwithstanding, the crisis is real and it falls heavily at the feet of the “disembodied empathic few policy wonks.”



A simpler concept to understand is of a frail elderly person confined to his home because of age by his well-meaning care-givers. “No. no you must not do that and no, no you must not do this,” they cry. All the while the muscles lack the exercise and the brain lacks the motivation and suddenly they who could have had some liberty of thought and action are relegated to a heap of burden. Empathically downed by the rigors of “do good.” Love is misapplied when it denies the liberty and freedom of another. A love does not imprison the body and the mind to the demands of good wishes. It allows freedom to express and allows for adventure so the soul does not suffocate and wither.

Empathy can also harm a child where every demand is met. Every wish is granted and every action is met with ovation. That child’s soul is crafted in the perplexing vexation of tumult for the rest of her or his life. As he or she grows, all demands that aren’t met, become a source of torment and a tantrum. Entitlement breeds, nay emboldens a tyrant who rants and raves for “no good reasons.” Perhaps too much early is too little, late. Perhaps, for these so enabled, reality is a dystopian environment away from the carefully crafted utopia.

So, is empathy a double-edged sword? I think too much is! Compassion on the other hand is indeed the right sentiment. To help those down on their luck, health and wealth. A false compassion is akin to excess empathy. And from such empathic disguise come the demands of tyrants. Lest it be forgot, empathy can be used as a primal tool for self-serving public figures as well. Be very careful when you hear the words “For the Public Good.” There is much sinister in that.



Should we therefore pull out this signpost and abjure empathy? No, not really! We should instead be careful in how we blow on empathy’s trumpets. Misusing empathy, as those vested heavily in psychopathology do, is immoral at best and an unjust dispensation of subliminal influence to manipulate and/or marginalize. It is important not to be pulled into the masquerade of this form of willfully blind passion. Empathy should not be made as catch-all term for human folly and failing. 

To apprehend the real inherent virtue of the empathic emotion rather than one invoked by journalistic kaleidoscopic force du jour of the pseudo-intellectual, who aims to gain from it, carries with it the art of critical thinking. 


Be compassionate towards others, rather than just “feel” for someone, and always know the difference.

Sunday, January 1, 2017

SURVIVORSHIP BIAS

My inclination is to stop here, but my bias propels me to continue, as with most of humanity, bias holds sway.



I write about the pervasiveness of pseudoscience bridging the gap between the known knowns and the unknown unknowns. The bridge is made of ropes and missing wooden planks from peak to peak across a deep chasm of mist and a rocky river below. And yet false science continues to replace the missing planks as they fall off trying to keep the path opened between what is and what is not.



We live in a world filled with survivorship bias. We accumulate data and call it evidence. We add to the burgeoning asymmetry of information and call it fact. The nuance of such charlatanism is lost on the populace as the deluge of information overcomes doubt in most minds. But there it is. It is still, bias.

Remember Amgen a pharmaceutical company failed to verify 46 of the landmark 53 studies and the iconoclastic John Ionnadis searched the literature and discovered that 53% of all the “important” studies could not be validated?



Those two findings are the hallmark of the crumbling bridge of bias. In medicine we have fought our way from the basic science to the science of probability. And even though that gives us reasons to pursue a hypothesis, it does not become a tested fact. Survivorship bias is alive and well in the field of medicine as in science. Even met analytical studies include a larger subset of "positive" studies to prove the Author's bias. More and more articles are written only to prove through statistical fiat that a product, a drug or an action has merit. No negative studies are printed. It is akin to the Morningstar assessment of the Bond funds. If one only continues to monitor the surviving bond funds and does not add the bankrupt ones then the optimistic advantage is easily leant to those managers that are still in the game. Such biases can bring in double digit percentage of benefit to those who survive and make them look like heroes; just by surviving the time duration being tested. Just like nominal returns differ greatly from real returns and a perfectly timed market yields very high returns based on retrospective analysis, survivorship bias falls prey to the travails of such fallacies.



I am not going to belabor this monolog more than it needs to be. It is meant to tweak the critical thinking lens of those who dare to aspire a better understanding in the halls of current scientific inquiry and literacy. The misinformed, misguided few can stoke the emotions of the well-meaning many and visit an ocean of storms of untold misery upon the rest.


As Abraham Wald did during WWII, maybe we should look at the fighters that never came back and ask the question, Why! Why armor plating the engines is a better idea than the fuselage where the bullet holes show damage? Maybe we will learn as he did, that fighters that did not return, didn’t because a single bullet to the engine sealed the fate for the pilot and his aircraft.



So for all those piloting the future of health, plots of the forests that you see in well-meaning high impact journals, it would behoove us to take the time to see where the bias resides before making decisions on other’s lives and livelihoods.


Truth matters!

Saturday, December 17, 2016

WHAT IS EVIDENCE?

From Aristarchus of Samos’ 3rd century BC geocentric concepts to Copernicus and Galileo to Johannes Kepler’s heliocentrism, science is always in a state of exploration and flux. Whether it is in the Newtonian mechanics of force and gravity to the Quantum mechanics of ethereal entanglements, humans have dared to go further, taking the road less travelled. Today’s scientific world, bowing at the altar of evidence seems forcing itself into an exile of the ossified “what is.” Yet evidence is fluid and ever-changing. Today’s evidence is tomorrow’s discard.



What if we could harness the miseries of cancer by turning on and off genes? Well that has been done. What if we could shut down pathways from the surface of the cancer cell to its innards; the nucleus, and stop it from dividing? Done that too. What if we could suppress the oncogenes that trigger the cancer cell growth? Done that as well. What if we could grow a battalion of tumor suppressor genes within the cell to prevent its doubling and dividing? Well we seem to be there now. And what if we could shut down the cargo proteins from transporting material in and out of the cells to allow them to bloat and die? We might be there as well. You see, don't you, that science progresses on the shoulders of giants in a drip, drip fashion; one idea igniting another thought and then another and then empiricism begins...if one would allow it, that is. (BTW: I have NO Conflict of interest with the Karyopharm Therapeutics). 



A drug called Selinexor (KPT-330) made by Karyopharm Therapeutics seems to fit the bill. It has been used in Multiple Myeloma with significant results in previously heavy-treated patients with Multiple Myeloma and found a 20% Response Rate. That may not appear significant unless one thinks about the previous heavy therapeutic exposure. (STORM Trial Data). Additionally Selinexor has been used in Diffuse Large B-Cell Lymphoma and initial reports are seeing benefits there as well. “To date, Selinexor has been administered to more than 1800 patients across company-sponsored and investigator-sponsored clinical trials. Evidence of single-agent anti-cancer activity has been observed in many patients and Selinexor has been sufficiently well-tolerated to allow several of these patients to remain on therapy for prolonged periods. Over 20 patients have remained on study for over 12 months, with the longest patients on study for over 24 months” (1). In the solid tumor world there are reports of Selinexor having some impact in Sarcomas. (2).



Another mode of action being utilized by the same pharmaceutical agency is to inhibit the cargo protein transit. Two products, PAK4 and NAMPT “causing co-inhibition by catalyzes the rate-limiting step in one of the two intracellular salvage pathways that generate nicotinamide adenine dinucleotide, or NAD. NAD is a universal energy- and signal-carrying molecule involved in mitochondrial function, energy metabolism, calcium homeostasis, anti-oxidation, and paradoxically generation of oxidative stress, gene expression, immunological functions, aging, and cell death. leads to synergistic anti-tumor effects through energy depletion, inhibition of DNA repair, cell cycle arrest, inhibition of proliferation, and ultimately apoptosis.”

So harnessing the tumor suppressor elements and blocking the cargo movement shuts down the process of cell division. In biz terms it would be like a block in the supply chain of materials, inventory drops, revenue diminishes and sustainability is questioned.

This brings me back to the premise of using “evidence” as a hard and fast rule in treating patients. Science is continuously evolving due to exploration and discovery. The limits are only those of the limits of thought. Maria Sklodowska better known as Marie Curie who founded the science of Radioactivity, twice a Nobel winner continued to work in refining the knowledge till her last breath. Evidence to her was a snapshot in time of what we know at the moment. The "why" always tinkered with her thought process and pushed her into her intellectual grist mill. So today's well versed bureaucrats constantly serving the "public's best interests" seem to forget what made today's progress and achievements. Limiting progress under the guise of guidelines and templates to achieve uniformity thus limits the art and stifles the science of science and medicine.

The two examples above are how progress flows, never in a straight line but through tortuous paths hitting pay-dirt sometime and sometime just dirt. The idea to illustrate such principles of thought needs historical background and a future unseen but imagined foreground. To limit our knowledge within the pages of books is akin to imprisonment of the soul of discovery. Our thoughts and ideas need to skim the surface of information and thus enter the depth of newer spheres. Perhaps we should consider the innovator, discoverer in all of us physicians and continue to explore venues unseen, unheard and unknown rather than punch time clocks, check boxes and fill our eyes with the glow of the flickering computer screens.