seduced by surrogate markers

Seduced by Surrogate Markers

Medical prowess in acute and emergent care is no less than heroic. Where once a heart attack or severed limb might spell the end of life, now it may be no more than a minor setback. Advances in medical technology and innovation have led to robotic surgeries, replacement joints and cardiac pacemakers becoming, not the stuff of science fiction, but commonplace. Imaging technologies allow us to see what was previously unseen and advances in laboratory testing, allow the measurement of more and more compounds. We have software to calculate patterns from enormous data sets; software to predict disease; even software that can render a diagnosis on par or better than most physicians and quickly link pharmaceutical or other medical treatments to the designated disease. By all intents and purposes, we have become masters of modern medicine. This was no small feat, considering a little over 150 years ago, the simple notion of washing one’s hands between patients was considered heretical, as was the idea that essentially invisible microorganisms might be responsible for illness. Modern medicine has come a long way, indeed.

Perhaps bolstered by these advances, we lost track of the most basic components of health. We are living longer, sure, at least until recently, but whether we are living healthier remains open to debate, due in no small measure to how we define health. For the last several decades, medicine has relied increasingly on what are called surrogate markers, things like blood pressure, body mass index (BMI), cholesterol, blood glucose, etc., to define health. The thinking is that these markers represent some aspect of health, and thus, if they fall within a normal range, then one can be considered healthy. Whether one has to achieve those results using a myriad of medications, all of which have side effects, is unimportant. The critical point is that for health, we must meet those surrogate markers. We must weigh a certain amount and blood pressure, cholesterol, glucose, liver enzymes and the like, must fall within designated parameters. If they do not, then something is amiss.

On the surface, these markers appear to be legitimate indicators of health or disease. Certainly, at the tail ends of any curve, at the lowest of lows and the highest highs, evidence of an underlying disease process is clearer with surrogate markers. Where we run into problems is not at the extremes, but in the ever dwindling middle and at the cutoffs between what is considered normal or healthy and what is considered pathological. Here, nothing is as black and white as it appears. Innumerable variables come into play, some having nothing to do with medicine or evidence, and frequently, everything to do with garnering drug approval. That is, drug makers define and test their drugs against the surrogate markers of disease that their drugs were designed manipulate; not against the health of the patient or a reduction in morbidity or mortality, but against the marker.

This is problematic for any number of reasons, not the least of which is the power that this affords organizations with indisputable economic interests. As the arbiters of health guidelines spuriously tied to the use of their products, these companies effectively foreclose any and all rational thought about their products beyond the obvious: does the drug alter the surrogate marker in the manner suggested? If so, it can be considered effective, and to the extent that the other effects of the drug can be obfuscated successfully, it can be considered safe too.

To that end, between 2010 and 2012, the FDA says it approved 45 percent of new drugs on the basis of a surrogate endpoint. Surrogate measures have become the norm in several disease processes. One analysis showed that 67% percent of cancer drug approvals over a five-year period were based on surrogates. This is despite that fact that only 12% of these drugs improved patient survival. Similarly, from 2003 to 2012 the FDA used surrogates for seven out of nine drugs approved for chronic obstructive pulmonary disease, all 26 approved drugs for diabetes, and all nine drugs approved for glaucoma; in only a few cases did surrogate measures predict actual benefits for patients. Inasmuch as physicians rely on prescribing guidelines established by these trials and to the extent that they are adopted by the various medical societies and insurer and even electronic health records companies, surrogate markers quickly become the established tenets of health; so much so, that few question their legitimacy, at least for the first several years, and often never.

Consider just how many tenets of modern medicine are based upon overly simplistic representational markers of disease that do little to identify or correct the root cause of illness and are only cursorily tied the disease process in question, but because there are medications available to manipulate that marker, its parameters define health versus disease and curtail any further discussion. For treatment of type 2 diabetes, as an example, a condition caused largely by diet and lifestyle choices and no small degree of high calorie malnutrition, there are approximately 158 drugs currently on the market to manipulate blood sugar levels to give the approximation of health. Each of these medications comes with its own host of side effects, capable of inducing diseases processes anew for which additional medications will be added. None of these drugs address the root cause of the disease; none improves the health of the patient, but they manage its surrogate markers and often do so quite well.

The converse is also true. When a patient presents with symptoms that are undetectable by current diagnostic parameters using the acceptable surrogate markers, they can be considered healthy even when symptoms suggest otherwise. In these cases, so strong is the assumption that modern medicine has identified and perfected its diagnostic tools and its markers, that when these tools fail to identify illness, the default diagnosis is the familiar ‘all in the head syndrome’; a diagnosis afforded an ever-increasing percentage of individuals with chronic or complicated illnesses for which medicine has no response.

While it is true that surrogate markers can provide a window into a disease process and offer us glimmers of what might be happening, they rarely tell us what caused the disease process, why it progressed in the manner it did, or most importantly, how to heal from it. All they tell us is that something may or may not be awry, depending upon the validity of the marker, and point to the medications that will manipulate that marker. When those medications place the marker into the designated acceptable range, but do nothing to improve the health of the patient, and indeed, often worsen it, all that can be offered are additional medications. It becomes an interminable cycle of pain and suffering with limited returns for either the patient or the physician.

Despite these limitations or perhaps because of them, surrogate markers have come to dominate modern medicine, and in so doing, have precluded more rational thought about health and disease. A disease process is either identifiable by accepted markers and remediable with current therapeutic options or it simply does not exist and the patient is crazy. It is a zero sum proposition; one that has done much to harm the field of medicine and its practitioners despite the obvious gains in economic fortune and sovereign authority for both.

I would argue that reliance on these markers, not only forestalls independent thinking, but also, fundamentally robs us of our humanity. Their use detaches us from the realities of illness; first from the language, then from imagination, and finally, from any sense of humility regarding our own intellectual shortcomings. For once those markers are mastered, we too become masters, and heady with our own sense of accomplishment, become unwavering in our certainty. This is a dangerous position. Here, the incontrovertible rightness of our reason hijacks our humanity and we no longer see or even sense the suffering that stands before us.

When the boundaries of what can be known about an illness are predefined by rules and descriptors several steps removed from the actual illness, the ability to see the illness for what it is becomes impossible. The ability to think through its mechanisms and conceptualize a path towards resolution is constrained to manipulation of the accepted markers. The language of the labs defines what can be known. Perhaps it is unconscious at first, at least for the practitioner and especially for the patient, but over time, it becomes easier to bathe in the simplicity of the predefined, than question the limitations of understanding. That is the seduction of surrogates. They give us an illusion of competence, control, and success without any of the pesky attributes of reality attached. In so doing, they rob us of agency, humility, and humanity.

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Chandler Marrs, PhD

Chandler Marrs MS, MA, PhD spent the last dozen years in women’s health research with a focus on steroid neuroendocrinology and mental health. She has published and presented several articles on her findings. As a graduate student, she founded and directed the UNLV Maternal Health Lab, mentoring dozens of students while directing clinical and Internet-based research. Post graduate, she continued at UNLV as an adjunct faculty member, teaching advanced undergraduate psychopharmacology and health psychology (stress endocrinology). Dr. Marrs received her BA in philosophy from the University of Redlands; MS in Clinical Psychology from California Lutheran University; and, MA and PhD in Experimental Psychology/ Neuroendocrinology from the University of Nevada, Las Vegas.

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