Uncertainty in Medicine: An Endocrinologist’s Perspective

decision tree
decision tree
The role of uncertainty in clinical practice, and its implications for physicians, is thoughtfully examined by an endocrinologist in this opinion piece.

“Medicine is a science of uncertainty and an art of probability.” —William Osler, MD

We all know that uncertainty plays a prominent role in medicine, especially in clinical practice. There are so many things we do not yet know or have a solid explanation for. In clinic, for instance, we do not always know whether a patient will adhere to our recommendations, why EMPA-REG demonstrated a reduction in cardiovascular events, or whether a medication change we recommend to a patient struggling to improve her glycemic control will be effective, and to what degree.

Yet, we — both patients and physicians — are uncomfortable with uncertainty. Is that not what has been ingrained in us since medical school?

Arabella L. Simpkin, BM, BCh, and Richard M. Schwartzstein, MD, authors of a perspective piece published in the New England Journal of Medicine, noted:

“Although physicians are rationally aware when uncertainty exists, the culture of medicine evinces a deep-rooted unwillingness to acknowledge and embrace it. Embodied in our teaching, our case-based learning curricula, and our research is the notion that we must unify a constellation of signs, symptoms, and test results into a solution. We demand a differential diagnosis after being presented with few facts and exhort our trainees to ‘put your money down’ on a solution to the problem at hand despite the powerful effect of cognitive biases under these conditions. Too often, we focus on transforming a patient’s gray-scale narrative into a black-and-white diagnosis that can be neatly categorized and labeled. The unintended consequence — an obsession with finding the right answer, at the risk of oversimplifying the richly iterative and evolutionary nature of clinical reasoning — is the very antithesis of humanistic, individualized patient-centered care.”

The authors make a substantive case for not only acknowledging the uncertainty inherent in medicine but also preparing those we teach to be comfortable with navigating through its waves. I try to teach my students and residents that we must embrace uncertainty in medicine.

At first glance, dealing with uncertainty appears to involve binary options. We can:

1. Push back against it.

Is this not, in some ways, the default? Some patients want — no, they (at times) clamor for — certainty. They see us depicted on television or in the movies as white-coated paragons of answers, where, as in a good detective story, all clinical mysteries are neatly solved in 60 minutes, minus time for commercials. “If I can just get a test, a blood test, a magnetic resonance imaging scan, to tell me what’s wrong and why,” you hear.

Denying uncertainty is like sticking your head in the sand. Some patients do this out of fear: “I’m going to keep doing what I’m doing” — or not doing — they say. They are leaning on what they know, rather than venturing out with a toe in the unknown, and with the potential promise of a greater quality of life or taking back control over their diabetes.

Yet, sometimes, what we truly know is that we do not know.

2. Embrace it.

To some degree, we all have to make peace with this and reconcile ourselves with the fact that we may not ever completely know for sure why someone’s A1c skyrocketed or plummeted. This is challenging not only for patients but also for physicians. At some point, even with incomplete historical or laboratory information, we have to stop analyzing and commit: to our working differential diagnosis, or to a treatment course to start. We can still push forward, despite uncertainty, and do our best, adjusting course when needed.

Do we not have to contend with this in other spheres, such as research? I’ve been leading a research study that has been the epitome of uncertainty. We received more grants than initially expected — a pleasant outcome. Not long after learning that news, our team ran right into delays with institutional review board approval, equipment malfunctions, and hiring a clinical study coordinator.

Everything was ultimately resolved, but it took longer than anticipated. Recently, different technical issues cropped up, which the engineers are still deciphering. Among our challenges is how to spend down funds without a precise idea of when we can start the study procedures. I took the view of optimistic perseverance.

If we change our perspective, by interpreting delays or obstacles as opportunities to learn and to make incremental progress, not only can we be more attuned to potentially developing innovative solutions but also we would enjoy the daily steps along the way.

3. The first 2 paths are reactive. Is there a third way?

Are we conveying this to our trainees — the physicians of tomorrow? Should we anticipate uncertainty, and think in advance of how to deal with it? What about building this into our patient cases for discussion? Or our rounds in the hospital, or our teaching sessions with students, residents, and fellows, in the clinic? Should this be formalized into the curriculum, or taught in a more informal manner? Or both?

Dr Simpson and Dr Schwartzstein advocate for a paradigm shift in how we test our medical students to gauge how they think, not just seeking the “best answer” from among 5 options in a multiple-choice question.

Life itself is rife with uncertainty. Why should we in medicine expect any different?


Simpkin AL, Schwartzstein RM. Tolerating uncertainty — the next medical revolution? N Engl J Med. 2016;375:1713-1715. doi: 10.1056/NEJMp1606402