Out of order: When numbers fail

What is normal?

 

The question may sound absurdly philosophical, particularly for the pages of DDNews, and yet healthcare directly or indirectly deals with this question on a daily basis. And the clinical response can be as life-altering as the societal and political responses that we see on the news every night.

 

An entire industry has been created to test and monitor health using various diagnostic assays, to the most recent of which DDNews dedicates an entire section. In some cases, the results of these assays are binary—the classic example is being a little bit pregnant. But in most cases, healthy (or normal) falls within a range of values—think LDL/HDL, blood glucose or body temperature.

 

In part, this is a recognition that results can vary within an individual throughout the day, and on the larger scale, because individuals are products of their genetics and environments. What might be a healthy level for me in Toronto may actually be limiting in Johannesburg.

 

But even with the recognition of variability, we must always be vigilant in questioning how the normal range was defined. Was it based on the combined results of 200 male Manitoba bush pilots (I have read such a study), or a sampling of tens of thousands of individuals from around the world? If only for economic reasons, the former is more likely to be the case.

 

In 2011, Boston University’s Shalinder Bhasin and colleagues examined this challenge by identifying reference ranges for testosterone in healthy men. Suggesting that these ranges “have been derived previously mostly from small convenience samples or from hospital or clinic-based patients,” they examined a much larger cohort from the Framingham Heart Study (Gen 3), publishing their results in the Journal of Clinical Endocrinology & Metabolism.

 

Although most values were consistent with historic values, their lower limit of total testosterone was higher than that used historically but was “closer to the thresholds associated with sexual and physical symptoms in a recent investigation of older men.” Thus, when it comes to testosterone, it seems (sample) size matters.

 

But what about the outliers, the norms who don’t fit the norms and the unwell who do?

 

As a bit of a sidestep, just over a year ago, the International Association of Athletics Federations (IAAF) banned Indian sprinter Dutee Chand from competing in sanctioned competitions because her blood testosterone levels fell into the normal range of male athletes rather than that of her female competitors. Thus, the group decided, she would have an unfair advantage over her fellow runners.

 

What made this ruling particularly challenging, however, was that Chand’s testosterone levels were natural; they did not come about from doping. Her levels simply fell outside of the clinically accepted norm for women.

 

Closer to home for me are two friends who live with symptoms of hypothyroidism and have resorted to alternative medicine because they were dissatisfied with the medical establishment. In both cases, standard thyroid function tests suggest they fall within the normal range and therefore would not benefit from standard treatment. This may be true, but neither knows because it was never tried.

 

Admittedly, these are anecdotes. Three women struggle because they do not fit ascribed definitions, whether of health or pathology. And for every anecdote I can list, the healthcare establishment can rightly point to hundreds if not thousands of individuals who fit the defined ranges of normalcy.

 

It’s a conundrum I have discussed previously: healthcare is population-based while health is personal.

 

In our zeal to standardize healthcare and make medicine more scientific, we have to be careful not to ignore the natural variabilities of individuals within those populations. So-called normal ranges should suggest action, not dictate it.

 

Even as we pursue the precision medicine mandate, spending billions (and possibly trillions) of dollars on expanding our understanding of human biology and generating technologies to value every facet of it, we have to make sure that our knowledge doesn’t blind us to the patient’s truth. If that happens, if all we accomplish is a bigger monolith, then we have failed in the mission.

 

As to Chand’s racing career, the Court of Arbitration in Sport recently overturned the IAAF’s rule, giving them two years to prove that the higher testosterone levels truly give the runner an unfair advantage.