{"id":1766,"date":"2026-11-08T18:22:58","date_gmt":"2026-11-09T01:22:58","guid":{"rendered":"https:\/\/www.ghosh.com\/blog\/?p=1766"},"modified":"2026-11-08T18:23:55","modified_gmt":"2026-11-09T01:23:55","slug":"the-average-patient-doesnt-exist","status":"publish","type":"post","link":"https:\/\/www.ghosh.com\/blog\/the-average-patient-doesnt-exist\/","title":{"rendered":"The Average Patient Doesn&#8217;t Exist"},"content":{"rendered":"<div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 fusion-flex-container has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:1248px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-0 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-title title fusion-title-1 fusion-sep-none fusion-title-text fusion-title-size-three\" style=\"--awb-margin-top-small:0px;--awb-margin-right-small:0px;--awb-margin-bottom-small:20px;--awb-margin-left-small:0px;\"><h3 class=\"fusion-title-heading title-heading-left\" style=\"margin:0;\"><strong>How the average hides the patients it harms.<\/strong><\/h3><\/div><div class=\"fusion-text fusion-text-1\"><p>The operation went fine. That was the maddening part.<\/p>\n<p>A tonsillectomy is half an hour of routine surgery, the kind children get every day, and for decades the standard prescription for the pain afterward was codeine \u2014 dosed by weight, checked twice, exactly as the pediatric textbooks said. Parents gave it as instructed. Pharmacists filled it as instructed. Nobody did anything wrong.<\/p>\n<p>And then, in a small number of cases, a child went to sleep and didn\u2019t wake up.<\/p>\n<p>It took years to work out why, and the answer was worse than anyone expected: the dose wasn\u2019t a mistake at all. Codeine itself is inert \u2014 the liver converts it to morphine, using an enzyme called CYP2D6. In most people the conversion is steady and the dose is safe. But a small genetic minority are <em>ultra-rapid metabolizers<\/em>: in them, a textbook dose becomes a flood of morphine, and breathing slows, and sometimes stops. (At the other pole, <em>poor metabolizers<\/em> get almost no relief at all \u2014 children undertreated for pain, quietly, in the same system.)<\/p>\n<p>In 2013, the FDA formally warned that a correctly prescribed dose could kill a child who seemed perfectly normal; by 2017 codeine carried a boxed warning and was contraindicated for everyone under twelve. Not because the average child was in danger \u2014 the average child was fine. The drug was banned because the average dose was lethal for a patient the prescription never looked at.<\/p>\n<p>The dose was right. It was right for a patient who didn\u2019t exist.<\/p>\n<p>Before going further: this is not an essay against averages. Averages are among the most useful tools our species has ever built. Seat belts, iodized salt, vaccination schedules, statins \u2014 population-scale interventions that save millions of lives, and none of them makes sense except as averages. The average is not the problem. The problem is what we do after we compute it: we stop. We treat the summary as if it were the person.<\/p>\n<p>To see how deep that failure runs \u2014 and why it turns dangerous exactly at the edges of a population \u2014 it helps to start not with medicine, but with machines.<\/p>\n<h2>The man who never existed<\/h2>\n<p>In 1950, the U.S. Air Force had a mystery on its hands. Its new jets were mechanically sound, and they were crashing at rates no one could explain. The investigation reports said <em>pilot error<\/em>, over and over, in planes that had nothing wrong with them.<\/p>\n<p>A young researcher named Gilbert Daniels suspected the problem was in the cockpit. It had been designed around the average pilot \u2014 height, limb length, torso, all the dimensions that decide whether a man can see over the nose and reach the rudder pedals. So Daniels and his colleagues did something almost nobody had thought to do: they measured the actual population. More than four thousand pilots, 140 dimensions each, at an Air Force laboratory in Ohio.<\/p>\n<p>Then Daniels asked the question the whole aviation industry had skipped: how many of them were average?<\/p>\n<p>He started with the ten dimensions that mattered most for fitting a cockpit. He defined \u201caverage\u201d generously \u2014 anyone in the middle 30 percent on a dimension counted. Out of 4,063 pilots, the number who fit the average on all ten was zero. Even loosened to any three dimensions, fewer than 3.5 percent qualified. His conclusion, published in a 1952 technical note with a title that reads like an epitaph \u2014 <em>The \u201cAverage Man\u201d?<\/em> \u2014 was that if you want to design for an individual human being, the average is useless.<\/p>\n<p>The crashes weren\u2019t pilot error. The cockpit was built for a man who never existed.<\/p>\n<p>The Air Force\u2019s fix became one of the quiet triumphs of engineering: not a better average, and not a custom jet for every pilot, but <em>adjustability<\/em> \u2014 seats that slide, pedals that extend, straps that cinch. Let the machine meet the person, because the person will never meet the average.<\/p>\n<p>Medicine, unlike aviation, has never fully had that epiphany. And in medicine, the cockpit fits you whether you like it or not.<\/p>\n<h2>The dose and the target<\/h2>\n<p>In 2004, three researchers gave the failure a name: <em>the trouble with averages<\/em>. Writing in the Milbank Quarterly, Richard Kravitz, Naihua Duan, and Jeremy Braslow pointed out that a clinical trial\u2019s average result is not a description of what happens to patients \u2014 it\u2019s a census of wildly different outcomes flattened into one number. Behind an \u201caverage benefit\u201d can sit \u201csubstantial benefits for some, little benefit for many, and harm for a few.\u201d Apply the average to everyone and you give the first group their benefit, the second a waste of hope \u2014 and the third their harm.<\/p>\n<p>Four years later, the harm arrived on schedule.<\/p>\n<p>By the mid-2000s, diabetes medicine had a conviction: lower is better. Population studies showed that, on average, higher glucose meant more complications, so the field set a population target \u2014 push patients toward <em>normal<\/em>, an HbA1c below 6 percent \u2014 and built a trial to prove the obvious. ACCORD enrolled more than ten thousand middle-aged and older patients with long-standing type 2 diabetes and high cardiovascular risk, and randomized them to intensive or standard glucose control.<\/p>\n<p>The intensive arm was stopped early. After three and a half years, more people were dead: 257 versus 203, a 22 percent higher risk of death from the <em>more<\/em> aggressive treatment of the <em>same<\/em> disease. The target that was correct for the population curve was lethal for a meaningful number of the individuals sitting in the chairs. To this day, no analysis has cleanly isolated exactly who was harmed \u2014 which is itself part of the lesson: the average can\u2019t tell you which of your patients it will be.<\/p>\n<p>The aftermath is telling. Not one guideline doubled down. They dropped the universal target and replaced it with individualized ones. The field had rediscovered, in the most expensive way available, that a population\u2019s number is not a person\u2019s goal.<\/p>\n<p>These patients weren\u2019t missed because they fell outside the system. The system worked exactly as designed \u2014 and that was the problem.<\/p>\n<h2>The correction that hid the disease<\/h2>\n<p>There is a second, subtler failure. Sometimes the average doesn\u2019t just mistreat the outlier \u2014 it actively hides the outlier\u2019s danger, so that no alarm ever sounds. For this, look at what may be the most consequential number in medicine: the estimate of your kidney function.<\/p>\n<p>Kidney function is inferred from blood creatinine, and the equations that do the inferring carry assumptions \u2014 age, sex, and, for two decades, race. From the 1990s onward, the standard equations included a \u201ccorrection\u201d that assigned Black patients higher kidney function at the same creatinine, on the assumption of greater average muscle mass. The assumption traced to studies from the 1960s and \u201870s \u2014 potassium content and bone density in a few hundred patients \u2014 and in one of the source studies, ethnicity had been assigned, in the authors\u2019 own words, \u201cprobably by examination of skin color.\u201d<\/p>\n<p>The correction made charts read healthier than kidneys were. In 2020, researchers at two Boston medical centers quantified it in a registry of 56,845 patients. Remove the multiplier, and a third of Black patients \u2014 743 of 2,225 \u2014 would be reclassified into a <em>more severe<\/em> stage of kidney disease. Most consequentially, 64 patients would cross below an eGFR of 20, the territory where kidney-transplant priority begins to accrue. Of those 64 patients, exactly zero had ever been referred for a transplant evaluation. Under the default equation, nearly a fifth of patients at that threshold had been.<\/p>\n<p>No one missed a form. The math ran correctly every time. The equation \u2014 validated on populations, corrected by averages, applied to individuals \u2014 wrote a healthier number on the chart in precise proportion to how far each patient\u2019s body stood from the population the average loved. In 2021, after a national reckoning, the nephrology societies removed race from the equations altogether.<\/p>\n<p>The pulse oximeter fails the same way, at the speed of light. The device clips onto a finger and passes light through it; pigmentation absorbs light, and the devices were calibrated, historically, on populations that were mostly light-skinned. In December 2020, a study in the New England Journal of Medicine examined what the reassuring number was hiding: among patients whose pulse oximeter read \u201cnormal\u201d \u2014 92 to 96 percent \u2014 an arterial blood gas revealed truly dangerous oxygen levels, below 88 percent, in 11.7 percent of Black patients versus 3.6 percent of white patients. A 2024 meta-analysis of 15 studies and more than 730,000 paired measurements found the hidden condition almost twice as common. The FDA warned about the devices in 2021; in January 2025 it went further, proposing that manufacturers be required to demonstrate performance across skin tones.<\/p>\n<p>The number on the screen said <em>normal<\/em>, because the device was built to define normal without that body in it.<\/p>\n<p>This is why the objection \u201cso what, outliers are rare\u201d misreads every one of these cases. These patients were not rare \u2014 they were Black Americans with kidney disease, they were every patient with dark skin and shortness of breath, they were children with one copy of a common gene variant. The harm did not fall on the fringes of a system. It fell on the center of one that had mistaken a population\u2019s shadow for the people in it.<\/p>\n<h2>Not only medicine<\/h2>\n<p>If the pattern were only medical, it would be a tragedy of one field. It isn\u2019t. For decades, crash testing used a single kind of body: the 50th-percentile male. The result, in the NHTSA\u2019s own data: a belted woman in the driver\u2019s seat or front passenger\u2019s seat is about 17 percent more likely to die in the same frontal crash as a man \u2014 and 73 percent more likely to be seriously injured \u2014 partly because seats, belts, and airbags were geometrically built around an average body that women are not. In November 2025, the U.S. announced new crash-test standards that finally incorporate female dummies. The average body had a body count.<\/p>\n<p>And in the softer register, the same default shows up as simple slowness: the roughly 30 million Americans \u2014 one in ten \u2014 with a rare disease wait four to five years on average for a diagnosis, because a system built for the common thing answers an uncommon body with a shrug.<\/p>\n<h2>The honest objections<\/h2>\n<p>Two objections to all this deserve to be answered, because they are right.<\/p>\n<p>The first is <em>the prevention paradox<\/em>. In a famous 1985 essay, the epidemiologist Geoffrey Rose showed that a large number of people at small risk can produce more disease than a small number at high risk \u2014 so population strategies, shifting the entire distribution, prevent more illness than targeting outliers. This is true, and it is the greatest argument for averages ever made. It is also, notice, an argument about populations. Seat belts and iodized salt are correctly designed for the average precisely because no one is fastening a seat belt <em>into<\/em> an average body. The prevention paradox tells a government what to do. It does not tell a doctor what to do at 2 a.m. with one patient, one liver, and one number.<\/p>\n<p>The second objection cuts the other way: perhaps individualization is not the cure its marketers claim. Fair. When researchers tested genotype-guided dosing of warfarin against a well-built clinical algorithm in a randomized trial, it didn\u2019t win. And in 2020, a review in the Lancet Digital Health looked at 927 machine-learning \u201cprecision medicine\u201d papers and found that none had yet made a genuine difference in practice. The lesson of \u201ctreat the individual, not the average\u201d has too often been sold as a product \u2014 an algorithm, a gene panel, a subscription \u2014 rather than what the evidence actually supports.<\/p>\n<p>But look again at every fix in this essay: a contraindication for children under twelve. An individualized glucose target. A corrected equation. A clip-on device made to read darker fingers. An adjustable seat. Not one of them required precision medicine. They required noticing that the average had stopped being safe, and using information that was already in the room.<\/p>\n<h2>The adjustable seat<\/h2>\n<p>Zero out of 4,063. Daniels\u2019 number is not about pilots. It is a statement about what an average is: a summary, a starting point \u2014 the widest possible net thrown over the most possible people. It was never a person, and the moment we treat it as one, we are designing cockpits for the dead center of a dataset and blaming the people who don\u2019t fit.<\/p>\n<p>The whole record in this essay \u2014 the deaths, the hidden hypoxemia, the un-referred patients, the injured women \u2014 comes down to two questions that any practitioner can carry:<\/p>\n<p><strong>Is this patient\u2019s variation structured or noise?<\/strong> If it\u2019s structured \u2014 genotype, body, age, pigmentation, illness \u2014 the average alone is unsafe, and the specific check is the treatment.<\/p>\n<p><strong>If I\u2019m wrong, is the cost symmetric?<\/strong> When missing a danger costs more than double-checking, treat the \u201cnormal\u201d reading as provisional.<\/p>\n<p>The average is a starting point, never a stopping point.<\/p>\n<p>That is all the Air Force understood, seventy years ago, that we keep forgetting. They didn\u2019t fix the crashes with a better average. They fixed them by admitting nobody was average \u2014 and building machines that could meet each pilot where he sat.<\/p>\n<h2>Sources<\/h2>\n<ul>\n<li>The ACCORD Study Group. \u201cEffects of Intensive Glucose Lowering in Type 2 Diabetes.\u201d <em>New England Journal of Medicine<\/em>, 2008. \u2014 <a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa0802743\" target=\"_blank\" rel=\"noopener\">https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa0802743<\/a><\/li>\n<li>Kravitz, Duan &amp; Braslow. \u201cEvidence-Based Medicine, Heterogeneity of Treatment Effects, and the Trouble with Averages.\u201d <em>Milbank Quarterly<\/em>, 2004. \u2014 <a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC2690188\/\" target=\"_blank\" rel=\"noopener\">https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC2690188\/<\/a><\/li>\n<li>Daniels, G. S. \u201cThe \u2018Average Man\u2019?\u201d Wright Air Force Base technical note, 1952. (DTIC AD0010203; retold in Todd Rose, <em>The End of Average<\/em>, 2016.)<\/li>\n<li>S. Food and Drug Administration. Drug safety communications on codeine in children, 2013 and 2017 (boxed warning; contraindicated under 12). Corroborated: \u201cImpact of the 2017 FDA Drug Safety Communication on Codeine Prescribing.\u201d \u2014 <a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC9647590\/\" target=\"_blank\" rel=\"noopener\">https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC9647590\/<\/a><\/li>\n<li>\u201cExamining the Potential Impact of Race Multiplier Utilization in Estimated GFR Calculation on African-American Care Outcomes.\u201d 2020. \u2014 <a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC7878608\/\" target=\"_blank\" rel=\"noopener\">https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC7878608\/<\/a> ; equation change: Inker et al., <em>NEJM<\/em>, 2021.<\/li>\n<li>Sjoding, M. W. et al.\u00a0\u201cRacial Bias in Pulse Oximetry Measurement.\u201d <em>NEJM<\/em>, 2020. \u2014 https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC7808260\/ ; meta-analysis: <em>Journal of General Internal Medicine<\/em>, 2024. \u2014 https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC11436614\/ ; FDA skin-tone guidance proposal, Jan 2025. \u2014 <a href=\"https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-proposes-updated-recommendations-help-improve-performance-pulse-oximeters-across-skin-tones\" target=\"_blank\" rel=\"noopener\">https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-proposes-updated-recommendations-help-improve-performance-pulse-oximeters-across-skin-tones<\/a><\/li>\n<li>Selvin, E. et al.\u00a0\u201cAssociation of Sickle Cell Trait With Hemoglobin A1c in African Americans.\u201d <em>JAMA<\/em>, 2017. \u2014 <a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC5713881\/\" target=\"_blank\" rel=\"noopener\">https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC5713881\/<\/a><\/li>\n<li>Consumer Reports, \u201cA Crash Test Bias Puts Female Drivers at Risk,\u201d 2019 (NHTSA data); <em>New York Times<\/em>, \u201cU.S. Introduces New Female Crash-Test Dummy Standards,\u201d Nov 2025.<\/li>\n<li>Rose, G. \u201cSick Individuals and Sick Populations.\u201d <em>International Journal of Epidemiology<\/em>, 1985.<\/li>\n<li>Kimmel, S. E. et al.\u00a0(COAG). \u201cA Pharmacogenetic versus a Clinical Algorithm for Warfarin Dosing.\u201d <em>NEJM<\/em>, 2013. \u2014 <a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC3942158\/\" target=\"_blank\" rel=\"noopener\">https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC3942158\/<\/a><\/li>\n<li>\u201cTime to reality check the promises of machine learning-powered precision medicine.\u201d <em>Lancet Digital Health<\/em>, 2020.<\/li>\n<li>Chung et al.\u00a0\u201cA guide for the diagnosis of rare and undiagnosed disease.\u201d <em>Journal of Medical Genetics<\/em>, 2021. \u2014 <a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC8883622\/\" target=\"_blank\" rel=\"noopener\">https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC8883622\/<\/a><\/li>\n<\/ul>\n<\/div><\/div><\/div><\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":1768,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[59,39],"tags":[],"class_list":["post-1766","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health","category-life"],"_links":{"self":[{"href":"https:\/\/www.ghosh.com\/blog\/wp-json\/wp\/v2\/posts\/1766","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ghosh.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ghosh.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ghosh.com\/blog\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ghosh.com\/blog\/wp-json\/wp\/v2\/comments?post=1766"}],"version-history":[{"count":5,"href":"https:\/\/www.ghosh.com\/blog\/wp-json\/wp\/v2\/posts\/1766\/revisions"}],"predecessor-version":[{"id":1772,"href":"https:\/\/www.ghosh.com\/blog\/wp-json\/wp\/v2\/posts\/1766\/revisions\/1772"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.ghosh.com\/blog\/wp-json\/wp\/v2\/media\/1768"}],"wp:attachment":[{"href":"https:\/\/www.ghosh.com\/blog\/wp-json\/wp\/v2\/media?parent=1766"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ghosh.com\/blog\/wp-json\/wp\/v2\/categories?post=1766"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ghosh.com\/blog\/wp-json\/wp\/v2\/tags?post=1766"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}