{"id":44784,"date":"2019-06-07T10:03:19","date_gmt":"2019-06-07T09:03:19","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=44784"},"modified":"2019-06-14T11:43:27","modified_gmt":"2019-06-14T10:43:27","slug":"jeffrey-aronson-when-i-use-a-word-biomarkers","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2019\/06\/07\/jeffrey-aronson-when-i-use-a-word-biomarkers\/","title":{"rendered":"Jeffrey Aronson: When I use a word . . . Biomarkers\u2014definition and uses"},"content":{"rendered":"

\"jeffrey_aronson\"<\/a>Many clinical outcomes, both primary and secondary, which I <\/span>discussed<\/a> two <\/span>weeks ago, are not the desired outcomes, but markers of such\u2014surrogate markers or biomarkers.<\/span><\/p>\n

The term \u201cbiomarker\u201d comes from the Greek combining form \u03b2\u03b9\u03bf-, from <\/span>\u03b2\u03af\u03bf\u03c2 <\/span>life, and Old English forms of words meaning a mark, such as mearc. The IndoEuropean root MERG meant a boundary or border, which is what \u201cmark\u201d originally meant in English. Any object that indicated the position of a boundary was then called a mark, and the word was later extended to any indicator. Whence countermark, remark, and remarkable. A marque is the mark of a brand, especially a brand of car. Marquetry is fancy marks on furniture. A margin was also a border; white cells are marginated when they adhere to the sides of blood vessels. A march was another kind of border, typically that between England and Wales or England and Scotland. To demarcate is to draw a border. Margraves, marquises, and marchionesses owned or ruled over borderlands. A Celtic variant, MROG, territory or land, gives us the Welsh name for Wales, Cymru, and its nationalist party, Plaid Cymru. <\/span><\/p>\n

The term \u201cbiomarker\u201d emerged in the 1970s, for example in the title of a 1973 <\/span>article<\/span><\/a>, referring to the presence of material of biological origin. It continues to be used in this way in geological and ecological texts. An early clinical example, from 1977, is in a publication titled \u201cTumor biomarkers of value in the management of gynecologic malignancy will also be correlated with clinical course\u201d. However, the concept itself is much older. For example, there are references to \u201cbiochemical markers\u201d in <\/span>1949<\/span><\/a> and to \u201cbiological \u2018markers\u2019\u201d in <\/span>1957<\/span><\/a>. The figure below shows how interest in biomarkers has burgeoned in the last 15 years or so.<\/span><\/p>\n

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Figure 1.<\/b> Numbers of publications since 1975 containing the term \u201cbiomarker\/s\u201d or any of the alternative terms listed below (source PubMed); the increase since 2005 has been so steep that about half of all the publications have appeared since 2014; the numbers and the shape of the curve are strikingly similar to those of \u201cprimary outcomes\/endpoints\u201d and \u201csecondary outcomes\/endpoints\u201d, which I <\/span><\/i>published<\/span><\/i><\/a> two weeks ago<\/span><\/i><\/p>\n

There is a gallimaufry of terms that have been used to describe the concept of biomarkers. They include \u201cbiological markers\u201d, \u201csurrogate markers\u201d, \u201csurrogate endpoints\u201d, \u201csurrogate response variables\u201d, \u201cintermediate endpoints\u201d, \u201cintermediate markers\u201d, \u201cbiomarker endpoints\u201d, and even \u201cintermediate marker endpoints\u201d. Robin Ferner and I have <\/span>proposed<\/span><\/a> that \u201cbiomarker\u201d should replace all of these, defined as follows:<\/span><\/p>\n\n\n\n
biomarker, n. \/\u02ccb\u028c\u026a\u0259\u02c8m\u0251rk\u0259r\/ A biological observation that substitutes for and ideally predicts a clinically relevant endpoint or intermediate outcome that is more dif\ufb01cult to observe. [ancient Greek \u03b2\u03b9\u03bf- combining form, life + Old English mearc, a boundary, a limit +-er suf\ufb01x]<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

In this definition, the phrase \u201cdif\ufb01cult to observe\u201d encompasses dif\ufb01culties with outcomes that are, for example, hard to access or temporally remote.<\/span><\/p>\n

The various uses of biomarkers include:<\/span><\/p>\n