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But sometimes a clinical database is so large that a parameter common to both efficacy and safety can be quantified with reasonable certainty: myocardial infarction (MI) is used here as an example. Recently the Food and Drug Administration (FDA) proposed set limits for the incidence of MI as a safety threshold for diabetes treatment. Setting a threshold before something is considered as a safety concern opens the possibility of setting a threshold for clinically important efficacy. When a parameter is common to both safety and efficacy, then logically a unit change in either direction should be of equal weight in the risk and benefit analysis. For example, a doubling in the incidence of myocardial infarction as a safety signal should be given equal weight to the halving of the incidence of myocardial infarction as an efficacy signal. Similarly, if FDA guidance suggests that a less than a 30% increase in the incidence of MI as a safety parameter is considered acceptable, for example for diabetes treatment, when there is no other major toxicity, this opens a debate about a possible inverse threshold for clinical benefit for drugs that reduce a risk factor, such as antihypertensives.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2012.04265.x","type":"journal-article","created":{"date-parts":[[2012,3,8]],"date-time":"2012-03-08T16:09:46Z","timestamp":1331222986000},"page":"757-761","source":"Crossref","is-referenced-by-count":11,"title":["Symmetrical analysis of risk\u2013benefit"],"prefix":"10.1111","volume":"74","author":[{"given":"John B.","family":"Warren","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Day","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Feldschreiber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,10,9]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/oso\/9780199534678.003.0006","volume-title":"The Law and Regulation of Medicines","author":"Warren JB","year":"2008"},{"key":"e_1_2_8_3_2","unstructured":"Food and Drug Administration.Guidance for Industry. 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