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Over a recent six-year period, all but one of the best-selling prescription drugs in the U.S. experienced “substantial” increases in cost, regardless of how long the medicines had been on the market or whether generic competition existed, according to a new study.

Of 49 medicines that were available between 2012 and 2017, the median increase in insurer and out-of-pocket patient costs was 76%. Drilling down further, the researchers looked at the 36 drugs that became available only as of 2012, and they found that costs rose for 28 of them by more than 50%. Prices more than doubled for another 16 medicines. And costs rose at least once, and sometimes twice, each year.

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