Early termination of drug trials

BMJ 2007; 334 doi: https://doi.org/10.1136/bmj.39113.534919.80 (Published 15 February 2007) Cite this as: BMJ 2007;334:326
  1. Gorm Boje Jensen (gorm.jensen@hvh.regionh.dk)1,
  2. John Hampton, emeritus professor of cardiology2
  1. 1Department of Cardiology, Copenhagen University Hospital, 2650 Hvidovre, Denmark
  2. 2Queen's Medical Centre, Nottingham NG7 2UH

    What are the ramifications for drug companies and drug safety monitoring boards?

    In December 2006 a randomised controlled trial of torcetrapib (a cholesteryl ester transfer protein inhibitor aimed at increasing high density lipoprotein cholesterol) was stopped after an unexpected increase in mortality in people taking the drug.1 The implications are widespread, ranging from the future direction of cardiovascular prevention, the willingness of drug companies to develop new drugs in the face of massive financial risk, to the role of data and safety monitoring boards.

    More than 12% of global mortality is caused by coronary heart disease.2 Reduction of low density lipoprotein cholesterol with statins has been successful in primary and secondary prevention of such disease, although mortality rates remain high. Because high density lipoprotein cholesterol is inversely associated with risk of cardiovascular disease, much investment has gone into newer drugs that increase concentrations of high density lipoprotein cholesterol (such as torcetrapib).

    Phase II trials found that torcetrapib increases high density lipoprotein cholesterol in a dose dependent manner when given with3 and without statins, and smaller trials found no significant increase in adverse events.34 High density lipoprotein increases by 46% with 120 mg torcetrapib daily (P<0.001) and 106% with …

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