xColorectal cancer (CRC) is common, affecting >40,000 people a year in the UK. Most cancers are sporadic but a few, such as those occurring at a younger age, have a clear genetic basis. Most are situated in the rectum or rectosigmoid and cause rectal bleeding, often with a looser or more frequent stool. Right-sided cancers typically result in anaemia, because the blood in the stool is occult and unnoticed by the patient. Almost all symptoms of malignancy can also be caused by benign disease. Diagnosis relies on luminal imaging, with colonoscopy being the gold standard.
In April 2001, Druker et al. reported a targeted therapy for chronic myelogenous leukemia. Based on the knowledge that BCR-ABL, a constitutively activated tyrosine kinase, causes CML, the authors tested with success an inhibitor of this tyrosine kinase in patients who had failed first-line therapy. The finding helped begin the era of designing cancer drugs to target specific molecular abnormalities.[18]
In the early 2000s, the New England Journal of Medicine was involved in a controversy around problems with research on the drug Vioxx. A study was published in the journal in November 2000 which noted an increase in myocardial infarction amongst those taking Vioxx.[27] According to Richard Smith, the former editor of the British Medical Journal, concerns about the correctness of that study were raised with the journal's editor, Jeff Drazen, as early as August 2001. That year, both the US Food and Drug Administration and the Journal of the American Medical Association also cast doubt on the validity of the data interpretation that had been published in the NEJM.[28] Merck withdrew the drug from market in September 2004. In December 2005, NEJM published an expression of concern about the original study following discovery that the authors knew more about certain adverse events than they disclosed at the time of publication. From the Expression of Concern: "Until the end of November 2005, we believed that these were late events that were not known to the authors in time to be included in the article published in the Journal on November 23, 2000. It now appears, however, from a memorandum dated July 5, 2000, that was obtained by subpoena in the Vioxx litigation and made available to the Journal, that at least two of the authors knew about the three additional myocardial infarctions at least two weeks before the authors submitted the first of two revisions and 4 1/2 months before publication of the article."[29] During the five-year period between publication and Expression of Concern, it has been estimated that Merck paid NEJM as much as US$836,000 for article reprints that Merck used for promotional purposes.[30] The journal was publicly rebuked for its response to the research issues in editorials appearing in publications including the British Medical Journal[28] and the Journal of the Royal Society of Medicine.[31]