On 2015 Jan 05, Peter Gøtzsche commented:

Gastrointestinal cancers in the The SOLID-TIMI 52 trial

The SOLID-TIMI 52 trial assessed whether darapladib had any effect on major coronary events compared with placebo (1). A small table of adverse events showed that people on active drug had diarrhea twice as often as those on placebo whereas there was no difference in “any adjudicated gastrointestinal cancer.” Readers may wonder why gastrointestinal cancers were listed in such a small table, as diarrhea doesn’t usually lead to cancer. The word cancer was only mentioned in the table, with no comment in the text as to why. I think the reason for listing it in the table is that studies in rats and mice have shown that they developed jejunal adenocarcinomas – a very rare cancer - after exposure to darapladib (2). This should have been mentioned in the paper. I also believe that the investigators and the sponsor, GlaxoSmithKline, have an ethical duty to follow-up the 13,026 participants in the trial in the coming years to find out whether they develop jejunal cancers. A patient who stopped his participation in the trial because of diarrhea felt he had been used as a human guinea pig, as these animal studies had not been carried out when he was asked to enroll in the trial (3).

Conflicts of interest: none.

1. O'Donoghue ML, Braunwald E, White HD, et al. Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial. JAMA;312:1006-15.

2. GlaxoSmithKline. Toxicology section from the Investigator's Brochure on darapladip (24 pages). RM2003/00513/06. Undated.

3. Gøtzsche PC. “Human guinea pig” asks for animal studies. BMJ 2014;349:g6714.

On 2015 Jan 05, Peter Gøtzsche commented:

Gastrointestinal cancers in the The SOLID-TIMI 52 trial

The SOLID-TIMI 52 trial assessed whether darapladib had any effect on major coronary events compared with placebo (1). A small table of adverse events showed that people on active drug had diarrhea twice as often as those on placebo whereas there was no difference in “any adjudicated gastrointestinal cancer.” Readers may wonder why gastrointestinal cancers were listed in such a small table, as diarrhea doesn’t usually lead to cancer. The word cancer was only mentioned in the table, with no comment in the text as to why. I think the reason for listing it in the table is that studies in rats and mice have shown that they developed jejunal adenocarcinomas – a very rare cancer - after exposure to darapladib (2). This should have been mentioned in the paper. I also believe that the investigators and the sponsor, GlaxoSmithKline, have an ethical duty to follow-up the 13,026 participants in the trial in the coming years to find out whether they develop jejunal cancers. A patient who stopped his participation in the trial because of diarrhea felt he had been used as a human guinea pig, as these animal studies had not been carried out when he was asked to enroll in the trial (3).

Conflicts of interest: none.

1. O'Donoghue ML, Braunwald E, White HD, et al. Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial. JAMA;312:1006-15.

2. GlaxoSmithKline. Toxicology section from the Investigator's Brochure on darapladip (24 pages). RM2003/00513/06. Undated.

3. Gøtzsche PC. “Human guinea pig” asks for animal studies. BMJ 2014;349:g6714.