Oxford, UK - Sir Richard Peto (Clinical Trials Service Unit [CTSU], Oxford, UK) responded to the US House of Representatives Committee on Energy and Commerce and reiterated his conclusions that there is "no credible evidence" Vytorin causes cancer [1].

"The key scientific points that our reports make would be self-evidently true to any competent statistician, who, in examining the data, distinguishes appropriately between the hypothesis-generating data set and the hypothesis-testing data set," states Peto in a letter sent to committee chair Rep John Dingell (D-MI), and Rep Bart Stupak (D-MI), chair of the Subcommittee on Oversight and Investigations.

The letter is posted on the website of the CTSU, and in it, Peto responds directly to questions and requests raised by Dingell and Stupak in their August 21, 2008 and September 2, 2008 letters seeking further information about the cancer analysis and financial support provided by the sponsors to the CTSU.

In addition to laying out the sequence of events that led to the analysis of available cancer data, Peto's tersely worded response to the committee makes clear that despite extensive funding from Merck and Schering-Plough Pharmaceuticals to CTSU for research purposes over the past decade, his salary is not paid by industry or from industry-sponsored projects.

"The CTSU has a staff policy of not accepting any honoraria, consultancy fees, or other payments directly or indirectly from industry," the letter states.

The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study was first presented earlier this summer and showed that among those treated with the ezetimibe/simvastatin combination, there were significantly more cases of fatal or nonfatal cancer compared with those treated with placebo [2]. This sparked concern about a possible safety risk and led to an analysis of ongoing ezetimibe/simvastatin studies by Peto, an expert in clinical-trial meta-analyses and cancer epidemiology.

The cancer association, concluded Peto, was likely the play of chance rather than a real finding. The cancer analysis, which involved testing the hypothesis that ezetimibe increased the cancer risk in two ongoing ezetimibe studies, SHARP and IMPROVE-IT, was published in the New England Journal of Medicine along with the SEAS study [3]. The Journal also published an editorial, however, that expressed uncertainty about the safety and efficacy of ezetimibe, as well as a second analysis by Dr Thomas Fleming (University of Washington, Seattle) that concluded it was impossible to rule out the cancer risk at this stage of the game [4,5].

In his letter to the Subcommittee on Oversight and Investigations, Peto lays out the sequence of events leading up to his analysis of the other ezetimibe studies. Other investigators, including SHARP investigator Dr Rory Collins (CTSU) and the steering committee chairs of IMPROVE-IT, Drs Robert Califf (Duke Clinical Research Institute, Durham, NC) and Eugene Braunwald (Brigham and Women's Hospital, Boston, MA), were told of the cancer signal in SEAS and agreed to allow for an independent analysis of the interim cancer data from their trials.

Peto stresses that Merck and Schering-Plough were not involved in the cancer analysis, nor did they have any input into preparing the paper that later appeared in the New England Journal of Medicine.

"The companies were told what was being done but did not know the results or receive any draft of my report before it was finalized and sent out by email to the FDA and others on July 21, 2008," Peto writes in his letter. "Knowing when my report would be sent to the FDA (but not what it would contain), the companies arranged beforehand that a televised press conference would take place later on July 21 that would give journalists the results directly and let them question me freely."

Peto adds that it is not in the interest of public health to prematurely label potentially useful drugs unsafe "if there is no credible evidence that they are—or, of course, to overlook reliable evidence of hazard if it does emerge."

In responding to the questions posed by Dingell and Stupak, Peto reveals that the CTSU has received roughly £105 million from Merck and Schering-Plough since 1997. This includes £35 million for the SHARP trial as well as £70 million for three other major CTSU studies, including the Heart Protection Study, the SEARCH trial, and THRIVE/HPS-2, and genetic analyses of stored samples from those trials.

In their August 21, 2008 letter, Stupak and Dingell request all communications between Merck, Schering-Plough, or the joint venture and Peto and the CTSU, as well as any communications with attorneys, lobbyists, and government officials. In response to the request, Peto's writes that this would involve an "unreasonably vast amount of effort" and would "constitute inappropriate harassment," given that the CTSU has worked on cholesterol-lowering trials with the companies for more than 10 years, something that requires extensive correspondence.

Tucked into a postscript at the end of his letter, Peto requests that the subcommittee declare its own conflict of interest, a not-so-nuanced dig at Dingell's investigation into cancer researcher Dr Bernard Fisher. Fisher was later cleared of any wrongdoing by government investigators, but Peto has previously written that Dingell was prosecutorial and made misleading statements in his investigation.