Follow-up: Secret panel hired by drug company revealed

More amazing than what is reported in the news is what isn’t.

It has been impossible not to notice that every day brings another press release about the purported benefits of statins. Meanwhile, the most shocking developments of the ENHANCE statin trial commotion continue to be cloaked in secrecy and haven't even made the nightly news.

Matthew Herper, writing for Forbes, has been the mainstream investigative reporter who has continued to uncover information and press for the truth. As JFS readers will remember, Merck/Schering-Plough Pharmaceuticals had repeatedly delayed and, after nearly two years, had still not published the results of the ENHANCE trial. This trial had been designed to see if a new combination drug of Zetia with Zocor worked better than Zocor (simvastatin) alone. Zetia (ezetimibe) had never been shown to be effective in improving clinical outcomes, despite bringing in $5 billion in annual sales, while Zocor’s patent was expiring. Multi-billions of dollars are at stake in the results of this trial.

Last November, Mr Herper exposed that the pharmaceutical company sponsor, Schering-Plough, had control over the study design and the data, a situation that isn’t standard in reputable trials. Worse, the primary investigator didn’t have access to the study data or any say in its analysis. After his article, the company denied that the results were being suppressed and announced that it had convened an independent expert panel which had recommended the primary endpoints of the trial be changed. It later came out that the primary investigator had been left out of this decision, too. Changing a study’s endpoints is never done in valid trials, as it’s easy to change the goals after the fact to match the findings a trial actually came up with. Finally, the company said only part of the trial results would be released this March. These actions drew criticism from the medical community and a Congressional investigation.

[A copy of the December, 11 2007 letter from the U.S. House of Representatives is here. It explains how the trial wasn't registered with ClinicalTrials.gov until 18 months after it was completed and the endpoints were different from those described in the initial study design. The congressmen want answers in a seven point list of requests, which included "retain all primary data and records relating to the ENHANCE trial and refrain from destroying or altering any data and records relating to the trial."]

A number of other questionable scientific techniques in the design of the ENHANCE trial, as well as the IMPROVE-IT trial, were also coming out, primarily from outside reviewers. These statin trials were looking like examples of worst-case scenarios of how pharmaceutical company sponsors can manipulate and control the design, completion, data analysis and reporting of a clinical trial, blurring the lines between scientific research and marketing.

Today, Mr. Herper wrote an article revealing that Forbes had finally obtained the names of the members of the secret expert panel that had advised Merck/Schering-Plough to change the scientific goal of the clinical trial. The list, he wrote, is “filled with well-regarded experts in the field,” including a former FDA official who “has expertise on exactly what regulatory challenges might be posed by changes to a clinical trial” design after the fact. There are no assertions that these doctors acted in anything but good faith as invited consultants, but no explanations were given as to why the pharmaceutical companies had refused to divulge their names until now.

While the drug company sponsors described this panel as independent, even when they disclosed their names to Forbes, they also didn’t reveal the members’ financial ties to the drug company sponsors. Dr. Roy Poses, of Health Care Renewal, hosted by the Foundation for Integrity and Responsibility in Medicine, took it from there. Dr. Poses investigated the conflict of interest disclosures for each of the members of panel and found they were not independent of the commercial sponsors of the study. All five panel members had financial arrangements with Merck or both Merck and Schering-Plough, he revealed. His post and the comments are worth reading.

During these years, while awaiting the results of this trial, millions of people have been prescribed Zocor with Zetia by their doctors, believing they prevent heart attacks and strokes. More troubling than how little coverage this ongoing controversy has received in the mainstream media, is that it’s been ignored in the medical literature. How many doctors are even aware of these controversies and are giving the evidence extra close scrutiny? Dr. Aubrey Blumsohn with Scientific Misconduct Blog did a literature search and was unable to find a single mention of this issue in the British Medical Journal, Lancet, Journal of the American Medical Association, or the New England Journal of Medicine. Blogs have been the primary source for information and analyses. Dr. Blumsohn has compiled a list of three dozen excellent articles from the top 100 medical blogs.

Anymore, blogs are where it’s at.