Speaking before an audience of both professors and students in the Alpert Medical School's first Alpha Omega Alpha visiting professor lecture, Drazen presented a detailed and incisive look at how researchers for pharmaceutical giant Merck withheld data from a clinical trial published in the New England Journal of Medicine in 2000 that indicated patients using the painkiller experienced a higher incidence of cardiovascular problems.
Vioxx, once one of Merck's most widely prescribed and profitable drugs, is an anti-inflammatory drug used to treat arthritis and was approved by the Food and Drug Administration in 1999.
Merck withdrew the drug from the market in 2004 after numerous studies - including information from the FDA - revealed that the drug caused an increased risk of "adverse cardiovascular events," including stroke and heart attack.
The drug worked by inhibiting proteins that cause inflammation and pain. Though it had similar efficacy outcomes as other anti-inflammatories, Vioxx was developed and marketed because it resulted in less gastrointestinal bleeding and ulcers than other anti-inflammatory drugs.
According to the Journal, more than 80 million patients took Vioxx, generating annual sales upwards of $2.5 billion. The drug's withdrawal represented the largest prescription-drug withdrawal in history. Over 27,000 lawsuits have been filed against Merck over Vioxx.
Drazen spoke at length about a study the Journal published in 2000 - the same year he took over as editor-in-chief - that indicated Vioxx did not present a significant negative risk for heart problems.
The study - Vioxx GI Outcomes Research study, or VIGOR - was frequently cited by Merck as showing that Vioxx did not increase the risk of heart disease or death, and its authors included two Merck employees.
Drazen - who holds professorships at the Harvard Medical School, Harvard School of Public Health and Boston University - said the Journal's editors became aware that the Merck authors of the study withheld key data pointing to the drug's increased risk for cardiovascular events in 2005 during litigation of a wrongful death suit involving Vioxx.
Drazen said Merck had claimed this data was not available at the time of the article's publication, but an internal memo produced during the trial showed the Merck authors knew about the data as early as four-and-a-half months prior to the article's publication.
The study's authors had originally included some of the relevant data in the article, but when Journal editors reviewed a computer disk of the document in track changes mode, they discovered that some of this data had been deleted two days before the article was submitted.
"The data in the article was accurate, but it was incomplete," Drazen said. "The article didn't reflect the available data."
After describing how the Vioxx story unfolded, Drazen addressed the case's implications.
"I think the general lesson to be learned is that science is not well-served if readers do not have the access to dispassionate renderings of the data," he said.
Drazen said he feared the case might jeopardize future patients' willingness to participate in clinical trials. He said because patients put themselves at risk in clinical trials - often to benefit the greater good - the bond of trust between clinicians and patients must be maintained.
"Patients will stop volunteering for clinical trials if they think they are being manipulated by a third party for profit," he said.
Drazen said the Journal has instituted more stringent editorial policies and called for greater transparency from authors to ensure the mistakes made in the Vioxx case are not repeated.
He described a 2006 incident in which authors of a clinical trial discovered a mistake at the last minute and passed it on to the Journal in time for it to be published.
"I remember speaking to someone in the company, and they said, 'I didn't want to be Mercked,' " he said.
In retrospect, Drazen said the Journal would have handled the Merck article differently.
"If we could do it all over again, with the full access to hindsight, I think we would have been more aggressive," he said.
Drazen told The Herald he didn't think the Journal's public image has been tarnished by the incident.
"It's easy to see problems in retrospect, but it's hard to see at the time," he said. "We still have a tremendous passion for obtaining and disseminating the best medical information possible."
Daniel Morris '07, who plans to attend medical school next year, said he found Drazen's lecture "clear and informative." Morris said he didn't have much background on the Vioxx case but that Drazen did a good job synthesizing and conveying his information.
"I thought he spoke honestly and pretty frankly," he said.
Jeffrey Lo '07, also a prospective medical student, said he thought the lecture "gave a lot of insight into the process involved in producing ... and publishing a big paper in a medical journal."
