Drug profits infect medical studies
SEVERAL OF OUR most venerated scientific journals have recently been besmirched by allegations of scientific misconduct. Shocking? We should be just as shocked as Inspector Renault when he discovered gambling at Rick's Cafe in Casablanca.First, the New England Journal of Medicine made public its concerns about crucial data having been withheld from its 2000 report on a study sponsored by Merck exaggerating the safety of its blockbuster drug Vioxx, now withdrawn. Then the lead author of a seminal article published in the journal Science reporting the creation of viable stem cells from cloned human embryos admitted he falsified results and resigned his academic post in disgrace.
This week brings the news that a Johnson & Johnson subsidiary failed to include the deaths of two patients in a clinical trial of its new drug for heart failure, Natrecor, in an article published in the Journal of Emergency Medicine.Why shouldn't we be surprised? Because over the last 25 years, clinical research has been largely privatized. Three-quarters of the clinical studies published in the three most respected medical journals (the New England Journal of Medicine, the Journal of the American Medical Assn. and the Lancet) are now commercially funded. As a result, our medical knowledge grows not in the direction that best improves our health but toward corporate profits, the way that plants grow toward sunlight.This wasn't always so. Before 1980, most medical studies were publicly funded, and most academic researchers scorned industry support. Now, however, the vast majority of clinical trials are commercially funded, and with the financial stakes so high, there is mounting evidence of individual scientists and corporations manipulating their findings.Even our most trusted journals are dependent on drug-company money. Drug makers don't just buy advertising in their pages. According to Richard Horton, editor of the Lancet, they also pay up to $1.75 million for reprints of articles favorable to their drugs, which sales reps then hand out to doctors.And many journal articles are biased in favor of their sponsors' products. A 2003 report in the Journal of the American Medical Assn. found that clinical studies funded by drug companies are three times more likely to conclude that the sponsor's drug is the treatment of choice, compared to studies of the same drug that were not commercially funded. (This study of the effects of commercial bias, by the way, was funded by Danish research institutions.) The disturbing conclusion is that most of the evidence in what doctors believe to be "evidence-based medicine" is more infomercial than dispassionate science.It's vital to protect the integrity of our medical knowledge. But the current peer review system alone can't do the job. The journals, and the peer reviewers they rely on, are in the untenable position of having to trust that corporate sponsors have accurately and completely reported their findings. At present, journal editors and peer reviewers typically are not allowed unrestricted access to the data from commercially sponsored research. Amazingly, many drug company-funded researchers who write the articles are also not allowed access to all of the data the company has collected.There is no better cautionary tale than the unwarranted success of Vioxx. Greater safety was the only reason for doctors to have prescribed Vioxx, given that it provided no better relief of arthritis symptoms or pain and cost up to 10 times more than the older anti-inflammatory drug, naproxen (sold without a prescription as Aleve). But Merck's own study clearly showed that Vioxx was more dangerous than naproxen overall and caused significantly more heart attacks, blood clots and strokes — whether or not the patient had a previous history of cardiovascular disease.SO WHY DID American doctors prescribe $7 billion worth of Vioxx after Merck and the Food and Drug Administration knew all this?Because the New England Journal article that ostensibly reported the results of Merck's study didn't even mention either the cardiovascular or the overall dangers of Vioxx. Instead, it reported only selective data on heart attacks and strokes, allowing Merck to claim that Vioxx wasn't a risk to people without a history of these problems.The Journal's editors are now accusing Merck of withholding critical data. Shame on Merck. But shame on the Journal too for not insisting that the article include a discussion of the most important complications. Doctors were left with the impression that Vioxx was safer than naproxen when exactly the opposite was true.The Journal again misled its readers in 2001, when one of its influential review articles dismissed the dangers of Vioxx as perhaps reflecting "the play of chance." This article was published seven months after FDA reviewers' concerns and Merck's own research data, which documented the dangers, had been posted on the FDA's website. Worse, the Journal violated its own policy prohibiting scientists with conflicts of interest from writing review articles. (Both authors had financial ties to Merck.) That the Journal disclosed those ties mitigates neither its ethical breach nor the consequences of its repeated understatement of the risks of Vioxx.This is hardly an academic argument. According to an article in the Lancet, based on Merck's own data Vioxx probably caused between 88,000 and 144,000 cases of serious heart disease.The stem cell and Natrecor debacles offer further evidence that the problem is not just individual bad actors or occasional lapses of scientific integrity by drug makers. It's that even the most prestigious journals are unable to perform the quality control that doctors take for granted.Sadly, the evidence shows that it's time for the journals to change their policies from trust to "trust, but verify." They should introduce a new standard requiring an independent audit of the accuracy and completeness of research reports before they are sent out for peer review. These scientific auditors should be statisticians and medical experts who are completely free of conflicts of interest and are given unfettered access to the data.The journals will rightfully claim they cannot afford to pay for such scientific oversight. But the lack of oversight is even more costly. Americans waste billions each year on drugs of dubious value. Until we find a way to fund quality controls on published research, the cost of our medical care will continue to soar and our health will suffer.
This week brings the news that a Johnson & Johnson subsidiary failed to include the deaths of two patients in a clinical trial of its new drug for heart failure, Natrecor, in an article published in the Journal of Emergency Medicine.Why shouldn't we be surprised? Because over the last 25 years, clinical research has been largely privatized. Three-quarters of the clinical studies published in the three most respected medical journals (the New England Journal of Medicine, the Journal of the American Medical Assn. and the Lancet) are now commercially funded. As a result, our medical knowledge grows not in the direction that best improves our health but toward corporate profits, the way that plants grow toward sunlight.This wasn't always so. Before 1980, most medical studies were publicly funded, and most academic researchers scorned industry support. Now, however, the vast majority of clinical trials are commercially funded, and with the financial stakes so high, there is mounting evidence of individual scientists and corporations manipulating their findings.Even our most trusted journals are dependent on drug-company money. Drug makers don't just buy advertising in their pages. According to Richard Horton, editor of the Lancet, they also pay up to $1.75 million for reprints of articles favorable to their drugs, which sales reps then hand out to doctors.And many journal articles are biased in favor of their sponsors' products. A 2003 report in the Journal of the American Medical Assn. found that clinical studies funded by drug companies are three times more likely to conclude that the sponsor's drug is the treatment of choice, compared to studies of the same drug that were not commercially funded. (This study of the effects of commercial bias, by the way, was funded by Danish research institutions.) The disturbing conclusion is that most of the evidence in what doctors believe to be "evidence-based medicine" is more infomercial than dispassionate science.It's vital to protect the integrity of our medical knowledge. But the current peer review system alone can't do the job. The journals, and the peer reviewers they rely on, are in the untenable position of having to trust that corporate sponsors have accurately and completely reported their findings. At present, journal editors and peer reviewers typically are not allowed unrestricted access to the data from commercially sponsored research. Amazingly, many drug company-funded researchers who write the articles are also not allowed access to all of the data the company has collected.There is no better cautionary tale than the unwarranted success of Vioxx. Greater safety was the only reason for doctors to have prescribed Vioxx, given that it provided no better relief of arthritis symptoms or pain and cost up to 10 times more than the older anti-inflammatory drug, naproxen (sold without a prescription as Aleve). But Merck's own study clearly showed that Vioxx was more dangerous than naproxen overall and caused significantly more heart attacks, blood clots and strokes — whether or not the patient had a previous history of cardiovascular disease.SO WHY DID American doctors prescribe $7 billion worth of Vioxx after Merck and the Food and Drug Administration knew all this?Because the New England Journal article that ostensibly reported the results of Merck's study didn't even mention either the cardiovascular or the overall dangers of Vioxx. Instead, it reported only selective data on heart attacks and strokes, allowing Merck to claim that Vioxx wasn't a risk to people without a history of these problems.The Journal's editors are now accusing Merck of withholding critical data. Shame on Merck. But shame on the Journal too for not insisting that the article include a discussion of the most important complications. Doctors were left with the impression that Vioxx was safer than naproxen when exactly the opposite was true.The Journal again misled its readers in 2001, when one of its influential review articles dismissed the dangers of Vioxx as perhaps reflecting "the play of chance." This article was published seven months after FDA reviewers' concerns and Merck's own research data, which documented the dangers, had been posted on the FDA's website. Worse, the Journal violated its own policy prohibiting scientists with conflicts of interest from writing review articles. (Both authors had financial ties to Merck.) That the Journal disclosed those ties mitigates neither its ethical breach nor the consequences of its repeated understatement of the risks of Vioxx.This is hardly an academic argument. According to an article in the Lancet, based on Merck's own data Vioxx probably caused between 88,000 and 144,000 cases of serious heart disease.The stem cell and Natrecor debacles offer further evidence that the problem is not just individual bad actors or occasional lapses of scientific integrity by drug makers. It's that even the most prestigious journals are unable to perform the quality control that doctors take for granted.Sadly, the evidence shows that it's time for the journals to change their policies from trust to "trust, but verify." They should introduce a new standard requiring an independent audit of the accuracy and completeness of research reports before they are sent out for peer review. These scientific auditors should be statisticians and medical experts who are completely free of conflicts of interest and are given unfettered access to the data.The journals will rightfully claim they cannot afford to pay for such scientific oversight. But the lack of oversight is even more costly. Americans waste billions each year on drugs of dubious value. Until we find a way to fund quality controls on published research, the cost of our medical care will continue to soar and our health will suffer.
posted by Chris Placitella at 6:19 AM
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