Post by Moses on Dec 1, 2004 10:50:59 GMT -5
Contracts Keep Drug Research Out of Reach
NY TimesExcerpt:
Academic institutions and researchers are widely viewed as the impartial, independent heart of the system this country uses to test drugs and medical devices. But that independence often comes with strings attached, sometimes making those institutions and their researchers obstacles to the exchange and discussion of test results. The upshot is that doctors may not get all the information they need. In the wake of revelations about unpublished test data showing the potential risks of pediatric antidepressants, some doctors have stopped prescribing them. And even doctors who continue to prescribe the drugs question why they were kept in the dark.
In recent months, the outrage over the withheld antidepressant data has led calls for change and promises of some. Drug companies, faced with widespread criticism about their handling of test information, have promised to release more of it. Legislation (House: “H.R.5252”, Sponsor: Rep Markey, Edward J. [MA-7] (introduced 10/7/2004);COSPONSORS(4):Rep Allen, Thomas H. [ME-1] - 11/18/2004 Rep Frank, Barney [MA-4] - 11/18/2004, Rep Schakowsky, Janice D. [IL-9] - 11/18/2004, Rep Waxman, Henry A. [CA-30] - 10/7/2004 thomas.loc.gov/cgi-bin/bdquery/z?d108:h.r.05252: ; Senate :“S.2933, FACT Act”: thomas.loc.gov/cgi-bin/bdquery/z?d108:s.02933: Sponsor: Sen Dodd, Christopher J. [CT] (introduced 10/7/2004); COSPONSORS(3): Sen Johnson, Tim [SD] - 10/7/2004 Sen Kennedy, Edward M. [MA] - 10/7/2004, Sen Wyden, Ron [OR] - 10/7/2004) has been introduced in Congress that would require all makers of drugs and medical devices to list clinical trials and their results in a public database.
Critics say, however, that academic institutions and their researchers need to examine their own practices because they share part of the blame.
The problem starts with the terms of the contracts that some universities sign for clinical trials, but of equal importance is how researchers choose to describe study results and even whether they pursue publication.
"People who are blaming this all on industry are missing the point," said Dr. Robert M. Califf, associate vice chancellor for clinical research at Duke University Medical Center. "I think that academia is part of the problem right now and not part of the solution."
Virtually all the pediatric antidepressant studies were run in part at medical schools, and in many cases the tests were led by academic scientists. But while one study of the drug Paxil, which showed positive results in depressed children, was published, another study showing that it was ineffective was not submitted to a medical journal. In addition, studies involving other antidepressants, like the drugs Remeron and Serzone, were also not published.
Makers of drugs and medical devices frequently turn to medical schools and academic teaching hospitals to run clinical trials and recruit patients for them. The industry pays many academic institutions millions of dollars annually to run such trials; the involvement of a leading academic researcher in an industry-sponsored test gives it both prestige and credibility. Medical researchers who attract studies reap the benefits of such rainmaking with bigger research budgets and career advancement.
Drug companies say that because they pay for a trial they own the data it generates. They say that contract clauses - including ones for confidentiality - are not intended to suppress possibly negative trial findings but to make sure that data is properly analyzed before it is released.
A look at the work of one medical school researcher, Dr. Karen Dineen Wagner, shows the challenges and possible pitfalls such research can entail. For example, from 1998 to 2001, university records show, Dr. Wagner was one of several academic researchers participating in more than a dozen industry-financed pediatric trials of antidepressants and other types of drugs. While some of the results were published, many were not.
Issues related to data disclosure vary between medical schools. Some schools take tougher stands on issues like confidentiality and test publication than others, and academic researchers in well-established fields like cardiology have more power in negotiating clinical trial agreements than those in relatively new ones like child psychiatry.
Leading academic research centers like Duke University and the Cleveland Clinic can often even dictate contract terms when they coordinate a trial by collecting data from various study sites and analyzing it. But Dr. Califf noted that Duke had far less ability to set terms when it was simply one site in a trial being run at many academic and private test centers, which is the way most drug trials are run.
How Trials Work
At one time, academic institutions dominated drug testing. But over the last decade, a private testing industry made up of doctors in private practice and clinics that recruit patients for studies has sprung up. Increasingly, private companies rather than universities coordinate the testing of a drug at different centers.
While industry financing of clinical trials has increased, for example, the share of it going to academic institutions has fallen to 35 percent in 2002 from 70 percent in 1991, according to Thompson CenterWatch, a Boston company that covers the testing industry.
Government financing of medical research has grown, too. But about 90 percent of that money goes to 40 of the country's 125 medical schools, said Dr. David Korn, an executive of the Association of American Medical Colleges. In addition, the government tends to finance basic medical research, not studies of drugs seeking regulatory approval or tests for potential new uses of medications already on the market or their potential use in different types of patients.
Specialists like Dr. Korn said that some medical schools, because of their reliance on industry money, might not negotiate aggressively over contract provisions for fear that companies would take test work elsewhere.
A large academic medical center like Dr. Wagner's, the University of Texas Medical Branch at Galveston, may become involved in as many as 100 new trials a year.
Officials at the Galveston center, which gets about 7 percent of its overall budget from industry-financed tests, say they do their best to win favorable contract terms for industry trials. The standard contract adopted by the University of Texas calls for member medical schools to hold study data confidential for 18 months - a period intended to allow a company to collect test data from multiple sites, analyze it and prepare it for publication. But Galveston officials say they often extend that period to two years when companies demand it.
Companies, of course, are free to release study results as soon as they choose and, in many cases, they do so promptly. But few medical schools - Galveston included - require that study findings be published or widely disseminated as a condition of taking part in a trial, according to a survey by Duke University researchers published two years ago in The New England Journal of Medicine.
"It takes two to tango, and academics are a part of this dance," said Dr. Drummond Rennie, an editor at The Journal of the American Medical Association and a longtime advocate of greater disclosure of the results of clinical trials.
Several studies of academic research have also found that investigators may overstate, unwittingly or not, test findings to please a study's sponsor or a medical journal editor. And university researchers, Dr. Wagner among them, are also sometimes paid significant amounts of money by a drug's manufacturer for work directly related to their study of that medication, creating a potential conflict of interest. ....
A Researcher's Role
It was hardly surprising that many manufacturers of popular antidepressants already approved for use in adults would turn to an established researcher like Dr. Wagner to test them in young patients.
In the late 1990's, she was one of a small number of researchers with experience in testing drugs intended to treat children with problems like attention deficit disorder and bipolar disorder. Over the last decade, Dr. Wagner has led or worked on some 20 studies published in medical journals, and the government has financed some of her work.
She has also attracted a large number of industry-financed studies, including those aimed at testing whether antidepressants approved for use in adults were safe and effective in children and adolescents.
Dr. Wagner's role varied in 12 industry-sponsored trials in which antidepressants were tested against placebos for depression or other problems. On three of them, including a Zoloft trial, she was a lead investigator, working with company researchers to plan, analyze and write results up for publication. On the others, her duties were limited to overseeing test patients at her clinic.
Of the 12 studies, all five of the reports claiming positive results, meaning the drug worked without worrisome side effects, that were submitted for possible regulatory approval were published. The seven other studies were inconclusive or negative, which can mean that the drug failed to work or that the test failed because of its design. (Two of them were never submitted to the Food and Drug Administration to support an application for the drug's approval.)
(continued)
NY TimesExcerpt:
Academic institutions and researchers are widely viewed as the impartial, independent heart of the system this country uses to test drugs and medical devices. But that independence often comes with strings attached, sometimes making those institutions and their researchers obstacles to the exchange and discussion of test results. The upshot is that doctors may not get all the information they need. In the wake of revelations about unpublished test data showing the potential risks of pediatric antidepressants, some doctors have stopped prescribing them. And even doctors who continue to prescribe the drugs question why they were kept in the dark.
"I think it would have been more helpful for everyone to have known what was going on at the time that it was happening," Dr. Robert Feder, a psychiatrist in Manchester, N.H., said.
In recent months, the outrage over the withheld antidepressant data has led calls for change and promises of some. Drug companies, faced with widespread criticism about their handling of test information, have promised to release more of it. Legislation (House: “H.R.5252”, Sponsor: Rep Markey, Edward J. [MA-7] (introduced 10/7/2004);COSPONSORS(4):Rep Allen, Thomas H. [ME-1] - 11/18/2004 Rep Frank, Barney [MA-4] - 11/18/2004, Rep Schakowsky, Janice D. [IL-9] - 11/18/2004, Rep Waxman, Henry A. [CA-30] - 10/7/2004 thomas.loc.gov/cgi-bin/bdquery/z?d108:h.r.05252: ; Senate :“S.2933, FACT Act”: thomas.loc.gov/cgi-bin/bdquery/z?d108:s.02933: Sponsor: Sen Dodd, Christopher J. [CT] (introduced 10/7/2004); COSPONSORS(3): Sen Johnson, Tim [SD] - 10/7/2004 Sen Kennedy, Edward M. [MA] - 10/7/2004, Sen Wyden, Ron [OR] - 10/7/2004) has been introduced in Congress that would require all makers of drugs and medical devices to list clinical trials and their results in a public database.
Critics say, however, that academic institutions and their researchers need to examine their own practices because they share part of the blame.
The problem starts with the terms of the contracts that some universities sign for clinical trials, but of equal importance is how researchers choose to describe study results and even whether they pursue publication.
"People who are blaming this all on industry are missing the point," said Dr. Robert M. Califf, associate vice chancellor for clinical research at Duke University Medical Center. "I think that academia is part of the problem right now and not part of the solution."
Virtually all the pediatric antidepressant studies were run in part at medical schools, and in many cases the tests were led by academic scientists. But while one study of the drug Paxil, which showed positive results in depressed children, was published, another study showing that it was ineffective was not submitted to a medical journal. In addition, studies involving other antidepressants, like the drugs Remeron and Serzone, were also not published.
Makers of drugs and medical devices frequently turn to medical schools and academic teaching hospitals to run clinical trials and recruit patients for them. The industry pays many academic institutions millions of dollars annually to run such trials; the involvement of a leading academic researcher in an industry-sponsored test gives it both prestige and credibility. Medical researchers who attract studies reap the benefits of such rainmaking with bigger research budgets and career advancement.
Drug companies say that because they pay for a trial they own the data it generates. They say that contract clauses - including ones for confidentiality - are not intended to suppress possibly negative trial findings but to make sure that data is properly analyzed before it is released.
A look at the work of one medical school researcher, Dr. Karen Dineen Wagner, shows the challenges and possible pitfalls such research can entail. For example, from 1998 to 2001, university records show, Dr. Wagner was one of several academic researchers participating in more than a dozen industry-financed pediatric trials of antidepressants and other types of drugs. While some of the results were published, many were not.
Issues related to data disclosure vary between medical schools. Some schools take tougher stands on issues like confidentiality and test publication than others, and academic researchers in well-established fields like cardiology have more power in negotiating clinical trial agreements than those in relatively new ones like child psychiatry.
Leading academic research centers like Duke University and the Cleveland Clinic can often even dictate contract terms when they coordinate a trial by collecting data from various study sites and analyzing it. But Dr. Califf noted that Duke had far less ability to set terms when it was simply one site in a trial being run at many academic and private test centers, which is the way most drug trials are run.
How Trials Work
At one time, academic institutions dominated drug testing. But over the last decade, a private testing industry made up of doctors in private practice and clinics that recruit patients for studies has sprung up. Increasingly, private companies rather than universities coordinate the testing of a drug at different centers.
While industry financing of clinical trials has increased, for example, the share of it going to academic institutions has fallen to 35 percent in 2002 from 70 percent in 1991, according to Thompson CenterWatch, a Boston company that covers the testing industry.
Government financing of medical research has grown, too. But about 90 percent of that money goes to 40 of the country's 125 medical schools, said Dr. David Korn, an executive of the Association of American Medical Colleges. In addition, the government tends to finance basic medical research, not studies of drugs seeking regulatory approval or tests for potential new uses of medications already on the market or their potential use in different types of patients.
Specialists like Dr. Korn said that some medical schools, because of their reliance on industry money, might not negotiate aggressively over contract provisions for fear that companies would take test work elsewhere.
A large academic medical center like Dr. Wagner's, the University of Texas Medical Branch at Galveston, may become involved in as many as 100 new trials a year.
Officials at the Galveston center, which gets about 7 percent of its overall budget from industry-financed tests, say they do their best to win favorable contract terms for industry trials. The standard contract adopted by the University of Texas calls for member medical schools to hold study data confidential for 18 months - a period intended to allow a company to collect test data from multiple sites, analyze it and prepare it for publication. But Galveston officials say they often extend that period to two years when companies demand it.
Companies, of course, are free to release study results as soon as they choose and, in many cases, they do so promptly. But few medical schools - Galveston included - require that study findings be published or widely disseminated as a condition of taking part in a trial, according to a survey by Duke University researchers published two years ago in The New England Journal of Medicine.
"It takes two to tango, and academics are a part of this dance," said Dr. Drummond Rennie, an editor at The Journal of the American Medical Association and a longtime advocate of greater disclosure of the results of clinical trials.
Several studies of academic research have also found that investigators may overstate, unwittingly or not, test findings to please a study's sponsor or a medical journal editor. And university researchers, Dr. Wagner among them, are also sometimes paid significant amounts of money by a drug's manufacturer for work directly related to their study of that medication, creating a potential conflict of interest. ....
A Researcher's Role
It was hardly surprising that many manufacturers of popular antidepressants already approved for use in adults would turn to an established researcher like Dr. Wagner to test them in young patients.
In the late 1990's, she was one of a small number of researchers with experience in testing drugs intended to treat children with problems like attention deficit disorder and bipolar disorder. Over the last decade, Dr. Wagner has led or worked on some 20 studies published in medical journals, and the government has financed some of her work.
She has also attracted a large number of industry-financed studies, including those aimed at testing whether antidepressants approved for use in adults were safe and effective in children and adolescents.
Dr. Wagner's role varied in 12 industry-sponsored trials in which antidepressants were tested against placebos for depression or other problems. On three of them, including a Zoloft trial, she was a lead investigator, working with company researchers to plan, analyze and write results up for publication. On the others, her duties were limited to overseeing test patients at her clinic.
Of the 12 studies, all five of the reports claiming positive results, meaning the drug worked without worrisome side effects, that were submitted for possible regulatory approval were published. The seven other studies were inconclusive or negative, which can mean that the drug failed to work or that the test failed because of its design. (Two of them were never submitted to the Food and Drug Administration to support an application for the drug's approval.)
(continued)