January 17, 2008 — A study of Food and Drug Administration (FDA)–registered clinical trials of 12 antidepressants found a bias toward publication of positive results. Almost all studies viewed by the FDA as positive were published. The clinical trials that the FDA deemed negative or questionable were largely not published or, in some cases, were published as positive outcomes.
For each of the 12 drugs, at least 1 study was not published or was reported in the literature as positive despite a conflicting judgment by the FDA.
The overall effect size of the antidepressants (vs placebo) that was reported in the published literature was nearly one-third larger than the effect size for these agents that was derived from FDA data.
"Selective reporting of clinical-trial results may have adverse consequences for researchers, study participants, healthcare professionals, and patients," they conclude.
These findings are published in the January 17 issue of the New England Journal of Medicine.
Evidence-Based or Biased Evidence?
"You might get the impression from the published literature that [these drugs] are consistently effective; however, the outcome of this study is that they are effective, but inconsistently so," lead study author, Eric H. Turner, MD, from Oregon Health and Science University, in Portland, Oregon, told Medscape Psychiatry.
"Evidence-based medicine is valuable to the extent that the evidence is complete and unbiased," he noted, adding that selective publication of clinical trials can alter the apparent risk/benefit ratio of drugs, which can affect prescribing decisions.
The current study sought to examine how accurately the published literature conveys data on drug efficacy to the medical community.
The team identified the phase 2 and 3 clinical-trial programs for 12 antidepressants approved by the FDA between 1987 and 2004, which involved 12,564 adult patients. They also determined whether the FDA judged the studies to be positive or negative with respect to primary end points.
To identify matching study publications, the researchers conducted a systematic literature search and contacted the sponsors of the drug studies.
Among the 74 FDA-registered antidepressant studies, the team found that 23 trials (31%) had not been published.
Among the 38 of 74 studies (51%) that the FDA deemed to be positive, 37 were published.
The remaining 36 studies (49%) were deemed to be either negative (24 studies) or questionable (12). Of these 36 studies, 22 were not published, 11 were published as positive, and 3 were published as negative.
Publication Status of FDA-Registered Antidepressant Studies
Publication Status
Number of Studies, n (%)
Published results agree with FDA decision
40 (54)
Published results conflict with FDA decision (published as positive)
11 (15)
Results not published
23 (31)
Total
74 (100)
For each drug, the effect-size value based on published literature was higher than the effect-size value based on FDA data. The increase in size ranged from 11% to 69% for individual drugs and was 32% overall.
"We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, decisions by journal editors and reviewers not to publish submitted manuscripts, or both," the group writes.
"Each drug, when submitted to a meta-analysis, was superior to placebo. On the other hand, the true magnitude of each drug's superiority to placebo was less than a diligent review of the literature would indicate," they note.
More Negative Studies Need to Be Published
"This is one of the first efforts to actually quantify the impact [of publication bias] in terms of reported efficacy, by medication," David Fassler, MD, from the University of Vermont College of Medicine, in Burlington, and a trustee-at-large of the American Psychiatric Association (APA), told Medscape Psychiatry. When published literature may overstate the efficacy or understate the risks of specific medications or interventions, this is clearly a significant problem for physicians, researchers, and the general public, he added.
Organized psychiatry has been in the forefront of trying to address this issue, he noted. In July 2004, the APA and the American Academy of Child and Adolescent Psychiatry (AACAP) brought a resolution about this topic to the American Medical Association, which prompted that organization to join in the call for a national registry, he added.
As a result of these and other efforts, today most major journals follow a policy set by the International Committee of Medical Journal Editors (ICMJE) and will consider only papers based on trials entered into 1 of 5 accepted, centralized, publicly accessible clinical-trial registries prior to study enrollment, he observed.
Additional steps are needed. "Journal editors need to ensure that well-designed studies with negative results are accepted for publication at the same rate as comparable studies with positive findings," Dr. Fassler said. "Researchers involved in clinical trials should have the ability to publish or present data from their efforts. Physicians, the media, and the general public . . . need to read and interpret new studies with appropriate caution."
APA and AACAP Renew Call for Mandatory Registry
In light of the report by Turner and colleagues, the APA and AACAP issued a statement renewing their call for a mandatory, public registry for clinical trials and reiterating their support for federal legislation to provide open access to clinical-trials data.
"Our patients deserve the best healthcare available, and having full disclosure of research findings — both positive and negative — will help clinicians develop the most effective treatment plans," APA president Carolyn Robinowitz, MD, said in the statement. Issues involving publication bias are not unique to psychiatry, she noted. "Publication bias has been well documented with cardiovascular and anti-inflammatory medications. A clinical-trials registry set up and overseen by the federal government would be good for all of medicine."
"Greater transparency in the clinical-trials process, particularly including open access to important data, is of significant benefit to the research community, to practitioners in the field, and to our patients," said AACAP president Robert L. Hendren, MD. "A national registry will allow patients to have access to data on a complete range of treatment options, including medication, to discuss with their physician."
Dr. Turner reports having served as a medical reviewer for the FDA. No other potential conflict of interest relevant to this article was reported.
N Engl J Med. 2008;358:252-60.
Tuesday, December 7, 2010
FDA: Not Necessary to Stop Taking Vytorin or Other Lipid-Lowering Drugs
Patients should not stop taking Vytorin or other cholesterol lowering medications," the FDA announced following review of the ENHANCE trial.
ENHANCE showed that despite Vytorin's lowering LDL cholesterol levels more than simvastatin (Zocor) after 2 years, there was no significant difference between these groups in carotid intima-media thickness.
"The results from ENHANCE do not change FDA's position that an elevated LDL cholesterol is a risk factor for cardiovascular disease and that lowering LDL cholesterol reduces the risk for cardiovascular disease," the agency wrote in a safety update posted on its website.
An ongoing study (scheduled for completion in 2012) aims to determine whether ezetimibe/simvastatin actually decreases the risk for cardiovascular events, compared with simvastatin alone. In addition, the FDA is still reviewing data from the SEAS study, which indicated that Vytorin may be associated with increased cancer incidence and cancer mortality.
ENHANCE showed that despite Vytorin's lowering LDL cholesterol levels more than simvastatin (Zocor) after 2 years, there was no significant difference between these groups in carotid intima-media thickness.
"The results from ENHANCE do not change FDA's position that an elevated LDL cholesterol is a risk factor for cardiovascular disease and that lowering LDL cholesterol reduces the risk for cardiovascular disease," the agency wrote in a safety update posted on its website.
An ongoing study (scheduled for completion in 2012) aims to determine whether ezetimibe/simvastatin actually decreases the risk for cardiovascular events, compared with simvastatin alone. In addition, the FDA is still reviewing data from the SEAS study, which indicated that Vytorin may be associated with increased cancer incidence and cancer mortality.
Sunday, November 7, 2010
Stopping a trial early in oncology: for patients or for
F. Trotta1, G. Apolone2, S. Garattini2 & G. Tafuri1,3*
1Italian Medicines Agency (AIFA), Rome; 2Mario Negri Institute for Pharmacological Research, Milan, Italy; 3Utrecht University, Utrecht Institute for Pharmaceutical
Sciences, Utrecht, The Netherlands
Received 18 December 2007; revised 25 January 2008; accepted 28 January 2008
Background: The aim of this study is to assess the use of interim analyses in randomised controlled trials (RCTs)
testing new anticancer drugs, focussing on oncological clinical trials stopped early for benefit.
Materials and methods: All published clinical trials stopped early for benefit and published in the last 11 years,
regarding anticancer drugs and containing an interim analysis, were assessed.
Results: Twenty-five RCTs were analysed. The evaluation of efficacy was protocol planned through time-related
primary end points, >40% of them overall survival. In 95% of studies, at the interim analysis, efficacy was evaluated
using the same end point as planned for the final analysis. As a consequence of early stopping after the interim
analysis, 3300 patients/events across all studies were spared. More than 78% of the RCTs published in the last 3
years were used for registration purposes.
Conclusion: Though criticism of the poor quality of oncological trials seems out of place, unfortunately early
termination raises new concerns. The relation between sparing patients and saving time and trial costs indicates that
there is a market-driven intent. We believe that only untruncated trials can provide a full level of evidence which can be
translated into clinical practice without further confirmative trials.
1Italian Medicines Agency (AIFA), Rome; 2Mario Negri Institute for Pharmacological Research, Milan, Italy; 3Utrecht University, Utrecht Institute for Pharmaceutical
Sciences, Utrecht, The Netherlands
Received 18 December 2007; revised 25 January 2008; accepted 28 January 2008
Background: The aim of this study is to assess the use of interim analyses in randomised controlled trials (RCTs)
testing new anticancer drugs, focussing on oncological clinical trials stopped early for benefit.
Materials and methods: All published clinical trials stopped early for benefit and published in the last 11 years,
regarding anticancer drugs and containing an interim analysis, were assessed.
Results: Twenty-five RCTs were analysed. The evaluation of efficacy was protocol planned through time-related
primary end points, >40% of them overall survival. In 95% of studies, at the interim analysis, efficacy was evaluated
using the same end point as planned for the final analysis. As a consequence of early stopping after the interim
analysis, 3300 patients/events across all studies were spared. More than 78% of the RCTs published in the last 3
years were used for registration purposes.
Conclusion: Though criticism of the poor quality of oncological trials seems out of place, unfortunately early
termination raises new concerns. The relation between sparing patients and saving time and trial costs indicates that
there is a market-driven intent. We believe that only untruncated trials can provide a full level of evidence which can be
translated into clinical practice without further confirmative trials.
Safety Results of Randomized Controlled Trials May Be Inconsistently Reported
Laurie Barclay, MD
October 26, 2009 — Safety results of randomized controlled trials (RCTs) may be inconsistently reported, according to the results of a review in the October 26 issue of the Archives of Internal Medicine.
"Reports of clinical trials usually emphasize efficacy results, especially when results are statistically significant," write Isabelle Pitrou, MD, MSc, from Université Denis Diderot, INSERM, in Paris, France, and colleagues. "Poor safety reporting can lead to misinterpretation and inadequate conclusions about the interventions assessed. Our aim was to describe the reporting of harm-related results from [RCTs]."
The reviewers searched the MEDLINE database for reports of RCTs published from January 1, 2006, through January 1, 2007, in 6 widely read and respected general medical journals. A standardized form used for data extraction allowed evaluation of how safety results were presented in the text and tables of published reports.
Among the 133 reports identified, 88.7% mentioned adverse events. However, 27.1% of reports gave no information concerning severe adverse events, and 47.4% of reports gave no information concerning withdrawal of patients because of an adverse event.
The reviewers noted restrictions in the reporting of harm-related data in 43 articles (32.3%), with 17 describing the most common adverse events only, 16 describing severe adverse events only, 5 describing statistically significant events only, and 5 having more than 1 restriction. Nearly two thirds of articles (65.6%) clearly reported the population considered for safety analysis.
"Our review reveals important heterogeneity and variability in the reporting of harm-related results in publications of RCTs," the study authors write."Despite the CONSORT statement extension for harm-related data, efforts should still be made to describe safety results with accuracy in reports of RCTs and to standardize practices for reporting."
Limitations of this review include exclusion of specialized medical journals or those with lower impact factors, exclusion of specific study designs, and extraction of all the data by a single reviewer.
"Perhaps conflicts of interest and marketing rather than science have shaped even the often accepted standard that randomized trials study primarily effectiveness, whereas information on harms from medical interventions can wait for case reports and nonrandomized studies," John P. A. Ioannidis, MD, from the University of Ioannina School of Medicine in Greece, writes in an accompanying editorial. "Nonrandomized data are very helpful, but they have limitations, and many harms will remain long undetected if we just wait for spontaneous reporting and other nonrandomized research to reveal them. In an environment where effectiveness benefits are small and shrinking, the randomized trials agenda may need to reprogram its whole mission, including its reporting, toward better understanding of harms."
Dr. Pitrou was supported by a grant from the Ministry of Higher Education and Research, France. The study authors and Dr. Ioannidis have disclosed no relevant financial relationships.
Arch Intern Med. 2009;169:1737–1739, 1756–1761.
October 26, 2009 — Safety results of randomized controlled trials (RCTs) may be inconsistently reported, according to the results of a review in the October 26 issue of the Archives of Internal Medicine.
"Reports of clinical trials usually emphasize efficacy results, especially when results are statistically significant," write Isabelle Pitrou, MD, MSc, from Université Denis Diderot, INSERM, in Paris, France, and colleagues. "Poor safety reporting can lead to misinterpretation and inadequate conclusions about the interventions assessed. Our aim was to describe the reporting of harm-related results from [RCTs]."
The reviewers searched the MEDLINE database for reports of RCTs published from January 1, 2006, through January 1, 2007, in 6 widely read and respected general medical journals. A standardized form used for data extraction allowed evaluation of how safety results were presented in the text and tables of published reports.
Among the 133 reports identified, 88.7% mentioned adverse events. However, 27.1% of reports gave no information concerning severe adverse events, and 47.4% of reports gave no information concerning withdrawal of patients because of an adverse event.
The reviewers noted restrictions in the reporting of harm-related data in 43 articles (32.3%), with 17 describing the most common adverse events only, 16 describing severe adverse events only, 5 describing statistically significant events only, and 5 having more than 1 restriction. Nearly two thirds of articles (65.6%) clearly reported the population considered for safety analysis.
"Our review reveals important heterogeneity and variability in the reporting of harm-related results in publications of RCTs," the study authors write."Despite the CONSORT statement extension for harm-related data, efforts should still be made to describe safety results with accuracy in reports of RCTs and to standardize practices for reporting."
Limitations of this review include exclusion of specialized medical journals or those with lower impact factors, exclusion of specific study designs, and extraction of all the data by a single reviewer.
"Perhaps conflicts of interest and marketing rather than science have shaped even the often accepted standard that randomized trials study primarily effectiveness, whereas information on harms from medical interventions can wait for case reports and nonrandomized studies," John P. A. Ioannidis, MD, from the University of Ioannina School of Medicine in Greece, writes in an accompanying editorial. "Nonrandomized data are very helpful, but they have limitations, and many harms will remain long undetected if we just wait for spontaneous reporting and other nonrandomized research to reveal them. In an environment where effectiveness benefits are small and shrinking, the randomized trials agenda may need to reprogram its whole mission, including its reporting, toward better understanding of harms."
Dr. Pitrou was supported by a grant from the Ministry of Higher Education and Research, France. The study authors and Dr. Ioannidis have disclosed no relevant financial relationships.
Arch Intern Med. 2009;169:1737–1739, 1756–1761.
Sunday, October 24, 2010
Psychiatrists Dominate "Doctor-Dollars" Database Listing Big Pharma Payments
October 22, 2010 — Psychiatrists dominate a list of physicians receiving the most in payments from pharmaceutical companies, according to a free, interactive database of such payments launched by investigative journalism group ProPublica, in partnership with other US media outlets
So far, the database includes payments made by 7 of the biggest pharmaceutical companies — some of which the US Department of Justice has required to disclose physician payments as part of settlement agreements over illegal drug marketing — which account for a boggling $258 million in payments to roughly 17,700 physicians. The plan is to add 70 more companies.
Any US physician is searchable by name in the database.
"Receiving payments isn't necessarily wrong," says the homepage for the Dollars for Docs, "but it does raise ethical issues."
The payments covered by the project include fees for such items as speaking, consulting, meals, and travel; the different types of payments from different companies have been compiled, streamlined, and tallied by ProPublica.
The 10 highest-paid physicians in 2009 to 2010 for each of the 7 companies are listed on the site, spanning all medical disciplines.
Endocrinologist Firhaad Ismail, MD, from Las Vegas, Nevada, ranked number one in pharmaceutical industry compensation, receiving $303,558 from GlaxoSmithKline, Eli Lilly, and Merck. Dr. Ismail did not return messages left with his office requesting an interview.
Top-Paid Psychiatrist Says Payments Do Not Cloud Clinical Judgment
ProPublica researchers also compiled a list of physicians who were paid more than $100,000 (typically from more than 1 company) during the past 18 months, turning up 384 names, including 41 who earned more than $200,000 through speaking or consulting arrangements and 2 who earned more than $300,000 from 1 or more of the 7 companies.
More psychiatrists are listed in the database than any other kind of specialist. Of the 384 physicians in the $100,000 group, 116 are psychiatrists. Leading all psychiatrists was Roueen Rafeyan, MD, in Chicago, Illinois, who received $203,936 from Eli Lilly, AstraZeneca, Johnson & Johnson, and Pfizer, mostly for professional education programs.
In an interview with Medscape Medical News, Dr. Rafeyan said that compensation from pharmaceutical companies does not cloud his clinical judgment at the expense of patients.
The day I'm influenced by that is the day I'm not fit to practice medicine.
"The day I'm influenced by that is the day I'm not fit to practice medicine," Dr. Rafeyan said.
He noted that the majority of the drugs he prescribed were generics. "If someone looked at my prescribing patterns, it would be the opposite of the [pharmaceutical] money I receive," said Dr. Rafeyan, an assistant clinical professor at Rush University Medical Center in Chicago.
Dr. Rafeyan said that although the extra income is always welcome, patient well-being was his prime motivation to talk to other physicians about brand-name psychiatric drugs. "When you educate other physicians, hopefully 1 patient will benefit from it."
When asked how he found the time to earn more than $200,000 as a pharmaceutical company educator over 18 months, Dr. Rafeyan said, "I work very hard, like many other physicians. None of us have 40-hour work weeks."
Dollar Value of Psychiatric Drugs Is Enormous
The preponderance of psychiatrists on the ProPublica list may reflect the proportion of prescription activity involving psychiatric drugs. In 2009, the dollar value of antipsychotic drugs came to $14.6 billion, topping all other therapeutic classes, according to research firm IMS Health. Antidepressants occupied the number 4 spot on the list, valued at $9.9 billion.
IMS Health put the total US prescription market in 2009 at $300.3 billion.
Carol Bernstein, MD, president of the American Psychiatric Association, told Medscape Medical News that the thorny issue of pharmaceutical industry compensation went beyond her specialty.
People with high-profile, high-visibility [positions] sometimes get carried away.
"Academic medicine needs a different relationship with the pharmaceutical industry," she said. Physicians must find new ways to facilitate the development of new drugs that do not compromise their ethics or patient care.
"People with high-profile, high-visibility [positions] sometimes get carried away," she said.
Research has shown, Dr. Bernstein added, that heavy pharmaceutical marketing indeed influences physician prescribing.
The Rest of the Compensation Leader Board
After psychiatry, the next largest specialty in the $100,000 group is internal medicine. However, this is an amorphous category, because many of the 114 physicians shown as board certified in internal medicine also are certified in fields such as endocrinology, neurology, cardiovascular disease, and medical oncology.
Table. 11 Most Compensated Specialties After Psychiatry and Internal Medicine
Specialty Number of Physicians*
Endocrinology 37
Pulmonology 23
Family Medicine 23
Cardiovascular Medicine 19
Urology 19
Obstetrics/Gynecology 16
Allergy and Immunology 15
Neurology 13
Oncology 13
Pain Medicine 10
Pediatrics 10
*Some physicians are listed with more than 1 board certification.
More to Come
By 2013, 70 additional companies will be required to disclose payments under federal healthcare reform legislation, a notion originally brought forward as the Physician Payments Sunshine Act.
ProPublica says it has launched a "rolling series" of stories generated by their research. The first addresses the high number of physicians paid to speak for drug companies who also have limited credentials or have faced disciplinary actions, criminal convictions, malpractice lawsuits, hospital sanctions, or US Food and Drug Administration warning letters.
Two of ProPublica's partners, the Chicago Tribune and the Boston Globe, have also used the database to research their own stories. The Globe's article focuses on payments to physicians at Harvard University and other Boston-area institutions, noting that "numerous doctors at Beth Israel Deaconess Medical Center and Boston Medical Center" also received payments, "despite hospital policies saying physicians cannot be paid speakers unless they control the content of the talks." The Tribune article zeroes in on payments being made to 4 Chicago-area practices: the psychiatry department at Rush University Medical Center, a headache clinic, a suburban urology practice, and a psychiatric hospital.
An editor's note on the ProPublica Web site urges interactivity and collaboration, inviting patients to search for their physicians and email the Web site with comments or stories. It also notes that stories of the kind being generated from this list would, in the past, have been "scoops" for single news organizations.
"We think we can achieve our primary mission at ProPublica — journalism that spurs change — by working in concert with other talented journalists and with the tens of thousands of people who will view, hear, and read stories by this partnership."
Medscape Medical News © 2010 WebMD, LLC
Send press releases and comments to news@medscape.net.
So far, the database includes payments made by 7 of the biggest pharmaceutical companies — some of which the US Department of Justice has required to disclose physician payments as part of settlement agreements over illegal drug marketing — which account for a boggling $258 million in payments to roughly 17,700 physicians. The plan is to add 70 more companies.
Any US physician is searchable by name in the database.
"Receiving payments isn't necessarily wrong," says the homepage for the Dollars for Docs, "but it does raise ethical issues."
The payments covered by the project include fees for such items as speaking, consulting, meals, and travel; the different types of payments from different companies have been compiled, streamlined, and tallied by ProPublica.
The 10 highest-paid physicians in 2009 to 2010 for each of the 7 companies are listed on the site, spanning all medical disciplines.
Endocrinologist Firhaad Ismail, MD, from Las Vegas, Nevada, ranked number one in pharmaceutical industry compensation, receiving $303,558 from GlaxoSmithKline, Eli Lilly, and Merck. Dr. Ismail did not return messages left with his office requesting an interview.
Top-Paid Psychiatrist Says Payments Do Not Cloud Clinical Judgment
ProPublica researchers also compiled a list of physicians who were paid more than $100,000 (typically from more than 1 company) during the past 18 months, turning up 384 names, including 41 who earned more than $200,000 through speaking or consulting arrangements and 2 who earned more than $300,000 from 1 or more of the 7 companies.
More psychiatrists are listed in the database than any other kind of specialist. Of the 384 physicians in the $100,000 group, 116 are psychiatrists. Leading all psychiatrists was Roueen Rafeyan, MD, in Chicago, Illinois, who received $203,936 from Eli Lilly, AstraZeneca, Johnson & Johnson, and Pfizer, mostly for professional education programs.
In an interview with Medscape Medical News, Dr. Rafeyan said that compensation from pharmaceutical companies does not cloud his clinical judgment at the expense of patients.
The day I'm influenced by that is the day I'm not fit to practice medicine.
"The day I'm influenced by that is the day I'm not fit to practice medicine," Dr. Rafeyan said.
He noted that the majority of the drugs he prescribed were generics. "If someone looked at my prescribing patterns, it would be the opposite of the [pharmaceutical] money I receive," said Dr. Rafeyan, an assistant clinical professor at Rush University Medical Center in Chicago.
Dr. Rafeyan said that although the extra income is always welcome, patient well-being was his prime motivation to talk to other physicians about brand-name psychiatric drugs. "When you educate other physicians, hopefully 1 patient will benefit from it."
When asked how he found the time to earn more than $200,000 as a pharmaceutical company educator over 18 months, Dr. Rafeyan said, "I work very hard, like many other physicians. None of us have 40-hour work weeks."
Dollar Value of Psychiatric Drugs Is Enormous
The preponderance of psychiatrists on the ProPublica list may reflect the proportion of prescription activity involving psychiatric drugs. In 2009, the dollar value of antipsychotic drugs came to $14.6 billion, topping all other therapeutic classes, according to research firm IMS Health. Antidepressants occupied the number 4 spot on the list, valued at $9.9 billion.
IMS Health put the total US prescription market in 2009 at $300.3 billion.
Carol Bernstein, MD, president of the American Psychiatric Association, told Medscape Medical News that the thorny issue of pharmaceutical industry compensation went beyond her specialty.
People with high-profile, high-visibility [positions] sometimes get carried away.
"Academic medicine needs a different relationship with the pharmaceutical industry," she said. Physicians must find new ways to facilitate the development of new drugs that do not compromise their ethics or patient care.
"People with high-profile, high-visibility [positions] sometimes get carried away," she said.
Research has shown, Dr. Bernstein added, that heavy pharmaceutical marketing indeed influences physician prescribing.
The Rest of the Compensation Leader Board
After psychiatry, the next largest specialty in the $100,000 group is internal medicine. However, this is an amorphous category, because many of the 114 physicians shown as board certified in internal medicine also are certified in fields such as endocrinology, neurology, cardiovascular disease, and medical oncology.
Table. 11 Most Compensated Specialties After Psychiatry and Internal Medicine
Specialty Number of Physicians*
Endocrinology 37
Pulmonology 23
Family Medicine 23
Cardiovascular Medicine 19
Urology 19
Obstetrics/Gynecology 16
Allergy and Immunology 15
Neurology 13
Oncology 13
Pain Medicine 10
Pediatrics 10
*Some physicians are listed with more than 1 board certification.
More to Come
By 2013, 70 additional companies will be required to disclose payments under federal healthcare reform legislation, a notion originally brought forward as the Physician Payments Sunshine Act.
ProPublica says it has launched a "rolling series" of stories generated by their research. The first addresses the high number of physicians paid to speak for drug companies who also have limited credentials or have faced disciplinary actions, criminal convictions, malpractice lawsuits, hospital sanctions, or US Food and Drug Administration warning letters.
Two of ProPublica's partners, the Chicago Tribune and the Boston Globe, have also used the database to research their own stories. The Globe's article focuses on payments to physicians at Harvard University and other Boston-area institutions, noting that "numerous doctors at Beth Israel Deaconess Medical Center and Boston Medical Center" also received payments, "despite hospital policies saying physicians cannot be paid speakers unless they control the content of the talks." The Tribune article zeroes in on payments being made to 4 Chicago-area practices: the psychiatry department at Rush University Medical Center, a headache clinic, a suburban urology practice, and a psychiatric hospital.
An editor's note on the ProPublica Web site urges interactivity and collaboration, inviting patients to search for their physicians and email the Web site with comments or stories. It also notes that stories of the kind being generated from this list would, in the past, have been "scoops" for single news organizations.
"We think we can achieve our primary mission at ProPublica — journalism that spurs change — by working in concert with other talented journalists and with the tens of thousands of people who will view, hear, and read stories by this partnership."
Medscape Medical News © 2010 WebMD, LLC
Send press releases and comments to news@medscape.net.
Wednesday, September 29, 2010
Vitalux for prevention of age related macular degeneration
An earlier, Cochrane Database Review of publications to 2007 found that the use of vitamin and mineral supplements, alone or in combination, by the general population had no effect on age-related macular degeneration,[34] a finding echoed by another review.[35] A 2006 Cochrane Review of the effects of vitamins and minerals on the slowing of ARMD found that positive results mainly came from a single large trial in the United States (the Age-Related Eye Disease Study, with funding from the eye care product company Bausch & Lomb who also manufactured the supplements used in the study[36]), and questioned the generalization of the data to any other populations with different nutritional status. The review also questioned the possible harm of such supplements, given the increased risk of lung cancer in smokers with high intakes of beta-Carotene, and the increased risk of heart failure in at-risk populations who consume high levels of vitamin E supplements.[37]
Tuesday, September 14, 2010
National drug plan could save billions: study
A universal prescription drug plan could chop more than $10 billion off Canada's annual health-care bill, according to a new policy study that its authors say "explodes the fallacy" that such a plan is unaffordable.
A new study on Canada's pharmaceutical policies concludes that a universal drug plan could save up to $10.7 billion a year in total drug expenditures. (Nati Harnik/Associated Press)
The report, released on Monday by the Canadian Centre for Policy Alternatives, concludes the existing patchwork of private and public plans in Canada is inequitable, inefficient and costly.
"Canada’s pharmaceutical policies are a total failure," the study's author, Marc-André Gagnon, told reporters on Monday in Ottawa.
The report also finds that Canada is either the third or fourth most expensive country for brand-name drugs every year — after the United States, Switzerland and Germany — because it deliberately inflates drug prices in order to attract pharmaceutical investment.
P.O.V.:
Would you support a universal pharmacare plan? Take our poll.
Meanwhile, Canada has one of the highest annual growth of drug costs among industrialized countries — much higher than countries that have universal pharmacare programs, such as France, Australia and Sweden, said Gagnon, a professor of public policy at Carleton University.
"The cost of such policies far exceed the benefits to Canadians from having a domestic pharmaceutical industry," he said.
The current system is also unfair, Gagnon said, because Canadians receive different coverage depending on what plan they're in and where they live.
Lower administrative costs
Universal pharmacare would lead to savings of nearly $3 billion a year if Canada keeps its current policy, Gagnon said.
But the savings could increase to $10.7 billion, or 43 per cent of annual drug costs, if Canada cut all privileges to the pharmaceutical industry for drug costs, according to the report.
Much of what Canadians spend on prescription drugs is eaten up by administration costs from hundreds of different private, public and company plans, according to the report.
A national drug plan would allow governments to buy drugs in bulk and be the sole administrator, which would mean billions of dollars in savings, agreed Dr. Michael Rachlis, a health policy analyst who teaches medicine at the University of Toronto.
"We reduce the administrative costs because private insurance is much more expensive to administer than public insurance, which is one of the reasons why U.S. health care costs are so much higher than ours," Rachlis said.
The report comes as provincial and territorial health ministers meet in St. John's, where rising health-care and drug costs are high on the agenda.
"Rising costs in health care are affecting every province, and any time that we can look at a program that will help contain those costs it's certainly worth looking at," Saskatchewan's Health Minister, Don McMorris, said in an interview from St. John's on Monday.
Timing right?
At the close of Monday's session in St. John's, Ontario Health Minister Deb Matthews said her province spends about $4 billion a year on drugs, and provinces collectively spend about $10 billion. The ministers think they can get better prices by working together, Matthews told reporters.
A national pharmacare program would require agreement from all provinces and territories.
The timing could be right for such a program, said Steve Morgan, a health economist with Centre for Health Service and Policy Research at the University of British Columbia.
For the first time in decades, drug prices are starting to fall as patents for "blockbuster" drugs like those used to control high blood pressure and cholesterol start to expire, Morgan said. The U.S. is already seeing a slight slowdown in spending, he said.
Meanwhile, the federal and provincial governments are looking for a new plan to replace the Canada Health Accord, which expires in 2014.
Morgan said universal pharmacare could signal a renewal that would benefit all Canadians. So far, the federal government has shown little interest.
The health ministers' meeting wraps up on Tuesday.
A new study on Canada's pharmaceutical policies concludes that a universal drug plan could save up to $10.7 billion a year in total drug expenditures. (Nati Harnik/Associated Press)
The report, released on Monday by the Canadian Centre for Policy Alternatives, concludes the existing patchwork of private and public plans in Canada is inequitable, inefficient and costly.
"Canada’s pharmaceutical policies are a total failure," the study's author, Marc-André Gagnon, told reporters on Monday in Ottawa.
The report also finds that Canada is either the third or fourth most expensive country for brand-name drugs every year — after the United States, Switzerland and Germany — because it deliberately inflates drug prices in order to attract pharmaceutical investment.
P.O.V.:
Would you support a universal pharmacare plan? Take our poll.
Meanwhile, Canada has one of the highest annual growth of drug costs among industrialized countries — much higher than countries that have universal pharmacare programs, such as France, Australia and Sweden, said Gagnon, a professor of public policy at Carleton University.
"The cost of such policies far exceed the benefits to Canadians from having a domestic pharmaceutical industry," he said.
The current system is also unfair, Gagnon said, because Canadians receive different coverage depending on what plan they're in and where they live.
Lower administrative costs
Universal pharmacare would lead to savings of nearly $3 billion a year if Canada keeps its current policy, Gagnon said.
But the savings could increase to $10.7 billion, or 43 per cent of annual drug costs, if Canada cut all privileges to the pharmaceutical industry for drug costs, according to the report.
Much of what Canadians spend on prescription drugs is eaten up by administration costs from hundreds of different private, public and company plans, according to the report.
A national drug plan would allow governments to buy drugs in bulk and be the sole administrator, which would mean billions of dollars in savings, agreed Dr. Michael Rachlis, a health policy analyst who teaches medicine at the University of Toronto.
"We reduce the administrative costs because private insurance is much more expensive to administer than public insurance, which is one of the reasons why U.S. health care costs are so much higher than ours," Rachlis said.
The report comes as provincial and territorial health ministers meet in St. John's, where rising health-care and drug costs are high on the agenda.
"Rising costs in health care are affecting every province, and any time that we can look at a program that will help contain those costs it's certainly worth looking at," Saskatchewan's Health Minister, Don McMorris, said in an interview from St. John's on Monday.
Timing right?
At the close of Monday's session in St. John's, Ontario Health Minister Deb Matthews said her province spends about $4 billion a year on drugs, and provinces collectively spend about $10 billion. The ministers think they can get better prices by working together, Matthews told reporters.
A national pharmacare program would require agreement from all provinces and territories.
The timing could be right for such a program, said Steve Morgan, a health economist with Centre for Health Service and Policy Research at the University of British Columbia.
For the first time in decades, drug prices are starting to fall as patents for "blockbuster" drugs like those used to control high blood pressure and cholesterol start to expire, Morgan said. The U.S. is already seeing a slight slowdown in spending, he said.
Meanwhile, the federal and provincial governments are looking for a new plan to replace the Canada Health Accord, which expires in 2014.
Morgan said universal pharmacare could signal a renewal that would benefit all Canadians. So far, the federal government has shown little interest.
The health ministers' meeting wraps up on Tuesday.
Sibutramine Increases Risk for MI and Stroke Among Patients with Heart Disease
The weight-loss drug sibutramine (Meridia) — up for review by FDA advisers on Sept. 15 — poses increased risk for cardiovascular events among adults with cardiovascular disease (CVD), according to a New England Journal of Medicine study.
Industry-supported researchers randomized nearly 10,000 overweight or obese adults with cardiovascular disease and/or diabetes to receive sibutramine or placebo. During 3.4 years' treatment, sibutramine recipients were at greater risk for nonfatal MI (4.1% vs. 3.2%) and stroke (2.6% vs. 1.9%), although not cardiovascular mortality. In subgroup analyses, the increased risks were seen among subjects with CVD and CVD plus diabetes, but not among those with diabetes alone.
The authors conclude that sibutramine "should continue to be excluded from use in patients with preexisting cardiovascular disease." Editorialists, however, take a stronger stance: "Given that sibutramine has minimal efficacy for weight loss, no apparent benefit for clinical outcomes, [and] a worrisome cardiovascular risk profile, ... it is difficult to discern a credible rationale for keeping this medication on the market."
Industry-supported researchers randomized nearly 10,000 overweight or obese adults with cardiovascular disease and/or diabetes to receive sibutramine or placebo. During 3.4 years' treatment, sibutramine recipients were at greater risk for nonfatal MI (4.1% vs. 3.2%) and stroke (2.6% vs. 1.9%), although not cardiovascular mortality. In subgroup analyses, the increased risks were seen among subjects with CVD and CVD plus diabetes, but not among those with diabetes alone.
The authors conclude that sibutramine "should continue to be excluded from use in patients with preexisting cardiovascular disease." Editorialists, however, take a stronger stance: "Given that sibutramine has minimal efficacy for weight loss, no apparent benefit for clinical outcomes, [and] a worrisome cardiovascular risk profile, ... it is difficult to discern a credible rationale for keeping this medication on the market."
Saturday, August 28, 2010
Dutasteride Gives Mixed Results in Preventing Prostate Cancer
Dutasteride lowers the incidence of prostate cancer, but not high-grade tumors, according to a New England Journal of Medicine study.
In a double-blind study designed by dutasteride's manufacturer, some 6700 high-risk men underwent randomization to either daily dutasteride or placebo. At entry, subjects were 50 to 75 years old, had PSA levels between 2.5 and 10 ng/mL, and had had a negative biopsy.
During 4 years' follow-up, the incidence of biopsy-detected cancer was lower in the treatment group than in controls (20% vs. 25%). The number of high-grade tumors, however, was significantly higher in the treatment group during the last 2 years of follow-up.
An editorialist concludes that the 5-alpha-reductase inhibitors like dutasteride "do not prevent ... but merely temporarily shrink tumors that have a low potential for being lethal." He adds that, because the drugs suppress PSA levels, "men may have a false sense of security," thus delaying diagnosis.
In a double-blind study designed by dutasteride's manufacturer, some 6700 high-risk men underwent randomization to either daily dutasteride or placebo. At entry, subjects were 50 to 75 years old, had PSA levels between 2.5 and 10 ng/mL, and had had a negative biopsy.
During 4 years' follow-up, the incidence of biopsy-detected cancer was lower in the treatment group than in controls (20% vs. 25%). The number of high-grade tumors, however, was significantly higher in the treatment group during the last 2 years of follow-up.
An editorialist concludes that the 5-alpha-reductase inhibitors like dutasteride "do not prevent ... but merely temporarily shrink tumors that have a low potential for being lethal." He adds that, because the drugs suppress PSA levels, "men may have a false sense of security," thus delaying diagnosis.
Tuesday, August 24, 2010
Broad Review of FDA Trials Suggests Antidepressants Only Marginally Better than Placebo
August 24, 2010 — A new review of 4 meta-analyses of efficacy trials submitted to the US Food and Drug Administration (FDA) suggests that antidepressants are only "marginally efficacious" compared with placebo and "document profound publication bias that inflates their apparent efficacy."
In addition, when the researchers also analyzed the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, "the largest antidepressant effectiveness trial ever conducted," they found that "the effectiveness of antidepressant therapies was probably even lower than the modest one reported...with an apparent progressively increasing dropout rate across each study phase.
"We found that out of the 4041 patients initially started on the SSRI [selective serotonin reuptake inhibitor] citalopram in the STAR*D study, and after 4 trials, only 108 patients had a remission and did not either have a relapse and/or dropped out by the end of 12 months of continuing care," lead study author Ed Pigott, PhD, a psychologist with NeuroAdvantage LLC in Clarksville, Maryland, told Medscape Medical News.
Sustained Benefit "Jaw Dropping"
"In other words, if you're trying to look at sustained benefit, you're only looking at 2.7%, which is a pretty jaw-dropping number," added Dr. Pigott.
Overall, "the reviewed findings argue for a reappraisal of the current recommended standard of care of depression," write the study authors.
"I believe there are likely some people where [antidepressants] are truly beneficial beyond placebo. The problem right now is that we simply have no way of knowing who those people are," noted Dr. Pigott. "My hope is that this kind of analysis creates 'more oxygen' for looking at other kinds of approaches to treatment."
The study was published in the August issue of Psychotherapy and Psychosomatics.
When registering new drug application trials with the FDA, drug companies must prespecify the primary and secondary outcome measures, the investigators report. "Prespecification is essential to ensure the integrity of a trial and enables the discovery of when investigators selectively publish the measures that show the outcome the sponsors prefer following data collection and analysis, a form of researcher bias known as HARKing or 'hypothesizing after the results are known'," they write.
For this article, Dr. Pigott and his team reviewed the following meta-analyses:
•1. Rising and colleagues (reviewed all efficacy trials for new drugs between 2001 and 2002)
•2. Turner and colleagues (reviewed 74 past trials of 12 antidepressants)
•3. Kirsch and colleagues, 2002 (reviewed 47 trials of 6 FDA-approved antidepressants)
•4. Kirsch and colleagues, 2008 (reviewed depression severity and efficacy in 35 trials)
The researchers also sought to reevaluate the methods and findings of STAR*D, a randomized, controlled trial of patients with depression. Its prespecified primary outcome measure was the Hamilton Rating Scale for Depression (HRSD), whereas the Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30) was secondary for identifying remitted and responder patients.
"STAR*D was designed to identify the best next-step treatment for the many patients who fail to get adequate relief from their initial SSRI trial," the study authors write.
"When I first read about STAR*D's step 1 phase, it just seemed biased to me," explained Dr. Pigott. "I thought of it as the 'tag, you're healed' research design. Patients who were scored as having a remission during the first 4 to 6 weeks of up to 14 weeks of acute care treatment were counted as remitted, taken out of the subject pool, and put into the follow-up care phase. In other words, they didn't have the ability to have a relapse. But as most people know, depression ebbs and flows.
"So what made me want to continue to follow this study was that it became clear that the only way that people were really going to be able to evaluate the antidepressants' effectiveness was to wait for the publication of the follow-up findings," he added. "After their major final summary study was published, I felt as though the results weren't really being portrayed in a manner that was consistent with the study's prespecified criteria."
High Dropout, Low Remission Rates
In addition to reporting on low efficacy of antidepressants compared with placebo, the 4 meta-analyses "also document a second form of bias in which researchers fail to report the negative results for the prespecified primary outcome measure submitted to the FDA, while highlighting in published studies positive results from a secondary or even a new measure, as though it was their primary measure of interest," the investigators write.
For example, they note, the meta-analysis from Rising and colleagues found that studies with favorable outcomes were almost 5 times more likely to be published and that over 26% of primary outcome measures were left out of journal articles. Turner and colleagues found that antidepressant studies were 16 times more likely to be published if favorable compared with those with unfavorable outcomes.
In reanalyzing the STAR*D methods, the researchers found that the high dropout rate resulted in frequently missed exit HRSD and IDS-C30 interviews. So the revised statistical analytical plan dropped the IDS-30 for the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), which was given at each visit.
"Even with the extraordinary care of STAR*D, only about one fourth of patients achieved remission in step 1 [and] the dropout rate was slightly larger than the success rate," the study authors write. Steps 2 through 4 also each showed increasingly fewer success rates and larger dropout rates.
Of the 4041 patients at the study's initiation, 370 (9.2%) dropped out within 2 weeks, and only 1854 patients (45.9%) obtained remission "using the lenient QIDS-SR criteria." Of these, 670 dropped out within a month of their remission, and only 108 "survived continuing care" and underwent the final assessment.
Dr. Pigott described reanalyzing STAR*D as being "a bit like an onion. Each time we thought we understood the results, we found another layer. It wasn't until about a year and a half ago that we discovered that the secondary outcome measure, the QIDS-SR, was not originally supposed to be used as a research measure. What was particularly disconcerting to me was that in their summary article, they basically used the QIDS-SR to report all of the results, which clearly had an inflationary effect on the outcome."
He also noted that STAR*D did not have a placebo design. "Because the patients knew they were receiving the active medication, I would have expected a higher remission rate than what you'd find normally in a placebo-controlled study.
"The inescapable conclusion from the STAR*D results is that we need to explore more seriously other forms of treatment (and combination thereof) that may be more effective. This effort will require developing new service delivery models to ensure that as treatments are identified, they are widely implemented," the investigators conclude.
Need for Biomarkers
"For STAR*D, we wanted to do a study that other people could then reanalyze and look at. So I'm very glad that these authors reexamined it and saw it slightly differently, which came mainly from ways of analyzing data," Maurizio Fava, MD, STAR*D trial investigator and executive vice chair of the Department of Psychiatry at Massachusetts General Hospital in Boston, told Medscape Medical News.
"I think their analysis is reasonable and not incompatible with what we had reported," added Dr. Fava, who was not involved with this review.
He noted that the review's message for clinicians is that "there's been a failure of the field to demonstrate robust advantages of antidepressants over placebo. It's doesn't mean that clinicians shouldn't use antidepressants, but they should recognize that there's a limitation. On the other hand, we have very plausible, reasonable explanations for such failure, including the fact that patients who don't actually have the disease have often been enrolled in the studies. Therefore, this failure may have to do with imperfect clinical trial design and conduct."
In addition, Dr. Fava said that the review points to a lack of long-term efficacy for antidepressants, although "this may be due to things such as inadequate management of patients without dose adjustments and other things that can increase the likelihood of remaining well.
"Regardless of how you look at it, this study suggests the importance of developing biomarkers to identify patients who really need these antidepressants both in the short and the long term," concluded Dr. Fava. "I'd say there's a real opportunity here for that."
Dr. Pigott reports consulting in the past 3 years for CNS Response, Midwest Center for Stress and Anxiety, and SmartBrain Technologies. Dr. Fava reports several disclosures, which are listed in the original STAR*D papers
In addition, when the researchers also analyzed the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, "the largest antidepressant effectiveness trial ever conducted," they found that "the effectiveness of antidepressant therapies was probably even lower than the modest one reported...with an apparent progressively increasing dropout rate across each study phase.
"We found that out of the 4041 patients initially started on the SSRI [selective serotonin reuptake inhibitor] citalopram in the STAR*D study, and after 4 trials, only 108 patients had a remission and did not either have a relapse and/or dropped out by the end of 12 months of continuing care," lead study author Ed Pigott, PhD, a psychologist with NeuroAdvantage LLC in Clarksville, Maryland, told Medscape Medical News.
Sustained Benefit "Jaw Dropping"
"In other words, if you're trying to look at sustained benefit, you're only looking at 2.7%, which is a pretty jaw-dropping number," added Dr. Pigott.
Overall, "the reviewed findings argue for a reappraisal of the current recommended standard of care of depression," write the study authors.
"I believe there are likely some people where [antidepressants] are truly beneficial beyond placebo. The problem right now is that we simply have no way of knowing who those people are," noted Dr. Pigott. "My hope is that this kind of analysis creates 'more oxygen' for looking at other kinds of approaches to treatment."
The study was published in the August issue of Psychotherapy and Psychosomatics.
When registering new drug application trials with the FDA, drug companies must prespecify the primary and secondary outcome measures, the investigators report. "Prespecification is essential to ensure the integrity of a trial and enables the discovery of when investigators selectively publish the measures that show the outcome the sponsors prefer following data collection and analysis, a form of researcher bias known as HARKing or 'hypothesizing after the results are known'," they write.
For this article, Dr. Pigott and his team reviewed the following meta-analyses:
•1. Rising and colleagues (reviewed all efficacy trials for new drugs between 2001 and 2002)
•2. Turner and colleagues (reviewed 74 past trials of 12 antidepressants)
•3. Kirsch and colleagues, 2002 (reviewed 47 trials of 6 FDA-approved antidepressants)
•4. Kirsch and colleagues, 2008 (reviewed depression severity and efficacy in 35 trials)
The researchers also sought to reevaluate the methods and findings of STAR*D, a randomized, controlled trial of patients with depression. Its prespecified primary outcome measure was the Hamilton Rating Scale for Depression (HRSD), whereas the Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30) was secondary for identifying remitted and responder patients.
"STAR*D was designed to identify the best next-step treatment for the many patients who fail to get adequate relief from their initial SSRI trial," the study authors write.
"When I first read about STAR*D's step 1 phase, it just seemed biased to me," explained Dr. Pigott. "I thought of it as the 'tag, you're healed' research design. Patients who were scored as having a remission during the first 4 to 6 weeks of up to 14 weeks of acute care treatment were counted as remitted, taken out of the subject pool, and put into the follow-up care phase. In other words, they didn't have the ability to have a relapse. But as most people know, depression ebbs and flows.
"So what made me want to continue to follow this study was that it became clear that the only way that people were really going to be able to evaluate the antidepressants' effectiveness was to wait for the publication of the follow-up findings," he added. "After their major final summary study was published, I felt as though the results weren't really being portrayed in a manner that was consistent with the study's prespecified criteria."
High Dropout, Low Remission Rates
In addition to reporting on low efficacy of antidepressants compared with placebo, the 4 meta-analyses "also document a second form of bias in which researchers fail to report the negative results for the prespecified primary outcome measure submitted to the FDA, while highlighting in published studies positive results from a secondary or even a new measure, as though it was their primary measure of interest," the investigators write.
For example, they note, the meta-analysis from Rising and colleagues found that studies with favorable outcomes were almost 5 times more likely to be published and that over 26% of primary outcome measures were left out of journal articles. Turner and colleagues found that antidepressant studies were 16 times more likely to be published if favorable compared with those with unfavorable outcomes.
In reanalyzing the STAR*D methods, the researchers found that the high dropout rate resulted in frequently missed exit HRSD and IDS-C30 interviews. So the revised statistical analytical plan dropped the IDS-30 for the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), which was given at each visit.
"Even with the extraordinary care of STAR*D, only about one fourth of patients achieved remission in step 1 [and] the dropout rate was slightly larger than the success rate," the study authors write. Steps 2 through 4 also each showed increasingly fewer success rates and larger dropout rates.
Of the 4041 patients at the study's initiation, 370 (9.2%) dropped out within 2 weeks, and only 1854 patients (45.9%) obtained remission "using the lenient QIDS-SR criteria." Of these, 670 dropped out within a month of their remission, and only 108 "survived continuing care" and underwent the final assessment.
Dr. Pigott described reanalyzing STAR*D as being "a bit like an onion. Each time we thought we understood the results, we found another layer. It wasn't until about a year and a half ago that we discovered that the secondary outcome measure, the QIDS-SR, was not originally supposed to be used as a research measure. What was particularly disconcerting to me was that in their summary article, they basically used the QIDS-SR to report all of the results, which clearly had an inflationary effect on the outcome."
He also noted that STAR*D did not have a placebo design. "Because the patients knew they were receiving the active medication, I would have expected a higher remission rate than what you'd find normally in a placebo-controlled study.
"The inescapable conclusion from the STAR*D results is that we need to explore more seriously other forms of treatment (and combination thereof) that may be more effective. This effort will require developing new service delivery models to ensure that as treatments are identified, they are widely implemented," the investigators conclude.
Need for Biomarkers
"For STAR*D, we wanted to do a study that other people could then reanalyze and look at. So I'm very glad that these authors reexamined it and saw it slightly differently, which came mainly from ways of analyzing data," Maurizio Fava, MD, STAR*D trial investigator and executive vice chair of the Department of Psychiatry at Massachusetts General Hospital in Boston, told Medscape Medical News.
"I think their analysis is reasonable and not incompatible with what we had reported," added Dr. Fava, who was not involved with this review.
He noted that the review's message for clinicians is that "there's been a failure of the field to demonstrate robust advantages of antidepressants over placebo. It's doesn't mean that clinicians shouldn't use antidepressants, but they should recognize that there's a limitation. On the other hand, we have very plausible, reasonable explanations for such failure, including the fact that patients who don't actually have the disease have often been enrolled in the studies. Therefore, this failure may have to do with imperfect clinical trial design and conduct."
In addition, Dr. Fava said that the review points to a lack of long-term efficacy for antidepressants, although "this may be due to things such as inadequate management of patients without dose adjustments and other things that can increase the likelihood of remaining well.
"Regardless of how you look at it, this study suggests the importance of developing biomarkers to identify patients who really need these antidepressants both in the short and the long term," concluded Dr. Fava. "I'd say there's a real opportunity here for that."
Dr. Pigott reports consulting in the past 3 years for CNS Response, Midwest Center for Stress and Anxiety, and SmartBrain Technologies. Dr. Fava reports several disclosures, which are listed in the original STAR*D papers
Saturday, August 14, 2010
National Center for Complementary and Alternative Medicine
Criticism
Critics attest that despite the publicized intentions at its founding, NCCAM and its predecessor, the Office of Alternative Medicine, have spent more than $800 million on such research since 1991 but have neither succeeded in demonstrating the efficacy of a single alternative method nor declared any alternative medicine treatment ineffective. "The NCCAM continues to fund and promote pseudoscience. Political pressures and the Center's charter would seem to make this inevitable," said Kimball C. Atwood IV, M.D.[5]
A policy forum in Science stated,
We believe that NCCAM [National Center for Complementary and Alternative Medicine] funds proposals of dubious merit; its research agenda is shaped more by politics than by science; and it is structured by its charter in a manner that precludes an independent review of its performance...In view of the popularity of alternative therapies, it is appropriate to evaluate the efficacy and safety of selected treatments.
but research falls below the standards of other NIH institutes. NCCAM budget for 2005 was $123.1 million. The charter said that 12 of the 18 members of the NCCAM Advisory Council "shall be selected from among the leading representatives of the health and scientific disciplines...in the area of complementary and alternative medicine. Nine of the members shall be practitioners licensed in one or more of the major systems with which the Center is involved". Clinical trials of St. John's wort, echinacea, and saw palmetto have been published; none was more effective than placebo, but manufacturers said the studies were flawed, and these studies are unlikely to change practices. 70% said they would continue using a supplement that a government agency said was ineffective. NCCAM is funding a study of EDTA chelation therapy for coronary artery disease with 2,300 patients, even though smaller controlled trials have found chelation ineffective. Another negative trial won't modify the practice of individuals who choose to ignore existing negative evidence. NCCAM is also funding a trial of gemcitabine with the Gonzalez regimen for stage II to IV pancreatic cancer, in the belief that cancer is caused by a deficiency of pancreatic proteolytic enzymes that would normally eliminate toxins; severe adverse effects are associated with the Gonzalez regimen. No evidence in peer-reviewed journals supports the plausibility or efficacy of chelation therapy or the Gonzalez protocol[6] and a test of the protocol reported in 2009 found patients receiving the treatment had worse quality of life and died faster than conventionally treated counterparts.[7]
Critics attest that despite the publicized intentions at its founding, NCCAM and its predecessor, the Office of Alternative Medicine, have spent more than $800 million on such research since 1991 but have neither succeeded in demonstrating the efficacy of a single alternative method nor declared any alternative medicine treatment ineffective. "The NCCAM continues to fund and promote pseudoscience. Political pressures and the Center's charter would seem to make this inevitable," said Kimball C. Atwood IV, M.D.[5]
A policy forum in Science stated,
We believe that NCCAM [National Center for Complementary and Alternative Medicine] funds proposals of dubious merit; its research agenda is shaped more by politics than by science; and it is structured by its charter in a manner that precludes an independent review of its performance...In view of the popularity of alternative therapies, it is appropriate to evaluate the efficacy and safety of selected treatments.
but research falls below the standards of other NIH institutes. NCCAM budget for 2005 was $123.1 million. The charter said that 12 of the 18 members of the NCCAM Advisory Council "shall be selected from among the leading representatives of the health and scientific disciplines...in the area of complementary and alternative medicine. Nine of the members shall be practitioners licensed in one or more of the major systems with which the Center is involved". Clinical trials of St. John's wort, echinacea, and saw palmetto have been published; none was more effective than placebo, but manufacturers said the studies were flawed, and these studies are unlikely to change practices. 70% said they would continue using a supplement that a government agency said was ineffective. NCCAM is funding a study of EDTA chelation therapy for coronary artery disease with 2,300 patients, even though smaller controlled trials have found chelation ineffective. Another negative trial won't modify the practice of individuals who choose to ignore existing negative evidence. NCCAM is also funding a trial of gemcitabine with the Gonzalez regimen for stage II to IV pancreatic cancer, in the belief that cancer is caused by a deficiency of pancreatic proteolytic enzymes that would normally eliminate toxins; severe adverse effects are associated with the Gonzalez regimen. No evidence in peer-reviewed journals supports the plausibility or efficacy of chelation therapy or the Gonzalez protocol[6] and a test of the protocol reported in 2009 found patients receiving the treatment had worse quality of life and died faster than conventionally treated counterparts.[7]
Phenfen pbs frontline
In our documentary segment about the Fen Phen disaster, we met Dr. Stuart Rich, a respected cardiologist and pulmonologist from the Rush Heart Institute in Chicago. During the mid-1990s, Rich played a central role in conducting the International Primary Pulmonary Hypertension study -- a large study of European men and women who were taking diet drugs, including Pondimin, which was on the market in the United states, and a closely-related "sister drug," Redux, which was not yet on the American market.
One of the main goals of the study was to evaluate the connection between these drugs and pulmonary hypertension, a devastating side effect that reduces the lung's ability to absorb oxygen, leading to constant shortness of breath and ultimately death. While a few cases had been reported around the world, drug manufacturers had long claimed that Pondimin and Redux only rarely caused pulmonary hypertension. Furthermore, they said, the benefit of losing weight was far more significant than the risk of developing the side effect.
In their three-year study, Dr. Rich and his colleagues found that Pondimin and Redux posed a "significant risk of dying from pulmonary hypertension," according to Rich. "And the risk went up the longer you took the drugs." Those results, and the fact that on average most people only lost a small amount of weight when they took these medicines, made Rich an opponent of FDA approval for Redux -- particularly for long-term use.
While Rich was appalled by the drug company's determination to put its drug on the American market, he was even more upset when the FDA acquiesced and approved the drug in the summer of 1996. "My reaction was despair," he told us. "Why despair? My specialty is I treat patients with pulmonary hypertension. These are the sickest cardiovascular patients that exist. They're young people. They're tragic stories. We have some treatments … but it's a death sentence. And it's a slow death, drowning, months to years."
Rich's only comfort was knowing that the European study would soon be published in The New England Journal of Medicine -- one of the most prestigious medical journals in the world. The drug company may have pushed this controversial product onto the market, thought Rich, and the FDA may have gone along with the idea, but doctors would soon read the study's findings about Redux when the Journal came out. Then, he hoped, doctors would stop prescribing the drug so often.
But getting out a clear message to consumers and the medical community about the risks posed by these diet drugs proved to be more difficult than Rich imagined.
• • •
The day before his article officially came out, Rich got a phone call from a newspaper reporter who had received an advance copy of the Journal and wanted Rich's reaction to an accompanying editorial -ã which Rich hadn't seen yet. (As was the custom at The New England Journal of Medicine, the magazine's editors had invited two prominent scientists to write an editorial about the European study to put it into perspective and help doctors determine whether and when the risk of using the diet drugs would be justified by the benefits.) Much to Dr. Rich's dismay, the editorial claimed that the benefits of using Pondimin and Redux far outweighed any risks and compared the risk of taking the diet drugs to taking penicillin for an infection. In effect, the editorial advised the medical community not to pay too much attention to Rich's study, and not to stop prescribing the drugs.
When Rich heard who the authors of the editorial were -- Dr. JoAnn Manson and Dr. Gerald Faich -- he realized immediately that both had financial ties to the drug companies that were making and/or selling Redux. And both had done work with those companies specifically in connection with Redux. "This was one of the greatest scandals that ever hit The New England Journal of Medicine," says Rich.
To guard against such potential conflicts of interest, it had been the Journal's policy to always ask editorial writers whether they had any "ongoing financial associations" with the company producing the product. In this case, the two scientists who authored the diet drug study editorial had told the magazine's editors -- in writing -- that they had "no financial interest or equity in any pharmaceutical company producing anti-obesity agents."
As word of the editorial controversy spread, the Journal's editors asked the two scientists to explain their written statement that they didn't have any financial interest in the company. In their defense, both authors downplayed their financial connections to the companies, and pointed out that the Journal had defined "ongoing financial associations" as "equity interest, regular consultancies, or major research support" and that their associations were neither "regular" nor "ongoing" but more occasional and not relevant to their editorial.
Despite the authors' explanations, a few weeks after publishing the pulmonary hypertension study the Journal's editors, Dr. Marcia Angell and Dr. Jerome Kassirer, ran a new editorial acknowledging that the authors may have misinterpreted the Journal's definition of "financial associations," but the editors also cast doubt on the credibility of any editorial written by someone with the kinds of financial ties that the authors had. (You can read the original Journal article [free registration required to read the full text] on the study and the accompanying editorial on the New England Journal's Web site. And you can also read the editors' follow-up editorial.)
But by that time, the damage may have been done. Thanks to the editorial that had run with the study article, many doctors around the world may well have dismissed the study's results and decided not to worry about prescribing Pondimin and Redux.
• • •
The Journal affair wasn't the only development that interfered with getting the story out about the European diet drug study, says Rich. The drug manufacturer, he says, tried to stop him from talking to the general public.
The news that popular diet drugs carried significant risks prompted NBC's Today show to invite Rich to appear on their morning program to talk about the study. Host Bryant Gumbel asked him to tell the country about the study and put it in perspective. "What I said," Rich recalls, "was nothing that was not mentioned in the paper: that the drug carried a very high risk of developing this fatal disease, that it should not be prescribed lightly."
A couple of hours after the live broadcast, Rich returned to his office where, he says, he received a phone call from a senior executive at Wyeth Pharmaceuticals.
"He told me he saw my interview on the Today show and warned me that it was very dangerous for me to talk to the press about that, that if I had any issues regarding their product that I wanted to publish in a scientific journal, so be it. But if I spoke to the media about their drug, bad things would happen. 'Bad things would happen' was the exact phrase he used. ... And I never talked to the press again. Because I didn't know what they had in mind. ... They are a very big, a very powerful company."
Rich has told his story under oath in several legal depositions as part of lawsuits brought by Fen Phen victims against the company.
For his part, the senior Wyeth executive has testified under oath in at least one deposition and denied having ever threatened Rich.
We will never know whose version of the facts is correct -- because none of the parties can prove one way or the other that they are being truthful. One thing is certain, however. Dr. Rich didn't speak to the popular press about Redux and Pondimin for many years after that appearance on the Today show -- and until now, he never told anybody in the media the details about that phone call.
One of the main goals of the study was to evaluate the connection between these drugs and pulmonary hypertension, a devastating side effect that reduces the lung's ability to absorb oxygen, leading to constant shortness of breath and ultimately death. While a few cases had been reported around the world, drug manufacturers had long claimed that Pondimin and Redux only rarely caused pulmonary hypertension. Furthermore, they said, the benefit of losing weight was far more significant than the risk of developing the side effect.
In their three-year study, Dr. Rich and his colleagues found that Pondimin and Redux posed a "significant risk of dying from pulmonary hypertension," according to Rich. "And the risk went up the longer you took the drugs." Those results, and the fact that on average most people only lost a small amount of weight when they took these medicines, made Rich an opponent of FDA approval for Redux -- particularly for long-term use.
While Rich was appalled by the drug company's determination to put its drug on the American market, he was even more upset when the FDA acquiesced and approved the drug in the summer of 1996. "My reaction was despair," he told us. "Why despair? My specialty is I treat patients with pulmonary hypertension. These are the sickest cardiovascular patients that exist. They're young people. They're tragic stories. We have some treatments … but it's a death sentence. And it's a slow death, drowning, months to years."
Rich's only comfort was knowing that the European study would soon be published in The New England Journal of Medicine -- one of the most prestigious medical journals in the world. The drug company may have pushed this controversial product onto the market, thought Rich, and the FDA may have gone along with the idea, but doctors would soon read the study's findings about Redux when the Journal came out. Then, he hoped, doctors would stop prescribing the drug so often.
But getting out a clear message to consumers and the medical community about the risks posed by these diet drugs proved to be more difficult than Rich imagined.
• • •
The day before his article officially came out, Rich got a phone call from a newspaper reporter who had received an advance copy of the Journal and wanted Rich's reaction to an accompanying editorial -ã which Rich hadn't seen yet. (As was the custom at The New England Journal of Medicine, the magazine's editors had invited two prominent scientists to write an editorial about the European study to put it into perspective and help doctors determine whether and when the risk of using the diet drugs would be justified by the benefits.) Much to Dr. Rich's dismay, the editorial claimed that the benefits of using Pondimin and Redux far outweighed any risks and compared the risk of taking the diet drugs to taking penicillin for an infection. In effect, the editorial advised the medical community not to pay too much attention to Rich's study, and not to stop prescribing the drugs.
When Rich heard who the authors of the editorial were -- Dr. JoAnn Manson and Dr. Gerald Faich -- he realized immediately that both had financial ties to the drug companies that were making and/or selling Redux. And both had done work with those companies specifically in connection with Redux. "This was one of the greatest scandals that ever hit The New England Journal of Medicine," says Rich.
To guard against such potential conflicts of interest, it had been the Journal's policy to always ask editorial writers whether they had any "ongoing financial associations" with the company producing the product. In this case, the two scientists who authored the diet drug study editorial had told the magazine's editors -- in writing -- that they had "no financial interest or equity in any pharmaceutical company producing anti-obesity agents."
As word of the editorial controversy spread, the Journal's editors asked the two scientists to explain their written statement that they didn't have any financial interest in the company. In their defense, both authors downplayed their financial connections to the companies, and pointed out that the Journal had defined "ongoing financial associations" as "equity interest, regular consultancies, or major research support" and that their associations were neither "regular" nor "ongoing" but more occasional and not relevant to their editorial.
Despite the authors' explanations, a few weeks after publishing the pulmonary hypertension study the Journal's editors, Dr. Marcia Angell and Dr. Jerome Kassirer, ran a new editorial acknowledging that the authors may have misinterpreted the Journal's definition of "financial associations," but the editors also cast doubt on the credibility of any editorial written by someone with the kinds of financial ties that the authors had. (You can read the original Journal article [free registration required to read the full text] on the study and the accompanying editorial on the New England Journal's Web site. And you can also read the editors' follow-up editorial.)
But by that time, the damage may have been done. Thanks to the editorial that had run with the study article, many doctors around the world may well have dismissed the study's results and decided not to worry about prescribing Pondimin and Redux.
• • •
The Journal affair wasn't the only development that interfered with getting the story out about the European diet drug study, says Rich. The drug manufacturer, he says, tried to stop him from talking to the general public.
The news that popular diet drugs carried significant risks prompted NBC's Today show to invite Rich to appear on their morning program to talk about the study. Host Bryant Gumbel asked him to tell the country about the study and put it in perspective. "What I said," Rich recalls, "was nothing that was not mentioned in the paper: that the drug carried a very high risk of developing this fatal disease, that it should not be prescribed lightly."
A couple of hours after the live broadcast, Rich returned to his office where, he says, he received a phone call from a senior executive at Wyeth Pharmaceuticals.
"He told me he saw my interview on the Today show and warned me that it was very dangerous for me to talk to the press about that, that if I had any issues regarding their product that I wanted to publish in a scientific journal, so be it. But if I spoke to the media about their drug, bad things would happen. 'Bad things would happen' was the exact phrase he used. ... And I never talked to the press again. Because I didn't know what they had in mind. ... They are a very big, a very powerful company."
Rich has told his story under oath in several legal depositions as part of lawsuits brought by Fen Phen victims against the company.
For his part, the senior Wyeth executive has testified under oath in at least one deposition and denied having ever threatened Rich.
We will never know whose version of the facts is correct -- because none of the parties can prove one way or the other that they are being truthful. One thing is certain, however. Dr. Rich didn't speak to the popular press about Redux and Pondimin for many years after that appearance on the Today show -- and until now, he never told anybody in the media the details about that phone call.
dangerous prescription pbs
Nov. 13, 2003
Whenever you make a television documentary, inevitably you shoot more material than can possibly fit into a one-hour program. That certainly happened to us in making "Dangerous Prescription." After we had researched our program and begun filming a broad story about drugs that had recently come off the market, current and former Food and Drug Administration employees began coming forward, little by little, to give us a powerful critique of what was going on inside the agency. Our story gradually began to evolve, and rather than making a documentary about drug safety in general, we ended up shifting our focus to the FDA.
But drug safety isn't just in the hands of the FDA. Americans -- and the Food and Drug Administration itself -- rely on pharmaceutical companies to be honest about what works and what doesn't. The ways in which pharmaceutical companies can "spin" bad news about their products, or influence the distribution of that news, in order to control damage and impede important information from reaching consumers and doctors, are revealed in two cases that didn't make it into the program.
What Bad News?
The first of these stories is about patients getting "less effective drugs" when better choices are available. If your doctor prescribes a less effective drug, you're not being helped as much as you could be helped. And when you think about it, that means you are being harmed.
About 50 million Americans have hypertension (commonly known as high blood pressure) -- and an estimated 30 million need some sort of medical treatment to bring their problem under control. Patients who fail to lower their blood pressure face increased risk of heart attacks, strokes and diabetes -- so the treatment of hypertension has become one of the largest markets for drugs in America and everywhere else in the developed world.
By some estimates, there are as many as 180 different prescription medications used in the United States to treat hypertension. Almost every major drug company has at least one product for lowering blood pressure, and doctors are generally happy to have these choices. But having so many choices does create a problem. Some drugs are bound to be more effective than others -- so doctors urgently want to know what's best.
Unfortunately, pharmaceutical companies rarely conduct clinical trials that fairly and objectively compare other companies' drugs against their own. And the FDA doesn't conduct such trials either, because the agency is not in the business of doing medical research -- only reviewing the results submitted by pharmaceutical companies.
• • •
With Americans spending $16 billion a year on blood pressure medicines, and no objective information to show which ones were most effective at reducing the problems caused by high blood pressure, about 10 years ago the National Heart Lung and Blood Institute (a division of the National Institutes of Health) started a long-term clinical trial that would honestly and fairly compare the effectiveness of the leading types of blood pressure medicines. The study, called ALLHAT (short for Anti-Hypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial) enrolled over 42,000 Americans, lasted for some eight years, and cost over $140 million.
It was the kind of study that only a government agency could organize -- comparing four major classes of competing hypertension drugs, each of which lowers blood pressure in its own unique way. The drugs included: a diuretic (one of the oldest and cheapest treatments for hypertension, and widely available as a generic drug); Lisinopril (one of the popular, widely prescribed "ACE inhibitors," a class of drugs that includes Capoten, Vasotec Lotensin, Monopril, Univasc, Aceon, Accupril, Altace, Mavic); Norvasc (a "calcium channel blocker" made by Pfizer and the country's largest selling treatment for hypertension according to a Pfizer annual report); and Cardura (an "alpha blocker").
According to ALLHAT's principal investigator, Dr. Curt Furberg, "since the early 1990s, ACE inhibitors and calcium channel blockers had captured maybe a third or maybe 40 percent of the market" for treating high blood pressure, cutting into the prescriptions for older drugs that had a long track record of effectiveness and that were much cheaper. "And there wasn't good evidence that the newer drugs were better, or even as good," says Furberg, "so this study was undertaken to help us figure that out."
About six years into the study, its organizers halted treatment with one of the drugs, Cardura, because an early data analysis showed that patients on Cardura were 25 percent more likely to develop cardiovascular disease than patients on diuretics, and twice as likely to develop heart failure. It wasn't that Cardura was bad, but for most people it was clear that diuretics were significantly better.
The study continued with the three remaining drugs until the summer of 2002, and then in December of last year the results were announced at a packed press conference in Washington. The news was dramatic.
While all the drugs helped lower patients' blood pressure to about the same degree, according to the ALLHAT results patients on Norvasc -- an expensive and highly-advertised product -- were 38 percent more likely to develop heart failure than patients on the cheap, tried-and-true diuretics. And patients on Lisinopril (also more expensive than diuretics, and just coming off patent) were 15 percent more likely to develop strokes, 19 percent more likely to develop heart failure, and 11 percent more like to have angina than patients on diuretics. So, as a first-line treatment, the cheapest, oldest and least-promoted drug was significantly better at preventing the serious problems that can arise from having high blood pressure.
"ALLHAT demonstrated that, in the past, we didn't spend our drug dollars wisely," says Furberg. "We put too much money into drugs that are now shown to be inferior. And we need to learn more from that. And I think it's important for society to step in and not just leave it to drug companies to promote their drugs."
In Furberg's opinion, the fact that millions of people took -- and are still taking -- less effective drugs means that tens of thousands of Americans have been developing health problems that could have been prevented by a more effective drug.
"If you eliminated all the ACE inhibitors and calcium antagonists [calcium channel blockers] for the first-line treatment of hypertension," says Furberg, and if patients were put on diuretics, "we would avert maybe 60,000 events per year -- 60,000 heart failures or strokes. These are devastating complications. So, if you want to know what has happened over the past five years, we'll you can multiply by five. So we're talking about a large number of people who unnecessarily have suffered these events because we didn't have the knowledge we have today."
Furberg does note that many patients need to combine two or more different drugs to adequately lower their blood pressure -- so there's an important role for less effective drugs. And some patients don't tolerate diuretics so they need other options. But for the vast majority of people who have just been diagnosed with high blood pressure, according to ALLHAT, diuretics were the best as a first-line treatment -- and also the cheapest.
• • •
Given the ALLHAT data about calcium channel blockers and ACE inhibitors, the question was, how to get doctors to change their prescribing habits? For that to happen, first they would have to get the news.
But as Furberg soon discovered, the maker of one of the less effective but highly popular hypertension drugs wasn't going to let its market share slip away without a fight.
On the same day that the NIH scientists announced their results to the nation, Pfizer, the manufacturer of Norvasc, started a quiet campaign to counter the study results. First, the company issued a press release highlighting all of the study findings that were positive for Norvasc -- but leaving out the findings that were negative. (The release did mention that patients should first be started on diuretics, but it didn't mention that starting patients on Norvasc would lead to more heart failure.)
See the Pfizer video release on ALLHAT in which Dr. Berelowitz speaks
Then the company sent to television stations a videotaped interview with Dr. Michael Berelowitz, vice president of Pfizer's Metabolic and Cardiovascular Group, who declared that the ALLHAT study was an affirmation for Norvasc. "This study confirms what I think we have felt all along," Dr. Berelowitz says on the tape. "And that is that Norvasc is a safe, effective, well-tolerated agent for lowering blood pressure. … Accepting that diuretics are safe and effective and decreased cardiovascular disease, ALLHAT looked to see how the new agents -- calcium channel blockers like Norvasc, and an ACE inhibitor -- compared to the diuretic. And these agents were equally effective."
Read a letter from Berelowitz responding to FRONTLINE's request for an interview.
Compare Dr. Berelowitz's statement in the video to a statement made by the NIH research team that conducted the study. "Each of the newer drugs had significantly higher rates of one or more forms of cardiovascular disease," the ALLHAT team said. They went on: "Because of their superiority in preventing one or more forms of cardiovascular disease and their lower cost … diuretics should be the drugs of choice for the initial treatment of hypertension in most patients requiring drug therapy."
In the eyes of Curt Furberg, who had spent almost 10 years organizing and supervising the ALLHAT study, Pfizer was not telling the whole story. "I have problems with any drug company pushing an inferior product," says Furberg. "I don't think that's in the best interest of the patients. This is a difficult issue that somehow I have to deal with, society has to deal with: how we handle the situation where we have good knowledge that there is a difference between drugs and whether we should allow both of them to be out there competing, or whether we should put some restriction on the inferior drugs."
It's not hard to imagine why Pfizer might have responded to the ALLHAT study the way it did. Norvasc is a very profitable drug. According to the company's summer 2002 quarterly report, "Sales of Norvasc, the world's largest-selling medicine for hypertension and angina and the fourth-largest selling pharmaceutical of any kind grew 8% … to $931 million in the first quarter, compared to the same period in 2001."
Watch a video clip in which Dr. Curt Furberg appears on a radio show called "The People's Pharmacy" to talk about the ALLHAT study.
In light of Pfizer's campaign to put its own positive spin on the ALLHAT study, Furberg decided to hit the road and start a "counter campaign" -- to make sure that doctors and patients got the entire story about ALLHAT. That meant getting himself booked on radio talk shows and traveling to medical conferences to set the record straight on the study.
Unfortunately, Furberg says, he has to play the same public-relations game the pharmaceutical companies play, or his message is going to get lost in the company's PR campaign. He has to go to the media, visit the offices of influential doctors -- and get them to look at the data. "One of our biggest problems, to tell you the truth," he says, "is that diuretics don't have any champions. They're all generic drugs nowadays and drug companies don't make much profit on them. By and large, companies are only going to promote what earns them profits. And sometimes that's not good for your health and safety."
Whenever you make a television documentary, inevitably you shoot more material than can possibly fit into a one-hour program. That certainly happened to us in making "Dangerous Prescription." After we had researched our program and begun filming a broad story about drugs that had recently come off the market, current and former Food and Drug Administration employees began coming forward, little by little, to give us a powerful critique of what was going on inside the agency. Our story gradually began to evolve, and rather than making a documentary about drug safety in general, we ended up shifting our focus to the FDA.
But drug safety isn't just in the hands of the FDA. Americans -- and the Food and Drug Administration itself -- rely on pharmaceutical companies to be honest about what works and what doesn't. The ways in which pharmaceutical companies can "spin" bad news about their products, or influence the distribution of that news, in order to control damage and impede important information from reaching consumers and doctors, are revealed in two cases that didn't make it into the program.
What Bad News?
The first of these stories is about patients getting "less effective drugs" when better choices are available. If your doctor prescribes a less effective drug, you're not being helped as much as you could be helped. And when you think about it, that means you are being harmed.
About 50 million Americans have hypertension (commonly known as high blood pressure) -- and an estimated 30 million need some sort of medical treatment to bring their problem under control. Patients who fail to lower their blood pressure face increased risk of heart attacks, strokes and diabetes -- so the treatment of hypertension has become one of the largest markets for drugs in America and everywhere else in the developed world.
By some estimates, there are as many as 180 different prescription medications used in the United States to treat hypertension. Almost every major drug company has at least one product for lowering blood pressure, and doctors are generally happy to have these choices. But having so many choices does create a problem. Some drugs are bound to be more effective than others -- so doctors urgently want to know what's best.
Unfortunately, pharmaceutical companies rarely conduct clinical trials that fairly and objectively compare other companies' drugs against their own. And the FDA doesn't conduct such trials either, because the agency is not in the business of doing medical research -- only reviewing the results submitted by pharmaceutical companies.
• • •
With Americans spending $16 billion a year on blood pressure medicines, and no objective information to show which ones were most effective at reducing the problems caused by high blood pressure, about 10 years ago the National Heart Lung and Blood Institute (a division of the National Institutes of Health) started a long-term clinical trial that would honestly and fairly compare the effectiveness of the leading types of blood pressure medicines. The study, called ALLHAT (short for Anti-Hypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial) enrolled over 42,000 Americans, lasted for some eight years, and cost over $140 million.
It was the kind of study that only a government agency could organize -- comparing four major classes of competing hypertension drugs, each of which lowers blood pressure in its own unique way. The drugs included: a diuretic (one of the oldest and cheapest treatments for hypertension, and widely available as a generic drug); Lisinopril (one of the popular, widely prescribed "ACE inhibitors," a class of drugs that includes Capoten, Vasotec Lotensin, Monopril, Univasc, Aceon, Accupril, Altace, Mavic); Norvasc (a "calcium channel blocker" made by Pfizer and the country's largest selling treatment for hypertension according to a Pfizer annual report); and Cardura (an "alpha blocker").
According to ALLHAT's principal investigator, Dr. Curt Furberg, "since the early 1990s, ACE inhibitors and calcium channel blockers had captured maybe a third or maybe 40 percent of the market" for treating high blood pressure, cutting into the prescriptions for older drugs that had a long track record of effectiveness and that were much cheaper. "And there wasn't good evidence that the newer drugs were better, or even as good," says Furberg, "so this study was undertaken to help us figure that out."
About six years into the study, its organizers halted treatment with one of the drugs, Cardura, because an early data analysis showed that patients on Cardura were 25 percent more likely to develop cardiovascular disease than patients on diuretics, and twice as likely to develop heart failure. It wasn't that Cardura was bad, but for most people it was clear that diuretics were significantly better.
The study continued with the three remaining drugs until the summer of 2002, and then in December of last year the results were announced at a packed press conference in Washington. The news was dramatic.
While all the drugs helped lower patients' blood pressure to about the same degree, according to the ALLHAT results patients on Norvasc -- an expensive and highly-advertised product -- were 38 percent more likely to develop heart failure than patients on the cheap, tried-and-true diuretics. And patients on Lisinopril (also more expensive than diuretics, and just coming off patent) were 15 percent more likely to develop strokes, 19 percent more likely to develop heart failure, and 11 percent more like to have angina than patients on diuretics. So, as a first-line treatment, the cheapest, oldest and least-promoted drug was significantly better at preventing the serious problems that can arise from having high blood pressure.
"ALLHAT demonstrated that, in the past, we didn't spend our drug dollars wisely," says Furberg. "We put too much money into drugs that are now shown to be inferior. And we need to learn more from that. And I think it's important for society to step in and not just leave it to drug companies to promote their drugs."
In Furberg's opinion, the fact that millions of people took -- and are still taking -- less effective drugs means that tens of thousands of Americans have been developing health problems that could have been prevented by a more effective drug.
"If you eliminated all the ACE inhibitors and calcium antagonists [calcium channel blockers] for the first-line treatment of hypertension," says Furberg, and if patients were put on diuretics, "we would avert maybe 60,000 events per year -- 60,000 heart failures or strokes. These are devastating complications. So, if you want to know what has happened over the past five years, we'll you can multiply by five. So we're talking about a large number of people who unnecessarily have suffered these events because we didn't have the knowledge we have today."
Furberg does note that many patients need to combine two or more different drugs to adequately lower their blood pressure -- so there's an important role for less effective drugs. And some patients don't tolerate diuretics so they need other options. But for the vast majority of people who have just been diagnosed with high blood pressure, according to ALLHAT, diuretics were the best as a first-line treatment -- and also the cheapest.
• • •
Given the ALLHAT data about calcium channel blockers and ACE inhibitors, the question was, how to get doctors to change their prescribing habits? For that to happen, first they would have to get the news.
But as Furberg soon discovered, the maker of one of the less effective but highly popular hypertension drugs wasn't going to let its market share slip away without a fight.
On the same day that the NIH scientists announced their results to the nation, Pfizer, the manufacturer of Norvasc, started a quiet campaign to counter the study results. First, the company issued a press release highlighting all of the study findings that were positive for Norvasc -- but leaving out the findings that were negative. (The release did mention that patients should first be started on diuretics, but it didn't mention that starting patients on Norvasc would lead to more heart failure.)
See the Pfizer video release on ALLHAT in which Dr. Berelowitz speaks
Then the company sent to television stations a videotaped interview with Dr. Michael Berelowitz, vice president of Pfizer's Metabolic and Cardiovascular Group, who declared that the ALLHAT study was an affirmation for Norvasc. "This study confirms what I think we have felt all along," Dr. Berelowitz says on the tape. "And that is that Norvasc is a safe, effective, well-tolerated agent for lowering blood pressure. … Accepting that diuretics are safe and effective and decreased cardiovascular disease, ALLHAT looked to see how the new agents -- calcium channel blockers like Norvasc, and an ACE inhibitor -- compared to the diuretic. And these agents were equally effective."
Read a letter from Berelowitz responding to FRONTLINE's request for an interview.
Compare Dr. Berelowitz's statement in the video to a statement made by the NIH research team that conducted the study. "Each of the newer drugs had significantly higher rates of one or more forms of cardiovascular disease," the ALLHAT team said. They went on: "Because of their superiority in preventing one or more forms of cardiovascular disease and their lower cost … diuretics should be the drugs of choice for the initial treatment of hypertension in most patients requiring drug therapy."
In the eyes of Curt Furberg, who had spent almost 10 years organizing and supervising the ALLHAT study, Pfizer was not telling the whole story. "I have problems with any drug company pushing an inferior product," says Furberg. "I don't think that's in the best interest of the patients. This is a difficult issue that somehow I have to deal with, society has to deal with: how we handle the situation where we have good knowledge that there is a difference between drugs and whether we should allow both of them to be out there competing, or whether we should put some restriction on the inferior drugs."
It's not hard to imagine why Pfizer might have responded to the ALLHAT study the way it did. Norvasc is a very profitable drug. According to the company's summer 2002 quarterly report, "Sales of Norvasc, the world's largest-selling medicine for hypertension and angina and the fourth-largest selling pharmaceutical of any kind grew 8% … to $931 million in the first quarter, compared to the same period in 2001."
Watch a video clip in which Dr. Curt Furberg appears on a radio show called "The People's Pharmacy" to talk about the ALLHAT study.
In light of Pfizer's campaign to put its own positive spin on the ALLHAT study, Furberg decided to hit the road and start a "counter campaign" -- to make sure that doctors and patients got the entire story about ALLHAT. That meant getting himself booked on radio talk shows and traveling to medical conferences to set the record straight on the study.
Unfortunately, Furberg says, he has to play the same public-relations game the pharmaceutical companies play, or his message is going to get lost in the company's PR campaign. He has to go to the media, visit the offices of influential doctors -- and get them to look at the data. "One of our biggest problems, to tell you the truth," he says, "is that diuretics don't have any champions. They're all generic drugs nowadays and drug companies don't make much profit on them. By and large, companies are only going to promote what earns them profits. And sometimes that's not good for your health and safety."
Expensive New Blood Pressure Meds No Better Than Generics, According to Long-Term Data
ScienceDaily (Aug. 14, 2010) — Expensive brand-name medications to lower blood pressure are no better at preventing cardiovascular disease than older, generic diuretics, according to new long-term data from a landmark study.
Paul Whelton, MB, MD, MSc, reported the results on Aug. 13 at the plenary session of the China Heart Congress and International Heart Forum in Beijing. Whelton is president and CEO of Loyola University Health System and chairman of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heat Attack Trial (ALLHAT), which has examined the comparative value of different blood pressure-lowering medications.
More than 33,000 patients with high blood pressure were randomly assigned to take either a diuretic (chlorthalidone) or one of two newer drugs, a calcium channel blocker (amlodipine) or an ACE inhibitor (lisinopril).
In 2002, ALLHAT researchers reported that among patients followed for four-to-eight years, the diuretic was better than the calcium channel blocker in preventing heart failure and better than the ACE inhibitor in preventing stroke, heart failure and overall cardiovascular disease.
In the new study, researchers followed ALLHAT participants for an additional four to five years after completion of the trial, bringing the total follow-up period to between eight and 13 years. During this longer follow-up period, the differences between the three drugs narrowed -- by most measures they were a statistical dead heat.
But the diuretic still was superior in two measures: Compared with the diuretic group, the ACE inhibitor group had a 20 percent higher death rate from stroke, and the calcium channel blocker group had a 12 percent higher rate of hospitalizations and deaths due to heart failure.
Diuretics, sometimes called "water pills," are the traditional medications for high blood pressure. They cause kidneys to remove sodium and water from the body, thereby relaxing blood vessel walls. ACE inhibitors such as lisinopril (brand names, Prinivil® and Zestril®) decrease chemicals that tighten blood vessels. Calcium channel blockers such as amlodipine (brand name, Norvasc®) relax blood vessels.
Diuretics cost $25 to $40 per year, while newer brand-name hypertension drugs can cost $300 to $600 per year.
The National Heart, Lung and Blood Institute recommends patients control their blood pressure by first controlling their weight, exercising, reducing sodium, increasing potassium and drinking alcohol in moderation. The institute says that if lifestyle changes are not sufficient, diuretics then normally should be the drug of first choice.
However, newer, higher-priced drugs are heavily marketed, and diuretics account for only about 30 percent of prescriptions written for high blood pressure medications, Whelton said.
Whelton is senior author of a study published in the May 24, 2010, Archives of Internal Medicine that found that using techniques similar to those employed by pharmaceutical sales reps can help persuade doctors to prescribe diuretics.
Like drug sales representatives, researchers in the study met with small groups of doctors, especially opinion leaders. They detailed guidelines for treating high blood pressure, and handed out studies, newsletters, exam room posters, etc. An examination of prescribing patterns found that this technique, known as "academic detailing," influenced what drugs doctors prescribed.
ALLHAT is sponsored by the National Heart, Lung and Blood Institute. "We are continuing to mine data that we collected during the trial," Whelton said.
Paul Whelton, MB, MD, MSc, reported the results on Aug. 13 at the plenary session of the China Heart Congress and International Heart Forum in Beijing. Whelton is president and CEO of Loyola University Health System and chairman of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heat Attack Trial (ALLHAT), which has examined the comparative value of different blood pressure-lowering medications.
More than 33,000 patients with high blood pressure were randomly assigned to take either a diuretic (chlorthalidone) or one of two newer drugs, a calcium channel blocker (amlodipine) or an ACE inhibitor (lisinopril).
In 2002, ALLHAT researchers reported that among patients followed for four-to-eight years, the diuretic was better than the calcium channel blocker in preventing heart failure and better than the ACE inhibitor in preventing stroke, heart failure and overall cardiovascular disease.
In the new study, researchers followed ALLHAT participants for an additional four to five years after completion of the trial, bringing the total follow-up period to between eight and 13 years. During this longer follow-up period, the differences between the three drugs narrowed -- by most measures they were a statistical dead heat.
But the diuretic still was superior in two measures: Compared with the diuretic group, the ACE inhibitor group had a 20 percent higher death rate from stroke, and the calcium channel blocker group had a 12 percent higher rate of hospitalizations and deaths due to heart failure.
Diuretics, sometimes called "water pills," are the traditional medications for high blood pressure. They cause kidneys to remove sodium and water from the body, thereby relaxing blood vessel walls. ACE inhibitors such as lisinopril (brand names, Prinivil® and Zestril®) decrease chemicals that tighten blood vessels. Calcium channel blockers such as amlodipine (brand name, Norvasc®) relax blood vessels.
Diuretics cost $25 to $40 per year, while newer brand-name hypertension drugs can cost $300 to $600 per year.
The National Heart, Lung and Blood Institute recommends patients control their blood pressure by first controlling their weight, exercising, reducing sodium, increasing potassium and drinking alcohol in moderation. The institute says that if lifestyle changes are not sufficient, diuretics then normally should be the drug of first choice.
However, newer, higher-priced drugs are heavily marketed, and diuretics account for only about 30 percent of prescriptions written for high blood pressure medications, Whelton said.
Whelton is senior author of a study published in the May 24, 2010, Archives of Internal Medicine that found that using techniques similar to those employed by pharmaceutical sales reps can help persuade doctors to prescribe diuretics.
Like drug sales representatives, researchers in the study met with small groups of doctors, especially opinion leaders. They detailed guidelines for treating high blood pressure, and handed out studies, newsletters, exam room posters, etc. An examination of prescribing patterns found that this technique, known as "academic detailing," influenced what drugs doctors prescribed.
ALLHAT is sponsored by the National Heart, Lung and Blood Institute. "We are continuing to mine data that we collected during the trial," Whelton said.
Friday, July 16, 2010
Testosterone in Older Men: More Clarity or More Confusion?
Results of three studies argue against wholesale use of this drug for anti-aging purposes.
Three new studies add to the literature — and perhaps to the confusion — about testosterone in older men.
To identify symptom-clusters associated with low testosterone levels in 3369 community-dwelling men (age range, 40–79), European researchers administered questionnaires and measured morning levels of total and free testosterone. Of 32 sexual, physical, and psychological symptoms considered as potentially related to hypogonadism, a cluster of three sexual symptoms — poor morning erection, low sexual desire, and erectile dysfunction — correlated most closely with low testosterone levels. In contrast, clusters of psychological and physical symptoms correlated poorly with low testosterone levels. The analysis suggested that late-onset hypogonadism is characterized by presence of the three sexual symptoms in men with total testosterone levels <317 ng/dL (11 nmol/L) and free testosterone levels <64 pg/mL (220 pmol/L).
Another study involved 1445 community-dwelling U.S. men (mean age, 61). In cross-sectional analyses, total testosterone and sex hormone–binding globulin levels were not associated with mobility limitation, subjective health, or any physical performance measures, whereas free testosterone was associated with subjective health and some (but not all) physical performance measures. During 7 years of follow-up, low free testosterone level at baseline was associated with subsequent decline in mobility but not in subjective health.
To study the effects of testosterone supplementation, U.S. researchers enrolled 209 men (age, 65) with limited mobility and with total testosterone levels of 100 to 350 ng/dL (3.5–12.1 nmol/L) or free testosterone levels <50 pg/mL (173 pmol/L). Men were randomized to receive either transdermal testosterone gel or placebo for 6 months, with testosterone doses adjusted to achieve serum levels of 500 ng/dL. Enrollment was halted early because significantly more adverse cardiovascular events occurred in the testosterone group than in the placebo group (23 vs. 5 events).
Comment: The first study summarized above suggests that sexual symptoms — and not vague physical and psychological symptoms — should be used if one wants to identify patients with late-onset hypogonadism. The second study shows correlations between free testosterone and some measures of physical performance; however, findings were mixed, and significant associations in observational studies do not necessarily indicate cause-and-effect. And the third study raises red flags about adverse effects of testosterone supplementation in older men. These studies — considered alongside other recent studies in which testosterone supplementation did not yield impressive results in frail older
Three new studies add to the literature — and perhaps to the confusion — about testosterone in older men.
To identify symptom-clusters associated with low testosterone levels in 3369 community-dwelling men (age range, 40–79), European researchers administered questionnaires and measured morning levels of total and free testosterone. Of 32 sexual, physical, and psychological symptoms considered as potentially related to hypogonadism, a cluster of three sexual symptoms — poor morning erection, low sexual desire, and erectile dysfunction — correlated most closely with low testosterone levels. In contrast, clusters of psychological and physical symptoms correlated poorly with low testosterone levels. The analysis suggested that late-onset hypogonadism is characterized by presence of the three sexual symptoms in men with total testosterone levels <317 ng/dL (11 nmol/L) and free testosterone levels <64 pg/mL (220 pmol/L).
Another study involved 1445 community-dwelling U.S. men (mean age, 61). In cross-sectional analyses, total testosterone and sex hormone–binding globulin levels were not associated with mobility limitation, subjective health, or any physical performance measures, whereas free testosterone was associated with subjective health and some (but not all) physical performance measures. During 7 years of follow-up, low free testosterone level at baseline was associated with subsequent decline in mobility but not in subjective health.
To study the effects of testosterone supplementation, U.S. researchers enrolled 209 men (age, 65) with limited mobility and with total testosterone levels of 100 to 350 ng/dL (3.5–12.1 nmol/L) or free testosterone levels <50 pg/mL (173 pmol/L). Men were randomized to receive either transdermal testosterone gel or placebo for 6 months, with testosterone doses adjusted to achieve serum levels of 500 ng/dL. Enrollment was halted early because significantly more adverse cardiovascular events occurred in the testosterone group than in the placebo group (23 vs. 5 events).
Comment: The first study summarized above suggests that sexual symptoms — and not vague physical and psychological symptoms — should be used if one wants to identify patients with late-onset hypogonadism. The second study shows correlations between free testosterone and some measures of physical performance; however, findings were mixed, and significant associations in observational studies do not necessarily indicate cause-and-effect. And the third study raises red flags about adverse effects of testosterone supplementation in older men. These studies — considered alongside other recent studies in which testosterone supplementation did not yield impressive results in frail older
Wednesday, July 14, 2010
AstraZeneca to Pay Over $500 Million for Off-Label Marketing of Quetiapine
AstraZeneca will pay federal and state governments $520 million to settle charges that it illegally marketed its antipsychotic drug quetiapine (Seroquel). It's the largest settlement of its kind, according to the U.S. Department of Justice.
Quetiapine is only approved to treat schizophrenia and bipolar disorder. The Justice Department contends that AstraZeneca marketed quetiapine to physicians (particularly those who do not treat the approved conditions) for the following unapproved uses: treatment of aggression, Alzheimer disease, anger management, anxiety, attention-deficit/hyperactivity disorder, bipolar maintenance, dementia, depression, mood disorder, post-traumatic stress disorder, and sleeplessness.
The government alleges that AstraZeneca promoted these uses by paying doctors to serve as authors of ghostwritten research articles, to travel to resort locales to "advise" the company about marketing strategies, and to give promotional lectures to other clinicians.
Quetiapine is only approved to treat schizophrenia and bipolar disorder. The Justice Department contends that AstraZeneca marketed quetiapine to physicians (particularly those who do not treat the approved conditions) for the following unapproved uses: treatment of aggression, Alzheimer disease, anger management, anxiety, attention-deficit/hyperactivity disorder, bipolar maintenance, dementia, depression, mood disorder, post-traumatic stress disorder, and sleeplessness.
The government alleges that AstraZeneca promoted these uses by paying doctors to serve as authors of ghostwritten research articles, to travel to resort locales to "advise" the company about marketing strategies, and to give promotional lectures to other clinicians.
FDA Asks Physicians to Report Misleading Drug Ads
The FDA has asked healthcare providers to identify and report any prescription drug ads and promotions that may be false or misleading.
The agency says it is launching its "Bad Ad Program" both to help clinicians "recognize misleading prescription drug promotion and provide them with an easy way to report this activity."
Providers can e-mail potential violations to badad@fda.gov or call 877-RX-DDMAC.
The agency says it is launching its "Bad Ad Program" both to help clinicians "recognize misleading prescription drug promotion and provide them with an easy way to report this activity."
Providers can e-mail potential violations to badad@fda.gov or call 877-RX-DDMAC.
Tuesday, July 13, 2010
Doctor Who Faked Celebrex Study Data Sentenced
The former chief at the acute pain clinic at Bay State Hospital in Springfield, Massachusetts was just sentenced in federal court for health care fraud, the U.S. Food and Drug Administration (FDA) announced.
Scott Reuben, 51, was charged with submitting fake research for a 2007 pain management study of knee surgery patients said The Republican. The test in question was undertaken for drug maker Pfizer under a $73,000 research grant and was intended to measure the efficacy of its pain medication Celebrex when used to manage post-operative pain, wrote The Republican.
U.S. District Judge Ponsor sentenced Reuben to six months imprisonment to be followed by three years of supervised release, a $5,000 fine, restitution of $361,932, and forfeiture of $50,000. Reuben pleaded guilty to engaging in health care fraud on February 22, 2010.
According to Reuben’s defense team, said The Republican, his disreputable behavior was blamed on a bipolar disorder the team claimed was diagnosed in 2008, but that was allegedly “long-running.” Since, Reuben has also been banned from conducting future drug research and has lost his license to practice medicine, added The Republican.
United States Attorney Carmen M. Ortiz; Mark Dragonetti, Special Agent in Charge of the FDA-Office of Criminal Investigations; Susan J. Waddell, Special Agent in Charge of Health and Human Services, Office of the Inspector General-Office of Investigations; and James C. Burrell, Acting Special Agent in Charge of the Federal Bureau of Investigation (FBI)–Boston Field Division, issued the announcement.
The Republican said that Reuben’s sentence was announced last week as a result of the February guilty plea to one count of health care fraud.
At the prior plea hearing, the prosecutor told the Court that had the case proceeded to trial the Government’s evidence would have proven that Reuben obtained research grants from pharmaceutical companies for the purpose of performing research on pain management, including one from Pfizer in 2005 regarding the use of multi-modal analgesia for patients having and recovering from anterior cruciate ligament reconstruction surgery.
Despite entering into contracts by which pharmaceutical companies funded his research and provided free drug for the studies, Reuben did not perform certain studies, including one funded by Pfizer on “Perioperative Administration of Celecoxib as a Component of Multimodal Analgesia for Outpatient Anterior Cruciate Ligament Reconstruction Surgery.” Reuben’s behavior resulted in medical journals, including Anesthesia and Analgesia, to publish articles touting his multi-modal analgesia therapy despite knowing that he had falsified the research.
The Republican wrote that 50 patients were to receive the drug, while another 50 were to receive a placebo; however, while Reuben published studies indicating the test was conducted, it never was. The ruse was revealed during a 2008 “routine audit” conducted by Bay State that led to the discovery that Reuben had distorted findings from 21 studies that dated as far back as 1996, said The Republican. In 2009, Reuben terminated his privileges at Bay State, The Republican added.
Scott Reuben, 51, was charged with submitting fake research for a 2007 pain management study of knee surgery patients said The Republican. The test in question was undertaken for drug maker Pfizer under a $73,000 research grant and was intended to measure the efficacy of its pain medication Celebrex when used to manage post-operative pain, wrote The Republican.
U.S. District Judge Ponsor sentenced Reuben to six months imprisonment to be followed by three years of supervised release, a $5,000 fine, restitution of $361,932, and forfeiture of $50,000. Reuben pleaded guilty to engaging in health care fraud on February 22, 2010.
According to Reuben’s defense team, said The Republican, his disreputable behavior was blamed on a bipolar disorder the team claimed was diagnosed in 2008, but that was allegedly “long-running.” Since, Reuben has also been banned from conducting future drug research and has lost his license to practice medicine, added The Republican.
United States Attorney Carmen M. Ortiz; Mark Dragonetti, Special Agent in Charge of the FDA-Office of Criminal Investigations; Susan J. Waddell, Special Agent in Charge of Health and Human Services, Office of the Inspector General-Office of Investigations; and James C. Burrell, Acting Special Agent in Charge of the Federal Bureau of Investigation (FBI)–Boston Field Division, issued the announcement.
The Republican said that Reuben’s sentence was announced last week as a result of the February guilty plea to one count of health care fraud.
At the prior plea hearing, the prosecutor told the Court that had the case proceeded to trial the Government’s evidence would have proven that Reuben obtained research grants from pharmaceutical companies for the purpose of performing research on pain management, including one from Pfizer in 2005 regarding the use of multi-modal analgesia for patients having and recovering from anterior cruciate ligament reconstruction surgery.
Despite entering into contracts by which pharmaceutical companies funded his research and provided free drug for the studies, Reuben did not perform certain studies, including one funded by Pfizer on “Perioperative Administration of Celecoxib as a Component of Multimodal Analgesia for Outpatient Anterior Cruciate Ligament Reconstruction Surgery.” Reuben’s behavior resulted in medical journals, including Anesthesia and Analgesia, to publish articles touting his multi-modal analgesia therapy despite knowing that he had falsified the research.
The Republican wrote that 50 patients were to receive the drug, while another 50 were to receive a placebo; however, while Reuben published studies indicating the test was conducted, it never was. The ruse was revealed during a 2008 “routine audit” conducted by Bay State that led to the discovery that Reuben had distorted findings from 21 studies that dated as far back as 1996, said The Republican. In 2009, Reuben terminated his privileges at Bay State, The Republican added.
jupiter trial
In another paper, investigators took a closer look at the JUPITER trial, in which rosuvastatin reportedly lowered cardiovascular risk by 50% among patients without heart disease or hypercholesterolemia but with high C-reactive protein. The investigators say the trial was "flawed" — it was stopped too early, data on cardiovascular mortality were lacking, and more than half the researchers had financial ties to industry. Accordingly, they conclude: "The results of the trial do not support the use of statin treatment for primary prevention."
Drug Maker Purportedly Hid Information on Rosiglitazone Risks for a Decade
GlaxoSmithKline has known about the elevated heart risks with its diabetes drug rosiglitazone (Avandia) since 1999 — and has been attempting to hide the data since then — according to the New York Times.
The Times reports that a 1999 study showed that the drug was no better than its competitor, pioglitazone (Actos), and that there were "clear signs that it was riskier to the heart." However, the company failed to publish the findings or submit them to federal regulators.
The paper cites a 2001 e-mail from a company executive, stating: "Per Sr. Mgmt request, these data should not see the light of day to anyone outside of GSK." Meanwhile, a company spokesperson told the Times the findings were not shared because they "did not contribute any significant new information."
The Times reports that a 1999 study showed that the drug was no better than its competitor, pioglitazone (Actos), and that there were "clear signs that it was riskier to the heart." However, the company failed to publish the findings or submit them to federal regulators.
The paper cites a 2001 e-mail from a company executive, stating: "Per Sr. Mgmt request, these data should not see the light of day to anyone outside of GSK." Meanwhile, a company spokesperson told the Times the findings were not shared because they "did not contribute any significant new information."
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