WASHINGTON (Reuters) Jul 26 - Drug companies that had medicines tested by contractor Cetero Research might have to reevaluate results, U.S. regulators warned after the firm was found faking documents and manipulating samples.
The Food and Drug Administration said on Tuesday two 2010 inspections, an internal company investigation and a third-party audit uncovered "significant instances of misconduct and violations" at a Cetero facility in Houston.
The Cary, North Carolina-based firm does early-phase clinical research and bioanalytics for a number of drugmakers. The pharmaceutical companies can then use those studies as supporting evidence in drug approval applications to the FDA.
"The pattern of misconduct was serious enough to raise concerns about the integrity of the data Cetero generated during the five-year time frame," the FDA said, warning drugmakers they might have to repeat or confirm any studies Cetero did in support of their applications between April 2005 and June 2010.
It remains unclear which drugmakers have used Cetero's services to apply for regulatory approvals and the FDA is asking companies to identify such instances. The regulators said the measure is precautionary and the safety and efficacy of drugs already on the market are unlikely to be affected.
The FDA inspected Cetero in May and December last year and found falsified records about studies.
Specifically, in at least 1,900 instances between April 2005 and June 2009, laboratory technicians identified as conducting certain studies were not actually present at Cetero facilities at that time, the FDA said in its May report.
The FDA also said at the time that Cetero might have "fixed" studies to get the desired result, or did not include failed results in their report.
"Cetero's May 2010 and December 2010 responses are inadequate because the scope of their internal investigation was far too narrow to identify and adequately address the root cause of these systemic failures," the regulators said.
Cetero was not immediately available for comment.
Thursday, July 28, 2011
Friday, July 15, 2011
Screening Does Not Reduce Ovarian Cancer Mortality
Screening with transvaginal ultrasound and CA-125 measurement does not reduce ovarian cancer mortality, according to results from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial published in JAMA.
Some 78,000 women aged 55 to 74 without histories of ovarian cancer were randomized to usual care, or to screening with annual transvaginal ultrasound for 4 years and annual CA-125 blood testing for up to 6 years. During roughly 12 years' follow-up, the primary endpoint — ovarian cancer mortality — did not differ between the groups.
Roughly 3000 women had false-positive results on screening, one third of whom had surgery (e.g., oophorectomy) as part of the diagnostic evaluation. Among these, the rate of major surgical complications was 21 per 100 procedures.
=Just wondering if transvaginal ultrasound and CA-125 measurement will decrease or stop. Cynics doubt it
Some 78,000 women aged 55 to 74 without histories of ovarian cancer were randomized to usual care, or to screening with annual transvaginal ultrasound for 4 years and annual CA-125 blood testing for up to 6 years. During roughly 12 years' follow-up, the primary endpoint — ovarian cancer mortality — did not differ between the groups.
Roughly 3000 women had false-positive results on screening, one third of whom had surgery (e.g., oophorectomy) as part of the diagnostic evaluation. Among these, the rate of major surgical complications was 21 per 100 procedures.
=Just wondering if transvaginal ultrasound and CA-125 measurement will decrease or stop. Cynics doubt it
Saturday, July 9, 2011
antidepressants dont work?
Abstract
Background: This paper examines the current status of research on the efficacy and effectiveness of antidepressants. Methods: This paper reviews four meta-analyses of efficacy trials submitted to America’s Food and Drug Administration (FDA) and analyzes STAR*D (Sequenced Treatment Alternatives to Relieve Depression), the largest antidepressant effectiveness trial ever conducted. Results: Meta-analyses of FDA trials suggest that antidepressants are only marginally efficacious compared to placebos and document profound publication bias that inflates their apparent efficacy. These meta-analyses also document a second form of bias in which researchers fail to report the negative results for the pre-specified 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 STAR*D analysis found that the effectiveness of antidepressant therapies was probably even lower than the modest one reported by the study authors with an apparent progressively increasing dropout rate across each study phase. Conclusions: The reviewed findings argue for a reappraisal of the current recommended standard of care of depression.
Efficacy and Effectiveness of
Antidepressants: Current Status of
Research
H. Edmund Pigott a Allan M. Leventhal b Gregory S. Alter a John J. Boren b
a NeuroAdvantage, LLC, Clarksville, Md. , b Department of Psychology, American University,
Washington, D.C. , USA
Background: This paper examines the current status of research on the efficacy and effectiveness of antidepressants. Methods: This paper reviews four meta-analyses of efficacy trials submitted to America’s Food and Drug Administration (FDA) and analyzes STAR*D (Sequenced Treatment Alternatives to Relieve Depression), the largest antidepressant effectiveness trial ever conducted. Results: Meta-analyses of FDA trials suggest that antidepressants are only marginally efficacious compared to placebos and document profound publication bias that inflates their apparent efficacy. These meta-analyses also document a second form of bias in which researchers fail to report the negative results for the pre-specified 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 STAR*D analysis found that the effectiveness of antidepressant therapies was probably even lower than the modest one reported by the study authors with an apparent progressively increasing dropout rate across each study phase. Conclusions: The reviewed findings argue for a reappraisal of the current recommended standard of care of depression.
Efficacy and Effectiveness of
Antidepressants: Current Status of
Research
H. Edmund Pigott a Allan M. Leventhal b Gregory S. Alter a John J. Boren b
a NeuroAdvantage, LLC, Clarksville, Md. , b Department of Psychology, American University,
Washington, D.C. , USA
Wednesday, June 29, 2011
ncep 2004 guidelines
The NCEP’s 2004 guideline update garnered headlines by recommending lower targets for bad cholesterol, which would put more Americans on the drugs. But there was also a heated controversy in the medical community over the fact that 8 of the 9 experts on the panel had financial ties to industry. “The guideline process went awry,” says Michigan State’s Barry. He and 34 other experts sent a petition of protest to the National Institutes of Health, saying the evidence was weak and the panel members were biased by their ties to companies.
Sunday, March 20, 2011
Meta-Analysis Favors Pioglitazone in 'Real World' Settings
In an analysis of observational studies comparing pioglitazone versus rosiglitazone, pioglitazone emerges as the safer of the two.
Analyzing studies comprising over 800,000 patients with type 2 diabetes, researchers report in BMJ that use of rosiglitazone was associated with a "modest but statistically significant increase in the odds of myocardial infarction, congestive heart failure, and death compared with patients receiving pioglitazone in real world settings."
In 2010, the European Medicines Agency recommended withdrawal of rosiglitazone from the market, and the U.S. FDA placed restrictions on its use.
Editorialists ask why, despite the association with increased risks for heart failure and the availability of other agents, thiazolidinediones remain among the leading prescribed drugs in the U.S. That popularity, they conclude, "says much about how healthcare has become less about promoting patients' interests ... and much more about promoting other interests, including those of the drug industry."
Analyzing studies comprising over 800,000 patients with type 2 diabetes, researchers report in BMJ that use of rosiglitazone was associated with a "modest but statistically significant increase in the odds of myocardial infarction, congestive heart failure, and death compared with patients receiving pioglitazone in real world settings."
In 2010, the European Medicines Agency recommended withdrawal of rosiglitazone from the market, and the U.S. FDA placed restrictions on its use.
Editorialists ask why, despite the association with increased risks for heart failure and the availability of other agents, thiazolidinediones remain among the leading prescribed drugs in the U.S. That popularity, they conclude, "says much about how healthcare has become less about promoting patients' interests ... and much more about promoting other interests, including those of the drug industry."
Saturday, March 12, 2011
benicar ups cv death but lowers protein in urine in type 2 dbtcs
Olmesartan, an angiotensin-receptor blocker, delays the development of microalbuminuria in patients with type 2 diabetes and well-controlled blood pressure, but its use is associated with an increased risk of death from cardiovascular events, according to a New England Journal of Medicine study.
The ROADMAP trial, sponsored by the drug's manufacturer, randomized some 4500 diabetic patients with normoalbuminuria to daily olmesartan or placebo. In addition, participants' blood pressures were treated to maintain values under 130/80 mm Hg.
After a median 3-year follow-up, the olmesartan group showed a significant advantage over placebo in delaying time to onset of microalbuminuria (the primary outcome). However, fatal cardiovascular events were more common with olmesartan.
An editorialist writes that the finding of delayed microalbuminuria was not unanticipated. And given the increased cardiovascular mortality found with olmesartan, she asks why wouldn't other renin-angiotensin blocking drugs be prescribed if they are not associated with fatal complications?
The ROADMAP trial, sponsored by the drug's manufacturer, randomized some 4500 diabetic patients with normoalbuminuria to daily olmesartan or placebo. In addition, participants' blood pressures were treated to maintain values under 130/80 mm Hg.
After a median 3-year follow-up, the olmesartan group showed a significant advantage over placebo in delaying time to onset of microalbuminuria (the primary outcome). However, fatal cardiovascular events were more common with olmesartan.
An editorialist writes that the finding of delayed microalbuminuria was not unanticipated. And given the increased cardiovascular mortality found with olmesartan, she asks why wouldn't other renin-angiotensin blocking drugs be prescribed if they are not associated with fatal complications?
Thursday, February 24, 2011
Statins for the primary prevention of cardiovascular disease
Summary
Statins for the primary prevention of cardiovascular disease
Cardiovascular disease (CVD) is ranked as the number one cause of mortality and is a major cause of morbidity world wide. Reducing high blood cholesterol which is a risk factor for CVD events is an important goal of medical treatment. Statins are the first-choice agents. Since the early statin trials were reported, several reviews of the effects of statins have been published highlighting their benefits particularly in people with a past history of CVD. However for people without a past history of CVD (primary prevention), the evidence is less clear. The aim of this systematic review is to assess the effects, both in terms of benefits and harms of statins for the primary prevention of CVD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE until 2007. We found 14 randomised control trials with 16 trial arms (34,272 patients) dating from 1994 to 2006. All were randomised control trials comparing statins with usual care or placebo. Duration of treatment was minimum one year and with follow up of a minimum of six months. All cause mortality. coronary heart disease and stroke events were reduced with the use of statins as was the need for revascularisations. Statin treatment reduced blood cholesterol. Taking statins did not increase the risk of adverse effects such as cancer. and few trials reported on costs or quality of life. This current systematic review highlights the shortcomings in the published trials and we recommend that caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2011 Issue 1, Copyright © 2011 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Taylor F, Ward K, Moore THM, Burke M, Davey Smith G, Casas J-P, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD004816. DOI: 10.1002/14651858.CD004816.pub4
Editorial Group: Heart Group
This version first published online: January 19. 2011
Last assessed as up-to-date: September 8. 2007
Abstract
Background
Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of coronary heart disease (CHD) is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with coronary artery disease. The case for primary prevention, however, is less clear.
Objectives
To assess the effects, both harms and benefits, of statins in people with no history of CVD.
Search strategy
To avoid duplication of effort, we checked reference lists of previous systematic reviews. We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007) and EMBASE (2003 to March 2007). There were no language restrictions.
Selection criteria
Randomised controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD, were included.
Data collection and analysis
Two authors independently selected studies for inclusion and extracted data. Outcomes included all cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), change in blood total cholesterol concentration, revascularisation, adverse events, quality of life and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95% confidence intervals) were calculated.
Main results
Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.83, 95% CI 0.73 to 0.95) as was combined fatal and non-fatal CVD endpoints (RR 0.70, 95% CI 0.61 to 0.79). Benefits were also seen in the reduction of revascularisation rates (RR 0.66, 95% CI 0.53 to 0.83). Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.
Authors' conclusions
Although reductions in all-cause mortality, composite endpoints and revascularisations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events and inclusion of people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
Statins for the primary prevention of cardiovascular disease
Cardiovascular disease (CVD) is ranked as the number one cause of mortality and is a major cause of morbidity world wide. Reducing high blood cholesterol which is a risk factor for CVD events is an important goal of medical treatment. Statins are the first-choice agents. Since the early statin trials were reported, several reviews of the effects of statins have been published highlighting their benefits particularly in people with a past history of CVD. However for people without a past history of CVD (primary prevention), the evidence is less clear. The aim of this systematic review is to assess the effects, both in terms of benefits and harms of statins for the primary prevention of CVD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE until 2007. We found 14 randomised control trials with 16 trial arms (34,272 patients) dating from 1994 to 2006. All were randomised control trials comparing statins with usual care or placebo. Duration of treatment was minimum one year and with follow up of a minimum of six months. All cause mortality. coronary heart disease and stroke events were reduced with the use of statins as was the need for revascularisations. Statin treatment reduced blood cholesterol. Taking statins did not increase the risk of adverse effects such as cancer. and few trials reported on costs or quality of life. This current systematic review highlights the shortcomings in the published trials and we recommend that caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2011 Issue 1, Copyright © 2011 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Taylor F, Ward K, Moore THM, Burke M, Davey Smith G, Casas J-P, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD004816. DOI: 10.1002/14651858.CD004816.pub4
Editorial Group: Heart Group
This version first published online: January 19. 2011
Last assessed as up-to-date: September 8. 2007
Abstract
Background
Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of coronary heart disease (CHD) is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with coronary artery disease. The case for primary prevention, however, is less clear.
Objectives
To assess the effects, both harms and benefits, of statins in people with no history of CVD.
Search strategy
To avoid duplication of effort, we checked reference lists of previous systematic reviews. We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007) and EMBASE (2003 to March 2007). There were no language restrictions.
Selection criteria
Randomised controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD, were included.
Data collection and analysis
Two authors independently selected studies for inclusion and extracted data. Outcomes included all cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), change in blood total cholesterol concentration, revascularisation, adverse events, quality of life and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95% confidence intervals) were calculated.
Main results
Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.83, 95% CI 0.73 to 0.95) as was combined fatal and non-fatal CVD endpoints (RR 0.70, 95% CI 0.61 to 0.79). Benefits were also seen in the reduction of revascularisation rates (RR 0.66, 95% CI 0.53 to 0.83). Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.
Authors' conclusions
Although reductions in all-cause mortality, composite endpoints and revascularisations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events and inclusion of people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
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