In its response, GSK states that the Staff Report fails to present an accurate, balanced, or complete view of the currently available information on Avandia® (rosiglitazone). The company rejects any allegations of concealing safety information or acting inappropriately on behalf of patients. GSK respectfully disagrees with the Committeeâs decision to publish a Staff Report with the errors of fact, omissions, and inferences detailed in GSKâs White Paper.
A fair examination of the company's record will show that GSK has been diligent in its efforts to thoroughly study the safety and effectiveness of rosiglitazone, and to widely communicate that information to governments, regulatory authorities, scientific peers, physicians and others in a variety of ways.
The following is a summary of GSKâs response:
- Among its most glaring omissions, the Staff Report does not include discussion of the final results of either the ADOPT, DREAM, or RECORD studies. ADOPT, DREAM and the interim data for RECORD were evaluated by an independent FDA advisory board in 2007 along with all the information available at that time on Avandia. That FDA advisory board voted 22-1 in favour of keeping Avandia available for patients.
RECORD provides the best, most reliable assessment of Avandia's cardiovascular safety. RECORD was initiated in 2001 and, in consultation with European regulators, was designed to compare cardiovascular outcomes of patients on rosiglitazone added to metformin or sulfonylurea to those on metformin and sulfonylurea. The study was sufficiently powered to confirm its primary hypothesis. It showed that cardiovascular hospitalisation or cardiovascular death (which includes heart attack, congestive heart failure, and stroke) was not statistically different between the two groups after an average of 5.5 years of therapy.
- The report also fails to mention multiple other studies (APPROACH, VICTORY, STARR, VADT, ACCORD, BARI 2D) that all corroborate the ischaemic cardiovascular safety of rosiglitazone. None of these studies show a statistically significant association between Avandia and heart attack or other ischaemic cardiovascular events.
The absence in the Staff Report of any reference to the final results of the ADOPT, DREAM and RECORD studies, as well as other important studies on the ischaemic cardiovascular safety of Avandia, leaves the record incomplete and does not serve the interests of physicians or patients who rely on this medicine to help them treat and deal with diabetes.
- Instead of reviewing the most recent and scientifically sound information, the Staff Report relies on a meta-analysis prepared by Dr. S Nissen in 2007, an analysis which has been criticised widely, and contradicted by larger, more recent meta-analyses.
- In addition, the Staff Report suggests that GSK did not work to actively monitor the safety of Avandia or inform the FDA of its investigations. That suggestion is fundamentally flawed and contradicted by a record of extensive, on-going interactions between GSK and the FDA, and the FDA's on-going review of Avandia in light of all the information available to the agency. The Timeline included in the Staff Report omits key dates (included in the GSK White Paper) that demonstrate the on-going and open exchange of information that has characterised the FDA's active review of this medicine and GSK's efforts to provide data and respond to the agency's inquiries.
- The report does not give full consideration of the extensive measures GSK undertook to study Avandia prior to marketing approval; GSK's continued efforts to study its safety and efficacy; and FDAâs determination that the risk-benefit profile of Avandia is favourable, which demonstrates that Avandia is an important option for physicians choosing a treatment for appropriate patients with type 2 diabetes. Since approval by the FDA in 1999 and beyond, GSK has rigorously maintained an extensive and long-term programme of scientific study for Avandia, which is the most comprehensive program of scientific analysis for any oral anti-diabetes medicine available to patients today, with experience in well over 52,000 patients.
- The company's response also provides context for incidents cited in the Committee report which mischaracterised efforts to ensure that information about the company's medicine was accurately presented by others. GSK does not condone the silencing of critics, nor did it attempt to subvert the independence of scientific debate around Avandia. However, GSK will seek to correct inaccuracies and misstatements to ensure that physicians have the most accurate information available about its medicines when making prescribing choices for patients.
GSK stands behind the safety of Avandia. Contrary to recent media reports, the FDA has not called for withdrawal of Avandia, and in a recent statement, has advised that "Patients should continue taking rosiglitazone unless told by their healthcare professional to stop." GSK welcomes the opportunity for an independent and scientific evaluation of the collective safety of rosiglitazone at the upcoming FDA advisory committee in July. In agreement with statements made recently by the Endocrine Society and the FDA, the safety of Avandia should be judged in light of all available scientific data with emphasis on long-term prospective studies.
The assessment of the safety of Avandia is continuing now with a clinical trial called TIDE, which was undertaken at the direction of the FDA, to include a randomised comparison of rosiglitazone and pioglitazone (Actos®) in addition to the comparison of rosiglitazone to placebo. The protocol for conducting the study was developed with and approved by FDA, and will provide the only large-scale, head-to-head comparison of the two medicines. TIDE has also been approved by an independent review board and appropriate safety boards that are responsible for monitoring and assessing the safety of the trial in Type 2 diabetes patients.
GSK is committed to transparency and has been diligent in reporting the results of clinical trials, observational studies and meta-analyses on the company's website, as well as reporting them to regulatory agencies in a timely fashion.
To view GSK's response, visit http://www.gsk.com/media/GSK-White-Paper-Avandia-23-Feb-2010.pdf
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