- Email: [email protected]
The “CONTROVERSY” is dead…long live the “CONTROVERSY”
Diabetes & Metabolic Syndrome: Clinical Research & Reviews 3 (2009) 129–131
Contents lists available at ScienceDirect
Diabetes & Metabolic Syndrome: Clinical Research & Reviews journal homepage: www.elsevier.com/locate/dsx
Editorial
The ‘‘CONTROVERSY’’ is dead. . .long live the ‘‘CONTROVERSY’’
We seem to go from controversy to controversy, and in the meantime, the pandemic of diabetes continues unabated! Controversies seem to have become a way of life. So much so, that we seem unable to carry on without having something to argue about! This is not to say that we must all think alike. In fact, disagreements can, if taken in the right spirit, lead to a more thorough discussion and if carried out with an open investigative mind and end up in increasing our understanding of a subject, which could allow us to manage our patients better. But there has to come a time when one needs to come to some sort of a consensus and put the controversy behind us. After all, at the end of the day, it is not just a question of increasing our knowledge of basic science. It is the translation of this knowledge to offer better care to our patients. With the publication of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study [1] one hoped that this would allow us to get a proper perspective of the ongoing rosiglitazone controversy and let us to come to some sort of a consensus about the use, if any, of rosiglitazone in clinical practice and its proper place in our diabetes management. But even before the RECORD, though somewhat scratched, could ‘‘play some music’’, along came the insulin glargine glitch! The seeds of the insulin glargine controversy, may have been sown a few years back [2] but few people took any notice. It was only recently that the journal Diabetologia published four papers [3–6], two of which showed a causal link between the use of insulin glargine and the increased risk for malignant neoplasms and mortality. If one looks at the numbers of ‘‘Statements’’ coming out and the heavy email traffic on this subject, one can only hope that cooler heads will prevail and we will not go down the rosiglitazone controversy pathway! To be fair, the approach which Diabetologia took appears fair and balanced, compared to the mayhem which accompanied the publication of the Nissen et al. [7] meta-analysis. Some time last year, Diabetologia was sent a paper [3] whose aim was to investigate the risk of malignant neoplasms and mortality in patients treated with either human insulin or with one of three insulin analogues. A positive association between cancer incidence and insulin dose was found for all insulin types; when adjusted for dose, a dose-dependant increase in cancer risk was found for treatment with insulin glargine compared with human insulin. Diabetologia sent the manuscript to six reviewers. Although three of the reviewers rejected the manuscript, they as well as the others did raise some questions about the possible limitations of the study. As these could have impacted the results, the Diabetologia Editorial Board, as well as the EASD, concluded that it would be misleading to publish these results in isolation, but at
the same time one could not totally ignore the possibility of the association between the use of insulin glargine and the increased risk for cancer, especially breast malignancies. They rightly decided that the results warranted replication before they should be published. Studies were thus carried out using databases from Sweden [4] and Scotland [5] and UK [6]. Compare this approach to what happened in the rosiglitazone imbroglio. The FDA received GlaxoSmithKline’s formal analysis of 42 randomized trials along with data from a large observational study. The meta-analysis suggested a possible ‘‘31% increase in cardiac ischemic events with rosiglitazone,’’ whereas the observational study showed no such increased risk [8]. In early spring, 2007 FDA staff called for prominent boxed warnings about the risk for heart failure and edema with peroxisome proliferator–activated receptor-g agonists and requested a meeting with GlaxoSmithKline. They planned to take the issue of heart failure and ischemic events for both rosiglitazone and pioglitazone to an Advisory Committee meeting in late summer or early fall. But before they could hold this meeting which would have allowed a more exhaustive examination of the risk associated with rosiglitazone, Nissen et al. [7] pre-empted them by publishing a meta-analysis in late May 2007, in the New England Journal of Medicine (NEJM) that claimed that rosiglitazone increased the risk for myocardial infarction by about 43% and cardiovascular death by about 64%. It would seem naı¨ve to believe that Nissen was not aware that the U.S. FDA was already looking into this matter! Moreover, in the same issue of NEJM, Psaty et al. [9] admitting that Nissen’s meta-analysis had many limitations, which even Nissen had admitted [7], concluded that the findings represented a valid estimate of the risk of cardiovascular events and that in view of the potential cardiovascular risks and in the absence of evidence of other health advantages, except for laboratory measures of glycemic control, the rationale for prescribing rosiglitazone at that point of time was unclear. They asked for urgent action from the Food and Drug Administration (FDA) saying that the availability of rosiglitazone represented a major failure of the drug-use and drugapproval processes in the United States. But as discussed in the review in this issue, ‘‘Putting The RECORD Straight?’’ the meta-analysis [7] with its significant limitations would be hard pressed to stand up to unbiased scientific scrutiny. After all, if we are to base our recommendations on just one meta-analysis, it must meet the most rigorous standards. And the role played by NEJM itself raises questions about its scientific bias. It is not my view that the meta-analysis should not
1871-4021/$ – see front matter ß 2009 Published by Elsevier Ltd on behalf of Diabetes India. doi:10.1016/j.dsx.2009.08.001
130
Editorial / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 3 (2009) 129–131
have been published, but the fact remains that it had substantial deficiencies and these should have been addressed at least in the editorial or an accompanying Commentary rather than the rush to publish what is accepted even by the authors as a study with deficiencies. Many authorities have called into question the NEJM ethics and have compared major medical journals including the NEJM with British tabloid newspapers in the way it went about its online publication [10]. The publication of the meta-analysis created a media furore in its aftermath with conspiracy theories amongst others taking center stage and scientific debate taking a backseat. In an editorial written in the Wall Street Journal [11], Scott Gottlieb a former deputy FDA commissioner made an accusation that the way the whole episode was managed was plainly an exercise to malign the FDA by creating a public panic which would preclude a scientific debate. He felt that this was nothing but a conspiracy by the study authors, the NEJM, and politicians with their own motives trying to upstage the FDA in an attempt to influence public debate. He questioned the undue hurry to publish the meta-analysis. The manuscript was submitted to NEJM on the 1st of May and neither the authors, or NEJM, bothered to inform and get a response from the FDA or GSK as should have been normally done in all fairness. Furthermore, knowing fully well, as documented by Steve Usdin in Biocentury [12] that the FDA was scheduled to issue a safety statement about Avandia around May 23, as he had been informed by a FDA official, the journal in fact expedited the review of the paper and also asked two well known critics of the FDA drug safety record Psaty and Furberg to write an Editorial. NEJM showing undue haste published this online on the 21st of May timed to overshadow the FDA’s more careful, evaluation of the same issues. The meta-analysis and the media outcry that it created with politicians getting into the act did nothing for the good of the patients. The then NEJM editor Dr Gregory Curfman told BioCentury that his journal was not responsible for the media reactions to the rosiglitazone paper and commentary: ‘‘We are a scholarly journal, not a news outlet. What happens in the media is beyond our control.’’ [12]. This is open to questioning. A scholarly journal would have asked the FDA and even GSK for its opinions and offered a more balanced perspective. Gottlieb [11] says the NEJM claims to have made the decision to publish quickly because of the medical importance of the research but, if that were the case, he wondered why it did not inform the FDA about its publication or the findings. ‘‘When it comes to drug safety, no description of medical research in a medical journal comes close to the detail level or scrutiny imposed by the FDA on study results before approval. Yet NEJM and other journals have tried on other occasions to upstage FDA investigations through well-timed but much less complete publications,’’ he asserted. He added that there was no mention in the NEJM paper or editorial of rosiglitazone’s benefits or of how doctors should advise patients. When compared to the approach shown by Nissen and his colleagues as well as NEJM, Diabetologia as well as the authors of the German study [3] seem to come out with flying colours. Not only did the journal take a measured approach but as importantly, the German investigators also accepted that they would wait for the results of the additional studies rather than take the tabloid route and go public! [13] Thus, the Swedish study [4] found that compared with patients on insulin glargine when compared to those not on this insulin had double the risk of breast cancer. The Scottish study [5] found a non-
significant increased risk for breast cancer specifically. The UK study [6] found no significant link between insulin glargine and cancer. Smith et al on behalf of the EASD [13] rightly say that they ‘‘believe people are entitled to know that use of Lantus insulin might be associated with greater risk, but this must also be balanced against the possibility that we might be causing unnecessary alarm by raising these concerns.‘‘ Unlike what happened in the Rosiglitazone controversy, the EASD has been in touch with sanofi-aventis, the manufacturers of Lantus insulin and have also communicated the findings of the studies to the EMEA, the European regulatory authorities. The final decision will have to be based on ‘‘a large combined analysis of the best available databases worldwide’’ [13]. This is due to the fact that a prospective clinical trial would be slow and definitely unethical. What would one say to a woman who is being asked to take part in such a trial, ‘‘Well, we have some evidence that your using insulin glargine may place you at an increased risk of breast malignancy!’’ Which person in his/her right mind would agree? The EASD also has made it clear to the patients [14] that ‘‘People with diabetes do however have the option of using long acting human insulin or a mixture of long- and short-acting human insulin twice a day instead of the once-daily analogue. You may wish to consider this option if you already have a cancer, or, for women, if there is a family history of breast cancer. You should not make any change in your insulin treatment without consulting your own doctor, and you should on no account stop taking your insulin.’’ This is correct position to take. But they also maintain that, ‘‘since Lantus does not offer better overall glucose control than human insulin in type 2 diabetes, patients can consider alternatives’’ [15]. If this is so, why not recommend that insulin glargine be removed from the market pending the results. After all, if it does not offer better overall glucose control, then where is the hitch. Why is it always that the people are put at risk whilst ‘‘more’’ results are awaited. Here there seems to be no difference between what happened with rosiglitazone and what is being done in the case of insulin glargine. If there are alternatives which will allow us to offer as good a control with alternate therapies, why not rule in favour of the people. The drugs could always come back into clinical use when, and if, they are given a clean bill of health! This is NOT a game of ‘‘Monopoly’’ (in more sense than one) that a ‘‘get out of jail’’ card should be given freely, especially when lives of innocent people are concerned. References [1] Home P, Pocock S, Beck-Nielsen H, Curtis P, Gomis R, Hanefeld M, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, openlabel trial. Lancet 2009;(373):2125–35. [2] Kurtzhals P, Scha¨ffer L, Sørensen A, Kristensen C, Jonassen I, Schmid C, et al. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes 2000;49:999–1005. [3] Hemkens L, Grouven U, Bender R, Gu¨nster C, Gutschmidt S, Selke S, et al. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study, Diabetologia, doi:10.1007/s00125009-1418-4. [4] Jonasson J, Ljung R, Talba¨ck M, Haglund B, Gudbjo¨rnsdottir S, Steineck G. Insulin glargine use and short-term cancer incidence—a population-based follow-up in Sweden, doi:10.1007/s00125-009-1444-2. [5] Colhoun H on behalf of SDRN. Insulin glargine use and cancer rates in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group, doi:10.1007/s00125-009-1453-1. [6] Currie C, Poole C, Gale E. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes, Diabetologia 2009 June 24, doi:10.1007/s00125-0091440-6. [7] Nissen S, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356:2457–71.
Editorial / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 3 (2009) 129–131 [8] Advisory Committee Briefing Document: Cardiovascular Safety of Rosiglitazone. Philadelphia: GlaxoSmithKline; Accessed at http://www.fda.gov/ohrms/ dockets/ac/07/briefing/2007-4308b1-01-sponsor-backgrounder.pdf on 14 July 2009. [9] Psaty B, Furberg C. Rosiglitazone and cardiovascular risk. N Engl J Med 2007;356:2522–4. [10] FDA Briefing Document: Joint meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. 30 July 2007. Philadelphia: GlaxoSmithKline; Accessed at http:// www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4308b1-02-fda-backgrounder.pdf on July 14, 2009. [11] Rosiglitazone meta-analysis continues to drive controversy in second week http://www.medscape.com/viewarticle/557511. Last accessed 14th July 2009.
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[12] Gottlieb S. Journalistic malpractice. Wall Street Journal, May 29, 2007. Available at: http://www.wsj.com, Last accessed 14th July 2009. [13] Usdin S. Political defibrillator. BioCentury, May 28, 2007. Available at: http:// www.biocentury.com. Last accessed 14th July 2009. [14] Smith U, Gale E. Does diabetes therapy influence the risk of cancer? Diabetologia, doi:10.1007/s00125-009-1441-5. [15] Available at http://www.diabetologia-journal.org/cancer.html. Last accessed 21st July 2009.
S.M. Sadikot 50, Manoel Gonsalves Road, Bandra (W), Mumbai 400050, India E-mail address: [email protected]
Contents lists available at ScienceDirect
Diabetes & Metabolic Syndrome: Clinical Research & Reviews journal homepage: www.elsevier.com/locate/dsx
Editorial
The ‘‘CONTROVERSY’’ is dead. . .long live the ‘‘CONTROVERSY’’
We seem to go from controversy to controversy, and in the meantime, the pandemic of diabetes continues unabated! Controversies seem to have become a way of life. So much so, that we seem unable to carry on without having something to argue about! This is not to say that we must all think alike. In fact, disagreements can, if taken in the right spirit, lead to a more thorough discussion and if carried out with an open investigative mind and end up in increasing our understanding of a subject, which could allow us to manage our patients better. But there has to come a time when one needs to come to some sort of a consensus and put the controversy behind us. After all, at the end of the day, it is not just a question of increasing our knowledge of basic science. It is the translation of this knowledge to offer better care to our patients. With the publication of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study [1] one hoped that this would allow us to get a proper perspective of the ongoing rosiglitazone controversy and let us to come to some sort of a consensus about the use, if any, of rosiglitazone in clinical practice and its proper place in our diabetes management. But even before the RECORD, though somewhat scratched, could ‘‘play some music’’, along came the insulin glargine glitch! The seeds of the insulin glargine controversy, may have been sown a few years back [2] but few people took any notice. It was only recently that the journal Diabetologia published four papers [3–6], two of which showed a causal link between the use of insulin glargine and the increased risk for malignant neoplasms and mortality. If one looks at the numbers of ‘‘Statements’’ coming out and the heavy email traffic on this subject, one can only hope that cooler heads will prevail and we will not go down the rosiglitazone controversy pathway! To be fair, the approach which Diabetologia took appears fair and balanced, compared to the mayhem which accompanied the publication of the Nissen et al. [7] meta-analysis. Some time last year, Diabetologia was sent a paper [3] whose aim was to investigate the risk of malignant neoplasms and mortality in patients treated with either human insulin or with one of three insulin analogues. A positive association between cancer incidence and insulin dose was found for all insulin types; when adjusted for dose, a dose-dependant increase in cancer risk was found for treatment with insulin glargine compared with human insulin. Diabetologia sent the manuscript to six reviewers. Although three of the reviewers rejected the manuscript, they as well as the others did raise some questions about the possible limitations of the study. As these could have impacted the results, the Diabetologia Editorial Board, as well as the EASD, concluded that it would be misleading to publish these results in isolation, but at
the same time one could not totally ignore the possibility of the association between the use of insulin glargine and the increased risk for cancer, especially breast malignancies. They rightly decided that the results warranted replication before they should be published. Studies were thus carried out using databases from Sweden [4] and Scotland [5] and UK [6]. Compare this approach to what happened in the rosiglitazone imbroglio. The FDA received GlaxoSmithKline’s formal analysis of 42 randomized trials along with data from a large observational study. The meta-analysis suggested a possible ‘‘31% increase in cardiac ischemic events with rosiglitazone,’’ whereas the observational study showed no such increased risk [8]. In early spring, 2007 FDA staff called for prominent boxed warnings about the risk for heart failure and edema with peroxisome proliferator–activated receptor-g agonists and requested a meeting with GlaxoSmithKline. They planned to take the issue of heart failure and ischemic events for both rosiglitazone and pioglitazone to an Advisory Committee meeting in late summer or early fall. But before they could hold this meeting which would have allowed a more exhaustive examination of the risk associated with rosiglitazone, Nissen et al. [7] pre-empted them by publishing a meta-analysis in late May 2007, in the New England Journal of Medicine (NEJM) that claimed that rosiglitazone increased the risk for myocardial infarction by about 43% and cardiovascular death by about 64%. It would seem naı¨ve to believe that Nissen was not aware that the U.S. FDA was already looking into this matter! Moreover, in the same issue of NEJM, Psaty et al. [9] admitting that Nissen’s meta-analysis had many limitations, which even Nissen had admitted [7], concluded that the findings represented a valid estimate of the risk of cardiovascular events and that in view of the potential cardiovascular risks and in the absence of evidence of other health advantages, except for laboratory measures of glycemic control, the rationale for prescribing rosiglitazone at that point of time was unclear. They asked for urgent action from the Food and Drug Administration (FDA) saying that the availability of rosiglitazone represented a major failure of the drug-use and drugapproval processes in the United States. But as discussed in the review in this issue, ‘‘Putting The RECORD Straight?’’ the meta-analysis [7] with its significant limitations would be hard pressed to stand up to unbiased scientific scrutiny. After all, if we are to base our recommendations on just one meta-analysis, it must meet the most rigorous standards. And the role played by NEJM itself raises questions about its scientific bias. It is not my view that the meta-analysis should not
1871-4021/$ – see front matter ß 2009 Published by Elsevier Ltd on behalf of Diabetes India. doi:10.1016/j.dsx.2009.08.001
130
Editorial / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 3 (2009) 129–131
have been published, but the fact remains that it had substantial deficiencies and these should have been addressed at least in the editorial or an accompanying Commentary rather than the rush to publish what is accepted even by the authors as a study with deficiencies. Many authorities have called into question the NEJM ethics and have compared major medical journals including the NEJM with British tabloid newspapers in the way it went about its online publication [10]. The publication of the meta-analysis created a media furore in its aftermath with conspiracy theories amongst others taking center stage and scientific debate taking a backseat. In an editorial written in the Wall Street Journal [11], Scott Gottlieb a former deputy FDA commissioner made an accusation that the way the whole episode was managed was plainly an exercise to malign the FDA by creating a public panic which would preclude a scientific debate. He felt that this was nothing but a conspiracy by the study authors, the NEJM, and politicians with their own motives trying to upstage the FDA in an attempt to influence public debate. He questioned the undue hurry to publish the meta-analysis. The manuscript was submitted to NEJM on the 1st of May and neither the authors, or NEJM, bothered to inform and get a response from the FDA or GSK as should have been normally done in all fairness. Furthermore, knowing fully well, as documented by Steve Usdin in Biocentury [12] that the FDA was scheduled to issue a safety statement about Avandia around May 23, as he had been informed by a FDA official, the journal in fact expedited the review of the paper and also asked two well known critics of the FDA drug safety record Psaty and Furberg to write an Editorial. NEJM showing undue haste published this online on the 21st of May timed to overshadow the FDA’s more careful, evaluation of the same issues. The meta-analysis and the media outcry that it created with politicians getting into the act did nothing for the good of the patients. The then NEJM editor Dr Gregory Curfman told BioCentury that his journal was not responsible for the media reactions to the rosiglitazone paper and commentary: ‘‘We are a scholarly journal, not a news outlet. What happens in the media is beyond our control.’’ [12]. This is open to questioning. A scholarly journal would have asked the FDA and even GSK for its opinions and offered a more balanced perspective. Gottlieb [11] says the NEJM claims to have made the decision to publish quickly because of the medical importance of the research but, if that were the case, he wondered why it did not inform the FDA about its publication or the findings. ‘‘When it comes to drug safety, no description of medical research in a medical journal comes close to the detail level or scrutiny imposed by the FDA on study results before approval. Yet NEJM and other journals have tried on other occasions to upstage FDA investigations through well-timed but much less complete publications,’’ he asserted. He added that there was no mention in the NEJM paper or editorial of rosiglitazone’s benefits or of how doctors should advise patients. When compared to the approach shown by Nissen and his colleagues as well as NEJM, Diabetologia as well as the authors of the German study [3] seem to come out with flying colours. Not only did the journal take a measured approach but as importantly, the German investigators also accepted that they would wait for the results of the additional studies rather than take the tabloid route and go public! [13] Thus, the Swedish study [4] found that compared with patients on insulin glargine when compared to those not on this insulin had double the risk of breast cancer. The Scottish study [5] found a non-
significant increased risk for breast cancer specifically. The UK study [6] found no significant link between insulin glargine and cancer. Smith et al on behalf of the EASD [13] rightly say that they ‘‘believe people are entitled to know that use of Lantus insulin might be associated with greater risk, but this must also be balanced against the possibility that we might be causing unnecessary alarm by raising these concerns.‘‘ Unlike what happened in the Rosiglitazone controversy, the EASD has been in touch with sanofi-aventis, the manufacturers of Lantus insulin and have also communicated the findings of the studies to the EMEA, the European regulatory authorities. The final decision will have to be based on ‘‘a large combined analysis of the best available databases worldwide’’ [13]. This is due to the fact that a prospective clinical trial would be slow and definitely unethical. What would one say to a woman who is being asked to take part in such a trial, ‘‘Well, we have some evidence that your using insulin glargine may place you at an increased risk of breast malignancy!’’ Which person in his/her right mind would agree? The EASD also has made it clear to the patients [14] that ‘‘People with diabetes do however have the option of using long acting human insulin or a mixture of long- and short-acting human insulin twice a day instead of the once-daily analogue. You may wish to consider this option if you already have a cancer, or, for women, if there is a family history of breast cancer. You should not make any change in your insulin treatment without consulting your own doctor, and you should on no account stop taking your insulin.’’ This is correct position to take. But they also maintain that, ‘‘since Lantus does not offer better overall glucose control than human insulin in type 2 diabetes, patients can consider alternatives’’ [15]. If this is so, why not recommend that insulin glargine be removed from the market pending the results. After all, if it does not offer better overall glucose control, then where is the hitch. Why is it always that the people are put at risk whilst ‘‘more’’ results are awaited. Here there seems to be no difference between what happened with rosiglitazone and what is being done in the case of insulin glargine. If there are alternatives which will allow us to offer as good a control with alternate therapies, why not rule in favour of the people. The drugs could always come back into clinical use when, and if, they are given a clean bill of health! This is NOT a game of ‘‘Monopoly’’ (in more sense than one) that a ‘‘get out of jail’’ card should be given freely, especially when lives of innocent people are concerned. References [1] Home P, Pocock S, Beck-Nielsen H, Curtis P, Gomis R, Hanefeld M, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, openlabel trial. Lancet 2009;(373):2125–35. [2] Kurtzhals P, Scha¨ffer L, Sørensen A, Kristensen C, Jonassen I, Schmid C, et al. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes 2000;49:999–1005. [3] Hemkens L, Grouven U, Bender R, Gu¨nster C, Gutschmidt S, Selke S, et al. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study, Diabetologia, doi:10.1007/s00125009-1418-4. [4] Jonasson J, Ljung R, Talba¨ck M, Haglund B, Gudbjo¨rnsdottir S, Steineck G. Insulin glargine use and short-term cancer incidence—a population-based follow-up in Sweden, doi:10.1007/s00125-009-1444-2. [5] Colhoun H on behalf of SDRN. Insulin glargine use and cancer rates in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group, doi:10.1007/s00125-009-1453-1. [6] Currie C, Poole C, Gale E. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes, Diabetologia 2009 June 24, doi:10.1007/s00125-0091440-6. [7] Nissen S, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356:2457–71.
Editorial / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 3 (2009) 129–131 [8] Advisory Committee Briefing Document: Cardiovascular Safety of Rosiglitazone. Philadelphia: GlaxoSmithKline; Accessed at http://www.fda.gov/ohrms/ dockets/ac/07/briefing/2007-4308b1-01-sponsor-backgrounder.pdf on 14 July 2009. [9] Psaty B, Furberg C. Rosiglitazone and cardiovascular risk. N Engl J Med 2007;356:2522–4. [10] FDA Briefing Document: Joint meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. 30 July 2007. Philadelphia: GlaxoSmithKline; Accessed at http:// www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4308b1-02-fda-backgrounder.pdf on July 14, 2009. [11] Rosiglitazone meta-analysis continues to drive controversy in second week http://www.medscape.com/viewarticle/557511. Last accessed 14th July 2009.
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[12] Gottlieb S. Journalistic malpractice. Wall Street Journal, May 29, 2007. Available at: http://www.wsj.com, Last accessed 14th July 2009. [13] Usdin S. Political defibrillator. BioCentury, May 28, 2007. Available at: http:// www.biocentury.com. Last accessed 14th July 2009. [14] Smith U, Gale E. Does diabetes therapy influence the risk of cancer? Diabetologia, doi:10.1007/s00125-009-1441-5. [15] Available at http://www.diabetologia-journal.org/cancer.html. Last accessed 21st July 2009.
S.M. Sadikot 50, Manoel Gonsalves Road, Bandra (W), Mumbai 400050, India E-mail address: [email protected]