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Rosiglitazone: seeking a balanced perspective
Editorial
The deteriorating health situation in Iraq
See Correspondence page 1860
For the UNAMI report on the humanitarian situation see http://www.uniraq.org For the UNICEF plan see http://www.unicef.org For more on the situation in Samarra see http://www.reliefweb.int/rw/ RWB.NSF/db900SID/LRON739HKV?OpenDocument
The health situation in Iraq is deteriorating on almost every level. In this week’s issue, two doctors from Basrah describe how insulin is unavailable because it is not safe to distribute it. Last month the first cases of cholera were reported. And in an interview with the non-governmental organisation Doctors for Iraq, Khaled Mahmud, head of resident doctors in Samarra General Hospital, described how power outages prevented the use of all the medical appliances in the hospital. The worsening humanitarian situation was recently outlined in a UNAMI report. 54% of Iraqis are now living on less than US$1 a day and almost half of all children are malnourished. Since the coalition invasion in 2003, 12 000 of Iraq’s 24 000 doctors have left Iraq. More encouragingly, 3·6 million children have just been immunised against measles, mumps, and rubella
and last week UNICEF launched a 6-month action plan, which will address the specific needs of Iraqi children. In addition, the National Center for Drug Control and Research which will analyse the quality of pharmaceutical products imported into Iraq opened last month. When devising health plans for Iraq it is vital to consider accessibility rather than availability. There is little point in having high quality drugs if it is not safe to distribute them, or new tertiary centres that people cannot access due to restrictive curfews and checkpoints. If Iraqi citizens are to have any hope of a better life, there must be a comprehensive yet realistic strategy—with input from all stakeholders, most importantly the Iraqi people—that adequately addresses the health needs in Iraq. Ignoring what is happening on the ground while planning for the future is a recipe for disaster. ■ The Lancet
Science Photo Library
Rosiglitazone: seeking a balanced perspective The printed journal includes an image merely for illustration Published Online May 23, 2007 DOI:10.1016/S01406736(07)60787-9
For the ADOPT study see N Engl J Med 2006; 355: 2427–43. DOI:10.1056/NEJMoa066224 For the DREAM study see Articles Lancet 2006; 368: 1096–105.
1834
“Health alert over diabetes drug linked to heart risks”, ran the headline in one UK newspaper. Shares in GlaxoSmithKline (GSK) proceeded to plummet. Financial analysts predicted troubled times for the company. And on May 21, 2007, the US Food and Drug Administration (FDA) published a “safety alert”, concluding that “serious concern” existed over GSK’s rosiglitazone, a drug approved for the treatment of type 2 diabetes. The occasion for this sudden anxiety was a systematic review of 42 trials published in the New England Journal of Medicine by Steven Nissen and Kathy Wolski from the Cleveland Clinic. They reported an odds ratio of 1·43 (95% CI 1·03–1·98) for myocardial infarction (MI) in those taking rosiglitazone compared with controls. The odds ratio for cardiovascular death was 1·64 (95% CI 0·98–2·74). GSK had already submitted its own pooled analysis to the FDA, which suggested that short-term use of rosiglitazone might increase the risk of heart attack by some 30–40%. The tone of the NEJM paper was one of urgency. In an accompanying editorial, Bruce Psaty and Curt Furberg went further and questioned the whole rationale for prescribing rosiglitazone. GSK has responded by saying that it “strongly disagrees” with the conclusions of the NEJM paper. Who is right?
The two most reliable studies to inform decisionmaking are ADOPT (published in the NEJM) and DREAM (published in The Lancet). DREAM included 5269 adults. The MI and MI/stroke/cardiovascular composite event rates in the rosiglitazone group were 0·6% (control, 0·3%) and 1·2% (control, 0·9%), respectively. Neither result was statistically significant. ADOPT included 4360 patients. The only significantly relevant finding was an excess of congestive heart failure episodes for rosiglitazone-treated patients compared with glyburide (22 vs nine events). Taken together, these results, although based on very small numbers of events, certainly raise a signal of concern and indicate the need for more reliable information about rosiglitazone’s safety. But the FDA, physicians, and patients can reasonably await the results of RECORD, a phase III trial designed specifically to study cardiovascular outcomes. Until the results of RECORD are in, it would be premature to overinterpret a meta-analysis that the authors and NEJM editorialists all acknowledge contains important weaknesses. To avoid unnecessary panic among patients, a calmer and more considered approach to the safety of rosiglitazone is needed. Alarmist headlines and confident declarations help nobody. ■ The Lancet www.thelancet.com Vol 369 June 2, 2007
The deteriorating health situation in Iraq
See Correspondence page 1860
For the UNAMI report on the humanitarian situation see http://www.uniraq.org For the UNICEF plan see http://www.unicef.org For more on the situation in Samarra see http://www.reliefweb.int/rw/ RWB.NSF/db900SID/LRON739HKV?OpenDocument
The health situation in Iraq is deteriorating on almost every level. In this week’s issue, two doctors from Basrah describe how insulin is unavailable because it is not safe to distribute it. Last month the first cases of cholera were reported. And in an interview with the non-governmental organisation Doctors for Iraq, Khaled Mahmud, head of resident doctors in Samarra General Hospital, described how power outages prevented the use of all the medical appliances in the hospital. The worsening humanitarian situation was recently outlined in a UNAMI report. 54% of Iraqis are now living on less than US$1 a day and almost half of all children are malnourished. Since the coalition invasion in 2003, 12 000 of Iraq’s 24 000 doctors have left Iraq. More encouragingly, 3·6 million children have just been immunised against measles, mumps, and rubella
and last week UNICEF launched a 6-month action plan, which will address the specific needs of Iraqi children. In addition, the National Center for Drug Control and Research which will analyse the quality of pharmaceutical products imported into Iraq opened last month. When devising health plans for Iraq it is vital to consider accessibility rather than availability. There is little point in having high quality drugs if it is not safe to distribute them, or new tertiary centres that people cannot access due to restrictive curfews and checkpoints. If Iraqi citizens are to have any hope of a better life, there must be a comprehensive yet realistic strategy—with input from all stakeholders, most importantly the Iraqi people—that adequately addresses the health needs in Iraq. Ignoring what is happening on the ground while planning for the future is a recipe for disaster. ■ The Lancet
Science Photo Library
Rosiglitazone: seeking a balanced perspective The printed journal includes an image merely for illustration Published Online May 23, 2007 DOI:10.1016/S01406736(07)60787-9
For the ADOPT study see N Engl J Med 2006; 355: 2427–43. DOI:10.1056/NEJMoa066224 For the DREAM study see Articles Lancet 2006; 368: 1096–105.
1834
“Health alert over diabetes drug linked to heart risks”, ran the headline in one UK newspaper. Shares in GlaxoSmithKline (GSK) proceeded to plummet. Financial analysts predicted troubled times for the company. And on May 21, 2007, the US Food and Drug Administration (FDA) published a “safety alert”, concluding that “serious concern” existed over GSK’s rosiglitazone, a drug approved for the treatment of type 2 diabetes. The occasion for this sudden anxiety was a systematic review of 42 trials published in the New England Journal of Medicine by Steven Nissen and Kathy Wolski from the Cleveland Clinic. They reported an odds ratio of 1·43 (95% CI 1·03–1·98) for myocardial infarction (MI) in those taking rosiglitazone compared with controls. The odds ratio for cardiovascular death was 1·64 (95% CI 0·98–2·74). GSK had already submitted its own pooled analysis to the FDA, which suggested that short-term use of rosiglitazone might increase the risk of heart attack by some 30–40%. The tone of the NEJM paper was one of urgency. In an accompanying editorial, Bruce Psaty and Curt Furberg went further and questioned the whole rationale for prescribing rosiglitazone. GSK has responded by saying that it “strongly disagrees” with the conclusions of the NEJM paper. Who is right?
The two most reliable studies to inform decisionmaking are ADOPT (published in the NEJM) and DREAM (published in The Lancet). DREAM included 5269 adults. The MI and MI/stroke/cardiovascular composite event rates in the rosiglitazone group were 0·6% (control, 0·3%) and 1·2% (control, 0·9%), respectively. Neither result was statistically significant. ADOPT included 4360 patients. The only significantly relevant finding was an excess of congestive heart failure episodes for rosiglitazone-treated patients compared with glyburide (22 vs nine events). Taken together, these results, although based on very small numbers of events, certainly raise a signal of concern and indicate the need for more reliable information about rosiglitazone’s safety. But the FDA, physicians, and patients can reasonably await the results of RECORD, a phase III trial designed specifically to study cardiovascular outcomes. Until the results of RECORD are in, it would be premature to overinterpret a meta-analysis that the authors and NEJM editorialists all acknowledge contains important weaknesses. To avoid unnecessary panic among patients, a calmer and more considered approach to the safety of rosiglitazone is needed. Alarmist headlines and confident declarations help nobody. ■ The Lancet www.thelancet.com Vol 369 June 2, 2007