"FDA and the manufacturer of these products have agreed on revised product labeling that includes updated warnings, a new boxed warning, and modifications to the dosing instructions. The new boxed warning advises physicians to monitor red blood cell levels (hemoglobin) and to adjust the ESA dose to maintain the lowest hemoglobin level needed to avoid the need for blood transfusions. Physicians and patients should carefully weigh the risks of ESAs against transfusion risks.
Recently completed studies describe an increased risk of death, blood clots, strokes, and heart attacks in patients with chronic kidney failure when ESAs were given at higher than recommended doses. In other studies, more rapid tumor growth occurred in patients with head and neck cancer who received these higher doses.
In studies where ESAs were given at recommended doses, an increased risk of death was reported in patients with cancer who were not receiving chemotherapy and an increased risk of blood clots was observed in patients following orthopedic surgery."
Now here is how the BMJ -- what an appropriate acronym -- covers it:
"Concerns about the safety of a class of drugs used to treat anaemia have triggered a federal alert in the United States. The alert comes after recent studies reported a higher incidence of fatal cancers and cardiovascular events among patients who were treated with drugs known as erythropoiesis stimulating agents when the drugs were used to raise haemoglobin concentrations to more than 120 g/l.
The US Food and Drug Administration issued the alert on 16 February, urging doctors "not to [give doses] to exceed haemoglobin levels of 12 g/dl" when treating patients with anaemia resulting from chronic renal failure, cancer or cancer chemotherapy, or HIV or AIDS."
See how BMJ traverses from proceeding with caution to prescribing beyond a specific hemoglobin level? Notice how things have moved from an advisory to a triggering a federal alert, like some terrorist warning? And note the inconsistency in metrics. Can we stick with 120g/l or 12g/dl from one graf to the next please?
Oh and leave it BMJ to allege a plot of some sort: conflicted scientists stuffed with cash hiding results about how plying patients with EPO kills them...as if there were no independent drug safety monitoring board reviewing the study as it progresses and if there were no mechanistic reason to explore the use of EPO in other cases...
"Issues of financial conflicts of interest and unpublished data have led to considerable controversy around the drugs. The New England Journal of Medicine decided not to publish an opinion piece it commissioned from Robert Steinbrook, one of the journal's senior physician writers, who questioned whether guidelines issued by the National Kidney Foundation to achieve higher concentrations of haemoglobin may have been tainted by multimillion dollar contributions from the manufacturers of the drugs, says a report in the Wall Street Journal (26 Dec 2006, p B1)."
Ok. I'm back. Had to shower after reading THAT again.
Let me state that I have always thought that the nextgen approach to EPO dosing - or dosing of any kind -- should be of the personalized sort, finding which dose works best with what subpopulation of patients. This is the right approach for any number of reasons.
Having said that, I am so sick and tired of this allegation of bribery regarding guidelines. If anyone -- including -- the lazy author of the first WSJ article on this subject had taken the time to read the NKF involvement in guideline development with respect to dialysis (a distinction that BM-J does not make in it's J'accuse) and use of EPO type meds they would see it is as transparent as BMJ's hatred of the pharmaceutical industry.
And moreover they would see that in the past Medicare reimbursement rates had kept EPO doses artificially low to the point that people were not getting sufficient hemocrit levels. Dosing is higher and so is survival. At least in anemia. We are finding that this is not always the case in other clinical situations. Absent biomarker driven or more aggressive use of observational studies, reliance on RCTs will cause us to stumble our way to better or more targeted care. That's the way science proceeds. It is not a function of malfeasance.