Dialysis Unplugged: The FDA, REMS and ESAs - Lost in Translation?

There is no question that ESAs have been overused in the US dialysis population. From 1991 onwards the data shows that there was a dramatic increase in the use of ESA  (Fig. 1A) and this use resulted in Hb levels much higher than even recommended by the National Kidney Foundation KDOQI (Fig. 1 B) and higher in the US than other countries.

Fig. 1 (click to enlarge)

In response to 3 RCT’s – Normal Hematocrit, CHOIR, and CREATE and accumulating evidence from various oncology studies, the FDA decided to introduce major changes to the ESA label, and perhaps belatedly also introduced REMS. In 2010 in a commentary I published in CJASN [It's available open access], I discussed the epo REMS and how the FDA planned to apply it. I made the point that REMS was not enough and that more studies were needed. Two years later, Cohen and Brown in an article in AJKD make the important points indeed REMS has been confusing, under-promoted by Amgen and rather ineffective. 

They write: “How successful has the REMS program been to date for patients with CKD? We believe that the FDA program would have benefited from greater input of the renal community before issuing rules regarding distribution of the guide to patients. For more than a year, the FDA mandated that the guide be distributed every 30 days to each renal patient receiving an ESA, a request both illogical and onerous. Fortunately, in response to a letter of protest about this mandate dated July 2010 from the Renal Physicians Association, the FDA decided as of June 2011 to modify enforcement of this requirement to monthly distribution of the guide for only those patients with CKD with cancer. But has the ESA guide actually been distributed to patients with CKD thus far? On a telephone survey that the authors conducted in July 2011, of 16 medical directors of 21 Eastern Massachusetts dialysis facilities selected at random, only 4 had knowledge of the REMS requirement and the patients of only 2 of the 21 facilities had received the guide on a single occasion. Therefore, we suspect that the major reason for the failure of nephrologists to comply with the program is the failure of Amgen to publicize the REMS program and distribute the guide to the dialysis facilities that dispense ESAs. In addition, some dialysis provider organizations also have failed to comply with the distribution of the documents to patients and have delegated the full responsibility to their staff nephrologists. Finally, our telephone survey of medical directors suggests that there has been a failure of some nephrologists knowledgeable about REMS to comply with the requirements. The impracticality of distributing the guide every 30 days, and perhaps its imbalanced content, may have led some to dismiss the REMS requirements as unreasonable.”

The bottom-line is that REMS has not worked because there hasn’t been a thoughtful approach to it’s introduction. Furthermore, pharma has appeared to only pay lip-service to it’s implementation. But, as I have stated before, what really needs to happen is that the FDA should insist on further studies to be performed by both Amgen and Johnson and Johnson.