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Testimony Presented Before the FDA

Creation/Revision Date: September 11, 2007

Testimony presented before the Food and Drug Administration (FDA) Cardiorenal Drug Advisory Committee and the Drug Safety and Risk Management Advisory Committee

By

Alan S. Kliger, M.D. 
Hospital of Saint Raphael 
Chairman, Department of Medicine 
September 11, 2007

 
Testimony of Alan S. Kliger MD, President Renal Physicians Association to FDA Sept 11, 2007

Members of the Cardiorenal Drug Advisory Committee and the Drug Safety and Risk Management Advisory Committee,

My name is Alan Kliger. I am president of the Renal Physicians Association, the professional organization of nephrologists who care for patients with kidney disease. I am speaking on behalf of both the RPA and the American Society of Pediatric Nephrology, the professional society of pediatric kidney specialists that promotes optimal care for children with kidney disease. The RPA and ASPN appreciate this opportunity to address you. Each day, thousands of our member nephrologists care for hundreds of thousands of patients on dialysis and those with chronic kidney disease. For most of these patients, we prescribe ESAs, to replace the diseaseinduced absence of patients’ own erythropoetin. The prescribed ESAs permit patients to generate their own normal RBCs.

You are holding this hearing and making recommendations to the FDA because recent studies in adults with chronic kidney disease have shown a higher risk of death or cardiovascular events with target Hb level 13.5 Gm/dL than with lower target Hb levels. We nephrologists use evidencebased guidelines to inform our prescribing practice, and these studies have surely raised our concerns – just as they have raised yours. With this in mind, we wish to make several points and ask your advisory committees to consider 4 issues as you formulate your recommendations.

First, consider uses and warnings that are patient and population specific. Cancer patients with anemia are very different than patients with CKD or those on dialysis. Children are different and more vulnerable than adults. Low EPO levels are a lifelong problem for kidney failure patients. Before ESAs were available, we regularly gave our dialysis patients blood transfusions to treat their anemia. Blood transfusions can cause infections such as hepatitis and can induce antibodies, making future kidney transplant difficult or impossible. Those of us who practiced before ESAs were available remember the debilities so common in our anemic patients, and the complications of frequent blood transfusions. As we seek to prevent the cardiovascular events associated with high Hb targets, please remember the hardships to our patients that would result if policies and warnings around ESA use were to drive Hb levels down to low levels again.

Second point: We know that different patients respond differently to treatment with ESAs and iron. Adult needs vary, and children need 
different doses than adults. Despite our best efforts, there will always be a distribution of achieved Hb levels – a “bell curve” of Hb. Warnings or prohibitions at the high end will surely shift the curve to the left, increasing the numbers of patients at the low Hb end. Should clinicians be warned that Hb should not be > 12, we know that the number of patients with Hb < 10 or even < 9 will increase substantially. Hb targets should not be above 13. We urge you to make recommendations that do not impede the ability of nephrologists to achieve the target Hb range as recommended by evidence based guidelines, 11 – 12.

Third: Please preserve improvement in quality of life as an indication for ESA use for anemia in kidney disease patients. In the 1980s, so 
many of our patients saw the introduction of EPO as life-altering. It was the most important improvement in dialysis care I saw for 
decades. This clinical experience is confirmed by the limited but consistent published evidence on quality of life, particularly at the 
lower end of the Hb curve. Please listen to what our patients say about the importance of these ESAs to their lives.

This brings me to my final, and perhaps most important point. Each patient is unique, each with their own risk profile, biologic and psychological response to anemia, and their own opinion and choices about their treatment. Good medicine is done one patient at a time, where 1 doctor and her patient together make best treatment choices. Clinical research and clinical practice guidelines inform these decisions, but do not dictate them. A recent meta-analysis published in Lancet reported that a Hb target of > 12 Gm/dL was associated with a 17% increase in mortality risk. On the other hand, a recent KDOQI meta-analysis showed only a 2% nonsignificant increased mortality risk for CKD patients, and a 12% nonstatistically significant increased mortality risk for dialysis patients. Patients and doctors weigh that risk against benefits of treatment – and in some cases choose that risk to avoid worse consequences for that individual.

 
Some of our ESRD Networks have already received patient complaints that their physician has drastically cut their EPO doses for fear that any patients will have Hb > 12. These patients say they feel much worse with lower Hb, and are willing to sign releases to allow better EPO dosing – but their doctors refuse. Please help to reverse this fear among nephrologists. Do not create the kinds of warnings and policies that cause patients to rise up and beg for more medicine. Each doctor and informed patient should be allowed to determine best dosing.

In summary: 

1. Create policies and warnings that are patientpopulation specific. 
2. Remember the irreducible biologic variation in response to ESAs, and create treatment policies that expect this variation 
and do not induce overreaction to the dangers at the high end. 
3. Preserve quality of life as an indication for ESA use – remember patient experiences in the pre-ESA era 
4. Respect the right of patients and their doctors to consider risks and benefits, and make best individual decisions. 

Thank you for allowing me this time and for your attention. 

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