Is the FHN Nocturnal Study Negative or Simply Null and Void?

By Peter Laird, MD

The FHN nocturnal hemodialysis study suffered severe recruitment difficulties leading to significantly lower total number of expected patients for this study. Today, despite the many flaws of this study, some are calling into question whether we should offer any patients home nocturnal dialysis any longer on the basis of this so called "negative" study.

Dialysis: Nocturnal hemodialysis - should we still provide this therapy?

Frequent nocturnal hemodialysis has emerged as a promising option for patients, with some studies demonstrating that it improves clinical outcomes. However, the negative results of a recent randomized trial have cast some doubt on whether nocturnal home hemodialysis has any advantages over conventional hemodialysis.

During my internal medicine training, learning how to evaluate medical studies became an important part of my learning experience. We were taught to apply the McMaster critical review process to all of the studies we evaluated in our monthly journal clubs presentations. This incorporated not only methods and analytical tools utilized in the study but also weaknesses in methodology and any bias that may have been inherent to the research. Understanding that the conclusions drawn by researchers are only as good as the evidence it is based upon is at the heart of incorporating any research article into daily medical practice.

One of the most important aspects of the McMaster critical review process is whether the conclusions are trustworthy and will apply to your practice as a physician. The nocturnal arm of the FHN is one study that is fraught with errors that render any conclusions null and void due to the serious flaws in methodology and execution of the planned study. To draw any conclusions when a study has such serious errors in methodology is simply ignoring the one conclusion you must assess with any medical study: does this study reflect my own patient population and how trustworthy are the results.

Despite nearly a decade of planning and executing this study, to state it represents a negative outcome for nocturnal dialysis misses the point that it is simply a null and void study that failed to answer any questions presented. It is not a study that should in any manner slow enthusiasm for nocturnal hemodialysis. Unfortunately,  it is one more example of how a randomized and controlled trial is not always the final answer to a clinical question especially one hampered by recruitment issues where patients simply did not consider the treatment options equal. The most serious failure of the FHN nocturnal study is the most important, it is not trustworthy or generalizable due to over selection, nor even repeatable. These are all failures that render any results essentially irrelevant to answering the questions it was designed to answer. In a word, the FHN nocturnal study is simply a failure that should not be repeated or utilized for any clinical decisions.

Comments

[MooseMom]

The FHN study DID show significant improvement in hypertension and hyperphosphatemia, and we know that these two factors are cardiovascularly lethal in dialysis patients, so on this evidence alone, can anyone really say that standard hemo is a more effective treatment than nocturnal hemo? And also considering this evidence alone, can we really say that the FHN study is, in fact, null and void? It sounds like the only criteria being considered in LVH, or am I just missing something?

[Peter Laird, MD]

Dear Moosemom, the HTN and phosphorus are secondary markers that are associated with improved outcomes when controlled in other studies. Certainly, many believe that these improvements will lead to better long term outcomes down the road. That being said, no one disputes the biochemical improvement of phosphorus and the improvement of HTN with nocturnal, or extended dialysis. That outcomes is consistent in study after study including the FHN nocturnal study.

LVH is a direct clinical marker reversing end organ damage from an intervention and this was the most important measured marker in the FHN study. In that sense, since it didn't show the expected change for the better, some are alleging that the FHN study is negative. I don't agree, for the measured outcomes that they were seeking, LVH and improved quality of life, the FHN nocturnal study is null and void due to serious flaws in execution of this study.

[MooseMom]

I understand the difference between a "direct clinical marker" and "secondary markers", and I understand why you are saying that the FHN nocturnal study is null and void; I don't disagree. But it seems to me that if nephs are asking the question "should nocturnal hemodialysis still be offered", the answer should be "yes" since there is no real debate regarding the improvement of HTN and phosphorus. Do you think the answer should be "no" if LVH was not proven to be improved?

Did the author even answer his own question? He did say that we should be "encouraged" that home hemo is safe and effective (notice he didn't specify "nocturnal home hemo"), but what do you think? Will this particular physicial offer nocturnal home hemo as an option to his dialysis patients? I really couldn't tell.

[Peter Laird, MD]

You are right, it was a very noncommittal editorial which in the long run only adds fuel to the fire of doubt about nocturnal home hemodialysis. I wish that these same pundits would invest the same energy into criticizing the study itself.

[MooseMom]

What does all of this mean for the patient who has done his research and has come to his own conclusion that NHHD is his RRT of choice? Based on what we know to be true AND suspect to be true, how would you advise said patient to craft his argument in requesting NHHD?

[Peter Laird, MD]

That is difficult. With all that I know, it is not available to me, only short daily dialysis which I have taken to the max getting about 24 hours per week. If the provider won't go beyond the FDA quidellnes for that machine, you won't get NHHD period.

[MooseMom]

I have often wondered why you have chosen SHHD over NHHD; is it because your provider won't go beyond the FDA guidelines? If this is the reason, and if, say, your provider changed his mind, would you change to NHHD given the opportunity? Or are you happy with the modality you now use? (I hope these questions aren't too intrusive. My apologies if they are.)

[Peter Laird, MD]

Moosemom, I get about 24 hours a week of dialysis which is way above and beyond incenter. My wife and i have talked about doing nocturnal at some point. Currently, it is not offered in Southern CA Kaiser. I like sleeping in my own bed and I already know that my wife would not sleep well with a machine humming away in the room. That is perhaps the thing she hates the most about doing home dialysis.

On the other hand, if I dialyzed in my chair in the living room, she wouldn't sleep well because I was not in the room with her. Lastly, I am a bit of a control freak so simply sleeping away the night while on dialysis goes against my grain. But I suspect that if available, it would free up more time during the day and we would quickly adjust as do other people that go onto nocturnal.

So, I am satisfied with my current regimen but at some point, my wife and I have already discussed going to nocturnal if it is ever available. In all likelihood, even though my nephrologist supports the concept of home nocturnal hemodialysis, he won't go beyond the current label.

[Christopher Blagg MD]

Dear Peter

I agree with you that it will be most unfortunate if the results of the flawed overnight FHN study are used to put off patients or their doctors from choosing home overnight dialysis.

As for the FDA and overnight hemodialysis, as far as I know every other dialysis machine has been used by at least some patients for nocturnal hemodialysis at least 3 times a week at some time or other since 1965. All the evidence from many observational studies over the years has shown that patient survival etc. is better with home hemodalysis whether by day or by night, and we also know that the more hours a week of dialysis a patient gets, the better they are.

If a dialysis machine is approved by the FDA as being safe and effective enough to be run by anybody in a U.S. dialysis unit, surely it is safe enough to be used by a well trained patient who wants to go home and dialyze.

[MooseMom]

Peter, yes, those are all important considerations since your wife has to live with your decisions. I'm sure she appreciates your consideration of her preferences.

[Peter Laird, MD]

Dear Chris, unfortunately, the NxStage nocturnal indication should not be an impediment to nephrologists prescribing it for that use, but many institutions such as Kaiser do adhere to the FDA labeling as it now stands. There isn't any medical reason why it could not be used as many have demonstrated safely and effectively. It is just one more aspect of American nephrology that is plain and simply frustrating.