A number of people have chastised me for demanding, in my
articles, that we need more evidence to prove the superiority of frequent daily
or nocturnal dialysis over conventional dialysis. In fact, I’ve agreed to
participate in a debate in NDT about this very issue.
So let me state for the record that I am a believer in more
dialysis. If a family member or I was on dialysis I would opt for more frequent
dialysis. And, I recommend home dialysis to my patient’s as they embark on dialysis. Yes, I am a believer.
But I do feel that we need more data. I really do feel that we have not
reached that point, described by Malcolm Gladwell in his famous book, of
tipping the majority to agree that more dialysis is better.
To reach the tipping point we need a fairly large randomized
controlled trial, properly powered and evaluating the effect on hard end-points
like mortality and cardiovascular complications. Besides, demanding for more
evidence isn't that unreasonable - we all know that there is enough money in the dialysis industry to fund
such a trial. After all, DaVita made over 3 billion in profit. Worse, Kent
Thiry DaVita’s CEO made over 13 million dollars in compensation.
The situation is similar at Fresenius I am sure.
We have gone as far as we can – short of a randomized trial
– to establish the superiority of more dialysis.
Take for example a study published in the current JASN. [One of the renal fellows had printed it over the weekend]. It's a nice study, well worth reading. Nesrallah and co-workers from London Ontario performed a analysis comparing outcomes in patient’s undergoing intensive versus in-center hemodialysis.
Take for example a study published in the current JASN. [One of the renal fellows had printed it over the weekend]. It's a nice study, well worth reading. Nesrallah and co-workers from London Ontario performed a analysis comparing outcomes in patient’s undergoing intensive versus in-center hemodialysis.
Nesrallah and co-workers identified 420 patients in the
International Quotidian Dialysis Registry who received intensive home
hemodialysis in France, the United States, and Canada between January 2000 and
August 2010. They matched 338 of these patients to 1388 patients in the
Dialysis Outcomes and Practice Patterns Study who received in-center
conventional hemodialysis during the same time period by country, ESRD
duration, and propensity score. The use of matching using propensity scores was
targeted to attenuate the effect of confounding. The investigators also
performed several sensitivity analysis to test the strength of their findings. Obviously one of the major limitations of the study is that they couldn't achieve perfect balance between the two groups (intensive vs. conventional HD) and they couldn't eliminate the potential effect of residual confounding.
The dialysis industry will never intentionally fund a study which undermines the current *successful* business model.
ReplyDeleteRegardless of how "ideal" or how much we would "prefer" a RCT, the reality is that equipoise no longer exists within the research community.
"Randomizing" patients to an inferior treatment arm is clearly unethical, when the very researchers who would be doing the randomizing are FULLY AWARE of hazard ratios on the order .55 as you indicate here.
Propensity-matching techniques are all we have. Deal with it. Accept it. That is how it is.
You might as well seek volunteers to participate in a RCT of the effects of gunshot wounds to the face. Is residual confounding in a well-thought-out study really any worse than an inevitable failure to achieve randomization?
Patients would be allocated merely based who has the resources to make the choice, i.e., "haves" vs. "have-nots" which is a sure fire recipe for confounding. The poor, the uninformed, and the elderly will get less dialysis. Yes, let't waste several hundred million dollars and yet another decade only to arrive at another FHN flop.
Dr. Singh, I am always interested in how theory is translated into practice. So, let me ask you this; if you are a believer in "more dialysis is better" yet also believe that more data is needed to support this, what would you tell your new CKD5 patient TOMORROW as s/he prepares for dialysis? S/he will be looking to you for advice on the best treatment. What would you advise?
ReplyDeleteThe ACTIVE trial is already recruiting patients for such a study in Australia. I don't believe RCT's will change treatment paradigms. The only thing that will is changes in technology where LDO's can make more money selling home dialysis machines than keeping the in-center tragedy going. I am hopeful that the FDA Innovation Pathway announcements this week signals a new movement away from the status quo. There are several companies on the verge of technical breakthroughs that could be a real game changer. RCT's involving the number of patients that will convince the Glenn Chertows of this world will never happen. The market place competition with new technology is the only hope of dialysis patients since the American academic nephrology community has quite abandoned us long ago to the misery of conventional care even though there is not a single RCT showing that this therapy was better than what Scribner and his team developed before Congress in 1978 shoved people into the hands of in-center LDO care.
ReplyDeleteThe very notion of needing a "tipping point" might actually have merit if the majority of American nephrologists still remained "unconvinced" - hence in need of "convincing."
ReplyDeleteBut this is clearly not the case. Both surveys as well as actual treatment decisions (for themselves and/or their family members) makes it extremely clear what on the order of at least 90% of American nephrologists really believe, which makes the fact that actual prescribing behavior is completely contrary to this all the more inexcusable.
Continued pretending that somehow we still don't know, when what we ACTUALLY BELIEVE is so clear, is a disservice to everyone. What needs to change is not "what American nephrologists believe"--it is what they actually DO.
Right now, doctors are recommending more dialysis by way of home dialysis 9 out of 10. That's a pretty hefty number, and people are going that way more and more. I was on NxStage for a short time, felt better, my numbers were much better, had more energy, felt excellent when my treatments were over. I have serious heart problems and my blood pressure stayed normal as well as my pulse. Now that I am back in center, my bp is so low that I have to take Midodrene three times a day to raise it enough to even get through dialysis. I have a flow rate of 450 and 4 kilos is all I can pull in a treatment.
ReplyDeleteI will not waste time with the medical terms, I will simply say that, "non disease fully functioning kidneys works 24/7. Patients are receiving 12/3. It's clearly simply, in my opinion, it should have never been introduced to the public only a 3 day 4 hour basis, you should have provided clinics open mon-fri and one clinic could with around the clock dialysis, and still at 4 hours, but everyday except sat-sun. It would do two things, improve health and provide jobs. The way something is introduced to someone, it is hard to get them to see it any other way. Changing at this time, it would appear that the companies are money hungry, but in all honesty, it would really provide a much needed service.
ReplyDelete