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99 failures behind every breakthrough: When a promising idea to treat disease doesn't pan out

The premise was sound: Given the known, albeit distant, connections between kidney disease and gout, would a treatment for the latter have an impact on the former?

Three years later, following a clinical study in two countries that enrolled 530 participants with diabetes and kidney disease, investigators had their answer.

It didn't.

"I think the basis for the theory was actually quite strong," said Peter Senior, an endocrinologist and professor of medicine at the University of Alberta who was involved in the research. Results of the trial were published last month in the New England Journal of Medicine.

"But until you do the proper study, you don't really know."

Gout, a form of inflammatory arthritis, is often characterized by a "swollen hot toe" and linked to too much drinking and too much rich food. The medical cause, though, is a buildup of uric acid, Senior said in an interview with CBC Radio's Edmonton AM.

Kidney disease can lead to kidney failure, requiring a transplant or dialysis for survival. Senior, a diabetes researcher who works in the university's endocrinology and metabolism division, said diabetes is a big driver for kidney disease, with half or more of Type 1 diabetics eventually developing it.

Enter the theory: To see if the development of kidney disease could be slowed by lowering levels of uric acid in diabetics using allopurinol, a gout medication developed in the 1960s.

Supplied from Faculty of Medicine & Dentistry
Supplied from Faculty of Medicine & Dentistry

The theory had some support in studies that found some populations with lower overall uric acid levels also seemed to have less kidney disease, he said.

"There were these different strands of ideas, of what we call epidemiological evidence … and that led people to kind of hypothesize that maybe lowering it would make a difference."

The three-year, placebo-controlled and double-blind trial did find that allopurinol successfully lowered uric acid levels in participants, but measurements of kidney function for patients in the trial didn't show any change.

A second study from Australia on patients with a variety of chronic kidney diseases, some with diabetes, published alongside the study, showed similar results.

Senior said he had mixed emotions about the study's result.

"We all want to do the study which moves things forward and pushes things on," he said. "On the other hand, if we clearly answer a question that says 'This treatment strategy or this approach does not work,' then we avoid wasting further time and effort on that."

With COVID-19 pushing research even more into the public eye, it's important to remember the role that scientific research plays in determining what works — and what will not, he said.

"I think the story of science is [that] for every breakthrough, there's been 99 failures," he said.

"Actually proving that the treatment or intervention or that pathway is really important, you have to do the studies," he said.

"We have been proven wrong in science many times before, where some of it seems to make sense, and should work on paper and doesn't work out in real life. I think it's because real life is more complicated, even more complicated than the complicated scientific models we proposed."

As for this particular study, Senior said he deems it a success that they were able to successfully complete the logistically complex clinical trial.

He said researchers will continue to explore new ideas for reducing rates of kidney disease which, despite many advances in health care, still remain stubbornly high.

"The problem still exists, it still needs to be addressed," he said. "This drug is not the way to go but there may be many other approaches."