Open Science for the Future of Clinical Trials
The Systolic Blood Pressure Intervention Trial (SPRINT) was funded by the National Institute of Health to answer one question: "Will lower blood pressure reduce the risk of heart and kidney diseases, stroke, or age-related declines in memory and thinking?"
The primary finding of SPRINT, published in the New England Journal of Medicine in 2015 was that intensive treatment for hypertension reduces risk of cardiovascular outcomes and stroke. An additional finding was that patients with chronic kidney disease had a lower risk of kidney injury when intensively treated than did patients with normal renal function, suggesting that more intensive treatment may have greater risk among normal subjects.
A reanalysis by our research team—three clinicians and four biostatisticians at the Mailman School—has provided a reinterpretation of the results that resolves a puzzle clinicians have been trying to solve since the findings were announced. Typically, intensive blood pressure control improves cardiovascular outcomes, but also increases the risk of kidney injury. So, why does chronic kidney disease protect against subsequent kidney impairment in SPRINT? And if this is the case, what are the implications for treating hypertensive patients with normal kidney function?
In the spirit of open science, to encourage new conclusions or confirm the original findings, the New England Journal of Medicine invited the public to participate in the analysis of the trial data through the SPRINT Challenge.
Our analysis concludes that the effect of chronic kidney disease appears to result from a problematic definition of kidney injury in SPRINT that differed between patients with normal kidney function and those with chronic kidney disease. After correcting this, using the same criteria for both treatment groups and using acute kidney injury as the kidney related outcome, we found that baseline chronic kidney disease actually predicted a much higher risk of acute kidney injury, in the group of patients receiving more intensive treatment.
This revised conclusion is clinically intuitive and seems to resolve the apparently contradictory findings of the original trial. The question now becomes: to what extent are the cardiovascular benefits of intensive treatment for hypertension significantly offset by an increase in adverse renal events?
Unfortunately, because the SPRINT Trial did not follow patients longer than five years, a clear answer is not currently available, although the incidence of dialysis dependent kidney failure did not differ between treatment arms.
We plan further work to see if over a longer period of time acute kidney impairment over a range of function following blood pressure treatment leads to more patients eventually requiring dialysis. We are exploring funding to answer this and related questions, so as to optimize intensive treatment of hypertension for patients with chronic kidney disease.
You can read more about our proposal on the SPRINT site. We believe that we have answered the important question of why the trial saw a protective benefit for renal outcomes in those with chronic kidney disease.
10 percent of each Challenge entry’s score is based on public voting. If you think our project is worthy, please cast your ballot for it. But if you think another proposal has greater merit, give them the nod.
The SPRINT Challenge is an innovative, transparent system for responsibly sharing clinical trial data and maximizing the impact from the work of many committed individuals and patients willing to enroll in a clinical trial and potentially put themselves at additional risk. Such opportunities allow those in clinical settings and in public health to have a meaningful impact on patient care and public health.
The Mailman School’s SPRINT team started with Dr. Laura Rosales. As a nephrologist she sought to understand why chronic kidney disease, appeared to protect against kidney issues in SPRINT. She and I are both members of the Executive MHA/MPH program in the Department of Health Policy and Management at Mailman. We discussed the puzzle, and decided to put together a team to analyze the SPRINT data to address it.
Our membership in the Executive MHA/MPH program allowed us to pair clinical experts with an experienced statistical group, to identify a key clinical question, find the data to describe it, and use the appropriate methods to address it.
The other members of our team are: George Kaysen, MD, PhD, Nathan Levin MD, Eun Jeong Oh, MA, John L. P. Thompson, PhD, and Julia Wrobel, MS.
Public voting closes Monday, February 27. If you think Mailman’s team should advance further with our research, show your support through the SPRINT site.
Joshua Kriger, MS, is a student in the Executive MHA/MPH program and the Statistical Program Manager for ICAP’s PHIA (Population HIV Impact Assessment) project. He is also a member of the Statistical Analysis Center (SAC) in the department of Biostatistics at Mailman School of Public Health.
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