Thursday, November 4, 2010
Science: Questions from China Snag U.S. Trial of Nerve-Rerouting Procedure
The following is a Science report in "Research Ethics," published on it's 11/5 edition. A Chinese version is also available here.
Questions From China Snag U.S. Trial Of Nerve-Rerouting Procedure
SCIENCE VOL 330 5 NOVEMBER 2010 Published by AAAS
A running 5-year medical brawl in China has spilled over into Michigan, where it has delayed a clinical trial about to enroll patients. The trial, based at the William Beaumont Hospital in Royal Oak, Michigan, aims to surgically reroute the nerves of spina bifida patients to give them control of their bladder. Principal investigator Kenneth Peters confirmed last week that the U.S. National Institutes of Health (NIH)—which is funding the work—has asked for a review.
The urologist who invented the nerve-rerouting procedure, Xiao Chuan-Guo, has claimed phenomenal results in China—including an 87% success rate for 110 spina bifida patients at their 1-year follow-up visits. But the controversy surrounding his work is phenomenal, too. Earlier this year police charged Xiao, head of urology at the Union Hospital affiliated with Huazhong University of Science and Technology in Wuhan, with organizing street attacks on two of his critics. Those injured were Fang Shimin, who under the pen name Fang Zhouzi operates the Xin Yu Si or New Threads Web site (www.xys.org), and journalist Fang Xuanchang (no relation to Fang Shimin), who has edited magazine articles about Chinese patients who failed to benefit from Xiao’s procedure.
Xiao was convicted of “causing disturbance” and sentenced to 5.5 months of detention (http://scim.ag/doctor-sentenced-Beijing). He has appealed the verdict. Science sent a request for comment to Xiao’s lawyer by e-mail but did not receive a response by presstime.
Questions about the clinical trial in Michigan based on Xiao’s procedure reached the U.S. Department of Health and Human Services in March, when the so-called New Threads Volunteers, a watchdog group that tracks Xiao’s research, sent a letter to the Office of Research Integrity (ORI) and the Office for Human Research Protections (OHRP). The letter alleged, among other things, that “the current clinical trials in the United States are based on dubious data.”
ORI declined to take action, according to Eddie Cheng, a blogger, software engineer, and member of the Volunteers, who mailed letters about Xiao’s study to ORI and OHRP. Cheng says ORI wrote back in March that the allegations weren’t specific and that Xiao’s work in China was out of its jurisdiction. Last week, however, OHRP confirmed in an e-mail to Cheng that it had asked the funding agency to evaluate the allegations.
Xiao has many friends in the scientific community. Peters, head of urology at the Beaumont Hospital, and 30 researchers signed an open letter in support of Xiao in September urging China to “protect his human rights” and praising Xiao as “a compassionate man who is respected worldwide for his integrity and his innovative scientific contributions to society.”
Xiao developed a nerve-rerouting procedure to treat neurogenic bladder disorder in patients with spinal cord injury (SCI). Nerve crossover was first proposed by an Australian surgeon in 1907; medical literature holds a scattering of partial success stories. But Xiao’s approach—which he proposed in the late 1980s—bypasses the central nervous system by grafting a lower lumbar nerve to one or two sacral nerves below the spinal cord lesion, rerouting signals to bladder and urinary muscles. Xiao claims to have established a new pathway that can be used to initiate voluntary urination by scratching or squeezing skin on the thigh.
After testing the idea on rats and cats, Xiao applied for and received an NIH grant in 1994 to study dogs at the Long Island College Hospital in Brooklyn, New York. According to his own published account, Xiao began a trial of the procedure with Chinese SCI patients at a hospital affiliated with a coal mine in Henan Province in 1995 and published final results from the SCI patients in 2003 in The Journal of Urology. This peer-reviewed article reported that of 15 male SCI patients—all with hyperreflexic neurogenic bladder (involuntary voiding)— who had the surgery, 10 gained satisfactory bladder function, two had partial recovery, two failed, and one was lost to follow-up.
Critics see inconsistencies in the data. For example, in early reports (some in Chinese), Xiao described patients’ recovery taking place between 10 and 12 months post-op, but the 2003 final report says that patients gained bladder function 12 to 18 months post-op. In addition, the depiction of all 15 patients as hyperreflexic in the 2003 report seems at odds with Xiao’s previous reports, which described treating a mix of patients with hyperreflexic bladder and areflexic bladder (failure to void).
Eric Kurzrock, chief of pediatric urology at the University of California, Davis, Children’s Hospital in Sacramento, California, says Xiao’s study is “extremely flawed” because of “patient selection bias.” Kurzrock is particularly critical of the claimed high success rate, because it is not based on data from a randomized, controlled trial.
After treating SCI patients, Xiao began using nerve rerouting to treat bladder malfunction in children with spina bifida, whose spinal cords are generally not as damaged as those of SCI patients. The first privately funded trial at Beaumont Hospital, which took place in 2006 and 2007, included nine spina bifida patients and two SCI patients; Peters and co-authors reported preliminary results from spina bifida patients, but results on SCI patients have not been reported. The current NIH-funded trial aims to enroll about 16 spina bifida patients; the original design was not blind and had no control group. Peters says NIH has “created an oversight committee for our study. We met with them a few weeks ago and are addressing their comments. We will be submitting a revised protocol soon for their review.”