Xiao Chuanguo Fabricates and Falsifies Clinical Data

Xiao Chuanguo published two papers on his clinical trials of his procedure in the Journal of Urology. Before the papers published, he also published related results in conference abstracts, articles in Chinese and other reports in Chinese. By comparing the results in the two papers with that from other sources, we clearly demonstrate that he fabricated and falsified his data.

Xiao reported his results of "the first 15 patients with SCI" ("clinical trial was started in 1995") in his 2003 paper [1]. Before that, he also reported the results of "14 SCI patients since 1995" in his 1998 abstract [2]. It is not the problem that there is a difference of one in the total numbers of patients. The problem is that all 15 patients are of hyperreflexic bladder in the 2003 paper, whereas only 6 patients are of hyperreflexic bladder in the 1998 abstract. Where did the other 9 patients with hyperreflexic bladder in [1] come from? and where had the 8 patients with areflexic bladder in [2] gone?

The pre-operative residual urine should remain the same no matter how long the follow-up is. But this is not the case in Xiao's data. The pre-operative residual urine of his 6 patients with hyperreflexic bladder is 300 ml in his 1998 abstract, but this data becomes 317 ml in his 6 patients with hyperreflexic bladder, among the same "first 14 SCI patients", described in his achievement [3] that was presented to the Holeung Ho Lee Foundation when he applied for the award from the Foundation in 2002.

Xiao reported the 18-month follow-up results of the "first" 20 patients with spina bifida in his 2005 paper [4], one failed among 6 patients with hyperreflexic bladder. Before that, he reported the 12-month results of 13 patients with spina bifida, published in Chinese in the Journal of Clinical Urology [5]. There are also 6 patients with hyperreflexic bladder. The difference is that the 6 cases in [5] are all successful. From the context of both two papers, the 6 cases are the same. Xiao did not mention in [4] that there was one case that was once successful but then failed later, which may suggest that there exists a problem in long-term prognosis of the procedure.

There is also an inconsistency in residual urine between his 2005 paper in English [4] and 2003 paper in Chinese [5]. The residual urine of the 6 patients with hyperreflexic bladder is 70.17 ml in [4], whereas that of the same 6 patients is 102 ml in [5].

The above described inconsistencies in the numbers of patients and the residual urine can only be explained by that Xiao Chuanguo fabricated and falsified his clinical data.

There are other inconsistencies in Xiao's papers. The source of funding is indicated to be NIH and PVA in Xiao's 1998 abstract [2], while it becomes 4 grants from China in his 2003 paper [1]. Xiao was awarded his first NIH grant in 1994 to study dogs. If the grant was indeed used for his human trial in China started in 1995, then the NIH should investigate the grant misuse, and the OHRP should investigate the ethical violation.

In addition, there are changes in the lists of authors. Comparing to 1998 abstract [2], Victor Nitti and William C. de Groat were added in 2003 paper [1]. Comparing to 2003 paper in Chinese [5], Ellen Shapiro and Herbert Lepor were added in 2005 paper in English [4]. Most of those U.S. co-authors are from New York University, the recipient of Xiao's second NIH grant for a clinical trial of SCI patients started in 1999 at NYU. What are their roles in the clinical trial in China? What are their contributions to the papers [1,4], after the preliminary results had already been reported in [2,5] by others? Are they responsible for the grant misuse and the ethical violation while enjoying the right of authorship? Does their authorship mean that Xiao's second NIH grant was also used to support his clinical trials in China?

Besides these, an Chinese expert also found contradiction of urodynamic data in Xiao's 2005 paper [4]. The expert pointed out [6] that the postoperative urodynamic studies in Fig. 3B and Fig. 4B clearly show that the patients urinated by intra-abdominal pressure instead of the detrusor pressure, suggesting the failure of establishment of the reflex arc. But Xiao misrepresented that it is the reflex arc that causes the urination.

Xiao's 2003 and 2005 papers [1,4] were cited by his 2006 review article [7] (NIH is one of the sponsors). Besides these two papers, he also cited a conference report [8] that does not exist in the said Proceedings. Later on, the review article became the major reference of Beaumont Hospital's pilot clinical trial [9], while the claim of more than 85% success rate originated from the non-existent report became the major supporting data in Beaumont Hospital's application to their NIH grant [10].

We are not surprised to find out that Xiao committed the aforementioned academic misconducts. It has already been discovered that he once fabricated an official document [11] testifying the 85% success rate of 117 patients in his private hospital after 8 months of follow-up, but the hospital itself came into existence less than 8 months before.

Finally, Xiao's fabrication and falsification in his data can well explain why his results could not be replicated by the doctors at Beaumont Hospital, who were commented by peer experts that their one-year outcomes [12] "challenge the excellent, previously published results", and that "the clinical benefit of the procedure is not at all similar to previous reports".

We will file a complaint to the Journal of Urology and European Urology on Xiao's fabrication and falsification. We will also present this case to related authorities.

References

[1] 2003 article
http://www.ncbi.nlm.nih.gov/pubmed/14501733
Xiao CG, Du MX, Dai C, Li B, Nitti VW, de Groat WC.: An artificial somatic-central nervous system-autonomic reflex pathway for controllable micturition after spinal cord injury: preliminary results in 15 patients. J Urol 2003; 170: 1237.
A total of 15 male volunteers with hyperreflexic neurogenic bladder...Of the 15 patients 10 (67%) regained satisfactory bladder control within 12 to 18 months after VR micro anastomosis. Average residual urine decreased from 332 to 31 ml and
urinary infection as well as overflow incontinence disappeared. Urodynamic studies revealed a change from detrusor hyperreflexia with DESD and high detrusor pressure to almost normal storage and synergic voiding without DESD.
...After successful experiments in animals, clinical trial was started in 1995. We report results in the first 15 patients with SCI.

[2] 1998 conference abstract
http://xysblogs.org/wp-content/blogs/107/uploads/1998xiao14sci.gif
Xiao CG, Godec CJ, Du MX, Dai C, and Zhu X.: A new procedure to restore bladder functions after SCI: Preliminary report on 14 patients. J.Urol. 159:304A, 1998
We have performed this procedure on 14 SCI patients since 1995 to try to restore controllable voiding....
Of 6 patient with hyperreflexic badder, 5 had successful recovery of bladder function. They are able to void by initiating the skin-CNS-Bladder reflex, which became functional from the 10th to 12th month postoperatively. Residual urine decreased from 300 ml to 31 ml in average, and no UTI occurred since the sixth month postsurgically. CMG study documented the changes of the bladder from hyperreflexia and high pressure to relatively normal.... Among 8 patients with areflexic bladder, 3 showed remarkable recovery and 1 had patial recovery.
SOURCE OF FUNDING: NIH, PVA

[3] Achievement of Xiao Chuanguo, from the Holeung Ho Lee Foundation
http://www.hlhl.org.cn/news/findnews/showsub.asp?id=476
(Translation) We started the clinical study in 1995 and have treated 14 SCI patients, and conducted 2.5 to 3.5 years of follow-up. Of 6 patient with hyperreflexic bladder, 5 restored bladder storage and emptying function. Average residual urine decreased from 317 ml to 29 ml. Six months after operations, they no longer suffer urinary tract infection. One case failed because of other reasons. Among 8 patients with areflexic bladder, 5 completely restored bladder storage and emptying function, 1 had partial recovery, average residual urine decreased from 288 ml to 32 ml.

[4] 2005 article
http://www.ncbi.nlm.nih.gov/pubmed/15879861
Xiao CG, Du MX, Li B, Liu Z, Chen M, Chen ZH, Cheng P, Xue XN, Shapiro E, Lepor H.: An artificial somatic-automonic reflex pathway procedure for bladder control in children with spina bifida. J Urol 2005; 173: 2112.
Preoperative urodynamic studies revealed 2 types of bladder dysfunction— areflexic bladder (14 patients) and hyperreflexic bladder with detrusor external sphincter dyssynergia (6). All children were incontinent. Of the 20 patients 17 gained satisfactory bladder control and continence within 8 to 12 months after VR microanastomosis. Of the 14 patients with areflexic bladder 12 (86%) showed improvement. In these cases bladder capacity increased from 117.28 to 208.71 ml, and mean maximum detrusor pressure increased from 18.35 to 32.57 cm H2O. Five of the 6 patients with hyperreflexic bladder demonstrated improvement, with resolution of incontinence.....In these cases mean bladder capacity increased from 94.33 to 177.83 ml, and post-void residual urine decreased from 70.17 to 23.67 ml. Overall, 3 patients failed to exhibit any
improvement.
Based on our success in restoring bladder function and continence associated with spinal cord injury (SCI) by means of artificial somatic-central nervous system (CNS)-autonomic reflex pathway surgery, we investigated the effectiveness of this innovative surgical procedure in children with spina bifida and neurogenic bladder. To our knowledge this report represents the first published experience applying this technique to the management of spina bifida.

[5] 2003 article (in Chinese)
http://en.cnki.com.cn/Article_en/CJFDTOTAL-LCMW200311001.htm
Xiao CG, Du X-X, Liu Z, Li B, Chen ZH, Cheng P, Chen M.: An artificial somatic-central nervous system-autonomic reflex pathway for spina bifida patients with neurogenic bladder and bowel. Journal of Clinical Urology 18(11).
Abstract (provided by authors)
A total of 30 patients with bladder and bowel dysfunctions caused by spina bifida underwent linited laminectomy and ventral root microanastomosis since 2000.... 13 patients had been followed up for at least one year. Four of 7 cases with areflexia bladder gained bladder control and automatic micturition abiliti within 6 months and 1 year after surgery.... All 6 cases with hyperreflexia bladder achieved controllable voiding, whose residual urine decreased from (102+/-39) ml to (22+/-15) ml and the detrusor external sphincter dyssynergia (DESD) disappeared.
http://www.cnki.com.cn/Article/CJFDTOTAL-LCMW200311001.htm
(Translation of the text) After our success in treating bladder and bowel dysfunction in patients with spinal cord injury started in 1995, we have applied the theory and the technique to treat bladder and bowel dysfunction in 30 patients with spina bifida. So far we have followed up 13 cases for at least 1 year.

[6] Contradiction of urodynamic data found by a Chinese expert
http://www.sciencenet.cn/m/user_content.aspx?id=280348
(Translation) Opinions on Xiao’s Reflex Arc
Science News. Dec 8, 2009
The figures reveal the truth inside the reflec arc. The postoperative urodynamic studies in Fig. 3B and Fig. 4B clearly show that the patients urinated by intra-abdominal pressure. But Xiao explained that it is the reflex arc that causes the urination. The flaw was ignored by editors. The evidence is that the intra-abdominal pressure (Pabd) is the same as intravesical pressure (Pves). And the detrusor pressure (Pdel) is very low (a flat line), nearly zero. Voiding happened only when intra-abdominal pressure existed.

[7] 2006 review
http://www.ncbi.nlm.nih.gov/pubmed/16314037/
Xiao CG: Reinnervation for neurogenic bladder: historic review and introduction of a somatic-autonomic reflex pathway procedure for patients with spinal cord injury or spina bifida. Eur Urol 2006; 49: 22.
Supported by grants from ... NIH (R01 DK44877 and R01 DK53063)

[8] Non-existent conference report cited by [7]
Xiao CG. A somatic-autonomic reflex pathway procedure for neurogenic bladder and bowel: results on 92 patients with SCI and 110 children with spina bifida. In: Proceedings of the International Conference of Urology; Shanghai, July 2-4, Shanghai, China; 2005.

[9] Clinical trial information of Beaumont Hospital's pilot study
http://www.clinicaltrials.gov/ct/show/NCT00378664
Lumbar to Sacral Ventral Nerve Re-Routing.
Identifier: NCT00378664

[10] Project information of Beaumont Hospital's NIH grant
http://projectreporter.nih.gov/project_info_description.cfm?aid=7696321
Safety and Efficacy of Nerve Rerouting for Treating Neurogenic Bladder in Spina Bifida.
Project Number: 1R01DK084034-01
He has reported that in 92 SCI patients, 88% regained bladder control within one year after the nerve rerouting surgery and in 110 children with spina bifida, reported success in 87% at one year.

[11] Faked certificate of success rate supporting Xiao's membership application to the Chinese Academy of Sciences.
http://xysblogs.org/wp-content/blogs/107/uploads/shenyuan.jpg
(Translation) Neuro-Urologic Surgery Research Center (a.k.a Shenyuan Hospital) at Zhengzhou University, February 28, 2007
Starting from Jan. of 2006, the Neuro-urological Surgery Research Center at Zhengzhou University has applied the "artificial somatic-autonomic reflex arc" technique invented by Professor Xiao Chuanguo to 117 patients with neurogenic bladder caused by spina bifida or meningomyelocele. Sixty cases were followed up for more than eight months. 85% of the patients have regained normal bladder and bowel functions.
(Note: The hospital was established in Auguest 2006.)

[12] Beaumont Hospital's one-year outcomes
http://www.ncbi.nlm.nih.gov/pubmed/20639040
Peters KM, Girdler B, Turzewski C, Trock G, Feber K, Nantau W, Bush B, Gonzalez J, Kass E, de Benito J, Diokno A.: Outcomes of lumbar to sacral nerve rerouting for spina bifida. J Urol. 2010 Aug;184(2):702-7. Epub 2010 Jun 19.