J Clin Neurol.  2018 Apr;14(2):215-224. 10.3988/jcn.2018.14.2.215.

Underregistration and Underreporting of Stem Cell Clinical Trials in Neurological Disorders

• Lee TE
• Kim A
• Jang M
• Jeon B

• KMID: 2407950
• DOI: http://doi.org/10.3988/jcn.2018.14.2.215

Abstract

BACKGROUND AND PURPOSE
Research on stem cells (SC) is growing rapidly in neurology, but clinical applications of SC for neurological disorders remain to be proven effective and safe. Human clinical trials need to be registered in registries in order to reduce publication bias and selective reporting.
METHODS
We searched three databases"”clinicaltrials.gov, the Clinical Research Information System (CRIS), and PubMed"”for neurologically relevant SC-based human trials and articles in Korea. The registration of trials, posting and publication of results, and registration of published SC articles were examined.
RESULTS
There were 17 completed trials registered at clinicaltrials.gov and the CRIS website, with results articles having been published for 5 of them. Our study found 16 publications, of which 1 was a review article, 1 was a protocol article, and 8 contained registered trial information.
CONCLUSIONS
Many registered SC trials related to neurological disorders are not reported, while many SC-related publications are not registered in a public registry. These results support the presence of biased reporting and publication bias in SC trials related to neurological disorders in Korea.

Keyword

stem cells; neurological disorders; Korea; registration; reporting

MeSH Terms

Bias (Epidemiology)
Humans
Information Systems
Korea
Nervous System Diseases*
Neurology
Publication Bias
Publications
Registries
Stem Cells*

Figure

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  Fig. 1 Studies at clinicaltrials.gov.

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  Fig. 2 Studies on the clinical research information system website. *Could not be found via PubMed search.

Reference

1. Cote DJ, Bredenoord AL, Smith TR, Ammirati M, Brennum J, Mendez I, et al. Ethical clinical translation of stem cell interventions for neurologic disease. Neurology. 2017; 88:322–328. PMID: 27927932.

2. Einsiedel EF, Adamson H. Stem cell tourism and future stem cell tourists: policy and ethical implications. Dev World Bioeth. 2012; 12:35–44. PMID: 22420450.

3. Wohn DY. Korea okays stem cell therapies despite limited peer-reviewed data. Nat Med. 2012; 18:329. PMID: 22395680.

4. Choi M, Han E, Lee S, Kim T, Shin W. Regulatory oversight of gene therapy and cell therapy products in Korea. Adv Exp Med Biol. 2015; 871:163–179. PMID: 26374218.

5. Simes RJ. Publication bias: the case for an international registry of clinical trials. J Clin Oncol. 1986; 4:1529–1541. PMID: 3760920.

6. Daley GQ, Hyun I, Apperley JF, Barker RA, Benvenisty N, Bredenoord AL, et al. Setting global standards for stem cell research and clinical translation: the 2016 ISSCR guidelines. Stem Cell Reports. 2016; 6:787–797. PMID: 27185282.

7. Kimmelman J, Hyun I, Benvenisty N, Caulfield T, Heslop HE, Murry CE, et al. Policy: global standards for stem-cell research. Nature. 2016; 533:311–313. PMID: 27193661.

8. Caulfield T, Kamenova K, Ogbogu U, Zarzeczny A, Baltz J, Benjaminy S, et al. Research ethics and stem cells: is it time to re-think current approaches to oversight? EMBO Rep. 2015; 16:2–6. PMID: 25476708.

9. Jung KW. Regulation of human stem cell research in South Korea. Stem Cell Rev. 2010; 6:340–344. PMID: 20506047.

10. Reveiz L, Cortés-Jofré M, Asenjo Lobos C, Nicita G, Ciapponi A, Garcìa-Dieguez M, et al. Influence of trial registration on reporting quality of randomized trials: study from highest ranked journals. J Clin Epidemiol. 2010; 63:1216–1222. PMID: 20430576.

11. Choi EK, Kim MJ, Lim NK, Park HY. Review of the registration in the clinical research information service. J Korean Med Sci. 2016; 31:1–8. PMID: 26770030.

12. Shin JC, Kim KN, Yoo J, Kim IS, Yun S, Lee H, et al. Clinical trial of human fetal brain-derived neural stem/progenitor cell transplantation in patients with traumatic cervical spinal cord injury. Neural Plast. 2015; 2015:630932. PMID: 26568892.

13. Oh KW, Moon C, Kim HY, Oh SI, Park J, Lee JH, et al. Phase I trial of repeated intrathecal autologous bone marrow-derived mesenchymal stromal cells in amyotrophic lateral sclerosis. Stem Cells Transl Med. 2015; 4:590–597. PMID: 25934946.

14. Min K, Song J, Kang JY, Ko J, Ryu JS, Kang MS, et al. Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: a double-blind, randomized, placebo-controlled trial. Stem Cells. 2013; 31:581–591. PMID: 23281216.

15. Sunwoo MK, Yun HJ, Song SK, Ham JH, Hong JY, Lee JE, et al. Mesenchymal stem cells can modulate longitudinal changes in cortical thickness and its related cognitive decline in patients with multiple system atrophy. Front Aging Neurosci. 2014; 6:118. PMID: 24982631.

16. Kang M, Min K, Jang J, Kim SC, Kang MS, Jang SJ, et al. Involvement of immune responses in the efficacy of cord blood cell therapy for cerebral palsy. Stem Cells Dev. 2015; 24:2259–2268. PMID: 25977995.

17. Kim HY, Kim H, Oh KW, Oh SI, Koh SH, Baik W, et al. Biological markers of mesenchymal stromal cells as predictors of response to autologous stem cell transplantation in patients with amyotrophic lateral sclerosis: an investigator-initiated trial and in vivo study. Stem Cells. 2014; 32:2724–2731. PMID: 24966156.

18. Oh SK, Choi KH, Yoo JY, Kim DY, Kim SJ, Jeon SR. A phase III clinical trial showing limited efficacy of autologous mesenchymal stem cell therapy for spinal cord injury. Neurosurgery. 2016; 78:436–447. PMID: 26891377.

19. Park JH, Kim DY, Sung IY, Choi GH, Jeon MH, Kim KK, et al. Long-term results of spinal cord injury therapy using mesenchymal stem cells derived from bone marrow in humans. Neurosurgery. 2012; 70:1238–1247. PMID: 22127044.

20. Yoon SH, Shim YS, Park YH, Chung JK, Nam JH, Kim MO, et al. Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: phase I/II clinical trial. Stem Cells. 2007; 25:2066–2073. PMID: 17464087.

21. Park KI, Goo K, Jung K, Kim M, Kim IS, Yun SH, et al. Therapeutic application of neural stem cells for neonatal hypoxic-ischemic brain injury. Neonatal Med. 2013; 20:343–353.

22. Lee PH, Lee JE, Kim HS, Song SK, Lee HS, Nam HS, et al. A randomized trial of mesenchymal stem cells in multiple system atrophy. Ann Neurol. 2012; 72:32–40. PMID: 22829267.

23. Rah WJ, Lee YH, Moon JH, Jun HJ, Kang HR, Koh H, et al. Neuroregenerative potential of intravenous G-CSF and autologous peripheral blood stem cells in children with cerebral palsy: a randomized, double-blind, cross-over study. J Transl Med. 2017; 15:16. PMID: 28109298.

24. Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY, et al. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells. 2010; 28:1099–1106. PMID: 20506226.

25. Lee PH, Kim JW, Bang OY, Ahn YH, Joo IS, Huh K. Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy. Clin Pharmacol Ther. 2008; 83:723–730. PMID: 17898702.

26. Kim SJ, Moon GJ, Chang WH, Kim YH, Bang OY. STARTING-2 (STem cell Application Researches and Trials In NeuroloGy-2) collaborators. Intravenous transplantation of mesenchymal stem cells preconditioned with early phase stroke serum: current evidence and study protocol for a randomized trial. Trials. 2013; 14:317. PMID: 24083670.

27. Lee YH, Choi KV, Moon JH, Jun HJ, Kang HR, Oh SI, et al. Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy. J Transl Med. 2012; 10:58. PMID: 22443810.

28. World Health Organization. WHO statement on public disclosure of clinical trial results [Internet]. Geneva: World Health Organization;2015. cited 2017 Jun 20. Available from: http://www.who.int/ictrp/results/reporting/en/.

29. Huić M, Marušić M, Marušić A. Completeness and changes in registered data and reporting bias of randomized controlled trials in ICMJE journals after trial registration policy. PLoS One. 2011; 6:e25258. PMID: 21957485.

30. Anderson ML, Chiswell K, Peterson ED, Tasneem A, Topping J, Califf RM. Compliance with results reporting at ClinicalTrials.gov. N Engl J Med. 2015; 372:1031–1039. PMID: 25760355.