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Achieving Informed Consent for Cellular Therapies: A Preclinical Translational Research Perspective on Regulations versus a Dose of Reality

Published online by Cambridge University Press:  01 January 2021

Aileen J. Anderson  and
Brian J. Cummings
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Abstract

A central principle of bioethics is “subject autonomy,” the acknowledgement of the primacy of the informed consent of the subject of research. Autonomy requires informed consent — the assurance that the research participant is informed about the possible risks and benefits of the research. In fact, informed consent is difficult when a single drug is being tested, although subjects have a baseline understanding of the testing of a pharmacological agent and the understanding that they can stop taking the drug if there were an adverse event. However, informed consent is even less easily achieved in the modern arena of complex new molecular and cellular therapies. In this article, we argue that as science confronts new issues such as transplantation of stem cell products, which may live within the participant for the rest of their lives, researchers must carefully consider and constantly re-examine how they properly inform subjects considering participation trials of these novel therapeutic strategies.

For example, the manufacture of a vial of a cell product that consists of a collection of growing cells is very different than the production of a vial of identical pills, which can be presumed to be identical. The scientific concepts on which these cellular approaches are based may seem alien and incomprehensible to a research subject, who thinks of a clinical trial as simply the selection and testing of the most efficacious pharmaceutical agent already proven to work in preclinical animal studies. The research subject would be wrong.

Type
Symposium Articles
Information
Journal of Law, Medicine & Ethics , Volume 44 , Issue 3: Contemporary Challenges in Informed Consent: Law, Research Practice, and Ethics , Fall 2016 , pp. 394 - 401
Copyright
Copyright © American Society of Law, Medicine and Ethics 2016

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References

World Health Organization, Spinal Cord Injury: As Many as 500 000 People Suffer Each Year, December 2, 2013, available at <http://www.who.int/mediacentre/news/releases/2013/spinal-cord-injury-20131202/en/> (last visited June 27, 2016); B. B. Lee, R. A. Cripps, M. Fitzharris, and P. C. Wing, “The Global Map for Traumatic Spinal Cord Injury Epidemiology: Update 2011, Global Incidence Rate,” Spinal Cord 52, no. 2 (2014): 110–116.+(last+visited+June+27,+2016);+B.+B.+Lee,+R.+A.+Cripps,+M.+Fitzharris,+and+P.+C.+Wing,+“The+Global+Map+for+Traumatic+Spinal+Cord+Injury+Epidemiology:+Update+2011,+Global+Incidence+Rate,”+Spinal+Cord+52,+no.+2+(2014):+110–116.>Google Scholar
CaDR Foundation, “One Degree of Separation | Paralysis and Spinal Cord Injury in the United States,” 2009.Google Scholar
NSCIS Center, “Facts and Figures at a Glance In: Birmingham UoAa,” Univeristy of Alabama at Birmingham, 2015, available at <https://www.nscisc.uab.edu/Public/Facts%202016.pdf> (last visited July 6, 2016).+(last+visited+July+6,+2016).>Google Scholar
Curt, A., Casha, S., Fehlings, M., Huhn S, S., editors, “Phase I/II Clinical Trial of HuCNS-SC Cells in Chronic Thoracic Spinal Cord Injury - Interim analysis,” AISA, May 16, 2014, San Antonio, TX; “StemCells, Inc. Announces Positive Top-Line 400 journal of law, medicine & ethics Anderson and Cummings Results of Its Thoracic Spinal Cord Injury Phase I/II Study [Internet],” Reuters, May 14, 2015.Google Scholar
See Foundation CaDR, supra note 3.Google Scholar
Cummings, B. J., Uchida, N., Tamaki, S. J., and Anderson, A. J., “Human Neural Stem Cell Differentiation Following Transplantation into Spinal Cord Injured Mice: Association with Recovery of Locomotor Function,” Neurological Research 28, no. 5 (2006): 474-481; B. J. Cummings, N. Uchida, S. J. Tamaki, D. L. Salazar, M. Hooshmand, and R. Summers et al., “Human Neural Stem Cells Differentiate and Promote Loco-motor Recovery in Spinal Cord-Injured Mice,” Proceedings of the National Academy of Sciences 102, no. 39 (2005): 14069-14074; M. J. Hooshmand, C. J. Sontag, N. Uchida, S. Tamaki, A. J. Anderson, and B. J. Cummings, “Analysis of Host-Mediated Repair Mechanisms after Human CNS-Stem Cell Transplantation for Spinal Cord Injury: Correlation of Engraftment with Recovery,” PLoS One 4, no. 6 (2009): e5871; K M. Piltti, S. N. Avakian, G. M. Funes, A. Hu, N. Uchida, and A. J. Anderson et al., “Transplantation Dose Alters the Dynamics of Human Neural Stem Cell Engraftment, Proliferation and Migration after Spinal Cord Injury,” Stem Cell Research 15, no. 2 (2015): 341-353; K. M. Piltti, D. L. Salazar, N. Uchida, B. J. Cummings, and A. J. Anderson, “Safety of Human Neural Stem Cell Transplantation in Chronic Spinal Cord Injury,” Stem Cells Translational Medicine 2, no. 12 (2013): 961-974; K. M. Piltti, D. L. Salazar, N. Uchida, B. J. Cummings, A. J. Anderson, “Safety of Epicenter Versus Intact Parenchyma as a Transplantation Site for Human Neural Stem Cells for Spinal Cord Injury Therapy,” Stem Cells Translational Medicine 2, no. 3 (2013): 204-216; D. L. Salazar, N. Uchida, F. P. Hamers, B. J. Cummings, and A. J. Anderson, “Human Neural Stem Cells Differentiate and Promote Locomotor Recovery in an Early Chronic Spinal Cord Injury NOD-Scid Mouse Model,” PLoS ONE 5, no. 8 (2010): e12272; C. J. Sontag, H. X. Nguyen, N. Kamei, N. Uchida, A. J. Anderson, and B. J. Cummings, “Immunosuppressants Affect Human Neural Stem Cells In Vitro ut Not in an In Vivo Model of Spinal Cord Injury,” Stem Cells Translational Medicine 2, no. 10 (2013): 731-744; C. J. Sontag, N. Uchida, B. J. Cummings, and A. J. Anderson, “Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem Cells,” Stem Cell Reports 2, no. 5 (2014): 620–632.CrossRefGoogle Scholar
Anderson, A. J., Piltti, K. M., Hooshmand, M. J., Nishi, R. A., and Cummings, B. J., “Pre-Clinical Analysis of the Efficacy of Human Central Nervous System Derived Stem Cells (HuCNSSC) for Therapeutic Application in the Phase II ‘Pathway StudyTM’ of Cervical Spinal Cord Injury, (article in submission).Google Scholar
Garitaonandia, I., Amir, H., Boscolo, F. S., Wambua, G. K., Schultheisz, H. L., and Sabatini, K. et al., “Increased Risk of Genetic and Epigenetic Instability in Human Embryonic Stem Cells Associated with Specific Culture Conditions,” PLoS One 10, no. 2 (2015): e0118307.Google Scholar
FDA, CBER Vision & Mission, 2016, available at <http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm122878.htm> (last visited June 28, 2016).+(last+visited+June+28,+2016).>Google Scholar
FDA, “Guidance, Compliance & Regulatory Information (Biologics) 2016,” available at <http://www.fda.gov/Biologics-BloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm> (last visited June 28, 2016).+(last+visited+June+28,+2016).>Google Scholar
Fink, D. W. and Bauer, S. R., “Stem Cell-Based Therapies: Food and Drug Administration Product and Pre-Clinical Regulatory Considerations,” in Essentials of Stem Cell Biology, 2nd ed. (Amsterdamn: Elsevier, 2009): at 619–630.Google Scholar
Id.Google Scholar
Id.Google Scholar
Id.; CEBR, Research CfBEa, “Guidance for Industry - Potency Tests for Cellular and Gene Therapy Products,” in Research CfBEa, Office of Communication, 2011.Google Scholar
Id. (CEBR).Google Scholar
Katz, R., “FDA: Evidentiary Standards for Drug Development and Approval,” NeuroRx 1, no. 3 (2004): 307–316.Google Scholar
Galipeau, J., “The Mesenchymal Stromal Cells Dilemma — Does a Negative Phase III trial of Random Donor Mesenchymal Stromal Cells in Steroid-Resistant Graft-Versus-Host Disease Represent a Death Knell or a Bump in the Road?” Cytotherapy 15, no. 1 (2013): 2-8; R. Chinnadurai, S. Ng, V. Velu, and J. Galipeau, “Challenges in Animal Modelling of Mesenchymal Stromal Cell Therapy for Inflammatory Bowel Disease,” World Journal of Gastroenterology 21, no. 16 (2015): 4779–4787.Google Scholar
See CEBR, supra note 14.Google Scholar
Interview on December 12, 2014. Notes on file with the author (BJC).Google Scholar
Interview on May 22, 2015. Notes on file with the author (BJC).Google Scholar
Wirth, E., “Early Clinical Development of hESC-Derived OPCs for Spinal Cord Injury: Trials and Tribulations,” Public Lecture, Tuesday September 15th 2015; Gross Hall Thorp Conference Center UCIGoogle Scholar
Goldacre, B., “All Trials Registered | All Results Reported 2016,” available at <http://www.alltrials.net//wp-content/uploads/2013/09/What-does-all-trials-registered-and-reported-mean.pdf> (last visited July 16, 2016).+(last+visited+July+16,+2016).>Google Scholar
Gage, F. H. and Temple, S., “Neural Stem Cells: Generating and Regenerating the Brain,” Neuron 80, no. 3 (2013): 588–601.CrossRefGoogle Scholar
Tadesse, T., Gearing, M., Senitzer, D., Saxe, D., Brat, D. J., and Bray, R. et al., “Analysis of Graft Survival in a Trial of Stem Cell Transplant in ALS,” Annals of Clinical Translational Neurology 1, no. 11 (2014): 900–908.Google Scholar
Hellmers, N., Obeng-Aduasare, Y., de Melo-Martin, I., and Henchcliffe, C., “Future Needs for Informed Consent in Stem Cell Clinical Trials in Neurodegenerative Diseases,” Neural Regenerational Research 11, no. 1 (2016): 83–85.Google Scholar