Regenerative medicine research as global
collaborative project: opportunities, challenges,
conflicts
Achim Rosemann
University of Sussex
ar253@sussex.ac.uk
Key terms
• “Stem Cells”
– Sources
– Therapeutic potential
– Broad range of medical applications
• “Regenerative Stem Cell Medicine”
– Evolving medical paradigm
– New types of risks
– Regulatory challenges / no international harmonization yet
• “Clinical translation”
– Translation of new therapeutic application from bench to bedside to
market
– Very divergent forms.
Outline Presentation
•
Part I: Overview Literature on clinical translation in stem cell (SC) field
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–
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Identification of analytical gaps
Theoretical relevancy of the study of international stem cell clinical trial partnerships
Part II: Introduction of Case Study – The China Spinal Cord Injury Net
–
Geographic scope and objectives
•
Part III: Standardization and scientific self-governance: forms and challenges
•
Part IV: Key-Findings in relation to theme of ‘standardization’ in context of China SCI Net
–
–
–
•
Situation and and context specificity of transnational research zones
Advantages of operating across heterogeneous forms of clinical experimentation
Forms of resistance and Alter-standardization
Conclusions
Part I:
Overview Literature and Gaps
Clinical translation in regenerative stem cell medicine: ethnographic studies
Four central study directions
•
(1) Preclinical Development (that precede first in human applications)
- Cribb, A., et al. (2008). Towards the applied: the construction of ethical positions in stem cell translational research. Medicine, Health Care & Philosophy.
- Martin, P., Brown, N., and A. Kraft (2008). From Bedside to Bench? Communities of Promise, Translational Research and the Making of Blood Stem Cells, Science as Culture.
- Wainwright, S.P., et al., 2006a. From bench to bedside? Biomedical scientists’ expectations of stem cell science as a future therapy for diabetes. Social Science & Medicine
- Wainwright, S.P, and Williams, C. (2009) Spaces of speech and places of performance: an outline of a geography of science approach to embryonic stem cell research and
diabetes, New Genetics and Society.
•
(2) The uptake of randomized controlled trials (in Europe and USA)
- Webster, A., et al. (2011). Experimental heterogeneity and standardization: stem cell products and the clinical trial process. Biosocieties
- Wilson-Kovacs DM, Hauskeller C. 2011. The clinician-scientist: professional dynamics in clinical stem cell research. Sociology of Health & Illness
- Wilson-Kovacs DM, Weber S, Hauskeller C. 2010. Stem cells clinical trials for cardiac repair: regulation as practical accomplishment. Sociol. Health Illn.
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(3) Experimental for-profit stem cell treatments (especially in Asia)
- Bharadwaj A, Glasner P. 2009. Local Cells, Global Science: The Rise of Embryonic Stem Cell Research in India. London: Routledge
- Patra PK, Sleeboom-Faulkner M. 2009. Bionetworking: experimental stem cell therapy and patient recruitment in India. Anthropological Medicine
- Patra KP, Sleeboom-Faulkner M. 2011. Recruiter-patients as ambiguous symbols of health: bionetworking and stem cell therapy in India. New Genet. Soc.
- Song, P. (2011) The proliferation of stem cell therapies in post-Mao China: Problematizing ethical regulation. New Genetics and Society 30(2): 141–153.
- Chen, H. (2009). Stem cell governance in China: from bench to bedside?. New Genetics and Society, 28(3), 267–282.
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(4) International flows and exchanges
- Chen, H.D., and H. Gottweis (2011). Stem Cell Treatments in China: Rethinking the patient role in the global bio-economy. Bioethics
- Kent, K. (2012) Regenerating bodies: tissue and cell therapies in the 21st century, Routledge
- Sleeboom-Faulkner, M. and P.K. Patra (2011). Experimental stem cell therapy: Biohierarchies and bionetworking in Japan and India, Social Studies of Science
Waldby C, Mitchell R. 2006. Tissue Economies: Blood, Organs and Cell Lines in Late Capitalism. Durham, NC: Duke Univ. Press
Gaps in Literature
Three unexplored dynamics
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(1) Increasing significance of randomized controlled clinical trials (RCTs) in Asian societies
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Aiming to formal approval of SC-based medicinal products, under review of drug regulatory agencies
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(2) Increasing formation of multi-country clinical trial partnerships in regenerative SC
medicine
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(3) Trend of Clinical Trial “Mimicry”
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Uptake of clinical trial methodology, by providers of unproven therapies
Focus in this presentation: theme 2
First clinical trials network in SC field USA/ Asia
Theoretical Relevancy:
Of the study of international clinical trial collaborations in regenerative stem
cell medicine field
• (1) Global Distribution of Evidence Based Medicine Standards
• (2) Processes of Standardization, Scientific Self-governance, and
International Harmonization
• (3) Development of large scale international collaborations
• (4) Implications of the increasing scientific significance of societies in Asia
(in this study especially, China)
Part II:
Introduction of Case Study
Introduction China SCI Net and SCI Net USA:
(1) China SCI Net founded in 2005 by HK born researcher from USA, under umbrella of HKU
(2) Close ties to US (parallel network in USA (since 2010 – 8 hospitals), but:
- Leadership of China SCI Net – from HK, and ML China
- Targeting benefits in first place for SCI researchers and patients in China
(3) Transnational flows:
- Transfer of data and clinical experience from China to USA
- Data in China shall be used for application at US FDA
(4) Several phase I & II trials have been conducted
Phase II and III trials are in preparation, in both US and China
Clinical Rationale and Approach
Organization tests a stem cell-based combination therapy of:
(1) Injection of Umbilical Cord Blood Mononuclear Cells into spinal cord,
following surgery
(2) Six week course of lithium
(3) One time high-dose injection of
Central Objective of Network:
Creation of a transcontinental standardized multi-center clinical trial infrastructure
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Creation of multi-center clinical trial network that is able to:
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Create fully standardized clinical data, that can be accepted by:
– Drug regulatory authorities in China, Hong Kong, Taiwan and the USA
– Goal: Realize maximum scope of access to SCI patients
Part III:
Standardization and scientific selfgovernance
Standards / Standardization & Scientific Self Governance
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International standards: (Timmerman and Epstein 2011)
– Crucial instruments for organization and governance of modern science
– Construct uniformities across time and space
– Create homogenized international research zones
– Allows for validation of data and findings, from highly dispersed communities
– Are controlled through gate-keeping institutions:
• drug regulatory authorities, editorial boards of scientific journals, peer-review, scientific
societies, ethics committees, etc
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Scientific Self-governance (in transnational contexts)
“Project-internal forms of self-regulation and capacity building that aim for the creation of a
standardized trans-institutional research infrastructure that is compliant with multi-country
regulatory requirements and/ or other international scientific standard systems.”
– China SCI Net – must meet regulatory requirements of :
• the SFDA (China), the DOH (HK), the TFDA (Taiwan), and the FDA (USA)
• Brief illustration:
Modes of clinical translation
among associated hospitals
(to China SCI Net)
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–
–
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China SCI Net (as a whole)
Hospitals A, B, C
Hospital D
Hospital E
• Differences with regard to:
– (1) Approval / Review
– (2) Research methodologies
– (3) Access to treatment (target
population)
– (4) Forms of capitalization
Standardization
1. Standardization of time: medical interventions, physical examinations, lab tests, etc
2. Standardization of Surgery
3. Standardization of Injection
4. Standardization of Cells
Standardization II:
5. Standardization of in- and exclusion criteria
6. Standardization of rehabilitation protocols
7. Standardization of outcome measures
Methods and techniques of standardization
• (1) Selection procedures (of hospitals):
– External assessment parameters:
• GCP qualifications of hospitals, GTP qual. of labs
– Practice Based assessment parameters
• Observation Trial
• (2) Training
– in clinical trial design and methodology
– in standardized procedures (surgery, injection, etc)
• (3) Implementation of control and supervision structure
• Web based monitoring system
• Supervisor- head of department – double signing system
• Work with CRO (contract research organization) in phase IIII trial
Part IV:
Key-Findings related to themes of
standardization and scientific selfgovernance
The situation and context specific character of:
Trans-continental standardized research zones
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Andrew Barry (2005): Technological zones
“A space within which differences between technical practices, procedures, and forms
have been reduced, or common standards have been established.”
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Standardized research zone China SCI Net:
– Only existent in context of network’s clinical trials
– Not permanent or enduring
– Standardized zones can be switched on and off
• Depending on situational requirements, partners, regulatory agencies involved,
objectives of research, etc.
– Multiple forms of clinical research co-exist side by side
• In same hospital, department, under supervision of same researcher
The co-existence of multiple forms of clinical experimentation:
opportunities and forms of knowledge transfer
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Coexistence of multiple forms of clinical experimentation, in context of regulatory flexibility:
– Allows the tapping of experiences and knowhow, not existent in USA
– Allows knowledge transfer from low to high regulated countries
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This forms:
– Alteration of dominant regulatory paradigm, through which clinical research is
regulated in USA
– Poses some questions about ethics, and regulation of international partnerships
Standardization and Resistance
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Standards stratify social realities and practices
• i.e. standards function as mechanisms of in- and exclusion
• Restructure existing normative systems
• Restructure livelihoods
– (for instance – if SC clinics are closed down)
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Definitions of what counts as “international” are highly contested
– Aura of universality, but:
• grounded in particular localities
• disguises local and trans-local power-play
• disguises the interests of particular stakeholders
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Result: Resistance and Alter-standardization
Alter-standardization and pluralization
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Resistance to international standards:
– Pronounced in clinical stem cell field in China
– Rigid adoption of “international” regulation would mean:
• Devaluation of various existing practices
• Closing down of clinics
• Loss of livelihoods
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What is at stake is:
– Clash between an evolving and in many respects imported form of regulatory authority, with
• Local forms of professionalism and research validation
• These local forms are based on:
– Historically evolved conceptions of medicine and medical research
– New forms and opportunities of capitalization and profit making
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Processes of ‘alter-standardization” (as counter strategy)
• i.e. the formation of novel transnational networks of institutional spaces, knowledge sharing
and publication
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These evolving transnational spaces of ‘alter-standardization:
• Endorse and validate alternative forms of experimental research
• With ethical and research protocols that – in numerous respects –
– Diverge from current international scientific standard cannon.
Case – The International Association of Neurorestoratology (IANR)
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IANR: good example of “alter-standardization”
– International Society founded by neurosurgeon from Beijing
– New sub-branch of the neurosciences: neurorestoratology
– Many members of IANR offer – experimental for-profit applications
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Neurorestoratology:
• Combines various medical approaches
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(cell and SC based approaches feature high)
• Patient Centered. Aims to:
– Restore neurological functions in patients
– Improve quality of life
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Focus – on patients wellbeing used to:
• Endorse the use of efficacy and safety assessment procedures other than randomized
controlled clinical trials (RCTs)
• To legitimize less rigorous forms of medical experimentation
• Such as self-comparison of patients
Case – The International Association of Neurorestoratology
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IANR:
– Creates platform for global sharing of knowledge – of research conducted outside of
international standard system
• Does so by
• (1) Creating new possibilities for publication
• (2) Organization of large scale conferences
– Plays a pivotal role in gradually transforming previously marginalized forms of experimental
clinical research from:
• Being unacceptable and critical
• To a slowly tolerated component of the ordinary
Conclusions
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Clinical research collaborations across contexts of regulatory diversity
– Perils:
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Daunting Tasks, multiple challenges
Intensive forms of trans-national scientific self-governance required
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Need to compensate / fill the gaps of state regulation
– Advantages:
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Tapping of unprecedented experiences
Access to low cost environment, large numbers of patients
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The fragility / polymorphous character of transnational technological zones
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Internationalization and its discontents:
– Processes of alter-standardization
– Pluralisation of the international / of international standard systems
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Dilemma: notions of suppressed “subalterns” that need a “voice” through a well-intended anthologist
doesn’t work here;
– we are dealing with risky and highly profit oriented forms of experimental medicine
– Formation of alternative transnational networks and platforms of knowledge sharing