Regenerative medicine research as global collaborative project: opportunities, challenges,

conflicts

Achim RosemannUniversity of Sussexar253@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

– 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 studiesFour 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.

• (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.

• (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

• (1) Increasing significance of randomized controlled clinical trials (RCTs) in Asian societies– Aiming to formal approval of SC-based medicinal products, under review of drug regulatory agencies

• (2) Increasing formation of multi-country clinical trial partnerships in regenerative SC medicine

• (3) Trend of Clinical Trial “Mimicry”– Uptake of clinical trial methodology, by providers of unproven therapies

Focus in this presentation: theme 2First 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 conductedPhase 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

• Creation of multi-center clinical trial network that is able to:

• 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 self-governance

Standards / Standardization & Scientific Self Governance

• 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

• 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)

– 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

2. Standardization of Surgery

3. Standardization of Injection 4. Standardization of Cells

1. Standardization of time: medical interventions, physical examinations, lab tests, etc

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

self-governance

The situation and context specific character of:Trans-continental standardized research zones

• 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.”

• 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

• 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

• 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• 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)

• 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

• Result: Resistance and Alter-standardization

Alter-standardization and pluralization• 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

• 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

• Processes of ‘alter-standardization” (as counter strategy)• i.e. the formation of novel transnational networks of institutional spaces, knowledge sharing

and publication

– 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)

• 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

• Neurorestoratology:

• Combines various medical approaches – (cell and SC based approaches feature high)

• Patient Centered. Aims to:– Restore neurological functions in patients– Improve quality of life

• 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

• 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• Clinical research collaborations across contexts of regulatory diversity

– Perils:• Daunting Tasks, multiple challenges• Intensive forms of trans-national scientific self-governance required

– Need to compensate / fill the gaps of state regulation

– Advantages:• Tapping of unprecedented experiences• Access to low cost environment, large numbers of patients

• The fragility / polymorphous character of transnational technological zones

• Internationalization and its discontents:

– Processes of alter-standardization

– Pluralisation of the international / of international standard systems • 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