The role of IRBs in Ethical
Interventional Stem Cell Research
6th Annual Columbia University IRB Conference
Boston, MA
Patrick Taylor
Children’s Hospital Boston, Harvard Medical School,
Petrie-Flom Center, Harvard Law School
Agenda
• Describe some problems you won’t have.
• Describe some problems you still will have in
different form, but with special resources to
manage them.
• Describe some new ideas to help manage
risks.
What will we see? We fear
• Pseudoscientific stem cell human research protocols
presenting great risks, unknowably larger than the
known risks of cancer, and uncertain benefit;
• Desperate patients for whom the voluntariness of
consent is questionable, yet also presenting an
extremely strong sort of claim for respect for
autonomous choices;
• Nondeterminative, or no, preclinical data;
• And little regulatory guidance; and
• With industry trial issues and regulatory judgments
confidential and inaccessible to others.
But actually the area has been preparing: Ethics
– Generally recognized ethical separation between
donation/derivation and uses of derived lines for research
purposes. Certain disputed ethical issues are outside IRB
review of most therapeutic studies.
– Consensus standards on most ethical issues involving the
original donation, informed consent, and provenance – the
criteria for IRB acceptance and reliance including the
elements of informed consent (literature, NIH, ISSCR and
NAS).
– Registries and stem cell distributional banks using those
ethical criteria to collect, and making data and
certifications available to investigators and IRBs.
– Ethical standards for use of animals and chimeras useful in
translational context.
Scientific path; regulatory + ethical integration
– Connecting the dots scientifically from pluripotency to
differentiation to controlled applications of derivatives.
– Direct attention to genes and factors affecting cancer risks
and uncontrolled development.
– Development of pluripotent alternatives w select
oncogene deletions for iPS cells.
– Agreement on certain elements of “production” pathway:
FDA tissue regulatory framework.
– Scientific agreement on strict, transparent, data-based and
controlled translational and clinical pathway.
Mechanisms for standards generation
• NAS: standards thru scientific experts; ESCROs with
specialized representation and authority.
• ISSCR: global scientific and ethical discussion; public
comment; general uniformity with some local differences
in substance and process; model consents and MTA.
• International and national stem cell registries and banks.
• Local specialized academic institutional review
committees.
• Education, policy-sharing and development through
PRIM&R and others.
Effects of preparation
• Translational path: standards for peer and scientific
review – institutions, funders and regulators.
• Scientifically well-characterized materials with
substantiated ethics histories.
• Regulatory path with ISSCR standards and basic FDA
tissue framework provides a basis for addressing certain
major risks.
• Unique preclinical and translational tools provide unusual
opportunities for testing risks, control mechanisms, etc.
• Eventually, substantial literature on factors affecting
some risks.
• Growing literature on mechanisms of action.
• Specialized pre-review to work with standards.
• Model consents + MTA with substantial literature behind
them.
Challenges: Donor Consent
• Unusual ethical demands on an IVF system typically
governed by nonresearch standards.
• Research purpose specificity, vs unusual or
unanticipated uses vs waivers re unanticipated uses –
does the net result harm autonomy more?
• Protection of donor privacy vs privacy intrusion
arising from rigorous examination of pt information
and donated materials (infectious diseases, genetic
information.
• Protecting privacy vs retaining donor traceability:
donor history, follow-up on newly identified genetic
traits pertinent to clinical uses.
Challenges re participants in treatment trials
• Therapeutic misconception, situational need and
vulnerability.
• Acceptance of unknown and unknowable risks, re
form of risk, severity and probability, life
implications, physicians and Medicine’s lack of
knowledge about course of adverse events,
treatability and care costs.
• Burdens and compliance w long term monitoring.
• Justice issues, particularly re research access and
therapeutic access.
Challenges: safety, risk and benefit
• Variability in cell lines – sources, maintenance
and behavior– and unknown participant
variation.
• Persistence, potential variation in expression
over time, and long-term safety and
effectiveness.
• Genetic modifications.
• Complexity of development factors affecting
gene expression.
• Xeno issues.
Tools
• Standard: adherence to specified incremental pathway
specially abundant in preclinical data and literature on
mechanism of action, generally and re the proposed
study.
• Standard: Well-established and characterized therapeutic
materials, biologically and in terms of donor consent and
legal use restrictions.
• Prior review is both scientific and ethical, without binding
IRB.
• Model consents.
• For hospital-based studies, link safety/QI/M&M systems
to detecting Adv Events (patterns and individually) and
unanticipated risks, and resourcing help.
• Problem-sharing conferences: PRIM&R, AAHRPP.
THANK YOU!