The Value of Tissue Banks to Drug and Dx Developers

	Barbara L. Handelin, Ph.D.
	Conflicts of Interest, Privacy/Confidentiality, and Tissue Repositories: Protections, Policies, and Practical Strategies

Tissue Banks for Tx and Dx Developers:  What is the need?

	Basic research: the biological revolution in the medicinal chemical industry
		Drug targets
		Molecular diagnostics
		Biomarkers for clinical research
	Clinical research: pharmacogenetic/genomic profiling
		Toxicity
		Drug responsiveness
		Rescuing failed drugs

What is needed from tissues?

	DNA:  gene, SNP, population association
	RNA:  gene expression array or profiling
	Proteins:  proteomics
	Cell morphology:  pathology

Pharmacogenetics Is….

	The influence of genetic traits on the magnitude or type of toxic effects of drugs.
	The influence of genetic traits on the magnitude or type of therapeutic effects of drugs.
	A genetic determinant of overall drug response;  not a measurement of physiological status!
	PGenetics:  Targeted study of gene variants determining drug response
	PGenomics: Genome wide study of genetic determinants, including the study of gene expression (requiring RNA as a study material)

FDA Guidance on PGx

	PGx will “help individualize therapy with the intent of maximizing effectiveness and minimizing risk.”
	Important “that FDA policy facilitate, not impede, the use of pharmacogenomic tests during drug development and, to the extent possible, encourage open and public sharing of data…on PGx test results.”
	“most experimental results may not be well enough established to be suitable for regulatory decision making”

FDA Guidance on PGx

	“the FDA is encouraging voluntary submission of such data…”
	“As…field of PGx advances, it is likely (and desirable) that sponsors will begin to use PGx tests to support drug development and/or to guide therapy”

Developing tests for marketed drugs

	Currently available drugs could be targeted to appropriate patients
	Leads to:
		Need for archival repositories with clinical records of all drug therapies
		Need to revisit stored tissues from prior clinical trials (as in original drug trials)
		Need to attach PGx testing to Phase III/IV studies

BIO perspectives, recommendations

	Review commensurate with risk; a two tiered review system
		Research involving intervention or interaction
		Research using medical records and tissue archives
	Federalize regulations/laws governing consent, use and retention of tissue to make consistent with all regulations (not State by State)

BIO perspectives, recommendations

	Subject’s authorization or specification of limitations on permissible uses of data and biological materials must be respected.
		E.g. Right to withdraw at any time must be honored

Sample PhRMA perspectives on privacy in tissue research

	Medical information, including genetic information, should have equal protection
	Researchers must have unrestricted access to anonymized or encrypted patient information
	Uniform national requirements should govern biomedical research, although individual states should be able to prescribe additional penalties for violations of privacy

Example Tissue Repositories

	Cooperative Groups (such as the Cooperative HumanTissue Network)
	Ardais
	GeneLogic
	International Genomics Consortium
	IMPATH
	Integrated Lab Services

Example Tissue Repositories

	LifeSpan Biosciences
	Oncotech
	PathServe
	The AlphaOne Foundation
	Genomics Collaborative
	Duke Center for Human Genetics
	Cancer centers

What is an appropriate posture or role for IRBs to take in this arena?

	IRBs represent the “interests” and welfare of subjects
		Gifting for the development of better medicine
		Do me no harm
		Allow me to understand my risks
		“Willing suspension of autonomy”?
	What is risk of NOT suspending autonomy?

How suspension of autonomy may lead to useful discoveries

	Complex test to profile newly diagnosed women with breast cancer re risk for recurrence. (Genomic Health, Inc.)
		Genetic risk factor for MI (DeCODE)
	New drug into development for MI targeted at genetic risk factor for MI (DeCODE/Bayer)
	New test for responders to Iressa among non-small cell lung cancers

How suspension of autonomy may lead to useful discoveries

	Collecting DNA for unknown future use:
		New test in development for response to treatment with statin drugs:  personalized medicine  (Gennaissance;Abbott Labs)