implications for the use of tissue in research p. pearl o’rourke, md partners healthcare boston,...

Implications for the Use of Tissue in

ResearchP. Pearl O’Rourke, MD

Partners HealthCare

Boston, MA

The Context

• Tissue is/has always been an important resource for biomedical education and discovery

• Tissue has become an even more valuable resource as a result of:– Genetic Research– Personalized Medicine

Consider the researcher

• What researchers ideally want:– Large numbers of tissue specimens that are

identifiable and updated in perpetuity with medical, social and environmental information that can be used for broad research uses

• What researchers often accept:– ‘De-identified’ tissue specimens

• Linked• Anonymized

Consider the researcher

• What researchers give-up– Potentially valuable updated clinical

information– Environmental data– Ability to re-contact individuals

• Why they are willing to compromise– Cost and logistics of obtaining identifiable

specimens (informed consent)– Remember they need large numbers

Consider the tissue source

• Increasing request/demand for– Recognition of ownership of specimens– Control over use/s– Participatory research– Information about research results and findings

• Evidence that my tissue/data was in fact used• What was found• Return of research results – individual as well as

aggregate

Consider the IRB

• Existing challenges of consent– Too long; too complicated; too legalistic– Too often not even remembered– Add the issues of tissue acquisition

• Often an ‘add-on’ to another protocol• Distance between individual and researcher• Distance between consent and tissue use

• What is identifiable?– Living with a regulatory paradigm that is driven by

identifiability

Consider the IRB

• Genetic risk assessment– Community risk

• Return of research results

• Data sharing

• The regulatory and ethical oversight of tissue research is under scrutiny

• Recent events in the news

The Immortal Life of Henrietta Lacks Rebecca Skloot

• The origin of the HeLa cell line

• Extra biopsies taken for research purposes – without consent or knowledge of the patient or her family

• Biopsies taken in the 1950s – prior to the creation of IRBs

Newborn Blood Spots (NBS)

• State-specific programs for diagnosis of specific diseases in neonatal period

• In some states the NBSs were kept and made available for research purposes

• Fact:– These NBSs are an invaluable research

resource– Status of consent/knowledge of – at best

variable

The Havasupai Settlement

• Adequacy of consent– Individual as well as community– For primary use/s– For secondary use/s

• Control of specimens• Researchers’ responsibility to participants• Genetic concern

– Perhaps exceptionalism

• Community Risk Assessment

So…• How are specimens obtained for

research?– Specifically for research purposes– Left-over clinical specimens

• What are the relevant regulations?

The Regulations

• Common Rule 45 CFR 46

• FDA Regulations – re: human subjects in research

• Health Insurance Portability and Accountability Act (HIPAA)

The Common Rule

• Definition of Human Subject– Human subject means a living individual

about whom an investigator (whether professional or student) conducting research obtains

• Data through intervention or interaction with the individual, or

• Identifiable private information.

Why was the tissue /data obtained?

For research For clinical care

THE RESEARCH LAB

How Your Tissue/Data May Get

to a Research

Lab

Informed Consent

Known donationUnknown donation

Why was the tissue /data obtained?

For research For clinical care

THE RESEARCH LAB

How Your Tissue/Data May Get

to a Research

Lab

Informed Consent

Known donationUnknown donation

De-identified

Why was the tissue /data obtained?

For research For clinical care

Is there excess tissue?

NOYES

Is it identifiable?

NO YES

Informed consent

NOYES

THE RESEARCH LAB

How Your Tissue/Data May Get

to a Research

Lab

Known donationUnknown donation

Why was the tissue /data obtained?

For research For clinical care

Is there excess tissue?

NOYES

Is it identifiable?

NO YES

Informed consent

NOYES

THE RESEARCH LAB

How Your Tissue/Data May Get

to a Research

Lab

Informed Consent

Known donationUnknown donation

De-identified

Why was the tissue /data obtained?

For research For clinical care

Is there excess tissue?

NOYES

Is it identifiable?

NO YES

Informed consent

NOYES

THE RESEARCH LAB

How Your Tissue/Data May Get

to a Research

Lab

Informed Consent

Known donationUnknown donation

De-identified

Human Subjects Research

What this means in practice

• Existing tissue/data, if not identifiable– Not a human subject– No worry about consent (Common Rule)– No worry about authorization (HIPAA)

• If identifiable– Yes, a human subject– IRB must determine need for consent– Privacy Board (IRB) must determine need for

authorization (HIPAA)

In Practice

• We spend much time trying to define identifiability– CCommon Rule– HIPAA– Evolving identifiability standards related to:

• Data mining• Genetic information

Is it IDENTIFIABLE?

YES NO

Is it IDENTIFIABLE?

YES NO

Is it IDENTIFIABLE?

YES NO

Is it IDENTIFIABLE?

YES NO

HIPAACommon RuleState LawsInstitutional Policies

Perhaps a Disconnect?

• People want to know how their data and tissue are being used in research

• Some want to control how their data and tissue are being used.

• People are NOT impressed with the use of ‘identifiability’ as the trigger for oversight

Specific Disconnects

• Informed consent– Particular issues in tissue banking

• Communication– Updates re: the research activities in general

• The category of tissue research that is considered not human subjects research

• AND besides – are we at a point that all tissue should be considered identifiable?

So where do we go from here?

• Option 1: Maintain the status quo– Improve consent process

• Relook at broad consent• Ongoing consent

– Educate clinicians, researchers, and the public

– Notification

So where do we go from here?

• Option 2: Consider all tissue identifiable and maintain the regulatory status quo– All tissue uses would be considered HS

research – HUGE burden for IRBs with likely little gain in terms of benefit

– In reality transparency for the public would NOT improve – most protocols would have a waiver of informed consent

So where do we go from here?

• Option 3: Consider all tissue identifiable and re-evaluate and potentially modify the regulatory process– Do we need more than the Common Rule?– Develop alternate levels of review for

categories of tissue research that is usually very low risk research

– Consider new models of notification and/or consent

So where do we go from here?• At the least we need:

– Broad-based discussion with all interested parties with the goal of developing common practices for today and the future

• Patients and research participants• Clinicians and researchers• Relevant Government agencies• Professional Societies• Banking professionals• Others