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Biospecimens Today & Tomorrow March 2016

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Speaker

Mitchell E. Parrish, JD, RAC, CIP

Currently

Experience

Memberships & Certifications

Consultant to the National Cancer Institute Regulatory counsel to Western IRB Senior Regulatory Attorney at Quorum Review IRB Associate attorney at the global law firm K&L Gates

Member of the Washington and Oregon State bars Member of Regulatory Affairs Professionals Society (RAPS) Regulatory Affairs Certification (RAC) Certified IRB Professional (CIP)

Discussing the buzz around biospecimens and the NPRM

Clarifying the Common Rule’s applicability

Defining human subject and the implications for biospecimens

Understanding biospecimen research that is exempt

Dissecting consent related to biospecimens

Determining whether and how to return research results to individuals

Comprehending privacy, confidentiality, and data security surrounding biospecimens

Overview

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Biospecimen (e.g., urine, blood, tissue, cells)

Common Rule (45 CFR 46) - Published in 1991 - Federal departments and agencies (e.g., HHS, DOD, DOT, NASA)

Notice of Proposed Rulemaking (NPRM) Published September 8, 2015

Terminology

Discussing the buzz around

biospecimens and the NPRM

This is a key moment to consider resetting the ethical boundaries of biospecimen research

Human genome is mapped

Genetic testing reveals more and more

The Buzz

The U.S. government is embracing the inherent power in biospecimens

NIH Precision Medicine Initiative

FDA’s endorsement of genetic sample collection in industry-sponsored research

Sponsors are embracing the power as well

Quorum rarely receives a protocol that does not include a biospecimen collection component for a potential future use

The Buzz (cont.)

As the biorepositories fill and the possibilities of new treatments or discoveries increase, the links between parts of ourselves that are stored somewhere and our identities become harder to break

This raises inherent complex issues…

The Buzz (cont.)

Privacy and Security: Ability to identify donors from their ostensibly anonymous specimens (e.g., Henrietta Lacks)

Complex issue examples

What protections should donors expect when they offer their tissues or blood for research?

Permissions and Future Use: Researchers will find ways to study specimens in unimaginable ways (e.g., Havasupai Tribe)

Complex issue examples (cont.)

How do researchers request consent for unknown uses?

Incidental Findings: Uncovering a previously unknown health risk (e.g., breast cancer)

Complex issue examples (cont.)

What are researchers’ responsibilities to report information back, what is their ability to do so, and how will they communicate this, if at all?

Collection of and research on biospecimens that leads to benefits for all

VERSUS

Respect, justice, and protection due the individual contributing the specimen

So, NPRM has tried to balance…

Stepping up…

IMPACT: Much larger than this percentage! Nearly every new guideline or section has a reference to managing biospecimens

Number of times “biospecimen”

appears in the NPRM

Words in the NPRM

73 12,500 0.6% ÷ =

Before we talk about NPRM changes impacting biospecimens we need to know the current regulatory framework governing biospecimens

NPRM is just that – Notice of Proposed Rulemaking

Hold your horses

- Is NOT in effect

- Effective date would be ONE (1) YEAR after publication in the Federal Register

- Compliance date for the new rules covering biospecimens would be THREE (3) YEARS after publication

- Prior collected specimens are not subject to the new rule

POLL

If the NPRM became final, would your organization modify its policies with respect to biospecimens?

Immediately

Sometime prior to the compliance date

I don’t know

Poll

Today & Tomorrow

Biospecimens today = CURRENT state

Biospecimens tomorrow = POTENTIAL FUTURE state

For the rest of the slides…

TODAY

TOMORROW

Clarifying the Common Rule’s

applicability

45 CFR 46 Applies to all research that:

Involves human subjects, and

Is conducted, supported or otherwise subject to regulation by a federal department or agency that follows the common rule, or

Is conducted at an institution that has an Federal Wide Assurance (FWA) and who has agreed to apply the common rule to research regardless of whether the Common Rule actually applies (i.e., “check the box”)

Common Rule applicability TODAY

NPRM Applies to all research that:

Involves human subjects, and

Is conducted, supported or otherwise subject to regulation by a federal department or agency that follows the common rule, or

Is conducted at an institution that has an Federal Wide Assurance (FWA) and who has agreed to apply the common rule to research regardless of whether the Common Rule actually applies (i.e., “check the box”)

Is a “clinical trial” – prospective assignment to “evaluate effects of interventions on biomedical or behavioral health-related outcomes”

Common Rule applicability TOMORROW

Defining human subject and the implications for biospecimens

45 CFR 46.102(f)

(f) Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains:

– (1) Data through intervention or interaction with the individual, or

– (2) Identifiable private information

Definition of human subject TODAY

Implication is research with biospecimens that are not identifiable is not “human subjects” research and thus, not beholden to the Common Rule

– IRB review not required

Definition of human subject TODAY

What is individually identifiable?

A biospecimen in which the identity of the source may “readily be ascertained by the investigator or associated with the information”

– Specimen linked to an individual through coding = identifiable

– Specimen cannot be linked to an individual through coding = not identifiable

Definition of human subject

Essentially, researcher cannot have access to the code’s key!

-HHS Guidance on Research Using Coded Private Information or Specimens Note: HIPAA definition of “individually identifiable” does differ somewhat from the Common Rule definition

TODAY

NPRM §__.102(e)(1):

(e)(1) Human subject means a living individual about whom an investigator (whether professional or student) conducting research:

(i) Obtains data through intervention or interaction with the individual, and uses, studies, or analyzes the data;

(ii) Obtains, uses, studies, analyzes, or generates identifiable private information; or

(iii) Obtains, uses, studies, or analyzes biospecimens

Definition of human subject TOMORROW

Implication is research with biospecimens, whether or not they are identifiable, is “human subjects” research and thus, beholden to the Common Rule

Definition discards the question of identifiability and establishes a new baseline assumption: research on a human biological specimen is research on a human!

Definition of human subject TOMORROW

Specimen Human =

New definition elicited strong opposition.

NPRM has identified two alternatives.

Expand the definition of “human subject”

to include the following…

Definition of human subject TOMORROW

Whole genome sequencing data, or any part of the data generated as a consequence of whole genome sequencing, regardless of the individual identifiability of the biospecimens used to generate such data; or

Research use of information produced using a technology applied to a biospecimen that generates information unique to an individual such that it is foreseeable that, when used in combination with publicly available information, the individual could be identified (“bio-unique information”)

Definition of human subject

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TOMORROW

Understanding biospecimen research that is exempt

EXEMPTION

Research involving the collection or study of existing biospecimens if:

Source of biospecimens is publicly available, or

If information from the biospecimens is recorded by the investigator in such a manner that the individuals in which the specimens came from cannot be identified, directly or through linked identifiers

Exempt biospecimen research TODAY

IRB review required:

YES

YES

NO

NO

Exempt biospecimen research

Implication is:

Not existing = not eligible for an exemption

Existing, but source of biospecimen is not publicly available and identifiable info is recorded = not eligible for an exemption

Existing & source of biospecimen is publicly available = eligible for an exemption

Existing & identifiable info is not recorded = eligible for an exemption

TODAY

EXCLUSION

The NPRM proposes to exclude secondary research use of a non-identified biospecimen that generates information about the individual that is already known

Exclusion would likely apply to the development and validation of:

– Certain tests and assays (e.g., research to develop a diagnostic test for a condition using specimens from individuals known to have the condition)

– Quality assurance and control activities

Exempt biospecimen research TOMORROW

EXEMPTION

1) Storage or maintenance of biospecimens or identifiable private information for secondary research use

Broad consent, and

Limited IRB Review

2) Secondary research use of biospecimens or identifiable private information

Broad consent obtained for the storage, maintenance, and secondary use of the biospecimens, however

*If individual research results are to be provided to research subject then NOT exempt

Exempt biospecimen research TOMORROW

QUIZ

Research with biospecimens is exempt from IRB review today if the following is true: A. The biospecimens are existing and recorded information does

include a code to identifiable information

B. The biospecimens are existing and recorded information does not include identifiable information or a code to such information

C. The biospecimens are not yet existing and recorded information does include a code to identifiable information

D. The biospecimens are not yet existing and recorded information does not include identifiable information or a code to such information

Quiz

Dissecting consent related to

biospecimens

Consent and biospecimens TODAY

ELEMENTS:

Explanation of research Risks Benefits Alternatives

Confidentiality Injury compensation

(if > min risk)

Contact information Voluntary

Unforeseeable risk, participation termination, additional costs, consequences of withdrawing, significant new findings, approximate # of subjects

Consent to future use

As specific as possible to allow for “informed” consent

– However, too specific limits future research with the biospecimen

Consent and biospecimens TODAY

Issues related to consent to future use

Future use of identifiable specimens is reviewable by the IRB, which will consider

– Compatibility with original consent

– Whether additional consent is required

– Whether consent can be waived

Biorepository and Honest Broker option

– Creation of repository requires IRB review and consent of persons providing biospecimens

Consent and biospecimens

BUT! If repository has an oversight committee and “honest broker” mechanisms in distributing biospecimens to researchers, then compatibility with original consent is secured and additional consent or waivers of consent are likely unnecessary

TODAY

Same Elements as today, and the following NEW Elements

Statement that identifiers may be removed and non-identifiable data may be used or disclosed for secondary research OR statement that data collected will not be used/disclosed for future research

If biospecimens will be used for commercial profit, a statement as to whether or not profits will be shared with participants

If clinically relevant results will be disclosed to participants and if so, under what conditions

An option to consent, or refuse to consent, to be re-contacted to seek additional information/ biospecimens or to discuss participation in another research study

Consent and biospecimens TOMORROW

Broad Consent for Biospecimen Research and Identifiable Information

HHS will publish templates for use (using may make biospecimen research exempt)

Some original elements of consent, plus…

– General description of types of research and information to be generated

– Types of biospecimens/information

– Types of institutions that might conduct research with the biospecimens/information

Consent and biospecimens TOMORROW

Cont. next slide

Period of time during which collection will occur – Cannot exceed 10 years from the date of consent – For children, not to exceed 10 years or the date of legal age (whichever is

shorter)

Can withdraw without penalty or loss of benefits – Unless de-identified – Unless already distributed

If applicable, that participant may not know details of research

If applicable, specimen/info likely to be used by multiple researchers at multiple institutions

If relevant, option to opt out of having HIPAA de-identified data listed on public database

Consent and biospecimens TOMORROW

The research involves no more than minimal risk to the subjects;

The waiver will not adversely affect the rights and welfare of subjects;

The research could not practicably be carried out without the waiver; and

Whenever appropriate, subjects will be provided with additional pertinent information

Waiver of consent and biospecimens

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TODAY

NPRM adds more stringent waiver of consent elements: The research has “compelling scientific reasons” for the research use

of biospecimens, and

The research could not be conducted with other biospecimens for which consent was or could have been obtained

Waiver of consent & biospecimens

NOTE! IRB cannot waive consent if individuals were asked and refused to provide broad consent for use of their biospecimens/information

TOMORROW

Determining whether and how

to return research results

to individuals

What is the potential that the results are inaccurate? Is it possible to re-test prior to returning results – though depending on the sample (quantity/quality)?

What can the “results” tell them about their health?

Determining whether to return results TODAY

How could this information negatively impact the individual or their family?

Anxiety, depression, and stress to individual and their family (increased risk if they aren’t able to interpret results)

The results could relate to the individual and also the health of a family member

Procedures or treatments that are risky or expensive, but may not offer much benefit

Negative impact TODAY

How will knowing this information help them/their family?

Could potentially avoid triggers or substances that are likely to increase the chance of having a disease/condition (e.g., alcohol and tobacco)

Could help in planning for the financial security of themselves and their family (obtain insurance coverage, adjust savings habits, etc.)

Could help in planning other tools – healthcare POA, wills, etc. in advance

Could lead to early treatments or preventative action to mitigate the impact of the disease or chance of getting a disease

Positive impact TODAY

Opt-out

Tiered consent approach

All or nothing:

– Results will be returned/Results will not be returned

Addressing return of results in consent TODAY

Same considerations as today, except that NPRM adds a new IRB approval criterion:

If a researcher proposes a research plan for returning clinically relevant results to participants, the IRB must determine that the plan is appropriate

Returning research results

NOTE! This new criterion does not require IRBs to determine whether a plan for returning results should exist

TOMORROW

POLL

Ms. X enrolled in a drug trial for an investigational product intended to help individuals with Type 2 diabetes. As part of the trial, she consented to the collection of her blood for genetic analysis. The consent form that Ms. X signed clearly states that the results of the genetic analysis will never be disclosed to Ms. X during or after the trial. The genetic analysis revealed that Ms. X, who is of childbearing age, has a significant condition that will prevent her from ever becoming pregnant.

Should the results of the genetic analysis be provided to Ms. X?

Yes

No

Poll

Comprehending privacy, confidentiality, and data security surrounding biospecimens

Privacy, confidentiality, and data security TODAY

The most relevant Common Rule regulation today provides that in order to approve research the IRB must:

Ensure that there are adequate provisions to protect the privacy of subjects and confidentiality of data

The NPRM recognizes that IRBs are often not in the position to assess certain privacy and confidentiality risks and protections (e.g., the sophistication of a proprietary computer system’s data security measures)

The NPRM takes the following steps to address this:

Proposes to set uniform privacy and confidentiality standards

Proposes to require that investigators and institutions implement reasonable and appropriate safeguards for protecting against risks to the security, integrity, and unintentional disclosure of biospecimens or identifiable private information

Privacy, confidentiality, and data security TOMORROW

Discussing the buzz around biospecimens and the NPRM

Clarifying the Common Rule’s applicability

Defining human subject and the implications for biospecimens

Understanding biospecimen research that is exempt

Dissecting consent related to biospecimens

Determining whether and how to return research results to individuals

Comprehending privacy, confidentiality, and data security surrounding biospecimens

Recap

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