Investigator’s Role with

Consent for Biospecimen

Research

Erin Rothwell, PhD

NPRM • Broad consent for future, unlimited

research

• Increase investigator independence

• Surprising, less attention given to:

– Transparency

– Trust

– Partnership – (Grady et al., 2015)

Federal Regulations

• Broad consent for future purposes

– NIH Genomic Data Sharing Policies

– HIPPA 2013 amendment

• For the most part, minimal risk research

• However, informed consent is not

engaged in a meaningful manner

Informed Consent

• Informed consent is the cornerstone for the ethical conduct of research

– Yet, it is seriously flawed

• Clinical informed consent for study specific research over 45 year period (Falagas et al., 2009)

• 54% understood aims

• 50% understood randomization and risks

• 47% knew participation was voluntary

• 44% knew they could withdrawal

• 57% understood the benefits

Promote Comprehension

• Multimedia

• Simplified paper based forms

• Teach Back

• Comprehension quizzes

Challenges to Broad Consent

• Clinical Setting

– Not the best time

– Conflicting consent choices

• Limited Public Knowledge about

Research (Rothwell et al., 2012; Botkin et al., 2014)

• Unknown future research uses

Participant Comprehension

• Should continue, but if we are concerned

with

– Public Trust

– Improving safeguards/confidentiality

– Partnership

• Should we focus on the investigator’s

responsibilities’ too?

Commitment Letter/Oath

• FDA has required an Investigator

Commitment Letter for decades (www.fda.gov)

• I agree to conduct the study(ies) in accordance with the relevant, current

protocol(s) and will only make changes in a protocol after notifying the

sponsor, except when necessary to protect the safety, rights, or welfare

of subjects

• I agree to personally conduct or supervise the described investigation(s).

• I agree to inform any patients, or any persons used as controls, that the

drugs are being used for investigational purposes and I will ensure that

the requirements relating to obtaining informed consent in 21 CFR Part

50 and institutional review board (IRB) review and approval in 21 CFR

Part 56 are met.

Questions

• What can improve safeguards of

biospecimen research?

• What can improve confidentiality?

• What can improve privacy?

• What can help with public trust?

• What can help build partnerships?

Culture of Investigator Research

with Biospecimens • Communicating to research subjects

about how investigators are committed to

responsibly use biospecimens may help

promote transparency and trust with

research subjects.

Methods

• Purpose

– Broad consent

– Oath/Commitment letter

• Qualitative Descriptive Interviews (n =18)

– Intermountain West

Methods

• Conducting in person and over the

telephone

• Interviews ranged from 15-50 minutes

• September 2015

• Notes and written summaries uploaded

into Atlas.ti (Fasick, 2001; Halcomb & Davidson, 2006)

Results

• moving purpose of consent;

• awareness and accountability;

• gray areas;

• comparisons to clinical care; and

• components of investigator oath.

Moving Purpose of Consent

• Changing interpretations of IRBs – We wrote in our consent form ‘researching genes’

and few years later they did not think that included

‘sequencing genes.’

• Hard to comprehend “unlimited” – Its scary because it’s unlimited, how do you

communicate that

• Difficulties of practical implementation in

the clinical setting

Moving Purpose of Consent

• Gives the option to say no or seek more

information

– Is broad consent trust in the regulatory

process? Is it trust in the investigator? Or is

just to give the option to say no?

Awareness and Accountability

with Oath • Gives awareness to research subjects

and investigators

– It will bring awareness so I guess that helps

with trust

• Tells research subjects you are doing this

for the right reason

– Have to let them know you are doing this for

the right reasons

Awareness and Accountability

with Oath • Unsure about improving trust

• Investigator accountability – Too many [investigators] have done things wrong

and that is just the ones we know about

– Not vouch for other investigator behavior

– To drop the hammer on questionable behavior

• Promotes respect of donations among

investigators

– Investigators do not appreciate the donation

Quotes Questioning Oath

• An oath would raise suspicious

• [Investigators are] trying to do the right

thing

• Another hoop to jump through

Gray Areas

• No definitive right or wrong answers

– There are such grey areas with research with

biospecimens.

– PhDs have no oath so they have to do what

they think or hope is right

• Investigator independence

– A lot of independence

– Integrity of the investigator is essential

Gray Areas

• Rapid changes in genomics and

technology

– Fluid is the definition of investigator research

– Need to stop and think about each case

individually the next time you use them

Comparisons to Clinical Care • Different but similar to clinical care

– Dealing with DNA not patients

– I’m not a physician, I’m a researcher.

• Their research may have implications for

individual health

– An investigator might have to wait five years

to see the outcomes of their research but it

might still yield life saving information

• Lack a relationship with research subject

Components of an Oath

• Transparency

• Awareness about the importance

• Respect to research subjects/donors

• Communication practices

• Safeguards

• Risks/Benefits/Examples

General Conclusions

• Investigator oath well received

• Transparency trust

• Accountability trust

• Changing nature of biospecimen research

– From broad societal impact to also include

individual impact

• Changing perception of research by the

public

• Efforts to promote research subjects’

comprehension should continue

Investigator Oath

• Do you really think an oath will work?

• Can it hurt?

• Should participants be aware of the oath?

• Is there another approach?

• Example of HIPPA

– Could we apply lessons learned?

Thank you!

• Questions?

FDA Investigator Commitment

Letter • I agree to conduct the study(ies) in accordance with the relevant,

current protocol(s) and will only make changes in a protocol after notifying the sponsor, except when necessary to protect the safety, rights, or welfare of subjects

• I agree to personally conduct or supervise the described investigation(s).

• I agree to inform any patients, or any persons used as controls, that the drugs are being used for investigational purposes and I will ensure that the requirements relating to obtaining informed consent in 21 CFR Part 50 and institutional review board (IRB) review and approval in 21 CFR Part 56 are met.

• I agree to report to the sponsor adverse experiences that occur in the course of the investigation(s) in accordance with 21 CFR 312.64. I have read and understand the information in the investigator’s brochure, including the potential risks and side effects of the drug.

FDA Investigator Commitment

Letter continued • I agree to ensure that all associates, colleagues, and employees

assisting in the conduct of the study(ies) are informed about their obligations in meeting the above commitments.

• I agree to maintain adequate and accurate records in accordance with 21 CFR 312.62 and to make those records available for inspection in accordance with 21 CFR 312.68.

• I will ensure that an IRB that complies with the requirements of 21 CFR Part 56 will be responsible for the initial and continuing review and approval of the clinical investigation. I also agree to promptly report to the IRB all changes in the research activity and all unanticipated problems involving risks to human subjects or others. Additionally, I will not make any changes in the research without IRB approval, except where necessary to eliminate apparent immediate hazards to human subjects.

• I agree to comply with all other requirements regarding the obligations of clinical investigators and all other pertinent requirements in 21 CFR Part 312.

Transparency and Awareness:

• to respect your donation to science by

allowing use of your biospecimen in

research.

• to respect your biospecimen as a limited

resource and use it wisely and carefully.

• to be open and transparent about

research with your biospecimen.

Respect to Donors/ Investigator

Promises • to appreciate the your donation for research and science in

general.

• to use the biospecimen in thoughtful and well-designed research in order to improve the well being of our society and health.

• to use the biospecimen only in research that is well designed and intended to have a benefit to society.

• to remember this is a donation from a person and not just data.

• to conduct research with this donation to improve health and prevent disease.

• to respect that all achievements in health and science are the result of previous work of others who have conducted beneficial and thoughtful research and to try to continue to build upon this knowledge for the health care of our society.

Communication

• to acknowledge that although research is

to improve health in general, there may

be times when it impacts your individual

health.

• to publish results for other investigators to

learn and build upon for future research.

Safeguards

• to adhere to all privacy, ethical and

confidential safeguards that are in place

for this research.

• to seek approval for my research from

appropriate institutional, ethics, or

governing committees before beginning

research

Risks and Benefits/Example of

Importance • to remember that there are some risks with

this donation and to seek to minimize these risks

• to not release the biospecimen donation to anyone who does not have appropriate approval and who would not adhere to the ethical standards in this oath.

• 16. to seek help when needed if I am unsure about the integrity of the research or the welfare of the donors.