FROM ADVERSARIES TO ALLIES: EFFECTIVE COMMUNICATION ... Adversaries … · from adversaries to...

FROM ADVERSARIES TO ALLIES:

EFFECTIVE COMMUNICATION BETWEEN

INVESTIGATORS AND IRBS

LY N N M . R O S E , P H . D .

D I R E C TO R , S C I E N T I F I C A D M I N I ST R AT I O N

B E N A R OYA R E S E A R C H I N ST I T U T E

1. General Perceptions of IRB and Investigator

2. Discuss common areas of misunderstanding

between investigators and IRB

3. Present some tools for improved

communication of medical risk to IRB

AGENDA

The IRB is a committee formally designated by the

FDA and DHHS to review, approve, and monitor

biomedical and behavioral research involving

humans with the aim of protecting the rights and

welfare of the research subjects.

INSTITUTIONAL REVIEW BOARD

Risk Averse

Anti-science

Bureaucratic “Black Box”

Unnecessary administrative delays

Don’t get it!

WORDS USED TO DESCRIBE IRBS

PERCEPTION OF INVESTIGATOR BY IRB

Can’t follow basic simple instructions

Provide incomplete information

Overly focused on efficacy – not safety

A bit fuzzy on the regulations

Don’t get it!

WORDS USED TO DESCRIBE APPLICANTS

THE REALITY

IRB, Investigator and Subject after

the same thing

Advance medicine

Improve human health

Be safe

Be part of something that is

meaningful

COMMUNICATE EFFECTIVELY

I R B

User-friendly submission forms

Make questions easily

understandable

Avoid verbatim recitation of

regulations

Be Timely

Provide a Transparent Process

I N V E ST I G ATO R

Provide complete answers to questions asked – Don’t assume, no “cut and paste”

Write clearly, concisely, and consistently

Supplement application with information, when necessary

Respect Timelines

Be aware of regulations

Medical Device Studies

Significant risk (SR) or an non-significant risk (NSR)?

Interventional Drug Studies

IND or no IND?

Tissue Collection Studies

Exempt, Not Exempt, Non-human subject research?

Chart Review Studies

Human Subject Research or Quality Improvement?

FREQUENT AREAS OF MISUNDERSTANDING

Implants (e.g., pacemaker) and present a potential for serious risk

to the health, safety, or welfare of a subject

Support or sustain or sustaining human life and presents a

potential for …

Diagnose, cure, mitigate, or treat disease, or otherwise prevent

impairment of human health and present a …

Otherwise presents a potential for …

MEDICAL DEVICES SIGNIFICANT RISK DETERMINATION

Investigator/Sponsors make initial determination and present to

IRB

Unless FDA has already determined risk level, it is the

responsibility of the IRB to make the final determination

FDA is available to consult with sponsor or IRB

In cases of disagreement, FDA trumps IRB

MEDICAL DEVICES WHO DECIDES?

Provide IRB with rationale for proposed determination

Provide sufficient data to help the IRB evaluate the risk of the

device

Description of device

Prior investigations with device

Proposed investigational plan

Subject selection criteria

MEDICAL DEVICES INVESTIGATOR CAN FACILITATE THE PROCESS

Provide Users Manual

Provide Diagrams – let them see!

Briefly describe regulatory status

Provide risk information from literature

Make it easy for the IRB to find and review the relevant

information.

MEDICAL DEVICE EXAMPLE: EUROPEAN DEVICE

The investigation will not support a new indication or other change in the product label or

advertising

The investigation does not involve a route of administration or dosage level or patient

population that significantly increases the risks (or decreases the acceptability of risks)

associated with use of the drug

The investigation is conducted in compliance with the requirements for institutional

review

The investigation is conducted in compliance regulations governing promotion and

charging for investigation drugs

THERAPEUTIC INTERVENTIONS IND WAIVERS FOR STUDIES WITH APPROVED MEDICATIONS IF

When the investigation does involve a route of administration or dosage level or

use in a patient population or other factor that significantly increases the risks (or

decreases the acceptability of risks) associated with use of the drug

The investigational drug is a dietary supplement

The investigational drug is a botanical substance

Clinical practice is “off-label”

Lack of an IND may slow process unless risks are clearly presented and

acceptable

THERAPEUTIC INTERVENTIONS WHERE IT GETS PROBLEMATIC:

Changes in route of administration can alter safety risks

• Target Organ may change (i.e. inhaled vs. parenteral)

• Pharmacokinetics may be altered (i.e. increased renal exposure)

Doses may exceed those in the label

• May limit usefulness of study if dose limited to the approved dose

Patient population is in an untested age range

Patient population has a disease condition that would put it at different and/or

greater risk than the population(s) studied for the approval

THERAPEUTIC INTERVENTIONS THINGS FOR IRB AND INVESTIGATOR TO CONSIDER

Provide the data needed to assess risks!

Know the safety findings for the original indication

Discuss relevance for the condition under study

Read the label!

Review the regulations

Dietary supplements are considered “drugs” if they are used to treat, cure, or mitigate disease

Understand difference between the label and clinical practice

THERAPEUTIC INTERVENTIONS HELP THE IRB

Discuss program with local IRB

Some IRBs require a letter of exemption from FDA OR the IND Number

Some IRBs will review the investigator’s rationale and make a decision

Submit “Request for Exemption”

A call can tell you if the division will entertain a Request for Exemption

Submit a request for a pre-IND meeting

Include rationale and request for exemption as part of submission

THERAPEUTIC INTERVENTIONS STILL NOT SURE?

Not a lot of regulatory guidance so the “it depends” rule comes into play

Need clear institutional policies, so investigators are not confused about what is eligible for

waiver of consent and what is not

Lack of clarity on the recipient investigators

Laboratory personnel often working outside of the clinical context, may lack training in Good

Clinical Practice, Consent Processes, and HIPAA

Conflicting Regulatory Processes for Secondary Uses of Stored Tissue

Waiver of consent appropriate for anonymous samples and possibly coded samples; however,

access to more information may become a research need

Requests for secondary uses often outstrip the initial purpose of the repository

TISSUE REPOSITORIES COMMON PROBLEMS

Unclear separation between quality initiatives and human subjects research

Need institution policies in place with clear definitions of research

Internally focused data versus generalizable results

Unanticipated Needs for Secondary Uses of Stored Data

Data collected for clinical or quality purposes may “morph” into human subject research and

require IRB review

Original data collected without consent may now require consent

Data collected without proper consent may not be eligible for publication

CHART REVIEW COMMON PROBLEMS:

1. IRBs and Investigators work together to protect human subjects in research.

2. IRBs need to understand what you are doing and why; no matter the type of

research.

3. Investigators must anticipate the focus on safety, either to the subjects

themselves or subject data

4. IRB includes lay members of the community so the language must be clear.

5. Be clear, don’t obscure. There is no point in altering a study to avoid human

subjects protections!

CONCLUSIONS

Clear Concise Consistent