# Presentation: 239307

## Vulnerability, decisional impairment, and research protections

- David H. Strauss, M.D.
- Chair, Institutional Review Board
- New York State Psychiatric Institute
- Director, Office of Human Subjects Research
- Department of Psychiatry
- Columbia University College of Physicians and Surgeons

- Strauss, VA ORO Sep 13, 06

## For consideration

- PET study in a neuro-psychiatric population involves:
- 3 weeks medication-free period prior to scan
- Diagnostic assessment
- MRI
- PET Scan
- Placement of arterial and venous lines
- Phlebotomy
- Injection of radioactive tracer
- 			More than minimal risk
- 			No (or low) direct benefit

- Strauss, VA ORO Sep 13, 06

## §46.111 Criteria for IRB approval of research

- (1) 	Risks to subjects are minimized:
- 	by using procedures which are consistent with sound research design and *which do not unnecessarily expose subjects to risk...*
- Risks to subjects are_ __*reasonable*_ in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may _*reasonably*_ be expected to result.

- Strauss, VA ORO Sep 13, 06

## 
How does the IRB define unreasonable risk
	(= unacceptable risk)?

How much of the risk-benefit analysis is left to the subject?

How do we resolve this tension between autonomy and protectionism?

How do we resolve the fundamental tension between the interests of science and the interests of the individual subject?

- How does the IRB define unreasonable risk
- 	(= unacceptable risk)?
- How much of the risk-benefit analysis is left to the subject?
- How do we resolve this tension between autonomy and protectionism?
- How do we resolve the fundamental tension between the interests of science and the interests of the individual subject?

**Risks and Benefits:**
**what is “reasonable”? **

- Strauss, VA ORO Sep 13, 06

## Some persons are in need of extensive protection, even to the point of excluding them from activities which may harm them; 

- other persons require little protection beyond making sure they undertake activities _freely_ and _with awareness_ of possible adverse consequence.
- 				The Belmont Report

- Strauss, VA ORO Sep 13, 06

## Vulnerable Populations: Regulatory Specifics

- §46.111 Approval
- (b) When...subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, ***additional safeguards have been included...***
- Subpart B (pregnant woman, fetuses, neonates)
- Subpart C (Prisoners)
- Subpart D (Children)

- Strauss, VA ORO Sep 13, 06

## Regulatory Specifics (Cont’d)

- §46.107 Membership:
- 	If an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons *consideration shall be given* to the inclusion of one or more individuals who are knowledgeable...and experienced...with these subjects
- §46.111 Approval
- (a)(3) Subject selection is equitable...be particularly cognizant *of **special problems...(with) vulnerable populations. *

- Strauss, VA ORO Sep 13, 06

## Regulatory Specifics (Cont’d)

- §46.116 General requirements for informed consent.
- ...the investigator has obtained the ***legally effective*** informed consent of the subject or the subject's legally authorized representative.
- ...an investigator shall seek such consent only under circumstances that provide...sufficient opportunity to consider whether or not to participate and that ***minimize the possibility of coercion or undue influence. ***

- Strauss, VA ORO Sep 13, 06

## Principles arising: implications for IRB review

- Vulnerability and decisional impairment are not simply *present or absent*.
- Neither are limited to those with disorders of the central nervous system
- 	mental illness ****** **mentally disabled ****** **impaired decision-making
- Protections must be tailored to the nature and proportional to the extent of vulnerability and the magnitude of the experimental risk.
- Protections are not limited to those which address consent (but include subject selection, recruitment, exclusion, the risk-benefit threshold, notions of acceptable risk etc).

- Strauss, VA ORO Sep 13, 06

## Preconditions for consent

- Information
- Understanding*
- Factual understanding of the information
- Rational manipulation of information
- Ability to appreciate the nature of the situation and its consequences
- Ability to evidence a choice
- Free exercise of choice (voluntariness)

- *Appelbaum and Roth

- Strauss, VA ORO Sep 13, 06

## We apply additional protections for those who are vulnerable... 

- By virtue of impaired ability *to protect themselves* through consent (i.e. and therefore are “vulnerable to coercion or undue influence”)
- e.g. patients with cognitive problems (understanding)
- e.g. prisoners (voluntariness)
- e.g. the terminally ill (understanding)
- e.g. immigrant populations (information)
- e.g. the under-educated (information, understanding)
- e.g. the poor (voluntariness, information)
-  cont’d

- Strauss, VA ORO Sep 13, 06

## Cont’d

- By virtue of impaired ability to decide *for themselves* through consent (and therefore their best interests are not known)
- e.g.  the unconscious patient
- By virtue of special *susceptibility* to research-related harms
- e.g. “minority” groups (sexual orientation, race, ethnicity): added stigma or burden
- e.g. HIV and risk of social stigma
- e.g. children, fetuses
- Others, because we think the group warrants special consideration
- e.g. children, Sep 11 victims, ? veterans

- Strauss, VA ORO Sep 13, 06

## The nature of decisional impairment ...at the bedside

- _Situational _vs. _disorder-related__  _impairment
- 	(e.g. emergency room, “institutions” vs. stroke)
- _Global_ vs. s_pecific_ impairment
- 	(e.g. sedative overdose vs. paranoid psychosis)
- _Static_ vs. _progressive _vs. _episodic__ _impairment
- 	(e.g. severe mental retardation vs. Alzheimer’s disease vs. manic depressive disorder)
- _Acute_ vs. _persistent_ impairment
- 	(e.g. hypoxia secondary to asthma or acute pain vs. autism)

- Strauss, VA ORO Sep 13, 06

## “Capacity to consent” is task specific

**Capacity to Consent**

- Unable to make decisions

- Able to appoint a proxy decision-maker

- Can consent to higher complexity/higher risk research

- Can consent to low complexity/low risk research

- Medical
- Decision-
- making

- Strauss, VA ORO Sep 13, 06

## IRB Review-1: SOPs

- Levels of review--are two levels of review adequate?
- Does the IRB have the necessary expertise?
- What kind of research monitoring is appropriate?
- Feedback
- Report back
- Consent monitoring
- Procedural observation
- Do policies guide investigators and reviewers regarding additional protections?
- Payment policies
- Who discusses and documents consent?
- When, how and by whom is an independent assessment of capacity done
- Required enhancements
- Rules for surrogate consent

- Strauss, VA ORO Sep 13, 06

## Defining the vulnerable group

- Classes of individuals
- who *may have* impaired
- decision-making abilities
- Individuals who *do have*
*impaired or diminished** *
- decision-making abilities
- Individuals who lack the
- capacity to consent to
- a research study

- Strauss, VA ORO Sep 13, 06

## 
Consent and assessment may require special training and expertise

Some disorders may impair decision-making

Disorders may be episodic, persistent or both

Some are associated with significant morbidity and mortality

Many are stigmatizing

Access to adequate care is often problematic 

- Consent and assessment may require special training and expertise
_*Some*_* *disorders _*may*_* *impair decision-making
- Disorders may be episodic, persistent or both
- Some are associated with significant morbidity and _*mortality*_
- Many are stigmatizing
- Access to adequate care is often problematic

**IRB Review-2: Subject characteristics**
**relevant to review of research with some neuro/psychiatric disorders**

- Strauss, VA ORO Sep 13, 06

## IRB Review-3: first steps

- Minimizing risks in the design
- Is the study design consistent with the state of the science?
- Does the study involve the least vulnerable group consistent with the aims of the study?
- Does it conform to IRB ethical standards?
- Are recruitment methods ones that optimize voluntariness?
- How is the study advertised?
- Where and when does recruitment and consent occur?

- Strauss, VA ORO Sep 13, 06

## Carefully consider the nature of the disorder
Consider the phase of illness under study
Carefully consider co-morbidities

Consider the effects and duration of delay to treatment
Consider restriction on treatments imposed by the research

Consider the safety of the research setting

- Consider the phase of illness under study
- Carefully consider co-morbidities
- Consider the effects and duration of delay to treatment
- Consider restriction on treatments imposed by the research
- Consider the safety of the research setting

**IRB Review-4: Identifying Risks**

- Strauss, VA ORO Sep 13, 06

## Carefully define subject inclusion criteria

Exclude most-at-risk subjects, where possible 	

Examine frequency and nature of assessments (and personnel)

Require operationalized clinical drop-out criteria e.g. for worsening, failure to improve, serious events

- Exclude most-at-risk subjects, where possible
- Examine frequency and nature of assessments (and personnel)
- Require operationalized _clinical _drop-out criteria e.g. for worsening, failure to improve, serious events

**IRB Review-5: Minimizing Risks**

- Strauss, VA ORO Sep 13, 06

## Wrap-up	

- Research risk, vulnerability and decisional-impairment occur along a spectrum. A simple categorical approach to protection (as in Subpart D) may not work.
- Acknowledge the complexity of “decisional impairment” and the populations and settings in which it is common
- Craft the necessary local policies and procedures to guide IRB members

- Strauss, VA ORO Sep 13, 06