Exception from Informed Consent in Emergency Research

• Designed for implementation of research in emergency settings when exception from informed consent is requested under 21 CFR 50.24

http://www.fda.gov/ora/compliance_ref/bimo/err_guide.htm

Criteria

• The exception applies when:– Human subjects cannot give informed

consent because of emerging, life-threatening medical condition

– Available treatments for the condition are unproven or unsatisfactory

– The intervention must be administered before informed consent from LAR is feasible

Benefits and Risks

• Participation must hold out prospect of direct benefit to the subject– If placebo design is used, standard care must be given

to all subjects

• Risks of the study are reasonable in relation to:– What is known about the medical condition of the

potential subjects– The risks and benefits of standard therapy– Any benefits of the proposed treatment

Study Design

• Design should be adequate to the task of evaluating whether the treatment provides the hypothesized effect

• The therapeutic window must be defined

• The amount of time spent in locating family members must be defined

Contact of Family Members

• Attempts to contact a legally authorized representative (LAR) or family member need not exhaust the entire therapeutic window

• The effect of delaying study treatment must be taken into account when determining the portion of the therapeutic window to be spent trying to locate family

Public Disclosure and Community Consultation

• Prior to start of the study -- public disclosure of sufficient information to describe :– the nature and purpose of the study– the fact that informed consent will not be obtained

for most study subjects

• Following completion of the study information about the study results must be disclosed– to the community where the research was done– the research community should have access to

comprehensive summary data

IRB Responsibilities Specific to Waiver of Consent• Review/approve proposed plan and procedures

for contacting LAR/family

• Review/approve community notification and consultation plan

• Attend/participate in community consultation activities

Community Notification and Consultation Plan

• Each center must submit a written plan for:

– Notification: activities to inform the community about the trial and use of waiver of consent

– Consultation: activities that permit community members to express their views and offer opinions, suggestions, and feedback about the trial and use of waiver of consent

Community Consultation

• Shared obligation of the clinical investigator, IRB, and sponsor

• Content should include discussions of:– The fact that informed consent will not be obtained

for most study subjects– The risks and potential benefits

for the subjects– Ways that individuals or

groups can indicate desire to be excluded

Notification Strategies

• Purpose: to provide information

• Options:– Public service announcements– Print media– Television and radio– Web site– 800 number with recorded message– Other?

Consultation Strategies• Hospital and non-hospital based groups

• Presentation/discussion/feedback– Hospital’s community outreach programs– Religious organizations– Academic groups– Civic groups – Patient advocacy groups

• “Talk radio” shows

• Television shows with call-in feature

Consultation Plan Elements

• Description of the community

• Strategies for notification

• Strategies for consultation

• Documentation procedures for activities, feedback and responses

Community Description

• Description of the community:– Major ethnic, racial, cultural groups– Significant health care issues– Major social influences– Other factors?

• Resources– US Census website– Hospital admission/service statistics– Newpapers/media

Reasons for Exclusion in NABIS:H I

Reason % Excluded

GCS = 3 AND unreactive pupils 22%

GCS 7-8 with normal CT scan 21%

AIS > 4, except head 19%

BP < 90 mm Hg after resuscitation 10%

O2 sat < 94% after resuscitation 9%

Rewarming required for bleeding 4%

Total excluded due to systemic injury 42%

• Surface Cooling Devices– Standard cooling pads

– Rapr-Round Cooling Suit by Gaymar Inc.

– Arctic Sun Temperature Pads by Medivance Inc.

• Intravascular Cooling Devices– Cool Line and Icy Catheters by Alsius Corp.

– Celsius Control System by Innercool Therapies

– Reprieve Set Point Endovascular System by Radiant Medical

Currently Available Cooling Technologies

Standard Cooling Pads

• Poor body surface area contact

• Placement of sheets or other materials between patient’s skin and blanket

• Stiff and inflexible

• Obscure patient’s body for observation and access for care

The Rapr-Round -- Gaymar

Designed to:• Provide maximal

surface contact

• Stay put with turning or moving the patient

• Permit access and

visualization of the patient

Arctic Sun -- Medivance

http://www.medivance.com

Cool Line and Icy -- Alsius

The Cool Line – smaller, 2 balloons

Icy – larger, 3 balloons

Celsius Control System – Innercool

Reprieve Endovascular System – Radiant Inc

Balance-beam PerformanceBalance-beam Performance

0

10

20

30

40

50

60

Lat

ency

(se

c)

0 min* 60 min* 90 min 120 min

Delay in Hypothermia Treatment

Sham Normo Hypo*p<0.05

Posture Reflex Scores

1.0

1.5

2.0

2.5

3.0

3.5

Sco

re

0 min* 60 min* 90 min 120 min

Delay in Hypothermia Treatment

Sham Normo Hypo*p<0.5

NABIS:H I Admission Temp and Outcome

< 35.0o C > 35.0o C

Hypo Normo Hypo Normo

% of patients 62 40 127 137

% poor outcome 61 78 54 52

% dead 29 35 26 23

NABIS:H IOutcome in Patients with Admission Temp < 35 C and Age < 45

Hypo Normo P

Dichotomized Glasgow Outcome Scale 0.03

Good Outcome (GR/MD) 48% 24%

Poor Outcome (SD/V/D) 52% 76%

Glasgow Outcome Scale 0.08

Good Recovery 14.6% 15.2%

Moderate Disability 33.3% 9.1%

Severe Disability 20.8% 39.4%

Vegetative 4.2% 3.0%

Dead 27.1% 33.3%

NABIS:H IEffect of Admission Temp on Outcome

The FDA requires a separate IDE for devices that are used in trials

using waiver of consent.