1

Focus Groups and SurveysThe PECARN Seizure Study

Community Consultation Experience

RAMPART Investigator Meeting

Jill Baren, MD, MBE, FACEP, FAAP

January 2008

Objectives

Describe the PECARN Seizure Study focus group and face to face survey methodologies for community consultation

Provide a justification for the use of focus groups and face to face surveys as effective community consultation methods

Draw parallels between the PECARN Seizure Study and RAMPART

What is PECARN?

First federally-funded multi-institutional research network in pediatric emergency medicine

4 nodes, > 20 ED affiliates

Academic, community, urban, rural, general, and children's hospitals

Network serves approximately 800,000 acutely ill and injured children/year 

PECARN Seizure Study

Two part study funded by NICHD through the BPCA mechanism

Lorazepam identified as highest priority drug for study to obtain FDA label

Study 1: Pharmacokinetics (completed)

11 sites; 65 subjects; dose established at 0.1 mg/kg

Significant consent and enrollment barriers identified

Study 2: Randomized controlled trial of lorazepam vs. diazepam for pediatric status epilepticus

Efficacy and safety study

Efficacy and Safety- the 10/30 rule

How efficacious is lorazepam compared to diazepam at stopping seizures within 10 minutes?

How efficacious is lorazepam compared to diazepam at maintaining seizure cessation at 30 minutes?

How safe is lorazepam compared to diazepam in terms of need for assisted ventilation or intubation within 4 hours of dosing?

PECARN Seizure StudyRegulatory History

Negotiation with FDA/NICHD on consent issues 18 months pre-trial activity seeking Exception from

Informed Consent Included national panel on “Emergency Research in

Children: Ethical, Regulatory, and Clinical Challenges” IND approved July ’07 using 21 CFR 50.24 regulations Community consultation and public disclosure required as

additional human subjects’ protections Ongoing activities at all active sites (10) Drop out of one site due to administrative denial of trial Possible addition of another site

Full IRB approval at 3 sites IRB approval to move forward with CC/PD at all sites

Patient enrollment beginning January ’08 with 3 sites ready

Study cohorts

Cohort 2: Exception from

Informed Consent(SE)

Cohort 1: Pre-consented

during healthcare visit

Study management

Co-PI structure at national level Coordinating scientific investigator

Protocol development Human subjects coordinating investigator

Develop and implement all aspects of regulatory process and human subjects protections

Create an overall EFIC plan

Joint activities Steering committee leadership IND preparation Interface with sponsor Trial preparation and conduct

Regulatory process IRB templated cover letter (7/06) Initial meeting with IRB chair (9/06)

Resource binder provided Community consultation methods discussed

IRB appointed liaison (9/06) IRB educational sessions (12/06) Initial protocol submission (12/06)

Requested two step approval process Step 1: Approval of EFIC plan (1/07-3/07)

Justification for study to be carried out under 21 CFR 50.24

Specific community consultation methods approved (1/07)

IRB resource binder

Regulatory process

Community consultation carried out (3/07-8/07) IRB received report of interim results

Final IRB submission prepared including analysis of results of community consultation (9/07-11/07)

Step 2: final IRB submission (12/07)

Full committee review of community consultation results (12/07)

Full approval of scientific protocol granted (1/08)

Frequent ongoing communication

Focus Group Methodology

69 parents and patients recruited from ED, neurology clinic and inpatient floors

Trained facilitator who participated in development of topic guide

IRB liaison present at 3 of 4 focus groups Study representative available to answer

technical questions Linked to an opt-out registry or possible

prospective consent Discussion recorded and transcribed

Focus Group Results

22 participants (31% of those recruited) Participants generally in favor of research being

performed without consent Common themes:

Concerns about side effects Community awareness of study How to “opt-out”

Concerns diminished after further discussion All adolescents expressed willingness to participate

91% parents expressed willingness to enroll their child in study

2 parents completed opt-out forms for clinical reasons

Focus group strengths and weaknesses

In-depth qualitative method that generates detailed and rich information

Dedicated time to examine the attitudes of a small group of individuals Selects for interested parties who are more likely to provide

meaningful input Potential for greater interaction among the participants Generates conversation directed by the group participants

Information obtained is likely to be of high quality and useful in IRB deliberations Diversity of information will be dictated by the composition

of the groups

Cost will depend on the number conducted Minimal to moderate in relation to overall study costs

(~$1000/group)

IRB response

Interim reports sent to IRB chair after each focus group

IRB liaison provided progress report during full committee meetings

Asked to conduct one additional focus group involving parents and teens without seizure disorder

Summaries and individual transcripts made available for IRB deliberations

Protocol fully approved for conduct under 21 CFR 50.24 after community consultation results reviewed

Survey methods

Adults accompanying a child in the ED or neurology clinic

No requirement for complaint related to seizure in ED Aimed to capture population where the clinical

investigation will be conducted and from which the subjects will be drawn

Cost-effective way to capture group that may represent first time seizure patients

Process linked to opt-out or possible prospective consent

Survey Results 170 surveys completed

80% of participants felt study was important and would allow their child to participate

17 participants completed opt-out forms

Common themes Concerns about side effects Concern about consent process Lorazepam not FDA approved for children

High agreement that medical research and “experiments” in emergency care are important but expressed concern about enrolling without consent 65% felt that emergency research without consent was

acceptable within their communities

Survey Strengths and Weaknesses

More controllable way to disseminate information One on one technique allows for greater interaction

between the investigator and participant and avoids group bias

Time consuming and can be costly depending on personnel used

Potential for influence on the part of the survey administrator Information produced is of moderate to high quality and

likely to inform IRB deliberations Random digit dialing telephone surveys mimic this but often

do not provide two way communication unless non-study personnel know how to answer study specific questions Less bias but do not have complete knowledge of study

True intent of community consultation is two-way communication!

Seizure Study/RAMPART parallels

Condition studied: Status epilepticus

Both studies compare drugs in common use, and have similar pharmacologic and adverse event profiles

Study drug comparator is unlabeled

Study population will be drawn from those who are known to have the condition as well as those developing the condition for the first time

EFIC and RAMPART

Much of the rationale for conducting the PECARN Seizure Study under 21 CFR 50.24 applies to RAMPART e.g. narrow therapeutic window of 5 min

Similar justification may be made in an overall EFIC plan

Many of the additional human subjects protections (community consultation) that have been used in the Seizure Study may be useful for RAMPART

Important Lessons Learned

This is not a random process and it takes a lot of thought and time

Don’t assume that IRBs are more educated about the regulations than you are

Do not take a “one size fits all” approach IRBs, investigators AND communities are

characterized by local customs and practices

There are a huge number of misconceptions about the regulations that you must correct

Do not assume that your materials are getting the right message across

Successful Strategies

Develop a plan and a strategy for global administration of the human research protections aspects of the trial Appoint a “human subjects czar”

Investigator initiated IRB guidance through the process is essential

Investigator-IRB communication is the cornerstone of the process

Correcting misconceptions about the regulations e.g. community consultation ≠ community consent

Pilot material and be willing to make changes based on community input (“glitch detection”)

Questions?