Synopsis of the RAMPART exception to informed consent for emergency research plan

and

Current Timeline

Foundational principles of the plan:

these are the underlying ethical purposes that we infer from the rules at 21 CFR 50.24. We use these as the goals to meet to define successful implementation. These principles are:

•Understanding•Respect•Transparency

Understanding

• the information we wish to obtain from community consultation is the variety of values and narratives of the people to whom we talk. The research to be conducted is the stimulus for the discussion, but the goal is for us to better understand them.

Respect

• local investigators will demonstrate respect by going to community gatherings to make presentations, rather than by asking the community to come to us. The process is one of humility that emphasizes personal interaction.

Transparency

• public notification is about having nothing to hide. Adequacy is determined by the fullness of disclosure and the ease of accessibility rather than a head count of recipients or viewers.

Community consultation:

• recognizing that the draft 2006 FDA guidance defined communities as distinctly including both a geographic community and a disease/risk-specific community, our plan addresses these separately.

Geographic CC

• Hub investigators will conduct presentations by seeking invitations to attend regularly scheduled meetings of community groups. These groups may include, but are not limited to: religious groups, neighborhood groups, political groups, service organizations, business clubs, health organizations, parent-teacher organizations, etc. Attempts should be made to cover a diversity of groups, but it is not necessary to meet separately with every single possible sub-group of the community. At each hub-spoke complex, fifteen presentations or more are expected over a 3 to 5 month period. Presentations will be designed to last sixty minutes, but shorter versions will be prepared for groups unable to commit that much of their agenda to this topic. Other trials have reported that going to existing organizations provides access to a bigger slice of the community than does holding special “town hall” style meetings sometimes used for this purpose. Additionally, the act of going to people where they meet is more respectful than having them come to us.

Seizure Specific CC

• Patients with a risk of entry into the study higher than that of the general population, and patients that have previously experienced and survived status epilepticus will be consulted. These consultations will take place in focus groups involving both an investigator and a trained facilitator will be used. The seizure-specific community does not have to be geographically confined, so expertise will be leveraged by having focus groups of particular subsets of patients performed at different hubs, and then having all the focus group experiences collated and distributed to all sites. One hub will focus on children and parents recruited from a pediatric epilepsy clinic, another on survivors of status epilepticus, another on members of the epilepsy foundation, another on patients from an adult epilepsy clinic, and so on.

Public notification:

• Hub sites will coordinate local public notification efforts with their hospitals media relations office. The Clinical Coordinating Center will coordinate national efforts with the NINDS media relations office. Public service announcements, press releases, paid print and broadcast advertising, community access cable TV, postings in existing hospital publications and mailings, and other modalities will all be used to ensure transparency has been achieved in public notification. A web site will be also be used. It will be created nationally and will have the ability to show local content to those identified by locale.

ER-EFIC Toolbox

• The Clinical Coordinating Center will provide a toolbox for these efforts. This includes pamphlets, advertising copy, and templates for IRB submissions, presentations, and reports on consultation and notification efforts. A high-production-quality series of video stimuli will be produced that can be used to make presentations more accessible to lay audiences. These feature a series of “on the street” interviews where members of the public colloquially ask questions about the nature of research, the trial, consent and why it is not possible, and how it is regulated. Short answers in simple language from experts are provided. These videos can also be strung together and used as broadcast or webcast public service announcements. A public web site is also part of the toolbox with opportunities for individual hubs to add site specific information for visitors to the site who identify themselves by location. The web site will serve primarily as a form of public notification, but will also have a link to a survey and open commentary box where by visitors can provide feedback.

Local IRB review

• To ensure that efforts conducted in all the communities participating in the NETT all meet our standards for understanding, respect, and transparency, and to promote equity across communities, we strongly encourage adherence to this plan across all the sites. We encourage IRB to participate in community presentations at each site to help explain their role, and to experience the feedback obtained. Investigators will report on their experiences and findings to their IRB using standardized templates and these reports will be collected centrally within the NETT as well. It is clearly recognized, however, that IRB may alter or supplement the plan as deemed necessary for local conditions. To enhance communication on exception from consent plans within the network, a meeting of investigators and IRB representatives from the different sites will be convened early in the process to share opinions and promote consensus.

Milestones

• The need to complete milestones in the exception to consent process to receive reimbursement payments provides incentives for efficient execution of these efforts. Anticipated milestones triggering payments will be discussed separately.

Process research

• In an effort to better understand and continually improve our exception from informed consent for emergency research processes, ethicists with a special interest in this area will study strategy and implementation in the NETT. They will attend trainings and community consultations, and will ask to interview investigators and IRB chairs. This will be limited in RAMPART and more extensive in ProTECT. If possible, please cooperate in their efforts to learn what works, what does not, and how things can be done better.

Timeline

• November – initial IRB contact, letter template, identify EMS coordinator

• End of November – IND submission, final protocol, complete CC PD plan, IRB template

• December – IRB submissions begin, identify EMS required approvals

• End of December – toolbox will include advertising copy, public web site, etc.

Timeline

• January – some centers begin CC PD, identify EMS training schedule, begin EMS train the trainers

• End of January – RAMPART ER-EFIC conference for investigators and IRB members, toolbox will have video materials for CC PD and advertising, EMS training materials

• February onward – High season for CC PD and EMS education, ongoing IRB and EMS approval processes

Timeline

• Summer – most centers expected to complete approval processes

• End of October – current scheduled delivery of experimental drug (earlier delivery under negotiation)

• Study team training, data training, and phase II EMS training takes place just prior to opening enrollment

Timeline

• End of 2008-2011– Enrollment– On-going EMS training– On-going AE reporting– One interim analysis at 350 subjects enrolled

• 2011– Last patient in – database lock– Analysis– Public notification again

nett.umich.edu