Toronto Site
Arthur Slutsky, MD
Principal Investigator
arthur.slutsky@utoronto.ca
Laurie Morrison, MD
Co-Principal Investigator
laurie.morrison@sw.ca
Paul Dorian, MD
Co-Principal Investigator
dorianp@smh.toronto.on.ca
Dear Research Ethics Board Chair/Coordinator:
This letter is written to the Research Ethics Board Chair/Coordinator of all Research Ethics Boards
that are likely to be asked to approve protocols for clinical trials in resuscitation research from cardiac
arrest or traumatic injury conducted by the Resuscitation Outcomes Consortium (ROC). This network
recently began operation in the US and Canada. Your Board will also be asked for approval of access
to critically important data related to the in-hospital care and survival of patients who are victims of
out-of-hospital cardiac arrest and/or traumatic injury and hospitalized at your institution. This letter will
describe the goals and commitments of the sponsors of this research. Funding for this consortium
began September 1, 2004, and will continue for nearly five years. Ten regional clinical centers (one in
your community) and one data coordinating center were chosen by the National Heart, Lung and
Blood Institute (NHLBI) after a peer review process. A steering committee comprised of members of
the regional centers, the data coordinating center, the NHLBI, and the study chairs govern the ROC
(see attached addendum for additional details).
Goals and plans for the Resuscitation Outcomes Consortium
Current resuscitation practice is based largely on empirical observation and findings from animal
research. Few controlled studies have been conducted to establish the actual benefit of interventions
presently employed. Results of basic research that have improved our understanding of the complex
biochemical pathways involved in shock and cardiac arrest have not yet greatly affected resuscitation
procedures and subsequent patient outcomes. Both the immediate pre- and post-resuscitation
dysfunctional phases represent critical periods that are under-investigated and that may be amenable
to therapeutic interventions to improve patient survival. The timing and selection of resuscitative
interventions and the ability to administer them effectively pose scientific and logistic challenges
shared by both trauma and cardiopulmonary arrest investigators.
The general aim of ROC will be to conduct multiple randomized trials to evaluate strategies to treat
both cardiac arrest and patients severely injured, with an emphasis on those that begin in the out-ofhospital setting.
Objective of ROC
The primary objective of each study conducted by the ROC will be to:

Evaluate whether interventions for cardiac arrest and life-threatening trauma are effective at
reducing morbidity and mortality.
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The key to achieving that objective will be to:


Develop collaborations between the community, community emergency service providers and
clinical research centers to permit resuscitation research early after injury or arrest.
Develop collaborations between the community, hospitals, and clinical research centers to
permit routine acquisition of outcome data.
Examples of Protocols to be Presented for REB Review
Specific Interventions
It is understood that full and detailed protocols will be submitted to all Research Ethics Boards for
approval. ROC has chosen a trauma protocol to implement and is developing a proposal for a
registry. In addition, a couple of cardiac arrest protocols are under consideration. Both trauma and
cardiac protocols will also be targeting two special populations: children.
Trauma Protocol
In the area of research as to survival from traumatic injury, we intend to conduct a randomized trial
comparing types of fluid resuscitation begun in the field immediately following severe traumatic injury.
We intend to randomly allocate patients to receive (1) routine fluid replacement therapy with normal
saline, (2) 7.5% hyperosmolar fluid replacement, and (3) fluid replacement with 7.5% saline plus
dextran 60. Two patient groups would be included in the study – those with evidence of blood loss
and circulatory compromise and those who have evidence of significant traumatic brain injury. The
two studies would be conducted concurrently. The primary outcome studied will be 28 day survival in
the hypotensive group and neurologic status at 6 months after injury in the brain injury group.
Cardiac Arrest Protocols
Which cardiac arrest trial will be implemented first has not yet been finalized but will likely be within
the next month. One potential study is of a valve apparatus which enhances venous return and
perfusion during cardiopulmonary resuscitation. This is accomplished through manipulation of airway
resistance in patients ventilated, or through an endotracheal tube, mask or other device, as is routine
in individual clinical centers within the network. The comparison in this study would be between a
dummy valve which offers no manipulation of airway pressure, and an airway valve which does
manipulate airway pressure such that negative intrathoracic pressures are generated between chest
compressions resulting in increased venous return to the central circulation and in turn increase
perfusion on subsequent chest compressions. This device shows benefit in experimental animals and
pilot studies in man in which there is a clear trend toward benefit. No significant safety issues have
been identified. The other potential cardiac arrest study would compare two different strategies of
initial treatment of ventricular fibrillation and pulseless ventricular tachycardia. In the first strategy
electrical therapy (defibrillation) would be applied immediately upon viewing the rhythm while in the
second strategy a period of CPR would be delivered prior to defibrillation. Animal models support the
concept as well as an observational study and a small randomized trial.
Clinical Trial Applications (CTA) for both the hypertonic saline and valve protocols must receive a ‘no
object letter’ from the Therapeutic Products Directorate (TPD) – Health Canada before they can be
conducted. But, we anticipate that such approval will not be a major obstacle to either of these two
studies as smaller NIH supported human studies are ongoing in these two areas. Of course, as
detailed protocols are finished and approved through the usual National Institutes of Health (NIH),
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Food and Drug Administration (FDA) and the TPD review process, they will be forwarded to the
individual Research Ethics Boards. Both of these studies will require justification and compliance with
the Canadian Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, Article
2.8 Research in Emergency Health Situations.
ROC International Resuscitation Registry
ROC investigators are developing a standardized reliable and valid registry of out of hospital cardiac
arrest and life threatening trauma cases that facilitates assessment of secular changes in
epidemiology and outcome of prehospital resuscitation, implementation and interpretation of ROC
interventional trials, and quality assurance of EMS practices. This database will describe the
incidence of out-of-hospital sudden cardiac arrest and life-threatening traumatic injury using
standardized definitions; describe structure, process and outcome of care before and during hospital
care for cardiac arrest and traumatic injury; enable a rigorous assessment of the potential causes of
outcome variation; describe secular changes in the epidemiology and outcome; determine whether
ongoing monitoring of EMS outcomes improves data quality or clinical outcome. This will require
storing the deidentified data acquired from EMS services and inhospital outcomes in a single data
warehouse in compliance with existing privacy legislation and ethical guidelines. Only aggregate data
will be reported.
Hospital Outcome Data
Another major issue that will need to be deliberated by the Research Ethics Board is the approach
that the investigators will need to take to gain outcome information including survival and in-hospital
data about complications, care delivery, and costs for patients entered into the study in the out-ofhospital arena and surviving to enter the hospital. We recognize the value and importance of the
adherence of Canada’s federal privacy law, the Personal Information Protection and Electronic
Documents Act 2000 (PIPEDA), and the Ontario privacy legislation, the Personal Health Information
Protection Act 2004 (PHIPA), in preserving patient confidentiality and the need where possible to
obtain informed consent for the subsequent follow-up of the patient in the research study.
Out-of-hospital cardiac arrest has a mortality rate nationwide of approximately 95%, and for severe
traumatic injury of at least 50% when one includes long-term disability. It is our intent to characterize
the EMS system and public aspects of programs in cardiopulmonary resuscitation in individual
communities within the consortium related to resuscitation outcomes. We believe that it will be of
tremendous value to the health of the public to understand those aspects of cardiopulmonary
resuscitation performed routinely which result in better outcomes versus those that result in
disappointing outcomes. We are interested in studying the quality of specific aspects of CPR and
resuscitation methods such as chest compressions and ventilations as they are performed in the field.
Such studies cannot reach their goal of improving quality of care and outcome unless they are related
to survival to hospital discharge as well as cost of care related to the resuscitation provided in the
field and throughout the hospital.
Working Together to Improve Human Health
Our hope is that we can work closely with you in pursuing these research objectives that have such
remarkable promise to increase the survival from the devastating events of cardiac arrest and
traumatic injury. We believe at this time in the US and Canada that there are some 250,000 to
400,000 cardiac arrests occurring yearly making this arguably the single most quantitatively
significant mechanism of cardiovascular death in this country. In the area of traumatic injury, a similar
picture is present where severe traumatic injury in the United States results in 2.6 million admissions
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and 150,000 deaths per year. We hope and anticipate that the remarkable improvement in survival
that has occurred in other cardiovascular and vascular conditions such as heart attack (acute
myocardial infarction) and heart failure will result here. There is no question that clinical trials and
outcome research are the ways in which advancements have been made in these other conditions.
The recent publication of the Public Access Defibrillation Trial, in the New England Journal of
Medicine shows the value of such approaches. That study showed that in public places where
defibrillators are placed and lay volunteers are trained to use the defibrillators, we can increase
survival from out-of-hospital cardiac arrest by a factor of two. The estimated survival rate in these
public settings was increased from approximately 17% to 34% by the distribution of defibrillators and
training the lay public. This study randomized individual facilities rather than individual patients, but a
waiver of informed consent was obtained and outcomes data were obtained on nearly 100% of all
patients who were entered into this study.
Thank you very much for your consideration and help. We anticipate working closely with you to
achieve the goals of the Resuscitation Outcomes Consortium.
Sincerely,
Laurie Morrison, MD, M.Sc., FRCPC
Co-Principal Investigator
On behalf of
Arthur Slutsky, MD, Principal Investigator
Paul Dorian, MD, Co-Principal Investigator
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