1. What is the Resuscitation Outcomes Consortium (ROC)?
The Resuscitation Outcomes Consortium (ROC) is a clinical research network of 11 Regional Clinical Centers (RCCs) and a Data Coordinating Center (DCC) that is studying better ways to help people who have cardiac arrest or severe traumatic injury in the out-of-hospital setting. Cardiac arrest is the loss of mechanical activity of the heart, causing the heart to suddenly stop beating effectively. Blood does not circulate, no pulse can be felt, and the patient collapses suddenly into unconsciousness. Severe traumatic injury is injury with very low blood pressure and altered level of consciousness or brain injury. The studies test if the use of promising drugs, tools, and techniques in real-world settings improves outcomes for these critically ill patients. In addition to the clinical trials, the ROC is enrolling patients into a registry of all out-of-hospital cardiac arrest and trauma events. ROC studies are being done in Emergency Medical Services (EMS) systems in 11 regions or cities in the United States and Canada.
The National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) is the lead sponsor of the ROC studies. Additional funding is provided by the NIH's National Institute of Neurological Disorders and Stroke, the Institute of Circulatory and Respiratory Health of the Canadian Institutes of Health Research, Defense Research and Development Canada, the Heart and Stroke Foundation of Canada, and the American Heart Association.
2. Why improve resuscitation strategies?
Severe traumatic injury and cardiac arrest are important public health problems. Current treatments still result in a very high failure or mortality rate. Traumatic injury is the leading cause of death in North America for persons between the ages of 1 and 44 years, and a leading cause of death in those over the age of 65 years. In addition, more than 180,000 treatable out-of-hospital cardiac arrests occur each year in the United States, with more than half occurring without warning. Only about 5 percent to 10 percent of patients who suffer cardiac arrest outside of the hospital return home after treatment. Outcomes after traumatic injury or cardiac arrest have not improved significantly in most cities for more than 30 years. Since these patients need immediate intervention to prevent death, ROC focuses on the prehospital period to conduct most of its research.
3. How will the ROC studies be conducted?
The ROC trials are testing treatments to improve survival in cardiac arrest or severe, traumatic injuries. The research will be conducted almost entirely where the patient collapses or is critically injured and before the patient arrives at the hospital. Therefore, working with EMS systems in the communities is essential. Participating EMS providers will provide standard emergency care to all patients; some patients will receive the new treatment being tested in addition to usual care.
In most cases, the participant or their representative will not be able to provide informed consent prior to treatment, as is done in most clinical trials. Instead, the ROC research studies will be conducted under federal regulations that allow a waiver of informed consent.
4. Why a waiver of informed consent?Participants enrolled in ROC research will either be in a semi-conscious or unconscious state. Life-supporting interventions must be given immediately in the field to save their life. They are too sick to consent to immediate treatment. Surviving patients and/or their authorized representatives are informed about the trial as soon as feasible after the intervention has been given.
The Food and Drug Administration (FDA) developed in 1996 specific regulations to permit research without prospective consent under carefully controlled circumstances. This is in recognition of the unique nature of emergency medical situations in which patients or family members cannot give informed consent before treatment as well as the need to allow emergency care to advance through research.
According to FDA regulations, to qualify for a waiver of informed consent, the research study must involve participants suffering from a life-threatening disease process or injury for which the current standard of care is associated with a very high failure or mortality rate. In addition, there must be reasonable evidence that the research has the potential to provide real and direct benefit to the patient. Furthermore, studies must be held to the highest ethical standards. The ROC trials have undergone multiple independent rigorous reviews to ensure that they meet these standards.
The use of a scientific trial is the "gold standard" for determining what works best for people. For treatments that must be given immediately to be effective, waiver of informed consent research is considered appropriate by federal regulatory bodies and many ethicists who study this field. The obligation to improve standard treatments that yield poor results in life-threatening conditions is also considered an ethical imperative, as is maintaining individual rights of citizens. In waiver of consent trials, citizens receive standard treatment in addition to research treatment. To be tested in this fashion, the research treatment has to have shown promise in earlier or smaller studies.
5. Has informed consent been waived in other clinical trials?
Yes. Other important studies have been conducted under the waiver of consent regulations approved by the FDA in 1996. The most notable example is the recent Public Access Defibrillation (PAD) Trial, the world’s largest test of whether community members can effectively use automated external defibrillators (AED), a device that shocks an ineffectively beating heart back into normal rhythm. The PAD trial was one of the largest studies to obtain approval for conducting emergency care research under the waiver of informed consent. The PAD Trial was an international, multi-center, randomized controlled study of two strategies for the initial care of patients with out-of-hospital sudden cardiac arrest. As part of this trial, nearly 20,000 volunteer rescuers at 24 sites in the U.S. and Canada were trained to use AEDs in community settings. Multiple local Institutional Review Boards approved the waiver of informed consent, so that patients in cardiac arrest could be enrolled in the trial. The study showed that significantly more lives could be saved in communities with AEDs and volunteers trained to use them.
6. How are ROC study participants protected when informed consent is waived?
The goal of the ROC research is to improve clinical care and patient survival while protecting research subjects. Investigators participating in ROC are among the most experienced researchers in prehospital emergency care, and they are highly committed to scientific excellence.
To qualify for a waiver of informed consent, each research study must be approved by the FDA, the National Institutes of Health (NIH), a Data and Safety Monitoring Board, and the local Institutional Review Board. If any one of these groups believes that a waiver of informed consent should be withheld for a particular study, the waiver will not be granted.
Before any ROC clinical trial begins, the study sites must meet the following additional conditions and take several steps. First, the new treatment must hold promise of success over the standard of care based on prior smaller studies. Second, the study must undergo rigorous scientific review by a Protocol Review Committee, an independent committee of the NIH. Third, the FDA must review and approve the study before it begins, and it must continue to monitor the study for safety issues throughout the study's duration.
Fourth, a local, independent group called the Institutional Review Board (IRB) (or Regional Ethics Board in Canada), must approve every study to be conducted, as well as the strategies for public notification and consultation. All citizen concerns during the consultation are reported to the local IRB. An IRB can require a change in the study design or even not allow the study to enroll patients in their local community.
Fifth, the community where the research is being conducted must be notified and consulted before the research is started, as outlined in FDA consent regulations. In addition, the community must also be notified of the results after the study ends.
Another independent group, which includes experts in medicine, ethics, statistics, and clinical trial methods, must be appointed to monitor the safety of the patients throughout the course of the study. This is called a Data and Safety Monitoring Board (DSMB). This group has access to the study outcome data and can recommend changes, including stopping the study, at any time if there is any indication of safety issues or the study is not progressing as planned. All adverse events are reported to the DSMB and the FDA.
Once the study begins, FDA regulations require that after a patient has been treated, research staff must notify the patient or their legally authorized representative of the participant's enrollment. They also provide the patient or representative an opportunity to withdraw from further participation in the study.
Any ROC studies that test treatments that do not need to be given within minutes of evaluating the patient -- such as therapies that are administered only after the patient has received other evaluation and treatment in the emergency room -- would not qualify for a waiver of informed consent. Under those conditions, the care provider would need to seek consent from the patient or their legally authorized representative before a patient could be enrolled in the study.
7. What is the community’s role in the ROC research?
Community consultation provides an opportunity for community members -- that is, potential study participants and their family members -- to provide feedback to the researchers. The community is made aware that informed consent will not be obtained for most study participants. In each community, the local IRB (or Regional Ethics Board in Canada) determines the process of notifying and consulting with the community. This may take the form of public meetings, advertisements, mailings of brochures, websites, etc., with ample opportunity for public comment, questions, and debate.
The IRB is required to consider the community's concerns when deciding whether and how a research study will be conducted. The local IRB also determines whether the community needs a way for individuals to discontinue participation in the study. Local IRBs often consult with ethicists.
ROC investigators from each participating site carefully evaluate all comments, discuss cases and issues at local as well as national investigators’ meetings, seek and obtain comments from ethicists on the ROC Protocol Review Committee, as well as from the DSMB, and adjust strategies as necessary. The local IRB and FDA receive annual reports on community notification. Specific cases of citizen concerns are reported to the local IRB and evaluated by the ROC as soon as they occur. In many cases, the local researcher directly responds to concerned citizens.8. How have participating communities learned about ROC research?
The ROC has a committee to specifically deal with community notification strategies. Each clinical site has a community notification policy which has been approved by the local IRB. A number of approaches have been used, depending on what the local IRB has approved for that specific site. Some examples are:
- Meetings with community leaders or targeted groups, as well as meetings open to the general public. In some areas, ROC investigators conducted focus group meetings, typically held in local libraries, schools, churches or community centers where the investigators also elicited feedback from focus group sessions targeting adolescents and minorities.
- Public notifications using a) broadcast media (TV, radio, cable access shows), b) print media (daily and weekly newspapers, billboards, interior bus displays on the routes in the relevant counties), and c) electronic media (internet, email, local and national ROC websites), including online surveys to inform ROC investigators about public opinion on the ROC studies. For example, study information was posted on Craig’s list (a popular website for public announcements) with the toll-free number and the website address in English, French and in Spanish.
- Telephone survey (a random digit dial phone survey done by an outside agency surveying some of the counties participating in the ROC) to obtain citizen feedback.
- Notifications through targeted community groups. For example, an article was printed in the electronic version of the Cascade Bicycle Club on July 10, 2006. This newsletter, which specifically targets active cyclists who are at increased risk of injury, was sent to 35,000 subscribers.
- In some communities, the IRB has required that the ROC site make wristbands available to individuals who choose to wear them prior to the onset of an acute, life-threatening condition to signify that they do not wish to be enrolled in the study. Such wristbands have been and are being distributed upon request in these communities.
If a community expresses concern about the study at the time of community consultation and public notification, an IRB can choose to not let the study go forward. Some sites, however, have received calls from citizens who learned about the ROC during the public notification process and expressed strong interest in participating in the study.
9. Are the treatments being tested in ROC safe?
Yes. The ROC trials have undergone rigorous reviews by local and national independent review boards, as well as the FDA and NIH. These groups have determined that there is a critical need for these studies and that the studies meet the highest scientific and ethical standards.
Studies conducted with waived consent are approved only when the best available scientific evidence suggests that the new treatment shows promise of success over the current standard of care. In the current ROC clinical trials, all participants will receive usual care (standard therapies that are routinely used). Some participants will also receive new treatments, which are added to usual care. The scientific evidence suggests that the new treatments have the potential to significantly improve survival compared to the standard therapies.
The selected participating regional clinical sites and the coordinating center that comprise ROC have a proven record of successfully conducting high-quality pre-hospital emergency care research.
The ROC studies have many levels of research review to protect patient safety. The FDA reviews and approves the proposed research before it begins. An independent group of experts convened by NIH reviews the scientific merit of the proposed research, and each protocol is evaluated for its safety. Once protocols are approved, the Data and Safety Monitoring Board (DSMB) reviews the safety features of the trial and monitors the safety of subjects throughout the study. Finally, each site undergoes a local review by an IRB that evaluates and monitors the research locally. All adverse events are reported to the DSMB, IRB and the FDA.
More information about ROC is available at https://roc.uwctc.org.