OPALS Research Protocol
RESEARCH PROTOCOL
Sudden cardiac arrest annually claims 30,000 Canadian lives and survival (4%) in most Canadian provinces is among the lowest reported in the Western world. Many feel that more lives would be saved if prehospital advanced life support (ALS) programs were widely implemented. Most Canadian communities provide prehospital basic life support (BLS; i.e. oxygen and CPR) or automated defibrillation (BLS-D; i.e. electrical countershock for lethal arrhythmias). Few provide rapid defibrillation which incorporates optimized ambulance response strategies and defibrillation by firefighters.
As well, few Canadian communities have the more expensive ALS programs that offer prehospital endotracheal intubation and intravenous (IV) drug administration. Each year, 10,000 Canadians suffer major trauma from blunt and penetrating injuries to the head, chest, abdomen, and bone. 22% of these patients die and many survivors are left with permanent disability. Another 100,000 Canadians are annually brought to hospital by ambulance with respiratory distress from congestive heart failure, chronic obstructive pulmonary disease (COPD), pneumonia, and asthma. Many of these patients require ventilator care in ICU and 18% die in hospital. Throughout the U.S. and in some parts of Canada, prehospital ALS care is routinely given by paramedics to these critically ill and injured patients. The medical literature, however, does not clearly indicate the relative effectiveness of community programs for rapid defibrillation versus ALS for cardiac arrest nor the benefit of ALS for trauma and respiratory distress. Widespread implementation throughout Canada of prehospital ALS programs would cost many millions of dollars. In this era of severely limited health care budgets, provincial ministries of health (MOH) require evidence to justify expenditures for new or existing programs.
The Ontario Prehospital Advanced Life Support (OPALS) Studyis designed to assess the incremental cost-effectiveness of community prehospital advanced life support (ALS) programs. We believe that results of this project will be invaluable in assisting provincial and municipal policy makers to determine priorities for funding prehospital care for all Canadians.
For cardiac arrest, there is no clear evidence to guide priorities for allocation of resources between competing strategies. Phase II of the OPALS Study demonstrated in 1,648 patients that implementation of community-wide rapid defibrillation programs lead to a 33% relative increase in survival (from 3.9% to 5.2%) when added to an existing, slower response BLS-D ambulance system.
An incremental cost-effectiveness analysis for various emergency medical services (EMS) systems for cardiac arrest was recently completed by the applicant and incorporated: a meta-analysis of the effectiveness of 41 EMS systems, calculation of Canadian costs, estimation of the quality of life of survivors, and a decision analysis. The study did not identify an improvement in survival among BLS, BLS-D, or ALS EMS systems and the most cost-effective system appeared to be a rapid defibrillation program. This study did not, however, consider the possible benefits of ALS for trauma or respiratory distress and was severely limited by the methodological weakness of the studies and missing data. We believe, therefore, that the framework of the OPALS Study offers a unique opportunity to assess the cost-effectiveness of rapid defibrillation and ALS programs in a methodologically rigorous fashion.
For major trauma and respiratory distress,the evidence for ALS programs is even less compelling. Endotracheal intubation may reduce neurologic sequelae for head injured patients or improve outcomes for other conditions but this has never been clearly demonstrated. Furthermore, there is significant risk of morbidity from increased intracranial pressure or aspiration when spontaneously breathing patients are intubated in the field. Similarly, recent studies have suggested that prehospital IV fluid infusion may exacerbate hemorrhage. Many studies have attempted to determine the value of prehospital ALS for trauma patients by comparing two competing strategies, rapid transportation versus field stabilization with ALS interventions. These studies are all limited by many methodological weaknesses. No studies have demonstrated improved respiratory distress patients survival or morbidity with prehospital ALS and there is some evidence that inappropriate prehospital drug therapy may actually increase mortality.
In Ontario,the MOH and partners are committed to determining the value of ALS programs. The MOH Emergency Health Services (EHS) Branch has been reluctant to fund implementation of prehospital ALS programs until their effectiveness has been clearly demonstrated and, therefore, sponsored 3 consensus conferences in 1993-94 to plan the OPALS Study. Involved were policy makers, advisors and regional managers for the EHS Branch as well as Base Hospital program and medical directors, ambulance service representatives, and health services researchers. The resultant cardiac arrest research protocol for the OPALS Study subsequently received peer-reviewed approval and funding by the MOH EHS Research Advisory Committee. The OPALS Study started in July 1994 after a public announcement by the Minister of Health. EHS has committed 15 million dollars over 5 years to the training, equipment, and salary support required for the operational component of the study in 20 Ontario communities. Subsequent Ministers of Health have reaffirmed the high priority which the MOH places on the evidence-based approach that the OPALS Study brings to EMS care in the province. Multiple organizations have contributed to the success of phases I and II, including 11 Base Hospital programs, municipal governments, local dispatch centres, ambulance services, fire departments, and hospitals.
Elsewhere in Canada, there is great variation in the configuration of EMS services among communities. Rapid defibrillation employing first responding firefighters has not been widely implemented. While some larger cities have ALS programs (e.g. Vancouver, Calgary, Edmonton), many others have no ALS (e.g. Montreal, Quebec City). Provincial MOH and municipalities throughout Canada recognize the importance of the OPALS Study and will make policy decisions regarding rapid defibrillation and ALS programs based on findings of the study.
In the U.S.,various health care payers have begun to question the value of prehospital ALS, which is available in almost all cities. U.S. policy makers understand that the OPALS Study has a unique opportunity to make a rigorous, controlled evaluation of the benefits of ALS. Such an evaluation cannot be made in the U.S.
The results of phase I of the OPALS Study should encourage municipal governments throughout Canada to enhance the role of firefighters and police officers in providing CPR and automated defibrillation for cardiac arrest. The relatively inexpensive implementation of rapid defibrillation in phase II lead to improved survival representing an additional 21 lives saved each year in the 20 study communities. We expect, based on these results (and those of the economic evaluation now in progress), that provincial MOH, municipal governments, and local ambulance and fire services will collaborate to effect rapid defibrillation programs throughout Canada.
Phase III of the OPALS Study will measure the incremental benefit and cost-effectiveness of adding an ALS program to a system with rapid defibrillation. The results are awaited with great interest by the Ontario MOH EHS Branch and will likely be used to make important emergency health services funding decisions throughout Canada. Provincial ministries of health and municipalities may choose to expand ALS services (if shown to be effective) or to curtail ALS (if shown not to be effective). In the current era of fiscal restraint that includes hospital closings , we believe payers for Canadian health services are unlikely to continue to fund a program which has been shown to be ineffective. Indeed, we expect the results to impact the use of ALS programs worldwide. The objectives for trauma and respiratory distress are very important for policy decisions. Many EMS providers believe that the greatest value of ALS programs is for patients other than cardiac arrest victims, who comprise only 2% of ambulance transports. The objective for cost-effectiveness is a unique opportunity that is unlikely to be met by any other EMS research project.
OBJECTIVES
a)Objectives:
i) To assess the incremental benefit in survival, morbidity, and processes of care that results from the introduction of prehospital ALS programs to multiple Ontario communities for patients with a) cardiac arrest (primary objective), b) major trauma, and c) respiratory distress.
ii) To conduct an economic evaluation of ALS programs for the same patient groups by estimating the incremental cost per life saved and per quality-adjusted life year.
b) Hypotheses:
Comparing the intervention period (after introduction of ALS) to the control period (before ALS), separately for cardiac arrest, trauma, and respiratory distress patients:
i) Survival (primary hypothesis) will be improved.
ii) Quality of life of survivors will not be reduced.
iii) Disability will not be increased.
iv) Process of care measures will be improved.
v) The incremental cost per quality-adjusted life year will be economically attractive.
METHODS
a) The Study Design is "before-after" with the unit of study being all eligible patients seen during two distinct periods before and after the introduction of ALS programs. Use of randomized or concurrent control designs were considered and discarded as not being feasible (see Assessment). For cardiac arrest patients, the control period is the completed 12-month rapid defibrillation period (OPALS phase II) and the intervention period will be the 36 months after the full introduction of ALS programs. The study periods will each be 36 months in duration for major trauma patients and six months for respiratory distress patients.
b) The Study Intervention is the implementation by each Base Hospital of a program of prehospital ALS that includes:
i) endotracheal intubation,
ii) IV therapy, and
iii) administration of IV drugs.
BLS-D attendants will be trained according to the Canadian Medical Association standards for EMT Level III at the Michener Institute in Toronto.
c) The Setting will be the 20 OPALS Study phase I/II urban/suburban Ontario communities which have populations ranging from 12,000 (Lindsay) to 750,000 (Ottawa-Carleton). All achieved the phase II target rapid defibrillation response time interval for at least 12 months.
d) The Study Population will be:
i) for cardiac arrest, all patients who suffer arrest (absence of a detectable pulse, unresponsiveness, and apnea) of presumed cardiac etiology and for whom EMS resuscitation is attempted, following the Utstein guidelines;
ii) for major trauma, all patients who have suffered injury from any mechanism with an Injury Severity Score (ISS) >12, who are transported by land ambulance within the study communities, and who are entered into the Ontario Trauma Registry (OTR) Comprehensive Data Set by virtue of being treated at one of the 13 trauma hospitals in Ontario (where most Ontario major trauma cases are transferred);
iii) for respiratory distress, all patients with a chief complaint of shortness of breath defined as: a) ACR problem codes 03, 05, 06, or 08, and b) prehospital assisted ventilation or abnormal respiratory rates (> 24 or < 10). Excluded will be patients under the age of 16 years. The appropriate institutional research ethics committees have approved the OPALS Study.
e) Data Collection will be conducted by the 11 Base Hospital sites and the Ottawa data collection centre and will include: Ambulance Call Reports (ACR), rhythm records, dispatch reports, in-hospital records, OTR Data Set, and telephone interviews. The feasibility of obtaining this data has been clearly established in Phases I and II of the OPALS Study as well as the Ottawa-Carleton feasibility reviews for trauma and respiratory patients.
f) Outcome Measures include:
i) survival to hospital discharge, according to the Utstein style and defined as leaving hospital alive or transfer to "alternate level of care", i.e. chronic care;
ii) generic quality of life at 1-year by the Health Utility Index Mark III (HUI3);
iii) disease-specific quality of life by the five-point scale of cerebral performance category (CPC) for cardiac arrest and respiratory distress and by the 18-item 7-level Functional Independence Measure (FIM)105-108 for major trauma;
iv) process of care measures (performance of ALS procedures, response time intervals, lengths of stay [on a ventilator, in ICU, in hospital]).
g) Economic Evaluation: The cost of each intervention will be identified by itemizing and costing each of these resources. Net cost will be calculated by multiplying the amount of each resource by its unit cost and adding the result. The study will adhere to current guidelines for economic evaluation. While the main analysis will adopt a societal perspective , a secondary analysis will consider the perspective of a provincial MOH. All costs will be converted to 1997 dollars, using the Consumer Price Index. Future costs and effects will be discounted to present value at 3% per annum.
The cost of each component of patient care will be identified using standardized methods. EMS costs will be collected from each OPALS site budget, including consumables used in the field, as well as a portion of the equipment, maintenance, training and staffing costs of ALS services. Hospital costs will be obtained for 960 patients admitted during the intervention period to the London Health Sciences Centre (LHSC) or Ottawa General Hospital (OGH) (the only OPALS hospitals with fully-allocated cost models). Post-discharge costs will be collected for all cardiac arrest and a random sample of trauma (1:10) and respiratory (1:50) patients discharged alive during a consecutive 12-month interval. This will yield 224 patients (60 cardiac arrest, 86 trauma and 78 respiratory). Post-discharge costs and quality of life will be determined prospectively using a standardized telephone questionnaire every 3 month and patients will be asked to give consent for collecting this data. Out-patient physician fees, and payments for allied health care or devices will be based on the Ontario fee schedule. Costs of outpatient medications will be based on the average wholesale price, and adjusted for patient compliance. Standard methods will be used to value outpatient tests and procedures. We will assume that post-discharge costs are equal for control and intervention patients.
h) Sample Size:
i) For cardiac arrest (primary hypothesis), 5,000 patients will be required for the 36-month intervention period, based on these assumptions: two-sided a =0.05, b =0.2, phase II survival rate 5.2%, 1:3 ratio of control to intervention period patients, 40% relative difference in survival from before to after (5.2% to 7.2%), and 1,648 patients enrolled in the completed 12-month phase II period. The minimally clinically important difference, as determined by the MOHConsensus Conferences experts, is a 2% absolute difference in survival (40% relative improvement) which would represent an additional 33 lives saved each year in the study communities.
ii) For major trauma, sample size is determined by the number of available cases and will be 3,180 cases for each of the 36-month study periods. This estimate is based upon the 191 major trauma cases identified during the 12-month feasibility review in Ottawa-Carleton and would afford 80% power to detect a 3% absolute survival difference from before to after (78.0% to 81.0%).
iii) For respiratory distress, sample size is also determined by feasibility and will be 4,630 cases (which can be enrolled in two 6-month study periods). This estimate is based upon the 1,666 cases identified during the 12-month Ottawa-Carleton feasibility review (Appendix 4) and would afford 80% power to detect a 2% absolute survival difference from before to after (82.6% to 84.7%).
iv) For the economic evaluation, due to feasibility, a random sample of patients will be assessed for HUI3 scores. In survivors of cardiac arrest (n=86), mean CPC score was 1.24 (SD=0.59); mean HUI3 score was 0.72 (SD=0.22); the correlation between the two measures was r=0.54. Hence, a sample of 224 consecutive survivors will be adequate to detect a difference of 0.1 (two-tailed a =0.05, b =0.2).
THE ANALYSIS
- Effectiveness Data Analysis:
i) For cardiac arrest, the primary hypothesis of improved survival from before to after will be tested by chi-square techniques. Logistic regression will also be used to control for possible confounders that could impact on survival (age, rhythm, CPR rates, and response times). One interim analysis will be performed on the primary outcome when 50% of the intervention period patients have been accrued according to the O'Brien-Fleming technique. A priori subgroups include initial rhythm, witnessed status, community size.
ii) For major trauma, logistic regression will assess the effect of the intervention period on survival after controlling for possible confounders, following the approach of TRISS methodology, which controls for Revised Trauma Score (RTS; systolic blood pressure, respiratory rate, GCS score), Injury Severity Score (ISS) and age. A priori subgroups include age, mechanism, ISS, GCS, community size.
iii) For respiratory distress, the hypothesis of improved survival from before to after will be tested by chi-square analysis techniques. A priori subgroups include final hospital diagnosis, respiratory rate, ventilation required, age.
b) Economic Analysis: The cost-effectiveness of ALS versus standard EMS services will be assessed by using statistical and decision analytic techniques. If one program is both more costly and less effective than the other, then costs and outcomes will be reported separately. Otherwise, the incremental cost-effectiveness ratio will be calculated.
i) For the statistical analysis , the costs of each intervention will be compared using parametric or non-parametric methods and it will be assumed that there is no difference in costs incurred more than 1 year after discharge. The net cost of treatment will be calculated as the sum of EMS, hospital and post-discharge costs. For EMS costs, multivariable regression will describe the response time interval as a function of community area, population size, and number of staffed vehicles. The cost of each call will be calculated by multiplying the vehicle hourly cost by the proportion of active duty that is used to provide medical care. For hospital costs, multivariable regression will describe hospitalization at LHSC or OGH as a function of diagnosis, duration of ICU or ward stay, and other covariates. Costs of care for other study patients will be estimated using this cost function. For quality of life, multivariable regression will describe the HUI3 score as a function of the disease-specific score (CPC or FIM) and other covariates among patients who complete both measures. A similar function was previously used to transform values into utilities. HUI3 scores will be estimated for all other patients using this function. Nonparametric methods will be used as appropriate.
ii) Decision analysis is necessary to project the costs and outcomes beyond the time horizon of the study, since adoption of a shorter time may bias the analysis. The post-discharge prognosis of all patients will be modeled using standard decision analytic techniques. The impact of uncertainty in clinical and economic data will be assessed using Monte Carlo simulation, bootstrapping131 and sensitivity analyses.
LINKAGES
i) In Canada, the OPALS Study will continue to have the same strong links with the Ontario MOH, Base Hospital programs, municipalities, ambulance and fire services that have been developed since 1994. Policy makers from the Minister of Health to the Director of the EHS Branch are kept abreast of progress. Mr. A. Erlenbusch, Senior Manager for Research within EHS, is responsible for funding the scientific component of the OPALS Study. The OPALS Steering Committee meets monthly to discuss research issues and includes two EHS staff members plus Dr. M. Lyver, medical consultant to EHS. Operational issues for the study are coordinated by an EHS employee, Mr. T. Campeau, and are reviewed by an Implementation Committee which has EHS regional manager, Base Hospital, and ambulance service representatives. Municipal governments, ambulance services, and fire departments will be regularly updated about study progress.
ii) In the U.S., we have important links through a member of the Steering Committee (Dr. Daniel Spaite; U. of Arizona; principal investigator for the U.S. National Highway & Traffic Safety Administration [NHTSA]), the principal investigator (IGS; consultant for the NHTSA sponsored EMS Outcomes Project), and a co-applicant (GN; member of the American Heart Association Emergency Cardiac Care BLS subcommittee).
KNOWLEDGE TRANSFER
i) Strategies to transfer EMS program research must consider non-physician providers (ambulance officers, firefighters), those responsible for medical supervision and quality control (Base Hospital directors), managers (regional EHS, dispatch centre, ambulance service, fire department), those responsible for training and intervention standards (EHS branch), policy makers (MOH, regional health councils), and payers (provincial and municipal governments). We will use the existing strong linkages described above as well as specific strategies described below to ensure that the research findings are used to improve Canadian emergency health services. The University of Ottawa Clinical Epidemiology Unit has considerable experience in the dissemination and implementation of other health services knowledge.
ii) Diffusion relies upon the passive use of traditional scientific publications and presentations to distribute research findings and we will continue to employ these methods to demonstrate the scientific validity of the evidence generated by the OPALS Study.
iii) Dissemination involves a more active and targeted process of distributing knowledge that has been interpreted for managers and providers. We will continue to: publish a monthly newsletter targeted for EMS providers, conduct annual interactive meetings for EHS and Base Hospital staff, cooperate with media coverage of the study, conduct workshops for universities, municipalities, and professional organizations. We will disseminate study results to local and provincial decision makers throughout Canada by using: an OPALS Study website (at www.lri.ca), direct mailings, news conferences, presentations, and the resources of the Institute of Clinical Evaluative Sciences in Ontario and similar provincial agencies. iv) Implementation is the most intensive and specific strategy and usually employs local measures (academic detailing, opinion leaders, audit and feedback) to overcome barriers and to alter behaviour. We are very proud of the record of the OPALS Study in demonstrating the unprecedented collaboration of provincial and municipal agencies in 20 different communities to achieve rapid defibrillation programs and we expect similar success in implementing ALS programs. If study results are positive, we will work with provincial and municipal governments and agencies throughout Canada to assist with the local implementation of our findings. If the study shows that ALS programs are not cost-effective, we will actively disseminate those findings and encourage the local implementation of the more modest and inexpensive rapid defibrillation programs.
OPALS STUDY TIMELINES
OPALS Study Phases I & II (Completed)
10/93 - 04/94 MOH sponsored Consensus Conferences to plan OPALS Study
06/94 Research protocol approved by EHS Research Advisory Committee
06/94 Minister of Health announces funding of OPALS Study for cardiac arrest
07/94 - 06/98 OPALS Newsletter published bimonthly
07/94 - 06/96 Retrospective data collection for Phase I (5,346 cardiac arrest patients)
07/94 - 06/96 21 OPALS communities optimize systems to achieve rapid defibrillation
07/95 - 10/97 Prospective data collection for Phase II (1,648 cardiac arrest patients)
10/97 20/21 OPALS sites qualify for Phase III
10/97 - 01/98 Data analysis Phase II
02/98 - 10/98 Economic evaluation Phase II
05/97 - 02/99 Scientific presentations and publications
05/98 - 04/99 Active dissemination of results to all provincial MOH and other policy makers
05/98 - 04/02 Assist implementation of rapid defibrillation programs throughout Canada
OPALS Study Phase III (Current and Projected)
06/97 - 02/98 Ottawa-Carleton feasibility review of trauma & respiratory patients (n=1,757)
06/97 - 02/98 Linkage between Ontario Trauma Registry and ambulance records established
02/98 EHS Research Advisory Committee approvals renewal of OPALS Study
02/98 MOH EHS Branch Commitment to fund Phase III (cardiac arrest) 1998-2002
04/98 Apply to CHSRF for phase III (trauma, respiratory, and economic evaluation)
01/95 - 12/99 Training for phase III (ALS) in OPALS communities
08/95 1st OPALS ALS paramedics complete training
04/98 50% of paramedics trained - NB each site will start phase III at a different time
07/98 - 10/98 Data base and data collection tools prepared
07/98 - 10/98 Economic evaluation tools prepared
07/98 - 06/02 OPALS Newsletter published bimonthly
07/98 - 06/00 Retrospective data collection for 36-month trauma control period (n=3,180)
07/98 - 06/00 Retrospective data collection for 6-month respiratory control period (n=4,630)
07/98 - 12/01 Prospective data collection 36-mo. cardiac arrest intervention period (n=5,000)
07/98 - 12/01 Prospective data collection 36-mo. trauma intervention period (n=3,180)
07/98 - 12/00 Prospective data collection 6-mo. respiratory intervention period (n=4,630)
07/98 - 12/01 Data collection economic evaluation
12/00 Interim analysis for cardiac arrest patients
01/02 - 03/02 Final analysis for all patient groups
01/02 - 03/02 Final analysis for economic evaluation
05/98 - 06/02 Scientific presentations and publications
03/02 - 06/02 Active dissemination of results to all provincial MOH and other policy makers
03/02 - 12/02 Assist implementation of most cost-effective program throughout Canada