We propose to conduct a matched-pair cluster design study that compares outcome measures during three consecutive 12-month "before," "after," and "decay" periods at six pairs of "intervention" and "control" sites (Figure ) [45
]. These 12 hospital ED sites will be stratified by the classification of "teaching" or "community" hospital, and matched according to baseline cervical spine radiography ordering rates during the "before" periods. Using computer-generated numbers, sites within each pair will be randomly allocated to either intervention or control groups by our senior biostatistician. During the "after" period at the control sites, there will be no specific implementation strategies, and physicians will order radiography according to personal judgment. During the "after" period at the intervention sites, strategies will be employed to actively implement the Canadian C-Spine Rule into physician practice. This "after" period will evaluate the time to full effect, as well as maximum effect of the implementation. During the third 12-month period – the "decay" period – implementation strategies will continue as in the "after" period. This will allow us to evaluate the sustainability of the effect of implementation, such as whether our simple and inexpensive implementation strategy can be expected to have a long-term effect, or whether there will be significant decay. Due to the nature of this intervention, blinding will not be possible.
Matched-Pair Design Allocation Scheme for "After" Period.
All alert and stable adults presenting to the study hospital EDs after sustaining acute blunt trauma to the head or neck will be eligible, and consecutive eligible trauma patients will be entered into the study. Patient eligibility will be determined based on these criteria at the time of arrival in the ED.
"Trauma to the head and neck" will include patients with either: i) neck pain with any mechanism of injury (subjective complaint by the patient of any pain in the posterior midline or posterolateral aspect of the neck); or ii) no neck pain, but all of the following: some visible injury above the clavicles, has not been ambulatory, and associated with a high-risk mechanism of injury (i.e., motor vehicle collision including motorcycle, pedestrian struck by a motor vehicle, bicycle collision, fall greater than or equal to 3 feet or 5 steps, diving, or contact sport with axial load to head and neck).
"Alert" is defined as a Glasgow Coma Scale [46
] score of 15 (converses, fully oriented, and follows commands).
"Stable" refers to normal vital signs as defined by the Revised Trauma Score [47
] (systolic blood pressure 90 mm Hg or greater, and respiratory rate between 10 and 24 breaths per minute).
"Acute" refers to injury within the past 48 hours.
Exclusion criteria include: a) patients under the age of 16 years; b) patients who do not satisfy the definition of "trauma to the head and neck" as defined above (e.g., patients with neither neck pain nor visible injuries above the clavicles will be excluded); c) patients with Glasgow Coma Scale score less than 15; d) patients with unstable vital signs (systolic BP < 90; respiratory rate less than 10 or more than 24); e) patients whose injury occurred more than 48 hours previously; f) patients with penetrating trauma from stabbing or gunshot wound; g) patients with acute paralysis (paraplegia, quadriplegia); h) patients with known vertebral disease (ankylosing spondylitis, rheumatoid arthritis, spinal stenosis, or previous cervical spine surgery); or i) patients who return for reassessment of the same injury.
We are convinced that the use of the Canadian C-Spine Rule is accurate and reliable, and that the proposed study will respect patient safety at all times. Use of the rule will be encouraged, but the decision to order radiography will always be at the discretion of the attending physician, as it is at present. Physicians will know that they can "override" the rule at any time when they have concerns about patient welfare. The Canadian C-Spine Rule has proven to be very sensitive in identifying CSI and, in fact, one could argue that the rule is more accurate than Canadian emergency physicians. We do know that, in current Canadian practice without the rule, patients are being discharged from the ED with undiagnosed fractures. We expect this occurrence to be less frequent in the proposed study when the rule is available as a guide.
All the respective research ethics boards have approved the study without the need for informed patient consent at the time of the ED visit. During a particular period in time at a given site, all eligible patients will be managed by the physicians in the same manner, because the unit of study allocation is the hospital, not the patient. As is typical of cluster allocated, matched-pair design studies, individual patients will not be randomized and physicians will order cervical spine radiography in a similar fashion for all patients at their site [48
]. Patients will not be subjected to new therapy, invasive procedures, undue risk or discomfort, or use of diagnostic radiography beyond that which would normally be required in the course of patient care. Physicians will be encouraged to use the Canadian C-Spine Rule as a guide for ordering radiography, but will ultimately base their decision on their own judgment as to what is the safest way to manage each individual patient. We note that Canadian physicians are already selective in ordering C-spine radiography, and omitted radiography for 28.3% of cases in phase II. At the same time, we know that the physicians missed some fractures. Patient confidentiality will be maintained throughout the study, and patient names will be removed from all records. The small numbers of patients who are selected for follow-up telephone interviews will have an opportunity to give verbal consent to the ED registered nurse who makes the call. This is consistent with the approach approved by the research ethics boards for follow-up in phases I and II. The safety of the study will be overseen by an independent data monitoring safety board, comprised of a biostatistician, an emergency physician, and a neurosurgeon. This board will have the mandate to terminate the study at any time should there be concerns about adverse patient outcomes.
The study setting will be six "teaching" and six large "community" hospital EDs, with a combined annual ED volume of approximately 670,000 patient visits. We believe that the generalizability of our findings will be greatly enhanced by including both teaching and community hospitals from a variety of cities (population range 30,000 to 4,000,000) in different areas of Canada. We define a "teaching" hospital as one that is a core educational institution for a medical school's undergraduate and postgraduate students, and whose hospital staff physicians have full-time appointments to that medical school. "Community" hospitals may provide experience for some medical trainees, but the majority of patient care is provided by staff physicians who do not have fulltime appointments with a medical school.
No specific interventions will be undertaken to alter the cervical spine radiography ordering behavior of the ED physicians. These sites will exemplify the impact of "diffusion" of new medical information. The Canadian C-Spine Rule will be familiar to some clinicians because of the publication of our phase I results in JAMA in October 2001, as well as scientific presentations at national meetings in Canada and the U.S. and a few presentations at continuing education meetings in Canada.
We intend to pursue simple and inexpensive strategies to actively implement the use of the Canadian C-Spine Rule at the intervention sites. Therefore, we have designed an intervention that we consider is deliverable throughout Canadian settings with few additional resources.
Details of planned interventions
Each ED physician group will be asked to discuss and agree to a policy of ordering cervical spine radiography for alert and stable trauma patients according to the Canadian C-Spine Rule. Minor educational initiatives for the ED physicians will include the distribution of manuscripts, pocket cards, and posters, as well as a single one-hour teaching session to review the evidence and clinical application of the Canadian C-Spine Rule. The ED and Radiology departments will collaborate to institute a process-of-care modification with a mandatory "online" reminder of the Canadian C-Spine Rule at the point of requisition for cervical spine radiography. All cervical spine radiography ordered in the ED will require that the ordering physician complete a special paper or computer-based requisition that includes the Canadian C-Spine Rule algorithm criteria. The physician must "check off" the criteria, or the radiology department will not process the request. The physician may override the rule, and order radiography according to his/her clinical judgment, but will be asked to indicate the reason. Those sites that use paper requisitions will implement a new pad of special cervical spine radiography requisitions. Those sites that order radiography by computer will have an on-screen version of the rule made available by software modification.
Rationale for choice of intervention
We have designed our intervention based upon theoretical considerations, currently available evidence, and discussions with collaborators. The theory of planned behavior proposes that behavior is determined by the individual's intentions to engage in a behavior, and the degree of control they feel they have over that behavior. Intention strength is determined by three variables: attitudes toward the behavior, subjective norms, and perceived behavioral control [49
]. ED physicians' intentions to use the Canadian C-Spine Rule would be weak if they were not convinced that the rule would reduce unnecessary x-rays, or if they thought that it was unimportant to reduce unnecessary x-rays (attitudes to the behavior), if they believed that important colleagues did not think that it was important to follow the C-spine rules (subjective norms), or if they did not think that it was possible to follow the rules (perceived behavioral controls). It is recognized increasingly that other factors (i.e., problems of information processing in busy clinical surroundings) intervene between intentions and behaviors that could result in failure to follow the C-spine rules, even if the physician intends to do so [50
]. Our interventions will target these different barriers. The educational interventions will target physicians' attitudes toward the C-spine rules. The local consensus process will target physicians' subjective norms by getting buy-in from all the local key stakeholders. The mandatory online reminder will prompt physicians to follow the rule, if they are considering radiography in alert and stable trauma patients.
Empirical evidence for our choice of intervention is available from the review by Solomon and colleagues [34
]. They suggest that local consensus processes predisposes to behavior change, especially if coupled with system changes. They also note that the combinations of educational and system changes are more likely to lead to improvements in test ordering. Grimshaw and colleagues conclude that "Reminders are the intervention that have been evaluated most ... [and]...are a potentially effective intervention ... likely to result in moderate improvements in process of care". Further, the use of obligatory reminders appears more successful than voluntary reminders [51
]. In discussion with our collaborators, these interventions appeared to be achievable and had face validity.
Outcome measures and data collection
Measures of clinical impact
The following will be collected at both the intervention and control sites during all three study periods by dedicated study personnel who will review daily patient logs, ED patient records, radiology reports, and inpatient records.
Cervical spine radiography ordering proportions will be the primary study outcome, such as the proportion of eligible blunt trauma patients referred for plain cervical spine radiography during the initial ED visit. Daily patient census logs will be reviewed to identify potential injury patients, and then ED patient records (e.g., ambulance call reports, nursing notes, and physician notes) will be assessed to determine eligibility. Radiology reports and census lists will be used to determine if cervical spine radiography was performed.
Number of missed CSI, such as number of clinically important CSI not identified during initial ED visit. We validated the safety of the Canadian C-Spine Rule with detailed follow-up of patients in phase II. In order to significantly reduce the resources required for phase III, we propose not to specifically follow all patients who do not undergo radiography in the ED. Telephone follow-up of patients is very labor intensive and expensive. Rather, we propose to institute a strategy of surveillance to identify the uncommon occurrence of a fracture missed because no radiography was ordered. The more common missed fracture cases due to mis-reading of the radiograph will be identified through the normal radiology department quality assurance processes. ED patient visit logs at each study site will be monitored for 30 days to identify return visits by patients who do not undergo radiography during their ED visit. In addition, we will review the neurosurgery patient logs at all neurosurgical centers that are the traditional referral sites for the study hospitals. In many cases, the regional neurosurgical centers will be our study hospitals. Application of the same surveillance approach, regardless of phase or intervention group, minimizes the likelihood of bias. We recognize that there is a very small risk of not identifying a missed fracture, but feel that this approach is pragmatic and feasible.
Number of serious adverse outcomes, such as development of neurological deficit after initial assessment in ED. We will use the same surveillance approach described above for identifying missed fractures to identify the extremely rare occurrence of motor weakness and disability that develops after initial assessment in the ED.
Length of stay in ED, such as the total length of stay from registration to discharge for patients who are neither admitted nor have a CSI. This will be considerably impacted by the duration of cervical spine immobilization and radiography procedures.
Patient satisfaction with ED care will be determined by a random sample of 5% of "before" and "after" period patients (both those who did and those who did not receive radiography), who will be asked via telephone interview to rate their satisfaction on a five-point Likert scale at 30 days.
Sustainability of the intervention
The same clinical impact measures will be collected during the "decay" period to determine whether the effects achieved during the "after" period have been sustained.
Performance of the Canadian C-Spine Rule
This is a secondary study outcome. The rule will be evaluated during the "after" period at the intervention sites for those cases where physicians have completed the special study requisition and checked off the rule criteria. Rule criteria are:
Accuracy of the rule, such as sensitivity and specificity for identifying clinically important CSI. In interpretation of the rule, physician accuracy will be determined by comparing the physicians' notation on the radiography requisition to the "gold standard" interpretation of the rule made by the investigators' steering committee. Attention will be focused on fractures missed or potentially missed by physician misinterpretation.
Physician comfort and compliance with use of the rule. On the radiography requisition, physicians will be asked to indicate their comfort in following the rule for that specific patient, using a five-point Likert scale. When physicians choose not to follow the rule, they will be asked to indicate reasons for non-compliance.
Economic evaluation measures
The following will be evaluated for the economic impact of the C-spine rule: radiography rates after discharge will be determined by a random sample of 5% of "after" phase patients, who will be followed by telephone interview 30 days after the initial ED visit. This will ascertain if the patient has obtained cervical spine radiography through a family physician, clinic, or ED. We also will examine the length of stay in the ED (in hospital), if admitted, hospital admission for CSI (as opposed to other injuries), and operative repair of CSI.
Measures of clinical impact
Every eligible patient who satisfies the inclusion and exclusion criteria during each of the three periods at all 12 sites will be included in the final analysis. No patient will be excluded due to non-compliance by the physicians or radiology departments. Sub-group analyses will evaluate teaching and community hospitals separately. Comparison of patient characteristics will be tested. All p values will be two-tailed. The primary analyses will compare the "before" and "after" periods. Secondary analyses will compare the "after" and "decay" periods in order to evaluate sustainability.
For the analysis of dichotomous data from this matched-pair design, a parametric approach will be used, based on the standard paired t-test (with k
-1 = 5 degrees of freedom) to the differences in the event rates in the intervention and control site pairs. Although the assumptions of equal variances and approximate normality may not be satisfied, empirical studies suggest that this test procedure is robust to departures from these assumptions [52
]. It is expected that the cluster sizes will be similar, but if they are highly variable, then a weighted t-test after transformation of the event rates to the logistic scale will be considered, as suggested by Donner and Donald [53
]. Given the small number of pairs, exact procedures based on permutation tests also will be considered. Further, 95% confidence intervals will be calculated for the relative reductions in event rates. Similarly for the analysis of continuous data, the standard paired t-test (with k
-1 = 5 degrees of freedom) to the differences in the mean response between the intervention and control site pairs will be used. If the relevant information from the previous period is available, the change from baseline for each cluster will be determined and used in the calculation of the difference in the event rate or response for each intervention and control site pair.
For each of the following clinical impact outcome variables, the change from the "before" to "after" periods in the proportions (or means) for each cluster will be determined, used in the calculation of the differences in the event rates (mean response) for each intervention and control site pair, and analyzed according to the above analysis plan. Clinical impact outcome variables include: cervical spine radiography ordering proportions, proportion of missed fractures, proportion of serious adverse outcomes, length of stay in ED in minutes and, patient satisfaction with the proportions indicating "very satisfied" or "satisfied."
Performance of the Canadian C-Spine Rule
Performance of the Canadian C-Spine Rule will be evaluated by the following measures.
Accuracy of the rule: The classification performance of the rule for clinically important CSI will be assessed with 95% CIs for sensitivity, specificity, negative predictive value, and positive predictive value. The "criterion interpretation" of the rule, such as positive or negative for CSI, will be made by the investigators based on the status of the patient for the component variables as documented by the physician.
Physician accuracy in interpretation of the rule will be calculated as the simple agreement between the physicians' notation on the requisition – to the investigators' "criterion interpretation" of the rule.
Physician comfort and compliance with use of the rule will be tabulated in a simple descriptive format.
We will adopt a decision analytic approach, whereby we will identify the incremental cost savings from both a health care sector and a societal perspective of the active strategy of implementation [55
]. The model will consider two hypothetical cohorts of patients, a "usual practice" cohort, and a cohort where practice is as dictated through the active dissemination of the decision rule. Results will be generated through probabilistic analysis, as this is superior to simple deterministic analysis [56
]. The principal resources in this analysis will be the costs of radiography and the associated patient time costs. In addition, the costs of settlement of litigation, the incremental costs of follow-up treatment due to missed fractures, and the costs of neurological deficits will be included. The design of the decision analytic model, sources of data, and analysis of uncertainty are provided in a supplemental file [58
] [see Additional file 1
Refer to the supplemental file for more details on the sample size calculation [45
] [see Additional file 2
]. The study is based on a complex, stratified, matched-pair cluster design, such as a stratification factor type of hospital (teaching vs. community), a matched-pair (hospitals matched according to baseline cervical spine radiography), and cluster randomization (unit of randomization is the hospital and unit of analysis is the patient) [45
]. Let k be the number of pairs needed to achieve power100(1-β)% for detecting a difference Δ in the cervical spine radiography event rates at the two-sided 100(1-α)% significance level. From the phase II study, the cervical spine radiography event rates for non-transfer patients at the participating sites ranged from 63.3% to 85.9%, with an average of 76% and an annual accrual per hospital of approximately 400 patients. We estimate that the between-cluster variance component is 0.00636, based on Gail et al (1992) for the COMMIT trial (i.e. Var
) = 0.0066125) [66
]. It is expected that the event rate in the control group will not change. Based on a consensus of the participating site investigators, we believe that for the intervention group, a 15% relative decrease (or an absolute decrease of 11.4% from the baseline rate of 76%) in the event rate would be considered a minimal clinically important change (i.e. Δ = 0.114). Then for a significance level of 0.05 and power of 80%, k
= 3.9891 and the number of matched-pairs required is (7/5)(3.9891) = 5.5847 where 7/5 adjusts for the small number of degrees of freedom [65
]. Thus, six matched-pair clusters will be required with 400 patients per hospital for each of the ''before'' and ''after'' periods in the primary analysis. Because the exact benefits of stratifying by teaching and community hospitals in this matched-pair design are difficult to quantify, a conservative approach is adopted and the six matched-pair clusters will be selected [67
]. Furthermore, we estimate that the sample size for the ''decay'' period will be the same as for the ''after'' period, and that this will allow sufficient power in the secondary analysis to identify complete decay of effect from the ''after'' to the ''decay'' period. In addition, this will provide a sufficient sample to calculate a precise estimate of the decay rate.
Feasibility and timing
Hence, we will require 4,800 eligible patients at the 12 sites for each of the three study periods, for a total of 14,400 patients. We plan three consecutive 12-month periods representing, respectively, the "before," "after," and "decay" periods. Based upon our knowledge of seven sites from phase II, and extrapolating from census information of five new sites, we expect no difficulty in achieving our sample size goals. Because all eligible patients are enrolled by default, and because no consent is required, we will not lose patients to physician non-compliance nor to patient refusal.
Why a matched-pair design? The matched-pair design is frequently used in community intervention studies and offers several advantages for studies like ours, in which the unit of allocation is the hospital rather than the patient. Matching on baseline data, such as radiography rates from the "before" period, helps prevent imbalance between the control and intervention groups. This design helps preserve power of analysis when relatively few (12) clusters are being studied.
Why three study periods? The "before" period will provide the baseline radiography rates, which will be the basis for the matching and the baseline for measuring change. The "after" period will measure the time to onset of the effect of the intervention, as well as the maximum effect. The "decay" period will allow us to evaluate the sustainability of the effect of implementation, such as whether our simple and inexpensive implementation strategy can be expected to have a long-term effect.
Will incorporation of phase II sites in phase III lead to contamination? Seven of the 12 sites participated in phase II, which will end at least six months prior to the onset of phase III. We believe there will be little or no carry-over effect on physician behavior in phase III because physicians did not apply the rule in phase II, but continued to order radiography according to their judgment. If anything, physicians ordered radiography at a higher rate (71.7%) during phase II than during the phase 0 baseline (58.0%).