The main finding of this study is that care delivered using CPs to patients with stroke was significantly more evidence-based than that delivered to patients with stroke receiving UC, and this seemed to translate to more effective treatment, because implementation of CPs resulted in a significant improvement of the outcomes.
There are several potential (and not mutually exclusive) explanations for these results, ranging from selection bias to improved performance. Selection bias may have occurred both at the individual and cluster levels. At the cluster level, no differences emerged; however, after randomization, some differences were seen between the CP and non-CP groups at the individual level. Therefore, interpretation of the outcomes before randomization could have been biased. Moreover, we could not use the National Institute of Health Stroke Scale (NHISS), because the study started before validation of this instrument in 2009 . Patient assessment before admission was partly performed, therefore the severity of stroke was not properly assessed. Except for mortality measures, we found a significant drop in sample size for certain outcomes in the non-intervention group. Thus, this may limit our findings regarding outcome improvement. However, CP use remained a significant determinant of the improved patient outcomes even after adjusting for potential confounders, including comorbidities at baseline and complications during the hospital stay. Therefore, the influence of selection bias, if any, is likely to be minor .
A second possible explanation for our findings is the different use of organized care in the two groups. The use of organized care and the access to the stroke units was were significantly higher in the CP group. Because use of organized care and stroke units are integrated approaches to managing stroke and are strong evidence-based independent predictors of in-hospital mortality, they were used as 'active components' promoted by the implementation of the CP [8, 24]. Therefore, the observed improvements in organized care and in use of stroke units and their positive effect on patient outcome were expected as part of the intervention.
With regard to outcomes, our results show how evidence-based care can be effectively implemented in real-world settings [6, 11]. Indeed, the use of evidence-based care was significantly improved in the CP group, which also made better use of the organized care, as mentioned above. These findings were apparent despite the complexity of objective evaluation of stroke, as has been reported by the primary stroke center certification program and the performance measurements of the Joint Commission [44–46]. Our findings were mostly based on short-term outcomes. Long-term and/or more qualitative outcomes, such as patient satisfaction and quality of life, were not evaluated. This was mainly due to the information system, especially in the method of documenting and collecting data (clinical records, paper-based abstraction tools), and could also be a limitation of our findings [12, 47].
In the study, we found a significant reduction only in 7-day mortality, whereas 30-day mortality was not significantly affected by the use of CPs. The 7-day mortality depends more on the early treatment of patients, but no specific protocol for factors influencing early arrival was implemented in the CP. Therefore, it is possible that the CP hospitals might have admitted patients earlier, and this would have artificially reduced their short-term in-hospital mortality rate. Although we did not have specific data on the events before admission, it is reasonable to assume that the randomization process would have controlled for this possible bias. However, after risk adjustment, the CP method remained a significant determinant of reduced 7-day mortality. Moreover, at discharge, patients in the CP group had a significantly higher rate of return to pre-stroke functioning compared with the UC group, and the process of care was significantly more consistent with evidence-based care. Based on our findings and those of other authors, we consider it reasonable to believe that the better outcomes observed for the CP group are attributable to an improvement in the quality of care achieved with the use of CPs [11, 44, 48, 49].
A limitation of our findings is that we could not examine the effect of CPs on the use of reperfusion therapy (tissue plasminogen activator; tPA), because in Italy the non-experimental use of this procedure was authorized only after the conclusion of this study. Early treatment based on tPA involves the expertise of several professionals, which can result in poor coordination or inefficiencies in the care process. Indeed, several studies have shown that tPA use in acute ischemic strokes can be enhanced by organized care, routine use of protocols, and multidisciplinary teamwork, which the current study also showed identified as active components of the implemented CP [48, 50]. Therefore, our findings suggest that the use of CPs through the implementation of better care might also be helpful for the effective use of tPA, but specific studies are required.
Because CPs are quality improvement initiatives it was not possible to blind the intervention or the assessment of the outcomes. Therefore it could have been that the awareness and attention associated with receiving a new intervention (Hawthorne effect) was responsible, in part, for the improved outcomes associated with the CPs. Given the type of intervention, a cluster randomized design was the most appropriate design to use [19, 22, 27, 40]. However, these studies have some limitations when applied to CPs . Indeed, context level adaptation, which is essential for the pathways to succeed, may be perceived as inappropriate in the trial design. Also, it may be difficult to replicate and maintain the original intervention. To reduce such issues, we implemented pathways that combined local standards with evidence-based indicators to maintain the integrity of the intervention at each site [21, 52].