This review of systematic reviews has been conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement [12] and the recommended methodological considerations when using existing systematic review as described by Whitlock et al [13].

On February 22, 2016, electronic searches were conducted on the MEDLINE, Cochrane Library, LILACS, and IEEE Library databases. To identify the EHR concept, standards for interoperability, and health information and its cost benefits, the search strategy was:

((“Electronic health records”[MeSH Terms] OR “Health Information Exchange”[MeSH Terms] OR (“Health Information Management”[MeSH Terms] OR (“Medical Informatics” [MeSH Terms]) AND (“Interoperability” OR “Standard of Information”)) AND (“Cost-Benefit Analysis”[MeSh] OR “Evaluation Studies”[Publication Type] OR “Program Evaluation”[MeSh] OR impact or effectiveness)

The search was limited by language of publication (English, Spanish, French, Italian, and Portuguese), studies in humans, type of study (systematic reviews and meta-analyses), and year of publication (since 2005). Two systematic reviews that satisfied the criteria were identified manually. To better define certain eHealth technology descriptions, additional sources of evidence were considered.

The inclusion criteria were as follows:

Studies in primary or secondary care scenarios, studies without the primary or secondary impact of eHealth actions, and duplications were excluded. Titles and abstracts of retrieved papers were independently screened and evaluated by 2 investigators (ZSNR and TAM). Abstracts providing insufficient information were retrieved for independent, full-text evaluation by 2 investigators to determine study eligibility. Disagreements were resolved by consensus. Additional publications were identified using the reference lists of selected manuscripts.

ZSNR prepared electronic data with paper contents abstracted using StArt software (Systematic Review System) to organize the analysis [14]. The data extraction of full-text analysis included the following: study design, number of studies evaluated, objectives, type of interventions/clinical data sources, eHealth interventions and terminology, interface/health information exchanges, duration of follow-up, cost-effectiveness, impact on quality of care, main results control group, potential bias, limitations, and lessons learned. The results were summarized into two subgroups according to the modality of intervention:

The methodological quality assessment was based on the AMSTAR (a measurement tool to assess systematic reviews) checklist [15].

Evidence of the cost-effectiveness of eHealth interventions that met the criteria was identified. Only one systematic review of the six performed a meta-analysis [16]. The quality assessment of the included studies followed AMSTAR (a measurement tool to assess systematic reviews) methodology and resulted in wide variability of the quality score. Two studies were classified with a moderate rating of quality with 5 positive points among 11 items [16,17], whereas other reports neglected many AMSTAR criteria [18-21]. Table 1 summarizes the quality assessment ratings, the study design, and the funding or support of the six included systematic reviews.

Table 2 summarizes the objective, the type of intervention/clinical data sources, eHealth intervention and terminology, interface/health information exchange, and duration of follow-up of the six included systematic reviews.

Among the included systematic reviews, only one was classified as showing an effect on eHealth implementation without electronic health information exchange (Subgroup 1), and the other five were ranked as showing effects of systems implementation with incorporated health information exchange among other electronic data sources (Subgroup 2).

This study found preliminary benefits in the use of electronically available inpatient data systems on the quality of care. Despite the limited number of studies that met the eligibility criteria, the heterogeneity of electronic systems reported, and different interventions on hospital routines, the identification of preliminary secondary benefits on patient mortality was possible [16]. eHealth systems with information exchange functionalities also showed potential impact on quality of care or patient outcomes. From five studies, one had inconclusive results on direct patient care [17] and four presented partial effects, as nursing staff efficiency led to a faster call response, a decrease in unplanned ICU admissions and hospital mortality [18], improvement of health data quality [17,18], and more efficient surveillance programs inside hospitals [19,20]. It is expected that the systems able to share health information would improve care at the time and point of attention, especially the surveillance systems and those that use common terminologies and vocabularies to support consistency in information collection [6,19,20,22].

However, no substantial review regarding the impact of electronic interventions on cost-effectiveness was identified. Among the six analyses included, only Thompson et al reported that some preliminary studies have identified decreases in cost, but the heterogeneity and the absence of information of follow-up impaired a proper analysis of cost-effectiveness [16]. Immediate cost savings are not anticipated for organizations when choosing to adopt eHealth strategies because the high cost of implementation limits the transition from paper-based to electronic systems and represents a significant challenge to their widespread adoption [23]. Regardless, medium and long-term positive results are expected, and the World Health Organization (WHO) recognized overall eHealth as cost- effective and secure [24]. Potential indirect cost saving was mentioned as a secondary outcome in three studies, with the reduction of person-hours harming surveillance and the increase in time spent on direct patient care [17,18,24].

Unfortunately, no study about interoperability, in the sense of syntactic and semantic meaning, on cost benefit was identified. Importantly, none of the studies in this review properly defined EHR concept as a longitudinal health record with entries by health care practitioners in multiple sites of care or mentioned interoperability applications among electronic systems. However, taking the antecedent step toward full interoperability, an effective information sharing between stakeholders and systems can be attained through the use of standards [6]. Standards adoption for the exchange of clinical data was mentioned in four studies [18-21], mostly terminologies adoptions, but the potential impact of such tools on continuity of care or costs remains an open question that needs investigation. Although within the limits of hospital systems, the analysis confirmed the potential to positively impact physician practice organizations, as previously reported [23]. Further longitudinal research is needed to determine the actual impact of eHealth adoption on health care costs and clinical outcomes.

The current results should be interpreted as a whole with the study limitations. Only four major databases were searched and gray literature sources were not evaluated. Additionally, the limitation to English, Spanish, French, Italian, and Portuguese languages prevented the capture of all relevant studies. Furthermore, the quality of included studies was poor, and they varied regarding the type of eHealth interventions, follow-up time, and goals. This systematic review summarized primary and secondary outcomes from different classes of intervention from which to draw results, analysis, and conclusions. Due to the variation in scenarios and lack of numeric goals, a meta-analysis was considered inappropriate.

This review identified some benefits on the quality of care but did not provide evidence that the eHealth interventions had a measurable impact on cost-effectiveness, mortality, or LOS in hospital settings. Preliminary evidence indicates that the use of eHealth interventions with information exchange may improve clinical process outcomes. The absence of studies precludes the assessment of impact of interoperability on benefits of health care or cost, and this aspect needs further research. Technological barriers might influence eHealth solutions implementation and data exchange for systems integration or interoperable interfaces. There are also issues with the lack of standardization of most aspects of health information and misuse of terms in the scientific publications. Authors should be explicit when they are using interfacing syntactic interoperability or semantic interoperability to reduce the confusion with different health information exchange possibilities. Further research with long-term follow-up is needed to determine the actual impact of eHealth adoption on health care costs to demonstrate (1) value for money (including clinical impacts) and (2) the clinical impact of semantic and synthetic interoperability.