A Systematic Review of Educational Interventions and Their Impact on Empathy and Compassion of Undergraduate Medical Students

Introduction: A compassionate and patient-centered care leads to improved clinical outcomes. Promoting empathy and compassion of medical students is a forerunner of their well-being, emotional stability, and a patient-centered care. However, there is slender evidence about best educational interventions that can inculcate empathy and compassion skills. Our objective was to conduct a systematic review of research evaluating the associations between spectrum, effectiveness, frequency of teaching modalities and their outcomes on compassion and empathy to highlight best practices. Methods: We searched the Web of Science, PubMed, Scopus, and EBSCO Host on 22nd July 2020. We adapted our search strategy from a previously published systematic review on education for compassion and empathy. Selected studies were required to have used unique educational interventions for promoting empathy and compassion of medical students. The research questions were based on Participants (medical students), Intervention (empathy and/or compassion related teaching), Comparison, and Outcome. Results: We analyzed 24 articles from the initial yield of 2,861. Twenty-two were quantitative studies with a mean of 12.8 on MERSQI. Twelve were randomized controlled trials while 5 measured outcomes with single group pre- and post-tests. There was no association found between duration, frequency and complexity of an educational intervention and its effectiveness. Twenty used multimodality curricula, and of those 18 reported statistically significant positive improvement in empathy, while 3 of 4 single modality were effective. Only three studies looked for long-term effects of educational interventions. Fourteen studies evaluated Kirkpatrick's level one (self-reported knowledge), 2 level three (behavior), and 6 level four (patient outcomes). We identified six major educational constructs of teaching empathy and compassion; communication, mindfulness, early clinical exposure, technology-enhanced learning, comics and arts and culture. Discussion: Our review couldn't identify a standard teaching construct in place and highlighted that different teaching tools carry similar impact in promoting compassion and empathy and a sustainable program rather than a single training activity is essential.

Introduction: A compassionate and patient-centered care leads to improved clinical outcomes. Promoting empathy and compassion of medical students is a forerunner of their well-being, emotional stability, and a patient-centered care. However, there is slender evidence about best educational interventions that can inculcate empathy and compassion skills. Our objective was to conduct a systematic review of research evaluating the associations between spectrum, effectiveness, frequency of teaching modalities and their outcomes on compassion and empathy to highlight best practices.
Methods: We searched the Web of Science, PubMed, Scopus, and EBSCO Host on 22nd July 2020. We adapted our search strategy from a previously published systematic review on education for compassion and empathy. Selected studies were required to have used unique educational interventions for promoting empathy and compassion of medical students. The research questions were based on Participants (medical students), Intervention (empathy and/or compassion related teaching), Comparison, and Outcome.
Results: We analyzed 24 articles from the initial yield of 2,861. Twenty-two were quantitative studies with a mean of 12.8 on MERSQI. Twelve were randomized controlled trials while 5 measured outcomes with single group pre-and post-tests. There was no association found between duration, frequency and complexity of an educational intervention and its effectiveness. Twenty used multimodality curricula, and of those 18 reported statistically significant positive improvement in empathy, while 3 of 4 single modality were effective. Only three studies looked for long-term effects of educational interventions. Fourteen studies evaluated Kirkpatrick's level one (self-reported knowledge), 2 level three (behavior), and 6 level four (patient outcomes). We identified six major educational constructs of teaching empathy and compassion; communication, mindfulness, early clinical exposure, technology-enhanced learning, comics and arts and culture.
Discussion: Our review couldn't identify a standard teaching construct in place and highlighted that different teaching tools carry similar impact in promoting compassion and empathy and a sustainable program rather than a single training activity is essential.

INTRODUCTION
The quality of the interaction between physicians and patients influences patient outcomes in clinical settings (1,2). A fundamental pillar of the healthcare mission is based upon compassionate care that forecasts greater patient trust and satisfaction, superior patient-physician connections, and better patient outcomes (2,3). Within healthcare organizations, compassionate care entails diverse responsibilities of healthcare professionals in explaining their roles, establishing rapport, and in spending time on attentively listening to the patients' concerns (4). Compassionate healthcare-a key competency is characterized by reflections of others' concerns, respect for persons, and contextualized understanding of the patient as a key player of healthcare systems (5).
The two leading elements of patient centered care include empathy and compassion. Empathy refers to "a capacity to understand but without joining the feeling of the patient" (6) while compassion refers to "the feeling that arises in witnessing another's suffering and that motivates a subsequent desire to help" (7). In the medical field, empathy pertains to a multifaceted strand with moral, cognitive and behavioral enlightenment (8). When applied with objective reasoning, empathy promotes the impact of medical care and facilitates physician-patient communication (9). Empathy, being a multi-construct concept, includes, but not limited to, physicianpatient interactions, interprofessional practice, self-compassion, empathy for others' pain, professional identity formation, stress awareness, and self-reflection and communication. Empathetic communication in patient-physicians interactions fosters information exchange and the impact of understanding and adherence to management plans, which lead to an early return to work, pain relief, mood elevation, and improved functional status of patients (10). Both empathy and compassion are generally considered to be interchangeable terms. However, empathy (understanding of patient feelings) is necessary to trigger compassion (emotional response including actions to alleviate patient sufferings) (11).
There is a compelling evidence in literature that treating patients without compassion can lead to deleterious outcomes (12). An absence of compassionate care results in poor quality of care and higher risk of complications through medical errors (13). Unfortunately, despite an explicit emphasis on the vital role of compassionate patient care, healthcare professionals often miss opportunities to be compassionate, rather they pay attention to biomedical data and management plans. From another perspective, sustaining compassion in medicine is hard as "compassion fatigue" prevails in ∼20-70% of healthcare professionals (14). Compassion fatigue refers to loss of compassion in healthcare providers due to work related stress (15). Compassion fatigue certainly impairs the ability of healthcare providers in providing compassionate care which is a fundamental pillar inpatient-centered service (16). Educators have argued that a great majority of medical students enter health care with a strong set of espoused ideals for providing high-quality, patient-centered care (17). Unfortunately, during their training, medical students witness dissonance between the personal and professional conducts of their faculty and clinical teachers, students become more frustrated, less empathetic and more distanced from patients (18).
By and large, the ethos of most health care professional curricula uses typical biomedical models that primarily focus on teaching, training, and practice of clinical medicine with less emphasis on patients' psycho-social well-being (19). In the absence of a rigorous integration of biomedical knowledge with the understanding of human behaviors will potentially further detach medical and health sciences students and healthcare professionals from the patient's emotions and contextualized perspectives (20). Likewise, empathy plays a vital role in interprofessional practice where physicians from various disciplines work together toward the safe and effective patient-related clinical outcomes by shared decision-making and by regular consultations among healthcare teams and patients (21). This interprofessional practice alleviates patients' anxiety, stress, and uncertainty. From another perspective, self-awareness and self-regulation with empathy facilitates patient-doctor therapeutic interactions by evolving physicians' self-discovery (22). Among the practicing physicians, the phenomenon of selfdiscovery is an ingredient to professional identity formation (23). An empathetic professional identity formation is considered to be an effective tool for therapeutic actions in the healthcare system (24). In summary, empathy embodies a constellation of inter-related and interchangeable attributes that collectively lead to improved positive patient-related outcomes and the quality of care.
In clinical practice, a compassionate care has shown a strong association between improved clinical outcomes, quality of life and well-being (25). Among health professionals, empathetic, and compassionate care helps in mitigating the risk of burnouts (26). From the neuroscience perspective, a study on the functional magnetic resonance imaging has shown that empathy activates distinct pain centers of the brain; whereas focusing on compassion activates the reward pathways (27). These findings propound that a synchronous teaching and practice of empathy and compassion enhance patient and clinician well-being. Such outcomes may be accomplished with great success if educators can inculcate structured training programs for empathy and compassion in undergraduate and residency programs. However, there is a compelling evidence of empathy decline during the course of educational and training programs (28) and there is an urgent need for developing evidence-based curricula that can secure a sustained change in attitudes and behaviors (29).
A wealth of teaching pedagogies has been used to develop empathy, compassion and respect for patients in medical students (30)(31)(32)(33) These include, but not limited to, patients' narratives and creative arts, drama workshops, communication skills, reflective writing, video-based learning and experiential learning (34)(35)(36)(37). Lastly, the impact of role modeling and hidden curriculum in teaching compassion and empathy is well-established (38)(39)(40). There is little evidence about how the learning contexts, including the structure and delivery of medical curricula, influence the understanding of medical students about empathy and compassion (41). However, some patient-reported studies about compassion and empathy have shown the influence of educational interventions on medical students in enhancing their approach toward patients and their families (42).
The analysis of existing body of literature emphasizes a need to introduce a standard teaching modalities within medical curricula that can enrich traits of empathy and compassion in undergraduate medical students. Currently, there is scarce evidence of horizontal or vertical integration of teaching programs of empathy and compassion in undergraduate medical curricula (43,44). Furthermore, there is little evidence about the effectiveness and quality of teaching programs for empathy and compassion. We conducted this systematic review of the literature to summarize and report the published work on educational interventions for empathy and/or compassion curricula in undergraduate medical students. This review also aims to highlight best practices to implement an evidencebased empathy and/or compassion curriculum in undergraduate medical training.

MATERIALS AND METHODS
In our study, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (45). The PRISMA tool provides an evidence-based minimum set of data for a standard reporting in systematic reviews and meta-analyses.

Research Objectives
Our research questions were based on Population, Intervention, Comparison, and Outcome (PICO) (46) as shown in Box 1.
We conducted this systematic review with two major objectives.
1. To describe and summarize the published literature about empathy and/or compassion curriculum in undergraduate medical education. 2. To summarize and highlight the best practices to implement an evidence-based empathy and/or compassion curriculum in undergraduate medical education.

Literature Search Strategy
We searched four major electronic databases of Web of Science, PubMed, Scopus and EBSCO Host for the Englishlanguage articles, published during 2015-2020. Our search strategy was adapted from a previously published systematic review on education for compassion and empathy (47,48

Data Extraction and Data Synthesis
Two researchers (PM and SSG) thoroughly scanned the full text of articles that met inclusion criteria and then using a standard data extraction form charted the required information.
The researcher SG independently reviewed the entire process and filled gaps in data mining, data extraction and synthesis. We considered the following components during data extraction; types and designs of studies, primary objectives of studies, quality of studies, invitees' study level, response rate, selfreported or objective measurements in each study, and type, duration, frequency, skills taught and modality of educational interventions. We also recorded the outcomes according to the following four levels of the Kirkpatrick's model (49); 1. Self-reported changes in knowledge, skills, and attitude 2. Changes in knowledge 3. Changes in behavior 4. Patient-reported outcomes We identified and classified the primary outcomes of the selected studies according to Kirkpatrick's level. A number of studies assessed multiple competencies such as empathy and compassion and self-compassion, and the highest-level outcome was considered as the primary outcome. While, in the studies where the primary outcomes did not relate to compassion or empathy, we used the highest-level empathy-specific variable as the primary outcome (Boxes 1, 2).

Effectiveness of Educational Interventions
To identify best educational practices for teaching compassion and/or empathy, we determined the effectiveness of interventions in the selected studies, where effective was defined as a statistically significant improvement in primary educational outcomes as measured by p-value or effect size, where applicable. A p < 0.05 and an effect size >0.25 was considered significant. This rule was applicable only for quantitative studies with a control group design or a single group pre and post-test design.

Quality Assessment
We used Medical Education Research Study Quality Instrument (MERSQI), a tool designed for evaluation of quantitative

Quality Assurance
All researchers (PM, SSG and SG) objectively reviewed the workflow of selection of studies. In case of discrepancies, the researchers reached consensus by comparing the studies with inclusion criteria and key words. The discrepancies, inconsistencies and controversies were resolved with consensus until all the concerns were resolved. Figure 1 outlines the workflow and algorithm of studies selection in this study. Our initial search yielded 2,861 studies. After removing duplicates, we screened 754 titles and abstracts. This led to the identification of 244 articles using PICO for a detailed full-text review. This helped us to exclude another 227 articles whose content did not meet the inclusion criteria. We reviewed reference lists of the included articles to identify additional studies for potential inclusion, used electronic citation tracking, and consulted the librarian. This hand search yielded 15 review articles with 7 additional articles for inclusion. Finally, authors agreed on a list of 24 articles (23,, that had used 24 unique educational interventions either de novo, validated or adapted from previous publications and explicitly met inclusion criteria of our research. The summarized and BOX 2 | The data mining rubric used in our study to record characteristics of each study (n = 24).

First Author Title
Year comprehensive information about each article is presented in Table 1.
A maximum number of 9/24 (37.5%) articles were published in 2017, while 11/24 (45.8 %) studies originated from the USA. The sample size varied greatly across the selected studies, ranging from 10 to 299 participants. Our research included a total of 2,657 respondents with a mean of 110.    (52,58,60,69) were also significantly effective. A great majority of studies were conducted in multiple sessions within one academic year.

Quality assessed (MERSQI) b
Mindfulness and self-compassion

DISCUSSION
Our study elucidates major findings of 24 studies that have collected data from 2,657 medical students using educational interventions on empathy and compassion. Overall, there is a positive impact of teaching empathy and compassion on medical students using a wide range of teaching pedagogies. The body of evidence from our research has deduced that effective communication skills, mindfulness, early clinical experience, comics, arts and culture, and technology-enhanced learning by virtual patients, hangouts and hot spotting had a positive impact on empathy and compassion of medical students. The overarching findings in our study underpin a need to teach empathy using the concepts of physician-patient

Students health and well-being
Brief differential emotions scale (64) Groningen reflection ability scale (58) Brief symptom inventory (54) Mental health continuum-short form (54) Five facet mindfulness questionnaire (54) Irrational beliefs inventory (54) Toronto mindfulness scale (59,64) Marlowe-Crowne short form C Self-compassion scale (64) Irrational beliefs inventory (71) Depression anxiety and stress scale (54) UCLA loneliness scale (64) Pittsburgh sleep scale (64) Substance use inventory (64) Behavior Micro expression training tool (73) Subtle expression training tool (73) Visual analog scale (59) interactions, interprofessional practice with professional identity formation, stress awareness, and self-reflection and communication. In our study, a substantial body of evidence has stressed on empathetic communication for better patient outcomes (51,57,60,63,66,72). Communication is the foremost determinant of a safe clinical practice and ensures satisfaction of both patients and healthcare providers (75). The outright benefits of timely and professional communication in the medical field are far ranging; greater patient understanding and compliance, superior clinical outcomes, improved patient safety and alleviation of patient stress (76). Kelley and Kelley have argued that verbal communication between a healthcare professional and a patient enacts an empathetic connection to the patient that carries a powerful transformative and healing power (77). Pity, sympathy, fellow-feeling, comfort, commiseration, assuagement, and reflexive encouragement constitute effective strands of practicing empathy and compassion (78). The identification of compassionate opportunities, conformation, and appreciation with pursuit provide a practice of compassionate and empathetic care (79) (12) This analysis reflects how the patient-related outcomes can be improved by using a wide range of educational tools and techniques (VALUE, CARE, and SALTED) for incorporating, measuring, and enhancing empathy and compassion in medical students. In our research, a great majority of studies have measured self-reported changes in knowledge and skills of participants and only two studies could tap into behavioral changes after an intervention (59,69). Sustained training sessions are essential for achieving such paradigm change in behaviors. Although literature has shown some controlled trials on empathy, a precursor for compassion, but there is scarce information on compassion training of medical students or healthcare professionals (80). One such compassion enhancing training exercise is provided by mindfulness, "a continuous awareness of present moment experience in a calm and non-judgmental manner" (81). Mindfulness is a multi-factorial construct that contains a host of correlates such as healthy lifestyle, health education, wellness, empathy, compassion, good quality of life, regular exercise, sleep and hygiene, yoga, and guided imagery (82). Training for enhancement of mindfulness can potentially enhance compassionate care in clinical practice (83), close physician-patient relationship and can help alleviate physician burnout (84). Mindful meditation, attention to breathing, didactic learning, reflection, mindful walking, journalism, and sitting meditation are some of the most popular mindfulness training exercises that have shown to enhance empathy and compassion in medical students and healthcare workers (59). In the study by van Dijik et al. (71), the authors incorporated a stress reduction training curriculum based on mindfulness strategies to improve the mental health of medical students during clinical clerkships. This intervention led to an insignificant betterment of mental health of students which was followed up longitudinally over a 20 month period. However, the researchers could not detect a difference in JSE at 12 months in the studied cohort of students. Such findings necessitate the incorporation of a sustained empathy training program, particularly empathetic communication, for undergraduate medical students.
Technology-enhanced learning has gained popularity in several branches of medical education. Likewise, virtual patients (VPs) and standardized patients (StPs) are used as attractive alternatives to real patients with promising results (58). Unfortunately, research has shown an empathy decline in medical students' , particularly in the third year of medical school (85). At this stage, medical students enter clinical clerkships that witness their encounters with patients and their relatives. A suitable ramification to sustain empathy and compassion is the use of VPs and StPs that can provide a constant source for medical students' experiential learning and behavioral development without endangering patient safety. Experiential learning such as patient shadowing or wellness programs can potentially enhance cognitive and behavioral dimensions of empathy. The long-lasting impact of experiential learning is further endorsed by a study conducted by Modi et al. which showed that volunteering students had better empathy than the non-volunteered medial students (65), who showed a decline in empathy over time.
The intelligent use of arts, culture, and humanities in medical education is an emerging and promising approach that can revitalize the declining empathy in medical students (70). Comics "the combined use of images and text, sequentially, to tell a story, where the images complement and/or enhance the text" (86) is a powerful means of portraying complexities of medical knowledge. Graphical illustration with juxtaposed texts, depicts stories in a tangible manner which help to amalgamate the pictorial and textual cues highlighting an innovative use of technology enhanced learning and comics. Our research has shown some evidence that comics may serve as a distinct tool to promote empathy in medical education (87). Finally, interprofessional education and practice carries great potential to promote empathy and compassion by alleviating anxiety, stress and burnout associated with medical education (21,88).
Our results highlight the fact that the educational interventions pitched at improving the knowledge outcomes can be significantly effective, followed by behaviors and finally, patient outcomes. This is understandable for some reasons; medical students are attuned to work hard to acquire knowledge which can be easily measured as an educational outcome. Behavioral change in students and improvement in patient outcomes demand a sustained interplay of generic and acquired traits and, therefore, it's hard to achieve. Another interesting finding of our research springs from the fact that frequency, duration and teaching modalities didn't have any bearing on the effectiveness of the educational intervention. Even single session interventions were as effective as longitudinal curricula and such curricula did not have a sustained and long-lasting impact. However, experiential learning drills lead to emotional and behavioral remodeling that can result in durable personality developments.

STUDY LIMITATIONS
There are number of limitations of this review. The first relates to the comprehensiveness of the search and included articles. We searched four databases quite rigorously, but there remains a chance that certain pertinent studies are not captured by our search of databases, time and language restrictions. Second, though we aimed at highlighting the best practices in teaching empathy and/or compassion, this turned out to be difficult due to profound heterogeneity in the educational interventions and measurement tools used and the types of accomplished outcomes. Third, we planned to find a common curriculum for teaching and assessing empathy and compassion in medical education, its diverse and heterogeneous nature did not allow us to achieve our goal.

CONCLUSION
In our systematic review, the identified 24 studies evaluated the empathy and/or compassion curricula for undergraduate medical students. There was a great diversity of teaching pedagogies, curriculum design, and duration of teaching that did not let us secure a single best-evidence teaching modality for empathy and/or compassion. Keeping the multidimensional construct nature in mind, a blend of teaching pedagogies is needed. However, major educational constructs of communication, mindfulness, self-care, self-regulation, reflective practice, early clinical exposure, technology-enhanced learning, comics and arts and culture should be targeted for teaching empathy and compassion. We found that even short standalone curriculum was as effective as longitudinal curriculum. In order to mitigate the risk of decline of empathy and compassion, a sustainable program rather than a single training activity is essential.

DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

AUTHOR CONTRIBUTIONS
PM and SSG contributed substantially to conceiving the idea, created, reviewed, and validated the search strategy, hand searched and screened the titles and abstract, extracted, analyzed and interpreted the data and came up with the initial draft of manuscript. Later SYG individually evaluated the search strategy, tweaked the data mining process, revised and improved the intellectual content of the initial draft. PM, SYG, and SSG agreed to take responsibility for the final draft. All authors contributed to the article and approved the submitted version.