Published on in Vol 21, No 7 (2019): July

Preprints (earlier versions) of this paper are available at https://preprints.jmir.org/preprint/14676, first published .
Virtual Patient Simulations in Health Professions Education: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration

Virtual Patient Simulations in Health Professions Education: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration

Virtual Patient Simulations in Health Professions Education: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration

Review

1Department of Bioinformatics and Telemedicine, Jagiellonian University Medical College, Kraków, Poland

2Institute of Medical and Biomedical Education, St George’s, University of London, London, United Kingdom

3Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden

4Department of Medical and Health Sciences, Linköping University, Linköping, Sweden

5Learning and Professional Development Group, School of Health Sciences, Örebro University, Örebro, Sweden

6Warwick Medical School, University of Warwick, Coventry, United Kingdom

7Health Services and Outcomes Research, National Healthcare Group, Singapore, Singapore

8Family Medicine and Primary Care, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

9Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom

10President’s Office, Nanyang Technological University, Singapore, Singapore

11Centre for Population Health Sciences, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

12Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom

13Games for Health Innovations Centre, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

14Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates

Corresponding Author:

Josip Car, MD, PhD, FRCPE, FFPH

Centre for Population Health Sciences

Lee Kong Chian School of Medicine

Nanyang Technological University

11 Mandalay Road, Clinical Science Building

Singapore,

Singapore

Phone: 65 6340 2480

Email: josip.car@ntu.edu.sg


Background: Virtual patients are interactive digital simulations of clinical scenarios for the purpose of health professions education. There is no current collated evidence on the effectiveness of this form of education.

Objective: The goal of this study was to evaluate the effectiveness of virtual patients compared with traditional education, blended with traditional education, compared with other types of digital education, and design variants of virtual patients in health professions education. The outcomes of interest were knowledge, skills, attitudes, and satisfaction.

Methods: We performed a systematic review on the effectiveness of virtual patient simulations in pre- and postregistration health professions education following Cochrane methodology. We searched 7 databases from the year 1990 up to September 2018. No language restrictions were applied. We included randomized controlled trials and cluster randomized trials. We independently selected studies, extracted data, and assessed risk of bias and then compared the information in pairs. We contacted study authors for additional information if necessary. All pooled analyses were based on random-effects models.

Results: A total of 51 trials involving 4696 participants met our inclusion criteria. Furthermore, 25 studies compared virtual patients with traditional education, 11 studies investigated virtual patients as blended learning, 5 studies compared virtual patients with different forms of digital education, and 10 studies compared different design variants. The pooled analysis of studies comparing the effect of virtual patients to traditional education showed similar results for knowledge (standardized mean difference [SMD]=0.11, 95% CI −0.17 to 0.39, I2=74%, n=927) and favored virtual patients for skills (SMD=0.90, 95% CI 0.49 to 1.32, I2=88%, n=897). Studies measuring attitudes and satisfaction predominantly used surveys with item-by-item comparison. Trials comparing virtual patients with different forms of digital education and design variants were not numerous enough to give clear recommendations. Several methodological limitations in the included studies and heterogeneity contributed to a generally low quality of evidence.

Conclusions: Low to modest and mixed evidence suggests that when compared with traditional education, virtual patients can more effectively improve skills, and at least as effectively improve knowledge. The skills that improved were clinical reasoning, procedural skills, and a mix of procedural and team skills. We found evidence of effectiveness in both high-income and low- and middle-income countries, demonstrating the global applicability of virtual patients. Further research should explore the utility of different design variants of virtual patients.

J Med Internet Res 2019;21(7):e14676

doi:10.2196/14676

Keywords



Background

Health care education is confronted with many global challenges. Shorter hospital stays, specialization of care, higher patient safety measures, and shortage of clinical teachers all diminish the traditional opportunities for the training of health professions through direct patient contact [Ramani S, Leinster S. AMEE Guide no. 34: teaching in the clinical environment. Med Teach 2008 Jan;30(4):347-364. [CrossRef] [Medline]1,Moalem J, Salzman P, Ruan DT, Cherr GS, Freiburg CB, Farkas RL, et al. Should all duty hours be the same? Results of a national survey of surgical trainees. J Am Coll Surg 2009 Jul;209(1):47-54, 54.e1-2. [CrossRef] [Medline]2]. Early health professions education is often dominated by theoretical presentations with insufficient connection to clinical practice [Dev P, Schleyer T. Computers in health care education. In: Shortliffe E, Cimino J, editors. Biomedical Informatics. London: Springer; 2014:675-693.3]. The need to increase numbers and quality of the health workforce is especially visible in low-and-middle-income countries, where the need to scale up high-quality health education and introduce educational innovations is most pressing [Frenk J, Chen L, Bhutta ZA, Cohen J, Crisp N, Evans T, et al. Health professionals for a new century: transforming education to strengthen health systems in an interdependent world. Lancet 2010 Dec 4;376(9756):1923-1958. [CrossRef] [Medline]4]. Therefore, the global medical education community is perpetually searching for methods that can be applied to improve the relevance, increase the spread, and accelerate the educational process for health professions [Crisp N, Gawanas B, Sharp I, Task Force for Scaling Up EducationTraining for Health Workers. Training the health workforce: scaling up, saving lives. Lancet 2008 Feb 23;371(9613):689-691. [CrossRef] [Medline]5].

Digital education (often referred to as e-learning) is “the act of teaching and learning by means of digital technologies” [Car J, Carlstedt-Duke J, Tudor Car L, Posadzki P, Whiting P, Zary N, Digital Health Education Collaboration. Digital education in health professions: the need for overarching evidence synthesis. J Med Internet Res 2019 Dec 14;21(2):e12913 [FREE Full text] [CrossRef] [Medline]6]. It encompasses a multitude of educational concepts, approaches, methods, and technologies. Digital health education comprises, for example, offline learning, mobile learning, serious games, or virtual reality environments. We have conducted this systematic review as part of a review series on digital health education [Car J, Carlstedt-Duke J, Tudor Car L, Posadzki P, Whiting P, Zary N, Digital Health Education Collaboration. Digital education in health professions: the need for overarching evidence synthesis. J Med Internet Res 2019 Dec 14;21(2):e12913 [FREE Full text] [CrossRef] [Medline]6-Wahabi HA, Esmaeil SA, Bahkali KH, Titi MA, Amer YS, Fayed AA, et al. Medical doctors' offline computer-assisted digital education: systematic review by the Digital Health Education Collaboration. J Med Internet Res 2019 Mar 1;21(3):e12998 [FREE Full text] [CrossRef] [Medline]19] and focused it on the simulation modality called virtual patients.

Virtual patients are defined as interactive computer simulations of real-life clinical scenarios for the purpose of health professions training, education, or assessment [Ellaway R, Candler C, Greene P, Smothers V. MedBiquitous. An Architectural Model for MedBiquitous Virtual Patients   URL: http://tinyurl.com/jpewpbt [accessed 2019-05-10] [WebCite Cache]20]. This broad definition encompasses a variety of systems that use different technologies and address various learning needs [Kononowicz AA, Zary N, Edelbring S, Corral J, Hege I. Virtual patients - what are we talking about? A framework to classify the meanings of the term in healthcare education. BMC Med Educ 2015;15:11 [FREE Full text] [CrossRef] [Medline]21]. The learner is cast into the role of a health care provider who makes decisions about the type and order of clinical information acquired, differential diagnosis, and management and follow-up of the patient. Virtual patients are hypothesized to primarily address learning needs in clinical reasoning [Cook DA, Triola MM. Virtual patients: a critical literature review and proposed next steps. Med Educ 2009 Apr;43(4):303-311. [CrossRef] [Medline]22,Posel N, McGee JB, Fleiszer DM. Twelve tips to support the development of clinical reasoning skills using virtual patient cases. Med Teach 2014 Dec 19:1-6. [CrossRef] [Medline]23]. However, an influence of the use of virtual patients on other educational outcomes has been reported in previous literature [Kononowicz AA, Zary N, Edelbring S, Corral J, Hege I. Virtual patients - what are we talking about? A framework to classify the meanings of the term in healthcare education. BMC Med Educ 2015;15:11 [FREE Full text] [CrossRef] [Medline]21,Berman NB, Durning SJ, Fischer MR, Huwendiek S, Triola MM. The role for virtual patients in the future of medical education. Acad Med 2016 Sep;91(9):1217-1222. [CrossRef] [Medline]24].

The educational use of virtual patients may be understood through experiential learning theory [Kolb DA. Experiential Learning: Experience As The Source Of Learning And Development. Upper Saddle River, New Jersey: Prentice Hall; 1984.25,Yardley S, Teunissen PW, Dornan T. Experiential learning: AMEE Guide No. 63. Med Teach 2012;34(2):e102-e115. [CrossRef] [Medline]26]. Following this theoretical model of action and reflection, virtual patients expose learners to simulated clinical experiences, providing mechanisms for information gathering and clinical decision making in a safe environment [Edelbring S, Dastmalchi M, Hult H, Lundberg IE, Dahlgren LO. Experiencing virtual patients in clinical learning: a phenomenological study. Adv Health Sci Educ Theory Pract 2011 Aug;16(3):331-345. [CrossRef] [Medline]27]. Exposing the learner to many simulated clinical scenarios supports learning diagnostic processes [Norman G. Research in clinical reasoning: past history and current trends. Med Educ 2005 Apr;39(4):418-427. [CrossRef] [Medline]28] while acquainting learners with a standardized set of clinical conditions common in the population, but rare or nonaccessible in highly specialized teaching hospitals [Berman N, Fall LH, Smith S, Levine DA, Maloney CG, Potts M, et al. Integration strategies for using virtual patients in clinical clerkships. Acad Med 2009 Jul;84(7):942-949. [CrossRef] [Medline]29].

Some concerns have been raised about educational use of virtual patients. Virtual patients should not replace but complement contact with real patients [Edelbring S, Dastmalchi M, Hult H, Lundberg IE, Dahlgren LO. Experiencing virtual patients in clinical learning: a phenomenological study. Adv Health Sci Educ Theory Pract 2011 Aug;16(3):331-345. [CrossRef] [Medline]27]. There are concerns around the use of virtual patients potentially resulting in less empathic learners [Kenny NP, Beagan BL. The patient as text: a challenge for problem-based learning. Med Educ 2004 Oct;38(10):1071-1079. [CrossRef] [Medline]30]. The use of unfamiliar technology as part of virtual patients’ education can represent a barrier to learning, even for younger generations [Button D, Harrington A, Belan I. E-learning & information communication technology (ICT) in nursing education: a review of the literature. Nurse Educ Today 2014 Oct;34(10):1311-1323. [CrossRef] [Medline]31,Watson JA, Pecchioni LL. Digital natives and digital media in the college classroom: assignment design and impacts on student learning. Educ Media Int 2011 Dec;48(4):307-320. [CrossRef]32]. Virtual patients may also prove ineffective when technological objectives drive teaching instead of being motivated by learning needs [Schifferdecker KE, Berman NB, Fall LH, Fischer MR. Adoption of computer-assisted learning in medical education: the educators' perspective. Med Educ 2012 Nov;46(11):1063-1073. [CrossRef] [Medline]33].

This virtual patient simulation review has been preceded by several narrative reviews [Cook DA, Triola MM. Virtual patients: a critical literature review and proposed next steps. Med Educ 2009 Apr;43(4):303-311. [CrossRef] [Medline]22,Baumann-Birkbeck L, Florentina F, Karatas O, Sun J, Tang T, Thaung V, et al. Appraising the role of the virtual patient for therapeutics health education. Curr Pharm Teach Learn 2017 Dec;9(5):934-944. [CrossRef] [Medline]34-Saleh N. The value of virtual patients in medical education. Ann Behav Sci Med Educ 2010 Oct 16;16(2):29-31. [CrossRef]37] and 2 systematic reviews with meta-analyses [Cook DA, Erwin PJ, Triola MM. Computerized virtual patients in health professions education: a systematic review and meta-analysis. Acad Med 2010 Oct;85(10):1589-1602. [CrossRef] [Medline]38,Consorti F, Mancuso R, Nocioni M, Piccolo A. Efficacy of virtual patients in medical education: a meta-analysis of randomized studies. Comput Educ 2012 Nov;59(3):1001-1008. [CrossRef]39]. Our preliminary literature analysis showed that the number of studies including the term virtual patient or virtual patients has more than doubled on the MEDLINE database in comparison with available evidence provided in previous systematic reviews (February 2009 [Cook DA, Erwin PJ, Triola MM. Computerized virtual patients in health professions education: a systematic review and meta-analysis. Acad Med 2010 Oct;85(10):1589-1602. [CrossRef] [Medline]38] and July 2010 [Consorti F, Mancuso R, Nocioni M, Piccolo A. Efficacy of virtual patients in medical education: a meta-analysis of randomized studies. Comput Educ 2012 Nov;59(3):1001-1008. [CrossRef]39]). Thus, our review will update the evidence base with studies not included in previous analyses.

Objectives

The objective of this review was to evaluate the effectiveness of virtual patient simulation for delivering pre- and postregistration health care professions education using the following comparisons:

  1. Virtual patient versus traditional education
  2. Virtual patient blended learning versus traditional education
  3. Virtual patient versus other types of digital education
  4. Virtual patient design comparison

By traditional education, we mean all nondigital educational methods. This includes lectures, reading exercises, group discussion in classroom, and nondigital simulation as standardized patients or mannequin-based training. Virtual patient blended learning is the addition of virtual patients as a supplement to traditional education when the control intervention uses nondigital education methods only. Other types of digital education may include interventions such as video recordings, Web-based tutorials, or virtual classrooms.

We assessed the impact of virtual patient interventions on learners’ knowledge, skills, attitude, and satisfaction. Our secondary objective was to assess the cost-effectiveness, patient outcomes, and adverse effects of these interventions.


Protocol and Registration

While conducting the review, we adhered to the Cochrane methodology [Higgins J, Green S. Cochrane Handbook For Systematic Reviews Of Interventions. Chichester, England: John Wiley & Sons; 2008.40], followed a published protocol [Kononowicz AA, Woodham L, Georg C, Edelbring S, Stathakarou N, Davies D, et al. Virtual patient simulations for health professional education. Cochrane Database Syst Rev 2016 May 19(5):CD012194. [CrossRef]41], and presented results following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines [Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 2009 Jul 21;6(7):e1000100 [FREE Full text] [CrossRef] [Medline]42].

Eligibility Criteria

We included randomized controlled trials (RCTs) and cluster RCTs (cRCTs). We excluded crossover trials because of the high likelihood of carryover effect.

Participants in the included studies had to be enrolled in a pre- or postregistration health-related education or training program (see glossary in

Multimedia Appendix 1

Glossary.

DOC File, 76KBMultimedia Appendix 1). This included students from disciplines such as medicine, dentistry, nursing and midwifery, medical diagnostic and treatment technology, physiotherapy and rehabilitation, and pharmacy.

This review focused on screen-based virtual patient simulations that form a computerized, dynamically unfolding representation of patient cases. A virtual patient simulation is introduced by a case description and might contain answers given by the patient, clinical data (eg, laboratory results, medical images), and descriptions of patients’ signs and symptoms. Only the representations of the patient as a whole were of interest, rather than studies that focused on single parts of the body. As a matter of a policy followed in the Digital Health Education Collaboration [Car J, Carlstedt-Duke J, Tudor Car L, Posadzki P, Whiting P, Zary N, Digital Health Education Collaboration. Digital education in health professions: the need for overarching evidence synthesis. J Med Internet Res 2019 Dec 14;21(2):e12913 [FREE Full text] [CrossRef] [Medline]6] and aiming at avoiding duplication of reviews, we deliberately excluded virtual patients in 3-dimensional (3D) virtual learning environments from this study. We judged that a higher level of immersion of learners in 3D virtual environments, connected with potential technical challenges (eg, difficulties in navigating such environments, lags because of increased computational time or limited internet bandwidth), was likely to influence the educational outcomes and therefore merited a separate analysis covered already by the virtual reality review [Kyaw BM, Saxena N, Posadzki P, Vseteckova J, Nikolaou CK, George PP, et al. Virtual reality for health professions education: systematic review and meta-analysis by the Digital Health Education collaboration. J Med Internet Res 2019 Jan 22;21(1):e12959 [FREE Full text] [CrossRef] [Medline]13] of this Digital Health Education Collaboration series. We also excluded those virtual patient interventions which require nonstandard equipment (eg, haptic devices, mannequins) or those virtual patients which are human controlled (eg, simulated email correspondence or chat room conversations). We excluded studies in which virtual patients were just a small part of the intervention and those in which the influence of virtual patients was not evaluated separately.

Furthermore, 2-arm RCTs comparing virtual patients with a control group not involved in any type of subject-related learning activity were not considered eligible as previous meta-analyses have already shown a large positive effect when virtual patients were compared with no intervention [Cook DA, Erwin PJ, Triola MM. Computerized virtual patients in health professions education: a systematic review and meta-analysis. Acad Med 2010 Oct;85(10):1589-1602. [CrossRef] [Medline]38].

We decided to introduce to the review a comparison of virtual patients blended learning with traditional education as a consequence of the discussion in the community on the need to eliminate traditional types of learning activities to make space for virtual patients. For instance, Berman et al [Berman N, Fall LH, Smith S, Levine DA, Maloney CG, Potts M, et al. Integration strategies for using virtual patients in clinical clerkships. Acad Med 2009 Jul;84(7):942-949. [CrossRef] [Medline]29] noticed that the students’ subjective learning effect perceptions and satisfaction with integration were lower at universities that increased the workload of students by adding virtual patients without releasing time resources in the curriculum. As most of health professions education is conducted on campus, an integrated effect of virtual patients is possible. Blending virtual patients with traditional education is challenging and qualitatively different than a nonintervention control group comparison.

Eligible primary outcomes were students’ (1) knowledge, (2) skills, (3) attitudes, and (4) satisfaction—together representing clinical competencies measured post intervention with validated or nonvalidated instruments. Secondary outcomes were (1) economic cost and cost-effectiveness, (2) patient outcomes, and (3) observed adverse effects.

Search Methods for Identification of Studies

We searched the following 7 databases: MEDLINE (via Ovid), EMBASE (via Elsevier), The Cochrane Library (via Wiley), PsycINFO (via Ovid), Educational Resource Information Centre (ERIC; via Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL; via EBSCO), and Web of Science Core Collection (via Thomson Reuters). We adapted the MEDLINE strategy and keywords presented in

Multimedia Appendix 2

MEDLINE (Ovid) search strategy.

DOC File, 47KBMultimedia Appendix 2 for use with each of the databases above. We searched databases from the year 1990 to September 20, 2018 to highlight recent developments and did not apply language restrictions. For all included studies, we searched references lists and conducted author and citation searches. We searched lists of references from other identified relevant systematic reviews while running our electronic searches.

Data Collection and Analysis

Data Selection, Extraction, and Management

The search results were combined in a single EndNote library (version X7; Thomson Reuters) [EndNote X7. Philadelphia, PA: Thomson Reuters; 2016.   URL: https://endnote.com/ [accessed 2019-05-10] 43]. Overall, 2 authors independently screened titles and abstracts to identify potentially eligible studies. In the next phase, full-text versions of these papers were retrieved and 2 review authors independently assessed these papers against eligibility criteria. We piloted data extraction to maximize consistency in the information extracted. Disagreements were resolved through discussion. A third review author was consulted to arbitrate when differences in opinion arose. All relevant data were extracted using a structured form in Microsoft Excel. We contacted study authors for crucial missing information, particularly if required to judge inclusion criteria and study outcomes.

Data Items

Information was extracted from each included study on (1) the characteristics of study participants (field of study; stage of education: pre/postregistered; year of study; and country where the study was conducted and its World Bank income category: high-income/low-and-middle-income country), (2) the type of outcome measure (type of tool used to measure outcome and information on whether the tool was validated), (3) the type of virtual patient intervention (topic and language of presented virtual patient simulations; information on whether the language of virtual patient was native to the majority of participants; source of virtual patient simulations: internal/external; was the study an individual or group assignment, and in case of group assignments, the number of students in a group; whether access to virtual patient simulation was from home or in a computer laboratory; number of virtual patient cases presented; time when the virtual patients were available; and duration of use of virtual patients), and (4) the type of virtual patient system (name of the system; navigation scheme: linear, branched, and free access; control mechanism: menu-based, keyboard, or speech recognition; feedback delivery and timing; and whether video clips where included in virtual patient cases). A glossary of the terms in use in the review may be found in

Multimedia Appendix 1

Glossary.

DOC File, 76KBMultimedia Appendix 1.

Measures of Treatment Effect

We reported the treatment effects for continuous outcomes as mean values and SDs post intervention in each intervention group, along with the number of participants and P values. As the studies presented data using different tools, the mean differences were recalculated into standardized mean difference (SMD). We interpreted the effect size as small (SMD=0.2), moderate (SMD=0.5), and large (SMD=0.8) effect sizes [Higgins J, Green S. Cochrane Handbook For Systematic Reviews Of Interventions. Chichester, England: John Wiley & Sons; 2008.40]. If studies had multiple arms and no clear main comparison, we compared the virtual patient intervention arm with the most common control arm, excluding the nonintervention and mixed-intervention controls. If that was impossible to decide, we selected the least active control arm. If multiple outcomes in the same category (knowledge, skills, attitudes, and outcomes) were reported, we selected the primary measure, and if that was impossible, we calculated the mean value of all measures. For papers that reported median and range for the outcomes, we converted these to mean and SD using methods described by Wan [Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 2014 Dec 19;14:135 [FREE Full text] [CrossRef] [Medline]44]. If a study did not report SD but provided CIs, we estimated SD from those using a method described in previous literature [Higgins J, Green S. Cochrane Handbook For Systematic Reviews Of Interventions. Chichester, England: John Wiley & Sons; 2008.40].

Data Synthesis and Analysis

Owing to the significant differences between studies, we employed a random-effects model in the meta-analysis using Review Manager (version 5.3; The Nordic Cochrane Centre) [Cochrane Community. Copenhagen, Denmark: The Nordic Cochrane Centre; 2014. Review Manager (RevMan) Version 5.3   URL: https://community.cochrane.org/help/tools-and-software/revman-5 [accessed 2019-05-10] 45]. We displayed the results of the meta-analysis in forest plots and evaluated heterogeneity numerically using I2 statistics. For comparisons with more than 10 outcomes in the meta-analysis, we attempted a subgroup analysis. As the planned 15 subgroup analyses in the protocol [Kononowicz AA, Woodham L, Georg C, Edelbring S, Stathakarou N, Davies D, et al. Virtual patient simulations for health professional education. Cochrane Database Syst Rev 2016 May 19(5):CD012194. [CrossRef]41] did not explain the heterogeneity, we visualized the outcomes using albatross plots [Harrison S, Jones HE, Martin RM, Lewis SJ, Higgins JP. The albatross plot: a novel graphical tool for presenting results of diversely reported studies in a systematic review. Res Synth Methods 2017 Sep;8(3):281-289 [FREE Full text] [CrossRef] [Medline]46]. These plots were implemented using a script created for the purpose of the study by one of the review authors (AK) in the statistical package R (version 3.4.3; R Foundation for Statistical Computing) [R: A Language and Environment for Statistical Computing. Vienna, Austria: R Core Team; 2017.   URL: https://www.r-project.org/ [accessed 2019-05-10] 47]. This explorative approach resulted in a new subgroup analysis in which we divided the control interventions into active (group discussion, mannequin-based simulation) and passive (lectures, reading assignments). Findings unsuitable for inclusion in a meta-analysis (eg, comparison of individual items in surveys) were presented using a narrative synthesis.

Assessment of Risk of Bias

Two authors independently assessed the risk of bias using the Cochrane tool [Higgins J, Green S. Cochrane Handbook For Systematic Reviews Of Interventions. Chichester, England: John Wiley & Sons; 2008.40]. We considered the following domains: random sequence generation, allocation sequence concealment, blinding of participants or personnel, blinding to outcome assessment, completeness of outcome data, selective outcome reporting, and other sources of bias (eg, differences in baseline evaluation, volunteer bias, commercial grants). For cRCTs, we also assessed the risk of the following additional biases: recruitment bias, baseline imbalance, loss of clusters, incorrect analysis, and comparability with individually randomized trials. The publication bias in our review was difficult to investigate in a formal way because of high levels of heterogeneity which limit the interpretation possibilities of funnel plots.

Summary of Findings Tables

We prepared summary of findings tables to present results of the meta-analysis [Higgins J, Green S. Cochrane Handbook For Systematic Reviews Of Interventions. Chichester, England: John Wiley & Sons; 2008.40]. We presented the results for major comparisons of the review and for each of the major primary outcomes. We considered the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to assess the quality of the evidence and downgraded the quality where appropriate [Higgins J, Green S. Cochrane Handbook For Systematic Reviews Of Interventions. Chichester, England: John Wiley & Sons; 2008.40].


Included Studies

Our searches yielded a total of 44,054 citations, and 51 studies with 4696 participants were included (Figure 1). Overall, 2 reports described results already included in the review [Kurihara Y, Kuramoto S, Matsuura K, Miki Y, Oda K, Seo H, et al. Academic performance and comparative effectiveness of computer- and textbook-based self-instruction. Stud Health Technol Inform 2004;107(Pt 2):894-897. [Medline]48,Succar T, Grigg J. A new vision for teaching ophthalmology in the medical curriculum: The Virtual Ophthalmology clinic. 2010 Presented at: ASCILITE Conference; December 5-8, 2010; Sydney, Australia p. 944-947. [CrossRef]49].

Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) study flow diagram.
View this figure

Types of Studies

All included studies were published in peer-reviewed journals. All included studies had an RCT design, with the exception of 3 cRCTs [Kononowicz AA, Krawczyk P, Cebula G, Dembkowska M, Drab E, Fraczek B, et al. Effects of introducing a voluntary virtual patient module to a basic life support with an automated external defibrillator course: a randomised trial. BMC Med Educ 2012 Jun 18;12:41 [FREE Full text] [CrossRef] [Medline]50-Succar T, Zebington G, Billson F, Byth K, Barrie S, McCluskey P, et al. The impact of the Virtual Ophthalmology Clinic on medical students' learning: a randomised controlled trial. Eye (Lond) 2013 Oct;27(10):1151-1157. [CrossRef] [Medline]52].

Types of Comparisons

A total of 25 studies compared virtual patients with traditional education [Al-Dahir S, Bryant K, Kennedy KB, Robinson DS. Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences. Am J Pharm Educ 2014 May 15;78(4):76 [FREE Full text] [CrossRef] [Medline]53-Williams C, Aubin S, Harkin P, Cottrell D. A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture. Med Educ 2001 Sep;35(9):847-854. [Medline]77], 11 compared a blend of virtual patients and traditional education with traditional education [Kononowicz AA, Krawczyk P, Cebula G, Dembkowska M, Drab E, Fraczek B, et al. Effects of introducing a voluntary virtual patient module to a basic life support with an automated external defibrillator course: a randomised trial. BMC Med Educ 2012 Jun 18;12:41 [FREE Full text] [CrossRef] [Medline]50,Succar T, Zebington G, Billson F, Byth K, Barrie S, McCluskey P, et al. The impact of the Virtual Ophthalmology Clinic on medical students' learning: a randomised controlled trial. Eye (Lond) 2013 Oct;27(10):1151-1157. [CrossRef] [Medline]52,Bryant R, Miller CL, Henderson D. Virtual clinical simulations in an online advanced health appraisal course. Clin Simul Nurs 2015 Oct;11(10):437-444. [CrossRef]78-Weverling GJ, Stam J, ten Cate TJ, van Crevel H. [Computer-assisted education in problem-solving in neurology; a randomized educational study]. Ned Tijdschr Geneeskd 1996 Feb 24;140(8):440-443. [Medline]86], 5 studies compared virtual patients with different forms of digital health education [Kumta SM, Tsang PL, Hung LK, Cheng JCY. Fostering critical thinking skills through a web-based tutorial programme for final year medical students--A randomized controlled study. J Educ Multimed Hypermedia 2003;12(3):267-273.51,Courteille O, Fahlstedt M, Ho J, Hedman L, Fors U, von Holst H, et al. Learning through a virtual patient vs recorded lecture: a comparison of knowledge retention in a trauma case. Int J Med Educ 2018 Mar 28;9:86-92 [FREE Full text] [CrossRef] [Medline]87-Trudeau KJ, Hildebrand C, Garg P, Chiauzzi E, Zacharoff KL. A randomized controlled trial of the effects of online pain management education on primary care providers. Pain Med 2017 Dec 1;18(4):680-692. [CrossRef] [Medline]90], and 10 studies compared different types of virtual patient interventions [Bearman M, Cesnik B, Liddell M. Random comparison of 'virtual patient' models in the context of teaching clinical communication skills. Med Educ 2001 Sep;35(9):824-832. [Medline]91-Tolsgaard MG, Jepsen RMHG, Rasmussen MB, Kayser L, Fors U, Laursen LC, et al. The effect of constructing versus solving virtual patient cases on transfer of learning: a randomized trial. Perspect Med Educ 2016 Feb;5(1):33-38 [FREE Full text] [CrossRef] [Medline]100].

The traditional education control group involved a reading assignment in 6 studies [Jeimy S, Wang JY, Richardson L. Evaluation of virtual patient cases for teaching diagnostic and management skills in internal medicine: a mixed methods study. BMC Res Notes 2018 Jun 5;11(1):357 [FREE Full text] [CrossRef] [Medline]59,Kandasamy T, Fung K. Interactive internet-based cases for undergraduate otolaryngology education. Otolaryngol Head Neck Surg 2009 Mar;140(3):398-402. [CrossRef] [Medline]60,Leong SL, Baldwin CD, Adelman AM. Integrating web-based computer cases into a required clerkship: development and evaluation. Acad Med 2003 Mar;78(3):295-301. [Medline]62,Qayumi AK, Kurihara Y, Imai M, Pachev G, Seo H, Hoshino Y, et al. Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience). Med Educ 2004 Oct;38(10):1080-1088. [CrossRef] [Medline]67-Schwid HA, Rooke GA, Michalowski P, Ross BK. Screen-based anesthesia simulation with debriefing improves performance in a mannequin-based anesthesia simulator. Teach Learn Med 2001;13(2):92-96. [CrossRef] [Medline]69]; 4 studies each involving a lecture [Li J, Li QL, Li J, Chen ML, Xie HF, Li YP, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach 2013;35(2):e963-e970. [CrossRef] [Medline]63,Miedzybrodzka Z, Hamilton NM, Gregory H, Milner B, Frade I, Sinclair T, et al. Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach. Eur J Hum Genet 2001 Dec;9(12):953-956 [FREE Full text] [CrossRef] [Medline]66,Subramanian A, Timberlake M, Mittakanti H, Lara M, Brandt ML. Novel educational approach for medical students: improved retention rates using interactive medical software compared with traditional lecture-based format. J Surg Educ 2012;69(2):253-256. [CrossRef] [Medline]72,Williams C, Aubin S, Harkin P, Cottrell D. A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture. Med Educ 2001 Sep;35(9):847-854. [Medline]77], group assignment [Al-Dahir S, Bryant K, Kennedy KB, Robinson DS. Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences. Am J Pharm Educ 2014 May 15;78(4):76 [FREE Full text] [CrossRef] [Medline]53,Maleck M, Fischer MR, Kammer B, Zeiler C, Mangel E, Schenk F, et al. Do computers teach better? A media comparison study for case-based teaching in radiology. Radiographics 2001;21(4):1025-1032. [CrossRef] [Medline]65,Sobocan M, Turk N, Dinevski D, Hojs R, Balon BP. Problem-based learning in internal medicine: virtual patients or paper-based problems? Intern Med J 2017 Jan;47(1):99-103. [CrossRef] [Medline]71,Tao H. Computer-based simulative training system—a new approach to teaching pre-hospital trauma care. J Med Coll PLA 2011 Dec;26(6):335-344. [CrossRef]73], and mannequin-based training [Haerling KA. Cost-utility analysis of virtual and mannequin-based simulation. Simul Healthc 2018 Feb;13(1):33-40. [CrossRef] [Medline]58,Liaw SY, Chan SW, Chen F, Hooi SC, Siau C. Comparison of virtual patient simulation with mannequin-based simulation for improving clinical performances in assessing and managing clinical deterioration: randomized controlled trial. J Med Internet Res 2014;16(9):e214 [FREE Full text] [CrossRef] [Medline]64,Secomb J, McKenna L, Smith C. The effectiveness of simulation activities on the cognitive abilities of undergraduate third-year nursing students: a randomised control trial. J Clin Nurs 2012 Dec;21(23-24):3475-3484. [CrossRef] [Medline]70,Wang CL, Chinnugounder S, Hippe DS, Zaidi S, O'Malley RB, Bhargava P, et al. Comparative effectiveness of hands-on versus computer simulation-based training for contrast media reactions and teamwork skills. J Am Coll Radiol 2017 Jan;14(1):103-10.e3. [CrossRef] [Medline]76]; and 1 each involving standardized patients [Triola M, Feldman H, Kalet AL, Zabar S, Kachur EK, Gillespie C, et al. A randomized trial of teaching clinical skills using virtual and live standardized patients. J Gen Intern Med 2006 May;21(5):424-429 [FREE Full text] [CrossRef] [Medline]74] and ward-based education [Vash JH, Yunesian M, Shariati M, Keshvari A, Harirchi I. Virtual patients in undergraduate surgery education: a randomized controlled study. ANZ J Surg 2007;77(1-2):54-59. [CrossRef] [Medline]75]. In 5 studies, the intervention was a mix of different forms of traditional education (eg, lecture, small group assignment, and mannequin-based training) [Bonnetain E, Boucheix JM, Hamet M, Freysz M. Benefits of computer screen-based simulation in learning cardiac arrest procedures. Med Educ 2010 Jul;44(7):716-722. [CrossRef] [Medline]54-Fleetwood J, Vaught W, Feldman D, Gracely E, Kassutto Z, Novack D. MedEthEx Online: a computer-based learning program in medical ethics and communication skills. Teach Learn Med 2000;12(2):96-104. [CrossRef] [Medline]57,Kinney P, Keskula DR, Perry JF. The effect of a computer assisted instructional program on physical therapy students. J Allied Health 1997;26(2):57-61. [Medline]61].

The digital education control group was in 2 studies—a Web tutorial or course [Dankbaar ME, Alsma J, Jansen EE, van Merrienboer JJ, van Saase JL, Schuit SC. An experimental study on the effects of a simulation game on students' clinical cognitive skills and motivation. Adv Health Sci Educ Theory Pract 2016 Aug;21(3):505-521. [CrossRef] [Medline]88,Trudeau KJ, Hildebrand C, Garg P, Chiauzzi E, Zacharoff KL. A randomized controlled trial of the effects of online pain management education on primary care providers. Pain Med 2017 Dec 1;18(4):680-692. [CrossRef] [Medline]90] and video recording [Courteille O, Fahlstedt M, Ho J, Hedman L, Fors U, von Holst H, et al. Learning through a virtual patient vs recorded lecture: a comparison of knowledge retention in a trauma case. Int J Med Educ 2018 Mar 28;9:86-92 [FREE Full text] [CrossRef] [Medline]87,Foster A, Chaudhary N, Murphy J, Lok B, Waller J, Buckley PF. The use of simulation to teach suicide risk assessment to health profession trainees—rationale, methodology, and a proof of concept demonstration with a virtual patient. Acad Psychiatry 2015 Dec;39(6):620-629. [CrossRef] [Medline]89]—and in 1 study, a mix of traditional lectures and Web materials including video clips [Kumta SM, Tsang PL, Hung LK, Cheng JCY. Fostering critical thinking skills through a web-based tutorial programme for final year medical students--A randomized controlled study. J Educ Multimed Hypermedia 2003;12(3):267-273.51] was used.

Studies comparing different types of virtual patients contrasted narrative with problem-solving structure of virtual patients [Bearman M, Cesnik B, Liddell M. Random comparison of 'virtual patient' models in the context of teaching clinical communication skills. Med Educ 2001 Sep;35(9):824-832. [Medline]91]; virtual patients with and without usability enhancements [Davids MR, Chikte UM, Halperin ML. Effect of improving the usability of an e-learning resource: a randomized trial. Adv Physiol Educ 2014 Jun;38(2):155-160 [FREE Full text] [CrossRef] [Medline]94]; different forms of feedback in virtual patients [Foster A, Chaudhary N, Kim T, Waller JL, Wong J, Borish M, et al. Using virtual patients to teach empathy: a randomized controlled study to enhance medical students' empathic communication. Simul Healthc 2016 Jun;11(3):181-189. [CrossRef] [Medline]95,Friedman CP, France CL, Drossman DD. A randomized comparison of alternative formats for clinical simulations. Med Decis Making 1991;11(4):265-272. [CrossRef] [Medline]96]; worked with unworked versions of virtual patients [Harris JM, Sun H. A randomized trial of two e-learning strategies for teaching substance abuse management skills to physicians. Acad Med 2013 Sep;88(9):1357-1362 [FREE Full text] [CrossRef] [Medline]97]; differences between self-determined and mandatory access to virtual patients [Mahnken AH, Baumann M, Meister M, Schmitt V, Fischer MR. Blended learning in radiology: is self-determined learning really more effective? Eur J Radiol 2011 Jun;78(3):384-387. [CrossRef] [Medline]98]; virtual patients collections in which all the cases were presented at once to those automatically activated spaced in time [Maier EM, Hege I, Muntau AC, Huber J, Fischer MR. What are effects of a spaced activation of virtual patients in a pediatric course? BMC Med Educ 2013 Mar 28;13:45 [FREE Full text] [CrossRef] [Medline]99]; effects of virtual patient solving with virtual patient construction exercises [Tolsgaard MG, Jepsen RMHG, Rasmussen MB, Kayser L, Fors U, Laursen LC, et al. The effect of constructing versus solving virtual patient cases on transfer of learning: a randomized trial. Perspect Med Educ 2016 Feb;5(1):33-38 [FREE Full text] [CrossRef] [Medline]100]; linear versus branched design of virtual patients [Berger J, Bawab N, de Mooij J, Widmer DS, Szilas N, de Vriese C, et al. An open randomized controlled study comparing an online text-based scenario and a serious game by Belgian and Swiss pharmacy students. Curr Pharm Teach Learn 2018 Dec;10(3):267-276. [CrossRef] [Medline]92]; and finally the addition of representation scaffolding (see glossary in

Multimedia Appendix 1

Glossary.

DOC File, 76KBMultimedia Appendix 1) to virtual patients [Braun LT, Zottmann JM, Adolf C, Lottspeich C, Then C, Wirth S, et al. Representation scaffolds improve diagnostic efficiency in medical students. Med Educ 2017 Nov;51(11):1118-1126. [CrossRef] [Medline]93].

Furthermore, 41 studies had 2 study arms (see the first table in

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KBMultimedia Appendix 3), 7 studies had 3 arms [Leong SL, Baldwin CD, Adelman AM. Integrating web-based computer cases into a required clerkship: development and evaluation. Acad Med 2003 Mar;78(3):295-301. [Medline]62,Dankbaar ME, Alsma J, Jansen EE, van Merrienboer JJ, van Saase JL, Schuit SC. An experimental study on the effects of a simulation game on students' clinical cognitive skills and motivation. Adv Health Sci Educ Theory Pract 2016 Aug;21(3):505-521. [CrossRef] [Medline]88,Bearman M, Cesnik B, Liddell M. Random comparison of 'virtual patient' models in the context of teaching clinical communication skills. Med Educ 2001 Sep;35(9):824-832. [Medline]91,Foster A, Chaudhary N, Kim T, Waller JL, Wong J, Borish M, et al. Using virtual patients to teach empathy: a randomized controlled study to enhance medical students' empathic communication. Simul Healthc 2016 Jun;11(3):181-189. [CrossRef] [Medline]95-Mahnken AH, Baumann M, Meister M, Schmitt V, Fischer MR. Blended learning in radiology: is self-determined learning really more effective? Eur J Radiol 2011 Jun;78(3):384-387. [CrossRef] [Medline]98], and 3 studies had 4 arms [Li J, Li QL, Li J, Chen ML, Xie HF, Li YP, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach 2013;35(2):e963-e970. [CrossRef] [Medline]63,Maleck M, Fischer MR, Kammer B, Zeiler C, Mangel E, Schenk F, et al. Do computers teach better? A media comparison study for case-based teaching in radiology. Radiographics 2001;21(4):1025-1032. [CrossRef] [Medline]65,Qayumi AK, Kurihara Y, Imai M, Pachev G, Seo H, Hoshino Y, et al. Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience). Med Educ 2004 Oct;38(10):1080-1088. [CrossRef] [Medline]67].

Types of Participants

In total, 41 studies involved preregistered professionals (see the first table in

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KBMultimedia Appendix 3), with 8 studies focused on postregistered participants [Schwid HA, Rooke GA, Ross BK, Sivarajan M. Use of a computerized advanced cardiac life support simulator improves retention of advanced cardiac life support guidelines better than a textbook review. Crit Care Med 1999 Apr;27(4):821-824. [Medline]68,Schwid HA, Rooke GA, Michalowski P, Ross BK. Screen-based anesthesia simulation with debriefing improves performance in a mannequin-based anesthesia simulator. Teach Learn Med 2001;13(2):92-96. [CrossRef] [Medline]69,Triola M, Feldman H, Kalet AL, Zabar S, Kachur EK, Gillespie C, et al. A randomized trial of teaching clinical skills using virtual and live standardized patients. J Gen Intern Med 2006 May;21(5):424-429 [FREE Full text] [CrossRef] [Medline]74,Wang CL, Chinnugounder S, Hippe DS, Zaidi S, O'Malley RB, Bhargava P, et al. Comparative effectiveness of hands-on versus computer simulation-based training for contrast media reactions and teamwork skills. J Am Coll Radiol 2017 Jan;14(1):103-10.e3. [CrossRef] [Medline]76,Bryant R, Miller CL, Henderson D. Virtual clinical simulations in an online advanced health appraisal course. Clin Simul Nurs 2015 Oct;11(10):437-444. [CrossRef]78,Trudeau KJ, Hildebrand C, Garg P, Chiauzzi E, Zacharoff KL. A randomized controlled trial of the effects of online pain management education on primary care providers. Pain Med 2017 Dec 1;18(4):680-692. [CrossRef] [Medline]90,Davids MR, Chikte UM, Halperin ML. Effect of improving the usability of an e-learning resource: a randomized trial. Adv Physiol Educ 2014 Jun;38(2):155-160 [FREE Full text] [CrossRef] [Medline]94,Harris JM, Sun H. A randomized trial of two e-learning strategies for teaching substance abuse management skills to physicians. Acad Med 2013 Sep;88(9):1357-1362 [FREE Full text] [CrossRef] [Medline]97]; 2 studies involved both pre- and postregistered participants [Jeimy S, Wang JY, Richardson L. Evaluation of virtual patient cases for teaching diagnostic and management skills in internal medicine: a mixed methods study. BMC Res Notes 2018 Jun 5;11(1):357 [FREE Full text] [CrossRef] [Medline]59,Courteille O, Fahlstedt M, Ho J, Hedman L, Fors U, von Holst H, et al. Learning through a virtual patient vs recorded lecture: a comparison of knowledge retention in a trauma case. Int J Med Educ 2018 Mar 28;9:86-92 [FREE Full text] [CrossRef] [Medline]87].

In 37 out of 51 studies, participants were from the field of medicine. The studies from fields other than medicine were as follows: 6 studies in nursing [Haerling KA. Cost-utility analysis of virtual and mannequin-based simulation. Simul Healthc 2018 Feb;13(1):33-40. [CrossRef] [Medline]58,Liaw SY, Chan SW, Chen F, Hooi SC, Siau C. Comparison of virtual patient simulation with mannequin-based simulation for improving clinical performances in assessing and managing clinical deterioration: randomized controlled trial. J Med Internet Res 2014;16(9):e214 [FREE Full text] [CrossRef] [Medline]64,Secomb J, McKenna L, Smith C. The effectiveness of simulation activities on the cognitive abilities of undergraduate third-year nursing students: a randomised control trial. J Clin Nurs 2012 Dec;21(23-24):3475-3484. [CrossRef] [Medline]70,Tao H. Computer-based simulative training system—a new approach to teaching pre-hospital trauma care. J Med Coll PLA 2011 Dec;26(6):335-344. [CrossRef]73,Bryant R, Miller CL, Henderson D. Virtual clinical simulations in an online advanced health appraisal course. Clin Simul Nurs 2015 Oct;11(10):437-444. [CrossRef]78,Gu Y, Zou Z, Chen X. The Effects of vSIM for Nursing™ as a teaching strategy on fundamentals of nursing education in undergraduates. Clin Simul Nurs 2017 Apr;13(4):194-197. [CrossRef]80]; 2 in pharmacy [Al-Dahir S, Bryant K, Kennedy KB, Robinson DS. Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences. Am J Pharm Educ 2014 May 15;78(4):76 [FREE Full text] [CrossRef] [Medline]53,Berger J, Bawab N, de Mooij J, Widmer DS, Szilas N, de Vriese C, et al. An open randomized controlled study comparing an online text-based scenario and a serious game by Belgian and Swiss pharmacy students. Curr Pharm Teach Learn 2018 Dec;10(3):267-276. [CrossRef] [Medline]92]; and 1 each in physical therapy [Kinney P, Keskula DR, Perry JF. The effect of a computer assisted instructional program on physical therapy students. J Allied Health 1997;26(2):57-61. [Medline]61], osteopathic medicine [Smith BD, Silk K. Cultural competence clinic: an online, interactive, simulation for working effectively with Arab American Muslim patients. Acad Psychiatry 2011;35(5):312-316. [CrossRef] [Medline]84], and dentistry [Schittek Janda M, Mattheos N, Nattestad A, Wagner A, Nebel D, Färbom C, et al. Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history-taking skills. Eur J Dent Educ 2004 Aug;8(3):111-119. [CrossRef] [Medline]83]. In addition, 3 studies involved interprofessional education [Triola M, Feldman H, Kalet AL, Zabar S, Kachur EK, Gillespie C, et al. A randomized trial of teaching clinical skills using virtual and live standardized patients. J Gen Intern Med 2006 May;21(5):424-429 [FREE Full text] [CrossRef] [Medline]74,Wang CL, Chinnugounder S, Hippe DS, Zaidi S, O'Malley RB, Bhargava P, et al. Comparative effectiveness of hands-on versus computer simulation-based training for contrast media reactions and teamwork skills. J Am Coll Radiol 2017 Jan;14(1):103-10.e3. [CrossRef] [Medline]76,Trudeau KJ, Hildebrand C, Garg P, Chiauzzi E, Zacharoff KL. A randomized controlled trial of the effects of online pain management education on primary care providers. Pain Med 2017 Dec 1;18(4):680-692. [CrossRef] [Medline]90].

A total of 44 out of 51 studies were conducted in high-income countries; 19 were from the United States (see the first table in

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KBMultimedia Appendix 3); 5 from Germany [Maleck M, Fischer MR, Kammer B, Zeiler C, Mangel E, Schenk F, et al. Do computers teach better? A media comparison study for case-based teaching in radiology. Radiographics 2001;21(4):1025-1032. [CrossRef] [Medline]65,Lehmann R, Thiessen C, Frick B, Bosse HM, Nikendei C, Hoffmann GF, et al. Improving pediatric basic life support performance through blended learning with web-based virtual patients: randomized controlled trial. J Med Internet Res 2015 Jul 2;17(7):e162 [FREE Full text] [CrossRef] [Medline]82,Braun LT, Zottmann JM, Adolf C, Lottspeich C, Then C, Wirth S, et al. Representation scaffolds improve diagnostic efficiency in medical students. Med Educ 2017 Nov;51(11):1118-1126. [CrossRef] [Medline]93,Mahnken AH, Baumann M, Meister M, Schmitt V, Fischer MR. Blended learning in radiology: is self-determined learning really more effective? Eur J Radiol 2011 Jun;78(3):384-387. [CrossRef] [Medline]98,Maier EM, Hege I, Muntau AC, Huber J, Fischer MR. What are effects of a spaced activation of virtual patients in a pediatric course? BMC Med Educ 2013 Mar 28;13:45 [FREE Full text] [CrossRef] [Medline]99]; 3 each from Australia [Succar T, Zebington G, Billson F, Byth K, Barrie S, McCluskey P, et al. The impact of the Virtual Ophthalmology Clinic on medical students' learning: a randomised controlled trial. Eye (Lond) 2013 Oct;27(10):1151-1157. [CrossRef] [Medline]52,Secomb J, McKenna L, Smith C. The effectiveness of simulation activities on the cognitive abilities of undergraduate third-year nursing students: a randomised control trial. J Clin Nurs 2012 Dec;21(23-24):3475-3484. [CrossRef] [Medline]70,Bearman M, Cesnik B, Liddell M. Random comparison of 'virtual patient' models in the context of teaching clinical communication skills. Med Educ 2001 Sep;35(9):824-832. [Medline]91] and Sweden [Schittek Janda M, Mattheos N, Nattestad A, Wagner A, Nebel D, Färbom C, et al. Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history-taking skills. Eur J Dent Educ 2004 Aug;8(3):111-119. [CrossRef] [Medline]83,Wahlgren CF, Edelbring S, Fors U, Hindbeck H, Ståhle M. Evaluation of an interactive case simulation system in dermatology and venereology for medical students. BMC Med Educ 2006;6:40 [FREE Full text] [CrossRef] [Medline]85,Courteille O, Fahlstedt M, Ho J, Hedman L, Fors U, von Holst H, et al. Learning through a virtual patient vs recorded lecture: a comparison of knowledge retention in a trauma case. Int J Med Educ 2018 Mar 28;9:86-92 [FREE Full text] [CrossRef] [Medline]87]; 2 each from Canada [Jeimy S, Wang JY, Richardson L. Evaluation of virtual patient cases for teaching diagnostic and management skills in internal medicine: a mixed methods study. BMC Res Notes 2018 Jun 5;11(1):357 [FREE Full text] [CrossRef] [Medline]59,Kandasamy T, Fung K. Interactive internet-based cases for undergraduate otolaryngology education. Otolaryngol Head Neck Surg 2009 Mar;140(3):398-402. [CrossRef] [Medline]60], the Netherlands [Weverling GJ, Stam J, ten Cate TJ, van Crevel H. [Computer-assisted education in problem-solving in neurology; a randomized educational study]. Ned Tijdschr Geneeskd 1996 Feb 24;140(8):440-443. [Medline]86,Dankbaar ME, Alsma J, Jansen EE, van Merrienboer JJ, van Saase JL, Schuit SC. An experimental study on the effects of a simulation game on students' clinical cognitive skills and motivation. Adv Health Sci Educ Theory Pract 2016 Aug;21(3):505-521. [CrossRef] [Medline]88], and the United Kingdom [Miedzybrodzka Z, Hamilton NM, Gregory H, Milner B, Frade I, Sinclair T, et al. Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach. Eur J Hum Genet 2001 Dec;9(12):953-956 [FREE Full text] [CrossRef] [Medline]66,Williams C, Aubin S, Harkin P, Cottrell D. A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture. Med Educ 2001 Sep;35(9):847-854. [Medline]77]; and 1 study was conducted each in Belgium and Switzerland [Berger J, Bawab N, de Mooij J, Widmer DS, Szilas N, de Vriese C, et al. An open randomized controlled study comparing an online text-based scenario and a serious game by Belgian and Swiss pharmacy students. Curr Pharm Teach Learn 2018 Dec;10(3):267-276. [CrossRef] [Medline]92], Denmark [Tolsgaard MG, Jepsen RMHG, Rasmussen MB, Kayser L, Fors U, Laursen LC, et al. The effect of constructing versus solving virtual patient cases on transfer of learning: a randomized trial. Perspect Med Educ 2016 Feb;5(1):33-38 [FREE Full text] [CrossRef] [Medline]100], France [Bonnetain E, Boucheix JM, Hamet M, Freysz M. Benefits of computer screen-based simulation in learning cardiac arrest procedures. Med Educ 2010 Jul;44(7):716-722. [CrossRef] [Medline]54], Hong Kong [Kumta SM, Tsang PL, Hung LK, Cheng JCY. Fostering critical thinking skills through a web-based tutorial programme for final year medical students--A randomized controlled study. J Educ Multimed Hypermedia 2003;12(3):267-273.51], Japan [Qayumi AK, Kurihara Y, Imai M, Pachev G, Seo H, Hoshino Y, et al. Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience). Med Educ 2004 Oct;38(10):1080-1088. [CrossRef] [Medline]67], Poland [Kononowicz AA, Krawczyk P, Cebula G, Dembkowska M, Drab E, Fraczek B, et al. Effects of introducing a voluntary virtual patient module to a basic life support with an automated external defibrillator course: a randomised trial. BMC Med Educ 2012 Jun 18;12:41 [FREE Full text] [CrossRef] [Medline]50], Singapore [Liaw SY, Chan SW, Chen F, Hooi SC, Siau C. Comparison of virtual patient simulation with mannequin-based simulation for improving clinical performances in assessing and managing clinical deterioration: randomized controlled trial. J Med Internet Res 2014;16(9):e214 [FREE Full text] [CrossRef] [Medline]64], and Slovenia [Sobocan M, Turk N, Dinevski D, Hojs R, Balon BP. Problem-based learning in internal medicine: virtual patients or paper-based problems? Intern Med J 2017 Jan;47(1):99-103. [CrossRef] [Medline]71]. From the 7 studies conducted in low-and-middle-income countries, 3 were from China [Li J, Li QL, Li J, Chen ML, Xie HF, Li YP, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach 2013;35(2):e963-e970. [CrossRef] [Medline]63,Tao H. Computer-based simulative training system—a new approach to teaching pre-hospital trauma care. J Med Coll PLA 2011 Dec;26(6):335-344. [CrossRef]73,Gu Y, Zou Z, Chen X. The Effects of vSIM for Nursing™ as a teaching strategy on fundamentals of nursing education in undergraduates. Clin Simul Nurs 2017 Apr;13(4):194-197. [CrossRef]80], 2 from Colombia [Botezatu M, Hult H, Tessma MK, Fors UGH. Virtual patient simulation for learning and assessment: superior results in comparison with regular course exams. Med Teach 2010;32(10):845-850. [CrossRef] [Medline]55,Botezatu M, Hult H, Tessma MK, Fors U. Virtual patient simulation: knowledge gain or knowledge loss? Med Teach 2010;32(7):562-568. [CrossRef] [Medline]56], and 1 each from the Republic of South Africa [Davids MR, Chikte UM, Halperin ML. Effect of improving the usability of an e-learning resource: a randomized trial. Adv Physiol Educ 2014 Jun;38(2):155-160 [FREE Full text] [CrossRef] [Medline]94] and Iran [Vash JH, Yunesian M, Shariati M, Keshvari A, Harirchi I. Virtual patients in undergraduate surgery education: a randomized controlled study. ANZ J Surg 2007;77(1-2):54-59. [CrossRef] [Medline]75].

In

Multimedia Appendix 4

Summary of technical and educational features of included studies.

DOC File, 458KBMultimedia Appendix 4 we present the technical characteristics of virtual patient systems, topics of educational content presented, applied instructional design methods, setting of use, information on the validity of outcome measurement, and applied educational theories in the included studies.

Multimedia Appendix 5

Summary of excluded studies.

DOC File, 60KB
Multimedia Appendix 5
summarizes the reasons for excluding studies following a review of their full-text versions.

Effects of Interventions

Knowledge

In total, 33 studies assessed outcomes of knowledge. In all studies, knowledge was measured using paper-based tests (see the second table in

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KBMultimedia Appendix 3). In 19 studies, the test consisted of multiple-choice questions (MCQs). Other knowledge test designs contained multiple-response questions [Tolsgaard MG, Jepsen RMHG, Rasmussen MB, Kayser L, Fors U, Laursen LC, et al. The effect of constructing versus solving virtual patient cases on transfer of learning: a randomized trial. Perspect Med Educ 2016 Feb;5(1):33-38 [FREE Full text] [CrossRef] [Medline]100], true/false questions [Kononowicz AA, Krawczyk P, Cebula G, Dembkowska M, Drab E, Fraczek B, et al. Effects of introducing a voluntary virtual patient module to a basic life support with an automated external defibrillator course: a randomised trial. BMC Med Educ 2012 Jun 18;12:41 [FREE Full text] [CrossRef] [Medline]50], and key feature format questions [Lehmann R, Thiessen C, Frick B, Bosse HM, Nikendei C, Hoffmann GF, et al. Improving pediatric basic life support performance through blended learning with web-based virtual patients: randomized controlled trial. J Med Internet Res 2015 Jul 2;17(7):e162 [FREE Full text] [CrossRef] [Medline]82]. In 4 studies, the participants had to formulate free-text answers [Vash JH, Yunesian M, Shariati M, Keshvari A, Harirchi I. Virtual patients in undergraduate surgery education: a randomized controlled study. ANZ J Surg 2007;77(1-2):54-59. [CrossRef] [Medline]75,Wahlgren CF, Edelbring S, Fors U, Hindbeck H, Ståhle M. Evaluation of an interactive case simulation system in dermatology and venereology for medical students. BMC Med Educ 2006;6:40 [FREE Full text] [CrossRef] [Medline]85,Davids MR, Chikte UM, Halperin ML. Effect of improving the usability of an e-learning resource: a randomized trial. Adv Physiol Educ 2014 Jun;38(2):155-160 [FREE Full text] [CrossRef] [Medline]94,Maier EM, Hege I, Muntau AC, Huber J, Fischer MR. What are effects of a spaced activation of virtual patients in a pediatric course? BMC Med Educ 2013 Mar 28;13:45 [FREE Full text] [CrossRef] [Medline]99]. In 4 studies [Li J, Li QL, Li J, Chen ML, Xie HF, Li YP, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach 2013;35(2):e963-e970. [CrossRef] [Medline]63,Miedzybrodzka Z, Hamilton NM, Gregory H, Milner B, Frade I, Sinclair T, et al. Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach. Eur J Hum Genet 2001 Dec;9(12):953-956 [FREE Full text] [CrossRef] [Medline]66,Braun LT, Zottmann JM, Adolf C, Lottspeich C, Then C, Wirth S, et al. Representation scaffolds improve diagnostic efficiency in medical students. Med Educ 2017 Nov;51(11):1118-1126. [CrossRef] [Medline]93,Harris JM, Sun H. A randomized trial of two e-learning strategies for teaching substance abuse management skills to physicians. Acad Med 2013 Sep;88(9):1357-1362 [FREE Full text] [CrossRef] [Medline]97], the knowledge tests comprised a mix of different formats. Li et al [Li J, Li QL, Li J, Chen ML, Xie HF, Li YP, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach 2013;35(2):e963-e970. [CrossRef] [Medline]63] used a combination of multiple-choice and short answer questions; Miedzybrodzka et al [Miedzybrodzka Z, Hamilton NM, Gregory H, Milner B, Frade I, Sinclair T, et al. Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach. Eur J Hum Genet 2001 Dec;9(12):953-956 [FREE Full text] [CrossRef] [Medline]66] used MCQs and modified essays; Harris et al [Harris JM, Sun H. A randomized trial of two e-learning strategies for teaching substance abuse management skills to physicians. Acad Med 2013 Sep;88(9):1357-1362 [FREE Full text] [CrossRef] [Medline]97] applied MCQs with confidence levels combined with script concordance testing questions; and Braun et al [Braun LT, Zottmann JM, Adolf C, Lottspeich C, Then C, Wirth S, et al. Representation scaffolds improve diagnostic efficiency in medical students. Med Educ 2017 Nov;51(11):1118-1126. [CrossRef] [Medline]93] used a test consisting of multiple-choice items, key feature problems, and problem-solving tasks. Secomb et al [Secomb J, McKenna L, Smith C. The effectiveness of simulation activities on the cognitive abilities of undergraduate third-year nursing students: a randomised control trial. J Clin Nurs 2012 Dec;21(23-24):3475-3484. [CrossRef] [Medline]70] measured cognitive growth using a survey requiring selection of the most significant items regarding learning environment preferences. In 3 studies [Leong SL, Baldwin CD, Adelman AM. Integrating web-based computer cases into a required clerkship: development and evaluation. Acad Med 2003 Mar;78(3):295-301. [Medline]62,Tao H. Computer-based simulative training system—a new approach to teaching pre-hospital trauma care. J Med Coll PLA 2011 Dec;26(6):335-344. [CrossRef]73,Berger J, Bawab N, de Mooij J, Widmer DS, Szilas N, de Vriese C, et al. An open randomized controlled study comparing an online text-based scenario and a serious game by Belgian and Swiss pharmacy students. Curr Pharm Teach Learn 2018 Dec;10(3):267-276. [CrossRef] [Medline]92], the nature of the knowledge test was unclear. In the case of MCQs in which the nature of items was unclear or mixed, we classified the outcome as knowledge instead of, for example, clinical reasoning skills, but the borderline between those was sometimes blurred. Meta-knowledge (eg, knowledge about the clinical reasoning process itself) was classified as knowledge outcomes following the framework by Kraiger [Kraiger K, Ford JK, Salas E. Application of cognitive, skill-based, and affective theories of learning outcomes to new methods of training evaluation. J Appl Psychol 1993;78(2):311-328. [CrossRef] [Medline]101].

The effects of interventions on knowledge outcomes are summarized in the second table in

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KBMultimedia Appendix 3.

Virtual Patient Versus Traditional Education

In 4 [Kandasamy T, Fung K. Interactive internet-based cases for undergraduate otolaryngology education. Otolaryngol Head Neck Surg 2009 Mar;140(3):398-402. [CrossRef] [Medline]60,Li J, Li QL, Li J, Chen ML, Xie HF, Li YP, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach 2013;35(2):e963-e970. [CrossRef] [Medline]63,Qayumi AK, Kurihara Y, Imai M, Pachev G, Seo H, Hoshino Y, et al. Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience). Med Educ 2004 Oct;38(10):1080-1088. [CrossRef] [Medline]67,Subramanian A, Timberlake M, Mittakanti H, Lara M, Brandt ML. Novel educational approach for medical students: improved retention rates using interactive medical software compared with traditional lecture-based format. J Surg Educ 2012;69(2):253-256. [CrossRef] [Medline]72] of 18 studies comparing virtual patients with traditional education, the intervention resulted in more positive knowledge outcomes. In 2, the control group attended a lecture [Li J, Li QL, Li J, Chen ML, Xie HF, Li YP, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach 2013;35(2):e963-e970. [CrossRef] [Medline]63,Subramanian A, Timberlake M, Mittakanti H, Lara M, Brandt ML. Novel educational approach for medical students: improved retention rates using interactive medical software compared with traditional lecture-based format. J Surg Educ 2012;69(2):253-256. [CrossRef] [Medline]72], whereas in the remaining 2 studies, students participated in a reading exercise [Kandasamy T, Fung K. Interactive internet-based cases for undergraduate otolaryngology education. Otolaryngol Head Neck Surg 2009 Mar;140(3):398-402. [CrossRef] [Medline]60,Qayumi AK, Kurihara Y, Imai M, Pachev G, Seo H, Hoshino Y, et al. Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience). Med Educ 2004 Oct;38(10):1080-1088. [CrossRef] [Medline]67]. In 1 study [Al-Dahir S, Bryant K, Kennedy KB, Robinson DS. Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences. Am J Pharm Educ 2014 May 15;78(4):76 [FREE Full text] [CrossRef] [Medline]53], the control intervention arm (Problem-based learning (PBL) small group discussion) had significantly better results than the virtual patient intervention (SMD=−0.65, 95% CI −1.02 to −0.28, P=.001). In the remaining 13 studies, the difference did not reach a statistically significant level (see the second table in

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KBMultimedia Appendix 3).

We excluded 2 studies [Leong SL, Baldwin CD, Adelman AM. Integrating web-based computer cases into a required clerkship: development and evaluation. Acad Med 2003 Mar;78(3):295-301. [Medline]62,Maleck M, Fischer MR, Kammer B, Zeiler C, Mangel E, Schenk F, et al. Do computers teach better? A media comparison study for case-based teaching in radiology. Radiographics 2001;21(4):1025-1032. [CrossRef] [Medline]65] from our meta-analysis because of missing crucial outcome data. Jeimy et al [Jeimy S, Wang JY, Richardson L. Evaluation of virtual patient cases for teaching diagnostic and management skills in internal medicine: a mixed methods study. BMC Res Notes 2018 Jun 5;11(1):357 [FREE Full text] [CrossRef] [Medline]59] presented outcomes of a knowledge test compared item-by-item and the study was therefore excluded from the meta-analysis. We also excluded 1 study [Subramanian A, Timberlake M, Mittakanti H, Lara M, Brandt ML. Novel educational approach for medical students: improved retention rates using interactive medical software compared with traditional lecture-based format. J Surg Educ 2012;69(2):253-256. [CrossRef] [Medline]72] owing to its outlier value of SMD=12.5 being most likely because of reporting error and excluded another study [Secomb J, McKenna L, Smith C. The effectiveness of simulation activities on the cognitive abilities of undergraduate third-year nursing students: a randomised control trial. J Clin Nurs 2012 Dec;21(23-24):3475-3484. [CrossRef] [Medline]70] as we regarded meta-knowledge as very different from the other types of core knowledge outcomes.

The pooled effect for knowledge outcomes (SMD=0.11, 95% CI −0.17 to 0.39, I2=74%, n=927; Figure 2) suggests that virtual patient interventions are as efficient as traditional education.

Figure 2. Forest plot of virtual patient to traditional education comparison for knowledge outcomes. df: degrees of freedom; IV: interval variable; random: random effects model.
View this figure
Virtual Patient Blended Learning Versus Traditional Education

In 4 [Kononowicz AA, Krawczyk P, Cebula G, Dembkowska M, Drab E, Fraczek B, et al. Effects of introducing a voluntary virtual patient module to a basic life support with an automated external defibrillator course: a randomised trial. BMC Med Educ 2012 Jun 18;12:41 [FREE Full text] [CrossRef] [Medline]50,Succar T, Zebington G, Billson F, Byth K, Barrie S, McCluskey P, et al. The impact of the Virtual Ophthalmology Clinic on medical students' learning: a randomised controlled trial. Eye (Lond) 2013 Oct;27(10):1151-1157. [CrossRef] [Medline]52,Gu Y, Zou Z, Chen X. The Effects of vSIM for Nursing™ as a teaching strategy on fundamentals of nursing education in undergraduates. Clin Simul Nurs 2017 Apr;13(4):194-197. [CrossRef]80,Lehmann R, Thiessen C, Frick B, Bosse HM, Nikendei C, Hoffmann GF, et al. Improving pediatric basic life support performance through blended learning with web-based virtual patients: randomized controlled trial. J Med Internet Res 2015 Jul 2;17(7):e162 [FREE Full text] [CrossRef] [Medline]82] of the 5 studies comparing virtual patients as a supplement with traditional education in the domain of knowledge, the group having the additional resource scored better than the control group. Only in 1 study [Wahlgren CF, Edelbring S, Fors U, Hindbeck H, Ståhle M. Evaluation of an interactive case simulation system in dermatology and venereology for medical students. BMC Med Educ 2006;6:40 [FREE Full text] [CrossRef] [Medline]85] did the addition of virtual patients not lead to statistically significant difference in knowledge outcomes (P=.11).

The pooled effect for knowledge outcomes (SMD=0.73, 95% CI 0.24 to 1.22, I2=81%, n=439; Figure 3) suggests moderate effects preferring the mix of virtual patients with traditional education over traditional education alone.

Figure 3. Forest plot of virtual patient blended learning to traditional education comparison for knowledge outcomes. df: degrees of freedom; IV: interval variable; random: random effects model; VP: virtual patients.
View this figure
Virtual Patient Versus Other Types of Digital Education

A total of 2 studies compared the difference in knowledge outcomes between virtual patients and digital health education interventions. Courteille et al [Courteille O, Fahlstedt M, Ho J, Hedman L, Fors U, von Holst H, et al. Learning through a virtual patient vs recorded lecture: a comparison of knowledge retention in a trauma case. Int J Med Educ 2018 Mar 28;9:86-92 [FREE Full text] [CrossRef] [Medline]87] compared virtual patients with a video-recorded lecture, whereas Trudeau et al [Trudeau KJ, Hildebrand C, Garg P, Chiauzzi E, Zacharoff KL. A randomized controlled trial of the effects of online pain management education on primary care providers. Pain Med 2017 Dec 1;18(4):680-692. [CrossRef] [Medline]90] compared with a static Web course. Neither of these comparisons showed significant differences in knowledge outcomes.

Virtual Patient Design Comparison

In total, 8 studies focused on detecting the difference between variants of virtual patient design in the domain of knowledge. Only in 1 study by Friedman et al [Friedman CP, France CL, Drossman DD. A randomized comparison of alternative formats for clinical simulations. Med Decis Making 1991;11(4):265-272. [CrossRef] [Medline]96] were the differences at a statistically significant level. In this study, the pedagogic design of virtual patients was better than problem-solving and high-fidelity designs (P<.01). Comparing linear and branched virtual patients [Berger J, Bawab N, de Mooij J, Widmer DS, Szilas N, de Vriese C, et al. An open randomized controlled study comparing an online text-based scenario and a serious game by Belgian and Swiss pharmacy students. Curr Pharm Teach Learn 2018 Dec;10(3):267-276. [CrossRef] [Medline]92], scaffolded versus nonscaffolded [Braun LT, Zottmann JM, Adolf C, Lottspeich C, Then C, Wirth S, et al. Representation scaffolds improve diagnostic efficiency in medical students. Med Educ 2017 Nov;51(11):1118-1126. [CrossRef] [Medline]93], worked and unworked examples [Harris JM, Sun H. A randomized trial of two e-learning strategies for teaching substance abuse management skills to physicians. Acad Med 2013 Sep;88(9):1357-1362 [FREE Full text] [CrossRef] [Medline]97], virtual patient with usability extensions [Davids MR, Chikte UM, Halperin ML. Effect of improving the usability of an e-learning resource: a randomized trial. Adv Physiol Educ 2014 Jun;38(2):155-160 [FREE Full text] [CrossRef] [Medline]94], self-determined versus mandatory integration [Mahnken AH, Baumann M, Meister M, Schmitt V, Fischer MR. Blended learning in radiology: is self-determined learning really more effective? Eur J Radiol 2011 Jun;78(3):384-387. [CrossRef] [Medline]98], spaced versus nonspaced release of cases [Maier EM, Hege I, Muntau AC, Huber J, Fischer MR. What are effects of a spaced activation of virtual patients in a pediatric course? BMC Med Educ 2013 Mar 28;13:45 [FREE Full text] [CrossRef] [Medline]99], and virtual patient solving versus virtual patient design exercises [Tolsgaard MG, Jepsen RMHG, Rasmussen MB, Kayser L, Fors U, Laursen LC, et al. The effect of constructing versus solving virtual patient cases on transfer of learning: a randomized trial. Perspect Med Educ 2016 Feb;5(1):33-38 [FREE Full text] [CrossRef] [Medline]100] resulted in no significant differences in knowledge outcomes.

Skills

A total of 28 studies assessed skills outcomes (see the third table in

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KBMultimedia Appendix 3). Skills were assessed by performance on a mannequin in 9 studies [Kononowicz AA, Krawczyk P, Cebula G, Dembkowska M, Drab E, Fraczek B, et al. Effects of introducing a voluntary virtual patient module to a basic life support with an automated external defibrillator course: a randomised trial. BMC Med Educ 2012 Jun 18;12:41 [FREE Full text] [CrossRef] [Medline]50,Bonnetain E, Boucheix JM, Hamet M, Freysz M. Benefits of computer screen-based simulation in learning cardiac arrest procedures. Med Educ 2010 Jul;44(7):716-722. [CrossRef] [Medline]54,Liaw SY, Chan SW, Chen F, Hooi SC, Siau C. Comparison of virtual patient simulation with mannequin-based simulation for improving clinical performances in assessing and managing clinical deterioration: randomized controlled trial. J Med Internet Res 2014;16(9):e214 [FREE Full text] [CrossRef] [Medline]64,Schwid HA, Rooke GA, Ross BK, Sivarajan M. Use of a computerized advanced cardiac life support simulator improves retention of advanced cardiac life support guidelines better than a textbook review. Crit Care Med 1999 Apr;27(4):821-824. [Medline]68,Schwid HA, Rooke GA, Michalowski P, Ross BK. Screen-based anesthesia simulation with debriefing improves performance in a mannequin-based anesthesia simulator. Teach Learn Med 2001;13(2):92-96. [CrossRef] [Medline]69,Tao H. Computer-based simulative training system—a new approach to teaching pre-hospital trauma care. J Med Coll PLA 2011 Dec;26(6):335-344. [CrossRef]73,Gu Y, Zou Z, Chen X. The Effects of vSIM for Nursing™ as a teaching strategy on fundamentals of nursing education in undergraduates. Clin Simul Nurs 2017 Apr;13(4):194-197. [CrossRef]80,Lehmann R, Thiessen C, Frick B, Bosse HM, Nikendei C, Hoffmann GF, et al. Improving pediatric basic life support performance through blended learning with web-based virtual patients: randomized controlled trial. J Med Internet Res 2015 Jul 2;17(7):e162 [FREE Full text] [CrossRef] [Medline]82,Dankbaar ME, Alsma J, Jansen EE, van Merrienboer JJ, van Saase JL, Schuit SC. An experimental study on the effects of a simulation game on students' clinical cognitive skills and motivation. Adv Health Sci Educ Theory Pract 2016 Aug;21(3):505-521. [CrossRef] [Medline]88], by performance on a live standardized patient in 8 studies [Fleetwood J, Vaught W, Feldman D, Gracely E, Kassutto Z, Novack D. MedEthEx Online: a computer-based learning program in medical ethics and communication skills. Teach Learn Med 2000;12(2):96-104. [CrossRef] [Medline]57,Qayumi AK, Kurihara Y, Imai M, Pachev G, Seo H, Hoshino Y, et al. Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience). Med Educ 2004 Oct;38(10):1080-1088. [CrossRef] [Medline]67,Bryant R, Miller CL, Henderson D. Virtual clinical simulations in an online advanced health appraisal course. Clin Simul Nurs 2015 Oct;11(10):437-444. [CrossRef]78,Kaltman S, Talisman N, Pennestri S, Syverson E, Arthur P, Vovides Y. Using technology to enhance teaching of patient-centered interviewing for early medical students. Simul Healthc 2018 Jun;13(3):188-194. [CrossRef] [Medline]81,Foster A, Chaudhary N, Murphy J, Lok B, Waller J, Buckley PF. The use of simulation to teach suicide risk assessment to health profession trainees—rationale, methodology, and a proof of concept demonstration with a virtual patient. Acad Psychiatry 2015 Dec;39(6):620-629. [CrossRef] [Medline]89,Bearman M, Cesnik B, Liddell M. Random comparison of 'virtual patient' models in the context of teaching clinical communication skills. Med Educ 2001 Sep;35(9):824-832. [Medline]91,Foster A, Chaudhary N, Kim T, Waller JL, Wong J, Borish M, et al. Using virtual patients to teach empathy: a randomized controlled study to enhance medical students' empathic communication. Simul Healthc 2016 Jun;11(3):181-189. [CrossRef] [Medline]95,Tolsgaard MG, Jepsen RMHG, Rasmussen MB, Kayser L, Fors U, Laursen LC, et al. The effect of constructing versus solving virtual patient cases on transfer of learning: a randomized trial. Perspect Med Educ 2016 Feb;5(1):33-38 [FREE Full text] [CrossRef] [Medline]100], and performance on virtual patients [Braun LT, Zottmann JM, Adolf C, Lottspeich C, Then C, Wirth S, et al. Representation scaffolds improve diagnostic efficiency in medical students. Med Educ 2017 Nov;51(11):1118-1126. [CrossRef] [Medline]93] and real patients [Schittek Janda M, Mattheos N, Nattestad A, Wagner A, Nebel D, Färbom C, et al. Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history-taking skills. Eur J Dent Educ 2004 Aug;8(3):111-119. [CrossRef] [Medline]83] in 1 study each. In 6 studies, outcomes were measured by a written assignment involving description of photographed clinical cases [Li J, Li QL, Li J, Chen ML, Xie HF, Li YP, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach 2013;35(2):e963-e970. [CrossRef] [Medline]63], radiographs [Maleck M, Fischer MR, Kammer B, Zeiler C, Mangel E, Schenk F, et al. Do computers teach better? A media comparison study for case-based teaching in radiology. Radiographics 2001;21(4):1025-1032. [CrossRef] [Medline]65], carrying out and structuring a mental state examination based on videotaped material [Williams C, Aubin S, Harkin P, Cottrell D. A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture. Med Educ 2001 Sep;35(9):847-854. [Medline]77], solving paper cases [Triola M, Feldman H, Kalet AL, Zabar S, Kachur EK, Gillespie C, et al. A randomized trial of teaching clinical skills using virtual and live standardized patients. J Gen Intern Med 2006 May;21(5):424-429 [FREE Full text] [CrossRef] [Medline]74,Weverling GJ, Stam J, ten Cate TJ, van Crevel H. [Computer-assisted education in problem-solving in neurology; a randomized educational study]. Ned Tijdschr Geneeskd 1996 Feb 24;140(8):440-443. [Medline]86], and a modular paper-based test [Vash JH, Yunesian M, Shariati M, Keshvari A, Harirchi I. Virtual patients in undergraduate surgery education: a randomized controlled study. ANZ J Surg 2007;77(1-2):54-59. [CrossRef] [Medline]75]. In 2 studies [Botezatu M, Hult H, Tessma MK, Fors UGH. Virtual patient simulation for learning and assessment: superior results in comparison with regular course exams. Med Teach 2010;32(10):845-850. [CrossRef] [Medline]55,Botezatu M, Hult H, Tessma MK, Fors U. Virtual patient simulation: knowledge gain or knowledge loss? Med Teach 2010;32(7):562-568. [CrossRef] [Medline]56], outcomes were measured by a mix of paper cases and virtual patients. Kumta et al [Kumta SM, Tsang PL, Hung LK, Cheng JCY. Fostering critical thinking skills through a web-based tutorial programme for final year medical students--A randomized controlled study. J Educ Multimed Hypermedia 2003;12(3):267-273.51] combined computer-based assessment, objective structured clinical examination (OSCE), and clinical examination comprising patients in the ward into 1 score.

The effects of interventions on skills outcomes are summarized in the third table in

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KBMultimedia Appendix 3.

Virtual Patient Versus Traditional Education

In 9 of 14 studies comparing virtual patients with traditional education, the intervention resulted in better skills outcomes (see the third table in

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KBMultimedia Appendix 3). The virtual patient intervention showed larger effects than lectures [Li J, Li QL, Li J, Chen ML, Xie HF, Li YP, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach 2013;35(2):e963-e970. [CrossRef] [Medline]63,Williams C, Aubin S, Harkin P, Cottrell D. A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture. Med Educ 2001 Sep;35(9):847-854. [Medline]77], reading exercises [Qayumi AK, Kurihara Y, Imai M, Pachev G, Seo H, Hoshino Y, et al. Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience). Med Educ 2004 Oct;38(10):1080-1088. [CrossRef] [Medline]67-Schwid HA, Rooke GA, Michalowski P, Ross BK. Screen-based anesthesia simulation with debriefing improves performance in a mannequin-based anesthesia simulator. Teach Learn Med 2001;13(2):92-96. [CrossRef] [Medline]69], group discussions [Tao H. Computer-based simulative training system—a new approach to teaching pre-hospital trauma care. J Med Coll PLA 2011 Dec;26(6):335-344. [CrossRef]73], and activities comprising traditional methods, including lectures or hands-on training with mannequins [Bonnetain E, Boucheix JM, Hamet M, Freysz M. Benefits of computer screen-based simulation in learning cardiac arrest procedures. Med Educ 2010 Jul;44(7):716-722. [CrossRef] [Medline]54-Botezatu M, Hult H, Tessma MK, Fors U. Virtual patient simulation: knowledge gain or knowledge loss? Med Teach 2010;32(7):562-568. [CrossRef] [Medline]56].

Those skills which improved were clinical reasoning [Botezatu M, Hult H, Tessma MK, Fors UGH. Virtual patient simulation for learning and assessment: superior results in comparison with regular course exams. Med Teach 2010;32(10):845-850. [CrossRef] [Medline]55,Botezatu M, Hult H, Tessma MK, Fors U. Virtual patient simulation: knowledge gain or knowledge loss? Med Teach 2010;32(7):562-568. [CrossRef] [Medline]56,Li J, Li QL, Li J, Chen ML, Xie HF, Li YP, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach 2013;35(2):e963-e970. [CrossRef] [Medline]63,Williams C, Aubin S, Harkin P, Cottrell D. A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture. Med Educ 2001 Sep;35(9):847-854. [Medline]77], procedural skills [Bonnetain E, Boucheix JM, Hamet M, Freysz M. Benefits of computer screen-based simulation in learning cardiac arrest procedures. Med Educ 2010 Jul;44(7):716-722. [CrossRef] [Medline]54,Qayumi AK, Kurihara Y, Imai M, Pachev G, Seo H, Hoshino Y, et al. Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience). Med Educ 2004 Oct;38(10):1080-1088. [CrossRef] [Medline]67-Schwid HA, Rooke GA, Michalowski P, Ross BK. Screen-based anesthesia simulation with debriefing improves performance in a mannequin-based anesthesia simulator. Teach Learn Med 2001;13(2):92-96. [CrossRef] [Medline]69], and a mix of procedural and team skills [Tao H. Computer-based simulative training system—a new approach to teaching pre-hospital trauma care. J Med Coll PLA 2011 Dec;26(6):335-344. [CrossRef]73].

We did not include in the meta-analysis 2 studies with incomplete reported data [Maleck M, Fischer MR, Kammer B, Zeiler C, Mangel E, Schenk F, et al. Do computers teach better? A media comparison study for case-based teaching in radiology. Radiographics 2001;21(4):1025-1032. [CrossRef] [Medline]65,Triola M, Feldman H, Kalet AL, Zabar S, Kachur EK, Gillespie C, et al. A randomized trial of teaching clinical skills using virtual and live standardized patients. J Gen Intern Med 2006 May;21(5):424-429 [FREE Full text] [CrossRef] [Medline]74]. We also excluded skills outcomes from the study by Haerling [Haerling KA. Cost-utility analysis of virtual and mannequin-based simulation. Simul Healthc 2018 Feb;13(1):33-40. [CrossRef] [Medline]58] as these were available for a randomly selected subgroup only and from Wang et al [Wang CL, Chinnugounder S, Hippe DS, Zaidi S, O'Malley RB, Bhargava P, et al. Comparative effectiveness of hands-on versus computer simulation-based training for contrast media reactions and teamwork skills. J Am Coll Radiol 2017 Jan;14(1):103-10.e3. [CrossRef] [Medline]76] as they were measured for teams of students only and not individually.

The pooled effect on skills outcomes was (SMD=0.90, 95% CI 0.49 to 1.32, I2=88%, n=897; Figure 4). Overall, this suggests that virtual patients have moderate to large positive effects in comparison with traditional education in the investigated types of skills.

Figure 4. Forest plot of virtual patient to traditional education comparison for skills outcomes. df: degrees of freedom; IV: interval variable; random: random effects model; VP: virtual patients.
View this figure
Virtual Patient Blended Learning Versus Traditional Education

In 3 [Lehmann R, Thiessen C, Frick B, Bosse HM, Nikendei C, Hoffmann GF, et al. Improving pediatric basic life support performance through blended learning with web-based virtual patients: randomized controlled trial. J Med Internet Res 2015 Jul 2;17(7):e162 [FREE Full text] [CrossRef] [Medline]82,Schittek Janda M, Mattheos N, Nattestad A, Wagner A, Nebel D, Färbom C, et al. Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history-taking skills. Eur J Dent Educ 2004 Aug;8(3):111-119. [CrossRef] [Medline]83,Weverling GJ, Stam J, ten Cate TJ, van Crevel H. [Computer-assisted education in problem-solving in neurology; a randomized educational study]. Ned Tijdschr Geneeskd 1996 Feb 24;140(8):440-443. [Medline]86] out of 7 studies, the groups using virtual patients blended learning scored better than the control group in the skills domain. Lehmann et al [Lehmann R, Thiessen C, Frick B, Bosse HM, Nikendei C, Hoffmann GF, et al. Improving pediatric basic life support performance through blended learning with web-based virtual patients: randomized controlled trial. J Med Internet Res 2015 Jul 2;17(7):e162 [FREE Full text] [CrossRef] [Medline]82] demonstrated significantly improved procedural skills (P<.001), whereas Weverling et al [Weverling GJ, Stam J, ten Cate TJ, van Crevel H. [Computer-assisted education in problem-solving in neurology; a randomized educational study]. Ned Tijdschr Geneeskd 1996 Feb 24;140(8):440-443. [Medline]86] reported on improved clinical reasoning skills (P<.001) and Schittek Janda et al [Schittek Janda M, Mattheos N, Nattestad A, Wagner A, Nebel D, Färbom C, et al. Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history-taking skills. Eur J Dent Educ 2004 Aug;8(3):111-119. [CrossRef] [Medline]83] on communication skills (P<.01). Furthermore, 2 studies [Bryant R, Miller CL, Henderson D. Virtual clinical simulations in an online advanced health appraisal course. Clin Simul Nurs 2015 Oct;11(10):437-444. [CrossRef]78,Gu Y, Zou Z, Chen X. The Effects of vSIM for Nursing™ as a teaching strategy on fundamentals of nursing education in undergraduates. Clin Simul Nurs 2017 Apr;13(4):194-197. [CrossRef]80] involving nursing students showed no significant difference. The study by Bryant et al [Bryant R, Miller CL, Henderson D. Virtual clinical simulations in an online advanced health appraisal course. Clin Simul Nurs 2015 Oct;11(10):437-444. [CrossRef]78] evaluated communication skills (P=.38), whereas Gu et al [Gu Y, Zou Z, Chen X. The Effects of vSIM for Nursing™ as a teaching strategy on fundamentals of nursing education in undergraduates. Clin Simul Nurs 2017 Apr;13(4):194-197. [CrossRef]80] measured procedural skills (P>.05). We excluded 3 studies [Kononowicz AA, Krawczyk P, Cebula G, Dembkowska M, Drab E, Fraczek B, et al. Effects of introducing a voluntary virtual patient module to a basic life support with an automated external defibrillator course: a randomised trial. BMC Med Educ 2012 Jun 18;12:41 [FREE Full text] [CrossRef] [Medline]50,Kaltman S, Talisman N, Pennestri S, Syverson E, Arthur P, Vovides Y. Using technology to enhance teaching of patient-centered interviewing for early medical students. Simul Healthc 2018 Jun;13(3):188-194. [CrossRef] [Medline]81,Schittek Janda M, Mattheos N, Nattestad A, Wagner A, Nebel D, Färbom C, et al. Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history-taking skills. Eur J Dent Educ 2004 Aug;8(3):111-119. [CrossRef] [Medline]83] from the meta-analysis because of insufficient data provided in the report or item-by-item comparison of a skills checklist.

The pooled effect for skills outcomes (SMD=0.60, 95% CI −0.07 to 1.27, I2=83%, n=247; Figure 5) suggests that virtual patients blended with traditional education have moderate positive effects in comparison with traditional education alone.

Figure 5. Forest plot of virtual patient blended learning to traditional education comparison for skills outcomes. df: degrees of freedom; IV: interval variable; random: random effects model; VP: virtual patients.
View this figure
Virtual Patient Versus Other Types of Digital Education

Out of 3 studies comparing skills outcomes in virtual patients with other types of digital education studies, Kumta et al [Kumta SM, Tsang PL, Hung LK, Cheng JCY. Fostering critical thinking skills through a web-based tutorial programme for final year medical students--A randomized controlled study. J Educ Multimed Hypermedia 2003;12(3):267-273.51] showed a significant difference (P<.001). In this study, virtual patients were better than a range of different traditional teaching methods supplemented by Web content that included video clips, PowerPoint presentations, digital notes, and handouts. The target outcomes were clinical skills assessed by OSCE stations and examination of patients in the wards. In a study by Dankbaar et al [Dankbaar ME, Alsma J, Jansen EE, van Merrienboer JJ, van Saase JL, Schuit SC. An experimental study on the effects of a simulation game on students' clinical cognitive skills and motivation. Adv Health Sci Educ Theory Pract 2016 Aug;21(3):505-521. [CrossRef] [Medline]88], virtual patients were not significantly better in teaching procedural skill than an electronic module only (P>.05). Finally, in the study by Foster et al [Foster A, Chaudhary N, Murphy J, Lok B, Waller J, Buckley PF. The use of simulation to teach suicide risk assessment to health profession trainees—rationale, methodology, and a proof of concept demonstration with a virtual patient. Acad Psychiatry 2015 Dec;39(6):620-629. [CrossRef] [Medline]89], virtual patients showed no significant difference when compared with video recordings in teaching communication skills (P>.05).

Virtual Patient Design Comparison

From the 4 studies that compared the influence of different virtual patient designs on skills outcomes, Foster et al [Foster A, Chaudhary N, Kim T, Waller JL, Wong J, Borish M, et al. Using virtual patients to teach empathy: a randomized controlled study to enhance medical students' empathic communication. Simul Healthc 2016 Jun;11(3):181-189. [CrossRef] [Medline]95] showed that virtual patients with emphatic feedback were significantly better in training communication skills than those virtual patients without feedback (P<.03). In the study by Bearman et al [Bearman M, Cesnik B, Liddell M. Random comparison of 'virtual patient' models in the context of teaching clinical communication skills. Med Educ 2001 Sep;35(9):824-832. [Medline]91], narrative virtual patients were significantly better than problem-solving virtual patients in conveying communication skills (P=.03). In a study by Braun et al [Braun LT, Zottmann JM, Adolf C, Lottspeich C, Then C, Wirth S, et al. Representation scaffolds improve diagnostic efficiency in medical students. Med Educ 2017 Nov;51(11):1118-1126. [CrossRef] [Medline]93], the addition of representational scaffolding to a virtual patient intervention significantly improved diagnostic efficiency (P=.045). Finally, in the study by Tolsgaard et al [Tolsgaard MG, Jepsen RMHG, Rasmussen MB, Kayser L, Fors U, Laursen LC, et al. The effect of constructing versus solving virtual patient cases on transfer of learning: a randomized trial. Perspect Med Educ 2016 Feb;5(1):33-38 [FREE Full text] [CrossRef] [Medline]100], there was no significant difference in integrated clinical performance when students constructed or solved virtual patients (P=.54).

Attitudes

A total of 11 studies reported attitudinal outcomes (see the third table in

Multimedia Appendix 1

Glossary.

DOC File, 76KBMultimedia Appendix 1). The attitudes related to confidence, preparedness, comfort, self-efficacy, and perceived ability in topics such as history taking and clinical breast examination [Deladisma AM, Gupta M, Kotranza A, Bittner JG, Imam T, Swinson D, et al. A pilot study to integrate an immersive virtual patient with a breast complaint and breast examination simulator into a surgery clerkship. Am J Surg 2009 Jan;197(1):102-106. [CrossRef] [Medline]79], diagnostic and management abilities [Jeimy S, Wang JY, Richardson L. Evaluation of virtual patient cases for teaching diagnostic and management skills in internal medicine: a mixed methods study. BMC Res Notes 2018 Jun 5;11(1):357 [FREE Full text] [CrossRef] [Medline]59], contrast reaction management and teamwork [Wang CL, Chinnugounder S, Hippe DS, Zaidi S, O'Malley RB, Bhargava P, et al. Comparative effectiveness of hands-on versus computer simulation-based training for contrast media reactions and teamwork skills. J Am Coll Radiol 2017 Jan;14(1):103-10.e3. [CrossRef] [Medline]76], ethical, legal, and communication issues [Fleetwood J, Vaught W, Feldman D, Gracely E, Kassutto Z, Novack D. MedEthEx Online: a computer-based learning program in medical ethics and communication skills. Teach Learn Med 2000;12(2):96-104. [CrossRef] [Medline]57,Kaltman S, Talisman N, Pennestri S, Syverson E, Arthur P, Vovides Y. Using technology to enhance teaching of patient-centered interviewing for early medical students. Simul Healthc 2018 Jun;13(3):188-194. [CrossRef] [Medline]81], opioid therapy [Trudeau KJ, Hildebrand C, Garg P, Chiauzzi E, Zacharoff KL. A randomized controlled trial of the effects of online pain management education on primary care providers. Pain Med 2017 Dec 1;18(4):680-692. [CrossRef] [Medline]90], cultural competence [Smith BD, Silk K. Cultural competence clinic: an online, interactive, simulation for working effectively with Arab American Muslim patients. Acad Psychiatry 2011;35(5):312-316. [CrossRef] [Medline]84], procedural knowledge in pediatric basic life support [Lehmann R, Thiessen C, Frick B, Bosse HM, Nikendei C, Hoffmann GF, et al. Improving pediatric basic life support performance through blended learning with web-based virtual patients: randomized controlled trial. J Med Internet Res 2015 Jul 2;17(7):e162 [FREE Full text] [CrossRef] [Medline]82], performing pharmacy triage [Berger J, Bawab N, de Mooij J, Widmer DS, Szilas N, de Vriese C, et al. An open randomized controlled study comparing an online text-based scenario and a serious game by Belgian and Swiss pharmacy students. Curr Pharm Teach Learn 2018 Dec;10(3):267-276. [CrossRef] [Medline]92], caring for distress disorders patients [Triola M, Feldman H, Kalet AL, Zabar S, Kachur EK, Gillespie C, et al. A randomized trial of teaching clinical skills using virtual and live standardized patients. J Gen Intern Med 2006 May;21(5):424-429 [FREE Full text] [CrossRef] [Medline]74], and anxiety [Williams C, Aubin S, Harkin P, Cottrell D. A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture. Med Educ 2001 Sep;35(9):847-854. [Medline]77].

The effects of interventions on attitudinal outcomes are presented in the fourth table in

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KBMultimedia Appendix 3. Furthermore, 3 studies presented pooled scores on students‘ self-assessment. In the study by Lehmann et al [Lehmann R, Thiessen C, Frick B, Bosse HM, Nikendei C, Hoffmann GF, et al. Improving pediatric basic life support performance through blended learning with web-based virtual patients: randomized controlled trial. J Med Internet Res 2015 Jul 2;17(7):e162 [FREE Full text] [CrossRef] [Medline]82], students felt more confident in their knowledge and skills on performing pediatric basic life support with additional access to virtual patients that supplemented their traditional course (P<.001). There were no significant differences in the remaining 2 studies focusing on communication-related self-efficacy [Kaltman S, Talisman N, Pennestri S, Syverson E, Arthur P, Vovides Y. Using technology to enhance teaching of patient-centered interviewing for early medical students. Simul Healthc 2018 Jun;13(3):188-194. [CrossRef] [Medline]81] and attitudes related to opioid therapy [Trudeau KJ, Hildebrand C, Garg P, Chiauzzi E, Zacharoff KL. A randomized controlled trial of the effects of online pain management education on primary care providers. Pain Med 2017 Dec 1;18(4):680-692. [CrossRef] [Medline]90].

In the study by Williams et al [Williams C, Aubin S, Harkin P, Cottrell D. A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture. Med Educ 2001 Sep;35(9):847-854. [Medline]77], more items related to self-assessment of competences (in dealing with ethical aspects and managing anxiety) were scored lower in the virtual patient group than in the traditional education groups. There were no differences in analyzed items related to attitudes in 4 studies [Fleetwood J, Vaught W, Feldman D, Gracely E, Kassutto Z, Novack D. MedEthEx Online: a computer-based learning program in medical ethics and communication skills. Teach Learn Med 2000;12(2):96-104. [CrossRef] [Medline]57,Jeimy S, Wang JY, Richardson L. Evaluation of virtual patient cases for teaching diagnostic and management skills in internal medicine: a mixed methods study. BMC Res Notes 2018 Jun 5;11(1):357 [FREE Full text] [CrossRef] [Medline]59,Triola M, Feldman H, Kalet AL, Zabar S, Kachur EK, Gillespie C, et al. A randomized trial of teaching clinical skills using virtual and live standardized patients. J Gen Intern Med 2006 May;21(5):424-429 [FREE Full text] [CrossRef] [Medline]74,Deladisma AM, Gupta M, Kotranza A, Bittner JG, Imam T, Swinson D, et al. A pilot study to integrate an immersive virtual patient with a breast complaint and breast examination simulator into a surgery clerkship. Am J Surg 2009 Jan;197(1):102-106. [CrossRef] [Medline]79]. In the study by Smith et al [Smith BD, Silk K. Cultural competence clinic: an online, interactive, simulation for working effectively with Arab American Muslim patients. Acad Psychiatry 2011;35(5):312-316. [CrossRef] [Medline]84], the results regarding attitudes toward clinical cultural competence were presented separately for bilingual and English-speaking students, which makes it difficult to aggregate not knowing the number of bilingual students in each study group. However, the descriptive conclusion of the authors was that general cultural competence measures were the same for the virtual patient and control group. In 2 studies [Wang CL, Chinnugounder S, Hippe DS, Zaidi S, O'Malley RB, Bhargava P, et al. Comparative effectiveness of hands-on versus computer simulation-based training for contrast media reactions and teamwork skills. J Am Coll Radiol 2017 Jan;14(1):103-10.e3. [CrossRef] [Medline]76,Berger J, Bawab N, de Mooij J, Widmer DS, Szilas N, de Vriese C, et al. An open randomized controlled study comparing an online text-based scenario and a serious game by Belgian and Swiss pharmacy students. Curr Pharm Teach Learn 2018 Dec;10(3):267-276. [CrossRef] [Medline]92], the results were compared item-by-item and only within the groups (pre/posttest), not between the study groups.

Satisfaction

In total, 17 studies measured satisfaction resulting from an intervention (see the fifth table in

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KBMultimedia Appendix 3). All outcomes in this category were measured by satisfaction questionnaires. Different facets of satisfaction were measured, which we classified in the following 5 dimensions: general impression (global score or willingness to recommend), comfort in use (learning style preference, engagement or motivation, positive climate or safety, and enjoyment or pleasure), integration in curriculum (time constraints, relevance, and level of difficulty), academic factors (feedback quality, structure, and clarity), and satisfaction with technical features (usability and information technology readiness).

In 4 out of 17 studies evaluating the satisfaction of students receiving a virtual patient intervention, the result was presented as 1 aggregated score of several items. Furthermore, 3 of those studies compared different design variants of virtual patients. In the study by Friedman et al [Friedman CP, France CL, Drossman DD. A randomized comparison of alternative formats for clinical simulations. Med Decis Making 1991;11(4):265-272. [CrossRef] [Medline]96], the pedagogic format (menus, guided) resulted in higher satisfaction scores than the high-fidelity (free text, unguided) format (P<.01). There was no statistically significant difference between the virtual patients with and without usability enhancements [Davids MR, Chikte UM, Halperin ML. Effect of improving the usability of an e-learning resource: a randomized trial. Adv Physiol Educ 2014 Jun;38(2):155-160 [FREE Full text] [CrossRef] [Medline]94] (P=.13) and solving versus constructing virtual patients [Tolsgaard MG, Jepsen RMHG, Rasmussen MB, Kayser L, Fors U, Laursen LC, et al. The effect of constructing versus solving virtual patient cases on transfer of learning: a randomized trial. Perspect Med Educ 2016 Feb;5(1):33-38 [FREE Full text] [CrossRef] [Medline]100] (P=.46). One study [Haerling KA. Cost-utility analysis of virtual and mannequin-based simulation. Simul Healthc 2018 Feb;13(1):33-40. [CrossRef] [Medline]58] presented comparison of virtual patients with mannequin-based training using a single score for student satisfaction and self-confidence in learning, showing no difference between the simulation modalities (P=.11).

In the remaining 13 out 17 studies, the survey responses were compared item-by-item. In 4 studies, the majority of the items indicated preference for the virtual patient intervention, in comparison with lecture [Li J, Li QL, Li J, Chen ML, Xie HF, Li YP, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach 2013;35(2):e963-e970. [CrossRef] [Medline]63], reading assignment [Qayumi AK, Kurihara Y, Imai M, Pachev G, Seo H, Hoshino Y, et al. Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience). Med Educ 2004 Oct;38(10):1080-1088. [CrossRef] [Medline]67], video-based learning [Foster A, Chaudhary N, Murphy J, Lok B, Waller J, Buckley PF. The use of simulation to teach suicide risk assessment to health profession trainees—rationale, methodology, and a proof of concept demonstration with a virtual patient. Acad Psychiatry 2015 Dec;39(6):620-629. [CrossRef] [Medline]89], and Web tutorial [Dankbaar ME, Alsma J, Jansen EE, van Merrienboer JJ, van Saase JL, Schuit SC. An experimental study on the effects of a simulation game on students' clinical cognitive skills and motivation. Adv Health Sci Educ Theory Pract 2016 Aug;21(3):505-521. [CrossRef] [Medline]88]. In 7 studies, most items were indifferent between the groups [Al-Dahir S, Bryant K, Kennedy KB, Robinson DS. Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences. Am J Pharm Educ 2014 May 15;78(4):76 [FREE Full text] [CrossRef] [Medline]53,Jeimy S, Wang JY, Richardson L. Evaluation of virtual patient cases for teaching diagnostic and management skills in internal medicine: a mixed methods study. BMC Res Notes 2018 Jun 5;11(1):357 [FREE Full text] [CrossRef] [Medline]59,Leong SL, Baldwin CD, Adelman AM. Integrating web-based computer cases into a required clerkship: development and evaluation. Acad Med 2003 Mar;78(3):295-301. [Medline]62,Maleck M, Fischer MR, Kammer B, Zeiler C, Mangel E, Schenk F, et al. Do computers teach better? A media comparison study for case-based teaching in radiology. Radiographics 2001;21(4):1025-1032. [CrossRef] [Medline]65,Miedzybrodzka Z, Hamilton NM, Gregory H, Milner B, Frade I, Sinclair T, et al. Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach. Eur J Hum Genet 2001 Dec;9(12):953-956 [FREE Full text] [CrossRef] [Medline]66,Triola M, Feldman H, Kalet AL, Zabar S, Kachur EK, Gillespie C, et al. A randomized trial of teaching clinical skills using virtual and live standardized patients. J Gen Intern Med 2006 May;21(5):424-429 [FREE Full text] [CrossRef] [Medline]74,Berger J, Bawab N, de Mooij J, Widmer DS, Szilas N, de Vriese C, et al. An open randomized controlled study comparing an online text-based scenario and a serious game by Belgian and Swiss pharmacy students. Curr Pharm Teach Learn 2018 Dec;10(3):267-276. [CrossRef] [Medline]92]. In 1 study [Wang CL, Chinnugounder S, Hippe DS, Zaidi S, O'Malley RB, Bhargava P, et al. Comparative effectiveness of hands-on versus computer simulation-based training for contrast media reactions and teamwork skills. J Am Coll Radiol 2017 Jan;14(1):103-10.e3. [CrossRef] [Medline]76], most items (5 out of 6) in a satisfaction survey were better rated in the mannequin-based training than in the virtual patient group.

Secondary Outcomes

One study had cost-effectiveness as an outcome [Haerling KA. Cost-utility analysis of virtual and mannequin-based simulation. Simul Healthc 2018 Feb;13(1):33-40. [CrossRef] [Medline]58]. In 9 studies, statements were made regarding the cost of the intervention—either monetary or in development time [Al-Dahir S, Bryant K, Kennedy KB, Robinson DS. Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences. Am J Pharm Educ 2014 May 15;78(4):76 [FREE Full text] [CrossRef] [Medline]53,Kandasamy T, Fung K. Interactive internet-based cases for undergraduate otolaryngology education. Otolaryngol Head Neck Surg 2009 Mar;140(3):398-402. [CrossRef] [Medline]60,Leong SL, Baldwin CD, Adelman AM. Integrating web-based computer cases into a required clerkship: development and evaluation. Acad Med 2003 Mar;78(3):295-301. [Medline]62,Liaw SY, Chan SW, Chen F, Hooi SC, Siau C. Comparison of virtual patient simulation with mannequin-based simulation for improving clinical performances in assessing and managing clinical deterioration: randomized controlled trial. J Med Internet Res 2014;16(9):e214 [FREE Full text] [CrossRef] [Medline]64-Miedzybrodzka Z, Hamilton NM, Gregory H, Milner B, Frade I, Sinclair T, et al. Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach. Eur J Hum Genet 2001 Dec;9(12):953-956 [FREE Full text] [CrossRef] [Medline]66,Deladisma AM, Gupta M, Kotranza A, Bittner JG, Imam T, Swinson D, et al. A pilot study to integrate an immersive virtual patient with a breast complaint and breast examination simulator into a surgery clerkship. Am J Surg 2009 Jan;197(1):102-106. [CrossRef] [Medline]79,Foster A, Chaudhary N, Kim T, Waller JL, Wong J, Borish M, et al. Using virtual patients to teach empathy: a randomized controlled study to enhance medical students' empathic communication. Simul Healthc 2016 Jun;11(3):181-189. [CrossRef] [Medline]95]. Only 1 study provided numerical data on both types of intervention [Foster A, Chaudhary N, Kim T, Waller JL, Wong J, Borish M, et al. Using virtual patients to teach empathy: a randomized controlled study to enhance medical students' empathic communication. Simul Healthc 2016 Jun;11(3):181-189. [CrossRef] [Medline]95]. The comparison was qualitative in 3 studies [Liaw SY, Chan SW, Chen F, Hooi SC, Siau C. Comparison of virtual patient simulation with mannequin-based simulation for improving clinical performances in assessing and managing clinical deterioration: randomized controlled trial. J Med Internet Res 2014;16(9):e214 [FREE Full text] [CrossRef] [Medline]64,Maleck M, Fischer MR, Kammer B, Zeiler C, Mangel E, Schenk F, et al. Do computers teach better? A media comparison study for case-based teaching in radiology. Radiographics 2001;21(4):1025-1032. [CrossRef] [Medline]65,Bryant R, Miller CL, Henderson D. Virtual clinical simulations in an online advanced health appraisal course. Clin Simul Nurs 2015 Oct;11(10):437-444. [CrossRef]78]. In 5 studies, estimations of costs were made for the virtual patient group without contrasting it with the cost of the control intervention [Al-Dahir S, Bryant K, Kennedy KB, Robinson DS. Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences. Am J Pharm Educ 2014 May 15;78(4):76 [FREE Full text] [CrossRef] [Medline]53,Kandasamy T, Fung K. Interactive internet-based cases for undergraduate otolaryngology education. Otolaryngol Head Neck Surg 2009 Mar;140(3):398-402. [CrossRef] [Medline]60,Leong SL, Baldwin CD, Adelman AM. Integrating web-based computer cases into a required clerkship: development and evaluation. Acad Med 2003 Mar;78(3):295-301. [Medline]62,Miedzybrodzka Z, Hamilton NM, Gregory H, Milner B, Frade I, Sinclair T, et al. Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach. Eur J Hum Genet 2001 Dec;9(12):953-956 [FREE Full text] [CrossRef] [Medline]66,Deladisma AM, Gupta M, Kotranza A, Bittner JG, Imam T, Swinson D, et al. A pilot study to integrate an immersive virtual patient with a breast complaint and breast examination simulator into a surgery clerkship. Am J Surg 2009 Jan;197(1):102-106. [CrossRef] [Medline]79]. None of the included studies had patient outcomes or adverse effects as the main outcome measure. Even though none of the studies reported direct patient outcomes, in 2 studies, the participants were observed by raters while performing tasks on real patients as an outcome assessment [Kumta SM, Tsang PL, Hung LK, Cheng JCY. Fostering critical thinking skills through a web-based tutorial programme for final year medical students--A randomized controlled study. J Educ Multimed Hypermedia 2003;12(3):267-273.51,Schittek Janda M, Mattheos N, Nattestad A, Wagner A, Nebel D, Färbom C, et al. Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history-taking skills. Eur J Dent Educ 2004 Aug;8(3):111-119. [CrossRef] [Medline]83]. In the study by Kumta et al [Kumta SM, Tsang PL, Hung LK, Cheng JCY. Fostering critical thinking skills through a web-based tutorial programme for final year medical students--A randomized controlled study. J Educ Multimed Hypermedia 2003;12(3):267-273.51], the score was included in more complex assessment (including MCQ tests and OSCE examination) and the patient-related outcome was not explicitly reported. In the study by Schittek Janda et al [Schittek Janda M, Mattheos N, Nattestad A, Wagner A, Nebel D, Färbom C, et al. Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history-taking skills. Eur J Dent Educ 2004 Aug;8(3):111-119. [CrossRef] [Medline]83], first year students of dentistry were asked to perform history taking with real patients and were rated by the instructor. The patients’ perspective was, however, not considered. Even though none of the studies had adverse effects as the major outcome, 6 studies [Al-Dahir S, Bryant K, Kennedy KB, Robinson DS. Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences. Am J Pharm Educ 2014 May 15;78(4):76 [FREE Full text] [CrossRef] [Medline]53,Botezatu M, Hult H, Tessma MK, Fors UGH. Virtual patient simulation for learning and assessment: superior results in comparison with regular course exams. Med Teach 2010;32(10):845-850. [CrossRef] [Medline]55,Qayumi AK, Kurihara Y, Imai M, Pachev G, Seo H, Hoshino Y, et al. Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience). Med Educ 2004 Oct;38(10):1080-1088. [CrossRef] [Medline]67,Secomb J, McKenna L, Smith C. The effectiveness of simulation activities on the cognitive abilities of undergraduate third-year nursing students: a randomised control trial. J Clin Nurs 2012 Dec;21(23-24):3475-3484. [CrossRef] [Medline]70,Smith BD, Silk K. Cultural competence clinic: an online, interactive, simulation for working effectively with Arab American Muslim patients. Acad Psychiatry 2011;35(5):312-316. [CrossRef] [Medline]84,Dankbaar ME, Alsma J, Jansen EE, van Merrienboer JJ, van Saase JL, Schuit SC. An experimental study on the effects of a simulation game on students' clinical cognitive skills and motivation. Adv Health Sci Educ Theory Pract 2016 Aug;21(3):505-521. [CrossRef] [Medline]88] reported findings related to noticed unexpected effects of the intervention.

Cost

Haerling [Haerling KA. Cost-utility analysis of virtual and mannequin-based simulation. Simul Healthc 2018 Feb;13(1):33-40. [CrossRef] [Medline]58] showed a better cost-utility ratio of US $1.08 for virtual patients versus US $3.62 for the mannequin-based training. Foster et al [Foster A, Chaudhary N, Kim T, Waller JL, Wong J, Borish M, et al. Using virtual patients to teach empathy: a randomized controlled study to enhance medical students' empathic communication. Simul Healthc 2016 Jun;11(3):181-189. [CrossRef] [Medline]95] compared the cost of human-provided (Mechanical Turk) feedback with backstory video feedback; the cost of human answers was US $0.05 per question assisted, whereas videos required 4 hours of development time and the license cost of a video game (Sims 3 by Electronic Arts). This does not provide a direct answer to the question of which method was more cost-efficient as it depends on the number of participants and time of use. It is also important to notice that the human-generated feedback in virtual patients showed positive effects on the communication skills outcomes, whereas the backstory video did not. Bryant et al [Bryant R, Miller CL, Henderson D. Virtual clinical simulations in an online advanced health appraisal course. Clin Simul Nurs 2015 Oct;11(10):437-444. [CrossRef]78] estimated, but without providing numerical evidence, that the cost of a virtual patient was similar to that of a course text that was eliminated by the new intervention. Liaw et al [Liaw SY, Chan SW, Chen F, Hooi SC, Siau C. Comparison of virtual patient simulation with mannequin-based simulation for improving clinical performances in assessing and managing clinical deterioration: randomized controlled trial. J Med Internet Res 2014;16(9):e214 [FREE Full text] [CrossRef] [Medline]64], without providing concrete numbers, noticed that despite “initial startup costs for developing the virtual patient simulation, its implementation was less resource intensive than the mannequin-based simulation.” The cost savings were because of reduced instructor time, use of expensive equipment, or simulation facilities. Maleck et al [Maleck M, Fischer MR, Kammer B, Zeiler C, Mangel E, Schenk F, et al. Do computers teach better? A media comparison study for case-based teaching in radiology. Radiographics 2001;21(4):1025-1032. [CrossRef] [Medline]65] saw cost savings in the virtual patient group because of spared radiograph printouts. The cost of the virtual patient intervention was expressed in hours of work; in 2 cases, the cost was 12 to 15 hours per virtual patient [Al-Dahir S, Bryant K, Kennedy KB, Robinson DS. Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences. Am J Pharm Educ 2014 May 15;78(4):76 [FREE Full text] [CrossRef] [Medline]53,Kandasamy T, Fung K. Interactive internet-based cases for undergraduate otolaryngology education. Otolaryngol Head Neck Surg 2009 Mar;140(3):398-402. [CrossRef] [Medline]60]; in 1 case it was 15 to 30 hours [Leong SL, Baldwin CD, Adelman AM. Integrating web-based computer cases into a required clerkship: development and evaluation. Acad Med 2003 Mar;78(3):295-301. [Medline]62] and 100 hours in another [Miedzybrodzka Z, Hamilton NM, Gregory H, Milner B, Frade I, Sinclair T, et al. Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach. Eur J Hum Genet 2001 Dec;9(12):953-956 [FREE Full text] [CrossRef] [Medline]66]. The cost expressed in amounts of money was estimated at US $500 for content development and technical implementation [Leong SL, Baldwin CD, Adelman AM. Integrating web-based computer cases into a required clerkship: development and evaluation. Acad Med 2003 Mar;78(3):295-301. [Medline]62] and US $4800 for a total clerkship restructuring, including adding virtual patients [Kandasamy T, Fung K. Interactive internet-based cases for undergraduate otolaryngology education. Otolaryngol Head Neck Surg 2009 Mar;140(3):398-402. [CrossRef] [Medline]60]. It is worth noticing that in both cases the virtual patients were developed by students. Deladisma et al [Deladisma AM, Gupta M, Kotranza A, Bittner JG, Imam T, Swinson D, et al. A pilot study to integrate an immersive virtual patient with a breast complaint and breast examination simulator into a surgery clerkship. Am J Surg 2009 Jan;197(1):102-106. [CrossRef] [Medline]79] used in their study a virtual patient system that involved a speech recognition engine, tracked user’s body movements, and projected a life-sized avatar on the wall. The cost of the technology used in the pilot study (including 2 networked personal computers, 1 data projector, and 2 Web cameras) was estimated in 2006 to be less than US $7000 [Stevens A, Hernandez J, Johnsen K, Dickerson R, Raij A, Harrison C, et al. The use of virtual patients to teach medical students history taking and communication skills. Am J Surg 2006 Jun;191(6):806-811. [CrossRef] [Medline]102].

Patient Outcomes

In the study by Schittek Janda et al [Schittek Janda M, Mattheos N, Nattestad A, Wagner A, Nebel D, Färbom C, et al. Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history-taking skills. Eur J Dent Educ 2004 Aug;8(3):111-119. [CrossRef] [Medline]83], an experienced clinician rated the professional behavior (language precision, order of question, and empathy) of first year students’ of dentistry toward real patients as significantly higher (P<.01) in the group having access to a supplementary virtual patient case than in the group that underwent standard instruction.

Adverse Effects

Dankbaar et al [Dankbaar ME, Alsma J, Jansen EE, van Merrienboer JJ, van Saase JL, Schuit SC. An experimental study on the effects of a simulation game on students' clinical cognitive skills and motivation. Adv Health Sci Educ Theory Pract 2016 Aug;21(3):505-521. [CrossRef] [Medline]88] hypothesize based on their study results that high-fidelity virtual patients may increase motivation, but at the same time be more distracting for novice students and by that impede learning. Authors of 2 studies [Secomb J, McKenna L, Smith C. The effectiveness of simulation activities on the cognitive abilities of undergraduate third-year nursing students: a randomised control trial. J Clin Nurs 2012 Dec;21(23-24):3475-3484. [CrossRef] [Medline]70,Smith BD, Silk K. Cultural competence clinic: an online, interactive, simulation for working effectively with Arab American Muslim patients. Acad Psychiatry 2011;35(5):312-316. [CrossRef] [Medline]84] observe that the language of virtual patients might be a significant factor showing greater effects on nonnative English speaking and bilingual learners than in native English speakers. In the study by Qayumi et al [Qayumi AK, Kurihara Y, Imai M, Pachev G, Seo H, Hoshino Y, et al. Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience). Med Educ 2004 Oct;38(10):1080-1088. [CrossRef] [Medline]67], it is observed that that lower-achieving students benefit more from virtual patients than high performers. In the study by Botezatu et al [Botezatu M, Hult H, Tessma MK, Fors UGH. Virtual patient simulation for learning and assessment: superior results in comparison with regular course exams. Med Teach 2010;32(10):845-850. [CrossRef] [Medline]55], students knowing about the possibility of being assessed by virtual patients opposed being tested with paper cases. In the study by Al-Dahir et al [Al-Dahir S, Bryant K, Kennedy KB, Robinson DS. Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences. Am J Pharm Educ 2014 May 15;78(4):76 [FREE Full text] [CrossRef] [Medline]53], it is observed that analysis of individual learner traces in the virtual patient system negates benefits of social learning.

Subgroup Analysis

None of the initially planned subgroup analyses explained the heterogeneity of the results.

Among many analyzed aspects, we looked into differences regarding the efficiency of learning with virtual patients between the health professions disciplines. Most of the located studies involved students of medicine as participants. For instance, when comparing virtual patients with traditional education in the domain of skills, out of the 12 outcomes included for subgroup analyses, only 2 were from other health profession disciplines than medicine (ie, studies from nursing [Liaw SY, Chan SW, Chen F, Hooi SC, Siau C. Comparison of virtual patient simulation with mannequin-based simulation for improving clinical performances in assessing and managing clinical deterioration: randomized controlled trial. J Med Internet Res 2014;16(9):e214 [FREE Full text] [CrossRef] [Medline]64,Tao H. Computer-based simulative training system—a new approach to teaching pre-hospital trauma care. J Med Coll PLA 2011 Dec;26(6):335-344. [CrossRef]73]). When analyzing knowledge outcomes out of the 12 included studies, 4 were nonmedical but represented 3 very different disciplines, nursing [Haerling KA. Cost-utility analysis of virtual and mannequin-based simulation. Simul Healthc 2018 Feb;13(1):33-40. [CrossRef] [Medline]58,Tao H. Computer-based simulative training system—a new approach to teaching pre-hospital trauma care. J Med Coll PLA 2011 Dec;26(6):335-344. [CrossRef]73], pharmacy [Al-Dahir S, Bryant K, Kennedy KB, Robinson DS. Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences. Am J Pharm Educ 2014 May 15;78(4):76 [FREE Full text] [CrossRef] [Medline]53], and physiotherapy [Kinney P, Keskula DR, Perry JF. The effect of a computer assisted instructional program on physical therapy students. J Allied Health 1997;26(2):57-61. [Medline]61]. The conducted subgroup analyses showed no significant differences between the subgroups and high heterogeneity.

While analyzing aspects of instructional design implemented in the virtual patient scenarios, we were able to locate a very balanced number of studies implementing the narrative and problem-solving designs [Bearman M, Cesnik B, Liddell M. Random comparison of 'virtual patient' models in the context of teaching clinical communication skills. Med Educ 2001 Sep;35(9):824-832. [Medline]91] in the domain of knowledge outcomes (6 studies in each branch). Yet, the pooled results showed no difference (narrative: SMD=0.12, 95% CI −0.41 to 0.64, I2=85%, n=525 versus problem solving: SMD=0.11, 95% CI −0.17 to 0.38, I2=51%, n=520; subgroup differences P=.97). Interestingly, when looking into the domain of skills outcomes, all studies had either the problem-solving or unclear design (in 2 cases). This might be an indication that narrative (linear, branched) virtual patients are seen as being better suited for knowledge outcomes rather than skills.

Figure 6. Albatross plot for studies comparing virtual patient with traditional education for knowledge outcomes. SMD: standardized mean difference.
View this figure

Finally, we were unable to see any pattern in efficiency when analyzing the timing of feedback as being either during activity or post activity. However, in almost half of the studies, we were unable to decide, based on the description of the intervention, which model of feedback was implemented or whether the study had a mixed (during/post activity) mode of providing feedback.

To further explore the reasons for heterogeneity, we visualized the outcomes in the form of albatross plots of the knowledge and skills outcomes for virtual patients to traditional education comparisons. Figure 6 presents an albatross plot for knowledge and Figure 7 for skills outcomes. Comparisons of virtual patients to passive forms of learning (reading exercises and lectures) tended to display large positive effect sizes, whereas those comparing virtual patients to active learning (group discussion or mannequin-based learning) show small effects or even negative effects (left hand side in the Figures 6 and Bajpai S, Semwal M, Bajpai R, Car J, Ho AH. Health professions' digital education: review of learning theories in randomized controlled trials by the Digital Health Education Collaboration. J Med Internet Res 2019 Mar 12;21(3):e12912 [FREE Full text] [CrossRef] [Medline]7 and

Multimedia Appendix 6

Subgroup analysis details.

DOC File, 66KBMultimedia Appendix 6).

Figure 7. Albatross plot for studies comparing virtual patient with traditional education for skills outcome. SMD: standardized mean difference.
View this figure

Risk of Bias

Following the Cochrane methodology [Higgins J, Green S. Cochrane Handbook For Systematic Reviews Of Interventions. Chichester, England: John Wiley & Sons; 2008.40], we have assessed the risk of bias in all included studies. The results of the analysis are summarized in Figure 8.

Overall, we do not consider allocation bias as a significant issue in the review as most of the studies either described an adequate randomization method (17 of 51 studies) or even when the description was unclear (31 of 51), it was judged unlikely that the randomization was seriously flawed. Performance bias in comparisons with traditional education is an issue but at the same time is impossible to avoid in this type of research. The blinding of participants in virtual patient design comparisons is possible, but those studies are still relatively uncommon (n=10). The risk of assessor bias was avoided in many studies by using automated or formalized assessment instruments. Consequently, we assessed the risk as low in 42 of 51 studies. However, it is often unclear whether the instruments (eg, MCQ tests, assessment rubrics) were properly validated. We felt that in the majority of studies, attrition bias was within acceptable levels (low risk in 36 of 51 studies). This does not exclude volunteer bias, which is likely to be common, but its influence is difficult to estimate. As there is little tradition of publishing protocols in medical education research, it was problematic to assess selective reporting bias, but we judged the risk as low in 35 out of 51 studies. We were unable to reliably assess publication bias considering the high heterogeneity of studies. None of the cRCT studies considered in the statistical analysis had corrections for clustering, but we have decreased the number of participants in those studies using a method from the Cochrane Handbook to compensate for that. We present more details of the risk of bias analysis in

Multimedia Appendix 7

Quality of the evidence.

DOC File, 89KBMultimedia Appendix 7.

We rated down the quality of evidence for knowledge and skills outcomes in virtual patients to traditional education comparison because of the high heterogeneity of included studies and limitations in study design (lack of participant blinding, nonvalidated instruments, and potential volunteer bias). For attitudinal and satisfaction outcomes and for other types of comparisons, we additionally rated down the quality as the outcomes were presented as independent items in questionnaires that were not amenable to statistical analysis or the analyses contained just a handful of studies and the CIs were wide. Summary of findings table (GRADE) are presented in

Multimedia Appendix 8

Summary of finding tables.

DOC File, 86KBMultimedia Appendix 8.

Figure 8. Risk of bias summary (+ low risk of bias; - high risk of bias, ? unclear risk of bias).
View this figure

Principal Findings

The aim of this review was to evaluate the effectiveness of virtual patients in comparison with other existing educational methods.

There is low quality evidence that virtual patients are at least as effective as traditional education for knowledge outcome and more effective for skills outcomes. On the basis of the visual analysis of albatross plots, we may hypothesize that replacing passive forms of traditional education with virtual patients brings more benefit than replacing active learning methods. We collected positive evidence of effectiveness from both high-income and low-and-middle-income countries demonstrating the global applicability of virtual patients. Students were generally satisfied with the use of virtual patients, but we also located studies in our review where the use of virtual patients was connected with diminished confidence.

The strength of our systematic review is the broad perspective which shows the landscape of RCTs in the domain of virtual patients. Our systematic review updates the evidence on virtual patient effectiveness, which was last summarized in a meta-analysis almost a decade ago.

Limitations

The limitation of our work is that the wide scope of the review does not allow nuances in the studies to be explored in detail. We were unable to make a firm assessment of publication bias. The high heterogeneity of the results leads to the conclusion that without further consideration of needs and implementation details, we cannot expect that the introduction of virtual patients will always lead to detectable positive outcomes. Evidence to determine the effective factors is sparse and represented by only 10 studies in our review, with very diverse research questions.

Our review is limited by the decision to exclude crossover design studies. However, this has been discussed in detail in the potential biases in the review process section in

Multimedia Appendix 7

Quality of the evidence.

DOC File, 89KBMultimedia Appendix 7. We excluded studies published before 1991 as we consider the technology available before the World Wide Web to be materially different from that currently available. Finally, we are limited by the sparse description of the interventions in some of the papers, which occasionally might have led to misclassification of the studies.

Comparison With Prior Work

Extending the results of the meta-analysis by Cook et al [Cook DA, Erwin PJ, Triola MM. Computerized virtual patients in health professions education: a systematic review and meta-analysis. Acad Med 2010 Oct;85(10):1589-1602. [CrossRef] [Medline]38] and in agreement with the one by Consorti et al [Consorti F, Mancuso R, Nocioni M, Piccolo A. Efficacy of virtual patients in medical education: a meta-analysis of randomized studies. Comput Educ 2012 Nov;59(3):1001-1008. [CrossRef]39], our review shows that virtual patients have an overall positive pooled effect when compared with some other types of traditional educational methods. Our observations regarding the influence of the type of outcome (knowledge/skills) and comparison (active/passive traditional learning) supplement the evidence in the previous reviews [Cook DA, Erwin PJ, Triola MM. Computerized virtual patients in health professions education: a systematic review and meta-analysis. Acad Med 2010 Oct;85(10):1589-1602. [CrossRef] [Medline]38,Consorti F, Mancuso R, Nocioni M, Piccolo A. Efficacy of virtual patients in medical education: a meta-analysis of randomized studies. Comput Educ 2012 Nov;59(3):1001-1008. [CrossRef]39], which included studies until 2010. This time point divides the evidence collected in 2 parts: (1) time already covered by previous reviews (1991-2010) and (2) time not included in the previous reviews (2011-2018). It is interesting to note that, though the former timeframe spans over 20 years compared with 8 years in the latter, more studies were included from the latter period, 22 studies (until 2010) versus 29 studies (after 2010). This demonstrates increased interest in virtual patients and medical education in general. The research community around digital health education has long been criticized for publishing media-comparative studies [Friedman CP. The research we should be doing. Acad Med 1994 Jun;69(6):455-457. [Medline]103,Cook DA. The research we still are not doing: an agenda for the study of computer-based learning. Acad Med 2005 Jun;80(6):541-548. [Medline]104]. Media-comparative research aims to make comparisons between different media formats such as paper, face-to-face, and digital education [Cook DA. The research we still are not doing: an agenda for the study of computer-based learning. Acad Med 2005 Jun;80(6):541-548. [Medline]104]. Both Friedman and Cook argue [Friedman CP. The research we should be doing. Acad Med 1994 Jun;69(6):455-457. [Medline]103,Cook DA. The research we still are not doing: an agenda for the study of computer-based learning. Acad Med 2005 Jun;80(6):541-548. [Medline]104] that the limitations of this type of comparison boils down to the inability to produce an adequate control group as interventions are bound to be influenced by too many confounding factors to be generalizable. Even though there are still many media-comparative studies, the number of studies comparing different forms of digital education seem to increase: 3/22 (14%) until 2010 versus 11/29 (38%) after 2010. The number of studies in which students worked from home as an intervention has also increased; before 2011 there was just 1/16 (6%; in 6 studies it was unclear), whereas after 2011, it was 11/22 (50%; in 7 studies it was unclear) studies. However, this potentially raises concerns about how controlled the interventions and measures were, and thus the validity of the conclusions.

Our observation that virtual patient simulations predominantly effect skills rather than knowledge outcomes can be interpreted as an indication that for lower levels of Bloom's taxonomy [Krathwohl DR. A revision of Bloom's taxonomy: an overview. Theory Pract 2002 Nov;41(4):212-218. [CrossRef]105], (remember, understands) there is little added value of introducing virtual patients when compared with traditional methods of education. Virtual patients can have greater impact when applied where knowledge is combined with skills and applied in problem solving, and when direct patient contact is not yet possible. We found little evidence to support the use of virtual patients at higher levels of the taxonomy. We also warn against using our result in justifying diminished hours of bedside teaching as this was investigated in just 1 study [Vash JH, Yunesian M, Shariati M, Keshvari A, Harirchi I. Virtual patients in undergraduate surgery education: a randomized controlled study. ANZ J Surg 2007;77(1-2):54-59. [CrossRef] [Medline]75] and did not show positive outcomes. Consequently, virtual patients can be said to be a modality for learning in which learners actively use and train their clinical reasoning and critical thinking abilities before bedside learning, as was previously suggested in their critical literature review by Cook and Triola [Cook DA, Triola MM. Virtual patients: a critical literature review and proposed next steps. Med Educ 2009 Apr;43(4):303-311. [CrossRef] [Medline]22].

The perceptions of students toward studying with virtual patients are generally positive. However, some exceptions can be noted. In 1 study [Williams C, Aubin S, Harkin P, Cottrell D. A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture. Med Educ 2001 Sep;35(9):847-854. [Medline]77], students were less confident in their skills when compared with facilitated group discussion and lecture. This is in contrast with no observable differences or even better performance in the virtual patient group when considering the objective outcomes in those studies. This could be explained by disbelief in the effectiveness of the new computer-based methods of learning or anxiety of losing direct patient contact.

The results of our subgroup analysis, though inconsistent, encourage the introduction of more active forms of education. Yet, we note that the range from active to passive learning forms a continuum, and the decision on how to classify each intervention is hampered by sparse descriptions in the reports. Nevertheless, questioning the utility of passive learning is not a new finding and is observed elsewhere, for instance, in the literature on the flipped-classroom learning approach [Chen F, Lui AM, Martinelli SM. A systematic review of the effectiveness of flipped classrooms in medical education. Med Educ 2017 Jun;51(6):585-597. [CrossRef] [Medline]106]. As the effects of comparing virtual patients with other forms of active learning were small and we could not detect any other variables explaining the heterogeneity, it seems reasonable to individually consider other factors such as cost of use, time flexibility, personnel shortage, and availability in different settings (eg, students’ homes or locations remote from academic centers) when determining which methods to use.

The need for more guidance within virtual patient simulations is apparent in studies differing by instructional methods where narrative virtual patient design was better than more autonomous problem-oriented designs [Bearman M, Cesnik B, Liddell M. Random comparison of 'virtual patient' models in the context of teaching clinical communication skills. Med Educ 2001 Sep;35(9):824-832. [Medline]91]. Feedback given by humans at distance in a virtual patient system was better than an animated backstory in increasing empathy [Foster A, Chaudhary N, Kim T, Waller JL, Wong J, Borish M, et al. Using virtual patients to teach empathy: a randomized controlled study to enhance medical students' empathic communication. Simul Healthc 2016 Jun;11(3):181-189. [CrossRef] [Medline]95], whereas more active constructing virtual patients with more time on a task but no feedback had no more positive result on the outcomes than learning from a virtual patient scenario [Tolsgaard MG, Jepsen RMHG, Rasmussen MB, Kayser L, Fors U, Laursen LC, et al. The effect of constructing versus solving virtual patient cases on transfer of learning: a randomized trial. Perspect Med Educ 2016 Feb;5(1):33-38 [FREE Full text] [CrossRef] [Medline]100]. This reminds us that presenting realistic patient scenarios with a great degree of freedom cannot be an excuse for neglecting guidance in relation to learning objectives [Kirschner PA, Sweller J, Clark RE. Why minimal guidance during instruction does not work: an analysis of the failure of constructivist, discovery, problem-based, experiential, and inquiry-based teaching. Educ Psychol 2006 Jun;41(2):75-86. [CrossRef]107,Edelbring S, Wahlström R. Dynamics of study strategies and teacher regulation in virtual patient learning activities: a cross sectional survey. BMC Med Educ 2016 Apr 23;16:122 [FREE Full text] [CrossRef] [Medline]108].

Outlook

We join the plea of Friedman [Friedman CP. The research we should be doing. Acad Med 1994 Jun;69(6):455-457. [Medline]103] and Cook [Cook DA. The research we still are not doing: an agenda for the study of computer-based learning. Acad Med 2005 Jun;80(6):541-548. [Medline]104] to abandon media-comparative research as it is difficult to interpret and we instead encourage greater focus on exploring the utility of different design variants of virtual patient simulations. The current knowledge on the influence of these factors is sparse. A carefully planned study backed up in sound educational theory should provide many valuable research opportunities. However, sufficiently powered samples are needed, as the effects are likely to be small. The second consideration pertains to the need to use previously validated measurement tools that are well-aligned with the learning objectives. Comparisons of outcomes in tools on an item-by-item basis is methodologically questionable and makes the aggregations of results difficult in systematic reviews. We also call for more studies in other health professions disciplines than medicine, as our subgroup analysis showed that evidence of virtual patient effectiveness in such programs as nursing, physiotherapy, or pharmacy is underrepresented. Investigations into patient outcomes and cost-effectiveness of virtual patients are not yet explored directly and form a key avenue for future efforts.

Conclusions

Low to modest and mixed evidence suggests that when compared with traditional education, virtual patients can more effectively improve skills, and at least as effectively improve knowledge outcomes as traditional education. Education with virtual patients provides an active form of learning that is beneficial for clinical reasoning skills. Implementations vary and are likely to be broad across pre- and postregistration education, although current studies do not provide clear guidance on when to use virtual patients. We recommend further research be focused on exploring the utility of different design variants of virtual patients.

Acknowledgments

The authors wish to acknowledge the help of Jayne Alfredsson, Carina Georg, Anneliese Lilienthal, Italo Masiello, and Monika Semwal at the stage of protocol writing. The authors would like to thank Jim Campbell for his contribution to coordination and conceptual formation of the Digital Health Education Collaboration. The authors would also like to thank Carl Gornitzki, GunBrit Knutssön, and Klas Moberg from the University Library, Karolinska Institute, for developing the search strategy and Ram Chandra Bajpai from Nanyang Technological University for statistical consulting and Pawel Posadzki for his supportive feedback on the manuscript.

At the time of the study, SE was affiliated with the Karolinska Institutet and Linköping University, and N Saxena was affiliated with Health Services and Outcomes Research, National Healthcare Group, Singapore, Singapore.

Authors' Contributions

JC conceived the idea for the review. AK drafted the protocol with substantial contributions from LW, SE, NS, DD, NSA, LTC, and NZ. The Digital Health Education Collaboration developed the search strategy, obtained copies of studies, and screened the studies. JC and JCD contributed to the coordination and conceptual formation of the Digital Health Education Collaboration. AK, LW, NS, and DD extracted data from studies and conducted the risk of bias assessment. LW contacted the authors in case of missing data. AK carried out the analysis of collected data. LTC provided methodological guidance. AK, LW, SE, NS, DD, LTC, and NZ interpreted the analysis and contributed to the discussion. AK drafted the final review with substantial contributions from all authors. All authors revised and approved the final version of review.

Conflicts of Interest

None declared.

Multimedia Appendix 1

Glossary.

DOC File, 76KB

Multimedia Appendix 2

MEDLINE (Ovid) search strategy.

DOC File, 47KB

Multimedia Appendix 3

Summary of included studies.

DOC File, 291KB

Multimedia Appendix 4

Summary of technical and educational features of included studies.

DOC File, 458KB

Multimedia Appendix 5

Summary of excluded studies.

DOC File, 60KB

Multimedia Appendix 6

Subgroup analysis details.

DOC File, 66KB

Multimedia Appendix 7

Quality of the evidence.

DOC File, 89KB

Multimedia Appendix 8

Summary of finding tables.

DOC File, 86KB

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3D: 3-dimensional
cRCT: cluster randomized controlled trials
GRADE: Grading of Recommendations Assessment, Development and Evaluation Working Group
MCQ: multiple-choice question
OSCE: objective structured clinical examination
RCT: randomized controlled trial
SMD: standardized mean difference


Edited by G Eysenbach, A Marusic; submitted 10.05.19; peer-reviewed by SY Liaw, M Sobocan; comments to author 31.05.19; revised version received 06.06.19; accepted 08.06.19; published 02.07.19

Copyright

©Andrzej A Kononowicz, Luke A Woodham, Samuel Edelbring, Natalia Stathakarou, David Davies, Nakul Saxena, Lorainne Tudor Car, Jan Carlstedt-Duke, Josip Car, Nabil Zary. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 02.07.2019.

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