Improved Study Design Research Articles

Opportunities for Engaging Patients in Kidney Research.

Purpose:The purpose of this review is to provide a summary of the rationale for engaging patients in research as well as to review the established and envisioned advantages and strategies for patient-researcher partnerships. The authors of this article, which include a patient and 4 researchers in kidney disease, discuss the expected benefits and opportunities for patient engagement in their respective research programs. The 4 research programs span the spectrum of kidney disease and focus on enhancing bone health, increasing living donor kidney transplants, improving medication adherence, and preventing kidney transplant rejection.Sources of Information:The sources of information for this review include published studies on the topics of patient engagement and the 4 research programs of the new investigators.Key Findings:(1) Patient, health care provider, and researcher partnerships can contribute useful insights capable of enhancing research in kidney disease. (2) Regardless of the research program, there are various strategies and opportunities for engagement of patients with lived experience across the various stages of research in kidney disease. (3) Envisioned advantages of patient-researcher partnerships include: targeting patient-identified research priorities, integrating patients’ experiential knowledge, improving study design and feasibility through patient-researcher input, facilitating dissemination of research findings to other patients, effectively responding to patient concerns about studies, and inspiring researchers to conduct their research.Limitations:The limitations of the current review include the relative scarcity of literature on patient engagement within the field of kidney disease.Implications:The findings of the current review suggest that it will be important for future studies to identify optimal strategies for patient engagement in setting research priorities, study design, participant recruitment, execution of research projects, and knowledge dissemination and translation.

Assessment of Statistical Methodologies and Pitfalls of Dissertations Carried Out at National Cancer Institute, Cairo University

Purpose:To identify statistical errors and pitfalls in dissertations performed as part of the requirements for the Medical Doctorate (MD) degree at the National Cancer Institute (NCI), Cairo University (CU) to improve the quality of medical research.Methods:A critical assessment of 62 MD dissertations conducted in 3 departments at NCI, CU, between 2009 and 2013 was carried out regarding statistical methodology and presentation of the results. To detect differences in study characteristics over time, grouping was into two periods; 2009-2010 and 2011-2013.Results:Statistical methods were appropriate in only 13 studies (24.5%). The most common statistical tests applied were chi-square, log-rank, and Mann-Whitney tests. Four studies estimated sample size and/or power. Only 37.1% and 38.7% of dissertation results supported aims and answered the research questions, respectively. Most of results were misinterpreted (82.3%) with misuse of statistical terminology (77.4%). Tabular and graphical data display was independently informative in only 36 dissertations (58.1%) with accurate titles and labels in only 17 (27.4%). Statistical tests fulfilled the assumptions only in 29 studies; with evident misuse in 33. Ten dissertations reported non-significance regarding their primary outcome measure; the median power of the test was 35.5% (range: 6-60%). There was no significant change in the characteristics between the time periods.Conclusion:MD dissertations at NCI have many epidemiological and statistical defects that may compromise the external validity of the results. It is recommended to involve a biostatistician from the very start to improve study design, sample size calculation, end points estimation and measures.

Sex Effect on Average Bioequivalence

PurposeGeneric formulations are by far the most prescribed drugs. This scenario is highly beneficial for society because medication expenses are significantly reduced after expiration of the exclusivity period conceded to the branded name drug. Correspondingly, these formulations must be adequately evaluated to avoid drug inefficacy and toxicity in the overall patient population. Bioequivalence studies are the only in vivo evaluation that a generic drug must overcome to reach the market. These clinical trials have not been exempt from underrepresentation of female subjects and a lack of sex-based analysis. Frequently, conclusions obtained in men are extrapolated to women. Furthermore, the obtained results are not analyzed to determine sex differences. The aim of this study was to discuss the effect that male and female differences in gastrointestinal physiology can have on bioequivalence conclusions and to show why a sex-based analysis must be conducted in these studies to improve the evaluation of generic drugs. MethodsThis discussion was based on observed sex differences in product bioavailability discrimination (sex-by-formulation interaction) and on residual variability through an analysis of average bioequivalence data previously reported by other researchers and data collected by our center. Bioequivalence studies of oral formulations, with a 2-period, 2-sequence, 2-treatment random crossover design performed in healthy subjects with at least 6 subjects of each sex, were included. In addition, the bioequivalence conclusion that would have been reached in each study if performed with only 1 sex was estimated. FindingsThe data reveal that differences in both product bioavailability discrimination and residual variability occur with a significant incidence in bioequivalence studies. In either Cmax or AUC, a significant sex-by-formulation interaction was present in 1 of 3 reviewed studies, whereas differences in residual variability between sexes were significant for >50% of studies. Moreover, the performed estimations suggest that the reported bioequivalence conclusions were not verified in at least 1 sex for 1 of 3 studies and were not verified in men and in women for 1 of 6 studies. ImplicationsThis research shows that extrapolation of bioequivalence results from the male population to the female population is not always valid. Bioequivalence studies must therefore be performed with both male and female subjects in similar proportions. Sex-based analysis in bioequivalence can improve study design, enhance the representativeness of conclusions, and provide important information regarding formulation performance, thereby promoting the efficacy and safety of generic drugs.

Identifying Potential Biases in the Nephrology Literature.

Observational studies are common in the nephrology literature, particularly given the lack of large randomized trials. While these studies have identified important associations, potential biases, if unrecognized, can result in misinterpreted conclusions. In this review, we present an example of four potentially important biases (lead time bias, survivor bias, immortal time bias, and index event bias) that can result in inaccurate estimates of association between risk factors or treatments and outcomes. Recognition of these potential biases can help improve study design and interpretation.

Tiny microbes, enormous impacts: what matters in gut microbiome studies?

Many factors affect the microbiomes of humans, mice, and other mammals, but substantial challenges remain in determining which of these factors are of practical importance. Considering the relative effect sizes of both biological and technical covariates can help improve study design and the quality of biological conclusions. Care must be taken to avoid technical bias that can lead to incorrect biological conclusions. The presentation of quantitative effect sizes in addition to P values will improve our ability to perform meta-analysis and to evaluate potentially relevant biological effects. A better consideration of effect size and statistical power will lead to more robust biological conclusions in microbiome studies.

A series of literature evaluation skill development interventions progressing in complexity

ObjectivesThe aim of this work was to design and evaluate a series of interactive literature evaluation skill development interventions for pharmacy students that progress in complexity. Related goals for this initiative were to design methods for (1) self-assessment of student abilities and (2) conducting a student-led journal club discussion in a high enrollment course. Educational activitiesSeven literature evaluation skills were targeted. Pharmacy students participated in six in-class article reviews, a written article review, a student-led journal club, and a final written exam. Students rated their skills pre- and post-course using an End-of-Course Self-Assessment. A Journal Club Self-Assessment was conducted after the student-led journal club. Both assessments used a five-point rating system of Novice, Developing, Skilled, Facilitating/Leading, and Educating. AssessmentA total of 165 students responded to both the self-assessments. In the Journal Club Self-Assessment, 56% of respondents rated their ability in preparing discussion questions as Skilled, and 32% of respondents stated that formulating discussion questions were the hardest component of the exercise. In the End-of-Course Self-Assessment, 46% of respondents reported “describing study design” as their strongest skill, while 23% reported “identifying ways to improve study design” as their weakest skill. All seven literature evaluation skills had statistically significant improvements (p < 0.001) pre- to post-course. Critical analysisEven after eight carefully constructed exercises with progressing levels of difficulty, all students did not self-assess their ability at the desired level of “Skilled.”

Abstract P130: Association Between PFOA, PFOS and Obesity Among Children in a Nationally Representative Sample

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are two types of perfluoroalkyl substances (PFASs) commonly used in the manufacturing process of many consumer products. Both have been detected in the blood of the majority of Americans. PFASs have been shown to be associated with intermediate cardiovascular disease (CVD) outcomes such as hypertension, hyperuricemia and dyslipidemia, but their relationship with obesity, a risk factor for intermediate and advanced CVD, remains largely unexplored. In this context, we examined the associations between PFOA and PFOS levels, and Body Mass Index (BMI) and waist circumference (WC) in a representative sample (N = 5,180) of US children. Our cross-sectional sample included participants aged 12-19 years from CDC’s National Health and Nutrition Examination Survey 1999-2000, 2003-2012. PFOA and PFOS were measured in ng/mL and modeled as quartiles of exposure, where quartile 1 is the referent group across models. Overweight/obesity was defined as age-, sex-specific BMI ≥85 th percentile; abdominal obesity was defined as age-, sex-specific waist circumference ≥90 th percentile. A multivariable model adjusting for age (years), sex (male, female), race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American, other), and annual household income category (&lt;$25,000, $25,500-$54,999, $55,000 and over), revealed an inverse association between PFOS and overweight/obesity. Odds ratios (ORs) for overweight/obesity were 0.81 (95% Confidence Interval [CI] 0.14-0.58) for exposure quartile 2, 0.28 (0.11-0.58) for quartile 3, and 0.26 (0.15-1.05) for quartile 4 (p-trend=0.001). Results were similar for abdominal obesity where, for example, children in quartile 2 of PFOS exposure experienced a multivariable-adjusted OR of 0.42 (0.25-0.72; p-trend=0.023). PFOA was not found to be significantly associated with either outcome. Results are paradoxical in that PFASs may be protective against a risk factor for conditions with which PFASs are positively associated. Because we could not identify any temporal relationships between exposure and outcomes in this cross-sectional study, more studies with improved study design (such as a cohort study) are warranted to confirm the association.

Refining human T-cell immunotherapy of cytomegalovirus disease: a mouse model with 'humanized' antigen presentation as a new preclinical study tool.

With the cover headline 'T cells on the attack,' the journal Science celebrated individualized cancer immunotherapy by adoptive transfer of T cells as the 'Breakthrough of the Year' 2013 (J. Couzin-Frankel in Science 342:1432-1433, 2013). It is less well recognized and appreciated that individualized T cell immunotherapy of cytomegalovirus (CMV) infection is approaching clinical application for preventing CMV organ manifestations, interstitial CMV pneumonia in particular. This coincident medical development is particularly interesting as reactivated CMV infection is a major viral complication in the state of transient immunodeficiency after the therapy of hematopoietic malignancies by hematopoietic cell transplantation (HCT). It may thus be attractive to combine T cell immunotherapy of 'minimal residual disease/leukemia (MRD)' and CMV-specific T cell immunotherapy to combat both risks in HCT recipients simultaneously, and ideally with T cells derived from the respective HLA-matched HCT donor. Although clinical trials of human CMV-specific T cell immunotherapy were promising in that the incidence of virus reactivation and disease was found to be reduced with statistical significance, animal models are still instrumental for providing 'proof of concept' by directly documenting the prevention of viral multiple-organ histopathology and organ failure under controlled conditions of the absence versus presence of the therapy, which obviously is not feasible in an individual human patient. Further, animal models can make predictions regarding parameters that determine the efficacy of T cell immunotherapy for improved study design in clinical investigations, and they allow for manipulating host and virus genetics. The latter is of particular value as it opens the possibility for epitope specificity controls that are inherently missing in clinical trials. Here, we review a recently developed new mouse model that is more approximated to human CMV-specific T cell immunotherapy by 'humanizing' antigen presentation using antigenically chimeric CMV and HLA-transgenic mice to allow for an in vivo testing of the antiviral function of human CMV-specific T cells. As an important new message, this model predicts that T cell immunotherapy is most efficient if CD4 T cells are equipped with a transduced TCR directed against an epitope presented by MHC/HLA class-I for local delivery of 'cognate' help to CD8 effector T cells at infected MHC/HLA class-II-negative host tissue cells.

Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases.

After sustained exposure to Mycobacterium leprae, only a subset of exposed individuals develops clinical leprosy. Moreover, leprosy patients show a wide spectrum of clinical manifestations that extend from the paucibacillary (PB) to the multibacillary (MB) form of the disease. This “polarization” of leprosy has long been a major focus of investigation for immunologists because of the different immune response in these two forms. But while leprosy per se has been shown to be under tight human genetic control, few epidemiological or genetic studies have focused on leprosy subtypes.Using PubMed, we collected available data in English on the epidemiology of leprosy polarization and the possible role of human genetics in its pathophysiology until September 2015. At the genetic level, we assembled a list of 28 genes from the literature that are associated with leprosy subtypes or implicated in the polarization process. Our bibliographical search revealed that improved study designs are needed to identify genes associated with leprosy polarization. Future investigations should not be restricted to a subanalysis of leprosy per se studies but should instead contrast MB to PB individuals. We show the latter approach to be the most powerful design for the identification of genetic polarization determinants. Finally, we bring to light the important resource represented by the nine-banded armadillo model, a unique animal model for leprosy.

Maximizing Patient Recruitment and Retention in a Secondary Stroke Prevention Clinical Trial: Lessons Learned from the STAND FIRM Study

Recruitment and retention of patients in a clinical trial is important for generalizability and robustness of findings. We aimed to investigate features of a study design that were associated with recruitment and retention in a Phase II and Phase III trial of a secondary prevention program for stroke. Following informed consent in hospital, Phase II participants were randomized to intervention or usual care. Baseline clinical assessments were conducted at home approximately 3 months after discharge. In Phase III study, informed consent was obtained at home. We compared the characteristics of participants recruited and retained to 12 months for both phases. Interviews with study nurses were undertaken in order to ascertain their opinions of features of study design. Triangulation was used to identify the features of study design that nurses thought had improved recruitment and retention. All 24 eligible participants were recruited to the Phase II pilot study (100% recruitment), with 67% retention at 12 months. In Phase III study, 570 participants were recruited, and 93% of these participants had reached their 12-month assessment (n = 532) and were still participating. Consistent with the greater patient retention in Phase III study, nurses reported that patients' willingness to participate was greater when consent was obtained at home. Following a change in the consent process from hospital to home, more participants continued participation to 12 months. Pilot studies can provide important data to improve study design and better understand potential barriers to recruitment and retention.

RTMS and disorders of the motor system

Recent guidelines of the IFCN (Lefaucheur et al., 2014) on the therapeutic use of rTMS list the are variety of diseases. Here the focus will be laid on movement disorders, stroke and ALS. No recommendation for the antiparkinsonian effect can be made for high frequency (HF) or low frequency (LF) rTMS of the hand representation in M1 and for HF rTMS of the SMA. Only a possible antiparkinsonian effect of HF rTMS of bilateral (multiple) sites in M1 (Level C) emerged from this meta-analysis. A probable antidepressant effect of HF rTMS of the left DLPFC in Parkinson’s disease (Level B) emerged from the literature analysis. In motor stroke a possible effect of LF rTMS of the contralesional motor cortex in (post-)acute motor stroke (Level C) and a probable effect of LF rTMS of the contralesional motor cortex in chronic motor stroke (Level B) emerged. Ipsilesional stimulation revealed only possible effects of HF rTMS of the ipsilesional motor cortex in (post-)acute motor stroke and of HF rTMS of the ipsilesional motor cortex in chronic motor stroke (Level C). No recommendation can be made for ALS. Possible pitfalls for negative studies are mentioned combined with suggestions for improved study designs.

Data gaps limit the translational potential of preclinical research.

The absence of mouse pharmacokinetic reference data hinders translation. An analysis of recent literature highlights a systematic lack of discussion regarding rationale for the selection of dosing paradigms in preclinical studies, and in particular for neuroscience studies in which the lack of brain penetration can limit target-organ exposure. We propose solutions to improve study design.

Effectiveness of Quality Improvement Interventions at Reducing Inappropriate Cardiac Imaging: A Systematic Review and Meta-Analysis.

Between 5% and 25% of cardiac imaging tests are performed for inappropriate indications. Studies have examined the impact of appropriate use criteria-based quality improvement initiatives on inappropriate testing, but they have not been systematically evaluated. We performed a systematic review of studies evaluating quality improvement initiatives aimed at reducing inappropriate cardiac imaging. The primary outcome was the proportion of inappropriate tests based on appropriate use criteria. Studies were analyzed using a random effects meta-analysis model, and heterogeneity was examined using subgroup analyses. We identified 6 observational studies and 1 randomized control trial. Most interventions (n=6) had a formal education component, and 5 included a mechanism for physician audit and feedback. Although these interventions were associated with lower odds of inappropriate testing (odds ratio, 0.44 [95% confidence interval, 0.32-0.61]; P<0.001), significant heterogeneity was observed (I(2)=70%), which was best explained by the utilization of physician audit and feedback. Interventions that employed physician audit and feedback were associated with significantly lower odds of inappropriate testing (odds ratio, 0.36 [95% confidence interval, 0.31-0.41]; P<0.001; I(2)=0%), whereas those that did not had no effect (odds ratio, 0.89 [95% confidence interval, 0.61-1.29]; P=0.51; I(2)=0%; P value for difference <0.001). All studies had potential sources of bias that could have affected the observed estimates. Interventions using physician audit and feedback are associated with lower odds of inappropriate cardiac testing. Further research is needed to evaluate a greater diversity of intervention types, with improved study designs.

Racial Disparities in Parkinson Disease: A Systematic Review of the Literature

Racial differences in the prevalence of Parkinson’s disease (PD) have been reported for decades. Many of the earliest reports were flawed because they were based on crude datasets, such as hospital databases, death certificates, door-to-door surveys and records of Medicare beneficiaries. These studies provided conflicting results and were found to have numerous biases. Publications with improved study designs in recent years have yielded higher quality findings that are worth reviewing. We reviewed studies published between 2005 and 2014 that analyzed the racial differences in Parkinson’s disease diagnosis, treatment—including deep brain stimulation—and access to care. Literature searches were conducted in PubMed and EBSCO. These studies highlight advances in the field and explore differences in PD among ethnic and racial groups. Our literature review focused on prevalence, treatment and diagnosis discrepancies, and racial variations in the perceptions of aging. An appraisal of twelve reviewed studies determined a decrease in prevalence and incidence of PD in Americans of African descent compared to Caucasians. The studies also showed multiple health disparities, including lack of access to care, treatment, and inclusion in research. More studies are needed to address the causes and prevention of health disparities, as well as solutions, such as community outreach.

The 3+3 versus model-based approach: implementation in the CAPCISUM pancreatic cancer trial

The 3+3 design is the method most commonly used to identify the maximum tolerated dose (MTD) and recommended dose for phase II testing of anti-cancer drugs. While this rule-based approach is easy to implement in practice, the true probability of toxicity at the MTD is unknown as no underlying statistical model is assumed. In the rule-based approach, decisions are made solely on information from the current dose level and may unnecessarily expose patients to sub-therapeutic doses. There has been an increased use in model-based approaches, improving study designs in practice. It is widely acknowledged by statisticians that this approach should be employed in all dose finding studies. S-1 (Teysuno) is approved in Japan for adjuvant and palliative treatment of gastrointestinal malignancies. Clinical trials suggest a population effect exists due to metabolic differences between Asian and Caucasian populations. The CAPCISUM trial is designed to identify the optimal dose of S-1 in a Western population and to assess efficacy of S-1 compared with standard treatment in advanced pancreatic patients. The study is designed with 4 dose levels, 2 patients per level with future doses chosen using the accruing data. The operating characteristics with various prior information and models (power or logistic model) are assessed via simulations. In practice, much work is required in the planning stage to apply the model-based approach to dose finding. Determining the level of process detail to include in the protocol, to achieve a balance between pre-specification and uncertainty of the dynamic process is a challenge.

Meta-analysis of the relationship between breaks in sedentary behavior and cardiometabolic health.

The concept of "breaks" in sedentary behavior has emerged as a potential modifier of detrimental effects on adiposity caused by sedentary behavior. The existing research investigating the relationship between breaks in sedentary behavior with adiposity and cardiometabolic health in adults was systematically reviewed and quantitatively synthesized by this study. Observational and experimental studies that examined the relationships between the frequency of interruptions of sedentary behavior and markers of adiposity and cardiometabolic health in adults were identified by a systematic search of the literature. A meta-analysis was conducted by using the inverse variance method for experimental trials and a Bayesian posterior probability of existence of an association between breaks with adiposity and cardiometabolic markers for observational studies. It was revealed by the pooled results from nine experimental studies that breaks in sedentary periods of at least light intensity may have a positive effect on glycemia but not on lipidemia for adults. It is unclear whether this effect is independent of total sitting time. However, the 10 identified observational studies showed an association with breaks, which was independent of total sedentary time, but only for obesity metrics. The theory that interrupting bouts of sedentary behavior with light-intensity activity might help control adiposity and postprandial glycemia was supported by the evidence. Further investigations with better methods of measuring sedentary behavior patterns and improved study designs are necessary to confirm this preliminary evidence.

Membranous Insulin-like Growth Factor-1 Receptor (IGF1R) Expression Is Predictive of Poor Prognosis in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma.

Background:Insulin-like growth factor-1 receptor (IGF1R) is a membrane receptor-type tyrosine kinase that has attracted considerable attention as a potential therapeutic target, although its clinical significance in non-small cell lung cancer (NSCLC) is controversial. This study aimed to clarify the clinical significance of IGF1R expression in human NSCLC.Methods:IGF1R protein expression was evaluated using immunohistochemistry in 372 patients with NSCLC who underwent curative surgical resection (146 squamous cell carcinomas [SqCCs] and 226 adenocarcinomas [ADCs]). We then analyzed correlations between expression of IGF1R and clinicopathological and molecular features and prognostic significance.Results:Membranous and cytoplasmic IGF1R expression were significantly higher in SqCCs than in ADCs. In patients with SqCC, membranous IGF1R expression was associated with absence of vascular, lymphatic, and perineural invasion; lower stage; and better progression-free survival (PFS) (hazard ratio [HR], 0.586; p = .040). In patients with ADC, IGF1R expression did not have a significant prognostic value; however, in the subgroup of epidermal growth factor receptor (EGFR)-mutant ADC, membranous IGF1R expression was associated with lymphatic and perineural invasion, solid predominant histology, and higher cancer stage and was significantly associated with worse PFS (HR, 2.582; p = .009).Conclusions:Lung ADC and SqCC showed distinct IGF1R expression profiles that demonstrated prognostic significance. High membranous IGF1R expression was predictive of poor PFS in EGFR-mutant lung ADC, while it was predictive of better PFS in SqCC. These findings will help improve study design for subsequent investigations and select patients for future anti-IGF1R therapy.

Evaluation of conceptual frameworks applicable to the study of isolation precautions effectiveness.

A discussion of conceptual frameworks applicable to the study of isolation precautions effectiveness according to Fawcett and DeSanto-Madeya's (2013) evaluation technique and their relative merits and drawbacks for this purpose. Isolation precautions are recommended to control infectious diseases with high morbidity and mortality, but effectiveness is not established due to numerous methodological challenges. These challenges, such as identifying empirical indicators and refining operational definitions, could be alleviated though use of an appropriate conceptual framework. Discussion paper. In mid-April 2014, the primary author searched five electronic, scientific literature databases for conceptual frameworks applicable to study isolation precautions, without limiting searches by publication date. By reviewing promising conceptual frameworks to support isolation precautions effectiveness research, this article exemplifies the process to choose an appropriate conceptual framework for empirical research. Hence, researchers may build on these analyses to improve study design of empirical research in multiple disciplines, which may lead to improved research and practice. Three frameworks were reviewed: the epidemiologic triad of disease, Donabedian's healthcare quality framework and the Quality Health Outcomes model. Each has been used in nursing research to evaluate health outcomes and contains concepts relevant to nursing domains. Which framework can be most useful probably depends on whether the study question necessitates testing multiple interventions, concerns pathogen-specific characteristics and yields cross-sectional or longitudinal data. The Quality Health Outcomes model may be slightly preferred as it assumes reciprocal relationships, multi-level analysis and is sensitive to cultural inputs.

Prognostic factors in the acute respiratory distress syndrome.

Despite improvements in critical care, acute respiratory distress syndrome (ARDS) remains a devastating clinical problem with high rates of morbidity and mortality. A better understanding of the prognostic factors associated with ARDS is crucial for facilitating risk stratification and developing new therapeutic interventions that aim to improve clinical outcomes. In this article, we present an up-to-date summary of factors that predict mortality in ARDS in four categories: (1) clinical characteristics; (2) physiological parameters and oxygenation; (3) genetic polymorphisms and biomarkers; and (4) scoring systems. In addition, we discuss how a better understanding of clinical and basic pathogenic mechanisms can help to inform prognostication, decision-making, risk stratification, treatment selection, and improve study design for clinical trials.

Evaluating Outcomes of Electronic Tools Supporting Physician Shift-to-Shift Handoffs: A Systematic Review.

Multiple organizations have recognized that handoffs are prone to errors, and there has been an increase in the use of electronic health records and computerized tools in health care. This systematic review evaluates the current evidence on the effectiveness of electronic solutions used to support shift-to-shift handoffs. We searched the English-language literature for research studies published between January 1, 2008, and September 19, 2014, using National Library of Medicine PubMed, EBSCO CINAHL, OvidSP All Journals, and ProQuest PsycINFO. Included studies focused on the evaluation of physician shift-to-shift handoffs and an electronic solution designed to support handoffs. We assessed articles using a quality scoring system, conducted a review of barriers and strategies, and categorized study outcomes into self-report, process, and outcome measures. Thirty-seven articles met inclusion criteria, including 20 single group pre- and posttest studies; 8 posttest only or cross-sectional studies; 4 nonrandomized controlled trials; 1 cohort study; 1 randomized crossover study; and 3 qualitative studies. Quality scores ranged from 3.5 to 14 of a possible 16. Most articles documented some positive outcomes, with 2 of the 3 studies evaluating patient outcomes yielding statistically significant improvements. The only other study that analyzed patient outcomes showed that interventions other than the electronic tool were responsible for most of the significant improvements. The majority of studies supported using an electronic tool, yet few measured patient outcomes, and numerous studies suffered from methodology issues. Future studies should evaluate patient outcomes, improve study design, assess the role of faculty oversight, and broaden the focus to recognize the role of human factors.