Building the evidence base for decision making in cancer genomic medicine using comparative effectiveness research

The clinical utility is uncertain for many cancer genomic applications. Comparative effectiveness research (CER) can provide evidence to clarify this uncertainty. The aim of this study was to identify approaches to help stakeholders make evidence-based decisions and to describe potential challenges and opportunities in using CER to produce evidence-based guidance. We identified general CER approaches for genomic applications through literature review, the authors’ experiences, and lessons learned from a recent, seven-site CER initiative in cancer genomic medicine. Case studies illustrate the use of CER approaches. Evidence generation and synthesis approaches used in CER include comparative observational and randomized trials, patient-reported outcomes, decision modeling, and economic analysis. Significant challenges to conducting CER in cancer genomics include the rapid pace of innovation, lack of regulation, and variable definitions and evidence thresholds for clinical and personal utility. Opportunities to capitalize on CER methods in cancer genomics include improvements in the conduct of evidence synthesis, stakeholder engagement, increasing the number of comparative studies, and developing approaches to inform clinical guidelines and research prioritization. CER offers a variety of methodological approaches that can address stakeholders’ needs and help ensure an effective translation of genomic discoveries.Genet Med advance online publication 19 April 2012     

Comparative effectiveness research and genomic medicine: An evolving partnership for 21st century medicine

The American Recovery and Reinvestment Act has provided resources for comparative effectiveness research that will lead to evidence-based decisions about health and health care choices. Some have voiced concerns that evidence-based comparative effectiveness research principles are only relevant to “average” patients and not as much to individuals with unique combinations of genes, exposures and disease outcomes, intrinsic to genomic medicine. In this commentary, we argue that comparative effectiveness research and genomic medicine not only can and should coexist but also they will increasingly benefit from each other. The promise and success of genomic medicine will depend on rigorous comparative effectiveness research to compare outcomes for genome-based applications in practice to traditional non–genome-based approaches. In addition, the success of comparative effectiveness research will depend on developing new methods and clinical research infrastructures to integrate genome-based personalized perspectives into point of care decisions by patients and providers. There is a need to heal the apparent schism between genomic medicine and comparative effectiveness research to enhance knowledge-driven practice of medicine in the 21st century.     

Bridging the gap. The separate worlds of evidence-based medicine and patient-centered medicine

Modern medical care is influenced by two paradigms: 'evidence-based medicine' and 'patient-centered medicine'. In the last decade, both paradigms rapidly gained in popularity and are now both supposed to affect the process of clinical decision making during the daily practice of physicians. However, careful analysis shows that they focus on different aspects of medical care and have, in fact, little in common. Evidence-based medicine is a rather young concept that entered the scientific literature in the early 1990s. It has basically a positivistic, biomedical perspective. Its focus is on offering clinicians the best available evidence about the most adequate treatment for their patients, considering medicine merely as a cognitive-rational enterprise. In this approach the uniqueness of patients, their individual needs and preferences, and their emotional status are easily neglected as relevant factors in decision-making. Patient-centered medicine, although not a new phenomenon, has recently attracted renewed attention. It has basically a humanistic, biopsychosocial perspective, combining ethical values on 'the ideal physician', with psychotherapeutic theories on facilitating patients' disclosure of real worries, and negotiation theories on decision making. It puts a strong focus on patient participation in clinical decision making by taking into account the patients' perspective, and tuning medical care to the patients' needs and preferences. However, in this approach the ideological base is better developed than its evidence base. In modern medicine both paradigms are highly relevant, but yet seem to belong to different worlds. The challenge for the near future is to bring these separate worlds together. The aim of this paper is to give an impulse to this integration. Developments within both paradigms can benefit from interchanging ideas and principles from which eventually medical care will benefit. In this process a key role is foreseen for communication and communication research.     

Barriers to GPs' use of evidence-based medicine: a systematic review

Background

GPs report various barriers to the use and practice of evidence-based medicine (EBM). A review of research on these barriers may help solve problems regarding the uptake of evidence in clinical outpatient practice.

Aim

To determine the barriers encountered by GPs in the practice of EBM and to come up with solutions to the barriers identified.

Design

A systematic review of the literature.

Method

The following databases were searched: MEDLINE® (PubMed®), Embase, CINAHL®, ERIC, and the Cochrane Library, until February 2011. Primary studies (all methods, all languages) that explore the barriers that GPs encounter in the practice of EBM were included.

Results

A total of 14 700 articles were identified, of which 22 fulfilled all inclusion criteria. Of the latter, nine concerned qualitative, 12 concerned quantitative, and one concerned both qualitative and quantitative research methods. The barriers described in the articles cover the categories: evidence (including the accompanying EBM steps), the GP’s preferences (experience, expertise, education), and the patient’s preferences. The particular GP setting also has important barriers to the use of EBM. Barriers found in this review, among others, include lack of time, EBM skills, and available evidence; patient-related factors; and the attitude of the GP.

Conclusion

Various barriers are encountered when using EBM in GP practice. Interventions that help GPs to overcome these barriers are needed, both within EBM education and in clinical practice.     

Genetics researchers' and IRB professionals' attitudes toward genetic research review: a comparative analysis

PurposeGenetic research involving human participants can pose challenging questions related to ethical and regulatory standards for research oversight. However, few empirical studies describe how genetic researchers and institutional review board (IRB) professionals conceptualize ethical issues in genetic research or where common ground might exist.MethodsParallel online surveys collected information from human genetic researchers (n = 351) and IRB professionals (n = 208) regarding their views about human participant oversight for genetic protocols.ResultsA range of opinions were observed within groups on most issues. In both groups, a minority thought it likely that people would be harmed by participation in genetic research or identified from coded genetic data. A majority of both groups agreed that reconsent should be required for four of the six scenarios presented. Statistically significant differences were observed between groups on some issues, with more genetic researcher respondents trusting the confidentiality of coded data, fewer expecting harms from reidentification, and fewer considering reconsent necessary in certain scenarios.ConclusionThe range of views observed within and between IRB and genetic researcher groups highlights the complexity and unsettled nature of many ethical issues in genome research. Our findings also identify areas where researcher and IRB views diverge and areas of common ground.Genet Med 2012:14(2):236–242     

The research rotation: competency-based structured and novel approach to research training of internal medicine residents

Background  

In the United States, the Accreditation Council of graduate medical education (ACGME) requires all accredited Internal medicine residency training programs to facilitate resident scholarly activities. However, clinical experience and medical education still remain the main focus of graduate medical education in many Internal Medicine (IM) residency-training programs. Left to design the structure, process and outcome evaluation of the ACGME research requirement, residency-training programs are faced with numerous barriers. Many residency programs report having been cited by the ACGME residency review committee in IM for lack of scholarly activity by residents.     

The research rotation: competency-based structured and novel approach to research training of internal medicine residents

Background

The extent of clinical exposure needed to ensure quality care has not been well determined during internal medicine training. We aimed to determine the association between clinical exposure (number of cases seen), self- reports of clinical competence, and type of institution (predictor variables) and quality of care (outcome variable) as measured by clinical vignettes.

Methods

Cross-sectional study using univariate and multivariate linear analyses in 11 teaching hospitals in Japan. Participants were physicians-in-training in internal medicine departments. Main outcome measure was standardized t-scores (quality of care) derived from responses to five clinical vignettes.

Results

Of the 375 eligible participants, 263 (70.1%) completed the vignettes. Most were in their first (57.8%) and second year (28.5%) of training; on average, the participants were 1.8 years (range = 1–8) after graduation. Two thirds of the participants (68.8%) worked in university-affiliated teaching hospitals. The median number of cases seen was 210 (range = 10–11400). Greater exposure to cases (p = 0.0005), higher self-reports of clinical competence (p = 0.0095), and type of institution (p < 0.0001) were significantly associated with higher quality of care, using a multivariate linear model and adjusting for the remaining factors. Quality of care rapidly increased for the first 100 to 200 cases seen and tapered thereafter.

Conclusion

The amount of clinical exposure and levels of self-reports of clinical competence, not years after graduation, were positively associated with quality of care, adjusting for the remaining factors. The learning curve tapered after about 200 cases.     

The effectiveness of self-administered treatments: a practice-friendly review of the research

Self-administered treatments are a cost-effective way to treat a broad spectrum of people. This article focuses on the existing research of self-administered treatments and their effectiveness when integrated with ongoing practice or when implemented alone. Evidence for their effectiveness is mixed; self-help has been proven successful in the treatment of depression, mild alcohol abuse, and anxiety disorders. It has proven less successful for smoking cessation and moderate to severe alcohol abuse. When determining whether self-administered treatment is appropriate, individual characteristics and attitude as well as the nature and severity of the problem should be taken into consideration. In addition, because many self-help treatments have not been evaluated, caution should be exercised when implementing self-administered treatment, and progress should be carefully monitored.     

从循证医学与转化医学谈中医药临床研究发展

中医药是中华文明的瑰宝,优势在于临床以整体观念和辨证论治为指导思想,强调以人为本的理念,具有科学和人文的双重属性。临床疗效体现了中医药的生命力,近年来,研究者聚焦中医临床优势病种和优势疗法,掌握循证医学方法,建立符合中医药特点的临床疗效评价新方法、新技术,与国际临床研究模式接轨,获得共识认可。运用转化医学思路和方法,从需求和疗效出发,构建临床与基础的转化平台,提高临床服务水平,促进新药物、新技术开发。总之,中医药临床研究发展应坚持国学原理,弘扬原创思维,兼容并蓄,文明互鉴,和合互动,多学科交叉协作,迎接大科学、大卫生背景下高概念、大数据、信息智能两化融合新纪元,把握中医药从中西医汇通到中西医并重来之不易的发展形势,实现我主人随,传承创新。     

三种比较基因组杂交技术及其在肿瘤研究中的应用

比较基因组杂交技术作为一种新型细胞一分子遗传学技术,已成为近年广泛应用的重要技术,其主要应用于实体瘤领域的研究中.高分辨比较基因组杂交在传统的比较基因组杂交基础上提高了分辨率,具有耗费低、分辨率较高、诊断效率高等特点而具有较好的临床应用前景.而微阵列比较基因组杂交不仅使分辨率提高,甚至可以确定肿瘤相关基因并提供精确的定位,该技术在肿瘤的临床研究及临床应用上具有重要意义.本文则对上述方法及其在肿瘤研究中的应用作一综述.     

A patient-centered gout information value chain: a scoping review

ObjectiveTo examine and identify the scope of research addressing health information requirements for gout patients using value chain analysis.MethodsFive electronic databases (PubMed, CINAHL, ERIC, PsycINFO, Embase, and Scopus) and grey literature (WorldCat) were searched in accordance with a published protocol. Only English language articles were included, with no limitations for date of publication. The findings of the 33 studies included for final analysis were subsequently divided into 6 groups according to the stages of the care delivery value chain their research most closely pertained to: screening/preventing (n = 2), diagnosing (n = 1), preparing (n = 7), intervening (n = 11), recovering/rehabilitating (n = 5), and monitoring/managing (n = 13).ResultsThe 33 studies focused on one or more of the following information phenotypes: 1) pathophysiology; 2) medical treatment; and 3) nonpharmaceutical interventions. Long term treatment adherence was a popular topic amongst studies that focused on gout patient education.ConclusionBased on the identified studies, gout patients are being told what to do, but are not being adequately educated regarding why recommended interventions are important or how to accomplish them.Practice implicationsThis review provides a foundation to develop and evaluate personalized education materials using value chain analysis.     

乳腺癌中比较基因组杂交研究的进展

近年来,随着比较基因组杂交（comparative genomic hybridization,CGH）技术在研究肿瘤相关染色体异常方面的应用,已发现乳腺癌发生、发展不同时期存在非随机性染色体基因组DNA拷贝数改变,而不同类型的肿瘤在基因组异常方面又存在很大的异质性;利用芯片-CGH技术的高分辨率还能鉴别肿瘤的不同亚型。[第一段]     

Assessing optimism and pessimism about genomic medicine: Development of a genomic orientation scale

Efforts to characterize stakeholder attitudes about the implementation of genomic medicine would benefit from a validated instrument for measuring public views of the potential benefits and harms of genomic technologies, which would facilitate comparison across populations and clinical settings. We sought to develop a scale to evaluate attitudes about the future of genomic medicine. We developed a 21-item scale that examined the likelihood of various outcomes of genomic medicine. The scale was administered to participants in a genomic sequencing study. Exploratory factor analysis was conducted and bivariate correlations were calculated. The genomic orientation (GO) scale was completed by 2895 participants. A two-factor structure was identified, corresponding to an optimism subscale (16 items, α = 0.89) and a pessimism subscale (5 items, α = 0.63). Genomic optimism was positively associated with a perceived value of genetic test results, higher health literacy, and decreased decisional conflict about participation in a genomic research study. Genomic pessimism was associated with concerns about genetic testing, lower health literacy, and increased decisional conflict about the decision to participate in the study. The GO scale is a promising tool for measuring both positive and negative views regarding the future of genomic medicine and deserves further validation.     

Defining and implementing patient-centered care: An umbrella review

ObjectivesPatient- or person-centered care (PCC) integrates people’s preferences, values, and beliefs into health decision-making. Gaps exist for defining and implementing PCC; therefore, we aimed to identify core elements of PCC and synthesize implementation facilitators and barriers.MethodsWe conducted an overview of systematic reviews (umbrella review) and included peer-reviewed literature for adults in community/primary care settings. Two reviewers independently screened at Level 1 and 2, extracted data and appraised the quality of reviews. Three reviewers conducted a thematic analysis, and we present a narrative synthesis of findings.ResultsThere were 2371 citations screened, and 10 systematic reviews included. We identified 10 PCC definitions with common elements, such as patient empowerment, patient individuality, and a biopsychosocial approach. Implementation factors focused on communication, training healthcare providers, and organizational structure.ConclusionsWe provide a synthesis of key PCC elements to include in a future definition, and an overview of elements to consider for implementing PCC into practice. We extend existing literature by identifying clinician empowerment and culture change at the systems-level as two future areas to prioritize to enable routine integration of PCC into practice.Practice implicationsFindings may be useful for researchers and or health providers delivering and evaluating PCC.     

Ambulatory rounds: a venue for evidence-based medicine.

OBJECTIVE: The format of inpatient morning reports and ward rounds is infrequently applied in ambulatory medical education. Published reports, however, suggest that this format provides for learner-centered, case-based discussions rather than topic-based lectures in the ambulatory setting.(1) We developed an ambulatory morning report with the specific objective of enhancing evidence-based medical inquiry among our pediatrics housestaff. DESCRIPTION: We developed a pediatric encounter form (PEF) by adapting and modifying an instrument described by Paccione et al.(2) The PEF was to be used by residents to document pertinent information and unanswered questions about patients seen during each ambulatory clinic session. Prompts were provided for documenting the patient's primary complaints, the patient's disposition, and questions that the resident needed answered. The PEF was piloted among a group of residents and faculty. The final version incorporated both resident and faculty input. Each resident was asked to complete a PEF for a maximum of two patients per clinic session. We did not direct residents as to what types of questions to formulate. All completed forms were maintained in a central folder. Next, we instituted a one-hour "Ambulatory Rounds" seminar once a week at lunch-time. During these seminars, faculty selected PEF cases from the previous week for discussion. Residents presented the cases and discussed the reasons behind the formulation of their questions. Faculty facilitated and guided residents toward resources for answering their questions. Faculty also helped residents to reformulate their questions to reflect an evidence-based medicine approach. At the end of each seminar, residents elected to research specific questions and present brief reports at the next seminar. To test the hypothesis that residents will formulate a higher proportion of evidence-based medicine (EBM) questions over time, we collected and analyzed 445 questions asked by 12 residents between July 2000 and August 2001. We categorized questions into EBM and non-EBM questions based on faculty assessment. We performed a trend analysis using chi-square to compare questions from July 2000 (as reference value) with the six-month periods of August 2000 to January 2001 and February to August 2001. By the end of the observation period, the proportion of EBM questions had significantly increased from 13% in July 2000 to 28% in the first six-month period and 59% in the second six-month period (p < 0.001). DISCUSSION: We describe a new application of outpatient morning reports. This format has been very well received. Housestaff gave the ambulatory rounds an average rating of 4.3 (out of 5) on a Likert scale. Our experience suggests that this format not only provides a forum for case-based learning but can be successfully used to enhance the principles of evidence-based medicine among residents.