Blueprint for cancer research: Critical gaps and opportunities.

We are experiencing a revolution in cancer. Advances in screening, targeted and immune therapies, big data, computational methodologies, and significant new knowledge of cancer biology are transforming the ways in which we prevent, detect, diagnose, treat, and survive cancer. These advances are enabling durable progress in the goal to achieve personalized cancer care. Despite these gains, more work is needed to develop better tools and strategies to limit cancer as a major health concern. One persistent gap is the inconsistent coordination among researchers and caregivers to implement evidence-based programs that rely on a fuller understanding of the molecular, cellular, and systems biology mechanisms underpinning different types of cancer. Here, the authors integrate conversations with over 90 leading cancer experts to highlight current challenges, encourage a robust and diverse national research portfolio, and capture timely opportunities to advance evidence-based approaches for all patients with cancer and for all communities.

Brachytherapy: An overview for clinicians.

Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high-level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high-risk prostate cancer to perform dose escalation and improve progression-free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer.

Equitably improving outcomes for cancer survivors and supporting caregivers: A blueprint for care delivery, research, education, and policy.

Cancer care delivery is being shaped by growing numbers of cancer survivors coupled with provider shortages, rising costs of primary treatment and follow-up care, significant survivorship health disparities, increased reliance on informal caregivers, and the transition to value-based care. These factors create a compelling need to provide coordinated, comprehensive, personalized care for cancer survivors in ways that meet survivors' and caregivers' unique needs while minimizing the impact of provider shortages and controlling costs for health care systems, survivors, and families. The authors reviewed research identifying and addressing the needs of cancer survivors and caregivers and used this synthesis to create a set of critical priorities for care delivery, research, education, and policy to equitably improve survivor outcomes and support caregivers. Efforts are needed in 3 priority areas: 1) implementing routine assessment of survivors' needs and functioning and caregivers' needs; 2) facilitating personalized, tailored, information and referrals from diagnosis onward for both survivors and caregivers, shifting services from point of care to point of need wherever possible; and 3) disseminating and supporting the implementation of new care methods and interventions.

A framework for an evidence-based gene list relevant to autism spectrum disorder.

Autism spectrum disorder (ASD) is often grouped with other brain-related phenotypes into a broader category of neurodevelopmental disorders (NDDs). In clinical practice, providers need to decide which genes to test in individuals with ASD phenotypes, which requires an understanding of the level of evidence for individual NDD genes that supports an association with ASD. Consensus is currently lacking about which NDD genes have sufficient evidence to support a relationship to ASD. Estimates of the number of genes relevant to ASD differ greatly among research groups and clinical sequencing panels, varying from a few to several hundred. This Roadmap discusses important considerations necessary to provide an evidence-based framework for the curation of NDD genes based on the level of information supporting a clinically relevant relationship between a given gene and ASD.

Lifting the veil off treatment effect heterogeneity.

Clinicians often suspect that a treatment effect can vary across individuals. However, they usually lack "evidence-based" guidance regarding potential heterogeneity of treatment effects (HTE). Potentially actionable HTE is rarely discovered in clinical trials and is widely believed (or rationalized) by researchers to be rare. Conventional statistical methods to test for possible HTE are extremely conservative and tend to reinforce this belief. In truth, though, there is no realistic way to know whether a common, or average, effect estimated from a clinical trial is relevant for all, or even most, patients. This absence of evidence, misinterpreted as evidence of absence, may be resulting in sub-optimal treatment for many individuals. We first summarize the historical context in which current statistical methods for randomized controlled trials (RCTs) were developed, focusing on the conceptual and technical limitations that shaped, and restricted, these methods. In particular, we explain how the common-effect assumption came to be virtually unchallenged. Second, we propose a simple graphical method for exploratory data analysis that can provide useful visual evidence of possible HTE. The basic approach is to display the complete distribution of outcome data rather than relying uncritically on simple summary statistics. Modern graphical methods, unavailable when statistical methods were initially formulated a century ago, now render fine-grained interrogation of the data feasible. We propose comparing observed treatment-group data to "pseudo data" engineered to mimic that which would be expected under a particular HTE model, such as the common-effect model. A clear discrepancy between the distributions of the common-effect pseudo data and the actual treatment-effect data provides prima facie evidence of HTE to motivate additional confirmatory investigation. Artificial data are used to illustrate implications of ignoring heterogeneity in practice and how the graphical method can be useful.

Temporal changes in the number of European and American guideline recommendations and underlying evidence base for the management of infective: An update of previous published data.

This report aimed to examine temporal changes in the number of recommendations on management of infective endocarditis in the European and American guidelines. The number of recommendations has increased since 2004 without an increment in evidence base in the European iteration. American guidelines have reduced the number of recommendations with a main evidence base of level B.

Similarities and Differences Between Pragmatic Trials and Hybrid Effectiveness-Implementation Trials.

Pragmatism in clinical trials is focused on increasing the generalizability of research findings for routine clinical care settings. Hybridism in clinical trials (i.e., assessing both clinical effectiveness and implementation success) is focused on speeding up the process by which evidence-based practices are developed and adopted into routine clinical care. Even though pragmatic trial methodologies and implementation science evolved from very different disciplines, Pragmatic Trials and Hybrid Effectiveness-Implementation Trials share many similar design features. In fact, these types of trials can easily be conflated, creating the potential for investigators to mislabel their trial type or mistakenly use the wrong trial type to answer their research question. Blurred boundaries between trial types can hamper the evaluation of grant applications, the scientific interpretation of findings, and policy-making. Acknowledging that most trials are not pure Pragmatic Trials nor pure Hybrid Effectiveness-Implementation Trials, there are key differences in these trial types and they answer very different research questions. The purpose of this paper is to clarify the similarities and differences of these trial types for funders, researchers, and policy-makers. In addition, recommendations are offered to help investigators choose, label, and operationalize the most appropriate trial type to answer their research question. These recommendations complement existing reporting guidelines for clinical effectiveness trials (TIDieR) and implementation trials (StaRI).

Transfusion of blood components in pediatric age groups: an evidence-based clinical practice guideline adapted for the use in Egypt using 'Adapted ADAPTE'.

Pediatric transfusion is a complex area of medicine covering a wide age range, from neonates to young adults. Compared to adult practice, there is a relative lack of high-quality research to inform evidence-based guidelines. We aimed to adapt the pre-existing high-quality practice guidelines for the transfusion of blood components in different pediatric age groups to be available for national use by general practitioners, pediatricians, and other health care professionals. The guideline panel included 17 key leaders from different Egyptian institutions. The panel used the Adapted ADAPTE methodology. The panel prioritized the health questions and recommendations according to their importance for clinicians and patients. The procedure included searching for existing guidelines, quality appraisal, and adaptation of the recommendations to the target context of use. The guideline covered all important aspects of the indications, dosing, and administration of packed red cells, platelets, and fresh frozen plasma. It also included transfusion in special situations, e.g., chronic hemolytic anemia and aplastic anemia, management of massive blood loss, malignancies, surgery, recommendations for safe transfusion practices, and recommendations for modifications of cellular blood components. The final version of the adapted clinical practice guideline (CPG) has been made after a thorough review by an external review panel and was guided by their official recommendations and modifications. A set of implementation tools included algorithms, tables, and flow charts to aid decision-making in practice. This adapted guideline serves as a tool for safe transfusion practices in different pediatric age groups.

Tipping point analysis for the between-arm correlation in an arm-based evidence synthesis.

Systematic reviews and meta-analyses are essential tools in contemporary evidence-based medicine, synthesizing evidence from various sources to better inform clinical decision-making. However, the conclusions from different meta-analyses on the same topic can be discrepant, which has raised concerns about their reliability. One reason is that the result of a meta-analysis is sensitive to factors such as study inclusion/exclusion criteria and model assumptions. The arm-based meta-analysis model is growing in importance due to its advantage of including single-arm studies and historical controls with estimation efficiency and its flexibility in drawing conclusions with both marginal and conditional effect measures. Despite its benefits, the inference may heavily depend on the heterogeneity parameters that reflect design and model assumptions. This article aims to evaluate the robustness of meta-analyses using the arm-based model within a Bayesian framework. Specifically, we develop a tipping point analysis of the between-arm correlation parameter to assess the robustness of meta-analysis results. Additionally, we introduce some visualization tools to intuitively display its impact on meta-analysis results. We demonstrate the application of these tools in three real-world meta-analyses, one of which includes single-arm studies.

How Systematic Review Can Shape Clinical Practice in Radiology.

Systematic reviews offer radiologists a comprehensive synthesis of all relevant evidence pertaining to a specific question, aiding them in shaping their clinical practices. It is crucial for radiologists to familiarize themselves with the methods used in systematic reviews and meta-analyses and to understand the limitations. By doing so, they can effectively appraise and interpret results, enabling them to make informed decisions based on the evidence provided in systematic reviews and meta-analyses.

A guide to conducting systematic reviews of clinical laboratory tests.

Clinical laboratory professionals have an instrumental role in supporting clinical decision making with the optimal use of laboratory testing for screening, risk stratification, diagnostic, prognostic, treatment selection and monitoring of different states of health and disease. Delivering evidence-based laboratory medicine relies on review of available data and literature. The information derived, supports many national policies to improve patient care through clinical practice guidelines or best practice recommendations. The quality, validity and bias of this literature is variable. Hence, there is a need to collate similar studies and data and analyse them critically. Systematic review, thus, becomes the most important source of evidence. A systematic review, unlike a scoping or narrative review, involves a thorough understanding of the procedure involved and a stepwise methodology. There are nuances that need some consideration for laboratory medicine systematic reviews. The purpose of this article is to describe the process of performing a systematic review in the field of laboratory medicine, describing the available methodologies, tools and software packages that can be used to facilitate this process.

A web-based knowledge database to provide evidence-based information to cancer patients: Utilization within the PIKKO study.

PURPOSE: Cancer is associated with an urgent need for understandable and reliable information, which is often not satisfied by information available online. Therefore, as part of the PIKKO project, a web-based knowledge database (WDB) was introduced to provide cancer patients with quality-assured, evidence-based information. This paper aims to provide insights into the usage (Who? How? What?) and the effects regarding health literacy of the WDB. METHODS: A patient survey and automatically generated logfile data were evaluated. Two user groups, patients and patient navigators (PNs), were compared. RESULTS: The 13 PNs were responsible for 1/3 of all accesses over the entire duration of the project. The 413 patients used WDB twice on average and spent an average of 12 min per session online (PNs: 9 min per session, more frequently). The top 3 topics of interest were 'therapy', 'nutrition' and 'carcinogenesis' for the patients, and 'therapy', 'naturopathy' and 'legal regulations/support' for the PNs. Of the patients surveyed, 69% said that WDB was helpful in making informed decisions, 76% found the information they wanted and 90% thought WDB was an appropriate way to provide information. CONCLUSION: Our WDB provided important information about cancer and its treatment on a digital way both, to patients and PNs. In routine cancer care, the WDB can improve health literacy and informed decision-making. TRIAL REGISTRATION: This study was retrospectively registered in the German Clinical Trial Register under DRKS00016703 (21 Feb 2019, retrospectively registered). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016703.

The Power of Rapid Reviews for Bridging the Knowledge-to-Action Gap in Evidence-Based Virtual Health Care.

Despite the surge in popularity of virtual health care services as a means of delivering health care through technology, the integration of research evidence into practice remains a challenge. Rapid reviews, a type of time-efficient evidence synthesis, offer a potential solution to bridge the gap between knowledge and action. This paper aims to highlight the experiences of the Fraser Health Authority's Virtual Health team in conducting rapid reviews. This paper discusses the experiences of the Virtual Health team in conducting 15 rapid reviews over the course of 1.5 years and the benefit of involving diverse stakeholders including researchers, project and clinical leads, and students for the creation of user-friendly knowledge products to summarize results. The Virtual Health team found rapid reviews to be a valuable tool for evidence-informed decision-making in virtual health care. Involving stakeholders and focusing on implementation considerations are crucial for maximizing the impact of rapid reviews. Health care decision makers are encouraged to consider implementing rapid review processes to improve the translation of research evidence into practice, ultimately enhancing patient outcomes and promoting a culture of evidence-informed care.

Surgical treatment of nasopharyngeal cancer - a consensus recommendation from two Chinese associations.

BACKGROUND: Surgical treatment is playing an increasingly important role in the management of nasopharyngeal carcinoma (NPC). This consensus focuses on the indications for optimal surgery, and surgical methods in the whole process of treatment for NPC to provide a useful reference to assist these difficult clinical decisions. METHODOLOGY: A thorough review of available literature on NPC and surgery was conducted by the Association for the prevention and treatment of nasopharyngeal carcinoma in China, international exchange and promotion Association for medicine and healthcare, and the Committee on nasopharyngeal cancer of Guangdong provincial anticancer association. A set of questions and a preliminary draft guideline was circulated to a panel of 1096 experienced specialists on this disease for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the experts in two authoritative medical science and technology academic groups in the prevention and treatment of NPC in China for review and reconsideration. RESULTS: The initial round of questions showed variations in clinical practice even among similar specialists, reflecting the lack of high-quality supporting data and resulting difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of surgery, including indications and surgical approaches. CONCLUSION: By standardizing the surgical indications and practice, we hope not only to improve the surgical outcomes, but also to highlight the key directions of future clinical research in the surgical management of NPC.

Patterns and Pitfalls of Short-cuts Used in Environmental Management Rapid Reviews.

Environmental managers and policy-makers need reliable evidence to make effective decisions. Systematic reviews are one way to provide this information but are time-consuming and may not meet the needs of decision-makers when faced with rapidly changing management requirements or transient policy-windows. Rapid reviews are one type of knowledge synthesis that follow simplified or truncated methods compared to systematic reviews. Rapid reviews on environmentally-relevant topics are growing in prevalence, but it is unclear if rapid reviews use similar short-cuts or follow available guidelines. In this methodological review, we assess 26 rapid reviews published between 2002 and 2023. Numerous rapid review short-cuts and approaches were identified, with few consistencies among studies. Short-cuts were present in all stages of the review process, with some of the most common short-cuts including not developing an a priori review protocol, not including stakeholder involvement, or not conducting critical appraisal of study validity. Poor quality in reporting of methods was observed. Fewer than half of assessed rapid reviews reported using available guidelines when developing their methods. Future rapid reviews should aim for improved reporting and adherence to published guidelines to help increase the useability and evidence-user confidence. This will also enable readers to understand where short-cuts were made and their potential consequences for the conclusions of the review.

Evidence-Based Intervention Adaptations Within the Veterans Health Administration: a Scoping Review.

BACKGROUND: Veterans receiving care within the Veterans Health Administration (VA) are a unique population with distinctive cultural traits and healthcare needs compared to the civilian population. Modifications to evidence-based interventions (EBIs) developed outside of the VA may be useful to adapt care to the VA healthcare system context or to specific cultural norms among veterans. We sought to understand how EBIs have been modified for veterans and whether adaptations were feasible and acceptable to veteran populations. METHODS: We conducted a scoping review of EBI adaptations occurring within the VA at any time prior to June 2021. Eligible articles were those where study populations included veterans in VA care, EBIs were clearly defined, and there was a comprehensive description of the EBI adaptation from its original context. Data was summarized by the components of the Framework for Reporting Adaptations and Modifications to Evidence-based interventions (FRAME). FINDINGS: We retrieved 922 abstracts based on our search terms. Following review of titles and abstracts, 49 articles remained for full-text review; eleven of these articles (22%) met all inclusion criteria. EBIs were adapted for mental health (n = 4), access to care and/or care delivery (n = 3), diabetes prevention (n = 2), substance use (n = 2), weight management (n = 1), care specific to cancer survivors (n = 1), and/or to reduce criminal recidivism among veterans (n = 1). All articles used qualitative feedback (e.g., interviews or focus groups) with participants to inform adaptations. The majority of studies (55%) were modified in the pre-implementation, planning, or pilot phases, and all were planned proactive adaptations to EBIs. IMPLICATIONS FOR D&I RESEARCH: The reviewed articles used a variety of methods and frameworks to guide EBI adaptations for veterans receiving VA care. There is an opportunity to continue to expand the use of EBI adaptations to meet the specific needs of veteran populations.

User experience of applying AMSTAR 2 to appraise systematic reviews of healthcare interventions: a commentary.

BACKGROUND: 'A Measurement Tool to Assess Systematic Reviews, version 2' (AMSTAR 2) is a validated 16-item scale designed to appraise systematic reviews (SRs) of healthcare interventions and to rate the overall confidence in their results. This commentary aims to describe the challenges with rating of the individual items and the application of AMSTAR 2 from the user perspective. DISCUSSION: A group of six experienced users (methodologists working in different clinical fields for at least 10 years) identified and discussed the challenges in rating of each item and the general use of AMSTAR 2 to appraise SRs. A group discussion was used to develop recommendations on how users could deal with the identified challenges. We identified various challenges with the content of items 2-16 and with the derivation of the overall confidence ratings on AMSTAR 2. These challenges include the need (1) to provide additional definitions (e.g., what constitutes major deviations from SR protocol on item 2), (2) to choose a rating strategy for multiple conditions on single items (e.g., how to rate item 5 if studies were selected in duplicate, but consensus between two authors was not reported), and (3) to determine rules for deriving the confidence ratings (e.g., what items are critical for such ratings). Based on these challenges we formulated specific recommendations for items 2-16 that AMSTAR 2 users could consider before applying the tool. Our commentary adds to the existing literature by providing the first in-depth examination of the AMSTAR 2 tool from the user perspective. The identified challenges could be addressed by additional decision rules including definitions for ambiguous items and guidance for rating of complex items and derivation of confidence ratings. We recommend that a team consensus regarding such decision rules is required before appraisal procedure begins. TRIAL REGISTRATION: Not applicable.

Representation of evidence-based clinical practice guideline recommendations on FHIR.

BACKGROUND: Various formalisms have been developed to represent clinical practice guideline recommendations in a computer-interpretable way. However, none of the existing formalisms leverage the structured and computable information that emerge from the evidence-based guideline development process. Thus, we here propose a FHIR-based format that uses computer-interpretable representations of the knowledge artifacts that emerge during the process of evidence-based guideline development to directly serve as the basis of evidence-based recommendations. METHODS: We identified the information required to represent evidence-based clinical practice guideline recommendations and reviewed the knowledge artifacts emerging during the evidence-based guideline development process. We then conducted a consensus-based design process with domain experts to develop an information model for guideline recommendation representation that is structurally aligned to the evidence-based guideline recommendation development process and a corresponding representation based on FHIR resources developed for evidence-based medicine (EBMonFHIR). The resulting recommendations were modelled and represented in conformance with the FHIR Clinical Guidelines (CPG-on-FHIR) implementation guide. RESULTS: The information model of evidence-based clinical guideline recommendations and its EBMonFHIR-/CPG-on-FHIR-based representation contain the clinical contents of individual guideline recommendations, a set of metadata for the recommendations, the ratings for the recommendations (e.g., strength of recommendation, certainty of overall evidence), the ratings of certainty of evidence for individual outcomes (e.g., risk of bias) and links to the underlying evidence (systematic reviews based on primary studies). We created profiles and an implementation guide for all FHIR resources required to represent the knowledge artifacts generated during evidence-based guideline development and their re-use as the basis for recommendations and used the profiles to implement an exemplary clinical guideline recommendation. CONCLUSIONS: The FHIR implementation guide presented here can be used to directly link the evidence assessment process of evidence-based guideline recommendation development, i.e. systematic reviews and evidence grading, and the underlying evidence from primary studies to the resulting guideline recommendations. This not only allows the evidence on which recommendations are based on to be evaluated transparently and critically, but also enables guideline developers to leverage computable evidence in a more direct way to facilitate the generation of computer-interpretable guideline recommendations.

Recommendations for Improving the Quality of Prehospital Evidence-Based Guidelines.

Evidence-based guidelines that provide recommendations for clinical care or operations are increasingly being published to inform the EMS community. The quality of evidence evaluation and methodological rigor undertaken to develop and publish these recommendations vary. This can negatively affect dissemination, education, and implementation efforts. Guideline developers and end users could be better informed by efforts across medical specialties to improve the quality of guidelines, including the use of specific criteria that have been identified within the highest quality guidelines. In this special contribution, we aim to describe the current state of published guidelines available to the EMS community informed by two recent systematic reviews of existing prehospital evidenced based guidelines (EBGs). We further aim to provide a description of key elements of EBGs, methods that can be used to assess their quality, and concrete recommendations for guideline developers to improve the quality of evidence evaluation, guideline development, and reporting. Finally, we outline six key recommendations for improving prehospital EBGs, informed by systematic reviews of prehospital guidelines performed by the Prehospital Guidelines Consortium.

Evidence-based Medicine and Mechanistic Evidence: The Case of the Failed Rollout of Efavirenz in Zimbabwe.

Evidence-based medicine (EBM) has long deemphasized mechanistic reasoning and pathophysiological rationale in assessing the effectiveness of interventions. The EBM+ movement has challenged this stance, arguing that evidence of mechanisms and comparative studies should both be seen as necessary and complementary. Advocates of EBM+ provide a combination of theoretical arguments and examples of mechanistic reasoning in medical research. However, EBM+ proponents have not provided recent examples of how downplaying mechanistic reasoning resulted in worse medical results than would have occurred otherwise. Such examples are necessary to make the case that EBM+ responds to a problem in clinical practice that urgently demands a solution. In light of this, we examine the failed rollout of efavirenz as a first-line HIV treatment in Zimbabwe as evidence of the importance of mechanistic reasoning in improving clinical practice and public health policy decisions. We suggest that this case is analogous to examples commonly given to support EBM.