Economic Evaluations of CAR-T Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review.

OBJECTIVES: This study aims to systematically review evidence on the cost-effectiveness of chimeric antigen receptor (CAR)-T therapies for patients with cancer. METHODS: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments and economic evaluations that compared costs and effects of CAR-T therapy in cancer patients were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US Dollars RESULTS: Our search yielded 1,809 records, 47 of which were included. The majority of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared to various standard-of-care chemotherapies. The incremental cost-effective ratio (ICER) for CAR-T therapies ranged from $9,424 to $4,124,105 per QALY in adults and from $20,784 to $243,177 per QALY in pediatric patients. ICERs were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects. CONCLUSIONS: CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness were uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations.

Evidence for clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications among adults with peripheral artery disease: protocol for a systematic review and meta-analysis.

INTRODUCTION: International guidelines recommend that adults with peripheral artery disease (PAD) be prescribed antiplatelet, statin and antihypertensive medications. However, it is unclear how often people with PAD are underprescribed these drugs, which characteristics predict clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications, and whether underprescription and non-adherence are associated with adverse health and health system outcomes. METHODS AND ANALYSIS: We will search MEDLINE, EMBASE and Evidence-Based Medicine Reviews from 2006 onwards. Two investigators will independently review abstracts and full-text studies. We will include studies that enrolled adults and reported the incidence and/or prevalence of clinician underprescription of or patient non-adherence to guideline-recommended cardiovascular medications among people with PAD; adjusted risk factors for underprescription of/non-adherence to these medications; and adjusted associations between underprescription/non-adherence to these medications and outcomes. Outcomes will include mortality, major adverse cardiac and limb events (including revascularisation procedures and amputations), other reported morbidities, healthcare resource use and costs. Two investigators will independently extract data and evaluate study risk of bias. We will calculate summary estimates of the incidence and prevalence of clinician underprescription/patient non-adherence across studies. We will also conduct subgroup meta-analyses and meta-regression to determine if estimates vary by country, characteristics of the patients and treating clinicians, population-based versus non-population-based design, and study risks of bias. Finally, we will calculate pooled adjusted risk factors for underprescription/non-adherence and adjusted associations between underprescription/non-adherence and outcomes. We will use Grading of Recommendations, Assessment, Development and Evaluation to determine estimate certainty. ETHICS AND DISSEMINATION: Ethics approval is not required as we are studying published data. This systematic review will synthesise existing evidence regarding clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications in adults with PAD. Results will be used to identify evidence-care gaps and inform where interventions may be required to improve clinician prescribing and patient adherence to prescribed medications. PROSPERO REGISTRATION NUMBER: CRD42022362801.

Quality improvement strategies for diabetes care: Effects on outcomes for adults living with diabetes.

BACKGROUND: There is a large body of evidence evaluating quality improvement (QI) programmes to improve care for adults living with diabetes. These programmes are often comprised of multiple QI strategies, which may be implemented in various combinations. Decision-makers planning to implement or evaluate a new QI programme, or both, need reliable evidence on the relative effectiveness of different QI strategies (individually and in combination) for different patient populations. OBJECTIVES: To update existing systematic reviews of diabetes QI programmes and apply novel meta-analytical techniques to estimate the effectiveness of QI strategies (individually and in combination) on diabetes quality of care. SEARCH METHODS: We searched databases (CENTRAL, MEDLINE, Embase and CINAHL) and trials registers (ClinicalTrials.gov and WHO ICTRP) to 4 June 2019. We conducted a top-up search to 23 September 2021; we screened these search results and 42 studies meeting our eligibility criteria are available in the awaiting classification section. SELECTION CRITERIA: We included randomised trials that assessed a QI programme to improve care in outpatient settings for people living with diabetes. QI programmes needed to evaluate at least one system- or provider-targeted QI strategy alone or in combination with a patient-targeted strategy. - System-targeted: case management (CM); team changes (TC); electronic patient registry (EPR); facilitated relay of clinical information (FR); continuous quality improvement (CQI). - Provider-targeted: audit and feedback (AF); clinician education (CE); clinician reminders (CR); financial incentives (FI). - Patient-targeted: patient education (PE); promotion of self-management (PSM); patient reminders (PR). Patient-targeted QI strategies needed to occur with a minimum of one provider or system-targeted strategy. DATA COLLECTION AND ANALYSIS: We dual-screened search results and abstracted data on study design, study population and QI strategies. We assessed the impact of the programmes on 13 measures of diabetes care, including: glycaemic control (e.g. mean glycated haemoglobin (HbA1c)); cardiovascular risk factor management (e.g. mean systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), proportion of people living with diabetes that quit smoking or receiving cardiovascular medications); and screening/prevention of microvascular complications (e.g. proportion of patients receiving retinopathy or foot screening); and harms (e.g. proportion of patients experiencing adverse hypoglycaemia or hyperglycaemia). We modelled the association of each QI strategy with outcomes using a series of hierarchical multivariable meta-regression models in a Bayesian framework. The previous version of this review identified that different strategies were more or less effective depending on baseline levels of outcomes. To explore this further, we extended the main additive model for continuous outcomes (HbA1c, SBP and LDL-C) to include an interaction term between each strategy and average baseline risk for each study (baseline thresholds were based on a data-driven approach; we used the median of all baseline values reported in the trials). Based on model diagnostics, the baseline interaction models for HbA1c, SBP and LDL-C performed better than the main model and are therefore presented as the primary analyses for these outcomes. Based on the model results, we qualitatively ordered each QI strategy within three tiers (Top, Middle, Bottom) based on its magnitude of effect relative to the other QI strategies, where 'Top' indicates that the QI strategy was likely one of the most effective strategies for that specific outcome. Secondary analyses explored the sensitivity of results to choices in model specification and priors.  Additional information about the methods and results of the review are available as Appendices in an online repository. This review will be maintained as a living systematic review; we will update our syntheses as more data become available. MAIN RESULTS: We identified 553 trials (428 patient-randomised and 125 cluster-randomised trials), including a total of 412,161 participants. Of the included studies, 66% involved people living with type 2 diabetes only. Participants were 50% female and the median age of participants was 58.4 years. The mean duration of follow-up was 12.5 months. HbA1c was the commonest reported outcome; screening outcomes and outcomes related to cardiovascular medications, smoking and harms were reported infrequently. The most frequently evaluated QI strategies across all study arms were PE, PSM and CM, while the least frequently evaluated QI strategies included AF, FI and CQI. Our confidence in the evidence is limited due to a lack of information on how studies were conducted.  Four QI strategies (CM, TC, PE, PSM) were consistently identified as 'Top' across the majority of outcomes. All QI strategies were ranked as 'Top' for at least one key outcome. The majority of effects of individual QI strategies were modest, but when used in combination could result in meaningful population-level improvements across the majority of outcomes. The median number of QI strategies in multicomponent QI programmes was three.  Combinations of the three most effective QI strategies were estimated to lead to the below effects:  - PR + PSM + CE: decrease in HbA1c by 0.41% (credibility interval (CrI) -0.61 to -0.22) when baseline HbA1c < 8.3%; - CM + PE + EPR: decrease in HbA1c by 0.62% (CrI -0.84 to -0.39) when baseline HbA1c > 8.3%;  - PE + TC + PSM: reduction in SBP by 2.14 mmHg (CrI -3.80 to -0.52) when baseline SBP < 136 mmHg; - CM + TC + PSM: reduction in SBP by 4.39 mmHg (CrI -6.20 to -2.56) when baseline SBP > 136 mmHg;  - TC + PE + CM: LDL-C lowering of 5.73 mg/dL (CrI -7.93 to -3.61) when baseline LDL < 107 mg/dL; - TC + CM + CR: LDL-C lowering by 5.52 mg/dL (CrI -9.24 to -1.89) when baseline LDL > 107 mg/dL. Assuming a baseline screening rate of 50%, the three most effective QI strategies were estimated to lead to an absolute improvement of 33% in retinopathy screening (PE + PR + TC) and 38% absolute increase in foot screening (PE + TC + Other). AUTHORS' CONCLUSIONS: There is a significant body of evidence about QI programmes to improve the management of diabetes. Multicomponent QI programmes for diabetes care (comprised of effective QI strategies) may achieve meaningful population-level improvements across the majority of outcomes. For health system decision-makers, the evidence summarised in this review can be used to identify strategies to include in QI programmes. For researchers, this synthesis identifies higher-priority QI strategies to examine in further research regarding how to optimise their evaluation and effects. We will maintain this as a living systematic review.

Beyond guideline knowledge: a theory-based qualitative study of low-value preoperative testing.

BACKGROUND: Choosing Wisely Canada and most major anesthesia and preoperative guidelines recommend against obtaining preoperative tests before low-risk procedures. However, these recommendations alone have not reduced low-value test ordering. In this study, the theoretical domains framework (TDF) was used to understand the drivers of preoperative electrocardiogram (ECG) and chest X-ray (CXR) ordering for patients undergoing low-risk surgery ('low-value preoperative testing') among anesthesiologists, internal medicine specialists, nurses, and surgeons. METHODS: Using snowball sampling, preoperative clinicians working in a single health system in Canada were recruited for semi-structured interviews about low-value preoperative testing. The interview guide was developed using the TDF to identify the factors that influence preoperative ECG and CXR ordering. Interview content was deductively coded using TDF domains and specific beliefs were identified by grouping similar utterances. Domain relevance was established based on belief statement frequency, presence of conflicting beliefs, and perceived influence over preoperative test ordering practices. RESULTS: Sixteen clinicians (7 anesthesiologists, 4 internists, 1 nurse, and 4 surgeons) participated. Eight of the 12 TDF domains were identified as the drivers of preoperative test ordering. While most participants agreed that the guidelines were helpful, they also expressed distrust in the evidence behind them (knowledge). Both a lack of clarity about the responsibilities of the specialties involved in the preoperative process and the ease by which any clinician could order, but not cancel tests, were drivers of low-value preoperative test ordering (social/professional role and identity, social influences, belief about capabilities). Additionally, low-value tests could also be ordered by nurses or the surgeon and may be completed before the anesthesia or internal medicine preoperative assessment appointment (environmental context and resources, beliefs about capabilities). Finally, while participants agreed that they did not intend to routinely order low-value tests and understood that these would not benefit patient outcomes, they also reported ordering tests to prevent surgery cancellations and problems during surgery (motivation and goals, beliefs about consequences, social influences). CONCLUSIONS: We identified key factors that anesthesiologists, internists, nurses, and surgeons believe influence preoperative test ordering for patients undergoing low-risk surgeries. These beliefs highlight the need to shift away from knowledge-based interventions and focus instead on understanding local drivers of behaviour and target change at the individual, team, and institutional levels.

A declaração PRISMA 2020: diretriz atualizada para relatar revisões sistemáticas / The PRISMA 2020 statement: an updated guideline for reporting systematic reviews / Declaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas

RESUMO A declaração dos Principais Itens para Relatar Revisões Sistemáticas e Meta-análises (PRISMA), publicada em 2009, foi desenvolvida para ajudar revisores sistemáticos a relatar de forma transparente por que a revisão foi feita, os métodos empregados e o que os autores encontraram. Na última década, os avanços na metodologia e terminologia de revisões sistemáticas exigiram a atualização da diretriz. A declaração PRISMA 2020 substitui a declaração de 2009 e inclui novas orientações para relato que refletem os avanços nos métodos para identificar, selecionar, avaliar e sintetizar estudos. A estrutura e apresentação dos itens foram modificadas para facilitar a implementação. Neste artigo, apresentamos a lista de checagem PRISMA 2020 de 27 itens, uma lista de checagem expandida que detalha as recomendações para relato para cada item, a lista de checagem PRISMA 2020 para resumos e os fluxogramas revisados para novas revisões e para atualização de revisões.

ABSTRACT The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

RESUMEN La declaración PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), publicada en 2009, se diseñó para ayudar a los autores de revisiones sistemáticas a documentar de manera transparente el porqué de la revisión, qué hicieron los autores y qué encontraron. Durante la última década, ha habido muchos avances en la metodología y terminología de las revisiones sistemáticas, lo que ha requerido una actualización de esta guía. La declaración PRISMA 2020 sustituye a la declaración de 2009 e incluye una nueva guía de presentación de las publicaciones que refleja los avances en los métodos para identificar, seleccionar, evaluar y sintetizar estudios. La estructura y la presentación de los ítems ha sido modificada para facilitar su implementación. En este artículo, presentamos la lista de verificación PRISMA 2020 con 27 ítems, y una lista de verificación ampliada que detalla las recomendaciones en la publicación de cada ítem, la lista de verificación del resumen estructurado PRISMA 2020 y el diagrama de flujo revisado para revisiones sistemáticas.

Perceived barriers and enablers to the provision of diabetic retinopathy screening for young adults: a cross-sectional survey of healthcare professionals working in the UK National Diabetic Eye Screening Programme.

INTRODUCTION: Diabetic retinopathy screening (DRS) attendance in young adults is consistently below recommended levels. The aim of this study was to conduct a survey of screening providers in the UK Diabetic Eye Screening Programme (DESP) to identify perceived barriers and enablers to DRS attendance in young adults and elicit views on the effectiveness of strategies to improve screening uptake in this population. RESEARCH DESIGN AND METHODS: Members of the British Association of Retinal Screening (n=580) were invited to complete an anonymous online survey in July 2020 assessing agreement with 37 belief statements, informed by the Theoretical Domains Framework (TDF) of behavior change, describing potential barrier/enablers to delivering DRS for young adults and further survey items exploring effectiveness of strategies to improve uptake of DRS. RESULTS: In total, 140 (24%) responses were received mostly from screener/graders (67.1%). There was a high level of agreement that the DESP had a role in improving attendance in young adults (96.4%) and that more could be done to improve attendance (90.0%). The most commonly reported barriers related to TDF domains Social influences and Environmental context and resources including lack of integration of DRS with other processes of diabetes care, which limited the ability to discuss diabetes self-management. Other barriers included access to screening services and difficulties with scheduling appointments. Less than half (46.4%) of respondents reported having a dedicated strategy to improve screening uptake in young adults. Strategies perceived to be effective included: screening within the community; prompts/reminders and integrating eye screening with other diabetes services. CONCLUSIONS: Screening providers were concerned about screening uptake in young adults, although many programs lacked a dedicated strategy to improve attendance. Problems associated with a lack of integration between DRS with other diabetes care processes were identified as a major barrier to providing holistic care to young adults and supporting diabetes self-management.

The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

Barriers to and enablers of attendance at diabetic retinopathy screening experienced by immigrants to Canada from multiple cultural and linguistic minority groups.

AIM: To identify barriers to/enablers of attendance at eye screening among three groups of immigrantsto Canada from cultural/linguistic minority groups living with diabetes. METHODS: Using a patient-oriented research approach leveraging Diabetes Action Canada's patient engagement platform, we interviewed a purposeful sample of people with type 2 diabetes who had immigrated to Canada from: Pakistan (interviews in Urdu), China (interviews in Mandarin) and French-speaking African and Caribbean nations (interviews in French). We collected and analysed data based on the Theoretical Domains Framework covering key modifiable factors that may operate as barriers to or enablers of attending eye screening. We used directed content analysis to code barrier/enabler domains. Barriers/enablers were mapped to behaviour change techniques to inform future intervention development. RESULTS: We interviewed 39 people (13 per group). Many barriers/enablers were consistent across groups, including views about harms caused by screening itself, practical appointment issues including forgetting, screening costs, wait times and making/getting to an appointment, lack of awareness about retinopathy screening, language barriers, and family and clinical support. Group-specific barriers/enablers included a preference to return to one's country of birth for screening, the impact of winter, and preferences for alternative medicine. CONCLUSION: Our results can inform linguistic and culturally competent interventions to support immigrants living with diabetes in attending eye screening to prevent avoidable blindness.

Behavioral Determinants of Canadian Radiation Oncologists' Use of Single Fraction Palliative Radiation Therapy for Uncomplicated Bone Metastases.

BACKGROUND: A mainstay therapy for pain relief from uncomplicated bone metastases is external beam radiation therapy. Single fraction radiation therapy (SFRT) is more convenient and cost-effective, causes fewer acute side effects, and is equivalent to multiple fraction radiation therapy for pain relief. Despite these advantages, radiation oncologists seldom prescribe SFRT. PURPOSE: To identify the behavioral determinants to Canadian radiation oncologists' use of SFRT for uncomplicated bone metastases. METHODS AND MATERIALS: Semistructured interviews were conducted with 38 radiation oncologists from all 10 Canadian provinces. The interview guide and analysis were guided by the Theoretical Domains Framework (TDF). Transcripts were analyzed using a 5-phase thematic content analysis process: coding, generation of belief statements, generation of themes within TDF domains, generation of overarching themes, and classification of themes as barriers or facilitators to SFRT use, or as divergent (a barrier or facilitator depending on the participant). RESULTS: Thirteen overarching themes were identified of which 2 were barriers, 7 were facilitators, and 4 were divergent. The most commonly identified theme was the facilitator "most radiation oncologists are aware of evidence and guidelines on the use SFRT" (n = 38, 100%). The 3 next most reported themes (n = 37, 97.4% ) were (1) "radiation oncologists' use of SFRT can influence their colleagues" use of it (divergent), (2) experience with SFRT can increase its use (facilitator), and (3) SFRT is convenient for patients (facilitator). The most commonly identified barrier (n = 31, 81.6%) was "SFRT is associated with a higher risk of retreatment." CONCLUSIONS: Our use of the TDF to explore the behavioral determinants of Canadian radiation oncologists' use of SFRT for uncomplicated bone metastases identified a range of factors that are perceived to encourage and discourage its use. Our results will inform the design of future interventions to increase the use of SFRT.

Manually-generated reminders delivered on paper: effects on professional practice and patient outcomes.

BACKGROUND: Health professionals sometimes do not use the best evidence to treat their patients, in part due to unconscious acts of omission and information overload. Reminders help clinicians overcome these problems by prompting them to recall information that they already know, or by presenting information in a different and more accessible format. Manually-generated reminders delivered on paper are defined as information given to the health professional with each patient or encounter, provided on paper, in which no computer is involved in the production or delivery of the reminder. Manually-generated reminders delivered on paper are relatively cheap interventions, and are especially relevant in settings where electronic clinical records are not widely available and affordable. This review is one of three Cochrane Reviews focused on the effectiveness of reminders in health care. OBJECTIVES: 1. To determine the effectiveness of manually-generated reminders delivered on paper in changing professional practice and improving patient outcomes. 2. To explore whether a number of potential effect modifiers influence the effectiveness of manually-generated reminders delivered on paper. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and two trials registers on 5 December 2018. We searched grey literature, screened individual journals, conference proceedings and relevant systematic reviews, and reviewed reference lists and cited references of included studies. SELECTION CRITERIA: We included randomised and non-randomised trials assessing the impact of manually-generated reminders delivered on paper as a single intervention (compared with usual care) or added to one or more co-interventions as a multicomponent intervention (compared with the co-intervention(s) without the reminder component) on professional practice or patients' outcomes. We also included randomised and non-randomised trials comparing manually-generated reminders with other quality improvement (QI) interventions. DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility and abstracted data independently. We extracted the primary outcome as defined by the authors or calculated the median effect size across all reported outcomes in each study. We then calculated the median percentage improvement and interquartile range across the included studies that reported improvement related outcomes, and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We identified 63 studies (41 cluster-randomised trials, 18 individual randomised trials, and four non-randomised trials) that met all inclusion criteria. Fifty-seven studies reported usable data (64 comparisons). The studies were mainly located in North America (42 studies) and the UK (eight studies). Fifty-four studies took place in outpatient/ambulatory settings. The clinical areas most commonly targeted were cardiovascular disease management (11 studies), cancer screening (10 studies) and preventive care (10 studies), and most studies had physicians as their target population (57 studies). General management of a clinical condition (17 studies), test-ordering (14 studies) and prescription (10 studies) were the behaviours more commonly targeted by the intervention. Forty-eight studies reported changes in professional practice measured as dichotomous process adherence outcomes (e.g. compliance with guidelines recommendations), 16 reported those changes measured as continuous process-of-care outcomes (e.g. number of days with catheters), eight reported dichotomous patient outcomes (e.g. mortality rates) and five reported continuous patient outcomes (e.g. mean systolic blood pressure). Manually-generated reminders delivered on paper probably improve professional practice measured as dichotomous process adherence outcomes) compared with usual care (median improvement 8.45% (IQR 2.54% to 20.58%); 39 comparisons, 40,346 participants; moderate certainty of evidence) and may make little or no difference to continuous process-of-care outcomes (8 comparisons, 3263 participants; low certainty of evidence). Adding manually-generated paper reminders to one or more QI co-interventions may slightly improve professional practice measured as dichotomous process adherence outcomes (median improvement 4.24% (IQR -1.09% to 5.50%); 12 comparisons, 25,359 participants; low certainty of evidence) and probably slightly improve professional practice measured as continuous outcomes (median improvement 0.28 (IQR 0.04 to 0.51); 2 comparisons, 12,372 participants; moderate certainty of evidence). Compared with other QI interventions, manually-generated reminders may slightly decrease professional practice measured as process adherence outcomes (median decrease 7.9% (IQR -0.7% to 11%); 14 comparisons, 21,274 participants; low certainty of evidence). We are uncertain whether manually-generated reminders delivered on paper, compared with usual care or with other QI intervention, lead to better or worse patient outcomes (dichotomous or continuous), as the certainty of the evidence is very low (10 studies, 13 comparisons). Reminders added to other QI interventions may make little or no difference to patient outcomes (dichotomous or continuous) compared with the QI alone (2 studies, 2 comparisons). Regarding resource use, studies reported additional costs per additional point of effectiveness gained, but because of the different currencies and years used the relevance of those figures is uncertain. None of the included studies reported outcomes related to harms or adverse effects. AUTHORS' CONCLUSIONS: Manually-generated reminders delivered on paper as a single intervention probably lead to small to moderate increases in outcomes related to adherence to clinical recommendations, and they could be used as a single QI intervention. It is uncertain whether reminders should be added to other QI intervention already in place in the health system, although the effects may be positive. If other QI interventions, such as patient or computerised reminders, are available, they should be preferred over manually-generated reminders, but under close evaluation in order to decrease uncertainty about their potential effect.

Imaging use for low back pain by Ontario primary care clinicians: protocol for a mixed methods study - the Back ON study.

BACKGROUND: At any one time, one in every five Canadians has low back pain (LBP), and LBP is one of the most common health problems in primary care. Guidelines recommend that imaging not be routinely performed in patients presenting with LBP without signs or symptoms indicating a potential pathological cause. Yet imaging rates remain high for many patients who present without such indications. Inappropriate imaging can lead to inappropriate treatments, results in worse health outcomes and causes harm from unnecessary radiation. There is a need to understand the extent of, and factors contributing to, inappropriate imaging for LBP, and to develop effective strategies that target modifiable barriers and facilitators. The primary study objectives are to determine: 1) The rate of, and factors associated with, inappropriate lumbar spine imaging (x-ray, CT scan and MRI) for people with non-specific LBP presenting to primary care clinicians in Ontario; 2) The barriers and facilitators to reduce inappropriate imaging for LBP in primary care settings. METHODS: The project will comprise an inception cohort study and a concurrent qualitative study. For the cohort study, we will recruit 175 primary care clinicians (50 each from physiotherapy and chiropractic; 75 from family medicine), and 3750 patients with a new episode of LBP who present to these clinicians. Clinicians will collect data in the clinic, and each participant will be tracked for 12 months using Ontario health administrative and self-reported data to measure diagnostic imaging use and other health outcomes. We will assess characteristics of the clinicians, patients and encounters to identify variables associated with inappropriate imaging. In the qualitative study we will conduct in-depth interviews with primary care clinicians and patients. DISCUSSION: This will be the first Canadian study to accurately document the extent of the overuse of imaging for LBP, and the first worldwide to include data from the main healthcare professions offering primary care for people with LBP. This study will provide robust information about rates of inappropriate imaging for LBP, along with factors associated with, and an understanding of, potential reasons for inappropriate imaging.

Inappropriateness of health care in Canada: a systematic review protocol.

BACKGROUND: There is increasing recognition in Canada and globally that a substantial proportion of health care delivered is inappropriate as evidenced by (1) harmful and/or ineffective practices being overused, (2) effective clinical practices being underused, and (3) other clinical practices being misused. Inappropriate health care leads to negative patient experiences, poor health outcomes, and inefficient use of scarce health care resources. The purpose of this study is to conduct a systematic review of inappropriate health care in Canada. Our specific objectives are to (1) systematically search and critically review published and grey literature for studies on inappropriate health care in Canada; (2) estimate the nature and magnitude of inappropriate health care in Canada and its provincial and territorial jurisdictions. METHODS: We will include all quantitative study designs reporting objective or subjective measurements of inappropriate health care in Canada over the last 10 years. We will search the following online databases: MEDLINE, Cochrane Central Register of Controlled Trials, EconLit, and ISI-Web of Knowledge, which contains Web of Science Core Collection-Citation Indexes, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and Conference Proceedings Citation Index-Social Science & Humanities. We will also search grey literature sources to identify provincial and national audits of inappropriate health care. Two authors will independently screen, assess data quality, and extract data for synthesis. Study findings will be synthesized narratively. We will organize our data into three care categorizations: preventive care, acute care, and chronic care. We will provide a compendium of inappropriate health care for each care category for Canada and each Canadian province and territory, where sufficient data exists, by calculating (1) overall medians of underuse, overuse, and misuse of clinical practices and (2) the range of medians of underuse, overuse, and misuse for each clinical practice investigated. DISCUSSION: This review will result in the first-ever evidence-based compendium of inappropriate health care in Canada. We will also develop detailed reports of inappropriate health care for each Canadian province and territory. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018093495.

Comparative, cross-sectional study of the format, content and timing of medication safety letters issued in Canada, the USA and the UK.

OBJECTIVES: To assess consistency in the format and content, and overlap of subject and timing, of medication safety letters issued by regulatory health authorities to healthcare providers in Canada, the USA and the UK. DESIGN: A cross-sectional study comparing medication safety letters issued for the purpose of alerting healthcare providers to newly identified medication problems associated with medications already on the market. SETTING: Online databases operated by Health Canada, the US Food and Drug Administration and the UK Medicines and Healthcare products Regulatory Agency were searched to select medication safety letters issued between 1 January 2010 and 31 December 2014. Format, content and timing of each medication safety letter were assessed using an abstraction tool comprising 21 characteristics deemed relevant by consensus of the research team. MAIN OUTCOME MEASURES: Main outcome measures included, first, characteristics (format and content) of medication safety letters and second, overlap of subject and release date across countries. RESULTS: Of 330 medication safety letters identified, 227 dealt with unique issues relating to medications available in all three countries. Of these 227 letters, 21 (9%) medication problems were the subject of letters released in all three countries; 40 (18%) in two countries and 166 (73%) in only one country. Only 13 (62%) of the 21 letters issued in all three countries were released within 6 months of each other. CONCLUSIONS: Significant discrepancies in both the subject and timing of medication safety letters issued by health authorities in three countries (Canada, the USA and the UK) where medical practice is otherwise comparable, raising questions about why, how and when medication problems are identified and communicated to healthcare providers by the authorities. More rapid communication of medication problems and better alignment between authorities could enhance patient safety.

Effect of audit and feedback on physicians' intraoperative temperature management and patient outcomes: a three-arm cluster randomized-controlled trial comparing benchmarked and ranked feedback.

PURPOSE: Audit and feedback can improve physicians' practice; however, the most effective type of feedback is unknown. Inadvertent perioperative hypothermia is associated with postoperative complications and remains common despite the use of effective and safe warming devices. This study aimed to measure the impact of targeted audit and feedback on anesthesiologists' intraoperative temperature management and subsequent patient outcomes. METHODS: This study was a three-arm cluster randomized-controlled trial. Anesthesiologists' intraoperative temperature management performance was analyzed in two phases. The first was a baseline phase with audit but no feedback for eight months, followed by an intervention phase over the next seven-month period after participants had received interventions according to their randomized group allocation of no feedback (control), benchmarked feedback, or ranked feedback. Anesthesiologists' percentage of hypothermic patients at the end of surgery (primary endpoint) and use of a warming device were compared among the groups. RESULTS: Forty-five attending anesthesiologists who took care of 7,846 patients over 15 months were included. The odds of hypothermia (temperature < 36°C at the end of surgery) increased significantly from pre- to post-intervention in the control and ranked groups (control odds ratio [OR], 1.27; 95% confidence interval [CI], 1.03 to 1.56; P = 0.02; ranked OR, 1.26; 95% CI, 1.01 to 1.56; P = 0.04) but not in the benchmarked group (OR, 1.05; 95% CI, 0.87 to 1.28; P = 0.58). Between-arm differences in pre- to post-intervention changes were not significant (benchmark vs control OR, 0.83; 95% CI, 0.62 to 1.10; P = 0.19; ranked vs control OR, 0.99; 95% CI, 0.73 to 1.33, P = 0.94). No significant overall effect on intraoperative warmer use change was detected. CONCLUSION: We found no evidence to suggest that audit and feedback, using benchmarked or ranked feedback, is more effective than no feedback at all to change anesthesiologists' intraoperative temperature management performance. Feedback may need to be included in a bundle to produce its effect. TRIALS REGISTRATION: www.clinicaltrials.gov (NCT02414191). Registered 19 March 2015.

What works to increase attendance for diabetic retinopathy screening? An evidence synthesis and economic analysis.

BACKGROUND: Diabetic retinopathy screening (DRS) is effective but uptake is suboptimal. OBJECTIVES: To determine the effectiveness of quality improvement (QI) interventions for DRS attendance; describe the interventions in terms of QI components and behaviour change techniques (BCTs); identify theoretical determinants of attendance; investigate coherence between BCTs identified in interventions and determinants of attendance; and determine the cost-effectiveness of QI components and BCTs for improving DRS. DATA SOURCES AND REVIEW METHODS: Phase 1 - systematic review of randomised controlled trials (RCTs) evaluating interventions to increase DRS attendance (The Cochrane Library, MEDLINE, EMBASE and trials registers to February 2017) and coding intervention content to classify QI components and BCTs. Phase 2 - review of studies reporting factors influencing attendance, coded to theoretical domains (MEDLINE, EMBASE, PsycINFO and sources of grey literature to March 2016). Phase 3 - mapping BCTs (phase 1) to theoretical domains (phase 2) and an economic evaluation to determine the cost-effectiveness of BCTs or QI components. RESULTS: Phase 1 - 7277 studies were screened, of which 66 RCTs were included in the review. Interventions were multifaceted and targeted patients, health-care professionals (HCPs) or health-care systems. Overall, interventions increased DRS attendance by 12% [risk difference (RD) 0.12, 95% confidence interval (CI) 0.10 to 0.14] compared with usual care, with substantial heterogeneity in effect size. Both DRS-targeted and general QI interventions were effective, particularly when baseline attendance levels were low. All commonly used QI components and BCTs were associated with significant improvements, particularly in those with poor attendance. Higher effect estimates were observed in subgroup analyses for the BCTs of 'goal setting (outcome, i.e. consequences)' (RD 0.26, 95% CI 0.16 to 0.36) and 'feedback on outcomes (consequences) of behaviour' (RD 0.22, 95% CI 0.15 to 0.29) in interventions targeting patients and of 'restructuring the social environment' (RD 0.19, 95% CI 0.12 to 0.26) and 'credible source' (RD 0.16, 95% CI 0.08 to 0.24) in interventions targeting HCPs. Phase 2 - 3457 studies were screened, of which 65 non-randomised studies were included in the review. The following theoretical domains were likely to influence attendance: 'environmental context and resources', 'social influences', 'knowledge', 'memory, attention and decision processes', 'beliefs about consequences' and 'emotions'. Phase 3 - mapping identified that interventions included BCTs targeting important barriers to/enablers of DRS attendance. However, BCTs targeting emotional factors around DRS were under-represented. QI components were unlikely to be cost-effective whereas BCTs with a high probability (≥ 0.975) of being cost-effective at a societal willingness-to-pay threshold of £20,000 per QALY included 'goal-setting (outcome)', 'feedback on outcomes of behaviour', 'social support' and 'information about health consequences'. Cost-effectiveness increased when DRS attendance was lower and with longer screening intervals. LIMITATIONS: Quality improvement/BCT coding was dependent on descriptions of intervention content in primary sources; methods for the identification of coherence of BCTs require improvement. CONCLUSIONS: Randomised controlled trial evidence indicates that QI interventions incorporating specific BCT components are associated with meaningful improvements in DRS attendance compared with usual care. Interventions generally used appropriate BCTs that target important barriers to screening attendance, with a high probability of being cost-effective. Research is needed to optimise BCTs or BCT combinations that seek to improve DRS attendance at an acceptable cost. BCTs targeting emotional factors represent a missed opportunity to improve attendance and should be tested in future studies. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016044157 and PROSPERO CRD42016032990. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Testing Behavior Change Techniques to Encourage Primary Care Physicians to Access Cancer Screening Audit and Feedback Reports: Protocol for a Factorial Randomized Experiment of Email Content.

BACKGROUND: Cancer Care Ontario's Screening Activity Report (SAR) is an online audit and feedback tool designed to help primary care physicians in Ontario, Canada, identify patients who are overdue for cancer screening or have abnormal results requiring follow-up. Use of the SAR is associated with increased screening rates. To encourage SAR use, Cancer Care Ontario sends monthly emails to registered primary care physicians announcing that updated data are available. However, analytics reveal that 50% of email recipients do not open the email and less than 7% click the embedded link to log in to their report. OBJECTIVE: The goal of the study is to determine whether rewritten emails result in increased log-ins. This manuscript describes how different user- and theory-informed messages intended to improve the impact of the monthly emails will be experimentally tested and how a process evaluation will explore why and how any effects observed were (or were not) achieved. METHODS: A user-centered approach was used to rewrite the content of the monthly email, including messages operationalizing 3 behavior change techniques: anticipated regret, material incentive (behavior), and problem solving. A pragmatic, 2x2x2 factorial experiment within a multiphase optimization strategy will test the redesigned emails with an embedded qualitative process evaluation to understand how and why the emails may or may not have worked. Trial outcomes will be ascertained using routinely collected administrative data. Physicians will be recruited for semistructured interviews using convenience and snowball sampling. RESULTS: As of April 2017, 5576 primary care physicians across the province of Ontario, Canada, had voluntarily registered for the SAR, and in so doing, signed up to receive the monthly email updates. From May to August 2017 participants received the redesigned monthly emails with content specific to their allocated experimental condition prompting use of the SAR. We have not yet begun analyses. CONCLUSIONS: This study will inform how to communicate effectively with primary care providers by email and identify which behavior change techniques tested are most effective at encouraging engagement with an audit and feedback report. TRIAL REGISTRATION: ClinicalTrials.gov NCT03124316; https://clinicaltrials.gov/ct2/show/NCT03124316 (Archived by WebCite at http://www.webcitation.org/6w2MqDWGu).

The evaluation of enhanced feedback interventions to reduce unnecessary blood transfusions (AFFINITIE): protocol for two linked cluster randomised factorial controlled trials.

BACKGROUND: Blood for transfusion is a frequently used clinical intervention, and is also a costly and limited resource with risks. Many transfusions are given to stable and non-bleeding patients despite no clear evidence of benefit from clinical studies. Audit and feedback (A&F) is widely used to improve the quality of healthcare, including appropriate use of blood. However, its effects are often inconsistent, indicating the need for coordinated research including more head-to-head trials comparing different ways of delivering feedback. A programmatic series of research projects, termed the 'Audit and Feedback INterventions to Increase evidence-based Transfusion practIcE' (AFFINITIE) programme, aims to test different ways of developing and delivering feedback within an existing national audit structure. METHODS: The evaluation will comprise two linked 2×2 factorial, cross-sectional cluster-randomised controlled trials. Each trial will estimate the effects of two feedback interventions, 'enhanced content' and 'enhanced follow-on support', designed in earlier stages of the AFFINITIE programme, compared to current practice. The interventions will be embedded within two rounds of the UK National Comparative Audit of Blood Transfusion (NCABT) focusing on patient blood management in surgery and use of blood transfusions in patients with haematological malignancies. The unit of randomisation will be National Health Service (NHS) trust or health board. Clusters providing care relevant to the audit topics will be randomised following each baseline audit (separately for each trial), with stratification for size (volume of blood transfusions) and region (Regional Transfusion Committee). The primary outcome for each topic will be the proportion of patients receiving a transfusion coded as unnecessary. For each audit topic a linked, mixed-method fidelity assessment and cost-effectiveness analysis will be conducted in parallel to the trial. DISCUSSION: AFFINITIE involves a series of studies to explore how A&F may be refined to change practice including two cluster randomised trials linked to national audits of transfusion practice. The methodology represents a step-wise increment in study design to more fully evaluate the effects of two enhanced feedback interventions on patient- and trust-level clinical, cost, safety and process outcomes. TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN15490813.

A multidimensional approach to assessing intervention fidelity in a process evaluation of audit and feedback interventions to reduce unnecessary blood transfusions: a study protocol.

BACKGROUND: In England, NHS Blood and Transplant conducts national audits of transfusion and provides feedback to hospitals to promote evidence-based practice. Audits demonstrate 20% of transfusions fall outside guidelines. The AFFINITIE programme (Development & Evaluation of Audit and Feedback INterventions to Increase evidence-based Transfusion practIcE) involves two linked, 2×2 factorial, cluster-randomised trials, each evaluating two theoretically-enhanced audit and feedback interventions to reduce unnecessary blood transfusions in UK hospitals. The first intervention concerns the content/format of feedback reports. The second aims to support hospital transfusion staff to plan their response to feedback and includes a web-based toolkit and telephone support. Interpretation of trials is enhanced by comprehensively assessing intervention fidelity. However, reviews demonstrate fidelity evaluations are often limited, typically only assessing whether interventions were delivered as intended. This protocol presents methods for assessing fidelity across five dimensions proposed by the Behaviour Change Consortium fidelity framework, including intervention designer-, provider- and recipient-levels. METHODS: (1) Design: Intervention content will be specified in intervention manuals in terms of component behaviour change techniques (BCTs). Treatment differentiation will be examined by comparing BCTs across intervention/standard practice, noting the proportion of unique/convergent BCTs. (2) Training: draft feedback reports and audio-recorded role-play telephone support scenarios will be content analysed to assess intervention providers' competence to deliver manual-specified BCTs. (3) Delivery: intervention materials (feedback reports, toolkit) and audio-recorded telephone support session transcripts will be content analysed to assess actual delivery of manual-specified BCTs during the intervention period. (4) Receipt and (5) enactment: questionnaires, semi-structured interviews based on the Theoretical Domains Framework, and objective web-analytics data (report downloads, toolkit usage patterns) will be analysed to assess hospital transfusion staff exposure to, understanding and enactment of the interventions, and to identify contextual barriers/enablers to implementation. Associations between observed fidelity and trial outcomes (% unnecessary transfusions) will be examined using mediation analyses. DISCUSSION: If the interventions have acceptable fidelity, then results of the AFFINITIE trials can be attributed to effectiveness, or lack of effectiveness, of the interventions. Hence, this comprehensive assessment of fidelity will be used to interpret trial findings. These methods may inform fidelity assessments in future trials. TRIAL REGISTRATION: ISRCTN 15490813 . Registered 11/03/2015.

Design and rationale for the Acute Congestive Heart Failure Urgent Care Evaluation: The ACUTE Study.

BACKGROUND: Heart failure (HF) is one of the leading reasons for emergency department (ED) visits and hospitalization. However, externally validated risk algorithms for acute prognostication of heart failure patients are not available. Thus, many low-risk patients are hospitalized and some high-risk patients are discharged home, which, in some cases, may lead to death. OBJECTIVES: The first objective of the ACUTE study is to perform a prospective validation of the Emergency Heart failure Mortality Risk Grade (EHMRG), which is a risk score derived to predict 7-day mortality in the ED setting. The second objective is to independently validate the 30-day model extension of the risk score (EHMRG30-ST) in the same cohort. STUDY DESIGN: Patients with HF presenting to the ED will be recruited with a waiver of informed consent as a minimal risk study. The ED physician will calculate the EHMRG 7-day risk score, but treatment decisions will not be influenced by the predictive models. Follow-up will be obtained using probabilistic linkage with the Registered Persons Database of vital statistics, whereby deaths will be ascertained. We will examine mortality rates according to EHMRG and EHMRG30-ST algorithms. We will also compare physician-judged risk estimates, based on clinical judgment alone, with the EHMRG score. CONCLUSION: The ACUTE study will determine if a retrospectively derived algorithm for simultaneous estimation of 7-day and 30-day mortality risk can accurately identify low- and high-risk patients with acute HF and improve upon physician-judged risk estimation.