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1.  Design, implementation, and evaluation of a knowledge translation intervention to increase organ donation after cardiocirculatory death in Canada: a study protocol 
Background
A shortage of transplantable organs is a global problem. There are two types of organ donation: living and deceased. Deceased organ donation can occur following neurological determination of death (NDD) or cardiocirculatory death. Donation after cardiocirculatory death (DCD) accounts for the largest increments in deceased organ donation worldwide. Variations in the use of DCD exist, however, within Canada and worldwide. Reasons for these discrepancies are largely unknown. The purpose of this study is to develop, implement, and evaluate a theory-based knowledge translation intervention to provide practical guidance about how to increase the numbers of DCD organ donors without reducing the numbers of standard NDD donors.
Methods
We will use a mixed method three-step approach. In step one, we will conduct semi-structured interviews, informed by the Theoretical Domains Framework, to identify and describe stakeholders’ beliefs and attitudes about DCD and their perceptions of the multi-level factors that influence DCD. We will identify: determinants of the evidence-practice gap; specific behavioural changes and/or process changes needed to increase DCD; specific group(s) of clinicians or organizations (e.g., provincial donor organizations) in need of behaviour change; and specific targets for interventions. In step two, using the principles of intervention mapping, we will develop a theory-based knowledge translation intervention that encompasses behavior change techniques to overcome the identified barriers and enhance the enablers to DCD. In step three, we will roll out the intervention in hospitals across the 10 Canadian provinces and evaluate its effectiveness using a multiple interrupted time series design.
Discussion
We will adopt a behavioural approach to define and test novel, theory-based, and ethically-acceptable knowledge translation strategies to increase the numbers of available DCD organ donors in Canada. If successful, this study will ultimately lead to more transplantations, reducing patient morbidity and mortality at a population-level.
doi:10.1186/1748-5908-9-80
PMCID: PMC4082291  PMID: 24950719
2.  The use of segmented regression in analysing interrupted time series studies: an example in pre-hospital ambulance care 
Background
An interrupted time series design is a powerful quasi-experimental approach for evaluating effects of interventions introduced at a specific point in time. To utilize the strength of this design, a modification to standard regression analysis, such as segmented regression, is required. In segmented regression analysis, the change in intercept and/or slope from pre- to post-intervention is estimated and used to test causal hypotheses about the intervention. We illustrate segmented regression using data from a previously published study that evaluated the effectiveness of a collaborative intervention to improve quality in pre-hospital ambulance care for acute myocardial infarction (AMI) and stroke. In the original analysis, a standard regression model was used with time as a continuous variable. We contrast the results from this standard regression analysis with those from segmented regression analysis. We discuss the limitations of the former and advantages of the latter, as well as the challenges of using segmented regression in analysing complex quality improvement interventions.
Findings
Based on the estimated change in intercept and slope from pre- to post-intervention using segmented regression, we found insufficient evidence of a statistically significant effect on quality of care for stroke, although potential clinically important effects for AMI cannot be ruled out.
Conclusions
Segmented regression analysis is the recommended approach for analysing data from an interrupted time series study. Several modifications to the basic segmented regression analysis approach are available to deal with challenges arising in the evaluation of complex quality improvement interventions.
doi:10.1186/1748-5908-9-77
PMCID: PMC4068621  PMID: 24943919
Interrupted time series design; Segmented regression analysis; Quality improvement collaborative
3.  Improving Diabetes care through Examining, Advising, and prescribing (IDEA): protocol for a theory-based cluster randomised controlled trial of a multiple behaviour change intervention aimed at primary healthcare professionals 
Background
New clinical research findings may require clinicians to change their behaviour to provide high-quality care to people with type 2 diabetes, likely requiring them to change multiple different clinical behaviours. The present study builds on findings from a UK-wide study of theory-based behavioural and organisational factors associated with prescribing, advising, and examining consistent with high-quality diabetes care.
Aim
To develop and evaluate the effectiveness and cost of an intervention to improve multiple behaviours in clinicians involved in delivering high-quality care for type 2 diabetes.
Design/methods
We will conduct a two-armed cluster randomised controlled trial in 44 general practices in the North East of England to evaluate a theory-based behaviour change intervention. We will target improvement in six underperformed clinical behaviours highlighted in quality standards for type 2 diabetes: prescribing for hypertension; prescribing for glycaemic control; providing physical activity advice; providing nutrition advice; providing on-going education; and ensuring that feet have been examined. The primary outcome will be the proportion of patients appropriately prescribed and examined (using anonymised computer records), and advised (using anonymous patient surveys) at 12 months. We will use behaviour change techniques targeting motivational, volitional, and impulsive factors that we have previously demonstrated to be predictive of multiple health professional behaviours involved in high-quality type 2 diabetes care. We will also investigate whether the intervention was delivered as designed (fidelity) by coding audiotaped workshops and interventionist delivery reports, and operated as hypothesised (process evaluation) by analysing responses to theory-based postal questionnaires. In addition, we will conduct post-trial qualitative interviews with practice teams to further inform the process evaluation, and a post-trial economic analysis to estimate the costs of the intervention and cost of service use.
Discussion
Consistent with UK Medical Research Council guidance and building on previous development research, this pragmatic cluster randomised trial will evaluate the effectiveness of a theory-based complex intervention focusing on changing multiple clinical behaviours to improve quality of diabetes care.
Trial registration
ISRCTN66498413.
doi:10.1186/1748-5908-9-61
PMCID: PMC4049486  PMID: 24886606
4.  Efficacy and safety of mesenchymal stromal cells in preclinical models of acute lung injury: a systematic review protocol 
Systematic Reviews  2014;3:48.
Background
Acute respiratory distress syndrome (ARDS) in humans is caused by an unchecked proinflammatory response that results in diffuse and severe lung injury, and it is associated with a mortality rate of 35 to 45%. Mesenchymal stromal cells (MSCs; ‘adult stem cells’) could represent a promising new therapy for this syndrome, since preclinical evidence suggests that MSCs may ameliorate lung injury. Prior to a human clinical trial, our aim is to conduct a systematic review to compare the efficacy and safety of MSC therapy versus controls in preclinical models of acute lung injury that mimic some aspects of the human ARDS.
Methods/Design
We will include comparative preclinical studies (randomized and non-randomized) of acute lung injury in which MSCs were administered and outcomes compared to animals given a vehicle control. The primary outcome will be death. Secondary outcomes will include the four key features of preclinical acute lung injury as defined by the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar capillary barrier, lung inflammatory response, and physiological dysfunction) and pathogen clearance for acute lung injury models that are caused by infection. Electronic searches of MEDLINE, Embase, BIOSIS Previews, and Web of Science will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. Search results will be screened independently and in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias will be assessed using the Cochrane risk of bias tool, and individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines.
Discussion
The results of this systematic review will comprehensively summarize the safety and efficacy of MSC therapy in preclinical models of acute lung injury. Our results will help translational scientists and clinical trialists to determine whether sufficient evidence exists to perform a human clinical trial. These results may also guide future acute lung injury preclinical and clinical research.
doi:10.1186/2046-4053-3-48
PMCID: PMC4046388  PMID: 24887266
Mesenchymal stromal cells; Mesenchymal stem cells; Acute lung injury; Acute respiratory distress syndrome; Preclinical; Systematic review protocol
5.  Variability in research ethics review of cluster randomized trials: a scenario-based survey in three countries 
Trials  2014;15:48.
Background
Cluster randomized trials (CRTs) present unique ethical challenges. In the absence of a uniform standard for their ethical design and conduct, problems such as variability in procedures and requirements by different research ethics committees will persist. We aimed to assess the need for ethics guidelines for CRTs among research ethics chairs internationally, investigate variability in procedures for research ethics review of CRTs within and among countries, and elicit research ethics chairs’ perspectives on specific ethical issues in CRTs, including the identification of research subjects. The proper identification of research subjects is a necessary requirement in the research ethics review process, to help ensure, on the one hand, that subjects are protected from harm and exploitation, and on the other, that reviews of CRTs are completed efficiently.
Methods
A web-based survey with closed- and open-ended questions was administered to research ethics chairs in Canada, the United States, and the United Kingdom. The survey presented three scenarios of CRTs involving cluster-level, professional-level, and individual-level interventions. For each scenario, a series of questions was posed with respect to the type of review required (full, expedited, or no review) and the identification of research subjects at cluster and individual levels.
Results
A total of 189 (35%) of 542 chairs responded. Overall, 144 (84%, 95% CI 79 to 90%) agreed or strongly agreed that there is a need for ethics guidelines for CRTs and 158 (92%, 95% CI 88 to 96%) agreed or strongly agreed that research ethics committees could be better informed about distinct ethical issues surrounding CRTs. There was considerable variability among research ethics chairs with respect to the type of review required, as well as the identification of research subjects. The cluster-cluster and professional-cluster scenarios produced the most disagreement.
Conclusions
Research ethics committees identified a clear need for ethics guidelines for CRTs and education about distinct ethical issues in CRTs. There is disagreement among committees, even within the same countries, with respect to key questions in the ethics review of CRTs. This disagreement reflects variability of opinion and practices pointing toward possible gaps in knowledge, and supports the need for explicit guidelines for the ethical conduct and review of CRTs.
doi:10.1186/1745-6215-15-48
PMCID: PMC3925119  PMID: 24495542
Cluster randomized trials; Informed consent; Research ethics guidelines; Research ethics review; Web-based survey
6.  No more ‘business as usual’ with audit and feedback interventions: towards an agenda for a reinvigorated intervention 
Background
Audit and feedback interventions in healthcare have been found to be effective, but there has been little progress with respect to understanding their mechanisms of action or identifying their key ‘active ingredients.’
Discussion
Given the increasing use of audit and feedback to improve quality of care, it is imperative to focus further research on understanding how and when it works best. In this paper, we argue that continuing the ‘business as usual’ approach to evaluating two-arm trials of audit and feedback interventions against usual care for common problems and settings is unlikely to contribute new generalizable findings. Future audit and feedback trials should incorporate evidence- and theory-based best practices, and address known gaps in the literature.
Summary
We offer an agenda for high-priority research topics for implementation researchers that focuses on reviewing best practices for designing audit and feedback interventions to optimize effectiveness.
doi:10.1186/1748-5908-9-14
PMCID: PMC3896824  PMID: 24438584
Audit and feedback; Synthesis; Best practice; Implementation; Optimization
7.  The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials 
PLoS Medicine  2012;9(11):e1001346.
The Ottawa Ethics of Cluster Trials Consensus Group sets out 15 recommendations for the ethical design and conduct of cluster randomized trials.
doi:10.1371/journal.pmed.1001346
PMCID: PMC3502500  PMID: 23185138
8.  Feedback GAP: pragmatic, cluster-randomized trial of goal setting and action plans to increase the effectiveness of audit and feedback interventions in primary care 
Background
Audit and feedback to physicians is a commonly used quality improvement strategy, but its optimal design is unknown. This trial tested the effects of a theory-informed worksheet to facilitate goal setting and action planning, appended to feedback reports on chronic disease management, compared to feedback reports provided without these worksheets.
Methods
A two-arm pragmatic cluster randomized trial was conducted, with allocation at the level of primary care clinics. Participants were family physicians who contributed data from their electronic medical records. The ‘usual feedback’ arm received feedback every six months for two years regarding the proportion of their patients meeting quality targets for diabetes and/or ischemic heart disease. The intervention arm received these same reports plus a worksheet designed to facilitate goal setting and action plan development in response to the feedback reports. Blood pressure (BP) and low-density lipoprotein cholesterol (LDL) values were compared after two years as the primary outcomes. Process outcomes measured the proportion of guideline-recommended actions (e.g., testing and prescribing) conducted within the appropriate timeframe. Intention-to-treat analysis was performed.
Results
Outcomes were similar across groups at baseline. Final analysis included 20 physicians from seven clinics and 1,832 patients in the intervention arm (15% loss to follow up) and 29 physicians from seven clinics and 2,223 patients in the usual feedback arm (10% loss to follow up). Ten of 20 physicians completed the worksheet at least once during the study. Mean BP was 128/72 in the feedback plus worksheet arm and 128/73 in the feedback alone arm, while LDL was 2.1 and 2.0, respectively. Thus, no significant differences were observed across groups in the primary outcomes, but mean haemoglobin A1c was lower in the feedback plus worksheet arm (7.2% versus 7.4%, p<0.001). Improvements in both arms were noted over time for one-half of the process outcomes.
Discussion
Appending a theory-informed goal setting and action planning worksheet to an externally produced audit and feedback intervention did not lead to improvements in patient outcomes. The results may be explained in part by passive dissemination of the worksheet leading to inadequate engagement with the intervention.
Trial registration
ClinicalTrials.gov NCT00996645
doi:10.1186/1748-5908-8-142
PMCID: PMC3878579  PMID: 24341511
9.  Evidence-based care of older people with suspected cognitive impairment in general practice: protocol for the IRIS cluster randomised trial 
Background
Dementia is a common and complex condition. Evidence-based guidelines for the management of people with dementia in general practice exist; however, detection, diagnosis and disclosure of dementia have been identified as potential evidence-practice gaps. Interventions to implement guidelines into practice have had varying success. The use of theory in designing implementation interventions has been limited, but is advocated because of its potential to yield more effective interventions and aid understanding of factors modifying the magnitude of intervention effects across trials. This protocol describes methods of a randomised trial that tests a theory-informed implementation intervention that, if effective, may provide benefits for patients with dementia and their carers.
Aims
This trial aims to estimate the effectiveness of a theory-informed intervention to increase GPs’ (in Victoria, Australia) adherence to a clinical guideline for the detection, diagnosis, and management of dementia in general practice, compared with providing GPs with a printed copy of the guideline. Primary objectives include testing if the intervention is effective in increasing the percentage of patients with suspected cognitive impairment who receive care consistent with two key guideline recommendations: receipt of a i) formal cognitive assessment, and ii) depression assessment using a validated scale (primary outcomes for the trial).
Methods
The design is a parallel cluster randomised trial, with clusters being general practices. We aim to recruit 60 practices per group. Practices will be randomised to the intervention and control groups using restricted randomisation. Patients meeting the inclusion criteria, and GPs’ detection and diagnosis behaviours directed toward these patients, will be identified and measured via an electronic search of the medical records nine months after the start of the intervention. Practitioners in the control group will receive a printed copy of the guideline. In addition to receipt of the printed guideline, practitioners in the intervention group will be invited to participate in an interactive, opinion leader-led, educational face-to-face workshop. The theory-informed intervention aims to address identified barriers to and enablers of implementation of recommendations. Researchers responsible for identifying the cohort of patients with suspected cognitive impairment, and their detection and diagnosis outcomes, will be blind to group allocation.
Trial registration
Australian New Zealand Clinical Trials Registry: ACTRN12611001032943 (date registered 28 September, 2011).
doi:10.1186/1748-5908-8-91
PMCID: PMC3765181  PMID: 23958469
10.  What supports do health system organizations have in place to facilitate evidence-informed decision-making? a qualitative study 
Background
Decisions regarding health systems are sometimes made without the input of timely and reliable evidence, leading to less than optimal health outcomes. Healthcare organizations can implement tools and infrastructures to support the use of research evidence to inform decision-making.
Objectives
The purpose of this study was to profile the supports and instruments (i.e., programs, interventions, instruments or tools) that healthcare organizations currently have in place and which ones were perceived to facilitate evidence-informed decision-making.
Methods
In-depth semi-structured telephone interviews were conducted with individuals in three different types of positions (i.e., a senior management team member, a library manager, and a ‘knowledge broker’) in three types of healthcare organizations (i.e., regional health authorities, hospitals and primary care practices) in two Canadian provinces (i.e., Ontario and Quebec). The interviews were taped, transcribed, and then analyzed thematically using NVivo 9 qualitative data analysis software.
Results
A total of 57 interviews were conducted in 25 organizations in Ontario and Quebec. The main findings suggest that, for the healthcare organizations that participated in this study, the following supports facilitate evidence-informed decision-making: facilitating roles that actively promote research use within the organization; establishing ties to researchers and opinion leaders outside the organization; a technical infrastructure that provides access to research evidence, such as databases; and provision and participation in training programs to enhance staff’s capacity building.
Conclusions
This study identified the need for having a receptive climate, which laid the foundation for the implementation of other tangible initiatives and supported the use of research in decision-making. This study adds to the literature on organizational efforts that can increase the use of research evidence in decision-making. Some of the identified supports may increase the use of research evidence by decision-makers, which may then lead to more informed decisions, and hopefully to a strengthened health system and improved health.
doi:10.1186/1748-5908-8-84
PMCID: PMC3750753  PMID: 23915278
11.  Threats to Validity in the Design and Conduct of Preclinical Efficacy Studies: A Systematic Review of Guidelines for In Vivo Animal Experiments 
PLoS Medicine  2013;10(7):e1001489.
Background
The vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is flawed preclinical research. We conducted a systematic review of preclinical research guidelines and organized recommendations according to the type of validity threat (internal, construct, or external) or programmatic research activity they primarily address.
Methods and Findings
We searched MEDLINE, Google Scholar, Google, and the EQUATOR Network website for all preclinical guideline documents published up to April 9, 2013 that addressed the design and conduct of in vivo animal experiments aimed at supporting clinical translation. To be eligible, documents had to provide guidance on the design or execution of preclinical animal experiments and represent the aggregated consensus of four or more investigators. Data from included guidelines were independently extracted by two individuals for discrete recommendations on the design and implementation of preclinical efficacy studies. These recommendations were then organized according to the type of validity threat they addressed. A total of 2,029 citations were identified through our search strategy. From these, we identified 26 guidelines that met our eligibility criteria—most of which were directed at neurological or cerebrovascular drug development. Together, these guidelines offered 55 different recommendations. Some of the most common recommendations included performance of a power calculation to determine sample size, randomized treatment allocation, and characterization of disease phenotype in the animal model prior to experimentation.
Conclusions
By identifying the most recurrent recommendations among preclinical guidelines, we provide a starting point for developing preclinical guidelines in other disease domains. We also provide a basis for the study and evaluation of preclinical research practice.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The development process for new drugs is lengthy and complex. It begins in the laboratory, where scientists investigate the causes of diseases and identify potential new treatments. Next, promising interventions undergo preclinical research in cells and in animals (in vivo animal experiments) to test whether the intervention has the expected effect and to support the generalization (extension) of this treatment–effect relationship to patients. Drugs that pass these tests then enter clinical trials, where their safety and efficacy is tested in selected groups of patients under strictly controlled conditions. Finally, the government bodies responsible for drug approval review the results of the clinical trials, and successful drugs receive a marketing license, usually a decade or more after the initial laboratory work. Notably, only 11% of agents that enter clinical testing (investigational drugs) are ultimately licensed.
Why Was This Study Done?
The frequent failure of investigational drugs during clinical translation is potentially harmful to trial participants. Moreover, the costs of these failures are passed onto healthcare systems in the form of higher drug prices. It would be good, therefore, to reduce the attrition rate of investigational drugs. One possible explanation for the dismal success rate of clinical translation is that preclinical research, the key resource for justifying clinical development, is flawed. To address this possibility, several groups of preclinical researchers have issued guidelines intended to improve the design and execution of in vivo animal studies. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), the authors identify the experimental practices that are commonly recommended in these guidelines and organize these recommendations according to the type of threat to validity (internal, construct, or external) that they address. Internal threats to validity are factors that confound reliable inferences about treatment–effect relationships in preclinical research. For example, experimenter expectation may bias outcome assessment. Construct threats to validity arise when researchers mischaracterize the relationship between an experimental system and the clinical disease it is intended to represent. For example, researchers may use an animal model for a complex multifaceted clinical disease that only includes one characteristic of the disease. External threats to validity are unseen factors that frustrate the transfer of treatment–effect relationships from animal models to patients.
What Did the Researchers Do and Find?
The researchers identified 26 preclinical guidelines that met their predefined eligibility criteria. Twelve guidelines addressed preclinical research for neurological and cerebrovascular drug development; other disorders covered by guidelines included cardiac and circulatory disorders, sepsis, pain, and arthritis. Together, the guidelines offered 55 different recommendations for the design and execution of preclinical in vivo animal studies. Nineteen recommendations addressed threats to internal validity. The most commonly included recommendations of this type called for the use of power calculations to ensure that sample sizes are large enough to yield statistically meaningful results, random allocation of animals to treatment groups, and “blinding” of researchers who assess outcomes to treatment allocation. Among the 25 recommendations that addressed threats to construct validity, the most commonly included recommendations called for characterization of the properties of the animal model before experimentation and matching of the animal model to the human manifestation of the disease. Finally, six recommendations addressed threats to external validity. The most commonly included of these recommendations suggested that preclinical research should be replicated in different models of the same disease and in different species, and should also be replicated independently.
What Do These Findings Mean?
This systematic review identifies a range of investigational recommendations that preclinical researchers believe address threats to the validity of preclinical efficacy studies. Many of these recommendations are not widely implemented in preclinical research at present. Whether the failure to implement them explains the frequent discordance between the results on drug safety and efficacy obtained in preclinical research and in clinical trials is currently unclear. These findings provide a starting point, however, for the improvement of existing preclinical research guidelines for specific diseases, and for the development of similar guidelines for other diseases. They also provide an evidence-based platform for the analysis of preclinical evidence and for the study and evaluation of preclinical research practice. These findings should, therefore, be considered by investigators, institutional review bodies, journals, and funding agents when designing, evaluating, and sponsoring translational research.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001489.
The US Food and Drug Administration provides information about drug approval in the US for consumers and for health professionals; its Patient Network provides a step-by-step description of the drug development process that includes information on preclinical research
The UK Medicines and Healthcare Products Regulatory Agency (MHRA) provides information about all aspects of the scientific evaluation and approval of new medicines in the UK; its My Medicine: From Laboratory to Pharmacy Shelf web pages describe the drug development process from scientific discovery, through preclinical and clinical research, to licensing and ongoing monitoring
The STREAM website provides ongoing information about policy, ethics, and practices used in clinical translation of new drugs
The CAMARADES collaboration offers a “supporting framework for groups involved in the systematic review of animal studies” in stroke and other neurological diseases
doi:10.1371/journal.pmed.1001489
PMCID: PMC3720257  PMID: 23935460
12.  Evaluation of a Theory-Informed Implementation Intervention for the Management of Acute Low Back Pain in General Medical Practice: The IMPLEMENT Cluster Randomised Trial 
PLoS ONE  2013;8(6):e65471.
Introduction
This cluster randomised trial evaluated an intervention to decrease x-ray referrals and increase giving advice to stay active for people with acute low back pain (LBP) in general practice.
Methods
General practices were randomised to either access to a guideline for acute LBP (control) or facilitated interactive workshops (intervention). We measured behavioural predictors (e.g. knowledge, attitudes and intentions) and fear avoidance beliefs. We were unable to recruit sufficient patients to measure our original primary outcomes so we introduced other outcomes measured at the general practitioner (GP) level: behavioural simulation (clinical decision about vignettes) and rates of x-ray and CT-scan (medical administrative data). All those not involved in the delivery of the intervention were blinded to allocation.
Results
47 practices (53 GPs) were randomised to the control and 45 practices (59 GPs) to the intervention. The number of GPs available for analysis at 12 months varied by outcome due to missing confounder information; a minimum of 38 GPs were available from the intervention group, and a minimum of 40 GPs from the control group. For the behavioural constructs, although effect estimates were small, the intervention group GPs had greater intention of practising consistent with the guideline for the clinical behaviour of x-ray referral. For behavioural simulation, intervention group GPs were more likely to adhere to guideline recommendations about x-ray (OR 1.76, 95%CI 1.01, 3.05) and more likely to give advice to stay active (OR 4.49, 95%CI 1.90 to 10.60). Imaging referral was not statistically significantly different between groups and the potential importance of effects was unclear; rate ratio 0.87 (95%CI 0.68, 1.10) for x-ray or CT-scan.
Conclusions
The intervention led to small changes in GP intention to practice in a manner that is consistent with an evidence-based guideline, but it did not result in statistically significant changes in actual behaviour.
Trial Registration
Australian New Zealand Clinical Trials Registry ACTRN012606000098538
doi:10.1371/journal.pone.0065471
PMCID: PMC3681882  PMID: 23785427
13.  Sustainability of knowledge translation interventions in healthcare decision-making: protocol for a scoping review 
BMJ Open  2013;3(5):e002970.
Introduction
Knowledge translation (KT also known as research utilisation, translational medicine and implementation science) is a dynamic and iterative process that includes the synthesis, dissemination, exchange and ethically sound application of knowledge to improve health. After the implementation of KT interventions, their impact on relevant outcomes should be monitored. The objectives of this scoping review are to: (1) conduct a systematic search of the literature to identify the impact on healthcare outcomes beyond 1 year, or beyond the termination of funding of the initiative of KT interventions targeting chronic disease management for end-users including patients, clinicians, public health officials, health services managers and policy-makers; (2) identify factors that influence sustainability of effective KT interventions; (3) identify how sustained change from KT interventions should be measured; and (4) develop a framework for assessing sustainability of KT interventions.
Methods and analysis
Comprehensive searches of relevant electronic databases (eg, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), websites of funding agencies and websites of healthcare provider organisations will be conducted to identify relevant material. We will include experimental, quasi-experimental and observational studies providing information on the sustainability of KT interventions targeting chronic disease management in adults and focusing on end-users including patients, clinicians, public health officials, health services managers and policy-makers. Two reviewers will pilot-test the screening criteria and data abstraction form. They will then screen all citations, full articles and abstract data in duplicate independently. The results of the scoping review will be synthesised descriptively and used to develop a framework to assess the sustainability of KT interventions.
Discussion and dissemination
Our results will help inform end-users (ie, patients, clinicians, public health officials, health services managers and policy-makers) regarding the sustainability of KT interventions. Our dissemination plan includes publications, presentations, website posting and a stakeholder meeting.
doi:10.1136/bmjopen-2013-002970
PMCID: PMC3657660  PMID: 23674448
knowledge translation; sustainability; implementation; research utilization; fidelity
14.  Improving quality of care for persons with diabetes: an overview of systematic reviews - what does the evidence tell us? 
Systematic Reviews  2013;2:26.
Background
Ensuring high quality care for persons with diabetes remains a challenge for healthcare systems globally with consistent evidence of suboptimal care and outcomes. There is increasing interest in quality improvement strategies to improve diabetes management as reflected by a growing number of systematic reviews. These reviews are of varying quality and dispersed across many sources. In this paper, we present an overview of systematic reviews evaluating the impact of interventions to improve the quality of diabetes care.
Methods
We searched for systematic reviews evaluating the effectiveness of any intervention intended to improve intermediate patient outcomes and process of care measures for patients with any type of diabetes. Two reviewers independently screened search results, appraised each systematic review using AMSTAR and extracted data from high quality reviews (AMSTAR score ≥ 5). Within reviews, we used vote counting by direction of effect to report the number of studies favouring an intervention for each outcome. We produced summaries of results for each intervention category.
Results
We identified 125 reviews of varying methodological quality and summarised key findings from 50 high quality reviews. We categorised reviews by quality improvement intervention. Eight reviews were broad based (involving a variety of strategies). Other reviews considered: patient education and support (n = 21), telemedicine (n = 10), provider role changes (n = 7), and organisational changes (n = 4). Reviews reported intermediate patient outcomes (e.g. glycaemic control) (n = 49) and process of care outcomes (n = 9). There was evidence of considerable overlap of included studies between reviews.
Conclusions
There is consistent evidence from high quality systematic reviews that patient education and support, provider role changes, and telemedicine are associated with improvements in glycaemic and vascular risk factor control in patients. There is less evidence about the impact of quality improvement interventions on other key process measures such as screening patients for diabetic complications. This paper provides decision makers with a comprehensive overview of evidence from high quality systematic reviews about the effects of quality improvement interventions on improving diabetes care.
doi:10.1186/2046-4053-2-26
PMCID: PMC3667096  PMID: 23647654
Diabetes mellitus; Quality assurance; Health care; Quality improvement; Evidence-based practice; Evidence-based medicine; Overview of systematic reviews; Diabetes management; Intervention strategies
15.  Understanding the Canadian adult CT head rule trial: use of the theoretical domains framework for process evaluation 
Background
The Canadian CT Head Rule was prospectively derived and validated to assist clinicians with diagnostic decision-making regarding the use of computed tomography (CT) in adult patients with minor head injury. A recent intervention trial failed to demonstrate a decrease in the rate of head CTs following implementation of the rule in Canadian emergency departments. Yet, the same intervention, which included a one-hour educational session and reminders at the point of requisition, was successful in reducing cervical spine imaging rates in the same emergency departments. The reason for the varied effect of the intervention across these two behaviours is unclear. There is an increasing appreciation for the use of theory to conduct process evaluations to better understand how strategies are linked with outcomes in implementation trials. The Theoretical Domains Framework (TDF) has been used to explore health professional behaviour and to design behaviour change interventions but, to date, has not been used to guide a theory-based process evaluation. In this proof of concept study, we explored whether the TDF could be used to guide a retrospective process evaluation to better understand emergency physicians’ responses to the interventions employed in the Canadian CT Head Rule trial.
Methods
A semi-structured interview guide, based on the 12 domains from the TDF, was used to conduct telephone interviews with project leads and physician participants from the intervention sites in the Canadian CT Head Rule trial. Two reviewers independently coded the anonymised interview transcripts using the TDF as a coding framework. Relevant domains were identified by: the presence of conflicting beliefs within a domain; the frequency of beliefs; and the likely strength of the impact of a belief on the behaviour.
Results
Eight physicians from four of the intervention sites in the Canadian CT Head Rule trial participated in the interviews. Barriers likely to assist with understanding physicians’ responses to the intervention in the trial were identified in six of the theoretical domains: beliefs about consequences; beliefs about capabilities; behavioural regulation; memory, attention and decision processes; environmental context and resources; and social influences. Despite knowledge that the Canadian CT Head Rule was highly sensitive and reliable for identifying clinically important brain injuries and strong beliefs about the benefits for using the rule, a number of barriers were identified that may have prevented physicians from consistently applying the rule.
Conclusion
This proof of concept study demonstrates the use of the TDF as a guiding framework to design a retrospective theory-based process evaluation. There is a need for further development and testing of methods for using the TDF to guide theory-based process evaluations running alongside behaviour change intervention trials.
doi:10.1186/1748-5908-8-25
PMCID: PMC3585785  PMID: 23433082
16.  Improving physician hand hygiene compliance using behavioural theories: a study protocol 
Background
Healthcare-associated infections affect 10% of patients in Canadian acute-care hospitals and are significant and preventable causes of morbidity and mortality among hospitalized patients. Hand hygiene is among the simplest and most effective preventive measures to reduce these infections. However, compliance with hand hygiene among healthcare workers, specifically among physicians, is consistently suboptimal. We aim to first identify the barriers and enablers to physician hand hygiene compliance, and then to develop and pilot a theory-based knowledge translation intervention to increase physicians’ compliance with best hand hygiene practice.
Design
The study consists of three phases. In Phase 1, we will identify barriers and enablers to hand hygiene compliance by physicians. This will include: key informant interviews with physicians and residents using a structured interview guide, informed by the Theoretical Domains Framework; nonparticipant observation of physician/resident hand hygiene audit sessions; and focus groups with hand hygiene experts. In Phase 2, we will conduct intervention mapping to develop a theory-based knowledge translation intervention to improve physician hand hygiene compliance. Finally, in Phase 3, we will pilot the knowledge translation intervention in four patient care units.
Discussion
In this study, we will use a behavioural theory approach to obtain a better understanding of the barriers and enablers to physician hand hygiene compliance. This will provide a comprehensive framework on which to develop knowledge translation interventions that may be more successful in improving hand hygiene practice. Upon completion of this study, we will refine the piloted knowledge translation intervention so it can be tested in a multi-site cluster randomized controlled trial.
doi:10.1186/1748-5908-8-16
PMCID: PMC3571966  PMID: 23379466
17.  Explaining clinical behaviors using multiple theoretical models 
Background
In the field of implementation research, there is an increased interest in use of theory when designing implementation research studies involving behavior change. In 2003, we initiated a series of five studies to establish a scientific rationale for interventions to translate research findings into clinical practice by exploring the performance of a number of different, commonly used, overlapping behavioral theories and models. We reflect on the strengths and weaknesses of the methods, the performance of the theories, and consider where these methods sit alongside the range of methods for studying healthcare professional behavior change.
Methods
These were five studies of the theory-based cognitions and clinical behaviors (taking dental radiographs, performing dental restorations, placing fissure sealants, managing upper respiratory tract infections without prescribing antibiotics, managing low back pain without ordering lumbar spine x-rays) of random samples of primary care dentists and physicians. Measures were derived for the explanatory theoretical constructs in the Theory of Planned Behavior (TPB), Social Cognitive Theory (SCT), and Illness Representations specified by the Common Sense Self Regulation Model (CSSRM). We constructed self-report measures of two constructs from Learning Theory (LT), a measure of Implementation Intentions (II), and the Precaution Adoption Process. We collected data on theory-based cognitions (explanatory measures) and two interim outcome measures (stated behavioral intention and simulated behavior) by postal questionnaire survey during the 12-month period to which objective measures of behavior (collected from routine administrative sources) were related. Planned analyses explored the predictive value of theories in explaining variance in intention, behavioral simulation and behavior.
Results
Response rates across the five surveys ranged from 21% to 48%; we achieved the target sample size for three of the five surveys. For the predictor variables, the mean construct scores were above the mid-point on the scale with median values across the five behaviors generally being above four out of seven and the range being from 1.53 to 6.01. Across all of the theories, the highest proportion of the variance explained was always for intention and the lowest was for behavior. The Knowledge-Attitudes-Behavior Model performed poorly across all behaviors and dependent variables; CSSRM also performed poorly. For TPB, SCT, II, and LT across the five behaviors, we predicted median R2 of 25% to 42.6% for intention, 6.2% to 16% for behavioral simulation, and 2.4% to 6.3% for behavior.
Conclusions
We operationalized multiple theories measuring across five behaviors. Continuing challenges that emerge from our work are: better specification of behaviors, better operationalization of theories; how best to appropriately extend the range of theories; further assessment of the value of theories in different settings and groups; exploring the implications of these methods for the management of chronic diseases; and moving to experimental designs to allow an understanding of behavior change.
doi:10.1186/1748-5908-7-99
PMCID: PMC3500222  PMID: 23075284
18.  A cross-country comparison of intensive care physicians’ beliefs about their transfusion behaviour: A qualitative study using the theoretical domains framework 
Background
Evidence of variations in red blood cell transfusion practices have been reported in a wide range of clinical settings. Parallel studies in Canada and the United Kingdom were designed to explore transfusion behaviour in intensive care physicians. The aim of this paper is three-fold: first, to explore beliefs that influence Canadian intensive care physicians’ transfusion behaviour; second, to systematically select relevant theories and models using the Theoretical Domains Framework (TDF) to inform a future predictive study; and third, to compare its results with the UK study.
Methods
Ten intensive care unit (ICU) physicians throughout Canada were interviewed. Physicians’ responses were coded into theoretical domains, and specific beliefs were generated for each response. Theoretical domains relevant to behaviour change were identified, and specific constructs from the relevant domains were used to select psychological theories. The results from Canada and the United Kingdom were compared.
Results
Seven theoretical domains populated by 31 specific beliefs were identified as relevant to the target behaviour. The domains Beliefs about capabilities (confident to not transfuse if patients’ clinical condition is stable), Beliefs about consequences (positive beliefs of reducing infection and saving resources and negative beliefs about risking patients’ clinical outcome and potentially more work), Social influences (transfusion decision is influenced by team members and patients’ relatives), and Behavioural regulation (wide range of approaches to encourage restrictive transfusion) that were identified in the UK study were also relevant in the Canadian context. Three additional domains, Knowledge (it requires more evidence to support restrictive transfusion), Social/professional role and identity (conflicting beliefs about not adhering to guidelines, referring to evidence, believing restrictive transfusion as professional standard, and believing that guideline is important for other professionals), and Motivation and goals (opposing beliefs about the importance of restrictive transfusion and compatibility with other goals), were also identified in this study. Similar to the UK study, the Theory of Planned Behaviour, Social Cognitive Theory, Operant Learning Theory, Action Planning, and Knowledge-Attitude-Behaviour model were identified as potentially relevant theories and models for further study. Personal project analysis was added to the Canadian study to explore the Motivation and goals domain in further detail.
Conclusions
A wide range of beliefs was identified by the Canadian ICU physicians as likely to influence their transfusion behaviour. We were able to demonstrate similar though not identical results in a cross-country comparison. Designing targeted behaviour-change interventions based on unique beliefs identified by physicians from two countries are more likely to encourage restrictive transfusion in ICU physicians in respective countries. This needs to be tested in future prospective clinical trials.
doi:10.1186/1748-5908-7-93
PMCID: PMC3527303  PMID: 22999460
19.  Identifying factors likely to influence compliance with diagnostic imaging guideline recommendations for spine disorders among chiropractors in North America: a focus group study using the Theoretical Domains Framework 
Background
The Theoretical Domains Framework (TDF) was developed to investigate determinants of specific clinical behaviors and inform the design of interventions to change professional behavior. This framework was used to explore the beliefs of chiropractors in an American Provider Network and two Canadian provinces about their adherence to evidence-based recommendations for spine radiography for uncomplicated back pain. The primary objective of the study was to identify chiropractors’ beliefs about managing uncomplicated back pain without x-rays and to explore barriers and facilitators to implementing evidence-based recommendations on lumbar spine x-rays. A secondary objective was to compare chiropractors in the United States and Canada on their beliefs regarding the use of spine x-rays.
Methods
Six focus groups exploring beliefs about managing back pain without x-rays were conducted with a purposive sample. The interview guide was based upon the TDF. Focus groups were digitally recorded, transcribed verbatim, and analyzed by two independent assessors using thematic content analysis based on the TDF.
Results
Five domains were identified as likely relevant. Key beliefs within these domains included the following: conflicting comments about the potential consequences of not ordering x-rays (risk of missing a pathology, avoiding adverse treatment effects, risks of litigation, determining the treatment plan, and using x-ray-driven techniques contrasted with perceived benefits of minimizing patient radiation exposure and reducing costs; beliefs about consequences); beliefs regarding professional autonomy, professional credibility, lack of standardization, and agreement with guidelines widely varied ( social/professional role & identity); the influence of formal training, colleagues, and patients also appeared to be important factors ( social influences); conflicting comments regarding levels of confidence and comfort in managing patients without x-rays ( belief about capabilities); and guideline awareness and agreements ( knowledge).
Conclusions
Chiropractors’ use of diagnostic imaging appears to be influenced by a number of factors. Five key domains may be important considering the presence of conflicting beliefs, evidence of strong beliefs likely to impact the behavior of interest, and high frequency of beliefs. The results will inform the development of a theory-based survey to help identify potential targets for behavioral-change strategies.
doi:10.1186/1748-5908-7-82
PMCID: PMC3444898  PMID: 22938135
Theoretical domains framework; Focus groups; Content analysis; Social/professional role and identity; Social influence; Chiropractors; Radiography; X-ray guidelines; Back pain
20.  Do incentives, reminders or reduced burden improve healthcare professional response rates in postal questionnaires? two randomised controlled trials 
Background
Healthcare professional response rates to postal questionnaires are declining and this may threaten the validity and generalisability of their findings. Methods to improve response rates do incur costs (resources) and increase the cost of research projects. The aim of these randomised controlled trials (RCTs) was to assess whether 1) incentives, 2) type of reminder and/or 3) reduced response burden improve response rates; and to assess the cost implications of such additional effective interventions.
Methods
Two RCTs were conducted. In RCT A general dental practitioners (dentists) in Scotland were randomised to receive either an incentive; an abridged questionnaire or a full length questionnaire. In RCT B non-responders to a postal questionnaire sent to general medical practitioners (GPs) in the UK were firstly randomised to receive a second full length questionnaire as a reminder or a postcard reminder. Continued non-responders from RCT B were then randomised within their first randomisation to receive a third full length or an abridged questionnaire reminder. The cost-effectiveness of interventions that effectively increased response rates was assessed as a secondary outcome.
Results
There was no evidence that an incentive (52% versus 43%, Risk Difference (RD) -8.8 (95%CI −22.5, 4.8); or abridged questionnaire (46% versus 43%, RD −2.9 (95%CI −16.5, 10.7); statistically significantly improved dentist response rates compared to a full length questionnaire in RCT A. In RCT B there was no evidence that a full questionnaire reminder statistically significantly improved response rates compared to a postcard reminder (10.4% versus 7.3%, RD 3 (95%CI −0.1, 6.8). At a second reminder stage, GPs sent the abridged questionnaire responded more often (14.8% versus 7.2%, RD −7.7 (95%CI −12.8, -2.6). GPs who received a postcard reminder followed by an abridged questionnaire were most likely to respond (19.8% versus 6.3%, RD 8.1%, and 9.1% for full/postcard/full, three full or full/full/abridged questionnaire respectively). An abridged questionnaire containing fewer questions following a postcard reminder was the only cost-effective strategy for increasing the response rate (£15.99 per response).
Conclusions
When expecting or facing a low response rate to postal questionnaires, researchers should carefully identify the most efficient way to boost their response rate. In these studies, an abridged questionnaire containing fewer questions following a postcard reminder was the only cost-effective strategy. An increase in response rates may be explained by a combination of the number and type of contacts. Increasing the sampling frame may be more cost-effective than interventions to prompt non-responders. However, this may not strengthen the validity and generalisability of the survey findings and affect the representativeness of the sample.
doi:10.1186/1472-6963-12-250
PMCID: PMC3508866  PMID: 22891875
21.  Correction: Diabetes Care Provision in UK Primary Care Practices 
PLoS ONE  2012;7(8):10.1371/annotation/1957ad3b-e192-4faa-bf4c-5dce22c5560e.
doi:10.1371/annotation/1957ad3b-e192-4faa-bf4c-5dce22c5560e
PMCID: PMC3414526
22.  Allocation techniques for balance at baseline in cluster randomized trials: a methodological review 
Trials  2012;13:120.
Reviews have repeatedly noted important methodological issues in the conduct and reporting of cluster randomized controlled trials (C-RCTs). These reviews usually focus on whether the intracluster correlation was explicitly considered in the design and analysis of the C-RCT. However, another important aspect requiring special attention in C-RCTs is the risk for imbalance of covariates at baseline. Imbalance of important covariates at baseline decreases statistical power and precision of the results. Imbalance also reduces face validity and credibility of the trial results. The risk of imbalance is elevated in C-RCTs compared to trials randomizing individuals because of the difficulties in recruiting clusters and the nested nature of correlated patient-level data. A variety of restricted randomization methods have been proposed as way to minimize risk of imbalance. However, there is little guidance regarding how to best restrict randomization for any given C-RCT. The advantages and limitations of different allocation techniques, including stratification, matching, minimization, and covariate-constrained randomization are reviewed as they pertain to C-RCTs to provide investigators with guidance for choosing the best allocation technique for their trial.
doi:10.1186/1745-6215-13-120
PMCID: PMC3503622  PMID: 22853820
Cluster-randomized trials; Balanced allocation; Restricted randomization
23.  Diabetes Care Provision in UK Primary Care Practices 
PLoS ONE  2012;7(7):e41562.
Background
Although most people with Type 2 diabetes receive their diabetes care in primary care, only a limited amount is known about the quality of diabetes care in this setting. We investigated the provision and receipt of diabetes care delivered in UK primary care.
Methods
Postal surveys with all healthcare professionals and a random sample of 100 patients with Type 2 diabetes from 99 UK primary care practices.
Results
326/361 (90.3%) doctors, 163/186 (87.6%) nurses and 3591 patients (41.8%) returned a questionnaire. Clinicians reported giving advice about lifestyle behaviours (e.g. 88% would routinely advise about calorie restriction; 99.6% about increasing exercise) more often than patients reported having received it (43% and 42%) and correlations between clinician and patient report were low. Patients’ reported levels of confidence about managing their diabetes were moderately high; a median (range) of 21% (3% to 39%) of patients reporting being not confident about various areas of diabetes self-management.
Conclusions
Primary care practices have organisational structures in place and are, as judged by routine quality indicators, delivering high quality care. There remain evidence-practice gaps in the care provided and in the self confidence that patients have for key aspects of self management and further research is needed to address these issues. Future research should use robust designs and appropriately designed studies to investigate how best to improve this situation.
doi:10.1371/journal.pone.0041562
PMCID: PMC3408463  PMID: 22859997
24.  What is the role and authority of gatekeepers in cluster randomized trials in health research? 
Trials  2012;13:116.
This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the CRT is to be set on a firm ethical foundation. This paper addresses the sixth of the questions posed, namely, what is the role and authority of gatekeepers in CRTs in health research? ‘Gatekeepers’ are individuals or bodies that represent the interests of cluster members, clusters, or organizations. The need for gatekeepers arose in response to the difficulties in obtaining informed consent because of cluster randomization, cluster-level interventions, and cluster size. In this paper, we call for a more restrictive understanding of the role and authority of gatekeepers.
Previous papers in this series have provided solutions to the challenges posed by informed consent in CRTs without the need to invoke gatekeepers. We considered that consent to randomization is not required when cluster members are approached for consent at the earliest opportunity and before any study interventions or data-collection procedures have started. Further, when cluster-level interventions or cluster size means that obtaining informed consent is not possible, a waiver of consent may be appropriate. In this paper, we suggest that the role of gatekeepers in protecting individual interests in CRTs should be limited. Generally, gatekeepers do not have the authority to provide proxy consent for cluster members. When a municipality or other community has a legitimate political authority that is empowered to make such decisions, cluster permission may be appropriate; however, gatekeepers may usefully protect cluster interests in other ways. Cluster consultation may ensure that the CRT addresses local health needs, and is conducted in accord with local values and customs. Gatekeepers may also play an important role in protecting the interests of organizations, such as hospitals, nursing homes, general practices, and schools. In these settings, permission to access the organization relies on resource implications and adherence to institutional policies.
doi:10.1186/1745-6215-13-116
PMCID: PMC3443001  PMID: 22834691
25.  Developing clinical practice guidelines: types of evidence and outcomes; values and economics, synthesis, grading, and presentation and deriving recommendations 
Clinical practice guidelines are one of the foundations of efforts to improve healthcare. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearinghouses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this second paper, we discuss issues of identifying and synthesizing evidence: deciding what type of evidence and outcomes to include in guidelines; integrating values into a guideline; incorporating economic considerations; synthesis, grading, and presentation of evidence; and moving from evidence to recommendations.
doi:10.1186/1748-5908-7-61
PMCID: PMC3436711  PMID: 22762158

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