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Introduction We Can Quit” (WCQ) is community-based stop-smoking program delivered by trained community facilitators, based on the socio-ecological framework and developed using a Community-based Participatory Research approach, targeting women living in socioeconomically disadvantaged (SED) areas of Ireland. Aims and Methods The We Can Quit2 (WCQ2) pilot trial assessed the feasibility of WCQ. A pragmatic cluster randomized controlled trial with a process evaluation WCQ2, was conducted in four matched pairs of SED districts (8–10 000 women per district). Districts were independently randomized to WCQ (group support + nicotine replacement therapy), or to individual support delivered by health professionals. Participants were adult women smokers interested in quitting, who were living or working in trial districts. Recruitment of districts and 194 women in four waves (49 women per wave); retention at 12 weeks and 6 months; fidelity to intervention delivery and acceptability of trial-related processes were assessed. Validated smoking abstinence at 12-week and 6-month post-intervention was recorded, missing data assumed as continued smoking. Results Eight districts were recruited. 125/188 (66.5%) eligible women consented. The 49 women target was reached in wave4. Retention at 12 weeks was (Intervention [I]: 55.4%; Control [C]: 51.7%), at 6 months (I: 47.7%; C: 46.7%). Smoking abstinence at 12 weeks was (I: 23.1%, [95% CI: 14.5 to 34.7]; C: 13%, [95% CI: 6.9 to 24.1]). 83.8% of session activities were delivered. Trial-related processes were acceptable to facilitators. Low literacy was highlighted as a barrier for participants’ acceptability. Conclusions WCQ was feasible to deliver by trained facilitators and indicated a positive direction in abstinence rates. Low literacy will need to be addressed in a future trial design. Implications This pilot trial showed that a stop-smoking intervention tailored to a group of women smokers living in SED areas which was delivered by trained local women within their local communities was feasible. Furthermore, although not formally compared, more WCQ women were abstinent from smoking at the end of treatment. The results are relevant to enhance the design of a fully powered effectiveness trial, and provide important evidence on the barriers to deliver a tailored smoking cessation service to SED women smokers in Ireland.

Background and Objectives A randomized controlled trial (RCT) may be intended either to support real-world decisions on choice between alternative interventions or to help researchers understand mechanisms of action of an intervention. PRECIS-2 is widely used to help investigators match detailed design elements to their main intention for that RCT. PRECIS-2 is increasingly being used retrospectively for assessing RCTs within reviews. In this commentary, we counter arguments that RCTs with a placebo control group, masking/blinding of participants or providers, or conducted in a single center should be retrospectively assessed as completely explanatory, overriding a detailed PRECIS-2 assessment. We also counter arguments that a trial cannot be assessed using only the main peer-reviewed trial report. Study Design and Setting This is a commentary on the use of PRECIS-2 for systematic reviews. Results Although placebos are seldom openly prescribed in real-world care, knowing that an intervention achieves its impact via the placebo effect might change some clinical and policy decisions, which means that this feature does not always preclude decision-making use and so should not override a full PRECIS-2 assessment. A domain describing the comparator should be added to PRECIS-2. Conduct of an RCT in only a single centre should also not override PRECIS-2 as the decision support value of a single-centre RCT could be high for decision makers in that centre and others like it. Many journals require that submitted RCT reports meet CONSORT reporting guidelines, which standardizes the available information for all RCTs in systematic reviews; whereas information from registration and protocol documents is unstandardized and undermines comparison between RCTs and across reviews. Published RCT reports are thus more suitable for retrospective PRECIS-2 assessments, but PRECIS-2 domains with missing information should be scored as blank. Wider use of the CONSORT extension specific to pragmatic trials may reduce domains with missing data. Conclusions PRECIS-2 can be used for retrospective assessments of trials in systematic reviews. The PRECIS-2 instrument should be expanded by including a domain describing the control group(s). Published RCT reports are suitable for retrospective PRECIS-2 assessments.

Background “We Can Quit2” (WCQ2) was a pilot cluster randomised controlled trial with an embedded process evaluation assessing the feasibility and acceptability of ‘We Can Quit’ (WCQ, a peer-delivered community-based stop-smoking programme for women in disadvantaged communities. The control group comprised ‘enhanced usual care’ offered by the Irish Health Service Executive (HSE). The PRagmatic Explanatory Continuum Indicator Summary (PRECIS-2) is a tool to assess whether a trial design is more explanatory (working under ideal conditions) or pragmatic (working under ‘real-world’ conditions). The aim of this paper was to retrospectively evaluate the WCQ2 pilot trial using PRECIS-2 to inform the decision-making process on progression to a future definitive trial (DT). Methods The WCQ2 trial protocol and HSE standard stop-smoking service were described across the nine PRECIS-2 domains: eligibility, recruitment, setting, organisation, flexibility-delivery, flexibility-adherence, follow-up and primary outcome. Team members scored the domains as pragmatic or explanatory for each arm in a half-day workshop. Results Seven team members (practitioners and researchers) assessed the overall trial design as more explanatory than pragmatic. Important differences emerged between the two arms. WCQ targeted adult women from disadvantaged communities whereas HSE run a limited enhanced service for all quitters. Trial recruitment was challenging, intense efforts were needed as the trial proceeded. WCQ was delivered in a non-clinical community setting, HSE services in a clinical setting. WCQ organisation was co-designed with community partners and comprises peer-to-peer group support delivered by trained lay community facilitators, whereas HSE one-to-one support is delivered by Smoking Cessation Officers with a clinical background. Only WCQ allowed flexibility in delivery and adherence. Follow-up was more intensive in WCQ. Greater efforts to improve participant retention will be required in a future DT. Conclusions PRECIS-2 allowed the reflection of practitioners and researchers on similarities and differences between intervention and control arms. Results will inform the decision on progression to an effectiveness DT, which will require more a pragmatic and less explanatory design. This novel use of PRECIS-2 to retrospectively evaluate a complex community-based pilot trial in advance of a full DT will also support learning for those undertaking hybrid trials of implementation and effectiveness. Trial registration This trial is registered with the ISRCTN registry (No. 74721694).

Background Smoking poses a serious risk of early preventable death and disease especially for women living with socio-economic disadvantage (SED). A smoking cessation programme, ‘We Can Quit’, was developed in Ireland tailored to SED women. This includes group-based support delivered by trained lay local community facilitators (CFs) and free nicotine replacement therapy (NRT). The intervention was pilot tested in a cluster randomised controlled trial, ‘We Can Quit 2’. This paper reports on the WCQ2 process evaluation which assessed feasibility and acceptability of the programme and trial processes. Methods Embedded qualitative design using the UK Medical Research Council’s process evaluation framework. Semi-structured interviews with trial participants (N = 21) and CFs (N = 8). Thematic analysis was utilised. Results Peer-modelling, a non-judgemental environment, CFs facilitation of group support were viewed as acceptable programme related factors. Some participants expressed concerns about NRT side effects. Provision of free NRT was welcomed and accepted by participants, although structural barriers made access challenging. Pharmacists took on a role that became larger than originally envisaged – and the majority provided additional support to women in their quit attempts between group meetings which augmented and supplemented the intervention sessions provided by the CFs. Participants reported good acceptance of repeated measures for data collection, but mixed acceptability of provision of saliva samples. Low literacy affected the feasibility of some women to fully engage with programme and trial-related materials. This was despite efforts made by intervention developers and the trial team to make materials (e.g., participant intervention booklet; consent forms and participant information leaflets) accessible while also meeting requirements under 2018 European General Data Protection Regulation legislation. Hypothetical scenarios of direct (e.g., researcher present during programme delivery) and indirect (e.g., audio recordings of programme sessions) observational fidelity assessments for a future definitive trial (DT) were acceptable. Conclusions Intervention and trial-related processes were generally feasible and acceptable to participants and CFs. Any future DT will need to take further steps to mitigate structural barriers to accessing free NRT; and the established problem of low literacy and low educational attainment in SED areas, while continuing to comply within the contemporary legislative research environment. Trial registration WCQ2 pilot trial (ISRCTN74721694).

Background First articulated by Schwartz and Lellouch (1967), randomized controlled trials (RCTs) can be conceptualized along a continuum from more explanatory to more pragmatic. The purpose and intent of the former is to test interventions under ideal contexts, and the purpose and intent of the latter is to test interventions in real-world contexts. The PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) is a validated tool that helps researchers make decisions about the elements of the trial to match the overall purpose and intent of the trial along the continuum. The PRECIS-2 tool has guided the design of hundreds of RCTs. However, a few aspects of the tool would benefit from greater clarity, including its application to provider-focused implementation trials rather than patient-focused intervention trials. Main text We describe the newly developed PRECIS-2-Provider Strategies (PRECIS-2-PS) tool, an extension of the PRECIS-2 tool, which has been adapted for trials testing provider-focused strategies. We elaborate on nine domains that can make a provider-focused trial more explanatory or more pragmatic, including eligibility, recruitment, setting, implementation resources, flexibility of provider strategies, flexibility of intervention, data collection, primary outcome, and primary analysis. We detail the complementary roles that researchers and stakeholders play in the trial design phase, with implications for generalizability of trial results to the contexts in which they are intended to be applied. Conclusions The PRECIS-2-PS tool is designed to help research and practice teams plan for provider-focused trials that reflect the overall intent and purpose of the trial. The tool has potential to help advance the science of provider-focused strategies across a range of trials, with the ultimate goal of facilitating the adoption, integration, and sustainability of provider-focused strategies outside the context of trials.

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Objective To compare two approaches for trial teams to apply PRECIS-2 to pragmatic trials: independent scoring and scoring following a group discussion. Study Design and Setting We recruited multidisciplinary teams who were conducting or had conducted trials in primary care in collaboration with the Pragmatic Clinical Trials Unit, Queen Mary University of London. Each team carried out two rounds of scoring on the 9 PRECIS-2 domains: first independently using an online version of PRECIS-2 and secondly following a discussion. Results Seven teams took part in the study. Prior to the discussion within-team agreement in scores was generally poor and not all raters were able to score all domains; agreement improved following the discussion. The PRECIS-2 wheels suggested that the trials were pragmatic, though some domains were more pragmatic than others. Conclusion PRECIS-2 can facilitate information exchange within trial teams. To apply PRECIS-2 successfully we recommend a discussion between those with detailed understanding of: what usual care is for the intervention, the trial’s design including operational and technical aspects, and the PRECIS-2 domains. For some cluster randomised trials greater insight may be gained by plotting two PRECIS-2 wheels, one at the individual participant level and one at the cluster level.

Background Tobacco use is the leading cause of preventable death in Ireland with almost 6000 smokers dying each year from smoking-related diseases. The ‘We Can Quit2’ (WCQ2) study is a pilot pragmatic two-arm, parallel-group, cluster randomised trial that aims to explore the feasibility and acceptability of trial processes including recruitment and to estimate parameters to inform sample size estimates needed for an effectiveness trial. This future trial will assess the effectiveness of a community-based smoking cessation intervention for women living in disadvantaged areas on short- and medium-term cessation rates. Methods/design Four matched pairs of districts (eight clusters) selected by area level of deprivation, geographical proximity, and eligibility for free medical services will be randomised to receive either WCQ (behavioural support + access to Nicotine Replacement Therapy (NRT)) delivered over 12 weeks by trained Community Facilitators (CFs) or to a form of usual care, a one-to-one smoking cessation service delivered by Smoking Cessation Officers from Ireland’s national health service, the Health Service Executive (HSE). Within each cluster, 24–25 women will be recruited (97 per arm; 194 in total) in 4 phases with consent obtained prior to cluster randomisation. The outcome measures will assess feasibility and acceptability of trial processes, including randomisation. Outcome data for a future definitive intervention (biochemically validated smoking abstinence) will be collected at end of programme (12 weeks) and at 6 months. WCQ2 has an embedded process evaluation using both qualitative and quantitative methods. This will be conducted (semi-structured client and CF interviews, intervention delivery checklist, and diary) to explore acceptability of trial processes, intervention fidelity, trial context, and implementation. Trial processes will be assessed against domains of the PRECIS-2 wheel to inform a future definitive trial design. Discussion Data from this pilot trial will inform the design and sample size for a full cluster randomised trial to determine the effectiveness of an intervention tailored to disadvantaged women in improving smoking cessation rates. It will provide transferable learning on the systems and implementation strategies needed to support effective design of future pragmatic community-based trials which address health promotion interventions for women in disadvantaged communities. Trial registration Concurrent to publication. Controlled trials ISRCTN74721694.

BackgroundBuilding capacity in research funding organizations to support the conduct of pragmatic clinical trials is an essential component of advancing biomedical and public health research. To date, efforts to increase the ability to design and carry out pragmatic trials have largely focused on training researchers. To complement these efforts, we developed an interactive workshop tailored to meet the roles and responsibilities of program scientists at the National Cancer Institute—the leading cancer research funding agency in the USA. The objectives of the workshop were to improve the understanding of pragmatic trials and enhance the capacity to distinguish between elements that make a trial more pragmatic or more explanatory among key programmatic staff. To our knowledge, this is the first reported description of such a workshop.Main bodyThe workshop was developed to meet the needs of program scientists as researchers and stewards of research funds, which often includes promoting scientific initiatives, advising prospective applicants, collaborating with grantees, and creating training programs. The workshop consisted of presentations from researchers with expertise in the design and interpretation of trials across the explanatory-pragmatic continuum. Presentations were followed by interactive, small-group exercises to solidify participants’ understanding of the purpose and conduct of these trials, which were tailored to attendees’ areas of expertise across the cancer control continuum and designed to reflect their scope of work as program scientists at NCI. A total of 29 program scientists from the Division of Cancer Control and Population Sciences and the Division of Cancer Prevention participated; 19 completed a post-workshop evaluation. Attendees were very enthusiastic about the workshop: they reported improved knowledge, significant relevance of the material to their work, and increased interest in pragmatic trials across the cancer control continuum.ConclusionTraining program scientists at major biomedical research agencies who are responsible for developing funding opportunities and advising grantees is essential for increasing the quality and quantity of pragmatic trials. Together with workshops for other target audiences (e.g., academic researchers), this approach has the potential to shape the future of pragmatic trials and continue to generate more and better actionable evidence to guide decisions that are of critical importance to health care practitioners, policymakers, and patients.

Background Pragmatic trials have been suggested as a way to improve the relevance of clinical trial results to practice. PRECIS-2 is a trial design tool which considers how pragmatic a trial is across a number of domains. It is not known whether a pragmatic approach to all PRECIS-2 domains leads to results being more relevant to primary care. The aim of this study was to investigate the views of people with influence on primary care practice towards the design of randomised trials, pragmatic approaches to trial design, and the PRECIS-2 domains. Methods We carried out semi-structured interviews with people who influence practice in primary care in the UK. A thematic analysis was undertaken using the framework approach. Results We conducted individual or small group interviews involving 17 individuals in total. We found a wide range of views. These highlighted that an exclusively pragmatic approach may not always make the results of trials more applicable to primary care. For example, it may be better to have less flexibility in the way interventions are delivered in randomised trials than in practice. In addition, an appropriate balance needs to be struck when thinking about levels of resourcing and the intensity of steps needed to improve adherence in a trial. Across other aspects of a trial’s design, for example the population and trial setting, a pragmatic approach was viewed as more appropriate. Conclusions To maximize the relevance of research directed at primary care, trials should be conducted with the same populations and settings that are found in primary care. Across other aspects of trials it is not always necessary to match the conditions found in practice.

Introduction The ‘We Can Quit2’ (WCQ2) study is a pilot pragmatic two-arm, parallel-group, cluster randomised trial, that aims to explore the feasibility and acceptability of trial processes including recruitment and to estimate parameters to inform sample size estimates needed for an effectiveness trial of a community-based smoking cessation intervention for women living in disadvantaged areas on short and medium term cessation rates. Methods Eight districts (clusters of four matched pairs) in Ireland selected by area level deprivation, geographical proximity and eligibility for free medical services, will be randomised to receive either WCQ (behavioural support+- access to Nicotine Replacement Therapy (NRT) delivered over 12 weeks by trained community facilitators) or usual care, a one-to-one smoking cessation service delivered by Smoking Cessation Officers. 25 women will be recruited per cluster (97 per arm; 194 in total) in four phases with consent obtained prior to cluster randomisation. Results The outcome measures will assess feasibility and acceptability of trial processes, including randomisation. Biochemically-validated smoking abstinence data for a future definitive intervention will be collected at end of programme (12 weeks), and at six months. WCQ2 incorporates a comprehensive process evaluation. Processes will be assessed against domains of the PRECIS-2 wheel to inform future a definitive trial design. Conclusions Data from this pilot trial will inform the design and sample size for a full cluster RCT. It will provide transferable learning on the systems and implementation strategies needed to support effective design, implementation and evaluation of tailored intervention trials to address behaviour change in disadvantaged communities.

Background Due to the worldwide rise in cancer incidence, and therefore the rise in the need for antineoplastic chemotherapy, it is important for both healthcare professionals and patients alike that the side effects of chemotherapy, such as chemotherapy-induced nausea and vomiting (CINV), are treated and prevented. Auriculotherapy is a type of acupuncture and may be a low-cost and safe antiemetic measure to control the side effects of chemotherapy. The goal of this systematic review is to synthesize the available evidence in the literature regarding the auriculotherapy effects to treat CINV in people with cancer. Methods The review will only include randomized controlled trials (RCTs) that compare the clinical effects of the auriculotherapy intervention (used alone or as an add-on), with sham auriculotherapy, routine treatment with antiemetic drugs, or other non-pharmacological interventions in patients with cancer with CINV who are undergoing chemotherapy. The outcomes to be evaluated are nausea and vomiting: in acute, delayed, or anticipated stages, when induced by chemotherapy. A comprehensive search for studies will be carried out in these databases: MEDLINE via PubMed, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, ICTRP, LILACS, CUMED, IBECS, BVS MTCI Americas, Web of Science, Scopus, PEDro, CNKI, and CBMdisc up until December 31, 2018. Only articles in English, Portuguese, and Spanish will be selected. Two independent reviewers will evaluate full texts, extract data, and assess the risk of bias of eligible articles. The quality of evidence will be assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). A meta-analysis will be undertaken to assess the interventions and outcomes’ homogeneity, assessing statistical heterogeneity using the Cochran’s Q test and quantified using Higgins’ inconsistency index. If there is insufficient data for a meta-analysis, a narrative synthesis will be presented. This protocol has been prepared according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. Discussion The results of this systematic review will summarize the strength of evidence for the use of auriculotherapy in the control of CINV of patients with cancer and will be used to identify evidence gaps. Systematic review registration PROSPERO CRD42018117513 Electronic supplementary material The online version of this article (10.1186/s13643-019-1124-3) contains supplementary material, which is available to authorized users.

Background. Evidence-based clinical guidelines could support shared decision-making and help patients to participate actively in their care. However, it is not well known how patients view guidelines as a source of health information. This qualitative study aimed to assess what patients know about guidelines, and what they think of their presentation formats. Research question. What is the role of guidelines as health information for patients and how could the implementation of evidence-based information for patients be improved? Methods. A qualitative study with focus groups that were built around a semi-structured topic guide. Focus groups were audiotaped and transcribed and analysed using a phenomenographic approach. Results. Five focus groups were carried out in 2012 with a total of 23 participants. Patients searched for health information from the Internet or consulted health professionals or their personal networks. The concepts of guidelines included instructions or standards for health professionals, information given by a health professional to the patient, and material to protect and promote the interests of patients. Some patients did not have a concept for guidelines. Patients felt that health information was abundant and its quality sometimes difficult to assess. They respected conciseness, clarity, clear structure, and specialists or well-known organizations as authors of health information. Patients would like health professionals to deliver and clarify written materials to them or point out to them the relevant Internet sites. Conclusions. The concept of guidelines was not well known among our interviewees; however, they expressed an interest in having more communication on health information, both written information and clarifications with their health professionals.

This work was supported by the Chief Scientist Office (CSO) of Scotland grant CZH/4/773 , the UK Medical Research Council, and the University of Dundee work through the provision of a stipend for K.L. and from the Health Services Research Unit at the University of Aberdeen, which is core funded by the CSO of the Scottish Government Health Directories. Objectives : PRagmatic Explanatory Continuum Indicator Summary (PRECIS)-2 is a tool that could improve design insight for trialists. Our aim was to validate the PRECIS-2 tool, unlike its predecessor, testing the discriminant validity and interrater reliability. Study Design and Setting : Over 80 international trialists, methodologists, clinicians, and policymakers created PRECIS-2 helping to ensure face validity and content validity. The interrater reliability of PRECIS-2 was measured using 19 experienced trialists who used PRECIS-2 to score a diverse sample of 15 randomized controlled trial protocols. Discriminant validity was tested with two raters to independently determine if the trial protocols were more pragmatic or more explanatory, with scores from the 19 raters for the 15 trials as predictors of pragmatism. Results : Interrater reliability was generally good, with seven of nine domains having an intraclass correlation coefficient over 0.65. Flexibility (adherence) and recruitment had wide confidence intervals, but raters found these difficult to rate and wanted more information. Each of the nine PRECIS-2 domains could be used to differentiate between trials taking more pragmatic or more explanatory approaches with better than chance discrimination for all domains. Conclusion: We have assessed the validity and reliability of PRECIS-2. An elaboration study and web site provide guidance to help future users of the tool which is continuing to be tested by trial teams, systematic reviewers, and funders. Postprint

Objectives: To review the reporting of key items of recruitment information in trial reports and estimate the number needed to screen to recruit one additional participant. Study Design and Setting: Review of breast cancer trials published in the years 2003–2005, 2007, and 2008. Results: The search identified 1,570 potentially eligible studies. After a random selection of 20% from each year and checking against inclusion criteria, a total of 207 studies were included in the review. Some items of information were well reported, such as the number included in the analysis. Sample size calculations were often not presented, but reporting is slowly improving. Who recruits participants and how many individuals were screened are often not reported. The median number needed to screen to recruit one additional participant was two (range, 1–593). Conclusions: Without reporting the when, where, by whom, and how many of recruitment, trialists deny readers part of the contextual description they need to judge whether a trial’s results are applicable to their own situation. Trialists and journal editors need to be more diligent in following the reporting recommendations of the Consolidated Standards of Reporting Trials statement.

Randomised trials are at the heart of evidence-based healthcare, but the methods and infrastructure for conducting these sometimes complex studies are largely evidence free. Trial Forge (www.trialforge.org) is an initiative that aims to increase the evidence base for trial decision making and, in doing so, to improve trial efficiency.\ud \ud This paper summarises a one-day workshop held in Edinburgh on 10 July 2014 to discuss Trial Forge and how to advance this initiative. We first outline the problem of inefficiency in randomised trials and go on to describe Trial Forge. We present participants’ views on the processes in the life of a randomised trial that should be covered by Trial Forge.\ud \ud General support existed at the workshop for the Trial Forge approach to increase the evidence base for making randomised trial decisions and for improving trial efficiency. Agreed upon key processes included choosing the right research question; logistical planning for delivery, training of staff, recruitment, and retention; data management and dissemination; and close down. The process of linking to existing initiatives where possible was considered crucial. Trial Forge will not be a guideline or a checklist but a ‘go to’ website for research on randomised trials methods, with a linked programme of applied methodology research, coupled to an effective evidence-dissemination process. Moreover, it will support an informal network of interested trialists who meet virtually (online) and occasionally in person to build capacity and knowledge in the design and conduct of efficient randomised trials.\ud \ud Some of the resources invested in randomised trials are wasted because of limited evidence upon which to base many aspects of design, conduct, analysis, and reporting of clinical trials. Trial Forge will help to address this lack of evidence.\ud \ud

Background: Clinical practice guidelines are typically written for healthcare providers but there is increasing interest in producing versions for the public, patients and carers. The main objective of this review is to identify and synthesise evidence of the public’s attitudes towards clinical practice guidelines and evidence-based recommendations written for providers or the public, together with their awareness of guidelines. Methods: We included quantitative and qualitative studies of any design reporting on public, patient (and their carers) attitudes and awareness of guidelines written for providers or patients/public. We searched electronic databases including MEDLINE, PSYCHINFO, ERIC, ASSIA and the Cochrane Library from 2000 to 2012. We also searched relevant websites, reviewed citations and contacted experts in the field. At least two authors independently screened, abstracted data and assessed the quality of studies. We conducted a thematic analysis of first and second order themes and performed a separate narrative synthesis of patient and public awareness of guidelines. Results: We reviewed 5415 records and included 26 studies (10 qualitative studies, 13 cross sectional and 3 randomised controlled trials) involving 24 887 individuals. Studies were mostly good to fair quality. The thematic analysis resulted in four overarching themes: Applicability of guidelines; Purpose of guidelines for patient; Purpose of guidelines for health care system and physician; and Properties of guidelines. Overall, participants had mixed attitudes towards guidelines; some participants found them empowering but many saw them as a way of rationing care. Patients were also concerned that the information may not apply to their own health care situations. Awareness of guidelines ranged from 0-79%, with greater awareness in participants surveyed on national guideline websites. Conclusion: There are many factors, not only formatting, that may affect the uptake and use of guideline-derived material by the public. Producers need to make clear how the information is relevant to the reader and how it can be used to make healthcare improvements although there were problems with data quality. Awareness of guidelines is generally low and guideline producers cannot assume that the public has a more positive perception of their material than of alternative sources of health information.

Background:If you want to know which of two or more healthcare interventions is most effective, the randomised controlled trial is the design of choice. Randomisation, however, does not itself promote the applicability of the results to situations other than the one in which the trial was done. A tool published in 2009, PRECIS (PRagmatic Explanatory Continuum Indicator Summaries) aimed to help trialists design trials that produced results matched to the aim of the trial, be that supporting clinical decision-making, or increasing knowledge of how an intervention works. Though generally positive, groups evaluating the tool have also found weaknesses, mainly that its inter-rater reliability is not clear, that it needs a scoring system and that some new domains might be needed. The aim of the study is to: Produce an improved and validated version of the PRECIS tool. Use this tool to compare the internal validity of, and effect estimates from, a set of explanatory and pragmatic trials matched by intervention. Methods: The study has four phases. Phase 1 involves brainstorming and a two-round Delphi survey of authors who cited PRECIS. In Phase 2, the Delphi results will then be discussed and alternative versions of PRECIS-2 developed and user-tested by experienced trialists. Phase 3 will evaluate the validity and reliability of the most promising PRECIS-2 candidate using a sample of 15 to 20 trials rated by 15 international trialists. We will assess inter-rater reliability, and raters’ subjective global ratings of pragmatism compared to PRECIS-2 to assess convergent and face validity. Phase 4, to determine if pragmatic trials sacrifice internal validity in order to achieve applicability, will compare the internal validity and effect estimates of matched explanatory and pragmatic trials of the same intervention, condition and participants. Effect sizes for the trials will then be compared in a meta-regression. The Cochrane Risk of Bias scores will be compared with the PRECIS-2 scores of pragmatism. Discussion: We have concrete suggestions for improving PRECIS and a growing list of enthusiastic individuals interested in contributing to this work. By early 2014 we expect to have a validated PRECIS-2.

Background The tendency for authors to submit, and of journals to accept, manuscripts for publication based on the direction or strength of the study findings has been termed publication bias. Objectives To assess the extent to which publication of a cohort of clinical trials is influenced by the statistical significance, perceived importance, or direction of their results. Search methods We searched the Cochrane Methodology Register (The Cochrane Library [Online] Issue 2, 2007), MEDLINE (1950 to March Week 2 2007), EMBASE (1980 to Week 11 2007) and Ovid MEDLINE In-Process & Other Non-Indexed Citations (March 21 2007). We also searched the Science Citation Index (April 2007), checked reference lists of relevant articles and contacted researchers to identify additional studies. Selection criteria Studies containing analyses of the association between publication and the statistical significance or direction of the results (trial findings), for a cohort of registered clinical trials. Data collection and analysis Two authors independently extracted data. We classified findings as either positive (defined as results classified by the investigators as statistically significant (P < 0.05), or perceived as striking or important, or showing a positive direction of effect) or negative (findings that were not statistically significant (P ≥ 0.05), or perceived as unimportant, or showing a negative or null direction in effect). We extracted information on other potential risk factors for failure to publish, when these data were available. Main results Five studies were included. Trials with positive findings were more likely to be published than trials with negative or null findings (odds ratio 3.90; 95% confidence interval 2.68 to 5.68). This corresponds to a risk ratio of 1.78 (95% CI 1.58 to 1.95), assuming that 41% of negative trials are published (the median among the included studies, range = 11% to 85%). In absolute terms, this means that if 41% of negative trials are published, we would expect that 73% of positive trials would be published. Two studies assessed time to publication and showed that trials with positive findings tended to be published after four to five years compared to those with negative findings, which were published after six to eight years. Three studies found no statistically significant association between sample size and publication. One study found no significant association between either funding mechanism, investigator rank, or sex and publication. Authors' conclusions Trials with positive findings are published more often, and more quickly, than trials with negative findings.

Trials can be described as being on a design spectrum between highly explanatory (roughly, ‘Can the intervention work?’) to highly pragmatic (‘Does the intervention work in routine care?’). A criticism levelled at trials that take a pragmatic approach is that they sacrifice internal validity for external validity, i.e. there is a trade-off to be made. Proponents of pragmatic trials argue that there is no trade-off. However, both critics and defenders of the pragmatic approach have made their arguments in the absence of empirical evidence one way or the other. As part of our work developing the PRECIS-2 trial design tool, we looked for evidence of the validity trade-off in two ways. Firstly, a sample of 14 cardiovascular explanatory trials was matched to trials of the same intervention but which took a more pragmatic design approach. Secondly, 23 trials included in a Cochrane review of first-line treatment for hypertension were compared. The Cochrane Risk of Bias tool was used to assess internal validity; PRECIS-2 was used to assess design approach. We found no clear difference in Cochrane Risk of Bias assessments between trials taking explanatory and pragmatic approaches. Work with a larger sample of trials is required before we can be completely confident in this result but this represents the first evidence that the suggested trade-off between internal and external validity in trials may be false. This work is part of the Trial Forge initiative to improve trial efficiency.

Randomised trials are hard work. Like much that is hard, this toil is only worth it because of the prospect of a substantial reward. Sadly, the reward to potential users such as patients, healthcare professionals and policy makers is often smaller than it should be because trial design decisions reduced the relevance of the trial to them. PRECIS-2 is a tool designed to help trialists match their design decisions to the information needs of those they hope will use the trial results. It is an update of the 2009 PRECIS tool, which though highly cited had some well-known weaknesses. PRECIS-2 was developed in collaboration with over 80 international trialists, methodologists and others to produce a tool that addressed those weaknesses but also supports improved design insight for trialists. PRECIS-2 retains the wheel format of the original tool. It has nine design domains including Eligibility, Recruitment, Setting and Primary outcome. A new domain Organisation is explicitly aimed at making trialists consider the resource requirements their intervention will place on health care systems if it were to be rolled out into routine care, the intention being to think about implementation at the design stage. The highly visual presentation makes inconsistent decision-making immediately obvious; it also highlights differences of opinion between trial team members. We will present the tool, explain how to use it and show examples of how it has been used already. This work is part of the Trial Forge initiative to improve trial efficiency. Authors’ details University of Aberdeen, Aberdeen, UK. University of Dundee, Dundee, UK. Western University, London, Canada. University of Toronto, Toronto, Canada.

For results from a randomised trial to be relevant to practice it is important that the needs of the end users of the trial, health care professionals, policymakers and patients are considered. Key aspects of a trial need to reflect how the intervention would be implemented. PRECIS-2 is an innovative way to display information about a trial's design, using a wheel with 9 spokes or domains, graphically illustrating which areas of the trial are more pragmatic, that is designed to test whether the intervention will work in usual care and which are more explanatory, designed to test the intervention under ideal conditions. This talk will describe the results of a two-part investigation applying PRECIS-2 to primary care trials. In the first part we worked with primary care trial teams to apply the tool to their trials. In the second part we interviewed people involved in trying to change practice based on research evidence to find out their views on PRECIS-2 and what is important to ensure the results of trials are relevant to practice. The interviewees included research funders, guideline developers and practicing GPs. We found that primary care trials vary considerably in the extent to which they can be viewed as pragmatic, that PRECIS-2 addresses aspects of trial design which policy makers, practitioners and guideline developers believe are important in assessing relevance to practice and that for some areas of a trial's design flexibility should not always be encouraged. Our interviewees also suggested some novel uses for PRECIS-2.

PRECIS is a tool to help trialists make design decisions consistent with the intended purpose of their trial. This paper gives guidance on how to use an improved, validated version, PRECIS-2, which has been developed with the help of over 80 international trialists, clinicians, and policymakers. Keeping the original simple wheel format, PRECIS-2 has nine domains—eligibility criteria, recruitment, setting, organisation, flexibility (delivery), flexibility (adherence), follow-up, primary outcome, and primary analysis—scored from 1 (very explanatory) to 5 (very pragmatic) to facilitate domain discussion and consensus. It is hoped PRECIS-2 will be valuable in supporting the explicit matching of design decisions to how the trial results are intended to be used

Background Improving patient versions of guidelines is one way to support an increasing role for patients in health decision making. Objectives To evaluate evidence on the public’s attitudes and knowledge of clinical practice guidelines AND what strategies have been used to communicate guideline recommendations to this group. Methods We conducted a systematic review of public attitudes and knowledge of clinical practice guidelines to inform the development of dissemination strategies for this population. We searched health databases from 2000 to 01/2013, grey literature, and we contacted guideline producers. Two reviewers independently abstracted, coded, synthesised themes from the studies. Results We included 25 published studies and three reports (CCPG, NICE, SIGN). There was a huge variation in the public’s awareness of guidelines (12 studies) from 25–75%. The key themes to communicate guidelines (15 studies) to the public included, predictive factors (amount of education), personalisation, access to care, trustworthiness (evidence behind recommendations), and self-management. Discussion Although there were few studies for thematic analysis there were recurrent themes. When developing patient versions, the danger could be to focus on detailed formatting instead of fundamental issues around whether patients dismiss guidelines as not applicable to their unique situation and restricts care. The results will inform work focused on the public and patients being done in EU FP7 DECIDE project. Implications Guideline producers will need to increase the public’s awareness of clinical guidelines and developing communication strategies that are clearly personally applicable, trustworthy and useful for patients and carers managing their care.

Background Systematic reviews have shown uncertainty about the size or direction of any 'trial effect' for patients in trials compared to those treated outside trials. We are not aware of any systematic review of whether there is a 'trial effect' related to being treated by healthcare practitioners or institutions that take part in research. Methods We searched the Cochrane Methodology Register and MEDLINE (most recently in January 2009) for studies in which patients were allocated to treatment in one or other setting, and cohort studies reporting the outcomes of patients from different settings. We independently assessed study quality, including the control of bias in the generation of the comparison groups, and extracted data. Results We retrieved and checked more than 15,000 records. Thirteen articles were eligible: five practitioner studies and eight institution studies. Meta-analyses were not possible because of heterogeneity. Two practitioner studies were judged to be 'controlled' or better. A Canadian study among nurses found that use of research evidence was higher for those who took part in research working groups and a Danish study on general practitioners found that trial doctors were more likely to prescribe in accordance with research evidence and guidelines. Five institution studies were 'controlled' but provided mixed results. A study of North American patients at hospitals that had taken part in trials for myocardial infarction found no statistically significant difference in treatment for patients in trial and non-trial hospitals. A Canadian study of myocardial infarction patients found that trial participants had better survival than patients in the same hospitals who were not in trials or those in non-trial hospitals. A study of general practices in Denmark did not detect differences in guideline adherence between trial and non-trial practices but found that trial practices were more likely to prescribe the trial sponsor's drugs. The other two 'controlled' studies of institutions found lower mortality in trial than non-trial hospitals. Conclusions The available findings from existing research suggest that there might be a 'trial effect' of better outcomes, greater adherence to guidelines and more use of evidence by practitioners and institutions that take part in trials. However, the consequences for patient health are uncertain and the most robust conclusion may be that there is no apparent evidence that patients treated by practitioners or in institutions that take part in trials do worse than those treated elsewhere.

A 2-fold increase in hepatic alanine concentration was observed in rats bearing a Walker 256 carcinoma growing sub-cutaneously. Decreases were observed in the activities of both cytosolic and mitochondrial isozyme forms of L-alanine-2-oxoglutarate aminotransferase. Activities of two enzymes involved in a secondary pathway of haem synthesis involving alanine, L-alanine-4,5-dioxovalerate aminotransferase and the NADP-requiring isozyme form of 4-oxo-5-hydroxyvalerate dehydrogenase were also reduced but there was no change in liver porphyrin concentration. L-alanine-glyoxalate aminotransferase activity was unaffected. The results are discussed in relation to the utilisation of alanine as a gluconeogenic substrate in the tumor-bearing host.

Results Brainstorming sessions identified the PRECIS presentation (a wheel), lack of a scoring system and domain weighting as issues for exploration in the Delphi process. Thirty four completed responses from 90 invitees were received in Round 1 of the Delphi; Round 2 involved 23 individuals (response rate 82%). 45% selected a 1-5 Likert scale, 56.5% wanted to use a table (to justify decisions) and a PRECIS wheel, 26% were in favour of weighting domains. Suggestions for extra domains included: recruitment process for participants and integration of the intervention into the healthcare system. An expert panel in Toronto used the Delphi suggestions to help create alternative versions of PRECIS-2 for user-testing in spring 2013. Conclusions PRECIS can be improved by the addition of a Likert scale and additional domains. We expect to have a validated PRECIS-2 by the beginning of 2014.