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Objectives:\ud We aimed to review how ‘Risk of Bias In Non-randomized Studies–of Interventions’ (ROBINS-I), a Cochrane risk of bias assessment tool, has been used in recent systematic reviews.\ud \ud Study Design and Setting:\ud Database and citation searches were conducted in March 2020 to identify recently published reviews using ROBINS-I. Reported ROBINS-I assessments and data on how ROBINS-I was used were extracted from each review. Methodological quality of reviews was assessed using AMSTAR 2 (‘A MeaSurement Tool to Assess systematic Reviews’).\ud \ud Results:\ud Of 181 hits, 124 reviews were included. Risk of bias was serious/critical in 54% of assessments on average, most commonly due to confounding. Quality of reviews was mostly low, and modifications and incorrect use of ROBINS-I were common, with 20% reviews modifying the rating scale, 20% understating overall risk of bias, and 19% including critical-risk of bias studies in evidence synthesis. Poorly conducted reviews were more likely to report low/moderate risk of bias (predicted probability 57% [95% CI: 47–67] in critically low-quality reviews, 31% [19–46] in high/moderate-quality reviews).\ud \ud Conclusion:\ud Low-quality reviews frequently apply ROBINS-I incorrectly, and may thus inappropriately include or give too much weight to uncertain evidence. Readers should be aware that such problems can lead to incorrect conclusions in reviews.

In the context of worldwide ageing, increasing numbers of older people are lonely, isolated and excluded, with serious implications for health, and cognitive and physical functioning. Access to good public transport can improve mobility and social participation among older adults, and policies that improve access and promote use, such as concessionary travel schemes, are potentially important in promoting healthy and successful ageing. Concessionary travel schemes for older people are in place in many countries but are under threat following the global financial crisis. Evidence regarding their success in encouraging activity and social participation is generally positive but based largely on qualitative or observational associations and, in particular, is often limited by the lack of appropriate comparison groups. We use changes in the English statutory scheme, in particular the rising eligibility age from 2010 onwards, as a natural experiment to explore its impact on older people's travel. A difference-in-difference-in-difference analysis of National Travel Surveys (2002–2016) compares three age groups differentially affected by eligibility criteria: 50–59 years (consistently ineligible), 60–64 years (decreasing eligibility from 2010) and 65–74 years (consistently eligible). Compared with 50–59-year-olds, bus travel by 60–74-year-olds increased year-on-year from 2002 to 2010 then fell following rises in eligibility age (annual change in weekly bus travel: −2.9 per cent (−4.1%, −1.7%) in 60–74- versus 50–59-year-olds). Results were consistent across gender, occupation and rurality. Our results indicate that access to, specifically, free travel increases bus use and access to services among older people, potentially improving mobility, social participation and health. However, the rising eligibility age in England has led to a reduction in bus travel in older people, including those not directly affected by the change, demonstrating that the positive impact of the concession goes beyond those who are eligible. Future work should explore the cost–benefit trade-off of this and similar schemes worldwide.

Objective To re-evaluate the impact of England’s Teenage Pregnancy Strategy (1999 to 2010) on pregnancy and birth rates. Hailed as a unique, nation-wide, comprehensive, evidence-based intervention, the strategy has been promoted as a reproducible model for other countries with high teenage pregnancy rates. Design Controlled interrupted time series and synthetic control analyses using routinely collected data on births and abortions in 16 countries. Setting The Strategy was published in July 1999 and implemented from 2000-2010, with increased investment in areas with higher rates of under-18 pregnancies from 2006 onwards. Participants Women aged under 20 living in England during the intervention period were considered to be the target population. Women in Scotland and Wales were the control population in our interrupted time series analyses. Women from European and English-speaking high-income countries were the control population in our synthetic control analyses. Main outcome measures The pregnancy rate among women aged under-18 was our primary outcome, as this was the target of the Strategy. We used under-18 births and under-20 pregnancies as secondary outcomes. Results In the controlled interrupted time series analyses, trends in rates of teenage pregnancy in England were similar to Scotland (0.08 fewer pregnancies per 1,000 women per year in England; −0.74 to 0.59) and Wales (0.14 more pregnancies per 1,000 women per year in England; −0.48 to 0.76). In synthetic control analyses, under-18 birth rates were very similar in England and the synthetic control. Under-20 pregnancy rates were marginally higher in England than in the synthetic control. Placebo testing and other sensitivity analyses supported the finding of little observable effect. Conclusion Although teenage pregnancies and births in England fell following implementation of the Teenage Pregnancy Strategy, comparisons with other countries suggest the strategy had little, if any, effect. This raises doubts about whether the strategy should be used as a model for future public health interventions in England or in other countries aiming to reduce teenage pregnancy. The protocol for the analysis was published online at https://osf.io/tdbr8/ SUMMARY BOX What is already known on this topic: Teenage pregnancy is associated with numerous health risks, and efforts to reduce rates of pregnancy may lead to improved health outcomes The Teenage Pregnancy Strategy was launched in 1999 with the goal of reducing teenage pregnancies in England Initial observations showed a drop in rate across the strategy period; this has been interpreted as demonstrating the success of the intervention. What this study adds: Our study suggests there was little or no effect of the strategy, and that the rapid decline in rates would have occurred without the intervention, in line with similar countries.

Many interventions that may have large impacts on health and health inequalities, such as social and public health policies and health system reforms, are not amenable to evaluation using randomised controlled trials. The United Kingdom Medical Research Council's guidance on the evaluation of natural experiments draws attention to the need for ingenuity to identify interventions which can be robustly studied as they occur, and without experimental manipulation. Studies of intervention withdrawal may usefully widen the range of interventions that can be evaluated, allowing some interventions and policies, such as those that have developed piecemeal over a long period, to be evaluated for the first time. In particular, sudden removal may allow a more robust assessment of an intervention's long-term impact by minimising ‘learning effects’. Interpreting changes that follow withdrawal as evidence of the impact of an intervention assumes that the effect is reversible and this assumption must be carefully justified. Otherwise, withdrawal-based studies suffer similar threats to validity as intervention studies. These threats should be addressed using recognised approaches, including appropriate choice of comparators, detailed understanding of the change processes at work, careful specification of research questions, and the use of falsification tests and other methods for strengthening causal attribution.\ud \ud Evaluating intervention withdrawal provides opportunities to answer important questions about effectiveness of population health interventions, and to study the social determinants of health. Researchers, policymakers and practitioners should be alert to the opportunities provided by the withdrawal of interventions, but also aware of the pitfalls.

Population health interventions are essential to reduce health inequalities and tackle other public health priorities, but they are not always amenable to experimental manipulation. Natural experiment (NE) approaches are attracting growing interest as a way of providing evidence in such circumstances. One key challenge in evaluating NEs is selective exposure to the intervention. Studies should be based on a clear theoretical understanding of the processes that determine exposure. Even if the observed effects are large and rapidly follow implementation, confidence in attributing these effects to the intervention can be improved by carefully considering alternative explanations. Causal inference can be strengthened by including additional design features alongside the principal method of effect estimation. NE studies often rely on existing (including routinely collected) data. Investment in such data sources and the infrastructure for linking exposure and outcome data is essential if the potential for such studies to inform decision making is to be realized.

Kidney transplant recipients and transplant physicians face important clinical questions where machine learning methods may help improve the decision-making process. This mini-review explores potential applications of machine learning methods to key stages of a kidney transplant recipient's journey, from initial waitlisting and donor selection, to personalization of immunosuppression and prediction of post-transplantation events. Both unsupervised and supervised machine learning methods are presented, including k-means clustering, principal components analysis, k-nearest neighbors, and random forests. The various challenges of these approaches are also discussed.

No abstract available.

The Consolidated Standards of Reporting Trials (CONSORT) statement is a guideline designed to improve the transparency and quality of the reporting of randomised controlled trials (RCTs). In this article we present an extension to that statement for randomised pilot and feasibility trials conducted in advance of a future definitive RCT. The checklist applies to any randomised study in which a future definitive RCT, or part of it, is conducted on a smaller scale, regardless of its design (eg, cluster, factorial, crossover) or the terms used by authors to describe the study (eg, pilot, feasibility, trial, study). The extension does not directly apply to internal pilot studies built into the design of a main trial, non-randomised pilot and feasibility studies, or phase II studies, but these studies all have some similarities to randomised pilot and feasibility studies and so many of the principles might also apply. The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct. We followed recommended good practice to develop the extension, including carrying out a Delphi survey, holding a consensus meeting and research team meetings, and piloting the checklist. The aims and objectives of pilot and feasibility randomised studies differ from those of other randomised trials. Consequently, although much of the information to be reported in these trials is similar to those in randomised controlled trials (RCTs) assessing effectiveness and efficacy, there are some key differences in the type of information and in the appropriate interpretation of standard CONSORT reporting items. We have retained some of the original CONSORT statement items, but most have been adapted, some removed, and new items added. The new items cover how participants were identified and consent obtained; if applicable, the prespecified criteria used to judge whether or how to proceed with a future definitive RCT; if relevant, other important unintended consequences; implications for progression from pilot to future definitive RCT, including any proposed amendments; and ethical approval or approval by a research review committee confirmed with a reference number. This article includes the 26 item checklist, a separate checklist for the abstract, a template for a CONSORT flowchart for these studies, and an explanation of the changes made and supporting examples. We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials. Editor’s note: In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites. Electronic supplementary material The online version of this article (doi:10.1186/s40814-016-0105-8) contains supplementary material, which is available to authorized users.

Background Liver resections (LRs) are performed with increasing frequency for metastatic disease. To minimize the risk of postoperative complications, a period of 6 weeks between the last dose of chemotherapy and LR is typically recommended. The current study examines postoperative morbidity and mortality following LR in patients who received chemotherapy within 30 days prior to LR. Methods The merged 2005–2007 National Surgical Quality Improvement Program (NSQIP) Participant Use File was queried for perioperative risk factors, laboratory values and postoperative occurrences or complications in patients who underwent LR. Patients were grouped according to their receipt or non-receipt of chemotherapy within 30 days prior to LR and major postoperative complications. Results A total of 2331 patients underwent LR; 2147 did not receive chemotherapy within 30 days of resection (No Chemo group) and 184 received chemotherapy within 30 days prior to resection (Chemo group). The groups were similar with regard to preoperative co-morbidities and operative factors. The median NSQIP statistically computed morbidity probability was similar between the groups (No Chemo 0.32, Chemo 0.34; P = 0.07), whereas the median mortality probability was higher in the Chemo group (0.02) than the No Chemo group (0.014; P = 0.001). Thirty-day survival was similar between the two groups (No Chemo 97%, Chemo 98%; P = 0.44). Major complication rates did not differ between the groups (No Chemo 20%, Chemo 18%; P = 0.51). Factors associated with major complications in the Chemo group included: extent of resection; intraoperative transfusion; preoperative ascites, and preoperative haematocrit. Discussion Major morbidity was not increased in Chemo patients. The strongest predictors of major postoperative complications in the Chemo group were extent of resection and intraoperative red cell transfusion. Although the NSQIP dataset does not include data about tumour type or chemotherapy regimen, these data suggest that LR may be safely performed within 30 days of chemotherapy, thereby minimizing the length of time during which patients do not receive systemic treatment.

The use of vaccination against the influenza virus remains the most effective method of mitigating the significant morbidity and mortality caused by this virus. Antibodies elicited by currently licensed influenza vaccines are predominantly hemagglutination-inhibition (HI)-competent antibodies that target the globular head of HA thus inhibiting influenza virus entry into target cells. These antibodies predominantly confer homosubtypic/strain specific protection and only rarely confer heterosubtypic protection. However, recent academia or pharma-led R&D towards the production of a universal vaccine has centered on the elicitation of antibodies directed against the stalk of the influenza HA that has been shown to confer broad protection across a range of different subtypes (H1 to H16). The accurate and sensitive measurement of antibody responses elicited by these next-generation influenza vaccines is however hampered by the lack of sensitivity of the traditional influenza serological assays hemagglutinin inhibition (HI), single radial hemolysis (SRH) and microneutralization (MN). Assays utilizing pseudotypes, chimeric viruses bearing influenza glycoproteins, have been shown to be highly efficient for the measurement of homosubtypic and heterosubtypic broadly-neutralizing antibodies, making them ideal serological tools for the study of cross-protective responses against multiple influenza subtypes with pandemic potential. In this review, we will analyze and compare literature involving the production of influenza pseudotypes with particular emphasis on their use in serum antibody neutralization assays. This will enable us to establish the parameters required for optimization and propose a consensus protocol to be employed for the further deployment of these assays in influenza vaccine immunogenicity studies.

The importance and difficultly of asset tracking make it worthy of attention. We focus on data centers consisting of vertical racks where each rack may accommodate a variety of equipment. We describe an asset tracking system which automatically detects and identifies equipment within rack; has "pinpoint" accuracy, i.e., location resolution equals asset size; relays this information to possibly several management back-ends; includes a back-end application that maintains a location history for all equipment; and uses a visualization tool to display both the current state and the history of deployment. The solution features a flexible architecture that simplifies the connection with both existing and future asset management applications. The architecture supports simple configuration, load balancing, and redundancy. Care has been taken to use widely recognized standards wherever possible.

Even though scripting languages like Pig allow for simpler coding, performing analytics over Big Data using Map-Reduce engines remains challenging. To further assist developers, and support novice users, we offer "The Farm", a catalog of scriptable services supporting creation, discovery, composition, and optimized execution. Each Pig script added to The Farm becomes an executable service, with inputs and outputs defined by relation schemas. Those services are discoverable using natural language search, and composable using a drag-and-drop interface. To support efficient execution, composed services are automatically merged to a single executable script, which can then be run by a growing selection of platform-specific optimizers and interpreters.

Background Rapid access chest pain clinics have facilitated the early diagnosis and treatment of patients with coronary heart disease and angina. Despite this important service provision, coronary heart disease continues to be under-diagnosed and many patients are left untreated and at risk. Recent advances in imaging technology have now led to the widespread use of noninvasive computed tomography, which can be used to measure coronary artery calcium scores and perform coronary angiography in one examination. However, this technology has not been robustly evaluated in its application to the clinic. Methods/design The SCOT-HEART study is an open parallel group prospective multicentre randomized controlled trial of 4,138 patients attending the rapid access chest pain clinic for evaluation of suspected cardiac chest pain. Following clinical consultation, participants will be approached and randomized 1:1 to receive standard care or standard care plus ≥64-multidetector computed tomography coronary angiography and coronary calcium score. Randomization will be conducted using a web-based system to ensure allocation concealment and will incorporate minimization. The primary endpoint of the study will be the proportion of patients diagnosed with angina pectoris secondary to coronary heart disease at 6 weeks. Secondary endpoints will include the assessment of subsequent symptoms, diagnosis, investigation and treatment. In addition, long-term health outcomes, safety endpoints, such as radiation dose, and health economic endpoints will be assessed. Assuming a clinic rate of 27.0% for the diagnosis of angina pectoris due to coronary heart disease, we will need to recruit 2,069 patients per group to detect an absolute increase of 4.0% in the rate of diagnosis at 80% power and a two-sided P value of 0.05. The SCOT-HEART study is currently recruiting participants and expects to report in 2014. Discussion This is the first study to look at the implementation of computed tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease. Trial registration ClinicalTrials.gov Identifier: NCT01149590

By more closely integrating email with the web we aim to bring organization to email and more collaboration to the web. To this end we developed the Sidebar, a web-browser plug which displays email messages which link to the currently displayed URL. We conducted longitudinal studies on two versions of Sidebar to observe the usage of Sidebar and determine if it improves communications productivity. We found that providing an email summary in Sidebar resulted in raised awareness of the email collaborations, increased serendipitous discovery of information, and resulted in higher reported communication productivity. This paper summarizes Sidebar's operation, describes the user studies, and presents conclusions.

Simple division (5 mm) of the anterior surface of the sphincter of Oddi (sphincterotomy) was utilized in the mid 20th century for presumed biliary-pancreatic pain from sphincter of Oddi dysfunction (biliary dyskinesia). Lack of success led to a longer (2–3 cm) division of the sphincter with formal sphincteroplasty, but the improvement in outcome was only marginal. Most groups currently perform a generous sphincteroplasty with division of the transampullary septum to include division of the pancreatic component of the sphincter, and with this extended approach, have achieved good to excellent results in appropriately selected patients. This procedure allows free egress of bile and pancreatic juice into the duodenum after stimulation from ingestion of a meal. Stenting of the pancreatic duct of even the septotomy when needed can now be accomplished after endoscopic sphincteroplasty in experienced hands.

The unification of Semantic Web query languages under the SPARQL standard and the development of commercial-quality implementations are encouraging industries to use semantic technologies for managing information. Current implementations, however, lack the performance monitoring and management services that the industry expects. In this paper, we present a performance and management framework interface to a generic SPARQL web server. We leverage existing standards for instrumentation to make the system ready-to-manage through existing monitoring applications, and we provide a performance framework which has the distinct feature of providing measurement results through the same SPARQL interface used to query data, eliminating the need for special interfaces.

Asset management in state of the art data centers is still a manual process. An automated system to track the location of servers and create a real-time inventory would not only improve operations management but also reduce operational costs. This demo shows a novel application of location aware wireless networks, RFID technology and visualization software integrated in end-to-end system to track servers in a data center.

Sharing ontology, sensing context and reasoning are crucial to the realization of context-aware software agents. This document describes our effort on using Resource Description Framework (RDF) and the Prolog Forward Chaining (P fc ) system to provide support for ontology sharing and reasoning in the CoolAgent Recommendation System (CoolAgent RS), a context-aware multi-agent system. This document also describes the implementation of the CoolAgent RS document and cuisine recommendation services that provide tailored services by exploiting user’s context.

s / Pancreatology 13 (2013) S2–S98 S64 the test cohorts and lack of a standard reference method, more studies are needed to conclude that the trypsinmethod is superior. We are developing a reference method using confocal microscopy. PII-36 Abstract id: 17. Effect of osteocalcin on human beta cell proliferation and function and its role on insulin secretion Anita Kaw, Daniel Fraga, Craig Fischer. The Methodist Hospital Research Institute, Houston, Texas, United States Introduction: Osteocalcin, a hormone produced by bone cells, has been found to increase insulin production, enhance insulin sensitivity, and promote b-cell proliferation in mouse models, however most mouse studies do not reliably affect humans in the same manner. Aims: This study sought to confirm the effect of osteocalcin on human b-cell proliferation and function and its role, if any, on insulin secretion. Materials & methods: Three variants of osteocalcin extracted and purified from bovine tibial cortical bone were investigated: osteocalcin (OC), decarboxylated osteocalcin (D-OC), and osteocalcin hexapeptide (HOC) were utilized in conjunction with a well-established islet model. Protocol included human pancreatic islet isolation from brain dead donors, islet cell culture in Memphis serum free mediumwith heparin, assessment of islet viability with flow cytometry, insulin secretion and content in vitro with western blot analysis and analysis of cellular composition by immunofluorescence. Results: Our results indicate that after 7 days in culture all three types of osteocalcin improved insulin-content and b-cell proliferation of glucose-stimulated islets, with D-OC showing the most significant and dose-dependent effect. The greatest effect on insulin enhancement was noted at the earliest time point (7 days), and this effect progressively deteriorated at later time points, reflecting perhaps senescence in our culture while apoptosis was not impacted by either osteocalcin or time in culture. Conclusion: Our findings indicate that osteocalcin or one of its variants may be utilized in patients whose disease conditions show a progressive loss of b-cell mass and function namely type 2 and, in some cases type 1 diabetes. PII-37 Abstract id: 226. Impact of pancreatic enzymes on blood glucose and insulin release in a porcine model Liudmyla Lozinska, Olena Prykhod’ko, Katarzyna Szwiec, Bj€ orn Westr€ om, Stefan Pierzynowski. Lund University, Dept Biology, Sweden Introduction: Exocrine pancreatic insufficiency (EPI) induced in young pigs by pancreatic duct ligation (PDL) results in growth arrest and a decreased ability to retain/assimilate nutrients. Aims: The aim of the study was to explore the effects of pancreatic enzyme replacement therapy (PERT) on glucose utilization and insulin secretion in this model. Materials & methods: Five EPI pigs and six control pigs were studied andmeal (MGTT), oral (OGTT), and i.v. glucose tolerance tests (IVGTT) were performed, either with or without PERT (Creon 10,000). Blood glucose was measured with a glucose-meter and plasma insulin using an ELISA kit. Results: The MGTT resulted in increased plasma glucose levels similar to that in the controls, but only a negligible increase in insulin levels. The MGTT following PERT, resulted in a prolonged increase in blood glucose (above those in controls) and insulin (below that in controls) levels. The OGTT, both with and without PERT, caused a prolonged increase in blood glucose levels compared to controls. A parallel increase in insulin levels were observed, however the increase was smaller in comparison to the controls. PERT before IVGTT, accelerated the elimination of glucose and at the same time lowered the insulin levels, with a shift in the curve peak towards that observed in the controls. Conclusion: In conclusion, the data indicates that pancreatic enzymes not only affect the availability of glucose from the food, but also affect the post-prandial insulin response in line with the incretin concept and thus suggests a factor released in response to PERT which affects glucose utilization. PII-38 Abstract id: 177. Pancreatic and pancreatic-like enzymes decrease insulin secretion together with an enhanced insulin efficiency or provoke insulin-independent glucose utilisation Olena Prykhodko, Liudmyla Lozinska, Katarzyna Szwiec, Adam Lada, Olexandr Fedkiv, Bj€ orn Westr€ om, Stefan Pierzynowski. Dept of Biology, Lund University, Sweden Introduction: The role of the exocrine pancreas in food digestion is well-studied but its’ possible (para-digestive) effects on insulin release and glucose tolerance has received less attention. Aims: We aimed to study the effects of pancreatic enzyme supplementation on blood glucose and plasma insulin in normal pigs. Materials & methods: Twelve pigs, 2.5 months old, were fasted overnight and then administered either porcine enzymes (Creon 10 000) or a mixture of pancreatic-like enzymes of microbial origin (PLEM), or empty capsules as a placebo. After 1h an intravenous glucose tolerance test (IVGTT) was performed (by infusion of 1g glucose/kg, using 50% solution). Repeated blood samples were taken and blood glucose was measured with a glucose-meter and plasma insulin levels with an ELISA-kit. Results: Blood glucose decreased 1h after enzyme administration (12.8% for Creon, 15.5% for PLEM, p

The Navajo and Hopi GIS Project was established to assess the feasibility and impact of implementing GIS techology at Tribal institutions. Los Alamos and Lawrence Livermore National Laboratories funded the Navajo and Hopi Geographic Information System (G.I.S.) Project and assigned a mentor from LANL to help guide the project for three summer months of 1995. The six organizations involved were: LANL, LLNL, Navajo Community College, Navajo Nation Land Office, Northern Arizona University and San Juan College. The Navajo Land Office provided the system software, hardware and training. Northern Arizona University selected two students to work at Hopi Water Resource Department. Navajo Community College provided two students and two faculty members. San Juan College provided one student to work with the N.C.C. group. This made up two project teams which led to two project sites. The project sites are the Water Resource Department on the Hopi reservation and Navajo Community College in Shiprock, New Mexico.

BackgroundThe Medical Research Council published the second edition of its framework in 2006 on developing and evaluating complex interventions. Since then, there have been considerable developments in the field of complex intervention research. The objective of this project was to update the framework in the light of these developments. The framework aims to help research teams prioritise research questions and design, and conduct research with an appropriate choice of methods, rather than to provide detailed guidance on the use of specific methods.MethodsThere were four stages to the update: (1) gap analysis to identify developments in the methods and practice since the previous framework was published; (2) an expert workshop of 36 participants to discuss the topics identified in the gap analysis; (3) an open consultation process to seek comments on a first draft of the new framework; and (4) findings from the previous stages were used to redraft the framework, and final expert review was obtained. The process was overseen by a Scientific Advisory Group representing the range of relevant National Institute for Health Research and Medical Research Council research investments.ResultsKey changes to the previous framework include (1) an updated definition of complex interventions, highlighting the dynamic relationship between the intervention and its context; (2) an emphasis on the use of diverse research perspectives: efficacy, effectiveness, theory-based and systems perspectives; (3) a focus on the usefulness of evidence as the basis for determining research perspective and questions; (4) an increased focus on interventions developed outside research teams, for example changes in policy or health services delivery; and (5) the identification of six ‘core elements’ that should guide all phases of complex intervention research: consider context; develop, refine and test programme theory; engage stakeholders; identify key uncertainties; refine the intervention; and economic considerations. We divide the research process into four phases: development, feasibility, evaluation and implementation. For each phase we provide a concise summary of recent developments, key points to address and signposts to further reading. We also present case studies to illustrate the points being made throughout.LimitationsThe framework aims to help research teams prioritise research questions and design and conduct research with an appropriate choice of methods, rather than to provide detailed guidance on the use of specific methods. In many of the areas of innovation that we highlight, such as the use of systems approaches, there are still only a few practical examples. We refer to more specific and detailed guidance where available and note where promising approaches require further development.ConclusionsThis new framework incorporates developments in complex intervention research published since the previous edition was written in 2006. As well as taking account of established practice and recent refinements, we draw attention to new approaches and place greater emphasis on economic considerations in complex intervention research. We have introduced a new emphasis on the importance of context and the value of understanding interventions as ‘events in systems’ that produce effects through interactions with features of the contexts in which they are implemented. The framework adopts a pluralist approach, encouraging researchers and research funders to adopt diverse research perspectives and to select research questions and methods pragmatically, with the aim of providing evidence that is useful to decision-makers.Future workWe call for further work to develop relevant methods and provide examples in practice. The use of this framework should be monitored and the move should be made to a more fluid resource in the future, for example a web-based format that can be frequently updated to incorporate new material and links to emerging resources.FundingThis project was jointly funded by the Medical Research Council (MRC) and the National Institute for Health Research (Department of Health and Social Care 73514).