***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background High-risk prescribing of non-steroidal anti-inflammatory drugs ( NSAIDs ) and antiplatelet agents accounts for a significant proportion of hospital admissions due to preventable adverse drug events . The recently completed PINCER trial has demonstrated that a one-off pharmacist-led information technology (IT)-based intervention can significantly reduce high-risk prescribing in primary care , but there is evidence that effects decrease over time and employing additional pharmacists to facilitate change may not be sustainable . Methods / design We will conduct a cluster r and omised controlled with a stepped wedge design in 40 volunteer general practice s in two Scottish health boards . Eligible practice s are those that are using the INPS Vision clinical IT system , and have agreed to have relevant medication-related data to be automatically extracted from their electronic medical records . All practice s ( clusters ) that agree to take part will receive the data -driven quality improvement in primary care ( DQIP ) intervention , but will be r and omised to one of 10 start date s. The DQIP intervention has three components : a web-based informatics tool that provides weekly up date d feedback of targeted prescribing at practice level , prompts the review of individual patients affected , and summarises each patient 's relevant risk factors and prescribing ; an outreach visit providing education on targeted prescribing and training in the use of the informatics tool ; and a fixed payment of 350 GBP ( 560 USD ; 403 EUR ) up front and a small payment of 15 GBP ( 24 USD ; 17 EUR ) for each patient review ed in the 12 months of the intervention . We hypothesise that the DQIP intervention will reduce a composite of nine previously vali date d measures of high-risk prescribing . Due to the nature of the intervention , it is not possible to blind practice s , the core research team , or the data analyst . However , outcome assessment is entirely objective and automated . There will additionally be a process and economic evaluation alongside the main trial . Discussion The DQIP intervention is an example of a potentially sustainable safety improvement intervention that builds on the existing National Health Service IT-infrastructure to facilitate systematic management of high-risk prescribing by existing practice staff . Although the focus in this trial is on Non-steroidal anti-inflammatory drugs and antiplatelets , we anticipate that the tested intervention would be generalisable to other types of prescribing if shown to be effective . Trial registration Clinical Trials.gov , dossier number : This article is part of a series of papers examining ethical issues in  cluster r and omized 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 cluster trial is to be set on a firm ethical foundation . This paper addresses the second of the questions posed , namely , from whom , when , and how must informed consent be obtained in CRTs in health research ? The ethical principle of respect for persons implies that research ers are generally obligated to obtain the informed consent of research subjects . Aspects of CRT design , including cluster r and omization , cluster level interventions , and cluster size , present challenges to obtaining informed consent . Here we address five questions related to consent and CRTs : How can a study proceed if informed consent is not possible ? Is consent to r and omization always required ? What information must be disclosed to potential subjects if their cluster has already been r and omized ? Is passive consent a valid substitute for informed consent ? Do health professionals have a moral obligation to participate as subjects in CRTs design ed to improve professional practice ? We set out a framework based on the moral foundations of informed consent and international regulatory provisions to address each of these questions . First , when informed consent is not possible , a study may proceed if a research ethics committee is satisfied that conditions for a waiver of consent are satisfied . Second , informed consent to r and omization may not be required if it is not possible to approach subjects at the time of r and omization . Third , when potential subjects are approached after cluster r and omization , they must be provided with a detailed description of the interventions in the trial arm to which their cluster has been r and omized ; detailed information on interventions in other trial arms need not be provided . Fourth , while passive consent may serve a variety of practical ends , it is not a substitute for valid informed consent . Fifth , while health professionals may have a moral obligation to participate as subjects in research , this does not diminish the necessity of informed consent to study participation This article is part of a series of papers examining ethical issues in cluster r and omized trials ( CRTs ) in health research . In the introductory paper in this series , Weijer and colleagues set out six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation . This paper addresses the third of the questions posed , namely , does clinical equipoise apply to CRTs in health research ? The ethical principle of beneficence is the moral obligation not to harm needlessly and , when possible , to promote the welfare of research subjects . Two related ethical problems have been discussed in the CRT literature . First , are control groups that receive only usual care unduly disadvantaged ? Second , when accumulating data suggests the superiority of one intervention in a trial , is there an ethical obligation to act?In individually r and omized trials involving patients , similar questions are addressed by the concept of clinical equipoise , that is , the ethical requirement that , at the start of a trial , there be a state of honest , professional disagreement in the community of expert practitioners as to the preferred treatment . Since CRTs may not involve physician- research ers and patient-subjects , the applicability of clinical equipoise to CRTs is uncertain . Here we argue that clinical equipoise may be usefully grounded in a trust relationship between the state and research subjects , and , as a result , clinical equipoise is applicable to CRTs . Clinical equipoise is used to argue that control groups receiving only usual care are not disadvantaged so long as the evidence supporting the experimental and control interventions is such that experts would disagree as to which is preferred . Further , while data accumulating during the course of a CRT may favor one intervention over another , clinical equipoise supports continuing the trial until the results are likely to be broadly convincing , often coinciding with the planned completion of the trial . Finally , clinical equipoise provides research ethics committees with formal and procedural guidelines that form an important part of the assessment of the benefits and harms of  CRTs in health research OBJECTIVE To evaluate an educational intervention design ed to prevent traffic accidents among workers that use the bicycle for commuting . METHODS A longitudinal intervention study with a stepped wedge implementation was carried out between January 2006 and May 2007 . Five neighborhoods with distinct geographic characteristics were selected in the city of Pelotas , Brazil , and 42 census tracts were r and omly selected from these neighborhoods . All households were screened for male bicycle commuters , result ing in a sample of 1,133 individuals . The outcomes analyzed were " traffic accidents " and " near accidents " . The cyclists were interviewed monthly by phone to record traffic accidents and " near accidents " . Every 15 days , from the second month of study , a group of about 60 cyclists was invited to attend the intervention meeting that included an educational component ( a talk and a video presentation ) , distribution of a safety kit ( reflective belt & sash , reflective tape and an educational booklet ) and a bicycle breaks check-up ( maintenance performed if necessary ) . Poisson regression adjusted for time effect was used to assess the intervention effect . RESULTS Nearly 45 % of the cyclists did not attend the intervention . During the study period , 9 % of the study individuals reported a traffic accident and 88 % reported a " near accident " . In total there were 106 accidents and 1,091 near accidents . There was no effect observed from the intervention on either of the outcomes . CONCLUSIONS The intervention tested was not capable of reducing traffic accidents among bicycle commuters . Lack of interest in safety by commuters and external factors , such as road design and motorist behavior , may have together influenced this result R and omized trials in which the unit of r and omization is a community , worksite , school or family are becoming widely used in the evaluation of life-style interventions for the prevention of disease . The increasing interest in adopting a cluster r and omization design is being matched by rapid method ological developments . In this paper we describe several of these developments . Brief mention is also made of issues related to economic analysis and to the planning and conduct of meta-analyses for cluster r and omization trials . Recommendations for reporting are also discussed Background Indigenous Australians suffer a disproportionate burden of preventable chronic disease compared to their non-Indigenous counterparts – much of it diet-related . Increasing fruit and vegetable intakes and reducing sugar-sweetened soft-drink consumption can reduce the risk of preventable chronic disease . There is evidence from some general population studies that subsidising healthier foods can modify dietary behaviour . There is little such evidence relating specifically to socio-economically disadvantaged population s , even though dietary behaviour in such population s is arguably more likely to be susceptible to such interventions .This study aims to assess the impact and cost-effectiveness of a price discount intervention with or without an in-store nutrition education intervention on purchases of fruit , vegetables , water and diet soft-drinks among remote Indigenous communities . Methods / Design We will utilise a r and omised multiple baseline ( stepped wedge ) design involving 20 communities in remote Indigenous Australia . The study will be conducted in partnership with two store associations and twenty Indigenous store boards . Communities will be r and omised to either i ) a 20 % price discount on fruit , vegetables , water and diet soft-drinks ; or ii ) a combined price discount and in-store nutrition education strategy . These interventions will be initiated , at one of five possible time-points , spaced two-months apart . Weekly point-of-sale data will be collected from each community store before , during , and for six months after the six-month intervention period to measure impact on purchasing of discounted food and drinks . Data on physical , social and economic factors influencing weekly store sales will be collected in order to identify important covariates . Intervention fidelity and mediators of behaviour change will also be assessed . Discussion This study will provide original evidence on the effectiveness and cost-effectiveness of price discounts with or without an in-store nutrition education intervention on food and drink purchasing among a socio-economically disadvantaged population in a real-life setting .Trial registration Australian New Zeal and Clinical Trials Registry : This article is part of a series of papers examining ethical issues in  cluster r and omized 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 r and omization , cluster-level interventions , and cluster size . In this paper , we call for a more restrictive underst and ing 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 r and omization 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 practice s , and schools . In these setting s , permission to access the organization relies on re source implication s and adherence to institutional policies Background Comprehensive rehabilitation , involving health professionals from various disciplines , is widely used as an adjunct to pharmacological and surgical treatment in people with rheumatic diseases . However , the evidence for the clinical - and cost-effectiveness of such interventions is limited , and the majority of those who receive rehabilitation are back to their initial health status six to 12 months after discharge . Methods / design To evaluate the goal attainment , health effects and cost-effectiveness of a new rehabilitation programme compared to current traditional rehabilitation programmes for people with rheumatic diseases , a stepped-wedge cluster r and omized trial will be performed . Patients admitted for rehabilitation at six centres in the south-eastern part of Norway will be invited to participate . In the trial , six participating centres will switch from a control ( current rehabilitation programme ) to an intervention phase ( the new rehabilitation programme ) in a r and omized order . Supported by recent research , the new programme will be a supplement to the existing programme at each centre , and will comprise four elements design ed to enhance and support lifestyle changes introduced in the rehabilitation period : structured goal -planning , motivational interviewing , a self-help booklet and four follow-up telephone calls during the first five months following discharge . The primary outcome will be health-related quality of life and goal attainment , as measured by the Patient Generated Index directly before and after the rehabilitation stay , as well as after six and 12 months . Secondary outcomes will include self-reported pain , fatigue , a global assessment of disease activity and motivation for change ( measured on 11-point numeric ratings scales ) , health-related quality of life as measured by the Short Form 36 Health Survey ( SF-36 ) and utility assessed by the SF6D utility index . The main analysis will be on an intention to treat basis and will assess the clinical - and cost-effectiveness 
    Output:
    
In stepped wedge trials , equipoise is likely to lie in the degree of effect , effectiveness in a specific operational milieu , and the balance of benefit and harm , including the social value of better evaluation .
The design is advantageous when simultaneous roll-out is impractical and when it increases the acceptability of using counterfactuals .
Conclusions The logistic convenience of phased implementation is context -dependent , and may be vitiated by the additional requirements of phasing .