Design of treatment trials for functional gastrointestinal disorders. Seeing the forests and the trees—innovative approaches to exploring heterogeneity in systematic reviews of complex interventions to enhance health system decision-making: a protocol Methodological index for non‐randomized studies (MINORS): development and validation of a new instrument Impact of clinical registries on quality of patient care and health outcomes: protocol for a systematic review Sustained effects of online genetics education: a randomized controlled trial on oncogenetics CONSORT adoption and quality of reporting of randomized controlled trials: a systematic analysis in two dermatology journals Evaluating the Quality of Randomized Controlled Trials that Examine the Efficacy of Natural Health Products: A Systematic Review of Critical Appraisal Instruments Balancing the strengths of systematic and narrative reviews. Designing clinical trials for kidney cancer based on newly developed prognostic and predictive tools Systematic review of outcome measures in pediatric eosinophilic esophagitis treatment trials CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomized Trials Improving the reporting of randomised trials: the CONSORT Statement and beyond. The genetic family history as a risk assessment tool in internal medicine Impact of an interprofessional shared decision-making and goal-setting decision aid for patients with diabetes on decisional conflict – study protocol for a randomized controlled trial Clinical trials for predictive medicine. The Development and Validation of a Quality Assessment and Rating of Technique for Injections of the Spine (AQUARIUS) Methodological quality of systematic reviews in subfertility: a comparison of Cochrane and non-Cochrane systematic reviews in assisted reproductive technologies.
Until recently many clinical trials of functional gastrointestinal disorders ( FGIDs ) suffered from important weaknesses in trial design , study execution , and data analysis . This makes it difficult to determine whether truly efficacious therapies exist for these disorders . One of the important method ologic problems is the absence of vali date d outcome measures and lack of consensus among stakeholders on how to measure outcome . Currently much of the effort is being put into the development of vali date d outcome measures for several of the FGIDs . The r and omized , controlled trial with parallel groups is the design of choice . In this report , guidelines are given for the basic architecture of intervention studies of FGIDs . Further studies on design issues are required to ensure the recommendations will become evidence based in the future Background To improve quality of care and patient outcomes , health system decision-makers need to identify and implement effective interventions . An increasing number of systematic review s document the effects of quality improvement programs to assist decision-makers in developing new initiatives . However , limitations in the reporting of primary studies and current meta- analysis methods ( including approaches for exploring heterogeneity ) reduce the utility of existing syntheses for health system decision-makers . This study will explore the role of innovative meta- analysis approaches and the added value of enriched and up date d data for increasing the utility of systematic review s of complex interventions . Methods / Design We will use the data set from our recent systematic review of 142 r and omized trials of diabetes quality improvement programs  to evaluate novel approaches for exploring heterogeneity . These will include exploratory methods , such as multivariate meta-regression analyses and all-subsets combinatorial meta- analysis . We will then up date our systematic review to include new trials and enrich the data set by surveying authors of all included trials . In doing so , we will explore the impact of variables not , reported in previous publications , such as details of study context , on the effectiveness of the intervention . We will use innovative analytical methods on the enriched and up date d data set to identify key success factors in the implementation of  quality improvement interventions  for diabetes . Decision-makers will be involved throughout to help identify and prioritize variables to be explored and to aid in the interpretation and dissemination of results . Discussion This study will inform future systematic review s of complex interventions and describe the value of enriching and updating data for exploring heterogeneity in meta- analysis . It will also result in an up date d comprehensive systematic review of diabetes quality improvement interventions that will be useful to health system decision-makers in developing interventions to improve outcomes for people with diabetes . Systematic review registration PROSPERO registration no. Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument Introduction Many developed countries have regional and national clinical registries aim ed at improving health outcomes of patients diagnosed with particular diseases or cared for in particular healthcare setting s.  Clinical quality registries ( CQRs ) are clinical registries established with the purpose of monitoring quality of care and providing feedback to improve health outcomes . The aim of this systematic review is to underst and the impact of CQRs on ( 1 ) mortality/survival ; ( 2 ) measures of outcome that reflect a process or outcome of healthcare ; ( 3 ) healthcare utilisation and ( 4 ) costs . Methods and analysis The PRISMA -P methodology , checklist and st and ard strategy using predefined inclusion and exclusion criteria and structured data abstract ion tools will be followed . A search of the electronic data bases MEDLINE , EMBASE , Cochrane Central Register of Controlled Trials ( CENTRAL ) and CINAHL will be undertaken , in addition to Google Scholar and grey literature , to identify studies in English covering the period January 1980 to December 2014 . Case – control , cohort , r and omised controlled trials and controlled clinical trials which describe the registry as an intervention will be eligible for inclusion . Narrative synthesis of study findings will be conducted , guided by a conceptual framework developed to analyse the outcome measure of the registry using defined criteria . If sufficient studies are identified with a similar outcome of interest and measure using the same comparator and time of interval , results will be pooled for r and om-effects meta- analysis . Test for heterogeneity and sensitivity analysis will be conducted . To identify reporting bias , forest plots and funnel plots will be created and , if required , Egger 's test will be conducted . Ethics and dissemination Ethical approval is not required as primary data will not be collected . Review results will be published as a part of thesis , peer- review ed journal and conferences . Trial registration number CRD42015017319 Medical professionals are increasingly expected to deliver genetic services in daily patient care . However , genetics education is considered to be suboptimal and in urgent need of revision and innovation . We design ed a Genetics e-learning Continuing Professional Development ( CPD ) module aim ed at improving general practitioners ’ ( GPs ’ ) knowledge about oncogenetics , and we conducted a r and omized controlled trial to evaluate the outcomes at the first two levels of the Kirkpatrick framework ( satisfaction , learning and behavior ) . Between September 2011 and March 2012 , a parallel-group , pre- and post-retention ( 6-month follow-up ) controlled group intervention trial was conducted , with repeated measurements using vali date d question naires . Eighty Dutch GP volunteers were r and omly assigned to the intervention or the control group . Satisfaction with the module was high , with the three item ’s scores in the range 4.1–4.3 ( 5-point scale ) and a global score of 7.9 ( 10-point scale ) . Knowledge gains post test and at retention test were 0.055 ( P<0.05 ) and 0.079 ( P<0.01 ) , respectively , with moderate effect sizes ( 0.27 and 0.31 , respectively ) . The participants appreciated applicability in daily practice of knowledge aspects ( item scores 3.3–3.8 , five-point scale ) , but scores on self-reported identification of disease , referral to a specialist and knowledge about the possibilities/ limitations of genetic testing were near neutral ( 2.7–2.8 , five-point scale ) . The Genetics e-learning CPD module proved to be a feasible , satisfactory and clinical ly applicable method to improve oncogenetics knowledge . The educational effects can inform further development of online genetics modules aim ed at improving physicians ’ genetics knowledge and could potentially be relevant internationally and across a wider range of potential audiences Background CONSORT ( Consoli date d St and ards for Reporting Trials ) guidelines were constructed to ensure optimal reporting quality of r and omized controlled trials ( RCTs ) . The purpose of this project was to conduct a systematic review to identify instruments design ed to evaluate the quality of r and omized controlled trials ( RCTs ) of natural health products ( NHPs ) . Instruments were examined for inclusion of items assessing methods , identity and content of the NHP , generalizability of results and instructions for use . Online data bases , websites , textbooks and reference lists were search ed to identify instruments . Relevance assessment and data extraction of articles were completed by two investigators and disagreements were settled by the third investigator . Data were analyzed using descriptive statistics . Of the 4442 citations identified , 29 were potentially relevant with 16 meeting the criteria for inclusion . None of the instruments stated they were vali date d ; content in the four areas of interest varied considerably . The most common items included r and omization sequence generation ( 100 % ) , blinding ( 100 % ) , allocation concealment ( 75 % ) and participant flow ( 75 % ) . Only nine of the NHP instruments included at least one item to appraise the specific content of the NHP . The CONSORT Statement for Herbal Interventions most closely addressed the four areas of interest ; however , this instrument was specific for herbs . There is a need for the development of a vali date d instrument for assessment of the quality of RCTs that would be useful for herbs as well as other NHPs The m and ate of Human Reproduction Up date involves several roles : ( i ) to provide a synthesis of evidence that can aid scientists and clinicians in their daily work ; ( ii ) to help reproductive specialists underst and concepts from related disciplines ; and ( iii ) to summarize current knowledge generated by basic science as the foundation of future scientific and clinical advancement . Given that review and synthesis are central to good scientific and clinical practice , and that a grasp of the current state of knowledge is a prerequisite to design ing new studies , it is pertinent to ask which review s are most likely to fulfil the needs of readers . A related question concerns whether systematic review s meet the needs of all review topics and all readers . Summarizing evidence or knowledge is a difficult problem in reproductive medicine , as in other branches of science and medical care ( Eddy et al. , 1992 ) . For each question there may be multiple studies that use different design s and inclusion criteria . For clinical questions , the interventions , outcomes and measures of effect may vary : the effect measures in treatment studies include odds ratios , relative risks and absolute differences . For scientific questions , the experimental species , models and design s may differ . Moreover , it is always uncertain whether all of the relevant evidence has been evaluated . Even when the search has been exhaustive , there are no simple guides on how to interpret conflicting results and whether to accept apparently outlying studies . The choices that the review er makes to address the variable conditions and uncertainties may be conservative , strict and exclusive , or liberal , open and inclusive . The decisions made by the review er may not be consistent throughout and these choices may or may not satisfy the reader who seeks out the review to address a clinical or research question . Faced with uncertainty and doubt , readers nonetheless must form an impression of the evidence and synthesize the state of knowledge in order to address the clinical or research question that stimulated their interest in the review . We argue that the reader is better served when the choices made in the review , regardless of whether they are strict or open , should be explicit , transparent , clearly stated and reproducible by interested readers . This list of objectives for review s is more easily satisfied by systematic review s , which use explicit methods to method ically search , critically appraise and synthesize the available literature on a specific issue . The question or issue need not be clinical : indeed , the concept evolved primarily in psychology studies ( Light and Pillemer , 1984 ) . The systematic review attempts to reduce review er bias through the use of objective , reproducible criteria to select relevant individual publications and assess their validity . A systematic review may include a meta- analysis or statistical summary of the individual study results : the aggregate of effects from several studies yields an average treatment effect that is more precise than the individual study results ( Schlesselman and Collins , 2003 ) . Thus , the systematic review involves explicit , transparent methods which are clearly stated , and reproducible by others . Whether a systematic review of r and omized controlled trials adheres to the guidelines can easily be evaluated by means of a widely used checklist ( the QUORUM statement ) ( Moher et al. , 1999 ) . The strengths of the systematic review include the narrow focus of the question , the comprehensive search for evidence , the criterion-based selection of relevant evidence , the rigorous appraisal of validity , the objective or quantitative summary , and the evidence -based inferences ( Cook et al. , 1997 ) . For some review topics , however , the strengths of the systematic review may turn into weaknesses . The primary problem is that the narrow focus and prescribed methods of the systematic review do not allow for comprehensive coverage . For example , the historical review is an irreplaceable means of tracing the development of a scientific principle or clinical concept , but the narrative thread could be lost in the strict rules of systematic review . As other examples , it would be burdensome to apply systematic methods to a survey on  aneuploidy and fertility in the aging female or to an assessment of mouse knockout models and polycystic ovarian phenotype . Such topics would require the wider scope of a traditional narrative review , in Human Reproduction Up date , Vol.11 , No.2 pp . 103–104 , 2005 doi:10.1093/humupd/dmh058 Advance Access publication December 23 , Several advances have been made in our underst and ing of the molecular aberrations in renal cell carcinoma that have led to the identification of novel prognostic and predictive biomarkers . At the same time , several novel agents targeting these molecular aberrations have shown promising efficacy in the therapy of advanced renal cancer . As these agents enter more advancedstage clinical trials , efforts must be made to integrate exploration of these novel prognostic and predictive markers into clinical trial design . These elements then can be combined with more traditional prognostic features to form more robust prognostic models . Finally , predictive markers and prognostic models should be vali date d prospect ively , either as part of clinical trials design ed specifically for that purpose or as part of large phase-3 trials . Once vali date d , these features can be used to best inform prognosis and guide therapy based on individual patient characteristics Abstract Background Heterogeneity has been noted in the selection and reporting of disease-specific , pediatric outcomes in r and omized controlled trials ( RCTs ) . The consequence is invalid results or difficulty comparing results across trials . The primary objective of this systematic review was to assess primary outcome and outcome measure selection and reporting , in pediatric eosinophilic esophagitis ( EoE ) treatment trials . As secondary objectives , we compared trial disease definition to established concensus guidelines , and the efficacy of current EoE treatments . Methods We search ed MEDLINE , EMBASE , The Cochrane Library , Cochrane Central Register of Controlled Trials ( CENTRAL ) , and CINAHL since 2001 . We also search ed clinical trial registries ( portal.nihr.ac.uk ; clinical trials.gov ; is rct n.com ; and anzctr.org.au ) and references of included studies . We included RCTs of EoE treatment in patients 0–18 years . Two authors independently assessed articles . Results Eleven studies met inclusion criteria . All identified primary outcomes , however , of 9 unique primary outcomes , only 2 were used in more than one study . In total , 25 unique primary and secondary outcome measures were employed for pediatric EoE treatment trials . Measurement properties and rationale for their selection was rarely provided . Uptake of consensus-based diagnostic criteria was 25 % in trials initiated after 2011 . Due to the small number and heterogeneity of studies obtained , no meta- analysis of treatment efficacy could be undertaken . This SR was limited to exclusively pediatric RCTs . Conclusions The results of this study confirm the need for a st and ardized set of core outcomes that are universally reported in pediatric EoE trials . Consistent disease definition and st and ardized outcome reporting will facilitate meta-analyses across similar trials and inform future clinical decision-making . Systematic review registration number The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . An extensive and growing number of review s of the published literature demonstrate that health research publications have frequent deficiencies . Of particular concern are poor reports of r and omised trials , which make it difficult or impossible for readers to assess how the research was conducted , to evaluate the reliability of the findings , or to place them in the context of existing research evidence . As a result , published reports of trials often can not be used by clinicians to inform patient care or to inform public health policy , and the data can not be included in systematic review s. Reporting guidelines are design ed to identify the key information that research ers should include in a report of their research . We describe the history of reporting guidelines for r and omised trials culminating in the CONSORT Statement in 1996 . We detail the subsequent development and extension of CONSORT and consider related initiatives aim ed at improving the reliability of the medical research literature Purpose : The study goals were to ( 1 ) determine the proportion of unselected individuals at increased risk for diseases with known genetic components and ( 2 ) compare the documentation and quality of risk assessment between a question naire , a pedigree interview , and chart review . Methods : Seventy-eight patients seen in a division of internal medicine were r and omized into two groups , which completed a question naire or underwent a pedigree interview . Chart notes were compared to both study tools . Results : Sixty-two ( 79.5 % ) of the 78 participants scored at increased risk for at least one category . Either of the two study tools found significantly more people at high risk ( 48/78 , 61.5 % ) than the chart review ( 31/78 , 39.7 % ) ( P = 0.01 ) . Conclusions : Approximately 20 % of patients in an unselected internal medicine practice were at an increased risk that was not documented in review ed chart notes . Targeted family history analysis reveals patients who require increased medical surveillance , preventive measures , or genetic counseling/testing Background Competing health concerns present real obstacles to people living with diabetes and other chronic diseases as well as to their primary care providers . Guideline implementation interventions rarely acknowledge this , leaving both patients and providers feeling overwhelmed by the volume of recommended actions . Interprofessional ( IP ) shared decision-making ( SDM ) with the use of decision aids may help to set treatment priorities . We developed an evidence -based SDM intervention for patients with diabetes and other conditions that was framed by the IP-SDM model and followed a user-centered approach . Our objective in the present study is to pilot an IP-SDM and goal - setting toolkit following the Knowledge-to-Action Framework to assess ( 1 ) intervention fidelity and the feasibility of conducting a larger trial and ( 2 ) impact on decisional conflict , diabetes distress , health-related quality of life and patient assessment of chronic illness care . Methods / Design A two-step , parallel-group , clustered r and omized controlled trial ( RCT ) will be conducted , with the primary goal being to assess intervention fidelity and the feasibility of conducting a larger RCT . The first step is a provider-directed implementation only ; the second ( after a 6-month delay ) involves both provider- and patient-directed implementation . Half of the clusters will be assigned to receive the IP-SDM toolkit , and the other will be assigned to be mailed a diabetes guidelines summary . Individual interviews with patients , their family members and health care providers will be conducted upon trial completion to explore toolkit use . A secondary purpose of this trial is to gather estimates of the toolkit ’s impact on decisional conflict . Secondary outcomes include diabetes distress , quality of life and chronic illness care , which will be assessed on the basis of patient-completed question naires of vali date d scales at baseline and at 6 and 12 months . Multilevel hierarchical regression models will be used to account for the clustered nature of the data . Discussion An individualized approach to patients with multiple chronic conditions using SDM and goal setting is a desirable strategy for achieving guideline -concordant treatment in a patient-centered fashion . Our pilot trial will provide insights regarding strategies for the routine implementation of such interventions in clinical practice , and it will offer an assessment of the impact of this approach . Trial registration Clinical trials.gov Identifier : NCT02379078 . Date of Registration : 11 February 2015 Developments in biotechnology and genomics are providing a biological basis for the heterogeneity of clinical course and response to treatment that have long been apparent to clinicians . The ability to molecularly characterize human diseases presents new opportunities to develop more effective treatments and new challenges for the design and analysis of clinical trials . In oncology , treatment of broad population s with regimens that benefit a minority of patients is less economically sustainable with expensive molecularly targeted therapeutics . The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of r and omized clinical trials as a reliable basis for predictive medicine . We review prospect i ve design s for the development of new therapeutics and predictive biomarkers to inform their use . We cover design s for a wide range of setting s. At one extreme is the development of a new drug with a single c and i date biomarker and strong biological evidence that marker negative patients are unlikely to benefit from the new drug . At the other extreme are Phase III clinical trials involving both genome-wide discovery of a predictive classifier and internal validation of that classifier . We have outlined a prediction-based approach to the analysis of r and omized clinical trials that both preserves the Type I error and provides a reliable internally vali date d basis for predicting which patients are most likely or unlikely to benefit from the new regimen Background and Objectives Systematic review s evaluate the utility of procedural interventions of the spine , including epidural steroid injections ( ESIs ) . However , existing quality assessment tools either fail to account for proper technical quality and patient selection or are not vali date d. We developed and vali date d a simple scale for ESIs to provide a quality assessment and rating of technique for injections of the spine ( AQUARIUS ) . Methods Seven experts generated items iteratively based on prior ESI technique studies and professional judgment . Following testing for face and content validity , a 17-item instrument was used by 8 raters from 2 different background s to assess 12 r and omized controlled trials , selected from 3 different categories . Using frequency of assessment , a 12-item instrument was also generated . Both instruments underwent reliability ( intraclass correlation coefficient ) , validity ( ability to distinguish “ low , ” “ r and om , ” and “ high ” study categories ) , and diagnostic accuracy ( receiver operating characteristics ) testing . Results Both 17- and 12-item instruments were scored consistently by raters regardless of background , with overall intraclass correlation coefficients of 0.72 ( 95 % confidence interval [ CI ] , 0.53–0.89 ) and 0.71 ( 95 % CI , 0.51–0.89 ) , respectively . Both instruments discriminated between clinical trials from all 3 categories . Diagnostic accuracy was similar for the 2 instruments , with areas under receiver operating characteristic curves of 0.89 ( 95 % CI , 0.82–0.96 ) and 0.90 ( 95 % CI , 0.82–0.97 ) , respectively . Conclusions The instrument in both 17- and 12-item formats demonstrates good reliability and diagnostic accuracy in rating ESI studies . As a complement to other tools that assess bias , the instrument may improve the ability to evaluate evidence for systematic review s and improve clinical trial design STUDY QUESTION Are there differences in the method ological quality of Cochrane systematic review s ( CRs ) and non-Cochrane systematic review s ( NCRs ) of assisted reproductive technologies ? SUMMARY ANSWER CRs on assisted reproduction are of higher method ological quality than similar review s published in other journals . WHAT IS KNOWN ALREADY The quality of systematic review s varies . STUDY DESIGN , SIZE AND DURATION This was a cross-sectional study of 30 CR and 30 NCR systematic review s that were r and omly selected from the eligible review s identified from a literature search for the years 2007 - 2011 . MATERIAL S , SETTING AND METHODS We extracted data on the reporting and method ological characteristics of the included systematic review s. We assessed the method ological quality of the review s using the 11-domain Measurement Tool to Assess the Method ological Quality of Systematic Review s ( AMSTAR ) tool and subsequently compared CR and NCR systematic review s. MAIN RESULTS AND THE ROLE OF CHANCE The AMSTAR quality assessment found that CRs were superior to NCRs . For 10 of 11 AMSTAR domains , the requirements were met in > 50 % of CRs , but only 4 of 11 domains showed requirements being met in > 50 % of NCRs . The strengths of CRs are the a priori study design , comprehensive literature search , explicit lists of included and excluded studies and assessment s of internal validity . Significant failings in the CRs were found in duplicate study selection and data extraction ( 67 % meeting requirements ) , assessment for publication bias ( 53 % meeting requirements ) and reporting of conflicts of interest ( 47 % meeting requirements ) . NCRs were more likely to contain method ological weaknesses as the majority of the domains showed < 40 % of review s meeting requirements , e.g. a priori study design ( 17 % ) , duplicate study selection and data extraction ( 17 % ) , assessment of study quality ( 27 % ) , study quality in the formulation of conclusions ( 23 % ) and reporting of conflict of interests ( 10 % ) . LIMITATIONS , REASONS FOR CAUTION The AMSTAR assessment can only judge what is reported by authors . Although two of the five authors are involved in the production of CRs , the risk of bias was reduced by not involving these authors in the assessment of the systematic review quality . WIDER IMPLICATION S OF THE FINDINGS Not all systematic review s are equal . The reader needs to consider the quality of the systematic review when they consider the results and the conclusions of a systematic review . STUDY FUNDING /COMPETING INTEREST(S ) There are no conflicts with any commercial organization . Funding was provided for the students by the summer studentship programme of the Faculty of Medical and Health Sciences of the University of Auckl and
No single vali date d outcome measure encompassed all potential patient benefits from using a CGS .
A variety of different domains were identified , including anxiety and depression , coping , decision-making , distress , family environment , health status , knowledge , mood , perception of risk , perceived personal control , psychological impact , quality of life , satisfaction and expectations , self-esteem , spiritual well-being , and worry .
Some important aspects of patient benefit from CGS are not covered by existing outcome measures .
OBJECTIVE This systematic review aim ed to inform research ers and policymakers about what vali date d outcome measures are available to evaluate clinical genetics services ( CGS ) and the need for new measures .