title: The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials Selenium supplementation and lung cancer incidence: an update of the nutritional prevention of cancer trial. Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Organisation of a proposed Cochrane Diet and Nutrition Field Is There a “Best” Way to Detect and Minimize Publication Bias? Oral calcium supplementation and blood pressure: an overview of randomized controlled trials. Reporting Randomized, Controlled Trials of Herbal Interventions: An Elaborated CONSORT Statement
abstract: To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Interest in the chemopreventive effects of the trace element selenium has spanned the past three decades . Of > 100 studies that have investigated the effects of selenium in carcinogen-exposed animals , two-thirds have observed a reduction in tumor incidence and /or preneoplastic endpoints ( G. F. Combs and S. B. Combs , The Role of Selenium in Nutrition Chapter 10 , pp . 413 - 462 . San Diego , CA : Academic Press , 1986 , and B. H. Patterson and O. A. Lev and er , Cancer Epidemiol . Biomark . Prev . , 6 : 63 - 69 , 1997 ) . The Nutritional Prevention of Cancer Trial , a r and omized clinical trial reported by Clark et al. ( L. C. Clark et al. , JAMA , 276 : 1957 - 1963 , 1996 ) , showed as a secondary end point , a statistically significant decrease in lung cancer incidence with selenium supplementation . The adjusted hazard ratio ( HR ) was 0.56 [ 95 % confidence interval ( CI ) , 0.31 - 1.01 ; P = 0.05 ] . These results were based on active follow-up of 1312 participants . This re analysis used an extended Nutritional Prevention of Cancer Trial participant follow-up through the end of the blinded clinical trial on February 1 , 1996 . The additional 3 years added 8 cases to the selenium-treated group and 4 cases to the placebo group , and increased follow-up to 7.9 years . The relative risk of 0.70 ( 95 % CI , 0.40 - 1.21 ; P = 0.18 ) is not statistically significant . Whereas the overall adjusted HR is not significant ( HR = 0.74 ; 95 % CI , 0.44 - 1.24 ; P = 0.26 ) , and the HR for current and former smokers was not significant , the trend is toward a reduction in risk of incident lung cancer with selenium supplementation . In a subgroup analysis there was a nominally significant HR among subjects with baseline plasma selenium in the lowest tertile ( HR = 0.42 ; 95 % CI , 0.18 - 0.96 ; P = 0.04 ) . The analysis for the middle and highest tertiles of baseline showed HRs of 0.91 and 1.25 . The current re analysis indicates that selenium supplementation did not significantly decrease lung cancer incidence in the full population , but a significant decrease among individuals with low baseline selenium concentrations was observed BACKGROUND A meta- analysis of 19 trials suggested a small increase in the risk of all-cause mortality with high-dose vitamin E supplementation . Little is known , however , about the relation between mortality and circulating concentrations of vitamin E result ing from dietary intake , low-dose supplementation , or both . OBJECTIVE We examined whether baseline serum alpha-tocopherol concentrations are associated with total and cause-specific mortality . DESIGN A prospect i ve cohort study of 29 092 Finnish male smokers aged 50 - 69 y who participated in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention ( ATBC ) Study was carried out . Fasting serum alpha-tocopherol was measured at baseline by using HPLC . Only 10 % of participants reported vitamin E supplement use at baseline , and thus serum concentrations of vitamin E mainly reflected dietary intake and other host factors . Risks of total and cause-specific mortality were estimated by using proportional hazards models . RESULTS During up to 19 y of follow-up , 13 380 deaths ( including 4518 and 5776 due to cancer and cardiovascular disease , respectively ) were identified . Men in the higher quintiles of serum alpha-tocopherol had significantly lower risks of total and cause-specific mortality than did those in the lowest quintile [ relative risk ( RR ) = 0.82 ( 95 % CI : 0.78 , 0.86 ) for total mortality and 0.79 ( 0.72 , 0.86 ) , 0.81 ( 0.75 , 0.88 ) , and 0.70 ( 0.63 , 0.79 ) for deaths due to cancer , cardiovascular disease , and other causes , respectively ; P for trend for all < 0.0001 ] . Cubic regression spline analysis of continuous serum alpha-tocopherol values indicated greater risk reductions with increasing concentrations up to approximately 13 - 14 mg/L , after which no further benefit was noted . CONCLUSION Higher circulating concentrations of alpha-tocopherol within the normal range are associated with significantly lower total and cause-specific mortality in older male smokers The Nutritional Prevention of Cancer Trial was a r and omized , clinical trial design ed to evaluate the efficacy of selenium as selenized yeast ( 200 microg daily ) in preventing the recurrence of nonmelanoma skin cancer among 1312 residents of the Eastern United States . Original secondary analyses through December 31 , 1993 showed striking inverse associations between treatment and the incidence of total [ hazard ratio ( HR ) = 0.61 , 95 % confidence interval ( CI ) = 0.46 - 0.82 ] , lung , prostate , and colorectal cancer and total cancer mortality . This report presents results through February 1 , 1996 , the end of blinded treatment . Effect modification by baseline characteristics is also evaluated . The effects of treatment overall and within subgroups of baseline age , gender , smoking status , and plasma selenium were examined using incidence rate ratios and Cox proportional hazards models . Selenium supplementation reduced total ( HR = 0.75 , 95 % CI = 0.58 - 0.97 ) and prostate ( HR = 0.48 , 95 % CI = 0.28 - 0.80 ) cancer incidence but was not significantly associated with lung ( HR = 0.74 , 95 % CI = 0.44 - 1.24 ) and colorectal ( HR = 0.46 , 95 % CI = 0.21 - 1.02 ) cancer incidence . The effects of treatment on other site-specific cancers are also described . The protective effect of selenium was confined to males ( HR = 0.67 , 95 % CI = 0.50 - 0.89 ) and was most pronounced in former smokers . Participants with baseline plasma selenium concentrations in the lowest two tertiles ( < 121.6 ng/ml ) experienced reductions in total cancer incidence , whereas those in the highest tertile showed an elevated incidence ( HR = 1.20 , 95 % CI = 0.77 - 1.86 ) . The Nutritional Prevention of Cancer trial continues to show a protective effect of selenium  on cancer incidence , although not all site-specific cancers exhibited a reduction in incidence . This treatment effect was restricted to males and to those with lower baseline plasma selenium concentrations BACKGROUND It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer . To date , however , the published results of r and omized , placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect . We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population . METHODS The Supplementation en Vitamines et Mineraux Antioxydants ( SU.VI.MAX ) study is a r and omized , double-blind , placebo-controlled primary prevention trial . A total of 13 017 French adults ( 7876 women aged 35 - 60 years and 5141 men aged 45 - 60 years ) were included . All participants took a single daily capsule of a combination of 120 mg of ascorbic acid , 30 mg of vitamin E , 6 mg of beta carotene , 100 mug of selenium , and 20 mg of zinc , or a placebo . Median follow-up time was 7.5 years . RESULTS No major differences were detected between the groups in total cancer incidence ( 267 [ 4.1 % ] for the study group vs 295 [ 4.5 % ] for the placebo group ) , ischemic cardiovascular disease incidence ( 134 [ 2.1 % ] vs 137[2.1 % ] ) , or all-cause mortality ( 76 [ 1.2 % ] vs 98 [ 1.5 % ] ) . However , a significant interaction between sex and group effects on cancer incidence was found ( P = .004 ) . Sex-stratified analysis showed a protective effect of antioxidants in men ( relative risk , 0.69 [ 95 % confidence interval [ CI ] , 0.53 - 0.91 ] ) but not in women ( relative risk , 1.04 [ 95 % CI , 0.85 - 1.29 ] ) . A similar trend was observed for all-cause mortality ( relative risk , 0.63 [ 95 % CI , 0.42 - 0.93 ] in men vs 1.03 [ 95 % CI , 0.64 - 1.63 ] in women ; P = .11 for interaction ) . CONCLUSIONS After 7.5 years , low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women . Supplementation may be effective in men only because of their lower baseline status of certain antioxidants , especially of beta carotene The Cochrane Collaboration helps people make well-informed decisions about health care by preparing , maintaining and promoting the accessibility of systematic review s of the effects of healthcare interventions . In all , 51 Cochrane Review Groups are responsible for preparing and maintaining the review s. Most of these Review Groups are problem-based . However , there are a number of areas or dimensions of health care , such as the setting of care ( eg primary care ) or the type of patient/consumer ( eg older persons ) , that can not be usefully conceptualised as ‘ health problems ’ . In order to reflect the interests of these dimensions , or ‘ fields ’ , of health care more effectively , the Cochrane Collaboration created another type of entity : Cochrane Fields or Networks . The core functions of these Fields are described . It is proposed that a new Cochrane Subfield for Diet and Nutrition should be set up to attract a cadre of new review ers in order to ensure the proper representation of diet and nutrition expertise in the relevant Collaborative Review Groups . The method ological pitfalls of the use of nonr and omised studies will be a key issue for the new Subfield , since the focus of the Cochrane Collaboration 's programme of search ing data bases , journals and conference proceedings has been on the identification of reports of r and omised controlled trials ( RCTs ) . Some of these sources will be need to be search ed again for non- RCT studies . The financial considerations of establishing of a Cochrane Subfield for Diet and Nutrition are discussed Using 14 meta-analyses that included both published ( n = 199 ) and unpublished ( n = 50 ) r and omized trials , we evaluated the utility of different analytical approaches to detect , assess robustness , and minimize publication bias in meta- analysis . The rank correlation and graphical tests indicated funnel plot asymmetry in 3 and 7 of the 14 meta-analyses , respectively . The file drawer number estimates using Iyengar-Greenhouse method were between 1.5 and 4.7 times smaller compared to Rosenthal ’s estimates . The median difference between the Trim and Fill estimates and the actual number of missing studies was 1 ( range -4 , 6 ) . Weighted estimation methods adjusted for publication bias and provided estimates of intervention effect close to the reference st and ard , on average . We showed there are differences in the conclusions one would reach clinical ly based on the different analytical approaches dealing with publication bias . Our results also suggest that the appropriate use of these methods improves the reliability and accuracy of meta- analysis Over the past few years , several trials on the effect of oral calcium supplementation on blood pressure have been undertaken both in normal subjects and in patients with high blood pressure . Of these , 15 r and omized , controlled studies were review ed : 10 included patients with high blood pressure , three studied normal subjects , and two used a low-calcium diet for comparison . The 15 studies review ed investigated a total of nearly 400 peoples . No significant evidence for a supine blood pressure-lowering effect of oral calcium supplementation was found in the trials as a whole or in those trials carried out in hypertensives only . However , a small effect on st and ing blood pressure was detected . Our study indicates that the overall effect of oral calcium on blood pressure , if any , is very small and confined to st and ing blood pressure , it is , therefore , inappropriate to recommend oral calcium supplementation for the treatment of essential hypertension R and omized , controlled trials ( RCTs ) of herbal interventions often inadequately describe important aspects of their methods ( 1 - 4 ) . Although the quality of reporting of these trials may be improving with time , many still lack important information , particularly about the composition of the herbal intervention ( 4 , 5 ) . Crude herbal drugs are natural products and their chemical composition varies depending on several factors , such as geographic source of the plant material , climate in which it was grown , and time of harvest . Commercially available herbal medicinal products also vary in their content and concentration of chemical constituents from batch to batch and when products containing the same herbal ingredient are compared among manufacturers ( 6 - 14 ) . Even when herbal products are st and ardized for content of known active or marker compounds to achieve more consistent pharmaceutical quality , there is variation in the concentrations of other constituents . These variations can result in differences in pharmacologic activity in vitro ( 15 ) and in bioavailability in humans ( 16 ) . Mindful of these issues , we elaborated on the 22-item checklist of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement ( 17 ) to help authors and editors improve reporting of RCTs of herbal interventions . Methods We developed these reporting recommendations in 3 phases that included premeeting item generation , a consensus meeting , and postmeeting feedback . The individuals who participated are listed in the Appendix . To generate items , 1 investigator conducted telephone interviews of 16 participants with expertise in the method and reporting of RCTs ( 5 participants ) , pharmacognosy ( 4 participants ) , herbal medicinal products ( 5 participants ) , medical statistics ( 1 participant ) , and herbal product manufacturing ( 1 participant ) . The investigator asked participants to suggest revisions to existing CONSORT checklist items and also to additional items required for reporting trials of herbal interventions . He asked participants to nominate revisions or new items on the basis of empirical evidence that not reporting the item would bias estimates of treatment effect . When no empirical evidence was available , commonsense reasoning was acceptable . After completing all telephone calls , the investigator thematically grouped items and circulated them by e-mail to each participant for review . Fourteen participants attended the consensus meeting . The meeting began with a review of the premeeting checklist item suggestions . We emphasized minimizing item elaborations and additions and basing elaborations on evidence whenever possible . Each item suggestion was presented and followed by debate for its inclusion , deletion , or modification . This process was repeated until all items were review ed and a consensus emerged . After the consensus meeting , we circulated a draft summary report to all participants to ensure that it accurately represented decisions made during the consensus meeting . We then circulated the report to the wider CONSORT Group for input and revised it on the basis of their suggestions . Ethical approval was obtained from The University of Toronto Health Sciences Ethics Review Committee on 23 January 2004 . Financial support for the consensus meeting was provided by the Canadian Institutes of Health Research . The funding body had no role in the design , conduct , or analysis of this study and did not influence the decision to su bmi t the manuscript for publication . All research ers are independent of the funders . Results The group did not recommend any new CONSORT checklist items or modifications in the CONSORT flow diagram . We did , however , elaborate on 9 of the 22 CONSORT checklist items to enhance their relevance to trials of herbal interventions ( Table , Figure ; Appendix Table ) , including minor recommendations for 8 items ( item 1 [ title and abstract ] , item 2 [ background ] , item 3 [ participants ] , item 6 [ outcomes ] , item 15 [ baseline data ] , item 20 [ interpretation ] , item 21 [ generalizability ] , and item 22 [ overall evidence ] ) and detailed recommendations for 1 item ( item 4 [ interventions ] ) . Table . Proposed Elaboration of CONSORT Checklist Item 4 for Reporting R and omized , Controlled Trials of Herbal Medicine Interventions Figure . The high-pressure liquid chromatography chemical fingerprint for the extract of Ginkgo biloba L Appendix Table . Proposed Elaborations of CONSORT Items for R and omized , Controlled Trials of Herbal Medicine Interventions The Table shows the detailed recommendations for item 4 and an example of good reporting related to each recommendation . These recommendations begin with the words where applicable to indicate that all information suggested may not be applicable to every type of herbal medicine intervention . For example , an herbal medicinal product comprising crude herbal material ( for example , leaves and stems ) simply prepared as a tea or decoction does not require description of the type and concentration of solvent used and the ratio of herbal drug to extract ( item 4B.3 ) . Also , not every herbal medicine intervention will have a finished product or extract name or manufacturer ( item 4A.2 ) , but instead may be made by the investigators specifically for the study . In such circumstances , all methods used in preparing and formulating the product must be reported . Similarly , item 4F is not required for herbal interventions when the practitioner is not a part of the intervention . With these exceptions , we recommend that all information shown in the Table be reported for all herbal interventions . Discussion We developed recommendations to be used in conjunction with the existing CONSORT checklist when reporting RCTs of herbal interventions . In particular , we thought it imperative that reports of RCTs provide clear and complete descriptions of the herbal intervention . We think that our recommendations might also be relevant for reporting herbal interventions in other research design s , whether pre clinical ( for example , in vivo or in vitro ) or clinical ( for example , N of 1 trials ) , and refer interested readers to a detailed explanatory document that further describes each of our recommendations and provides additional examples of good reporting ( 22 ) . We hope that authors find our recommendations instructive and that journals will endorse their use and modify their instructions to authors accordingly
target: The reporting quality of SRs has improved 3 y after publication of SR reporting st and ards , but the reporting of nutrition variables has not .
  Improved adherence to consensus methods and reporting st and ards should improve the utility of nutrition SRs
background: BACKGROUND The quality of nutrition-related systematic review s ( SRs ) is an unstudied but important factor affecting their usefulness .
  OBJECTIVES The objectives were to evaluate the reporting quality of published SRs and to identify areas of improvement .