• The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.

    15 December 2017

    Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement-a reporting guideline published in 1999-there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.

  • The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.

    15 December 2017

    Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users.Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement--a reporting guideline published in 1999--there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions.The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.

  • Publication bias in clinical trials due to statistical significance or direction of trial results.

    15 December 2017

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

  • The COMET Handbook: version 1.0.

    12 December 2017

    The selection of appropriate outcomes is crucial when designing clinical trials in order to compare the effects of different interventions directly. For the findings to influence policy and practice, the outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. It is now widely acknowledged that insufficient attention has been paid to the choice of outcomes measured in clinical trials. Researchers are increasingly addressing this issue through the development and use of a core outcome set, an agreed standardised collection of outcomes which should be measured and reported, as a minimum, in all trials for a specific clinical area.Accumulating work in this area has identified the need for guidance on the development, implementation, evaluation and updating of core outcome sets. This Handbook, developed by the COMET Initiative, brings together current thinking and methodological research regarding those issues. We recommend a four-step process to develop a core outcome set. The aim is to update the contents of the Handbook as further research is identified.

  • Effects on patients of their healthcare practitioner's or institution's participation in clinical trials: a systematic review.

    12 December 2017

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

  • Serotonin receptor antagonists for highly emetogenic chemotherapy in adults.

    7 December 2017

    BACKGROUND: Serotonin receptor antagonists (5-HT(3) RAs) are used to control chemotherapy-induced emesis. Although they have the same general mechanism of action (blockade of serotonin receptors), they have different chemical structures and may have different effects. OBJECTIVES: To compare efficacy of different serotonin receptor antagonists (5-HT(3) RAs) in the control of acute and delayed emesis induced by highly emetogenic chemotherapy. SEARCH STRATEGY: We searched CENTRAL, the Specialised Register of the Cochrane PaPaS Group, PubMed, EMBASE, and LILACS databases. Our most recent search was in March 2009. SELECTION CRITERIA: Randomised trials comparing 5-HT(3) RAs in an adult cancer population. DATA COLLECTION AND ANALYSIS: We extracted information from the included studies on the control of acute and delayed nausea and vomiting, either as a single or a combined outcome. Where appropriate, we combined the results of similar trials. We carried out sensitivity and subgroup analyses to test the robustness of our findings. MAIN RESULTS: We included 16 randomised trials (7808 participants). Nine of the trials compared granisetron versus ondansetron. No other drug comparison was studied in more than one trial. The meta-analyses of the granisetron versus ondansetron trials found similar results for the two drugs on acute vomiting (eight trials, 4256 participants, odds ratio (OR) 0.89; 95% CI 0.78 to 1.02), acute nausea (seven trials, 4160 participants, OR 0.97; 95% CI 0.85 to 1.10), delayed vomiting (three trials, 1119 participants, OR 1.00; 95% CI 0.74 to 1.34) and delayed nausea (two trials, 1024 participants, OR 0.96; 95% CI 0.75 to 1.24). Granisetron and ondansetron showed similar effects on headache and diarrhoea, with the possible exception of less constipation associated with ondansetron.One study of 1114 participants comparing palonosetron plus dexamethasone versus granisetron plus dexamethasone showed superiority of palonosetron in controlling delayed vomiting (OR 1.45; 95% CI 1.14 to 1.85) and delayed nausea (OR 1.63; 95% CI 1.27 to 2.10). Complete response for delayed nausea and vomiting was also in favour of the combination palonosetron and dexamethasone (OR 1.63; 95% CI 1.29 to 2.07). AUTHORS' CONCLUSIONS: Ondansetron and granisetron appear to be equivalent drugs for the prevention of acute and delayed emesis following the use of highly emetogenic chemotherapy.According to one single trial the combination of palonosetron and dexamethasone was superior to granisetron and dexamethasone in controlling delayed emesis. However, more evidence is needed before palonosetron could become the candidate 5-HT(3) RA for the control of delayed emesis induced by highly emetogenic chemotherapy.

  • Compression stockings for preventing deep vein thrombosis in airline passengers.

    13 December 2017

    BACKGROUND: Air travel might increase the risk of deep vein thrombosis (DVT). It has been suggested that wearing compression stockings might reduce this risk. OBJECTIVES: To assess the effects of wearing compression stockings versus not wearing them among people travelling on flights lasting at least four hours. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group's Specialized Register (January 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library, Issue 4, 2005), MEDLINE (January 1966 to November 2005), EMBASE (January 1980 to December 2005) and several other electronic or grey literature sources, detailed in full in the review. The most recent searches were done in January 2006. SELECTION CRITERIA: Randomized trials of compression stockings versus no stockings in passengers on flights lasting at least four hours. Trials in which passengers wore a stocking on one leg but not the other, or those comparing stockings and another intervention were also eligible. DATA COLLECTION AND ANALYSIS: At least two authors independently assessed the quality of each study and extracted data. We sought additional information from trialists. MAIN RESULTS: Ten randomized trials (n = 2856) were included; nine (n = 2821) compared wearing stockings on both legs versus not wearing them, and one (n = 35) compared wearing a stocking on one leg for the outbound flight and on the other leg on the return flight. Of the nine trials, seven included people judged to be at low or medium risk (n = 1548) and two included high risk participants (n = 1273). All flights lasted at least seven hours. Fifty of 2637 participants with follow-up data available in the trials of wearing stockings on both legs had a symptomless DVT; three wore stockings, 47 did not (odds ratio 0.10, 95% confidence interval 0.04 to 0.25, P < 0.00001). There were no symptomless DVTs in three trials. No deaths, pulmonary emboli or symptomatic DVTs were reported. Wearing stockings had a significant impact in reducing oedema (based on six trials). No significant adverse effects were reported. AUTHORS' CONCLUSIONS: Airline passengers similar to those in this review can expect a substantial reduction in the incidence of symptomless DVT and leg oedema if they wear compression stockings. We cannot assess the effect of wearing stockings on death, pulmonary embolus or symptomatic DVT because no such events occurred in these trials. Randomized trials to assess these outcomes would need to include a very large number of people.