***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 The method ological quality of animal studies is an important factor hampering the translation of results from animal studies to a clinical setting . Systematic review s of animal studies may provide a suitable method to assess and thereby improve their method ological quality . Objectives The aims of this study were : 1 ) to evaluate the risk of bias assessment in animal-based systematic review s , and 2 ) to study the internal validity of the primary animal studies included in these systematic review s. Data Sources We systematic ally search ed Pubmed and Embase for SRs of pre clinical animal studies published between 2005 and 2012 . Results A total of 91 systematic review s met our inclusion criteria . The risk of bias was assessed in 48 ( 52.7 % ) of these 91 systematic review s. Thirty-three ( 36.3 % ) SRs provided sufficient information to evaluate the internal validity of the included studies . Of the evaluated primary studies , 24.6 % was r and omized , 14.6 % reported blinding of the investigator/caretaker , 23.9 % blinded the outcome assessment , and 23.1 % reported drop-outs . Conclusions To improve the translation of animal data to clinical practice , systematic review s of animal studies are worthwhile , but the internal validity of primary animal studies needs to be improved . Furthermore , risk of bias should be assessed by systematic review s of animal studies to provide insight into the reliability of the available evidence Correctable weaknesses in the design , conduct , and analysis of biomedical and public health research studies can produce misleading results and waste valuable re sources . Small effects can be difficult to distinguish from bias introduced by study design and analyses . An absence of detailed written protocol s and poor documentation of research is common . Information obtained might not be useful or important , and statistical precision or power is often too low or used in a misleading way . Insufficient consideration might be given to both previous and continuing studies . Arbitrary choice of analyses and an overemphasis on r and om extremes might affect the reported findings . Several problems relate to the research workforce , including failure to involve experienced statisticians and method ologists , failure to train clinical research ers and laboratory scientists in research methods and design , and the involvement of stakeholders with conflicts of interest . Inadequate emphasis is placed on recording of research decisions and on reproducibility of research . Finally , reward systems incentivise quantity more than quality , and novelty more than reliability . We propose potential solutions for these problems , including improvements in protocol s and documentation , consideration of evidence from studies in progress , st and ardisation of research efforts , optimisation and training of an experienced and non-conflicted scientific workforce , and reconsideration of scientific reward systems Antidepressants , in particular newer agents , are among the most widely prescribed medications worldwide with annual sales of billions of dollars . The introduction of these agents in the market has passed through seemingly strict regulatory control . Over a thous and r and omized trials have been conducted with antidepressants . Statistically significant benefits have been repeatedly demonstrated and the medical literature is flooded with several hundreds of " positive " trials ( both pre-approval and post-approval ) . However , two recent meta-analyses question this picture . The first meta- analysis used data that were su bmi tted to FDA for the approval of 12 antidepressant drugs .  While only half of these trials had formally significant effectiveness , published reports almost ubiquitously cl aim ed significant results . " Negative " trials were either left unpublished or were distorted to present " positive " results . The average benefit of these drugs based on the FDA data was of small magnitude , while the published literature suggested larger benefits . A second meta- analysis using also FDA -su bmi tted data examined the relationship between treatment effect and baseline severity of depression . Drug-placebo differences increased with increasing baseline severity and the difference became large enough to be clinical ly important only in the very small minority of patient population s with severe major depression . In severe major depression , antidepressants did not become more effective , simply placebo lost effectiveness . These data suggest that antidepressants may be less effective than their wide marketing suggests . Short-term benefits are small and long-term balance of benefits and harms is understudied . I discuss how the use of many small r and omized trials with clinical ly non-relevant outcomes , improper interpretation of statistical significance , manipulated study design , biased selection of study population s , short follow-up , and selective and distorted reporting of results has built and nourished a seemingly evidence -based myth on antidepressant effectiveness and how higher evidence st and ards , with very large long-term trials and careful prospect i ve meta-analyses of individual-level data may reach closer to the truth and clinical ly useful evidence Industry funding and author financial conflicts of interest may influence the production and synthesis of scientific evidence ( 1 ) . Associations with the pharmaceutical company developing and marketing a drug have been found to influence the design of trials ( 2 ) , the conduct of trials ( 3 ) , and the reporting of trial results ( 47 ) . Furthermore , financial ties and industry funding seem to result in greater rates of favorable conclusions in clinical trials examining new drugs ( 812 ) . Fewer studies have considered the potential influence of financial conflicts of interest on the synthesis of clinical evidence in systematic review s ( 13 , 14 ) . Neuraminidase inhibitors , which are used in the prophylaxis and treatment of seasonal and p and emic influenza , have been the subject of ongoing uncertainty about their specific clinical benefits ( 15 , 16 ) . This is the result of not only the continuing emergence of strains with unknown drug responses but also the increasing awareness in the medical community that , until recently , its knowledge of the safety and efficacy of these drugs has been incomplete ( 17 ) . Despite the abundance of clinical trials and publications on neuraminidase inhibitors , the details of many key trials had not been disclosed ( 18 , 19 ) . As a result , systematic review ers analyzing and synthesizing evidence on the effectiveness of these agents have faced incomplete information , unresolved discrepancies in the data , and a high risk of publication and reporting biases among the primary clinical trials ( 20 , 21 ) . This prompted extensive efforts to access complete records of all published and unpublished clinical trials from manufacturers , culminating in the publication of several review s on the basis of comprehensive clinical study reports and potentially changing the way systematic review s will be undertaken in the future ( 2227 ) . Review s of neuraminidase inhibitors exhibit wide variation in their conclusions , ranging from strong endorsements of the use of these agents in the prophylaxis and treatment of influenza ( 28 , 29 ) to more conservative assessment s question ing the evidence on the drugs ' safety and efficacy ( 15 , 30 ) . The reasons for this discordance in review conclusions are likely multifactorial and may be related in part to the manner in which evidence is accessed , synthesized , and presented ( 23 , 27 ) , both in terms of the numerical results and the authors ' emphasis and interpretation ( 31 , 32 ) . Our aim was to determine whether there is an association between financial conflicts of interest and the favorable presentation of evidence in systematic review s on the use of neuraminidase inhibitors for the prophylaxis and treatment of influenza . Methods Data Sources Systematic review s were identified in PubMed , PubMed In Process , EMBASE , and the Cochrane Data base of Systematic Review s. Search es were done using the keywords influenza , neuraminidase inhibitors , oseltamivir , zanamivir , peramivir , and laninamivir . Articles were retrieved if the search terms appeared in the title or abstract or were included as data base-specific keywords . In PubMed and EMBASE , search es were also constrained to review publication types . We limited our search to English- language articles published since 1 January 2005 . These articles were manually review ed to identify those that focused on the use of neuraminidase inhibitors for influenza prophylaxis or treatment ( such as excluded articles primarily about drug development or other manufacturing processes ) . We selected all review s that used a systematic search protocol , which we defined as the inclusion and reporting of an explicit search strategy , including reasons for subsequent exclusion of articles . The final search es were done on 26 May 2014 . Cochrane review s are periodically up date d to incorporate new evidence , and the results and conclusions are resynthesized as indicated . The authors of these review s are typically different , and there may be differences in the methods as well as the results and language of the review . These up date d review s were included separately . Other Cochrane review s are occasionally rewritten by a subset of the authors for publication in medical journals as abridged versions to increase dissemination . These reports have separate peer review s and are prepared on the basis of a selection of the complete results . We considered these review s separately as well but also did a sensitivity analysis in which they were combined with the original Cochrane review s. Data Extraction Financial conflicts of interest were identified for all authors of the review s and included affiliations with or funding from the pharmaceutical company manufacturing any of the neuraminidase inhibitors under review . We defined financial conflicts of interest as employment , the funding of grants paid to an author or an author 's research group , and the funding of medical writers for the systematic review . These financial conflicts of interest were identified using information about affiliations or funding listed in the systematic review s , as well as in any other articles published by one of the authors during the 3 years before the publication of the index systematic review . In addition , we search ed authors ' personal and institutional Web sites ; lists of disclosures from GlaxoSmithKline ( Research Triangle Park , North Carolina ) and Roche Pharmaceuticals ( Basel , Switzerl and ) ; and performed Web search es combining the names of the authors , drugs , and pharmaceutical companies to identify any additional information about financial relationships . Details of the specific financial conflicts of interest identified for each author are listed in Appendix Table 1 . Appendix Table 1 . Financial Conflicts of Interest Among Authors of the Systematic Review s For each systematic review , we recorded whether prophylaxis or treatment was assessed , the forms of evidence to be included ( such as r and omized , controlled trials and observational studies ) , the specific clinical outcomes assessed , the population s examined , and whether meta-analyses were done . We also examined whether the review s included information about the validity or quality of the primary literature . In particular , we recorded whether there were statements addressing nonpublication of primary studies or publication bias , including tests done by the review ers to assess for bias in meta-analyses ( such as the Egger or Begg test [ 33 , 34 ] ) , difficulty in accessing comprehensive study data , and the prevalence or role of industry in conducting and funding the primary studies . Data Analysis Two investigators were provided with redacted copies of each review that did not include the review s ' authors , their affiliations , or information on financial conflicts of interest . These versions also did not contain the journal name , journal formatting , or the article 's acknowledgments or references . The investigators independently evaluated the review s and classified the prophylaxis and treatment assessment s as favorable or not favorable toward the use of neuraminidase inhibitors . They were instructed to do this grading on the basis of the entirety of the review text without restriction to conclusions or recommendations made in any specific section of the review , thus allowing them to take into account the emphasis and interpretation of the authors throughout the review . The agreement between the investigators was strong at 86 % ( Cohen , 0.72 ; P < 0.001 ) . Disagreements were resolved by a third investigator using the same redacted copies . Descriptive analyses were done to examine the associations between financial conflicts of interest and the grading of the systematic review s. A sensitivity analysis excluding the summary review s was done to further examine this association . We also assessed the association between financial conflicts of interest and the inclusion of statements addressing the validity or quality of the primary evidence . Role of the Funding Source This study was funded by the Australian National Health and Medical Research Council . The funding source had no role in the design and conduct of the study , analysis of the results , or the decision to su bmi t the manuscript for publication . Results We identified 827 published articles across the 4 data bases using the specified search criteria , with 26 systematic review s included in the final cohort ( Figure ) . Thirteen review s examined prophylaxis and 24 examined treatment of influenza , accounting for 37 distinct assessment s ( Appendix Table 2 ) . In terms of review methods , 7 were Cochrane systematic review s and 19 conducted and reported a meta- analysis ( 73 % ) . The evidence inclusion criteria were limited to r and omized , controlled trials for 14 of the systematic review s ( 54 % ) , and 5 included evidence from clinical study reports or patient-level data . The main population s examined were healthy adults ( 18 of 26 systematic review s ) , children ( 13 of 26 ) , and hospitalized patients ( 6 of 24 ) . The outcome measures for prophylaxis assessment s included influenza-like illness and laboratory-confirmed influenza . For the treatment assessment s , the outcomes were illness duration , influenza-related complications , hospitalization , and mortality , mostly in combination . Five review s were up date s of previous Cochrane review s , and 3 were summary review s based on Cochrane review s. Figure . Summary of evidence search and selection . Eligible systematic review s included those with outcomes related to the prophylaxis or treatment of influenza . Appendix Table 2 . Characteristics of Systematic Review s Examining Prophylaxis and Treatment Outcomes for Neuraminidase Inhibitors Association Between Financial Conflicts of Interest and Favorable Assessment s Seven of the 26 systematic review s ( 27 % ) , corresponding to 8 of the 37 assessment s ( 22 % ) , were associated with a financial conflict of interest ( Appendix Table 1 ) . We identified financial conflicts of interest in publications other than the index systematic review in 2 cases , and no additional Background Systematic review s ( SRs ) can help decision makers interpret the deluge of published biomedical literature . However , a SR may be of limited use if the methods used to conduct the SR are flawed , and reporting of the SR is incomplete . To our knowledge , since 2004 there has been no cross-sectional study of the prevalence , focus , and completeness of reporting of SRs across different special 
    Output:
    
Few systematic review s and meta-analyses are both non-misleading and useful .