While<unk> s involve a highly rigorous approach to synthesizing the evidence, they still have several limitations. Out-dated or risk of bias While<unk> s are regarded as the strongest form of evidence, a 2003<unk>  of 300 studies found that not all<unk> s were equally reliable, and that their reporting can be improved by a universally agreed upon set of standards and guidelines. A further study by the same group found that of 100<unk> s monitored, 7% needed updating at the time of publication, another 4% within a year, and another 11% within 2 years; this figure was higher in rapidly changing fields of medicine, especially cardiovascular medicine. A 2003 study suggested that extending searches beyond major databases, perhaps into grey literature, would increase the effectiveness of<unk> s. Some authors have highlighted problems with<unk> s, particularly those conducted by Cochrane, noting that published<unk> s are often biased, out of date and excessively long. Cochrane<unk> s have been criticized as not being sufficiently critical in the selection of trials and including too many of low quality. They proposed several solutions, including limiting studies in meta-analyses and<unk> s to registered clinical trials, requiring that original data be made available for statistical checking, paying greater attention to sample size estimates, and eliminating dependence on only published data. Some of these difficulties were noted as early as 1994: DG Altman, 1994 Methodological limitations of meta-analysis have also been noted. Another concern is that the methods used to conduct a<unk>  are sometimes changed once researchers see the available trials they are going to include. Some website have described retractions of<unk> s and published reports of studies included in published<unk> s. Eligibility criteria must be justifiable and not arbitrary (for example, the date range searched) as this may affect the perceived quality of the<unk> . Limited reporting of clinical trials and data from human studies The 'AllTrials' campaign highlights that around half of clinical trials have never reported results and works to improve reporting. This lack of reporting has extremely serious implications for research, including<unk> s, as it is only possible to synthesize data of published studies. In addition, 'positive' trials were twice as likely to be published as those with 'negative' results. At present, it is legal for for-profit companies to conduct clinical trials and not publish the results. For example, in the past 10 years 8.7 million patients have taken part in trials that have not published results. These factors mean that it is likely there is a significant publication bias, with only 'positive' or perceived favourable results being published. A recent<unk>  of industry sponsorship and research outcomes concluded that 'sponsorship of drug and device studies by the manufacturing company leads to more favorable efficacy results and conclusions than sponsorship by other sources' and that the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.<unk> s of such a bias may amplify the effect, although it is important to note that the flaw is in the reporting of research generally, not in the<unk>  method. Poor compliance with<unk>  reporting guidelines The rapid growth of<unk> s in recent years has been accompanied by the attendant issue of poor compliance with guidelines, particularly in areas such as declaration of registered study protocols, funding source declaration, risk of bias data, issues resulting from data abstraction, and description of clear study objectives. A host of studies have identified weaknesses in the rigour and reproducibility of search strategies in<unk> s. To remedy this issue, a new PRISMA guideline extension called PRISMA-S is being developed to improve the quality, reporting, and reproducibility of<unk>  search strategies. Furthermore, tools and checklists for peer-reviewing search strategies have been created, such as the Peer<unk>  of Electronic Search Strategies (PRESS) guidelines. A key challenge for using<unk> s in clinical practice and healthcare policy is assessing the quality of a given<unk> . Consequently, a range of appraisal tools to evaluate<unk> s have been designed. The two most popular measurement instruments and scoring tools for<unk>  quality assessment are AMSTAR 2 (a measurement tool to assess the methodological quality of<unk> s) and ROBIS (Risk Of Bias In<unk> s); however, these are not appropriate for all<unk>  types.
Systematic review
Natural history study
Subgroup analysis
Platform trial
Clinical study report
Electronic patient-reported outcome
Cohort study
Intersalt study