A simplified search strategy for identifying randomised controlled trials for systematic reviews of health care interventions : a comparison with more exhaustive strategies

Background It is generally believed that exhaustive searches of bibliographic databases are needed for systematic reviews of health care interventions. The CENTRAL database of controlled trials (RCTs) has been built up by exhaustive searching. The CONSORT statement aims to encourage better reporting, and hence indexing, of RCTs. Our aim was to assess whether developments in the CENTRAL database, and the CONSORT statement, mean that a simplified RCT search strategy for identifying RCTs now suffices for systematic reviews of health care interventions. Methods RCTs used in the Cochrane reviews were identified. A brief RCT search strategy (BRSS), consisting of a search of CENTRAL, and then for variants of the word random across all fields (random$.af.) in MEDLINE and EMBASE, was devised and run. Any trials included in the meta-analyses, but missed by the BRSS, were identified. The meta-analyses were then re-run, with and without the missed RCTs, and the differences quantified. The proportion of trials with variants of the word random in the title or abstract was calculated for each year. The number of RCTs retrieved by searching with "random$.af." was compared to the highly sensitive search strategy (HSSS). Results The BRSS had a sensitivity of 94%. It found all journal RCTs in 47 of the 57 reviews. The missing RCTs made some significant differences to a small proportion of the total outcomes in only five reviews, but no important differences in conclusions resulted. In the post-CONSORT years, 1997–2003, the percentage of RCTs with random in the title or abstract was 85%, a mean increase of 17% compared to the seven years pre-CONSORT (95% CI, 8.3% to 25.9%). The search using random$.af. reduced the MEDLINE retrieval by 84%, compared to the HSSS, thereby reducing the workload of checking retrievals. Conclusion A brief RCT search strategy is now sufficient to locate RCTs for systematic reviews in most cases. Exhaustive searching is no longer cost-effective, because in effect it has already been done for CENTRAL

Bibliometrics of NIHR HTA monographs and their related journal articles

Objectives: A bibliometric analysis of the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) monographs and their related journal articles by: (1) exploring the differences in citations to the HTA monographs in Google Scholar (GS), Scopus and Web of Science (WoS), and (2) comparing Scopus citations to the monographs with their related journal articles. Setting: A study of 111 HTA monographs published in 2010 and 2011, and their external journal articles. Main outcome measures: Citations to the monographs in GS, Scopus and WoS, and to their external journal articles in Scopus. Results: The number of citations varied among the three databases, with GS having the highest and WoS the lowest; however, the citation-based rankings among the databases were highly correlated. Overall, 56% of monographs had a related publication, with the highest proportion for primary research (76%) and lowest for evidence syntheses (43%). There was a large variation in how the monographs were cited, compared to journal articles, resulting in more frequent problems, with unlinked citations in Scopus and WoS. When comparing differences in the number of citations between monograph publications with their related journal articles from the same project, we found that monographs received more citations than their journal articles for evidence syntheses and methodology projects; by contrast, journal articles related to primary research monographs were more highly cited than their monograph. Conclusions: The numbers of citations to the HTA monographs differed considerably between the databases, but were highly correlated. When a HTA monograph had a journal article from the same study, there were more citations to the journal article for primary research, but more to the monographs for evidence syntheses. Citations to the related journal articles were more reliably recorded than citations to the HTA monographs

Literature searching for clinical and cost-effectiveness studies used in health technology assessment reports carried out for the National Institute for Clinical Excellence appraisal system

Background In the UK, one part of the remit of the National Institute for Clinical Excellence (NICE) is to carry out a programme of technology appraisals. These are done to a fairly tight timetable in order not to delay the guidance on new technologies. Each appraisal is underpinned by a Technology Assessment Report (TAR) commissioned from a group of academic units. As the TAR process is relatively new, and is still evolving, the methods used for its literature searching have been largely based on the well-established and documented methods used for Cochrane reviews. These involve comprehensive searching of a variety of sources to protect against bias, but can add substantially to the time and costs of carrying out a review. However, resource constraints require that TARs are produced as efficiently as possible, and to a tight timetable, which means that not all of the Cochrane methods can be applied, or are appropriate. In addition, it is not known whether the marginal benefits of exhaustive searching justify the costs. The challenge for those undertaking TARs is to know how best to adapt and optimise, and extend when necessary, the Cochrane-based search strategies, so that searching can be done both rapidly and systematically. Objective To contribute to making searching for TARs more cost-effective by suggesting an optimum literature retrieval strategy, based on empirical data obtained from a sample of recent TARs, which balances comprehensiveness and efficiency. Methods A sample of 20 recent TARs was studied. All sources used to search for clinical and cost-effectiveness studies were recorded. In addition, all studies that were included in the clinical and cost-effectiveness sections of the TARs were identified, and their characteristics recorded, including author, journal, year, study design, study size and quality score. Each was also classified by publication type, and then checked to see whether it was indexed in the following databases: MEDLINE, EMBASE, and then either the Cochrane Controlled Trials Register (CCTR) for clinical effectiveness studies or the NHS Economic Evaluation Database (NHS EED) for the cost-effectiveness studies. Any study not found in at least one of these databases was checked to see whether it was indexed in the Science Citation Index (SCI) and BIOSIS, and the American Society of Clinical Oncology (ASCO) Online if a cancer review. Any studies still not found were investigated further to see whether they were in a number of additional databases. Results Sources searched The median number of sources searched per TAR was 20, and the range was from 13 to 33 sources. Six sources (CCTR, DARE, EMBASE, MEDLINE, NHS EED and sponsor/industry submissions to NICE) were used in all reviews. Clinical effectiveness studies There were 424 studies in total. The publication types were: published 80%, meeting abstracts 11.3% and unpublished 8.7%. Eighty per cent of reviews included at least one abstract or unpublished study (60% included at least one abstract and 50% included at least one unpublished study). The median number of studies included per TAR was 19.5 (range 2–41). The median number of participants included per TAR was 2787 (range 69–97,570). Evidence from non-randomised controlled trial (RCT) studies was used in 45% of TARs. The proportion of studies classified either as published in full or as abstracts, and found indexed in the following databases, was: MEDLINE 82.7%, EMBASE 78.6% and CCTR 50.1%. The cumulative percentage of studies found after searching these three databases was 87.3%. Adding SCI, BIOSIS and ASCO Online increased this to 98.2%. Eighty-seven per cent of studies were indexed in both MEDLINE and EMBASE. Cost-effectiveness studies The 130 studies were classified as: published 73.1%, unpublished 23.8%, abstracts 1.5% and grey literature 1.5%. The median number of studies used was 4.0. The percentage of studies classified as either published in full or as abstracts, and found indexed in the following databases, was: MEDLINE 86.6%, EMBASE 86.6% and NHS EED 40.2%. The cumulative percentage of these studies found indexed after searching the three databases was 94.8%. Adding SCI and ASCO Online increased this to 97.9%. Studies used in the economic modelling The 121 articles were classified as: published 50.4%, abstracts 5.0%, reference sources 17.4%, unpublished 17.4% and grey literature 9.8%. The median number of studies used for the 14 TARs that included an economic model was 9.0 per TAR. Search terms for identifying non-RCTs A sensitive search filter, constructed for MEDLINE and using the search terms from the bibliographic records in the included studies, retrieved only 85% of the known sample. Therefore, it is recommended that when searching for non-RCT studies a search is done for the intervention alone, and records are then scanned manually for those that look relevant. Conclusions Searching additional databases beyond the Cochrane Library (which includes CCTR, NHS EED and the HTA database), MEDLINE, EMBASE and SCI, plus BIOSIS limited to meeting abstracts only, is seldom effective in retrieving additional studies for inclusion in the clinical and cost-effectiveness sections of TARs (apart from reviews of cancer therapies, where a search of the ASCO database is recommended). A more selective approach to database searching would suffice in most cases and would save resources, thereby making the TAR process more efficient. However, searching non-database sources (including submissions from manufacturers, recent meeting abstracts, contact with experts and checking reference lists) does appear to be a productive way of identifying further studies

Liraglutide for the treatment of type 2 diabetes : a single technology appraisal

This paper presents a summary of the Evidence Review Group (ERG) report into the clinical effectiveness and cost-effectiveness of liraglutide in the treatment of type 2 diabetes mellitus, based upon the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The manufacturer proposed the use of liraglutide as a second or third drug in patients with type 2 diabetes whose glycaemic control was unsatisfactory with metformin, with or without a second oral glucoselowering drug. The submission included six manufacturer-sponsored trials that compared the efficacy of liraglutide against other glucose-lowering agents. Not all of the trials were relevant to the decision problem. The most relevant were Liraglutide Effects and Actions in Diabetes 5 (LEAD-5) (liraglutide used as part of triple therapy and compared against insulin glargine) and LEAD-6 [liraglutide in triple therapy compared against another glucagon like peptide-1 (GLP-1) agonist, exenatide]. Five of the six trials were published in full and one was then unpublished. Two doses of liraglutide, 1.2 and 1.8 mg, were used in some trials but in the two comparisons in triple therapy, against glargine and exenatide, only the 1.8-mg dose was used. Liraglutide in both doses was found to be clinically effective in lowering blood glucose concentration [glycated haemoglobin (HbA1c)], reducing weight (unlike other glucose-lowering agents, such as sulphonylureas, glitazones and insulins, which cause weight gain) and also reducing systolic blood pressure (SBP). Hypoglycaemia was uncommon. The ERG carried out meta-analyses comparing the 1.2- and 1.8-mg doses of liraglutide, which suggested that there was no difference in control of diabetes, and only a slight difference in weight loss, insufficient to justify the extra cost

Evidence review : liraglutide for the treatment of type 2 diabetes

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of liraglutide in the treatment of type 2 diabetes mellitus, based upon the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The manufacturer proposed the use of liraglutide as a second or third drug in patients with type 2 diabetes whose glycaemic control was unsatisfactory with metformin, with or without a second oral glucose-lowering drug. The submission included six manufacturer-sponsored trials that compared the efficacy of liraglutide against other glucose-lowering agents. Not all of the trials were relevant to the decision problem. The most relevant were Liraglutide Effects and Actions in Diabetes 5 (LEAD-5) (liraglutide used as part of triple therapy and compared against insulin glargine) and LEAD-6 [liraglutide in triple therapy compared against another glucagon-like peptide-1 agonist, exenatide]. Five of the six trials were published in full and one was then unpublished. Two doses of liraglutide, 1.2 and 1.8 mg, were used in some trials, but in the two comparisons in triple therapy, against glargine and exenatide, only the 1.8-mg dose was used. Liraglutide in both doses was found to be clinically effective in lowering blood glucose concentration [glycated haemoglobin (HbA1c)], reducing weight (unlike other glucose-lowering agents, such as sulphonylureas, glitazones and insulins, which cause weight gain) and also reducing systolic blood pressure (SBP). Hypoglycaemia was uncommon. The ERG carried out meta-analyses comparing the 1.2- and 1.8-mg doses of liraglutide, which suggested that there was no difference in control of diabetes, and only a slight difference in weight loss, insufficient to justify the extra cost. The cost-effectiveness analysis was carried out using the Center for Outcomes Research model. The health benefit was reported as quality-adjusted life-years (QALYs). The manufacturer estimated the cost-effectiveness to be £15,130 per QALY for liraglutide 1.8 mg compared with glargine, £10,054 per QALY for liraglutide 1.8 mg compared with exenatide, £10,465 per QALY for liraglutide 1.8 mg compared with sitagliptin, and £9851 per QALY for liraglutide 1.2 mg compared with sitagliptin. The ERG conducted additional sensitivity analyses and concluded that the factors that carried most weight were: in the comparison with glargine, the direct utility effects of body mass index (BMI) changes and SBP, with some additional contribution from HbA1c in the comparison with exenatide, HbA1c, with some additional effects from cholesterol and triglycerides in the comparison with sitagliptin, HbA1c and direct utility effects of BMI changes. The European Medicines Agency has approved liraglutide in dual therapy with other oral glucose-lowering agents. NICE guidance recommends the use of liraglutide 1.2 mg in triple therapy when glycaemic control remains or becomes inadequate with a combination of two oral glucose-lowering drugs. The use of liraglutide 1.2 mg in a dual therapy is indicated only in patients who are intolerant of, or have contraindications to, three oral glucose-lowering drugs. The use of liraglutide 1.8 mg was not approved by NICE. The ERG recommends research into the (currently unlicensed) use of liraglutide in combination with long-acting insulin

Systematic reviews of epidemiology in diabetes: finding the evidence

BACKGROUND: Methodological research to support searching for those doing systematic reviews of epidemiological studies is a relatively neglected area. Our aim was to determine how many databases it is necessary to search to ensure a comprehensive coverage of the literature in diabetes epidemiology, with the aim of examining the efficiency of searching in support of systematic reviews of the epidemiology of diabetes METHODS: Three approaches were used. First, we defined a set of English language diabetes journals and examined their coverage in bibliographic databases. Second, we searched extensively for diabetes epidemiology articles (in all languages) to determine which are the most useful databases; and third, we analysed the scattering of these articles to determine the core journals in the area. RESULTS: The overlap between MEDLINE and Embase for diabetes journals was 59%. A search for diabetes epidemiology articles across both MEDLINE and Embase, showed that MEDLINE alone retrieved about 94% of the total articles. Searching for diabetes epidemiology studies beyond MEDLINE and Embase retrieved no additional English language journal articles. The only diabetes epidemiology studies found by searching beyond MEDLINE and Embase were found in LILACS, and were Spanish or Portuguese language studies from Latin America; no additional English language studies were found. Only 30% of the meeting abstracts were converted to full publication after three years. One third of journal articles were published in just six journals, with Diabetes Care contributing 14.3% of the articles, followed by Diabetic Medicine (5.0%); Diabetes Research & Clinical Practice (4.1%); Diabetologia (4.0%); Diabetes & Metabolism (2.4%) and Diabetes (2.0%). CONCLUSIONS: Our results show that when searching for articles on diabetes epidemiology, MEDLINE and Embase would suffice for English language papers, with LILACS giving some additional non-English articles from Latin America. Although a MEDLINE-only search will retrieve the vast majority of the relevant literature, Embase and LILACs should also be searched to ensure the search is comprehensive. Searching for meeting abstracts is recommended to alert reviewers to unpublished work. The low rate of full publication of meeting abstracts has the danger of producing bias in reviews. Our findings on scattering show that the core literature in this field is concentrated in just six journals

Community-onset sepsis and its public health burden : protocol of a systematic review

Background: Sepsis is a life-threatening condition and major contributor of public health and economic burden in the industrialised world. The heterogeneity, absence of more specific definition, and difficulties in accurate diagnosis lead to great variability in the estimates of sepsis incidence. There has been uncertainty regarding the incidence and risk factors attributable to community-onset as opposed to hospital-acquired sepsis. Community-onset sepsis has distinct host characteristics, risk factors, pathogens, and prognosis. A systematic assessment of recent evidence is warranted in light of secular changes in epidemiology, pathogens, and the uncertainties around the incidence and risk factors of community-onset sepsis. This protocol describes a systematic review which aims to synthesise the recent empirical evidence on the incidence and risk factors of community-onset sepsis, severe sepsis, and septic shock in high-income countries. Methods/design: English-language publications of cohort and case-control studies reporting incidence and risk factors of community-onset sepsis will be eligible for inclusion. MEDLINE and Embase databases will be searched from 2002 and onwards. References of relevant publications will be hand-searched. Two reviewers will independently screen titles/abstracts and full texts as well as extract data and appraise the risk of bias of included studies. The data extractions and risk of bias assessments will be cross-checked. Any disagreements will be resolved via consensus. The data on incidence and risk factors of sepsis will be organised and synthesised in text, tables, and forest plots. The evidence will be pooled given sufficient data and degree of similarity across study populations, exposures, and outcomes. The heterogeneity will be assessed through visual inspection of forest plots, Chi-square-based p value, and I (2) statistic. The sources of heterogeneity will be explored via subgroup analysis. Discussion: Timeliness and accuracy of diagnosis of sepsis are both crucial aspects for improving the patient's outcome. The findings of this review will be discussed with a view to better inform future recommendations on improving public-facing campaigns, timely presentation, and diagnosis of sepsis in the community. The review will also discuss gaps in evidence and highlight future research and policy-making avenues for improving public health planning. Systematic review registration: PROSPERO CRD42015023484

Acessibilidade e utilização dos espaços verdes urbanos nas cidades de Coimbra (Portugal) e Salamanca (Espanha)

ACCESSIBILITY AND USE OF URBAN GREEN SPACES IN THE CITIES OF COIMBRA (PORTUGAL) AND SALAMANCA (SPAIN). In a society that values more and more wellbeing, health and free time, the introduction of urban green spaces (UGS) next to residential areas has become a citizen’s right and requirement. This paper analyses the distribution and accessibility of UGS in the cities of Coimbra and Salamanca and evaluates their influence on the needs of the resident populations, in terms of users’ age, frequency of usage, as well as of motivation and ways to enjoy the facilities. In Coimbra there is a concentration of UGS, whereas in Salamanca there is a dispersion of such spaces, which has resulted in the different usage that people make of them. In fact, although Coimbra offers more urban green space (per inhabitant), their usage is reduced as people go there mainly by car, contrary to what happens in Salamanca. Consequently, Coimbra’s inhabitants choose these green spaces because of the activities they can be used for, whereas Salamanca’s inhabitants choose them for their proximity

A systematic review of economic evaluations assessing the cost-effectiveness of licensed drugs used for previously treated epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) negative advanced/metastatic non-small cell lung cancer

Background Non-small cell lung cancer (NSCLC) is one of the most commonly diagnosed cancers. There are many published studies of cost-effectiveness analyses of licensed treatments, but no study has compared these studies or their approaches simultaneously. Objective To investigate the methodology used in published economic analyses of licensed interventions for previously treated advanced/metastatic NSCLC in patients without anaplastic lymphoma kinase or epidermal growth factor receptor expression. Methods A systematic review was performed, including a systematic search of key databases (e.g. MEDLINE, EMBASE, Web of Knowledge, Cost-effectiveness Registry) limited to the period from 01 January 2001 to 26 July 2019. Two reviewers independently screened, extracted data and quality appraised identified studies. The reporting quality of the studies was assessed by using the Consolidated Health Economic Evaluation Reporting Standards and the Philips’ checklists. Results Thirty-one published records met the inclusion criteria, which corresponded to 30 individual cost-effectiveness analyses. Analytical approaches included partitioned survival models (n = 14), state-transition models (n = 7) and retrospective analyses of new or published data (n = 8). Model structure was generally consistent, with pre-progression, post-progression and death health states used most commonly. Other characteristics varied more widely, including the perspective of analysis, discounting, time horizon, usually to align with the country that the analysis was set in. Conclusions There are a wide range of approaches in the modelling of treatments for advanced NSCLC; however, the model structures are consistent. There is variation in the exploration of sensitivity analyses, with considerable uncertainty remaining in most evaluations. Improved reporting is necessary to ensure transparency in future analyses