Anti-IL-4R versus anti-IL-5/5R after anti-IL-5/5R failure in asthma: An emulated target trial.

BACKGROUND: Switching biologics is now common practice in severe eosinophilic asthma. After insufficient response to anti-IL-5 or 5 receptor (anti-IL-5/5R), the optimal switch between an anti-IL-4R mAb (interclass) or another anti-IL-5/5R drug (intraclass) remains unknown. OBJECTIVE: We sought to compare the effectiveness of these 2 strategies in asthma control in patients with severe eosinophilic asthma and insufficient response to an anti-IL-5/5R mAb. METHODS: We emulated a target randomized trial using observational data from the Recherche sur les AsthMes SEvèreS (RAMSES) cohort. Eligible patients were switched to an anti-IL-4R mAb or another anti-IL-5/5R drug after insufficient response to an anti-IL-5/5R mAb. The primary outcome was the change in Asthma Control Test score at 6 months. RESULTS: Among the 2046 patients in the cohort, 151 were included in the study: 103 switched to an anti-IL-4R mAb and 48 to another anti-IL-5/5R. At 6 months, the difference in Asthma Control Test score improvement was not statistically significant (mean difference groups, 0.82 [-0.47 to 2.10], P = .213). The interclass group exhibited greater cumulative reduction in oral corticosteroid dose (Pinter-intra, -1.05 g [-1.76 to -0.34], P = .041). The interclass group had a better effect, although not significantly, on reducing exacerbations (Δinter-intra, -0.37 [-0.77 to 0.02], P = .124) and increasing lung function (FEV1) (126.8 mL [-12.7 to 266.4], P = .124). CONCLUSIONS: After anti-IL-5/5R mAb insufficient response, switching to dupilumab demonstrated similar improvement in Asthma Control Test scores compared with intraclass switching. However, it appeared more effective in reducing oral corticosteroid use. Larger studies are warranted to confirm these results.

Benzodiazepines for pediatric epilepsies and their risks in a cohort within the French health care data.

OBJECTIVE: The management of antiseizure treatment in patients with epilepsy relies on the benefit-risk ratio. Data on antiseizure medication (ASM) use in children are limited. We described antiseizure medication use in children with epilepsy (CwE) in France, with a focus on the chronic use of benzodiazepines and related implications. METHODS: We conducted a 5-year cohort study from January 2012, using data from the French national health care data system (Système National des Données de Santé). We included CwE identified through International Classification of Diseases, 10th Revision codes and medications from January 2012 to December 2015 and followed them until December 2016. We described ASMs and assessed whether the risk of initiating a polytherapy after a bitherapy depends on whether benzodiazepine was included in the bitherapy. RESULTS: We identified 62 885 CwE. Valproate was the most reimbursed ASM (40%), followed by lamotrigine (17.6%), levetiracetam (9.3%), clobazam (6.1%), and carbamazepine (5.8%). Prescriptions were initiated at the hospital in 74.5% of CwE. We observed a decrease in the number of CwE with at least one benzodiazepine reimbursement from 15.3% in 2013 to 10.1% in 2016 (p < .0001). The prevalence of CwE with levetiracetam reimbursements increased, whereas that of CwE with valproate decreased. A switch from a bitherapy to a polytherapy was more likely when the bitherapy included a benzodiazepine (subdistribution hazard ratio [sHR] = 1.20 [1.03-1.39]). SIGNIFICANCE: The prevalence of CwE with at least one benzodiazepine reimbursement decreased during the study period. Benzodiazepines were associated with an increased use of subsequent ASM polytherapy.

Safety and Persistence of Nalmefene Treatment for Alcohol Dependence. Results from Two Post-authorisation Safety Studies.

AIMS: Two post-authorisation studies assessed the safety and persistence of patients' use of nalmefene. METHODS: The START study (EUPAS5678) was a non-interventional, multi-country, prospective, 18-month (8 follow-up visits) cohort study including outpatients initiating nalmefene for the first time. The multi-database retrospective cohort study (MDRC, EUPAS14083) included baseline and follow-up data from German, Swedish and UK healthcare databases. Both studies permitted 'all comers' without explicit exclusion criteria; predefined subgroups of interest included the elderly (≥65 years) as well as patients with significant psychiatric and/or somatic comorbidities. RESULTS: START study: Overall, the mean duration of nalmefene treatment was 10.3 ± 7.3 months (N = 1348), with 49.0% of patients treated for ≥1 year; frequent reasons for treatment discontinuation were 'goal reached' and 'drug cost'. The most frequently reported adverse drug reactions (ADRs) were nausea (4.7%), dizziness (3.2%) and insomnia (2.0%). ADR rates appeared higher in the elderly subpopulation (18.6% reported ≥1 ADR vs. 12.0% in the total population) but were not higher in the other predefined subgroups.MDRC study: The database follow-up analysis followed 2892 patients over 18 months for whom the duration of nalmefene treatment was between 2 and 3 months and <5% of patients used nalmefene for ≥1 year. CONCLUSIONS: Despite the inclusion of a wider patient population (e.g. elderly patients and those with relevant co-morbidities), the safety and tolerability profile of nalmefene given in routine practice was consistent with previous clinical studies. The differing rates of persistence beyond 1 year likely reflect the different methodologies and highlight the relevance of psychosocial support at follow-up visits.

2018 updated European League Against Rheumatism evidence-based recommendations for the diagnosis of gout.

Although gout is the most common inflammatory arthritis, it is still frequently misdiagnosed. New data on imaging and clinical diagnosis have become available since the first EULAR recommendations for the diagnosis of gout in 2006. This prompted a systematic review and update of the 2006 recommendations. A systematic review of the literature concerning all aspects of gout diagnosis was performed. Recommendations were formulated using a Delphi consensus approach. Eight key recommendations were generated. A search for crystals in synovial fluid or tophus aspirates is recommended in every person with suspected gout, because demonstration of monosodium urate (MSU) crystals allows a definite diagnosis of gout. There was consensus that a number of suggestive clinical features support a clinical diagnosis of gout. These are monoarticular involvement of a foot or ankle joint (especially the first metatarsophalangeal joint); previous episodes of similar acute arthritis; rapid onset of severe pain and swelling; erythema; male gender and associated cardiovascular diseases and hyperuricaemia. When crystal identification is not possible, it is recommended that any atypical presentation should be investigated by imaging, in particular with ultrasound to seek features suggestive of MSU crystal deposition (double contour sign and tophi). There was consensus that a diagnosis of gout should not be based on the presence of hyperuricaemia alone. There was also a strong recommendation that all people with gout should be systematically assessed for presence of associated comorbidities and risk factors for cardiovascular disease, as well as for risk factors for chronic hyperuricaemia. Eight updated, evidence-based, expert consensus recommendations for the diagnosis of gout are proposed.

Impact of a population-based asthma management program in France (Sophia Asthme): A matched controlled before-and-after quasi-experimental study using the French health insurance database (SNDS).

PURPOSE: Sophia Asthme (SA) is a chronic disease management program of the French national health insurance for adult patients with asthma. We evaluated the early impact of this intervention. METHODS: We conducted a matched controlled, before-and-after quasi-experimental study within the French Health Insurance Database (Système National Des Données de Santé [SNDS]). The SA program was implemented in a set of 18 Départements in France and targeted 18- to 44-year-old subjects, with at least two reimbursement dates for asthma drug therapy during the 12-month period prior to program targeting. Change in outcomes was assessed from the "before program" period (January-December 2014) to the "after program implementation" period (March 2015-February 2016) in the program group (eligible to SA program in the 18 Départements) and in the matched controlled group. The main outcome measure was the before-after change in proportion of subjects with a controllers/(controllers+relievers) ratio greater than 50%. RESULTS: Of the 99 578 subjects of the program group, 9225 (9.3%) actually participated in SA program. The program had no significant impact on the proportion of subjects with a ratio greater than 50%. However, subjects exposed to SA program were significantly more likely to be dispensed controller medications (OR = 1.04; 95% CI, 1.01-1.07) and to sustain their use of these medications (OR = 1.08; 95% CI, 1.05-1.12). CONCLUSION: We did not demonstrate any significant impact of the program on the primary outcome. The modest yet encouraging findings of this early evaluation suggest the need for reformulation of the program and its evaluation.

Self-controlled designs in pharmacoepidemiology involving electronic healthcare databases: a systematic review.

BACKGROUND: Observational studies are widely used in pharmacoepidemiology. Several designs can be used, in particular self-controlled designs (case-crossover and self-controlled case series). These designs offer the advantage of controlling for time-invariant confounders, which may not be collected in electronic healthcare databases. They are particularly useful in pharmacoepidemiology involving healthcare database. To be valid, they require the presence of some characteristics (key validity assumptions), and in such situations, these designs should be preferred. We aimed at describing the appropriate use and reporting of the key validity assumptions in self-controlled design studies. METHODS: Articles published between January 2011 and December 2014, and describing a self-controlled study design involving electronic healthcare databases were retrieved. The appropriate use (fulfilment of key assumptions) was studied in terms of major (abrupt onset event, rare or recurrent event, and intermittent exposure) and minor assumptions (those for which the design can be adapted). RESULTS: Among the 107 articles describing a self-controlled design, 35/53 (66%) case-crossover studies, and 48/55 (87%) self-controlled case series fulfilled the major validity assumptions for use of the design; 4/35 and 14/48 respectively did not fulfill the minor assumptions. Overall, 31/53 (58%) case-crossover studies and 34/55 (62%) self-controlled case series fulfilled both major and minor assumptions. The reporting of the methodology or the results was appropriate, except for power calculation. CONCLUSIONS: Self-controlled designs were not appropriately used in34% and 13% of the articles we reviewed that described a case-crossover or a self-controlled case series design, respectively. We encourage better use of these designs in situations in which major validity assumptions are fulfilled (i.e., for which they are recommended), accounting for situations for which the design can be adapted.

Underuse of self-controlled designs in pharmacoepidemiology in electronic healthcare databases: a systematic review.

PURPOSE: The self-controlled (SC) designs offer the advantage of inherently controlling for time-invariant confounders, which may not be collected in electronic healthcare databases. To be valid, the design requires that some characteristics must be present. Recommendations for their use have been published in 2012, which encourage their implementation when these key characteristics are valid. We aimed at describing the potentially missed opportunities for the use of SC in pharmacoepidemiological studies on electronic healthcare databases. METHODS: We searched Medline for the articles published in two different 6-month periods before and after the 2012 recommendations. The potentially opportunity for the use of SC design is based on major required characteristics (abrupt onset event, rare or recurrent event, and acute or intermittent exposure). RESULTS: In total, 94 papers in 2011 were analysed and 106 in 2014. SC designs were rarely used (2% in 2011 and 1% in 2014). A potentially missed opportunity for SC use was found in 16% of papers in 2011 and 15% in 2014. CONCLUSIONS: We found that SC designs were underused and identified situations in which they could have been applied, but were not. Their use should be encouraged.

Evolution of public funding since primary care research was considered as a priority research domain in france.

PURPOSE: Annually, the French Ministry of Health funds clinical research projects based on a national call for projects. Since 2013, the Ministry has prioritized funding of primary care. Projects selected for funding are made public without distinguishing the specific area of research. The objective of this study was to identify and describe the evolution of the primary care research projects funded by the Ministry of Health between 2013 and 2019. METHOD: We reviewed all of the 1796 medical research projects funded between 2013 and 2019 and categorized projects as primary care projects by using a list of specific keywords. This list was established through two approaches: (1) selected by an expert committee, the RECaP primary care working group, and (2) using an automated textual analysis of published articles in the field. The keywords were used to screen the titles of the medical research projects funded. The abstracts (at www. CLINICALTRIALS: gov ) or details (from project leaders) were then analyzed by two independent reviewers to determine true primary care projects. RESULTS: Finally, 49 primary care projects were identified, representing 2.7% of all medical research projects funded, without any significant change over the period. These projects were predominantly interventional (69%), with a median number of patients expected per project of 902. CONCLUSION: Despite the prioritization of primary care research in 2013 by the French ministry of health, the number and proportion of projects funded remains low, with no significant change over the years. TRIAL REGISTRATION: Not applicable.

Severe asthma care trajectories: the French RAMSES cohort.

Background: The French RAMSES study is an observational prospective multicentre real-life cohort including severe asthmatic subjects. The objective of the study was to compare the characteristics of patients, in terms of phenotype and asthma care trajectories, between those managed by tertiary referral centres (TRCs) or secondary care centres (SCCs). Methods: Patients were prospectively recruited and enrolled for a 5-year follow-up. Patients' characteristics were analysed at inclusion and compared between TRCs and SCCs. Results: 52 centres (24 TRCs and 28 SCCs) included 2046 patients: 1502 (73.4%) were included by a TRC and 544 (26.6%) by a SCC. Patients were mainly women (62%), 53±15 years old, 67% with Asthma Control Test <20; at inclusion, 14% received oral corticosteroids (OCS) and 66% biologics. Compared with the SCC group, the TRC group had more frequent comorbidities and lower blood eosinophil counts (262 versus 340 mm-3; p=0.0036). OCS and biologics use did not differ between groups, but patients in the TRC group benefited more frequently from an educational programme (26% versus 18%; p=0.0008) and received more frequently two or more sequential lines of biologics (33% versus 24%; p=0.0105). In-depth investigations were more frequently performed in the TRC group (allergy tests: 74% versus 62%; p<0.0001; exhaled nitric oxide fraction: 56% versus 21%; p<0.0001; induced sputum: 6% versus 3%; p=0.0390). Conclusions: Phenotypes and care trajectories differed in the RAMSES cohort between SCCs and TRCs, probably related to different levels of asthma severity and differences in medical resources and practices among centres. This highlights the need for standardisation of severe asthma care.

Evaluation of drug deliveries and refunds for obstructive airway diseases in France between 2012 and 2017.

BACKGROUND: The aim of this survey was to investigate variations of drugs for obstructive airway diseases delivery rates and refunds at a national level which are rarely reported. METHODS: The French national health data system (56 million, 87% of the population) was used to identify insurance beneficiaries with at least one drug delivery (Anatomical Therapeutic Classification R03) per year between 2012 and 2017. RESULTS: At least one drug delivery in 2017 was identified for 7.5 million people (12.9%). High proportions of people with at least one, two or three drug deliveries were observed between the ages of 0 to 2 years (22%, 10%, 5.5%), then decreased between the ages of 18 and 40 years (9.3%, 3.8%, 2.3%) and increased again in people 75 years and older (17.8%, 11.9% 9.9%), with strong variations between years. In 2017, the proportions of people with at least one delivery, either alone or in combination with other drugs, were 68% for inhaled corticosteroids (ICS) (median 1; IQR 1-4), 59% for short-acting beta2-agonists (SABA) (1; 1-3), 42% for long-acting beta2-agonists (LABA) (2; 1-6), 11% for leukotriene receptor antagonists (3; 1-9), and 12% for inhaled anti-cholinergics (4; 1-10). Younger patients more often received SABAs (0-2 years: 84%) and leukotriene receptor antagonists (3-6 years: 14%) and people 75 years and older more often received LABAs (59%) and ICS, either alone or in combination with other drugs (28%).The mean annual refund reimbursed per person decreased from €136 in 2012 to €118 in 2017. CONCLUSION: This study suggests a low level of use for drug classes associated with low delivery rates, suggesting inappropriate prescriptions and poor follow-up. These results highlight the difficulty of identifying these problems if delivery rates variations over several years are not taken into account.

Meta-analyses frequently pooled different study types together: a meta-epidemiological study.

OBJECTIVE: To evaluate the characteristics of therapeutic meta-analyses including both observational studies and randomized controlled trials (RCTs), how these studies were combined and whether there were differences in treatment effects. STUDY DESIGN AND SETTING: Meta-epidemiological study of meta-analyses, including both observational studies and RCTs. We searched MEDLINE for the five leading journals of each medical category according to Journal Citation Reports) and Cochrane Database of Systematic Reviews, from 2014 to 2018 for eligible meta-analyses and extracted how observational studies and RCTs were combined and results for each study. RESULTS: Of the 102 included meta-analyses, observational studies and RCTs were combined together without a subgroup analysis in 39 (38%) and with subgroup analysis in 15 (15%); they were pooled separately for the same outcome in 11 (11%) and not for the same outcome in 9 (9%). In 28 (27%) meta-analyses, only RCTs were combined, with a qualitative description of observational studies. Treatment effect estimates did not differ between observational studies and RCTs (ratio of estimates = 0.98 [95% confidence interval 0.80-1.21]), with substantial heterogeneity (I2 = 59%). CONCLUSION: Many meta-analyses, including both observational studies and RCTs pool results from both study types. Although treatment effects did not differ between them on average, we identified situations for which estimates differed.

Cervical cancer screening coverage, management of squamous intraepithelial lesions and related costs in France.

Until 2018, cervical cancer screening in France was an unorganized individual screening, with the exception of some pilot programs in some territories. We aimed to assess, before the implementation of organized cervical cancer screening and human papillomavirus (HPV) nonavalent vaccine introduction in the vaccination schedule in 2018, (i) the individual cervical cancer screening coverage, (ii) the management of squamous intraepithelial lesions (SIL) and (iii) the related costs. We used the Système National des Données de Santé (SNDS) (Echantillon Généraliste de Bénéficiaires [EGB] and Programme de Médicalisation des systèmes d'information [PMSI]) to assess the cervical screening coverage rate in France between January 1st, 2012 and December 31st, 2014, and to describe diagnostic investigations and therapeutic management of SIL in 2013. After extrapolation to the general population, a total of 10,847,814 women underwent at least one smear test over the 3-year study period, corresponding to a coverage rate of 52.4% of the women aged 25 to 64 included. In 2013, 126,095 women underwent HPV test, 327,444 women underwent colposcopy, and 9,653 underwent endocervical curettage; 31,863 had conization and 12,162 had laser ablation. Besides, 34,067 women experienced hospital stays related to management of SIL; 25,368 (74.5%) had high-grade lesions (HSIL) and 7,388 (21.7%) low-grade lesions (LSIL). Conization was the most frequent in-hospital therapeutic procedure: 89.5% (22,704) of women with an in-hospital procedure for HSIL and 64.7% (4,781) for LSIL. Mean cost of smear test, colposcopy and HPV tests were around 50€. Total cost for hospital stays in 2013 was estimated at M41€, or a mean cost of 1,211€ per woman; 76% were due to stays with HSIL. This study highlights the low coverage rate of individual cervical cancer screening and a high burden related to SIL management.

A prescription support-tool for chronic management of oral antithrombotic combinations in adults based on a systematic review of international guidelines.

BACKGROUND: Oral antithrombotic (AT) drugs, which include antiplatelet and anticoagulant therapies, are widely implicated in serious preventable bleeding events. Avoiding inappropriate oral AT combinations is a major concern. Numerous practical guidelines have been released; a document to enhance prescriptions of oral AT combinations for adults would be of great help. OBJECTIVE: To synthesize guidelines on the prescription of oral AT combinations in adults and to create a prescription support-tool for clinicians about chronic management (≥ one month) of oral AT combinations. METHODS: A systematic review of guidelines published between January 2012 and April 2017, in English or in French, from Trip database, Guideline International Network and PubMed, dealing with the prescription of oral ATs in adults was conducted. In-hospital management of ATs, bridging therapy and switches of ATs were not considered. Some specific topics requiring specialized follow-up (cancer, auto-immune disease, haemophilia, HIV, paediatrics and pregnancy) were excluded. Last update was made in November 2018. RESULTS: A total of 885 guidelines were identified and 70 met the eligibility criteria. A prescription support-tool summarizing medical conditions requiring chronic management of oral AT combinations in adults with drug types, dosage and duration, on a double-sided page, was provided and tested by an external committee of physicians. The lack of specific guidelines for old people (age 75 years and older) is questioned considering the specific vulnerability of this age group to serious bleedings. CONCLUSIONS: Recommendations on prescriptions about chronic management of oral AT combinations in adults were mainly consensual but dispersed in numerous guidelines according to the medical indication. We provide a prescription support-tool for clinicians. Further studies are needed to assess the impact of this tool on appropriate prescribing and the prevention of serious adverse drug events.

Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review.

BACKGROUND: Intensivists' clinical decision making pursues two main goals for patients: to decrease mortality and to improve quality of life and functional status in survivors. Patient-important outcomes are gaining wide acceptance in most fields of clinical research. We sought to systematically review how well patient-important outcomes are reported in published randomized controlled trials (RCTs) in critically ill patients. METHODS: Literature search was conducted to identify eligible trials indexed from January to December 2013. Articles were eligible if they reported an RCT involving critically ill adult patients. We excluded phase II, pilot and physiological crossover studies. We assessed study characteristics. All primary and secondary outcomes were collected, described and classified using six categories of outcomes including patient-important outcomes (involving mortality at any time on the one hand and quality of life, functional/cognitive/neurological outcomes assessed after ICU discharge on the other). RESULTS: Of the 716 articles retrieved in 2013, 112 RCTs met the inclusion criteria. Most common topics were mechanical ventilation (27%), sepsis (19%) and nutrition (17%). Among the 112 primary outcomes, 27 (24%) were patient-important outcomes (mainly mortality, 21/27) but only six (5%) were patient-important outcomes besides mortality assessed after ICU discharge (functional disability = 4; quality of life = 2). Among the 598 secondary outcomes, 133 (22%) were patient-important outcomes (mainly mortality, 92/133) but only 41 (7%) were patient-important outcomes besides mortality assessed after ICU discharge (quality of life = 20, functional disability = 14; neurological/cognitive performance = 5; handicap = 1; post-traumatic stress = 1). Seventy-three RCTs (65%) reported at least one patient-important outcome but only 11 (10%) reported at least one patient-important outcome besides mortality assessed after ICU discharge. CONCLUSION: Patient-important outcomes are rarely primary outcomes in RCTs in critically ill patients published in 2013. Among them, mortality accounted for the majority. We promote the use of patient-important outcomes in critical care trials.

International and multidisciplinary expert recommendations for the use of biologics in systemic lupus erythematosus.

BACKGROUND/PURPOSE: Despite conventional immunosuppressants, active and steroid-dependent systemic lupus erythematosus (SLE) represents a therapeutic challenge. Only one biologic, belimumab, has been approved, but other biologics are sometimes used off-label. Given the lack of evidence-based data in some clinical situations encountered in real life, we developed expert recommendations for the use of biologics for SLE. METHODS: The recommendations were developed by a formal consensus method. This method aims to formalize the degree of agreement among experts by identifying, through iterative ratings with feedback, the points on which experts agree, disagree or are undecided. Hence, the recommendations are based on the agreed-upon points. We gathered the opinion of 59 French-speaking SLE experts from 3 clinical networks dedicated to systemic autoimmune diseases (FLEUR, IMIDIATE, FAI2R) from Algeria, Belgium, France, Italy, Morocco, Switzerland and Tunisia. Represented medical specialities were internal medicine (49%), rheumatology (34%), nephrology (7%), dermatology (5%), pediatrics (3%) and cardiology (2%). Two methodologists and 3 strictly independent SLE expert groups contributed to developing these recommendations: a steering group (SG) (n=9), an evaluation group (EG) (n=28) and a reading group (RG) (n=22). Preliminary recommendations were drafted by the SG, then proposed to the EG. Each EG member rated the degree of agreement from 1 to 9 (1: lowest; 9: strongest) for each recommendation. After 2 rating rounds, the SG submitted a new version of the recommendations to the RG. With comments from the RG, the SG finalised the recommendations. RESULTS: A total of 17 final recommendations were formulated by the SG, considering all agreement scores and comments by the EG and RG members and the two methodologists. These recommendations define the subset of patients who require a biologic; the type of biologics to use (belimumab, rituximab, etc.) depending on the organ involvement and associated co-treatments; what information should be given to patients; and how to evaluate treatment efficacy and when to consider discontinuation. CONCLUSION: Overall, 17 recommendations for the good use of biologics in SLE were formulated by a large panel of SLE experts to provide guidance for clinicians in daily practice. These recommendations will be regularly updated according to the results of new randomized trials and increasing real life experience.

Standardization of search methods for guideline development: an international survey of evidence-based guideline development groups.

BACKGROUND: Effective literature searching is particularly important for clinical practice guideline development. Sophisticated searching and filtering mechanisms are needed to help ensure that all relevant research is reviewed. PURPOSE: To assess the methods used for the selection of evidence for guideline development by evidence-based guideline development organizations. METHODS: A semistructured questionnaire assessing the databases, search filters and evaluation methods used for literature retrieval was distributed to eight major organizations involved in evidence-based guideline development. RESULTS: All of the organizations used search filters as part of guideline development. The medline database was the primary source accessed for literature retrieval. The OVID or SilverPlatter interfaces were used in preference to the freely accessed PubMed interface. The Cochrane Library, embase, cinahl and psycinfo databases were also frequently used by the organizations. All organizations reported the intention to improve and validate their filters for finding literature specifically relevant for guidelines. DISCUSSION: In the first international survey of its kind, eight major guideline development organizations indicated a strong interest in identifying, improving and standardizing search filters to improve guideline development. It is to be hoped that this will result in the standardization of, and open access to, search filters, an improvement in literature searching outcomes and greater collaboration among guideline development organizations.