scholarly journals A systematic breakdown of the levels of evidence supporting the European Society of Cardiology guidelines

2019 ◽  
Vol 26 (18) ◽  
pp. 1944-1952 ◽  
Author(s):  
Wouter B van Dijk ◽  
Diederick E Grobbee ◽  
Martine C de Vries ◽  
Rolf H H Groenwold ◽  
Rieke van der Graaf ◽  
...  
Keyword(s):  
Expert Opinion ◽  
European Society ◽  
Randomised Controlled Trials ◽  
Class I ◽  
Controlled Trials ◽  
Specific Recommendation ◽  
Level Of Evidence ◽  
Surgical Interventions ◽  
European Society Of Cardiology ◽  
Randomised Controlled

Aims Reviews of clinical practice guidelines have repeatedly concluded that only a minority of guideline recommendations are supported by high-quality evidence from randomised controlled trials. The aim of this study is to evaluate whether these findings apply to the whole cardiovascular evidence base or specific recommendation types and actions. Methods All recommendations from current European Society of Cardiology guidelines were extracted with their class (I, treatment is beneficial; II, treatment is possibly beneficial; III, treatment is harmful) and level of evidence (A, multiple randomised controlled trials/meta-analyses; B, single randomised controlled trials/large observational studies; C, expert opinion/small studies). Recommendations were categorised by type (therapeutic, diagnostic, other) and actions (e.g. pharmaceutical intervention/non-invasive imaging/test). Results In total, 3531 recommendations (median 128, interquartile range 108–150) were extracted from 27 guidelines. Therapeutic recommendations comprised 2545 (72.1%) recommendations, 411 (16.1%) were supported by level of evidence A, 833 (32.7%) by B and 1301 (51.1%) by C. Class I/III (should/should not) recommendations on minimally invasive interventions were most supported by level of evidence A (55/183, 30.1%) (B [70/183, 38.3%], C [58/183, 31.7%]), while class I/III recommendations on open surgical interventions were least supported by level of evidence A (15/164, 9.1%) (B [34/164, 20.7%], C [115/164, 70.1%]). Of all (831, 23.5%) diagnostic recommendations, just 44/503 (8.7%) class I/III recommendations were supported by level of evidence A (B (125/503, 24.9%), C (334/503, 66.4%)). Conclusion Evidence levels supporting European Society of Cardiology guideline recommendations differ widely between recommendation types and actions. Attributing to this variability are different evidence requirements, therapeutic/diagnostic recommendations, different feasibility levels for trials (e.g. open surgical/pharmacological) and many off-topic/policy recommendations based on expert opinion.

scholarly journals Placebo comparator group selection and use in surgical trials: the ASPIRE project including expert workshop

2021 ◽  
Vol 25 (53) ◽  
pp. 1-52
Author(s):  
David J Beard ◽  
Marion K Campbell ◽  
Jane M Blazeby ◽  
Andrew J Carr ◽  
Charles Weijer ◽  
...  
Keyword(s):  
Randomised Controlled Trials ◽  
Medical Research Council ◽  
Placebo Control ◽  
Controlled Trials ◽  
Surgical Trials ◽  
Surgical Interventions ◽  
Placebo Controls ◽  
Randomised Controlled ◽  
The Uk ◽  
Future Work

Background The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. Objectives To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. Design To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. Setting A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. Results To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. Conclusions The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. Limitations Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. Future work Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space. Funding Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council–National Institute for Health Research Methodology Research programme.

scholarly journals Surgical interventions for women with stress urinary incontinence: systematic review and network meta-analysis of randomised controlled trials

BMJ ◽  
2019 ◽  
pp. l1842 ◽  
Author(s):  
Mari Imamura ◽  
Jemma Hudson ◽  
Sheila A Wallace ◽  
Graeme MacLennan ◽  
Michal Shimonovich ◽  
...  
Keyword(s):  
Urinary Incontinence ◽  
Stress Urinary Incontinence ◽  
Adverse Events ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Surgical Interventions ◽  
Randomised Controlled ◽  
Meta Analyses

Abstract Objectives To compare the effectiveness and safety of surgical interventions for women with stress urinary incontinence. Design Systematic review and network meta-analysis. Eligibility criteria for selecting studies Randomised controlled trials evaluating surgical interventions for the treatment of stress urinary incontinence in women. Methods Identification of relevant randomised controlled trials from Cochrane reviews and the Cochrane Incontinence Specialised Register (searched May 2017), which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Medline In-Process, Medline Epub Ahead of Print, CINAHL, ClinicalTrials.gov, and WHO ICTRP. The reference lists of relevant articles were also searched. Primary outcomes were “cure” and “improvement” at 12 months, analysed by means of network meta-analyses, with results presented as the surface under the cumulative ranking curve (SUCRA). Adverse events were analysed using pairwise meta-analyses. Risk of bias was assessed using the Cochrane risk of bias tool. The quality of evidence for network meta-analysis was assessed using the GRADE approach. Results 175 randomised controlled trials assessing a total of 21 598 women were included. Most studies had high or unclear risk across all risk of bias domains. Network meta-analyses were based on data from 105 trials that reported cure and 120 trials that reported improvement of incontinence symptoms. Results showed that the interventions with highest cure rates were traditional sling, retropubic midurethral sling (MUS), open colposuspension, and transobturator MUS, with rankings of 89.4%, 89.1%, 76.7%, and 64.1%, respectively. Compared with retropubic MUS, the odds ratio of cure for traditional sling was 1.06 (95% credible interval 0.62 to 1.85), for open colposuspension was 0.85 (0.54 to 1.33), and for transobtrurator MUS was 0.74 (0.59 to 0.92). Women were also more likely to experience an improvement in their incontinence symptoms after receiving retropubic MUS or transobturator MUS compared with other surgical procedures. In particular, compared with retropubic MUS, the odds ratio of improvement for transobturator MUS was 0.76 (95% credible interval 0.59 to 0.98), for traditional sling was 0.69 (0.39 to 1.26), and for open colposuspension was 0.65 (0.41 to 1.02). Quality of evidence was moderate for retropubic MUS versus transobturator MUS and low or very low for retropubic MUS versus the other two interventions. Data on adverse events were available mainly for mesh procedures, indicating a higher rate of repeat surgery and groin pain but a lower rate of suprapubic pain, vascular complications, bladder or urethral perforation, and voiding difficulties after transobturator MUS compared with retropubic MUS. Data on adverse events for non-MUS procedures were sparse and showed wide confidence intervals. Long term data were limited. Conclusions Retropubic MUS, transobturator MUS, traditional sling, and open colposuspension are more effective than other procedures for stress urinary incontinence in the short to medium term. Data on long term effectiveness and adverse events are, however, limited, especially around the comparative adverse events profiles of MUS and non-MUS procedures. A better understanding of complications after surgery for stress urinary incontinence is imperative. Systematic review registration PROSPERO CRD42016049339.

scholarly journals Development of a practical approach to expert elicitation for randomised controlled trials with missing health outcomes: Application to the IMPROVE trial

2017 ◽  
Vol 14 (4) ◽  
pp. 357-367 ◽  
Author(s):  
Alexina J Mason ◽  
Manuel Gomes ◽  
Richard Grieve ◽  
Pinar Ulug ◽  
Janet T Powell ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Missing Data ◽  
Expert Opinion ◽  
Randomised Controlled Trials ◽  
Open Repair ◽  
Sensitivity Analyses ◽  
Controlled Trials ◽  
Strategy Versus ◽  
Randomised Controlled

Background/aims: The analyses of randomised controlled trials with missing data typically assume that, after conditioning on the observed data, the probability of missing data does not depend on the patient’s outcome, and so the data are ‘missing at random’ . This assumption is usually implausible, for example, because patients in relatively poor health may be more likely to drop out. Methodological guidelines recommend that trials require sensitivity analysis, which is best informed by elicited expert opinion, to assess whether conclusions are robust to alternative assumptions about the missing data. A major barrier to implementing these methods in practice is the lack of relevant practical tools for eliciting expert opinion. We develop a new practical tool for eliciting expert opinion and demonstrate its use for randomised controlled trials with missing data. Methods: We develop and illustrate our approach for eliciting expert opinion with the IMPROVE trial (ISRCTN 48334791), an ongoing multi-centre randomised controlled trial which compares an emergency endovascular strategy versus open repair for patients with ruptured abdominal aortic aneurysm. In the IMPROVE trial at 3 months post-randomisation, 21% of surviving patients did not complete health-related quality of life questionnaires (assessed by EQ-5D-3L). We address this problem by developing a web-based tool that provides a practical approach for eliciting expert opinion about quality of life differences between patients with missing versus complete data. We show how this expert opinion can define informative priors within a fully Bayesian framework to perform sensitivity analyses that allow the missing data to depend upon unobserved patient characteristics. Results: A total of 26 experts, of 46 asked to participate, completed the elicitation exercise. The elicited quality of life scores were lower on average for the patients with missing versus complete data, but there was considerable uncertainty in these elicited values. The missing at random analysis found that patients randomised to the emergency endovascular strategy versus open repair had higher average (95% credible interval) quality of life scores of 0.062 (−0.005 to 0.130). Our sensitivity analysis that used the elicited expert information as pooled priors found that the gain in average quality of life for the emergency endovascular strategy versus open repair was 0.076 (−0.054 to 0.198). Conclusion: We provide and exemplify a practical tool for eliciting the expert opinion required by recommended approaches to the sensitivity analyses of randomised controlled trials. We show how this approach allows the trial analysis to fully recognise the uncertainty that arises from making alternative, plausible assumptions about the reasons for missing data. This tool can be widely used in the design, analysis and interpretation of future trials, and to facilitate this, materials are available for download.

No differences in healing among different closure methods of arthroscopic portals: a systematic review

2017 ◽  
Vol 2 (6) ◽  
pp. 297-307
Author(s):  
Chetan Muralidhara Rao Dojode ◽  
Murali Krishna ◽  
Andrew James Shepherd ◽  
Chandan Muralidhara Rao Dojode ◽  
Raviprasad Kattimani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomised Controlled Trials ◽  
Tissue Adhesive ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Adhesive Tape ◽  
Level Of Evidence ◽  
Safe Alternative ◽  
Significant Difference ◽  
Randomised Controlled

BackgroundDuring arthroscopy the small skin incisions made over the joints are called arthroscopy portals. There are different methods described for arthroscopic portal closure. Very few randomised controlled trials and no systematic reviews have compared the methods of arthroscopic portal closure, and there are no clear guidelines recommending any one closure method. There is therefore a need for a systematic review that provides high-quality evidence to help surgeons choose the appropriate arthroscopic portal closure technique.ObjectiveTo undertake a systematic review to ascertain the outcome with three different closure methods for arthroscopic portals: (1) suturing; (2) application of sterile adhesive tapes; and (3) leaving wounds open covered with a dressing.MethodsRandomised controlled trials comparing the closure methods of arthroscopic portals were selected using strict search criteria from electronic databases (MEDLINE, EMBASE, CINAHL, BNI and Cochrane Library) and trial registers. Two independent authors conducted the study selection, data extraction and quality assessment of each study. Quality appraisal was done using the Cochrane Collaboration risk of bias tool. Three studies were eligible for inclusion and a narrative synthesis of the findings is provided.ResultsOne study did not show a statistically significant difference between suturing and leaving the wound open with a dressing. However, two studies found that leaving wounds open covered with a dressing had a significantly better outcome. In one of these studies, sterile adhesive tapes were used and the outcomes were better than with suturing but not so good as leaving the wounds open covered with a dressing.ConclusionSuturing of arthroscopic portal wounds confers no benefit over leaving them open covered with a simple dressing or applying sterile adhesive tapes. Meta-analysis was not performed, so a full estimate of effect size cannot be derived from this review. Managing arthroscopic portals by leaving them open covered with a dressing or by applying tissue adhesive tape can be safe alternative techniques to suturing. There is a need for randomised controlled trials with a larger sample size representing different populations in a number of centres with better methodological quality and outcome measures.Level of evidenceLevel 1 Systematic review of Randomised Control Trials (Level I studies).

Probiotics for allergy prevention

2016 ◽  
Vol 7 (2) ◽  
pp. 171-179 ◽  
Author(s):  
C.E. West
Keyword(s):  
High Risk ◽  
Allergic Disease ◽  
Randomised Controlled Trials ◽  
Controlled Trials ◽  
Allergy Prevention ◽  
Level Of Evidence ◽  
Familial Predisposition ◽  
Randomised Controlled

Probiotics, given either as a supplement or in infant foods, have been evaluated in randomised controlled trials for allergy prevention. Here, the aim is to give an overview of the results from these primary prevention studies and to discuss current strategies. In most studies, single strains or a mixture of strains of lactic acid bacteria and bifidobacteria have been used – prenatally, postnatally or perinatally. Several meta-analyses have reported a moderate benefit of probiotics for eczema prevention, and the most consistent effect has been observed with a combined perinatal intervention in infants at high risk of allergic disease due to familial predisposition. In a recent meta-analysis, the use of multi-strain probiotics appeared to be most effective for eczema prevention. No preventive effect has been shown for other allergic manifestations. As long-term follow-up data on later onset allergic conditions (asthma and allergic rhinitis) are available only from a few of the initiated studies, reports from ongoing follow-up studies that are adequately powered to examine long-term outcomes are anticipated to provide more insight. Arguably, the differences in many aspects of study design and the use of different probiotic strains and combinations have made direct comparison difficult. To date, expert bodies do not generally recommend probiotics for allergy prevention, although the World Allergy Organization (WAO) in their recently developed guidelines suggests considering using probiotics in pregnant women, during breastfeeding and/or to the infant if at high risk of developing allergic disease (based on heredity). However, in concordance with other expert bodies, the WAO guideline panel stressed the low level of evidence and the need for adequately powered randomised controlled trials and a more standardised approach before clinical recommendations on specific strains, dosages and timing can be given.

Acupuncture in the Emergency Department: A Systematic Review of Randomised Controlled Trials

2018 ◽  
Vol 36 (3) ◽  
pp. 183-192 ◽  
Author(s):  
Kwan Leung Chia ◽  
Rex Pui Kin Lam ◽  
Chung Kwun Lam ◽  
Sik Hon Tsui
Keyword(s):  
Systematic Review ◽  
Emergency Department ◽  
Randomised Controlled Trials ◽  
Sham Acupuncture ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Level Of Evidence ◽  
Assessment Development ◽  
Bibliographic Search ◽  
Randomised Controlled

Introduction A comprehensive review of both English and Chinese language literature to inform acupuncture practice in emergency department (ED) settings is lacking. Accordingly, we aimed to conduct a systematic review of English and Chinese randomised controlled trials (RCTs) of acupuncture use in the ED. Methods Four English databases (Embase, PubMed, AMED and CENTRAL) and two Chinese databases (CNKI and Wanfang) were systematically searched using the keywords ‘acupuncture’ and ‘emergency department’, followed by a bibliographic search of references. The data were extracted and assessed by two independent authors. RCTs were selected based on pre-defined criteria. Data were extracted and a risk of bias assessment was performed using the Cochrane risk of bias tool. The quality of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results In total, 1461 articles were screened and six RCTs involving 651 patients were included. For various acute pain conditions, acupuncture was superior to sham acupuncture, more effective than intravenous morphine, comparable to conventional ED treatment, and superior to standard ED care alone when used on an adjuvant basis; however, the overall level of evidence was low. Studies that applied acupuncture in hypertension and cardiac arrest were deemed to be at high risk of bias, and the level of evidence for these outcomes was very low. No major adverse events were reported in the included studies. Conclusion There is a lack of high-quality evidence to support the use of acupuncture in the ED. Multicentre RCTs with rigorous designs are warranted.

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