Citations

Introduction Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits. Methods and analysis First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to-treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials. Ethics and dissemination Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline recommendations. Several knowledge users will disseminate results through presentations at clinical rounds as well as national and international conferences. We will prepare an evidence brief and facilitate dialogue to engage policymakers and stakeholders in acting on findings. Trial registration number PROSPERO CRD42013003526.

Abstract Patients who are diagnosed with localized prostate cancer need to make critical treatment decisions that are sensitive to their values and preferences. The role of decision aids in facilitating these decisions is unknown. The authors conducted a systematic review of randomized trials of decision aids for localized prostate cancer. Teams of 2 reviewers independently identified, selected, and abstracted data from 14 eligible trials (n = 3377 men), of which 10 were conducted in North America. Of these, 11 trials compared decision aids with usual care, and 3 trials compared decision aids with other decision aids. Two trials suggested a modest positive impact on decisional regret. Results across studies varied widely for decisional conflict (4 studies), satisfaction with decision (2 studies), and knowledge (2 studies). No impact on treatment choices was observed (6 studies). In conclusion, scant evidence at high risk of bias suggests the variable impact of existing decision aids on a limited set of decisional processes and outcomes. Because current decision aids provide information but do not directly facilitate shared decision making, subsequent efforts would benefit from user‐centered design of decision aids that promote shared decision making. CA Cancer J Clin 2015;65: 239–251. © 2015 American Cancer Society.

Introduction Chronic neuropathic pain is associated with reduced health-related quality of life and substantial socioeconomic costs. Current research addressing management of chronic neuropathic pain is limited. No review has evaluated all interventional studies for chronic neuropathic pain, which limits attempts to make inferences regarding the relative effectiveness of treatments. Methods and analysis We will conduct a systematic review of all randomised controlled trials evaluating therapies for chronic neuropathic pain. We will identify eligible trials, in any language, by a systematic search of CINAHL, EMBASE, MEDLINE, AMED, HealthSTAR, DARE, PsychINFO and the Cochrane Central Registry of Controlled Trials. Eligible trials will be: (1) enrol patients presenting with chronic neuropathic pain, and (2) randomise patients to alternative interventions (pharmacological or non-pharmacological) or an intervention and a control arm. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible trials and extract information from eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias of eligible studies, recommendations from the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes we will collect, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to evaluate our confidence in treatment effects. When possible, we will conduct: (1) in direct comparisons, a random-effects meta-analysis to establish the effect of reported therapies on patient-important outcomes; and (2) a multiple treatment comparison meta-analysis within a Bayesian framework to assess the relative effects of treatments. We will define a priori hypotheses to explain heterogeneity between studies, and conduct meta-regression and subgroup analyses consistent with the current best practices. Ethics and Dissemination We do not require ethics approval for our proposed review. We will disseminate our findings through peer-reviewed publications and conference presentations. Trial registration number PROSPERO (CRD42014009212).

AbstractBackgroundExploration of values and preferences in the context of anticoagulation therapy for atrial fibrillation (AF) remains limited. To better characterize the distribution of patient and physician values and preferences relevant to decisions regarding anticoagulation in patients with AF, we conducted interviews with patients at risk of developing AF and physicians who manage patients with AF.MethodsWe interviewed 96 outpatients and 96 physicians in a multicenter study and elicited the maximal increased risk of bleeding (threshold risk) that respondents would tolerate with warfarin vs. aspirin to achieve a reduction in three strokes in 100 patients over a 2‐year period. We used the probabilistic version of the threshold technique.ResultsThe median threshold risk for both patients and physicians was 10 additional bleeds (10 P = 0.7). In both groups, we observed large variability in the threshold number of bleeds, with wider variability in patients than clinicians [patient range: 0–100, physician range: 0–50]. We observed one cluster of patients and physicians who would tolerate <10 bleeds and another cluster of patients, but not physicians, who would accept more than 35.ConclusionsOur findings suggest wide variability in patient and physician values and preferences regarding the trade‐off between strokes and bleeds. Results suggest that in individual decision making, physician and patient values and preferences will often be discordant; this mandates tailoring treatment to the individual patient's preferences.

Background Although decision aids (DA) can help to communicate evidence to patients, their production is time consuming, often not based on the best available evidence or rapidly outdated. Linking trustworthy guidelines and DA for shared-decision making could both overcome these limitations and enhance guideline dissemination. Objectives To test the feasibility of automatically translating any recommendations from GRADE guidelines into generic and interactive DA accessible on tablet computers for clinicians and their patients in the clinical encounter. Methods As part of the DECIDE project, we developed a framework for translating components of GRADE into DA, following the International Patient Decision Aid Standards. Using a recently published guideline, we implemented that framework in our MAGIC (Making Grade the Irresistible Choice) application – a prototype electronic guideline tool and publication platform that can automatically display recommendations in multilayered presentation formats. Results Our prototype was able to automatically translate a large number of GRADE recommendations and their supporting evidence into electronic and interactive DA. Preliminary results of user-testing in real patient-clinician interactions suggest that these DA can be used at the point of care to discuss estimates of treatment effects for patient relevant outcomes, confidence in estimates, burden of treatment, and cost issues. Discussion This study provides a proof-of-concept that components of GRADE recommendations can be interactively displayed in generic tools for interactive shared-decision making in a wide range of treatment alternatives. Implications for Guideline Developers/Users Our electronic DA offer promising opportunities to disseminate guidelines at the point of care.

Background In 2005, the Endocrine Society (TES) adopted the GRADE system of developing clinical practice guidelines. This system facilitates the formulation of evidence-based recommendations by explicitly describing the confidence in estimates (quality of evidence) and strength of each recommendation. Objectives To describe and characterise the relationship between confidence in estimates and strength of recommendation in TES guidelines. Methods We included all published TES guidelines between 2005 (when TES started using GRADE) and 2011. Independently and in duplicate, reviewers extracted, for each recommendation: disease area, confidence in estimates and design of the studies considered, and strength of recommendation. In strong recommendations with low quality of we developed and applied a taxonomy of appropriate recommendations and identified those we considered inappropriate. Results Most of the 357 recommendations issued were supported by evidence warranting low or very low confidence in estimates (256, 72%). Evidence cited in support of these recommendations came exclusively from observational studies in 233 recommendations (65%). Most recommendations were strong (206, 58%); of these, 121 (59%) were supported by evidence warranting low or very low confidence in estimates. In 101/121 (83%), we identified a compelling rationale for the recommendations; in 20 (17%), we did not. Conclusions Most TES strong recommendation based on low quality evidence are justified and appropriate, but a substantial proportion are not. Implications for Guideline Developers Guideline developers should carefully justify any strong recommendations based on low confidence in effect estimates.