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PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendalls tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendalls tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.

PurposeThe sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT).Materials and methodsIndividual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality.ResultsOverall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT.ConclusionADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.

The Internet is considered to be one of the most important mechanisms for sharing research (Chavkin & Chavkin, 2008), raising questions about the scope and variety of research-based education resources available online. Whereas years ago, the challenge for educators was to find relevant research information for practice, this challenge has shifted to one of sorting through the "infoglut" (Edmunds & Morris, 2000), or the abundance of information claiming to be grounded in research, and being able to judge which resources are most valuable and reliable. Drawing on scholarship that seeks to mobilize evidence between researchers, practitioners, and policymakers (Levin, 2011), this study reports the results of a systematic search of online research-based resources for educators across seven subject areas. Our descriptive typology categorizes 333 products along various dimensions (e.g., producer organization, target audience, country of origin) and demonstrates a surprising variety claiming to be research-informed.

Background: Within the wider education industry, a large quantity of ideas, practices and products are routinely promoted as useful innovations. These innovations span many forms such as software applications, open source courseware, online learning platforms and web 2.0 technologies. Coupled with this promotion, there is increasing interest and debate around the possibilities that novel innovations can have on changing education practice and providing more effective learning solutions. The media plays an important role in facilitating the travel of educational ideas: the advent of the Internet and social media technologies allows for an abundance of innovation to be promoted and shared with and between educators, and, in classroom settings, the increasing use of technologies such as tablets results in the advertisement of numerous new education applications. For the educator, there is the difficult challenge of knowing how to sift through this material and separate those innovations that may hold value for their classroom situation from those that have gained wide appeal, but may or may not be substantiated. Purpose: The purpose of this study was to explore the persuasion techniques used across a variety of documents promoting a selection of popular education innovations of different types. Questions included: (1) How are popular education innovations promoted in the media? (2) What contributes to the appeal of these innovations? and (3) What is the role of evidence in this process? Design and Methods: The paper examines how seven innovations of different types have been promoted in the mass, professional and social medias through a content analysis (a research technique used to code and interpret text) of 63 documents including non-peer reviewed journal articles (education magazines and trade publications), mass media outlet newspapers and online blog posts. The content analysis involved inductively creating and labelling sub-categories of six "persuasion criteria": "compatibility"; "accessibility"; "practicality"; "evidence"; "credibility" and "appeal." The analysis performed was not examining the worth of the innovations themselves, but rather seeking to understand how the innovations were promoted. Findings: The language that was used to promote the innovations was often emotive or descriptive, rather than evidence-informed. Documents tended to emphasise the "appeal" and "credibility" of innovations over and above the evidence that supported, or did not support, them. Where evidence was cited, it was usually anecdotal, related to personal experiences, provided general statistics about problems that the innovation sought to address, or presented statistics related to use of the innovation. Conclusions: The results of this study offer insight into why various kinds of innovations, irrespective of whether or not they are supported by an evidence base, nevertheless "catch on." The study highlights the need for practitioners to develop the evaluative skills to distinguish evidence-based innovations that are effective, and of real value, from those that may simply sound or look good.

Background: Transdiagnostic group cognitive-behavioral therapy (tCBT) is a delivery model that could help overcome barriers to large-scale implementation of evidence-based psychotherapy for anxiety disorders. The aim of this study was to assess the effectiveness of combining group tCBT with treatment-as-usual (TAU), compared to TAU, for the treatment of anxiety disorders in community-based mental health care. Methods: In a multicenter single-blind, two-arm pragmatic superiority randomized trial, we recruited participants aged 18–65 who met DSM-5 criteria for principal diagnoses of generalized anxiety disorder, social anxiety disorder, panic disorder, or agoraphobia. Group tCBT consisted of 12 weekly 2 h sessions. There were no restrictions for TAU. The primary outcome measures were the Beck Anxiety Inventory (BAI) and clinician severity rating from the Anxiety and Related Disorders Interview Schedule for DSM-5 (ADIS-5) for the principal anxiety disorder at post-treatment, with intention-to-treat analysis. Results: A total of 231 participants were randomized to either tCBT + TAU (117) or TAU (114), with outcome data available for, respectively, 95 and 106. Results of the mixed-effects regression models showed superior improvement at post-treatment for participants in tCBT + TAU, compared to TAU, for BAI [ p < 0.001; unadjusted post-treatment mean (s.d.): 13.20 (9.13) v. 20.85 (10.96), Cohen's d = 0.76] and ADIS-5 [ p < 0.001; 3.27 (2.19) v. 4.93 (2.00), Cohen's d = 0.79]. Conclusions: Our findings suggest that the addition of group tCBT into usual care can reduce symptom severity in patients with anxiety disorders, and support tCBT dissemination in routine community-based care. [ABSTRACT FROM AUTHOR]