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Randomized clinical trials are critical for evaluating the safety and efficacy of interventions in oncology and informing regulatory decisions, practice guidelines, and health policy. Patient-reported outcomes (PROs) are increasingly used in randomized trials to reflect the impact of receiving cancer therapies from the patient perspective and can inform evaluations of interventions by providing evidence that cannot be obtained or deduced from clinicians’ reports or from other biomedical measures. This commentary focuses on how PROs add value to clinical trials by representing the patient voice. We employed 2 previously published descriptive frameworks (addressing how PROs are used in clinical trials and how PROs have an impact, respectively) and selected 9 clinical trial publications that illustrate the value of PROs according to the framework categories. These include 3 trials where PROs were a primary trial endpoint, 3 trials where PROs as secondary endpoints supported the primary endpoint, and 3 trials where PROs as secondary endpoints contrast the primary endpoint findings in clinically important ways. The 9 examples illustrate that PROs add valuable data to the care and treatment context by informing future patients about how they may feel and function on different treatments and by providing clinicians with evidence to support changes to clinical practice and shared decision making. Beyond the patient and clinician, PROs can enable administrators to consider the cost-effectiveness of implementing new interventions and contribute vital information to policy makers, health technology assessors, and regulators. These examples provide a strong case for the wider implementation of PROs in cancer trials.

Infectious illness is the biggest cause of death in children due to a physical illness, particularly in children under five years. If mortality is to be reduced for this group of children, it is important to understand factors affecting their pathways to hospital.The aim of this study was to retrospectively identify organisational and environmental factors, and individual child, family, and professional factors affecting timing of admission to hospital for children under five years of age with a serious infectious illness (SII).MethodsAn explanatory modified grounded theory mixed methods design was used in collaboration with parents. Two stages of data collection were conducted: Stage 1, interviews with 22 parents whose child had recently been hospitalised with a SII and 14 health professionals (HPs) involved in their pre-admission trajectories; Stage 2, focus groups with 18 parents and 16 HPs with past experience of SII in young children. Constant comparative analysis generated the explanatory theory.FindingsThe core category was ‘navigating uncertain illness trajectories for young children with serious infectious illness’. Uncertainty was prevalent throughout the parents’ and HPs’ stories about their experiences of navigating social rules and overburdened health services for these children. The complexity of and lack of continuity within services, family lives, social expectations and hierarchies provided the context and conditions for children’s, often complex, illness trajectories. Parents reported powerlessness and perceived criticism leading to delayed help-seeking. Importantly, parents and professionals missed symptoms of serious illness. Risk averse services were found to refer more children to emergency departments.ConclusionsParents and professionals have difficulties recognising signs of SII in young children and can feel socially constrained from seeking help. The increased burden on services has made it more difficult for professionals to spot the seriously ill child.

PURPOSE: Peer review (PR) is an important component in ensuring high-quality lung radiotherapy (RT) plans. However, there are inconsistencies in the extent, timing, and minimum requirements for PR. We sought to develop guidelines of best practices for PR in curative lung RT through an expert consensus process. METHODS: A modified Delphi process was conducted that consisted of an initial review by a dedicated steering committee followed by a pan-Canadian, multidisciplinary Delphi panel with 3 rounds (premeeting survey, face-to-face meeting, and postmeeting ratification survey). Candidate PR elements were ranked by importance and stratified by treatment of locally advanced (LA) disease with conventional RT or stereotactic ablative body RT (SABR) for early-stage disease. RESULTS: For the LA case, 6 elements (indications for RT, gross tumor volume [GTV], clinical target volume [CTV], internal target volume [ITV], dose/fractionation, and normal lung dosimetry) were considered as essential PR elements. Of these, 90%-100% of the panel endorsed them to be important to PR, and 80% believed that the PR should be done by a second radiation oncologist (RO). In the SABR case, 6 PR elements (indications for RT, GTV, CTV/ITV, organs at risk contours, dose/fractionation, and composite plan review) were deemed essential. Of these, 90%-100% of panel members believed these elements to be important to PR and unanimously agreed that PR should be done by a second RO. CONCLUSION: A suite of PR elements for lung RT has been developed and endorsed with high consensus. This suite should serve as a basis to help to harmonize PR practices across centers and to help to develop novel PR approaches going forward.

Purpose: Guidelines recommend that oncologists discuss goals of care (GOC) with patients who have advanced cancer and that these patients be referred for early palliative care (PC). An audit of practice between 2010 and 2015 at the Cancer Centre of Southeastern Ontario suggested that these rates were suboptimal. We sought to improve the rate of documentation of GOC and referral to PC through the implementation of a quality improvement (QI) initiative. Methods: Patients receiving palliative systemic treatment of lung, pancreatic, colorectal, and breast cancer were identified via electronic pharmacy records and the electronic patient care system. Using the Define, Measure, Analyze, Improve, Control QI methodology, we drafted a guideline for GOC documentation and PC referral and designed a standardized documentation system. E-mail reminders were sent to physicians and a QI scorecard was displayed to document overall and individual physician rates of GOC documentation. Data were analyzed monthly and presented on statistical process control P charts. Results: Between May 2016 and November 2017, a total of 303 unique patients were identified (52%, 21%, 17%, and 10% with lung, breast, colorectal, and pancreatic cancer, respectively). GOC documentation increased significantly over the study period (baseline, 0%; passive phase, 3%; active phase, 31%); this increase was likely because of our intervention. PC referral rates also increased over the study period (baseline, 36%; passive phase, 35%; active phase 48%). We did not identify any patient, physician, or disease factors that were associated with GOC discussion or referral to PC. Conclusion: Our QI initiative was successful in improving rates of GOC documentation in patients with advanced cancer.

Background Progression-free survival (PFS) is often used as a clinical trials outcome for evaluating new therapies for solid tumors. While PFS is a validated surrogate for overall survival (OS) or quality of life (QOL) in some settings, it is increasingly used in contexts where surrogacy is not established. PFS is a composite endpoint of survival, symptomatic progression, and imaging-only progression. The intrinsic value of asymptomatic (imaging-only) progression from the patient perspective is not known. Methods Patients with advanced metastatic cancer (lung, colorectal, or ovarian) participated in a discrete choice experiment, with a structured treatment choice trade-off exercise. The interview guide and visual aids were developed by a multidisciplinary team including patient representatives. Participants were provided with a hypothetical clinical scenario and treatment options resulting in the same OS duration. A sliding scale was used for duration of delay in imaging progression to determine each patient’s willingness to trade longer time for a given level of toxicity. Results 20 (11 M, 9 F) patients participated. 85 % (n = 17) of patients chose treatment with less toxicity and shorter duration even if associated with a shorter time to worsening imaging. Two patients chose a trade-off for a more toxic treatment with an increase in imaging PFS by 18 months and 24 months respectively. One patient chose to always opt for most aggressive treatment irrespective of PFS benefit and toxicity. Conclusions Most patients with metastatic cancer currently being treated with palliative chemotherapy considered delayed imaging progression in the absence of OS gain to be of low value. Policy statement PFS should not be assumed to have intrinsic value to patients in the absence of surrogacy for OS or QOL when making drug treatment and policy decisions.

Purpose Peer review of radiation oncology treatment plans is increasingly recognized as an important component of quality assurance in radiation treatment planning and delivery. Peer review of treatment plans can directly improve the quality of those plans and can also have indirect effects on radiation treatment programs. We undertook a systematic, qualitative approach to describing the indirect benefits of peer review, factors that were seen to facilitate or act as barriers to the implementation of peer review, and strategies to address these barriers across a provincial jurisdiction of radiation oncology programs (ROPs). Methods and materials Semistructured qualitative interviews were held with radiation oncology department heads and radiation therapy managers (or delegates) in all 14 ROPs in Ontario, Canada. We used a theoretically guided phenomenological qualitative approach to design and analyze the interview content. Themes were recorded by 2 independent reviewers, and any discordance was resolved by consensus. Results A total of 28 interviews were completed with 32 interviewees. Twenty-two unique themes addressed perceived benefits of peer review, relating to either peer review structure (n = 3), process (n = 9), or outcome (n = 10). Of these 22 themes, 19 related to indirect benefits to ROPs. In addition, 18 themes related to factors that facilitated peer review activities and 30 themes related to key barriers to implementing peer review were identified. Findings were consistent with, and enhanced the understanding of, previous survey-based assessments of the benefits and challenges of implementing peer review programs. Conclusions Although challenges and concerns regarding the implementation of peer review were evident, the indirect benefits to radiation programs are numerous, far outweigh the implementation challenges, and strongly complement the direct individual-patient benefits that result from peer review quality assurance of radiation treatment plans.

Importance It is unclear whether patients with advanced cancer value surrogate end points, particularly progression-free survival (PFS). Despite this uncertainty, surrogate end points form the basis of regulatory approval for the majority of new cancer treatments. Objective To summarize and qualitatively assess studies evaluating whether patients with advanced cancer understand and value PFS. Evidence Review MEDLINE, Embase, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature databases were searched from database inception to November 12, 2018. Articles eligible for inclusion investigated patient understanding, preference, or perceived value of disease progression or PFS in the setting of advanced cancer. Three authors independently reviewed and extracted data from all studies eligible for inclusion. Findings In total, 17 studies representing 3646 patients were included. Of these studies, 15 specifically aimed to assess patients’ values toward, and their willingness to trade off toxic effects for gains or losses in the end point of PFS. All studies examined used widely disparate definitions when attempting to describe the meaning of PFS to patients. Ten studies specifically presented patients with the termprogression-free survivalas an attribute choice. In the words used to define the attribute of PFS, 6 studies used the termsurvival. Five studies clarified that PFS may not translate into better overall survival, and 5 studies explained that improvements in PFS may not reflect how well the patient may feel. No study clarified that a PFS event could represent either progression or death, and no study defined for the patient what constituted progression. The studies assessed herein underrepresented ethnic and racial minorities (mean percentage of white patients, 88%; range, 77%-96%). Values and preferences may vary across cultural backgrounds given that different relative preferences were assigned to cost and efficacy outcomes in North American vs Asian studies, although only a few studies were evaluated. Conclusions and Relevance The existing literature evaluating patients’ understanding, preferences, and values toward the end point of PFS was severely limited by the heterogeneity of methods, attribute selection, and descriptions used to define PFS to patients. High-quality studies are needed that clearly define PFS for patients and that systematically document their understanding of the term. Only then can it be assessed whether PFS is an end point of value to patients with advanced cancer.

Peer review (PR) of treatment plans has been recognized internationally as a key component of quality care in radiation oncology programs (ROPs). We conducted a survey of Canadian ROPs to describe current PR practices and identify barriers/facilitators to PR optimization.A 42-item e-survey was sent to all Canadian ROPs (n = 44). Survey development was guided by expert consensus, literature review, and existing guidelines. One multidisciplinary response per ROP was requested.Response rate was 100.0% (44/44). All ROPs (100.0%) reported conducting some PR and rated its importance as 7/10 or higher (10 = extremely important). One-half of ROPs (52.3%) peer-reviewed80% of curative treatment plans. ROPs reported performing PR "always/almost always" pretreatment (38.6%) or before 25% of radiation therapy delivery (52.3%). The majority of ROPs reported recommending major plan changes in5% of plans (88.6%) and documenting findings in the medical record (58.1%). Barriers to PR were radiation oncologist availability (34.1%) and time constraints (27.3%). Facilitators included development of PR standards (97.7%) and education/support (90.9%).The ROPs perceive PR as highly important, but substantial variation in the extent, timing, and documentation of PR exists. The understanding of current PR activities, barriers, and facilitators will inform the development of initiatives to optimize PR in radiation oncology.

During the manufacture of the chemotherapeutic enzyme Erwinia chrysanthemi l -asparaginase, a small proportion (approximately 5–15%) of acidic variants, including deamidated species, are observed. Although the deamidated forms appear to have similar specific activity and quaternary structure to the unmodified enzyme, monitoring and control of these forms is important from a regulatory perspective. The extent of Asn to Asp deamidation directly correlates with the time taken to thaw the Erwinia cells. Erwinia l -asparaginase is a tetrameric enzyme containing one site, Asn281, theoretically very labile to deamidation due to the sequence Asn-Gly. Structurally, this part of the protein sequence is completely buried inside the tetramer, but solvent-exposed upon tetramer dissociation. During the cell thawing and alkaline lysis sequence of the process, lengthening the cell thaw times by up to 24 h allowed tetramer to reassociate, protected Asn281 from deamidation and reduced the acidic species content of the l -asparaginase from approximately 17% to 9% as measured by weak cation-exchange (WCX) HPLC. The correlation of cell thaw time with acidic species content was also confirmed using capillary zone electrophoresis (CZE) and peptide mapping. These studies demonstrate that cell thaw time is an important, if unexpected, control variable for l -asparaginase deamidation.

Purpose To describe the outcomes of peer review across all 14 cancer centers in Ontario. Methods and Materials We identified all peer-reviewed, curative treatment plans delivered in Ontario within a 3-month study period from 2013 to 2014 using a provincial cancer treatment database and collected additional data on the peer-review outcomes. Results Considerable variation was found in the proportion of peer-reviewed plans across the centers (average 70.2%, range 40.8%-99.2%). During the study period, 5561 curative plans underwent peer review. Of those, 184 plans (3.3%) had changes recommended. Of the 184 plans, the changes were major (defined as requiring repeat planning or having a major effect on planning or clinical outcomes, or both) in 40.2% and minor in 47.8%. For the remaining 12.0%, data were missing. The proportions of recommended changes varied among disease sites (0.0%-7.0%). The disease sites with the most recommended changes to treatment plans after peer review and with the greatest potential for benefit were the esophagus (7.0%), uterus (6.7%), upper limb (6.3%), cervix and lower limb (both 6.0%), head and neck and bilateral lung (both 5.9%), right supraclavicular lymph nodes (5.7%), rectum (5.3%), and spine (5.0%). Although the heart is an organ at risk in left-sided breast treatment plans, the proportions of recommended changes did not significantly differ between the left breast treatment plans (3.0%, 95% confidence interval 2.0%-4.5%) and right breast treatment plans (2.4%, 95% confidence interval 1.5%-3.8%). The recommended changes were more frequently made when peer review occurred before radiation therapy (3.8%) than during treatment (1.4%-2.8%; P =.0048). The proportion of plans with recommended changes was not significantly associated with patient volume ( P =.23), peer-review performance ( P =.36), or center academic status ( P =.75). Conclusions Peer review of treatment plans directly affects the quality of care by identifying important clinical and planning changes. Provincial strategies are underway to optimize its conduct in radiation oncology.

99 Background: Progression-free survival (PFS) is often used as a clinical trials outcome for evaluating new therapies for solid tumors. While PFS is a validated surrogate for overall survival (OS) or quality of life (QOL) in some settings, it is increasingly used in contexts where surrogacy is not established. The end point is a composite of survival, symptomatic progression, and imaging-only progression. The intrinsic value of asymptomatic (imaging-only) progression from the patient perspective is not known. Methods: Patients with advanced metastatic cancer (lung, colorectal, or ovarian) who had completed at least 3 months of chemotherapy and were attending a routine ambulatory clinic were recruited and participated in a structured discrete choice trade-off exercise. The interview guide and visual aids were developed by a multidisciplinary team including patient representatives. Participants were provided with a hypothetical clinical scenario and associated treatment options. Treatment options presented had the same OS time but longer time to imaging progression and were associated with various levels of toxicity and treatment time. A sliding scale was used for duration of imaging-only PFS to determine each patient’s willingness to trade longer time for a given level of toxicity. Results: 20 (11M, 9F) patients participated in interviews (Nov 2017 - Jun 2018). Given the scenario 85% (n = 17) of patients chose treatment with less toxicity and treatment duration even if associated with a shorter imaging-only PFS. Two patients chose a trade-off for a more toxic treatment with an increase in imaging PFS by 18 months and 24 months respectively. One patient chose to always opt for most aggressive treatment irrespective of PFS benefit and toxicity. Conclusions: Patients with metastatic cancer currently being treated with palliative chemotherapy overwhelmingly considered imaging-only PFS to be of low value when it was associated with increased toxicity but not with longer OS. In situations where surrogacy for OS and QOL has not been established, endpoints that de-emphasise the importance of imaging are required.

BackgroundThe use of aspirin is well established for secondary prevention of cardiovascular disease. However, a proportion of patients suffer repeat cardiovascular events despite being prescribed aspirin treatment. It is uncertain whether or not this is due to an inherent inability of aspirin to sufficiently modify platelet activity. This report aims to investigate whether or not insufficient platelet function inhibition by aspirin (‘aspirin resistance‘), as defined using platelet function tests (PFTs), is linked to the occurrence of adverse clinical outcomes, and further, whether or not patients at risk of future adverse clinical events can be identified through PFTs.ObjectivesTo review systematically the clinical effectiveness and cost-effectiveness evidence regarding the association between PFT designation of ‘aspirin resistance’ and the risk of adverse clinical outcome(s) in patients prescribed aspirin therapy. To undertake exploratory model-based cost-effectiveness analysis on the use of PFTs.Data sourcesBibliographic databases (e.g. MEDLINE from inception and EMBASE from 1980), conference proceedings and ongoing trial registries up to April 2012.MethodsStandard systematic review methods were used for identifying clinical and cost studies. A risk-of-bias assessment tool was adapted from checklists for prognostic and diagnostic studies. (Un)adjusted odds and hazard ratios for the association between ‘aspirin resistance’, for different PFTs, and clinical outcomes are presented; however, heterogeneity between studies precluded pooling of results. A speculative economic model of a PFT and change of therapy strategy was developed.ResultsOne hundred and eight relevant studies using a variety of PFTs, 58 in patients on aspirin monotherapy, were analysed in detail. Results indicated that some PFTs may have some prognostic utility, i.e. a trend for more clinical events to be associated with groups classified as ‘aspirin resistant’. Methodological and clinical heterogeneity prevented a quantitative summary of prognostic effect. Study-level effect sizes were generally small and absolute outcome risk was not substantially different between ‘aspirin resistant’ and ‘aspirin sensitive’ designations.No studies on the cost-effectiveness of PFTs for ‘aspirin resistance’ were identified. Based on assumptions of PFTs being able to accurately identify patients at high risk of clinical events and such patients benefiting from treatment modification, the economic model found that a test–treat strategy was likely to be cost-effective. However, neither assumption is currently evidence based.LimitationsPoor or incomplete reporting of studies suggests a potentially large volume of inaccessible data. Analyses were confined to studies on patients prescribed aspirin as sole antiplatelet therapy at the time of PFT. Clinical and methodological heterogeneity across studies precluded meta-analysis. Given the lack of robust data the economic modelling was speculative.ConclusionsAlthough evidence indicates that some PFTs may have some prognostic value, methodological and clinical heterogeneity between studies and different approaches to analyses create confusion and inconsistency in prognostic results, and prevented a quantitative summary of their prognostic effect. Protocol-driven and adequately powered primary studies are needed, using standardised methods of measurements to evaluate the prognostic ability of each test in the same population(s), and ideally presenting individual patient data. For any PFT to inform individual risk prediction, it will likely need to be considered in combination with other prognostic factors, within a prognostic model.Study registrationThis study is registered as PROSPERO 2012:CRD42012002151.FundingThe National Institute for Health Research Health Technology Assessment programme.

Derived conditional discrimination was evaluated in 2 men with mental retardation whose language was limited to gestural requests. In each conditional-discrimination task, sample stimuli were arbitrary visual forms and comparison stimuli were black squares presented in 2 of the 4 corners of a computer screen. Subjects learned to select 1 position (P1) in the presence of 2 different samples (A1 and 81), and to select a different position (P2) in the presence of another 2 samples (A2 and 82). Next, new position responses (P3 and P4) were taught in the presence of A 1 and A2, respectively. Tests then showed that the 81 and 82 sample stimuli controlled selection of P3 and P4, respectively. The data for 1 subject provided strong evidence for derived conditional responding, while the data for the other were suggestive. This is 1 of a very few studies of derived conditional discrimination in individuals without naming skills.

Two adults with mental retardation demonstrated the recombination of within-syllable units (onsets and rimes) using a spoken-to-printed-word matching-to-sample (MTS) procedure. Further testing with 1 participant showed comprehension of the printed words. Printed-word naming was minimal before, but greater after, comprehension tests. The findings suggest that these procedures hold promise for further basic and applied analyses of word-attack skills.

180 Background: Peer review (PR) is an essential component of quality assurance in radiation oncology practice, endorsed by Canadian cancer agencies as a national standard of quality care. However, reported patterns of care studies indicate that PR practice varies considerably, including which contours (e.g., target volumes, organs at risk (OARs)), which dose parameters (e.g., OAR constraints, homogeneity criteria), which decision making points (e.g., decision to treat, selection of anatomical regions), and which treatment imaging parameters are included in the PR process. Both qualitative and quantitative evidence support the need for guidance on PR best practices. Here we report processes for the establishment of best-practice guidelines/minimal standards for PR. Methods: A comprehensive literature review was done to quantify PR findings for each of 3 cancer streams: head/neck, lung, and breast. This evidence summarized which aspects of radiotherapy plans were most frequently "flagged" at PR. A modified Delphi process was used to develop cancer site-specific PR guidance documents: appropriate stakeholders were first identified; a pre-meeting survey determined opinions on which plan elements are essential/important to review; a face-to-face meeting considered the evidence base and survey results to reach consensus. Parallel processes were conducted separately for each stream. Results: The literature findings were compiled to summarize the reported proportion of plans flagged by PR, and the nature of the flag (i.e. volumes, dose, OARs, other) for each cancer stream. Stakeholders included radiation oncologists, physicists, radiation therapists, and patients, specific to each stream. Draft guidance documents were created on the basis of stakeholder consensus regarding which components of PR were deemed essential; other important or “second tier” elements were also identified. Conclusions: Guidance documents including minimum standards for PR can be successfully created based on structured consensus development informed by available evidence. This guidance promises to reduce variation in PR thereby optimizing the efficiencies of PR processes, and increasing the quality of radiation treatment plans.

Electric-shock punishment produces stimulus-generalization gradients with animals. The purpose of the present experiments was to determine whether response-cost punishment produces similar gradients with humans. In Experiment 1, psychophysical procedures were used to generate a set of 10 horizontal lines that differ in length such that adjacent lines were indiscriminable, then reinforcement gradients were obtained with those lines to show that gradients can be produced with those stimuli. In Experiment 2, subjects pressed a lever for points exchangeable for money on a VI schedule in the presence of each stimulus, then points were lost immediately after each response in the presence of Stimulus 6 (the middle value). Response rate decreased in the presence of Stimulus 6, but it had a similar increase in the presence of all other stimuli. Those results suggest that point loss and not line length was the discriminative stimulus for further point loss. To minimize stimulus control exerted by immediate point loss, and thus enhance control by line length, in Experiment 3 points were lost only at the end of the component correlated with Stimulus 6, and in Experiment 4 point loss was arranged on VR and VI schedules. Neither delayed nor intermittent point loss produced gradients: Unpunished response rate was similar in the presence of all line lengths. The present results suggest that the technique of reinforcing responding in the presence of several stimuli during baseline then punishing responding in the presence of only one of those stimuli does not produce with humans and response-cost punishment the gradients obtained with pigeons and electric-shock punishment.

238 Background: Peer review (PR) in radiation oncology (RO) has been endorsed as an indicator of treatment quality in North America and internationally. The direct benefits of PR include quality assurance (QA) on individual treatment plans. The indirect benefits for radiation oncology departments or programs (ROPs) have been postulated but not systematically evaluated. We used a rigorous and comprehensive qualitative approach to explore the indirect benefits of PR across a jurisdiction of cancer care, and to identify factors that facilitate PR, barriers to implementation, and strategies for expansion of PR across centers. Methods: Semi-structured qualitative interviews were held with all RO heads and Radiation therapy Managers (or delegate) in all 14 Radiation Oncology Programs (ROPs) in Ontario, Canada. The interview questions were developed using a Knowledge Translation Theoretical Domains Framework (TDF), guided by the results of a previous survey of Ontario cancer centers and by expert consensus. Interviews were audiotaped and abstracted for relevant themes by two independent analysts. Results: All interviewees endorsed numerous direct and indirect benefits of PR, and identified multiple facilitators and barriers to the implementation of PR. Thematic saturation was achieved. The structure-process-outcome model was used to categorize the results. Key findings included the identification of 34 independent benefits (structure n = 4, process n = 17, outcome n = 13), 40 key barriers (structure n = 9, process n = 26, outcome n = 5), and 22 facilitators (structure n = 4, process n = 15, outcome n = 3). Beyond QA, commonly endorsed benefits included enhanced knowledge sharing, efficiency, standardization, and education. Multiple potential strategies for the expansion of PR activities were revealed. Conclusions: The qualitative exploration of Ontario ROPs acknowledges that multiple barriers and facilitators to PR exist while clearly establishing the indirect benefit of PR on ROPs. Understanding reported barriers and facilitators and exploration of suggested strategies will inform continued implementation and expansion of PR activities, and seem generalizable to other jurisdictions.

205 Background: Review of treatment plans by a second radiation oncologist is an important quality indicator in radiation oncology. Peer review (PR) can improve quality of care in individual patients by detecting clinical and planning issues and recommending plan changes. This study reports the frequency and nature of these changes across all 14 radiation oncology programs (ROPs) in Ontario, Canada. Methods: We identified all peer-reviewed curative treatment plans delivered in Ontario within a 3-month study period between Dec 2013-Nov 2014 using Cancer Care Ontario’s Activity Level Reporting System, where data on treatment intent and date, disease site treated, PR status, timing of PR, and nature of recommended changes were available. Results: There was considerable variation in the proportion of plans peer-reviewed across ROPs (70.2%, range: 40.8-99.2%). Over the study period, 5,561 curative treatment plans were peer-reviewed and 3.3% had changes recommended. Of those, 21.0% had major clinical and re-planning implications. Recommended changes most often involved minor (63.1%) vs major (36.9%) re-planning implications. Highest proportions of changes were recommended for the treatment of the esophagus, uterus, upper limb, cervix, lower limb, H&N, bilateral lung, right supraclavicular nodes, rectum, and spine (5.0%-7.0%). Plans involving the left breast had slightly more changes recommended (3.0% [95%CI:2.0%-4.5%]) vs right breast (2.4% [95%CI:1.5%-3.8%]). Recommendations were more frequently made when PR was conducted pre-radiotherapy (3.8%) vs during (1.4%-2.8%; p = 0.005), however the nature and implementation of changes were not statistically associated with the timing of PR (p = 0.91; p = 0.23, respectively). Proportion of recommended changes to treatment plans was not statistically associated with ROP patient volume (p = 0.08), proportion of plans peer-reviewed (p = 0.36) or academic status (p = 0.75). Conclusions: Significant variation exists in the proportion of recommended changes across all disease sites and ROPs. PR seems effective in detecting treatment plans with important clinical and planning issues; strategies should be developed to optimize its conduct in radiation oncology.

The study of discriminative stimulus control of responding maintained by positive reinforcement has a long-standing and dominant role in the behavioral literature. In contrast, the literature on discriminative stimulus control of response suppression by punishment is small and moribund. Investigating the form of stimulus control that develops under conditions of punishment is a topic in need of further attention for both theoretical and practical reasons. In preparations wherein stimulus control can develop (e.g., multiple schedules), at least two stimuli can come to exert discriminative control over response suppression: an antecedent discriminative stimulus (e.g., multiple-schedule stimulus) and the punisher delivery itself. We reviewed the experimental and applied literatures involving punishment and found only a few unambiguous demonstrations of operant stimulus control by an antecedent stimulus. We discuss limitations in methods, and conventions of data analysis and presentation, that preclude unambiguous conclusions regarding the establishment of antecedent stimulus control with punishment. A consideration of these limitations is important because they bear on both basic and applied issues in behavior analysis.

Although previous studies have shown that the Balloon Analogue Risk Task (BART; [Lejuez, C.W., Read, J.P., Kahler, C.W., Richards, J.B., Ramsey, S.E., Stuart, G.L., et al. (2002). Evaluation of a Behavioral Measure of Risk Taking: The Balloon Analogue Risk Test (BART). J Exp Psychol, Appl, 8, 75-84.; Lejuez, C., Aklin, W., Jones, H., Richards, J., Strong, D., Kahler, C.W., et al. (2003a). The Balloon Analogue Risk Task (BART) Differentiates Smokers and Nonsmokers. Exp Clin Psychopharmacol, 11, 26-33.; Lejuez, C., Aklin, W., Zvolensky, M., & Pedulla, C. (2003b). Evaluation of the Balloon Analogue Risk Task (BART) as a Predictor of Adolescent Real-world Risk-taking Behaviors. J Adolesc, 26, 475-479.]) can be used to index real-world risk-taking behavior, questions remain regarding how performance on the task may vary as a function of reward/loss value and how this relationship may differ as a function of relevant personality traits. The present study examined BART score at 1, 5, and 25 cents per pump and how this relationship differed at low and high levels of impulsivity and sensation seeking. Results indicated that riskiness on the BART decreased as reward/loss magnitude increased. Further, this decrease was most prominent in those low in Impulsivity/Sensation Seeking, whereas those high in Impulsivity/Sensation Seeking were largely insensitive to variation in reward/loss magnitude. Findings are discussed in terms of sensitivity to reward and loss, and how these processes can be studied further using the BART including extensions to cognitive modeling and the measurement of neurobehavioral functioning.

The study of equivalence relations exhibited by individuals with mental retardation and language limitations holds the promise of providing information of both theoretical and practical significance. We reviewed the equivalence literature with this population, defined in terms of subjects having moderate, severe, or profound mental retardation. The literature includes 55 such individuals, most of whom showed positive outcomes on equivalence tests. The results to date suggest that naming skills are not necessary for positive equivalence test outcomes. Thus far, however, relatively few subjects with minimal language have been studied. Moreover, we suggest that the scientific contributions of studies in this area would be enhanced with better documentation of language skills and other subject characteristics. With recent advances in laboratory procedures for establishing the baseline performances necessary for equivalence tests, this research area is poised for rapid growth.

Two experiments demonstrated stimulus control and generalization of conditioned punishment with humans. In both studies, responses first were reinforced with points exchangeable for money on a variable-interval schedule in the presence of one line length (S(D)). Next, a second line length was introduced, and point loss followed every response in the presence of that line (S(D)p). In the final training condition, points were deducted at session end. Response rate was lower in the presence of the S(D)p despite equal rates of points for money in the presence of both stimuli. In generalization testing for Experiment 1, the two lines were included in a 10-line continuum; S(D)p fell in the middle and the trained SD was at one end. Lines were presented randomly, and point delivery and loss contingencies were as in training but with points available in the presence of all lines. For all subjects, response rates were lowest around S(D)p and increased towards the SD end of the continuum. Because testing included only one or two lines beyond S(D), this pattern did not rule out S(D) generalization. Thus, in Experiment 2, stimuli beyond S(D) were added to generalization tests. Response rates did not decrease as a function of distance from S(D), clarifying the demonstration of punishment generalization.

Four college students were exposed to a Sidman avoidance procedure to determine if an avoidance contingency involving 20% carbon dioxide-enriched air (CO2) would produce and maintain responding. In Phase 1, two conditions (contingent and noncontingent) were conducted each day. These conditions were distinguished by the presence or absence of a blue or green box on a computer screen. In the contingent condition, CO2 presentation were delivered every 3 s unless a subject pulled a plunger. Each plunger pull postponed CO2 presentations for 10 s. In the noncontingent condition, CO2 presentations occurred on the average of every 5 min independent of responding. Following stable responding in Phase 1, condition-correlated stimuli were reversed. In both conditions, plunger response rate was high during the contingent condition and low or zero during the noncontingent condition. Furthermore, subjects avoided most CO2 presentations. However, CO2 presentations did not increase verbal reports of fear. Overall, the results from the present study suggest that CO2 can be used effectively in basic studies of aversive control and in laboratory analogues of response patterns commonly referred to as anxiety.

Background The benefits of aspirin as an anti-platelet agent are well established; however, there has been much debate about the lack of uniformity in the efficacy of aspirin to inhibit platelet function. In some patients, aspirin fails to inhibit platelets even where compliance has been verified, a phenomenon which has been termed “aspirin resistance”. These patients may in turn be at a higher risk of future vascular events. The proportion of “resistant” patients identified depends on the type of platelet function test. Therefore, the aim of this systematic review is to determine which, if any, platelet function test has utility in terms of identifying patients with a high risk of vascular events. The review has been registered with PROSPERO (CRD42012002151). Methods Relevant studies will be sought from bibliographic databases. Trials registers will be searched for ongoing studies. Reference lists will be checked and subject experts contacted. There will be no date or language restrictions. Standard reviewing methodology to minimise bias will be employed. Any prospective studies in patients on aspirin therapy and assessing platelet function in relation to relevant clinical outcomes will be included, as will studies reporting prognostic models. Risk of bias assessment will be based on the Quality Assessment of Diagnostic Accuracy Studies guidelines, and suitable criteria for assessing quality of prognostic studies. Data on test accuracy measures, relative risks, odds or hazard ratios will be extracted and meta-analysed, where possible, using a random-effects model to account for between-study heterogeneity. Where appropriate, the causes of heterogeneity will be explored through meta-regression and sub-group or sensitivity analyses. If platelet function testing is demonstrated to have diagnostic/predictive utility in a specific population, the potential for a cost-effectiveness analysis will be considered and, if possible, an economic model constructed. This will be supported by a systematic review of existing economic evaluation studies. Discussion The results of the review could indicate if platelet function test(s) could lead to a reliable prediction of the risk of clinically important events in a defined population, and thus support investigations into adjustments to therapy in order to compensate for a predicted poor response to standard aspirin.