Development of a Symptom-Based Patient-Reported Outcome Instrument for Functional Dyspepsia: A Preliminary Conceptual Model and an Evaluation of the Adequacy of Existing Instruments.

OBJECTIVES: The aim was to document, from the perspective of the empirical literature, the primary symptoms of functional dyspepsia (FD), evaluate the extent to which existing questionnaires target those symptoms, and, finally, identify any missing evidence that would impact the questionnaires' use in regulated clinical trials to assess treatment efficacy claims intended for product labeling. METHODS: A literature review was conducted to identify the primary symptoms of FD and existing symptom-based FD patient-reported outcome (PRO) instruments. Following a database search, abstracts were screened and articles were retrieved for review. The primary symptoms of FD were organized into a conceptual model and the PRO instruments were evaluated for conceptual coverage as well as compared against evidentiary requirements presented in the FDA's PRO Guidance for Industry. RESULTS: Fifty-six articles and 16 instruments assessing FD symptoms were reviewed. Concepts listed in the Rome III criteria for FD (n = 7), those assessed by existing FD instruments (n = 34), and symptoms reported by patients in published qualitative research (n = 6) were summarized in the FD conceptual model. Except for vomiting, all of the identified symptoms from the published qualitative research reports were also specified in the Rome III criteria. Only three of the 16 instruments, the Dyspepsia Symptom Severity Index (DSSI), Nepean Dyspepsia Index (NDI), and Short-Form Nepean Dyspepsia Index (SF-NDI), measure all seven FD symptoms defined by the Rome III criteria. Among these three, each utilizes a 2-week recall period and 5-point Likert-type scale, and had evidence of patient involvement in development. Despite their coverage, when these instruments were evaluated in light of regulatory expectations, several issues jeopardized their potential qualification for substantiation of a labeling claim. CONCLUSIONS: No existing PRO instruments that measured all seven symptoms adhered to the regulatory principles necessary to support product labeling. As such, the development of a new FD symptom PRO instrument is supported.

Effectiveness of a risk-minimization activity involving physician education on metabolic monitoring of patients receiving quetiapine: results from two postauthorization safety studies.

Following Good Pharmacovigilance Practices Module XVI, two complementary studies were performed that included process and outcome measurements of the effectiveness of physician education on metabolic monitoring of patients receiving quetiapine. A multinational survey of 800 European Union physicians was utilized to assess the receipt of educational materials and also to assess the degree of monitoring as reported by physicians. Recall of receipt of educational materials ranged from 16.0 to 69.0% across the participating countries; however, physicians reported that 64.5% of patients were being monitored, with the majority reporting performance of three or more of four key metabolic-monitoring activities. Higher rates of monitoring were reported by those who reported receiving materials. Assessment of outcomes in a separate retrospective analysis of electronic medical record data showed lower levels of monitoring performed by specialist physicians. The monitoring activities observed were assessed as acceptable on the basis of the established performance of UK physicians, who are incentivized to deliver preventive screening.

Identification of topics for comparative effectiveness systematic reviews in the field of cancer imaging.

AIM: With rapid innovations in diagnostic and therapeutic interventions in cancer care, comparative effectiveness reviews (CERs) are essential to inform clinical practice and guide future research. However, the optimal means to identify priority CER topics are uninvestigated. We aimed to devise a transparent and reproducible process to identify ten to 12 CER topics in the area of cancer imaging relevant to a wide range of stakeholders. MATERIALS & METHODS: Environmental scans and explicit prioritization criteria supported interactions (email communications, web-based discussions and live teleconferences) with experts and stakeholders culminating in a three-phase deductive exercise for prioritization of CER topics. RESULTS: We prioritized 12 CER topics in breast, lung and gastrointestinal cancers that addressed screening, diagnosis, staging, monitoring and evaluating response to treatment. CONCLUSION: Our project developed and implemented a transparent and reproducible process for research prioritization and topic nomination that can be further refined to improve the relevance of future CERs.

An evidence-based systematic review of active hexose correlated compound (AHCC) by the Natural Standard Research Collaboration.

An evidence-based systematic review of active hexose correlated compound (AHCC) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

A Web-based archive of systematic review data.

Systematic reviews have become increasingly critical to informing healthcare policy; however, they remain a time-consuming and labor-intensive activity. The extraction of data from constituent studies comprises a significant portion of this effort, an activity which is often needlessly duplicated, such as when attempting to update a previously conducted review or in reviews of overlapping topics.In order to address these inefficiencies, and to improve the speed and quality of healthcare policy- and decision-making, we have initiated the development of the Systematic Review Data Repository, an open collaborative Web-based repository of systematic review data. As envisioned, this resource would serve as both a central archive and data extraction tool, shared among and freely accessible to organizations producing systematic reviews worldwide. A suite of easy-to-use software tools with a Web frontend would enable researchers to seamlessly search for and incorporate previously deposited data into their own reviews, as well as contribute their own.In developing this resource, we identified a number of technical and non-technical challenges, as well as devised a number of potential solutions, including proposals for systems and software tools to assure data quality, stratify and control user access effectively and flexibly accommodate all manner of study data, as well as means by which to govern and foster adoption of this new resource.Herein we provide an account of the rationale and development of the Systematic Review Data Repository thus far, as well as outline its future trajectory.

An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration.

An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

An evidence-based systematic review of cinnamon (Cinnamomum spp.) by the Natural Standard Research Collaboration.

An evidence-based systematic review of cinnamon (Cinnamomum spp.), including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing, by the Natural Standard Research Collaboration is discussed in this monograph.

An evidence review of active surveillance in men with localized prostate cancer.

BACKGROUND: Radical prostatectomy and radiation therapy for prostate cancer have side effects and unclear survival benefits for early stage and low-risk disease. Prostate cancer often has an indolent natural history, making observational management strategies potentially appealing. PURPOSE: To systematically review the role of active surveillance for triggers to begin curative treatment in men with low-risk prostate cancer. Key Questions address changes in prostate cancer characteristics over time, definitions of active surveillance and other observational strategies, factors affecting the offer of, acceptance of, and adherence to active surveillance, the comparative effectiveness of active surveillance with curative treatments, and research gaps. DATA SOURCES: MEDLINE(®), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and existing systematic reviews, evidence reports, and economic evaluations. STUDY SELECTION: Randomized controlled trials and nonrandomized comparative studies of treatments, multivariable association studies, and studies of temporal trends in prostate cancer natural history. Only published, peer-reviewed, English-language articles were selected based on predetermined eligibility criteria. DATA EXTRACTION: A standardized protocol was used to extract details on design, diagnoses, interventions, predictive factors, outcomes, and study validity. DATA SYNTHESIS: In total, 80 studies provided information on epidemiologic trends; 56 on definitions of active surveillance; 42 on factors affecting the offer of, acceptance of, or adherence to observational management strategies; and 26 on comparative effectiveness. Increased diagnosis of early-stage prostate cancer due to prostate-specific antigen (PSA) testing, led to an increase in prostate cancer incidence from the mid-1980s to the mid-1990s. The prostate cancer-specific mortality rate decreased for all age groups from the early-1990s to 1999. Currently, patients are diagnosed with earlier stage and lower risk prostate cancers compared to the pre-PSA era. Over time, a lower proportion of men received observational management versus active treatment, even among those with low-risk disease. There was no standardized definition of active surveillance. Sixteen cohorts used different monitoring protocols, all with different combinations of periodic digital rectal examination, PSA testing, rebiopsy, and/or imaging findings. Predictors that a patient received no initial active treatment generally included older age, presence of comorbidities, lower Gleason score, lower tumor stage, lower diagnostic PSA, and lower disease progression risk group. No trial provided results comparing men with localized disease on active surveillance with surgery or radiation therapy. LIMITATIONS: Because of the nonstandardized usages of the terms "active surveillance" and "watchful waiting" and their intended and often mixed (both curative and palliative) treatment objectives, it was difficult to determine which study patients received active monitoring for triggers indicative of curative treatment and which observation for clinical symptoms indicative of palliative treatment. CONCLUSIONS: More men are being diagnosed with early stage prostate cancer. Whether active monitoring with a curative intent is an appropriate option for these men remains unclear. A standard, universally agreed-upon definition of active surveillance that clearly distinguishes it from watchful waiting and other observational management strategies is needed to help clarify scientific discourse on this topic. Ongoing clinical trials may provide information on the comparative effectiveness of active surveillance compared to immediate active treatment, but will require long term followup.

An evidence-based systematic review of umckaloabo (Pelargonium sidoides) by the Natural Standard Research Collaboration.

An evidence-based systematic review, including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

An evidence-based systematic review of rosemary (Rosmarinus officinalis) by the Natural Standard Research Collaboration.

An evidence-based systematic review of rosemary (Rosmarinus officinalis), including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

EyeRIS: a general-purpose system for eye-movement-contingent display control.

In experimental studies of visual performance, the need often emerges to modify the stimulus according to the eye movements performed by the subject. The eye-movement-contingent display (EMCD) methodology enables accurate control of the position and motion of the stimulus on the retina. EMCD procedures have been used successfully in many areas of vision science, including studies of visual attention or eye movements and physiological characterization of neuronal response properties. Unfortunately, the difficulty of real-time programming and the unavailability of flexible and economical systems that can be easily adapted to the diversity of experimental needs and laboratory setups have prevented the widespread use of EMCD control. This article describes EyeRIS, a general-purpose system for performing EMCD experiments on a Windows computer. Based on a digital signal processor with analog and digital interfaces, this integrated hardware and software system is responsible for sampling and processing oculomotor signals and subject responses and for modifying the stimulus displayed on a CRT according to a gaze-contingent procedure specified by the experimenter. EyeRIS is designed to update the stimulus with a delay of only 10 msec. To thoroughly evaluate EyeRIS's performance, this study was designed to (1) examine the response of the system in a number of EMCD procedures and computational benchmarking tests; (2) compare the accuracy of implementation of one particular EMCD procedure, retinal stabilization, with that produced by a standard tool used for this task; and (3) examine EyeRIS's performance in one of the many EMCD procedures that cannot be executed by means of any other currently available device.

Miniature eye movements enhance fine spatial detail.

Our eyes are constantly in motion. Even during visual fixation, small eye movements continually jitter the location of gaze. It is known that visual percepts tend to fade when retinal image motion is eliminated in the laboratory. However, it has long been debated whether, during natural viewing, fixational eye movements have functions in addition to preventing the visual scene from fading. In this study, we analysed the influence in humans of fixational eye movements on the discrimination of gratings masked by noise that has a power spectrum similar to that of natural images. Using a new method of retinal image stabilization, we selectively eliminated the motion of the retinal image that normally occurs during the intersaccadic intervals of visual fixation. Here we show that fixational eye movements improve discrimination of high spatial frequency stimuli, but not of low spatial frequency stimuli. This improvement originates from the temporal modulations introduced by fixational eye movements in the visual input to the retina, which emphasize the high spatial frequency harmonics of the stimulus. In a natural visual world dominated by low spatial frequencies, fixational eye movements appear to constitute an effective sampling strategy by which the visual system enhances the processing of spatial detail.