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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.

The function of fixational eye movements, the tiny involuntary eye movements or 'retinal jitters' that occur when we fix our gaze on something, has been a matter of debate since they were first recognized in the 1950s. Using a combination of psychophysical experiments with statistical analysis of the visual signals entering the eye to counteract the visual effects of the eye movements, Rucci et al. show that without them, perception of fine-grained information is reduced. This suggests that fixational eye movements are part of a strategy used by the brain to extract fine details of visual information. Our eyes are constantly in motion. Even during visual fixation, small eye movements continually jitter the location of gaze1,2,3,4. It is known that visual percepts tend to fade when retinal image motion is eliminated in the laboratory5,6,7,8,9. However, it has long been debated whether, during natural viewing, fixational eye movements have functions in addition to preventing the visual scene from fading10,11,12,13,14,15,16,17. 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 stabilization18, 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.

Background Multiple myeloma (MM) is the second most common hematological malignancy in the U.S., and is characterized by bone pain, appetite loss, fatigue, and treatment-related symptoms. These symptoms can have potentially devastating effects on patients' health-related quality of life (HRQoL). While several instruments are available to evaluate the symptomatic profile and HRQoL of MM patients, it is unclear whether their conceptual coverages are adequate in the relapsed or refractory (R/R) setting. In order to address this concern, we conducted a qualitative study in R/R MM patients and compared the results to the conceptual frameworks of three instruments available for use in this population. Methods Qualitative concept elicitation (CE) interviews were conducted with MM patients in the U.S. Patients were considered eligible for participation if they were at least 18 years of age, fluent in U.S. English, currently receiving treatment for MM considered to be R/R, and had an ECOG Performance Status of 0-2. Patients who were receiving first-line therapy for their cancer; were mentally or legally incapable of consenting to the study; or had a concurrent diagnosis or condition that would interfere with their ability to participate in the study were excluded. Interviews were conducted according to a semi-structured interview guide. Questions were open-ended and focused primarily on patients' disease- and treatment-related symptoms and how those symptoms impacted their lives. Targeted follow-up questions were used to elicit additional information when appropriate. Interviews lasted approximately 60 minutes and were audio recorded; all interview recordings were transcribed and de-identified. Qualitative data were analyzed using a grounded theory approach that combined semi-quantitative and qualitative methods. The concepts reported by patients were evaluated for saturation and subsequently compared with the conceptual frameworks of the EORTC QLQ-C30 and QLQ-MY20, FACT-MM, and MDASI-MM instruments. Results A total of 15 MM patients (age range = 56 to 89 years; mean age = 68.8±10.4 years) participated in the CE interviews and were included in analysis. Most patients were white (n=13, 86.7%), and about half were male (n=8, 53.3%). Two-thirds of the sample had some form of college education (i.e., certificate, two- to four-year college degree, or graduate degree). Most were married (n=11, 73.3%), and all but one reported living with family or friends (n=14, 93.93%). Patients were most commonly retired (n=8, 53.3%). Time since diagnosis ranged from 1 to 7 years, with a mean of 3.2±2.0 years. Just over half of the participants (n=8, 53.3%) had stage 3 MM at diagnosis. Eight patients (53.3%) were on second line treatment, six patients (40.0%) on third line treatment, and one patient (6.7%) on seventh line treatment. A total of 27 disease-related symptom concepts were reported by MM patients. Of those, the most commonly reported were tiredness (n=8, 53.5%), back pain (n=4, 26.7%), lack of energy (n=3, 20.0%), pain (location not specified) (n=3, 20.0%), shortness of breath (n=3, 20.0%), and weakness (n=3, 20.0%). The remaining 21 symptom concepts were reported by ≤2 patients each (≤13.3%). A total of 43 disease-related HRQoL impacts were reported by MM patients during CE interviews. The most commonly reported were work (n=6, 40.0%), thinking about cancer (n=5, 33.3%), exercise (n=4, 26.7%), social activities (n=4, 26.7%), household activities (n=4, 26.7%), and financial (n=4, 26.7%). Saturation was reached for 22 MM symptoms and 35 HRQoL impacts, and was questionable for 4 symptoms and 11 impacts. Overall, of the 10 disease-related symptom concepts reported by >1 MM patient, 7 (70.0%) were covered by the QLQ-C30 and MY-20, 5 (50.0%) by the FACT-MM, and 6 (60.0%) by the MDASI-MM. Of the 28 disease-related impacts reported by >1 MM patient, 15 (53.6%) were covered by the QLQ-C30 and MY-20, 11 (39.3%) by the FACT-MM, and 9 (32.1%) by the MDASI-MM. Conclusions These findings indicate that the majority of symptoms reported by R/R MM patients are captured by the existing EORTC QLQ-C30 and QLQ-MY20 instruments. A non-trivial gap in conceptual coverage is evident, however, which suggests that there remains room for improvement in assessing the experience of this patient population. Additional patient recruitment is ongoing to ensure saturation, and to further evaluate the need for a fit-for-purpose measure. Disclosures: Trask: Sanofi: Employment. Taylor:Adelphi Values: Employment. Shields:Adelphi Values: Employment. Gallagher:Sanofi: Employment. Mehta:Sanofi: Employment. Foley:Adelphi Values: Employment. Olude:Adelphi Values: Employment. Lamoureux:Adelphi Values: Employment. Iovin:Adelphi Values: Employment. Hsu:Sanofi: Employment.