Overview of clinical outcome measures used in glaucoma randomised controlled trials (RCTs)

Background: In clinical trials the selection of appropriate outcomes is crucial to the assessment of whether one intervention is better than another. Glaucoma is a chronic eye disease and the leading cause of irreversible blindness in the world. A variety of outcomes has been used and reported in glaucoma RCTs.

Objectives: The purpose of this review is to identify different clinical outcome measures used in glaucoma RCTs between January 2006 and March 2012.

Methods: A systematic review was conducted using standard methodology. We searched for RCTs in glaucoma published in English with no restrictions on the population type or size, or applied interventions. All clinical outcomes were included. Patient-reported, pharmacokinetic and economic outcomes were excluded.

Results: The search strategy identified 4288 potentially relevant abstracts. There were 315 publications retrieved, of which 233 RCTs were included. A total of 967 clinical measures were reported. There were large variations in the definitions used to describe different outcomes and their measures. Intraocular pressure (IOP) was the most commonly reported outcome (used in 201 RCTs, 86%) with a total of 422 measures (44%). Amongst the IOPrelated measures, the most commonly used was mean IOP (n=143, 15% of all measures). Safety outcomes were commonly reported, in 145 RCTs (62%) whereas visual field outcomes were utilized in 38 RCTs (16%).

Conclusions: There is a large variability in clinical outcomes used for glaucoma RCTs and in the way each outcome is reported. This lack of standardisation may impair the ability to evaluate the evidence of glaucoma interventions.

Patient-reported outcomes in randomised controlled trials on age-related macular degeneration

BACKGROUND/AIMS: The purpose of this systematic review was to identify the frequency and type of patient-reported outcome measures (PROMs) used in recent randomised controlled trials (RCTs) for age-related macular degeneration (AMD).

METHODS: The authors conducted a systematic search between January 2010 and November 2013 in MEDLINE, EMBASE, Scopus, Cochrane Library (Central) and the clinical trials registries (http://www.controlled-trials.com and http://www.ClinicalTrials.gov) according to defined inclusion criteria (RCTs on AMD in English). Two independent reviewers evaluated studies for inclusion. One reviewer extracted data of included studies, and a second masked reviewer assessed 10% to confirm accuracy in data collection. Reference lists of included papers and appendices of relevant Cochrane systematic reviews were scanned to identify other relevant RCTs. Information collected on extracted outcomes was analysed using descriptive statistics.

RESULTS: Literature and registry search yielded 3816 abstracts of journal articles and 493 records from trial registries. A total of 177 RCTs were deemed to have met inclusion criteria. Of the 858 outcomes reported, 38 outcomes were identified as PROMs (4.4%). Of the 177 RCTs examined, PROMs were used in 25 trials (14.1%). The National Eye Institute Visual Function Questionnaire-25 was the most frequently used PROM instrument (64% of RCTs with PROMs included).

CONCLUSIONS: This review highlights that a small proportion of AMD RCTs included PROMs as outcome measures and that there was a variety in the instruments used.

UK publicly funded Clinical Trials Units supported a controlled access approach to share individual participant data but highlighted concerns

OBJECTIVES: Evaluate current data sharing activities of UK publicly funded Clinical Trial Units (CTUs) and identify good practices and barriers.

STUDY DESIGN AND SETTING: Web-based survey of Directors of 45 UK Clinical Research Collaboration (UKCRC)-registered CTUs.

RESULTS: Twenty-three (51%) CTUs responded: Five (22%) of these had an established data sharing policy and eight (35%) specifically requested consent to use patient data beyond the scope of the original trial. Fifteen (65%) CTUs had received requests for data, and seven (30%) had made external requests for data in the previous 12 months. CTUs supported the need for increased data sharing activities although concerns were raised about patient identification, misuse of data, and financial burden. Custodianship of clinical trial data and requirements for a CTU to align its policy to their parent institutes were also raised. No CTUs supported the use of an open access model for data sharing.

CONCLUSION: There is support within the publicly funded UKCRC-registered CTUs for data sharing, but many perceived barriers remain. CTUs are currently using a variety of approaches and procedures for sharing data. This survey has informed further work, including development of guidance for publicly funded CTUs, to promote good practice and facilitate data sharing.

Laboratory trials on the effects of different diets on growth and survival of the common whelk, Buccinum undatum L. 1758, as a candidate species for aquaculture.

Newly hatched juvenile Buccinum undatum can be reared under laboratory conditions. Good was growth is achieved when juveniles were fed on combined diets (blue mussel, cod, and fish pellets). Juveniles reached shell heights of 33.0 ± 4.2 mm, 26.9 ± 3.8 ± mm, 23.2 ± 2.2 mm, and 20.1 ± 1.6 mm, after 14 months of fedding on a combined diet, blue mussel, cod, and fish pellets, respectively under ambient sea temperature and salinity. After 14 months juveniles fed blue mussel had the highest survival rates (67%) followed by those fed a combination of all other experimental diets (61%), cod waste (53%) and fish-feed pellets (46%). High mortalities were recorded in most treatments during the summer months between June and September. This species appears to have an aquaculture potential, as juveniles readily feed on artificial diets at an early age, show high survival rates and could potentially reach market size in 2 years or less. The major constraint in realising this potential at present, is the relatively low value of the species; if market values increased as a result of serious depletion of natural populations, hatchery production of juveniles for intensive aquaculture or restocking could become economically viable.

Effects of n-3 long chain polyunsaturated fatty acids on depressed mood: Systematic review of published trials.

Background: Greater dietary intakes of n–3 long-chain polyunsaturated fatty acids (n–3 PUFAs) may be beneficial for depressed mood. Objective: This study aimed to systematically review all published randomized controlled trials investigating the effects of n–3 PUFAs on depressed mood. Design: Eight medical and health databases were searched over all years of records until June 2006 for trials that exposed participants to n–3 PUFAs or fish, measured depressed mood, were conducted on human participants, and included a comparison group. Results: Eighteen randomized controlled trials were identified; 12 were included in a meta-analysis. The pooled standardized difference in mean outcome (fixed-effects model) was 0.13 SDs (95% CI: 0.01, 0.25) in those receiving n–3 PUFAs compared with placebo, with strong evidence of heterogeneity (I2 = 79%, P <0.001). The presence of funnel plot asymmetry suggested that publication bias was the likely source of heterogeneity. Sensitivity analyses that excluded one large trial increased the effect size estimates but did not reduce heterogeneity. Metaregression provided some evidence that the effect was stronger in trials involving populations with major depression—the difference in the effect size estimates was 0.73 (95% CI: 0.05, 1.41; P = 0.04), but there was still considerable heterogeneity when trials that involved populations with major depression were pooled separately (I2 = 72%, P <0.001). Conclusions: Trial evidence that examines the effects of n–3 PUFAs on depressed mood is limited and is difficult to summarize and evaluate because of considerable heterogeneity. The evidence available provides little support for the use of n–3 PUFAs to improve depressed mood. Larger trials with adequate power to detect clinically important benefits are required.

The interference effects of non-rotated versus counter-rotated trials in visuomotor adaptation

An isometric torque-production task was used to investigate interference and retention in adaptation to multiple visuomotor environments. Subjects produced isometric flexion-extension and pronation-supination elbow torques to move a cursor to acquire targets as quickly as possible. Adaptation to a 30 degrees counter-clockwise (CCW) rotation (task A), was followed by a period of rest (control), trials with no rotation (task B0), or trials with a 60 degrees clockwise (CW) rotation (task B60). For all groups, retention of task A was assessed 5 h later. With initial training, all groups reduced the angular deviation of cursor paths early in the movements, indicating feedforward adaptation. For the control group, performance at commencement of the retest was significantly better than that at the beginning of the initial learning. For the B0 group, performance in the retest of task A was not dissimilar to that at the start of the initial learning, while for the B60 group retest performance in task A was markedly worse than initially observed. Our results indicate that close juxtaposition of two visuomotor environments precludes improved retest performance in the initial environment. Data for the B60 group, specifically larger angular errors upon retest compared with initial exposures, are consistent with the presence of anterograde interference. Furthermore, full interference occurred even when the visuomotor environment encountered in the second task was not rotated (B0). This latter novel result differs from those obtained for force field learning, where interference does not occur when task B does not impose perturbing forces, i.e., when B consists of a null field (Brashers-Krug et al., Nature 382:252-255, 1996). The results are consistent with recent proposals suggesting different interference mechanisms for visuomotor (kinematic) compared to force field (dynamic) adaptations, and have implications for the use of washout trials when studying interference between multiple visuomotor environments.