Progress on core outcomes sets for critical care research

Purpose of review: Appropriate selection and definition of outcome measures are essential for clinical trials to be maximally informative. Core outcome sets (an agreed, standardized collection of outcomes measured and reported in all trials for a specific clinical area) were developed due to established inconsistencies in trial outcome selection. This review discusses the rationale for, and methods of, core outcome set development, as well as current initiatives in critical care.

Recent findings: Recent systematic reviews of reported outcomes and measurement instruments relevant to the critically ill highlight inconsistencies in outcome selection, definition, and measurement, thus establishing the need for core outcome sets. Current critical care initiatives include development of core outcome sets for trials aimed at reducing mechanical ventilation duration; rehabilitation following critical illness; long-term outcomes in acute respiratory failure; and epidemic and pandemic studies of severe acute respiratory infection.

Summary: Development and utilization of core outcome sets for studies relevant to the critically ill is in its infancy compared to other specialties. Notwithstanding, core outcome set development frameworks and guidelines are available, several sets are in various stages of development, and there is strong support from international investigator-led collaborations including the International Forum for Acute Care Trialists.

Design characteristic of randomised controlled trials for geographic atrophy in age-related macular degeneration: selection of outcomes and sample size calculation

PurposeThe selection of suitable outcomes and sample size calculation are critical factors in the design of a randomised controlled trial (RCT). The goal of this study was to identify the range of outcomes and information on sample size calculation in RCTs on geographic atrophy (GA).MethodsWe carried out a systematic review of age-related macular degeneration (AMD) RCTs. We searched MEDLINE, EMBASE, Scopus, Cochrane Library, www.controlled-trials.com, and www.ClinicalTrials.gov. Two independent reviewers screened records. One reviewer collected data and the second reviewer appraised 10% of collected data. We scanned references lists of selected papers to include other relevant RCTs.ResultsLiterature and registry search identified 3816 abstracts of journal articles and 493 records from trial registries. From a total of 177 RCTs on all types of AMD, 23 RCTs on GA were included. Eighty-one clinical outcomes were identified. Visual acuity (VA) was the most frequently used outcome, presented in 18 out of 23 RCTs and followed by the measures of lesion area. For sample size analysis, 8 GA RCTs were included. None of them provided sufficient Information on sample size calculations.ConclusionsThis systematic review illustrates a lack of standardisation in terms of outcome reporting in GA trials and issues regarding sample size calculation. These limitations significantly hamper attempts to compare outcomes across studies and also perform meta-analyses.

Molecular markers for predicting recurrence, progression and outcomes of bladder cancer (do the poster boys need new posters

Purpose of review
Molecular markers for bladder cancer recurrence and
progression continue to drive many research programmes.
Translating the laboratory findings into the clinical environment
where these markers are used in clinical decision making has
proved problematic. In the clinical arena, stage and grade are
still the main focus for decisions about patient management.
There is however an evolution in bladder cancer research from
single-marker/single-pathway research to a more global
assessment of the tumour cell with DNA microarrays and
proteomics.
Recent findings
In the last year, DNA microarray assessment has revealed
several interesting molecular markers such as p33ING1 and
DEK. Parallel ‘conventional’ single-pathway research has
focused on new novel markers such as HER2/neu, survivin and
matrix metalloproteinase 2 (MMP-2). Molecular markers that
have a long-standing association with bladder cancer
progression such as p53, E-cadherin and Ki-67 have been
reviewed by both single-marker studies and by microarray
studies and their status remains important.
Summary
It is an exciting time in the molecular biology research of bladder
cancer as the focus changes to assess the global genetic and
protein expression within tumour cells. From such a wealth of
information it is likely that molecular markers will make the
translation from benchside to bedside.

Establishing a population-based patient-reported outcomes study (PROMs) using national cancer registries across two jurisdictions: The Prostate Cancer Treatment, your experience (PiCTure) study

Objective: To establish an international patient-reported outcomes (PROMs) study among prostate cancer survivors, up to 18 years postdiagnosis, in two countries with different healthcare systems and ethical frameworks. Design: A cross-sectional, postal survey of prostate cancer survivors sampled and recruited via two population-based cancer registries. Healthcare professionals (HCPs) evaluated patients for eligibility to participate. Questionnaires contained validated instruments to assess health-related quality of life and psychological well-being, including QLQ-C30, QLQPR-25, EQ-5D-5L, 21-question Depression, Anxiety and Stress Scale (DASS-21) and the Decisional Regret Scale. Setting: Republic of Ireland (RoI) and Northern Ireland (NI). Primary outcome measures: Registration completeness, predictors of eligibility and response, data missingness, unweighted and weighted PROMs. Results: Prostate cancer registration was 80% (95% CI 75% to 84%) and 91% (95% CI 89% to 93%) complete 2 years postdiagnosis in NI and RoI, respectively. Of 12 322 survivors sampled from registries, 53% (n=6559) were classified as eligible following HCP screening. In the multivariate analysis, significant predictors of eligibility were: being ≤59 years of age at diagnosis (p<0.001), short-term survivor (<5 years postdiagnosis; p<0.001) and from RoI (p<0.001). 3348 completed the questionnaire, yielding a 54% adjusted response rate. 13% of men or their families called the study freephone with queries for assistance with questionnaire completion or to talk about their experience. Significant predictors of response in multivariate analysis were: being ≤59 years at diagnosis (p<0.001) and from RoI (p=0.016). Mean number of missing questions in validated instruments ranged from 0.12 (SD 0.71; EQ-5D-5L) to 3.72 (SD 6.30; QLQ-PR25). Weighted and unweighted mean EQ-5D-5L, QLQ-C30 and QLQ-PR25 scores were similar, as were the weighted and unweighted prevalences of depression, anxiety and distress. Conclusions: It was feasible to perform PROMs studies across jurisdictions, using cancer registries as sampling frames; we amassed one of the largest, international, population-based data set of prostate cancer survivors. We highlight improvements which could inform future PROMs studies, including utilising general practitioners to assess eligibility and providing a freephone service.

Aquatic invasive alien species – top issues for their management. Outcomes from the IFI/EIFAAC conference “Freshwater Invasives – Networking for Strategy”

In November 2014, a new EU Regulation to address Invasive Alien Species (IAS) and protect biodiversity was published. This entered into force across the EU in January 2015. The aim of the Regulation is to ‘prevent the introduction of, control or eradicate alien species which threaten ecosystems, habitats or species’. In an effort to provide focus to the Regulation prior to its publishing and to identify the major issues relating to Invasive Alien Species in Europe, the views of invasive species experts from around the world were sought. These were consolidated at an international conference (Freshwater Invasives - Networking for Strategy (FINS)) that was held in Ireland in April 2013. A major outcome from this meeting of experts was the production of the Top 20 IAS issues that relate primarily to freshwater habitats but are also directly relevant to marine and terrestrial ecosystems. This list will support policy makers throughout the EU as preparations are made to implement this important piece of legislation. A further outcome from the conference was the formation of an expert IAS Advisory Group to support EIFAAC in its work on invasive species

Earthquake aftershock anxiety: An examination of psychosocial contributing factors and symptomatic outcomes.

This study examined the direct and indirect effects of cognitions and anxiety associated with aftershocks on psychological symptoms (anxiety, depression, acute stress) and daily functioning (general and relationship). Participants were 600 adults from Christchurch. Data collection was approximately four months after the fatal 2011 earthquake. Path analysis was used. Socioeconomic status was directly associated with appraisals of uncontrollability of response to aftershocks. These cognitions were directly related to aftershock anxiety, which heightened general anxiety, depression and acute stress symptoms. These symptoms were directly associated with relationship and general life dysfunction. Aftershock anxiety plays a significant role in ongoing psychological distress associated with earthquakes.

Towards core outcome set (COS) development: a follow-up descriptive survey of outcomes in Cochrane reviews

BACKGROUND: A core outcome set (COS) can address problems of outcome heterogeneity and outcome reporting bias in trials and systematic reviews, including Cochrane reviews, helping to reduce waste. One of the aims of the international Core Outcome Measures in Effectiveness Trials (COMET) Initiative is to link the development and use of COS with the outcomes specified and reported in Cochrane reviews, including the outcomes listed in the summary of findings (SoF) tables. As part of this work, an earlier exploratory survey of the outcomes of newly published 2007 and 2011 Cochrane reviews was performed. This survey examined the use of COS, the variety of specified outcomes, and outcome reporting in Cochrane reviews by Cochrane Review Group (CRG). To examine changes over time and to explore outcomes that were repeatedly specified over time in Cochrane reviews by CRG, we conducted a follow-up survey of outcomes in 2013 Cochrane reviews.

METHODS: A descriptive survey of outcomes in Cochrane reviews that were first published in 2013. Outcomes specified in the methods sections and reported in the results section of the Cochrane reviews were examined by CRG. We also explored the uptake of SoF tables, the number of outcomes included in these, and the quality of the evidence for the outcomes.

RESULTS: Across the 50 CRGs, 375 Cochrane reviews that included at least one study specified a total of 3142 outcomes. Of these outcomes, 32 % (1008) were not reported in the results section of these reviews. For 23 % (233) of these non-reported outcomes, we did not find any reason in the text of the review for this non-report. Fifty-seven percent (216/375) of reviews included a SoF table.

CONCLUSIONS: The proportion of specified outcomes that were reported in Cochrane reviews had increased in 2013 (68 %) compared to 2007 (61 %) and 2011 (65 %). Importantly, 2013 Cochrane reviews that did not report specified outcomes were twice as likely to provide an explanation for why the outcome was not reported. There has been an increased uptake of SoF tables in Cochrane reviews. Outcomes that were repeatedly specified in Cochrane reviews by CRG in 2007, 2011, and 2013 may assist COS development.

Survey of new 2007 and 2011 Cochrane reviews found 37% of prespecified outcomes not reported

OBJECTIVES: To survey the outcomes used in Cochrane Reviews, as part of our work within the Core Outcome Measures in Effectiveness Trials Initiative.

STUDY DESIGN AND SETTING: A descriptive survey of Cochrane Reviews, divided by Cochrane Review Group (CRG), published in full for the first time in 2007 and 2011. Outcomes specified in the methods section of each review and outcomes reported in the results section of each review were of interest, in this exploration of the common use of outcomes and core outcome sets (COS).

RESULTS: Seven hundred eighty-eight reviews, specifying 6,127 outcomes, were included. When we excluded specified outcomes from the 86 reviews that did not include any studies, we found that 1,996 (37%) specified outcomes were not reported. Of the 361 new reviews with studies from 2011, 113 (31%) had a "summary of findings" table (SoF). Fifteen broad outcome categories were identified and used to manage the outcome data. We found consistency in the use of these categories across CRGs but inconsistency in outcomes within these categories.

CONCLUSION: COS have been used rarely in Cochrane Reviews, but the introduction of SoF makes the development and application of COS timelier than ever.

Still Unequal at Birth: Birth Weight, Socioeconomic Status and Outcomes at Age 9

The prevalence of low birth weight is an important aspect of public health which has been linked to increased risk of infant death, increased cost of care, and a range of later life outcomes. Using data from a new Irish cohort study, I document the relationship between birth weight and socio-economic status. The association of maternal education with birth weight does not appear to be due to the timing of birth or complications during pregnancy, even controlling for a wide range of background characteristics. However, results do suggest intergenerational persistence in the transmission of poor early life conditions. Birth weight predicts a number of outcomes at age 9, including test scores, hospital stays and health. An advantage of the data is that I am able to control for a number of typically unmeasured variables. I determine whether parental investments (as measured by the quality of interaction with the child, parenting style, or school quality) mediate the association between birth weight and later indicators. For test scores, there is evidence of non-linearity, and boys are more adversely affected than girls. I also consider whether there are heterogeneous effects by ability using quantile regression. These results are consistent with a literature which finds that there is a causal relationship between early life conditions and later outcomes.