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International Journal of Stroke :... Feb 2023Central adjudication of outcomes is common in randomized clinical trials in stroke. The rationale for adjudication is clear; centrally adjudicated outcomes should have... (Review)
Review
BACKGROUND
Central adjudication of outcomes is common in randomized clinical trials in stroke. The rationale for adjudication is clear; centrally adjudicated outcomes should have less random and systematic errors than outcomes assessed locally by site investigators. However, adjudication brings added complexities to a clinical trial and can be costly.
AIM
To assess the evidence for outcome adjudication in stroke trials.
SUMMARY OF REVIEW
We identified 12 studies evaluating central adjudication in stroke trials. The majority of these were secondary analyses of trials, and the results of all of these would have remained unchanged had central adjudication not taken place, even for trials without sufficient blinding. The largest differences between site-assessed and adjudicator-assessed outcomes were between the most subjective outcomes, such as causality of serious adverse events. We found that the cost of adjudication could be upward of £100,000 for medium to large prevention trials. These findings suggest that the cost of central adjudication may outweigh the advantages it brings in many cases. However, through simulation, we found that only a small amount of bias is required in site investigators' outcome assessments before adjudication becomes important.
CONCLUSION
Central adjudication may not be necessary in stroke trials with blinded outcome assessment. However, for open-label studies, central adjudication may be more important.
Topics: Humans; Stroke; Outcome Assessment, Health Care; Research Design
PubMed: 35373672
DOI: 10.1177/17474930221094682 -
Epilepsia Nov 2022Several instruments and outcomes measures have been reported in pediatric patients undergoing epilepsy surgery. The objective of this systematic review is to summarize,... (Review)
Review
Several instruments and outcomes measures have been reported in pediatric patients undergoing epilepsy surgery. The objective of this systematic review is to summarize, evaluate, and quantify outcome metrics for the surgical treatment of pediatric epilepsy that address seizure frequency, neuropsychological, and health-related quality of life (HRQL). We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify publications between 2010 and June 2021 from PubMed, Embase, and the Cochrane Database of Systematic Reviews that report clinical outcomes in pediatric epilepsy surgery. Eighty-one articles were included for review. Overall, rates of postoperative seizure frequency were the most common metric reported (n = 78 studies, 96%). Among the seizure frequency metrics, the Engel Epilepsy Surgery Outcome Scale (n = 48 studies, 59%) was most commonly reported. Neuropsychological outcomes, performed in 32 studies (40%) were assessed using 36 different named metrics. HRQL outcomes were performed in 16 studies (20%) using 13 different metrics. Forty-six studies (57%) reported postoperative changes in antiepileptic drug (AED) regimen, and time-to-event analysis was performed in 15 (19%) studies. Only 13 outcomes metrics (1/5 seizure frequency, 6/13 HRQL, 6/36 neuropsychological) have been validated for use in pediatric patients with epilepsy and only 13 have been assessed through reliability studies (4/5 seizure frequency, 6/13 HRQL, and 3/36 neuropsychological). Of the 81 included studies, 17 (21%) used at least one validated metric. Outcome variable metrics in pediatric epilepsy surgery are highly variable. Although nearly all studies report seizure frequency, there is considerable variation in reporting. HRQL and neuropsychological outcomes are less frequently and much more heterogeneously reported. Reliable and validated outcomes metrics should be used to increase standardization and accuracy of reporting outcomes in pediatric patients undergoing epilepsy surgery.
Topics: Humans; Child; Quality of Life; Reproducibility of Results; Treatment Outcome; Epilepsy; Seizures; Outcome Assessment, Health Care
PubMed: 35847999
DOI: 10.1111/epi.17369 -
Headache Feb 2021To review the acute migraine clinical trial literature and provide a summary of the endpoints and outcomes used in such trials.
BACKGROUND/OBJECTIVE
To review the acute migraine clinical trial literature and provide a summary of the endpoints and outcomes used in such trials.
METHOD
A systematic literature review, following a prespecified (but unregistered) protocol developed to adhere to recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, was conducted to understand endpoints and outcomes used in acute migraine clinical trials. Predefined terms were searched in PubMed to locate clinical trials assessing acute migraine treatments. Final database search was conducted on October 28, 2019. Identified publications were reviewed against established inclusion and exclusion criteria to determine eligibility. Data related to general trial design characteristics, sample characteristics, and outcomes and endpoints reported in each publication were extracted from eligible publications. Descriptive summaries of design features, sample characteristics, and the endpoints and outcomes employed across publications were constructed. Outcomes are presented within four broad categories: (a) pain-related outcomes (pain relief, pain freedom, etc.), (b) associated symptoms (nausea, photophobia, etc.), (c) disability/impairment/impact, (d) patient-reported outcome measures (PROMs, general health and migraine/headache-specific). Endpoint types were categorized within three broad categories: (a) change from baseline, (b) fixed timepoint, and (c) responder definitions (e.g., 50% reduction). This review focuses on a subset of recent (1998 or later) randomized and blinded publications evaluating drugs or medical devices.
RESULTS
Of 1567 publications found through the initial search and reference section reviews, 705 met criteria and were included for data extraction. Inter-rater agreement kappas for the descriptive variables extracted had an average kappa estimate of 0.86. The more recent, randomized and blinded pharmaceutical and medical device article subset includes 451 publications (451/705, 63.9%). The outcomes and endpoints varied substantially across trials, ranging from pain relief or freedom, freedom from or relief of migraine-associated symptoms, use of acute or rescue medication, and various other PROMs, including measures of satisfaction and quality of life. Within the recent randomized and blinded article subset, most articles examined ≥1 pain-related outcome (430/451, 95.3%). Of the publications that examined pain, outcomes most often used were pain relief (310/430, 72.1%), pain freedom (279/430, 64.9%), and headache recurrence (202/43,051, 47.0%) or rescue medication use (278/430, 64.9%). Associated symptoms such as nausea, photophobia, and phonophobia were more frequently measured (299/451, 66.3%) compared to most bothersome associated symptom (16/451, 3.5%), as it is a new addition to regulatory guidance. Over one-third of eligible publications examined disability/impairment (186/451, 41.2%) or ≥1 PROM (159/451, 35.3%). The definition of the endpoints used (e.g., change from baseline, fixed timepoint comparisons, categorization of "responders" to treatment based on wide variety of "responder definitions") also differed substantially across publications.
CONCLUSION
Acute migraine clinical trials exhibit a large amount of variability in outcomes and endpoints used, in addition to the variability in how outcomes and endpoints were used from trial-to-trial. There were some common elements across trials that align with guidance from the International Headache Society, the Food and Drug Administration and other regulatory agencies (e.g., assessing pain and associated symptoms, 2-hour post-treatment). Other aspects of acute migraine clinical trial design did not follow guidance. For example, multi-item PROMs intended to measure constructs (e.g., scales) are rarely used, the use of pain-related outcomes is inconsistent, some associated symptom assessments are idiosyncratic, and the timing of the assessment of primary endpoints is variable. The development of a core set of outcomes and endpoints for acute migraine clinical trials that are patient-centered and statistically robust could improve the conduct of individual trials, facilitate cross-trial comparisons, and better support informed treatment decisions by healthcare professionals and patients.
Topics: Acute Disease; Clinical Trials as Topic; Humans; Migraine Disorders; Outcome Assessment, Health Care
PubMed: 33611818
DOI: 10.1111/head.14067 -
Translational Psychiatry Sep 2017Recent literature hints that outcomes of clinical trials in medicine are selectively reported. If applicable to psychotic disorders, such bias would jeopardize the... (Review)
Review
Recent literature hints that outcomes of clinical trials in medicine are selectively reported. If applicable to psychotic disorders, such bias would jeopardize the reliability of randomized clinical trials (RCTs) investigating antipsychotics and thus their extrapolation to clinical practice. We therefore comprehensively examined outcome reporting bias in RCTs of antipsychotic drugs by a systematic review of prespecified outcomes on ClinicalTrials.gov records of RCTs investigating antipsychotic drugs in schizophrenia and schizoaffective disorder between 1 January 2006 and 31 December 2013. These outcomes were compared with outcomes published in scientific journals. Our primary outcome measure was concordance between prespecified and published outcomes; secondary outcome measures included outcome modifications on ClinicalTrials.gov after trial inception and the effects of funding source and directionality of results on record adherence. Of the 48 RCTs, 85% did not fully adhere to the prespecified outcomes. Discrepancies between prespecified and published outcomes were found in 23% of RCTs for primary outcomes, whereas 81% of RCTs had at least one secondary outcome non-reported, newly introduced, or changed to a primary outcome in the respective publication. In total, 14% of primary and 44% of secondary prespecified outcomes were modified after trial initiation. Neither funding source (P=0.60) nor directionality of the RCT results (P=0.10) impacted ClinicalTrials.gov record adherence. Finally, the number of published safety endpoints (N=335) exceeded the number of prespecified safety outcomes by 5.5 fold. We conclude that RCTs investigating antipsychotic drugs suffer from substantial outcome reporting bias and offer suggestions to both monitor and limit such bias in the future.
Topics: Antipsychotic Agents; Humans; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 28895941
DOI: 10.1038/tp.2017.203 -
Systematic Reviews Jun 2021Cancer research on sexual and gender minority (SGM) populations is gaining momentum. The purpose of this systematic review was to examine what is currently known in the...
PURPOSE
Cancer research on sexual and gender minority (SGM) populations is gaining momentum. The purpose of this systematic review was to examine what is currently known in the research literature regarding patient-reported health outcomes after cancer treatment among SGM populations.
METHODS
In March 2021, a medical librarian conducted a systematic keyword search on PubMed, Embase, Scopus, Web of Science, PsycINFO, ClinicalTrials.gov , and the Cochrane Central Register of Controlled Trials. The primary inclusion criterion was assessment of at least one physical, psychosocial, emotional, or functional patient-reported health outcome related to the impacts of cancer diagnosis and/or treatment. Articles that met inclusion criteria were reviewed in their entirety, charted in a Word Table, and assessed for quality. Quality considerations included study design, sampling approach, diversity of sample, measures used, and analytic procedures. Studies were synthesized based on type of cancer study participants experienced.
RESULTS
Sixty-four studies were included in the final analysis: most were quantitative, secondary analyses or cross-sectional studies with convenience samples, and focused on people with a history of breast or prostate cancer. Differences between sexual minority men and women in terms of coping and resilience were noted. Few studies reported on experiences of transgender persons and none reported on experiences of intersex persons.
CONCLUSIONS
A growing literature describes the patient-reported health outcomes of SGM people with a history of cancer. This study summarizes important between-group differences among SGM and heterosexual, cisgender counterparts that are critical for clinicians to consider when providing care.
IMPLICATIONS FOR CANCER SURVIVORS
Sexual orientation and gender identity are relevant to cancer survivors' health outcomes. Subgroups of SGM people have differential experiences and outcomes related to cancer and its impacts.
Topics: Cross-Sectional Studies; Female; Gender Identity; Humans; Male; Neoplasms; Outcome Assessment, Health Care; Sexual Behavior; Sexual and Gender Minorities
PubMed: 34154645
DOI: 10.1186/s13643-021-01707-4 -
Health & Social Care in the Community May 2022Adults on the autism spectrum are affected by health disparities which significantly reduce life expectancy and experience barriers to accessing healthcare. Social... (Review)
Review
Adults on the autism spectrum are affected by health disparities which significantly reduce life expectancy and experience barriers to accessing healthcare. Social prescribing is a holistic approach that diverts patients from primary care to health-enhancing activities in communities. However, there has been a lack of research attention to how autistic people navigate the social prescribing pathway and the ability of these approaches to address existing disparities. This mapping review aimed to synthesise features of non-medical, community-based interventions for autistic adults to assess their suitability for a social prescribing approach. A systematic search and screening process was used to identify literature reviews from medical databases (Embase, Medline, PsycINFO, CINAHL and Cochrane reviews) and grey literature. We extracted data from 24 reviews and 19 studies including types of services, participants, outcomes, settings and procedures. A narrative and visual synthesis is used to map the variety of services and interventions identified, the outcome measures used, and the barriers and facilitators to progression through services in relation to a realist social prescribing framework. The review found that there has been minimal evaluation of holistic, low intensity services for autistic adults, such as those offered in social prescribing approaches. Outcome measures remain focused on features of autism and reveal less about the effects of interventions on health and wellbeing. Aspects of the social prescribing model were identified in the features of service pathways, but findings also suggested how social prescribing could be adapted to improve accessibility for autistic people.
Topics: Adult; Autistic Disorder; Humans; Outcome Assessment, Health Care
PubMed: 34738679
DOI: 10.1111/hsc.13635 -
Journal of the American Academy of... Jan 2019Experiencing depression in adolescence can disrupt important developmental processes, which can have longstanding effects on socioeconomic status and relationships. The... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Experiencing depression in adolescence can disrupt important developmental processes, which can have longstanding effects on socioeconomic status and relationships. The objective of this article was to systematically review the evidence examining associations between adolescent depression and adult psychosocial outcomes.
METHOD
Five databases (MEDLINE, Embase, PsycINFO, CINAHL, and ERIC) were searched for articles published from 1980 through March 2017. Eligible articles were peer reviewed, published in English, had prospective cohort study designs, and contrasted adult psychosocial outcomes in those with versus without adolescent depression. Outcomes with sufficient data were pooled using random-effects meta-analyses, with summary measures reported as odds ratios (ORs). A protocol for this review was registered on PROSPERO (CRD42017059662).
RESULTS
Of the 4,988 references screened for inclusion, 31 articles comprising 136 analyses were included for review. Twenty-four cohorts were represented. Seventy-seven analyses across 10 outcomes were meta-analyzed, with remaining analyses summarized narratively. Meta-analyses suggested that adolescent depression was associated with outcomes including, but not limited to, failure to complete secondary school (OR 1.76, 95% CI 1.29-2.39), unemployment (OR 1.66, 95% CI 1.29-2.14), and pregnancy/parenthood (OR 1.38, 95% CI 1.06-1.81).
CONCLUSION
This review demonstrates that adolescent depression is associated with a myriad of adult psychosocial outcomes. Many are linked and can lead to the propagation of difficulties across the lifespan. These findings can have important implications for encouraging the provision of targeted mental health care early in development to improve life chances.
Topics: Adolescent; Adult; Depressive Disorder; Humans; Longitudinal Studies; Outcome Assessment, Health Care; Socioeconomic Factors
PubMed: 30577941
DOI: 10.1016/j.jaac.2018.07.896 -
Pharmacoepidemiology and Drug Safety Dec 2016Because of an increasing demand for quality comparative effectiveness research (CER), methods guidance documents have been published, such as those from the Agency for... (Review)
Review
PURPOSE
Because of an increasing demand for quality comparative effectiveness research (CER), methods guidance documents have been published, such as those from the Agency for Healthcare Research and Quality (AHRQ) and the Patient-Centered Outcomes Research Institute (PCORI). Our objective was to identify CER methods guidance documents and compare them to produce a summary of important recommendations which could serve as a consensus of CER method recommendations.
METHODS
We conducted a systematic literature review to identify CER methods guidance documents published through 2014. Identified documents were analyzed for methods guidance recommendations. Individual recommendations were categorized to determine the degree of overlap.
RESULTS
We identified nine methods guidance documents, which contained a total of 312 recommendations, 97% of which were present in two or more documents. All nine documents recommended transparency and adaptation for relevant stakeholders in the interpretation and dissemination of results. Other frequently shared CER methods recommendations included: study design and operational definitions should be developed a priori and allow for replication (n = 8 documents); focus on areas with gaps in current clinical knowledge that are relevant to decision-makers (n = 7); validity of measures, instruments, and data should be assessed and discussed (n = 7); outcomes, including benefits and harms, should be clinically meaningful, and objectively measured (n = 7). Assessment for and strategies to minimize bias (n = 6 documents), confounding (n = 6), and heterogeneity (n = 4) were also commonly shared recommendations between documents.
CONCLUSIONS
We offer a field-consensus guide based on nine CER methods guidance documents that will aid researchers in designing CER studies and applying CER methods. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: Bias; Comparative Effectiveness Research; Confounding Factors, Epidemiologic; Consensus; Humans; Outcome Assessment, Health Care; Research Design
PubMed: 27365094
DOI: 10.1002/pds.4051 -
Neurocritical Care Dec 2016Intracerebral hemorrhage (ICH) has the highest mortality rate among all strokes. While ICH location, lobar versus non-lobar, has been established as a predictor of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Intracerebral hemorrhage (ICH) has the highest mortality rate among all strokes. While ICH location, lobar versus non-lobar, has been established as a predictor of mortality, less is known regarding the relationship between more specific ICH locations and functional outcome. This review summarizes current work studying how ICH location affects outcome, with an emphasis on how studies designate regions of interest.
METHODS
A systematic search of the OVID database for relevant studies was conducted during August 2015. Studies containing an analysis of functional outcome by ICH location or laterality were included. As permitted, the effect size of individual studies was standardized within a meta-analysis.
RESULTS
Thirty-seven studies met the inclusion criteria, the majority of which followed outcome at 3 months. Most studies found better outcomes on the Modified Rankin Scale (mRS) or Glasgow Outcome Score (GOS) with lobar compared to deep ICHs. While most aggregated deep structures for analysis, some studies found poorer outcomes for thalamic ICH in particular. Over half of the studies did not have specific methodological considerations for location designations, including blinding or validation.
CONCLUSIONS
Multiple studies have examined motor-centric outcomes, with few studies examining quality of life (QoL) or cognition. Better functional outcomes have been suggested for lobar versus non-lobar ICH; few studies attempted finer topographic comparisons. This study highlights the need for improved reporting in ICH outcomes research, including a detailed description of hemorrhage location, reporting of the full range of functional outcome scales, and inclusion of cognitive and QoL outcomes.
Topics: Cerebral Hemorrhage; Humans; Outcome Assessment, Health Care
PubMed: 27160888
DOI: 10.1007/s12028-016-0276-4 -
PloS One 2015Self-management has received growing attention as an effective approach for long-term condition management. Little is known about which outcomes of supported... (Review)
Review
INTRODUCTION
Self-management has received growing attention as an effective approach for long-term condition management. Little is known about which outcomes of supported self-management are valued by patients, their families, health professionals and those who commission self-management services. This study systematically reviewed published empirical evidence in accordance with PRISMA guidelines to determine the outcomes of self-management valued by these key stakeholder groups, using three prominent exemplar conditions: colorectal cancer, diabetes and stroke.
AIM
To systematically review the literature to identify which generic outcomes of self-management have been targeted and are considered important using three exemplar conditions (colorectal cancer, diabetes and stroke), which collectively have a range of features that are likely to be representative of generic self-management issues.
METHODS
Systematic searching of nine electronic databases was conducted in addition to hand searches of review articles. Abstracts were identified against inclusion criteria and appraised independently by two reviewers, using a critical appraisal tool. Synthesis of findings was conducted using mixed research synthesis.
RESULTS
Over 20,536 abstracts were screened. 41 studies which met the review criteria were fully retrieved and appraised. The majority of evidence related to diabetes. Few studies directly focussed on stakeholders' views concerning desired self-management outcomes; the majority of evidence was derived from studies focusing upon the experience of self-management. The views of health care commissioners were absent from the literature. We identified that self-management outcomes embrace a range of indicators, from knowledge, skills, and bio-psychosocial markers of health through to positive social networks.
CONCLUSIONS
Patients', families', health professionals' and commissioners' views regarding which outcomes of self-management are important have not been clearly elicited. The extent to which bio-psychosocial indicators relate to successful self-management from the perspectives of all groups of stakeholders is unknown. Further investigation regarding which self-management outcomes are considered important by all stakeholders is necessary to guide the commissioning and design of future self-management services.
Topics: Colorectal Neoplasms; Diabetes Mellitus; Family; Female; Health Personnel; Humans; Male; Outcome Assessment, Health Care; Self Care; Stroke
PubMed: 26162086
DOI: 10.1371/journal.pone.0130990