The search for disease modification in moderate to severe Alzheimer disease: A critical review of current evidence

Abstract Background: Several forms of bias, including ethnic and gender bias, are thought to impact evaluations on Clinical Performance Assessments (CPAs). Unfairness may influence student learning attitudes if a loss of trust causes a lack of engagement in learning. Understanding the biases occurring in CPAs can lead to well-designed examiner training to ensure equality and fairness. The purpose of this systematic review is to determine the current evidence in the literature for ethnic and/or gender bias by examiners evaluating pre-licensure healthcare students in CPAs using standardized patients (SPs). Methods: Literature was systematically searched in CINAHL, PubMed and Medline from inception to February 2019, and no date range was set. Studies related to the investigation of ethnic and/or gender biases occurring in CPAs using SPs for examining health professions students were selected. A systematic review was conducted to assess the methodological quality and strength of evidence of relevant research and to identify if any potential ethnic and/or gender bias occurred in CPAs. The Guidelines for Critical Review were used to appraise the selected studies. Results: Nine studies published from 2003 to 2017 were retrieved for review. Three studies met all the Guidelines for Critical Review quality criteria, indicating stronger evidence of their outcomes, two of the studies reported ethnic and/or gender bias existing in the CPAs. Overall, four studies found ethnic and/or gender bias in CPAs, but all study results had small effect sizes. Conclusions: No systematic and consistent bias was found across the studies; nonetheless, the possibility of ethnic or gender bias by some examiners cannot be ignored. To minimize potential examiner bias, the investigation of Frame of Reference training, multiple examiners per station, and combination assessments in CPAs is recommended.

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Use of Assistance and Therapy Dogs for Children with Autism Spectrum Disorders: A Critical Review of the Current Evidence

The Journal of Alternative and Complementary Medicine ◽

10.1089/acm.2011.0835 ◽

2013 ◽

Vol 19 (2) ◽

pp. 73-80 ◽

Cited By ~ 56

Author(s):

Alessandra Berry ◽

Marta Borgi ◽

Nadia Francia ◽

Enrico Alleva ◽

Francesca Cirulli

Keyword(s):

Autism Spectrum Disorders ◽

Critical Review ◽

Children With Autism ◽

Autism Spectrum ◽

Current Evidence ◽

Therapy Dogs ◽

Spectrum Disorders

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Impact of Potential Modifications to Alzheimer’s Disease Clinical Trials in Response to Disruption by COVID-19

10.21203/rs.3.rs-752620/v1 ◽

2021 ◽

Author(s):

Lon S Schneider ◽

Yuqi Qiu ◽

Ronald G Thomas ◽

Carol Evans ◽

Diane M. Jacobs ◽

...

Keyword(s):

Clinical Trials ◽

Alzheimer Disease ◽

Statistical Power ◽

Randomized Clinical Trials ◽

Adaptive Methods ◽

Disease Modification ◽

Threats To Validity ◽

Remote Assessment ◽

Political Milieu ◽

The Impact

Abstract BackgroundThe COVID-19 pandemic disrupted Alzheimer disease randomized clinical trials (RCTs)forcing investigators to make changes in the conduct of such trials while endeavoring to maintain their validity. Changing ongoing RCTs carries risks for biases and threats to validity. To understand the impact of exigent modifications due to COVID-19 we examined several scenarios in symptomatic and disease modification trials that could be made.MethodsWe identified both symptomatic and disease modification Alzheimer disease RCTs as exemplars of those that would be affected by the pandemic and considered the types of changes that sponsors could make to each. We modeled three scenarios for each of the types of trialsusing existing datasets, adjusting enrollment, follow-ups, and dropouts to examine the potential effects COVID-19-related changes.Simulations were performed that accounted for completion and dropout patterns using linear mixed effects models, modeling time as continuous and categorical. The statistical power of the scenarios was determined.ResultsTruncating both symptomatic and disease modification trials, led to underpowered trials.By contrast, adapting the trials byextending the treatment period, temporarily stopping treatment, delaying outcomes assessments, and performing remote assessment allowed for increased statistical power nearly to the level originally planned.DiscussionThese analyses support the idea that disrupted trials under common scenarios are better continued and extended even in the face of dropouts, treatment disruptions, missing outcomes, and other exigencies, and that adaptations can be made that maintain the trials validity. We suggest some adaptive methods to do this noting that some changes become under-powered to detect theoriginal effect sizes and expected outcomes. These analyses provide insight to better plan trials that are resilient to unexpected changes to the medical, social, and political milieu.

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Invited Commentary: Examining Sex/Gender Differences in Risk of Alzheimer Disease and Related Dementias—Challenges and Future Directions

American Journal of Epidemiology ◽

10.1093/aje/kwz047 ◽

2019 ◽

Vol 188 (7) ◽

pp. 1224-1227 ◽

Cited By ~ 11

Author(s):

Elizabeth Rose Mayeda

Keyword(s):

Gender Differences ◽

Alzheimer Disease ◽

Death Certificate ◽

Current Issue ◽

Sample Selection ◽

Conclusive Evidence ◽

Current Evidence ◽

Biological Mechanisms ◽

Future Directions ◽

Study Designs

Abstract The majority of people living with Alzheimer disease (AD) and related dementias are women. Longer life expectancy is one factor thought to contribute to this observation, but possible sex-specific biological mechanisms have received considerable attention from the research community. In the current issue of the Journal, Buckley et al. (Am J Epidemiol. 2019;188(7):1213–1223) use death certificate information on all deaths occurring among adults aged ≥60 years in Australia between 2006 and 2014 to evaluate sex/gender differences in rates of death with dementia (all types), AD dementia, and vascular dementia listed on the death certificate. The paper by Buckley et al. highlights several important methodological challenges for research examining sex/gender differences in risk of AD and related dementias, including challenges in measurement, survival bias and competing risks, and selection bias arising from sample selection. The current evidence on possible sex-specific biological risk factors for AD is intriguing, but there are numerous alternative explanations for differences in AD dementia and AD biomarkers between women and men. Triangulation of evidence from study designs with different strengths and weaknesses and transdisciplinary collaboration will be vital to generating conclusive evidence about sex/gender differences in risk of AD and related dementias.

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