Browsing by Author "Grill, Joshua D."

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Alzheimer’s disease progression by geographical region in a clinical trial setting
    (BioMed Central, 2015-06-25) Henley, David B.; Dowsett, Sherie A.; Chen, Yun-Fei; Liu-Seifert, Hong; Grill, Joshua D.; Doody, Rachelle S.; Aisen, Paul; Raman, Rema; Miller, David S.; Hake, Ann M.; Cummings, Jeffrey; Department of Medicine, IU School of Medicine
    INTRODUCTION: To facilitate enrollment and meet local registration requirements, sponsors have increasingly implemented multi-national Alzheimer's disease (AD) studies. Geographic regions vary on many dimensions that may affect disease progression or its measurement. To aid researchers designing and implementing Phase 3 AD trials, we assessed disease progression across geographic regions using placebo data from four large, multi-national clinical trials of investigational compounds developed to target AD pathophysiology. METHODS: Four similarly-designed 76 to 80 week, randomized, double-blind placebo-controlled trials with nearly identical entry criteria enrolled patients aged ≥55 years with mild or moderate NINCDS/ADRDA probable AD. Descriptive analyses were performed for observed mean score and observed mean change in score from baseline at each scheduled visit. Data included in the analyses were pooled from the intent-to-treat placebo-assigned overall (mild and moderate) AD dementia populations from all four studies. Disease progression was assessed as change from baseline for each of 5 scales - the AD Assessment Scale-cognitive subscale (ADAS-cog11), the AD Cooperative Study- Activities of Daily Living Scale (ADCS-ADL), Mini-Mental State Examination (MMSE), the Clinical Dementia Rating scored by the sum of boxes method (CDR-SB), and the Neuropsychiatric Inventory (NPI). RESULTS: Regions were heterogeneous at baseline. At baseline, disease severity as measured by ADAS-cog11, ADCS-ADL, and CDR-SB was numerically worse for Eastern Europe/Russia compared with other regions. Of all regional populations, Eastern Europe/Russia showed the greatest cognitive and functional decline from baseline; Japan, Asia and/or S. America/Mexico showed the least cognitive and functional decline. CONCLUSIONS: These data suggest that in multi-national clinical trials, AD progression or its measurement may differ across geographic regions; this may be in part due to heterogeneity across populations at baseline. The observed differences in AD progression between outcome measures across geographic regions may generalize to 'real-world' clinic populations, where heterogeneity is the norm.
  • Thumbnail Image
    Item
    Biomarker disclosure protocols in prodromal Alzheimer’s disease clinical trials
    (Wiley, 2023) Rahman-Filipiak, Annalise; Bolton, Corey; Grill, Joshua D.; Rostamzadeh, Ayda; Chin, Nathaniel; Heidebrink, Judith; Getz, Sarah; Fowler, Nicole R.; Rosen, Allyson; Lingler, Jennifer; Wijsman, Ellen; Clark, Lindsay; Advisory Group on Risk Evidence Education in Dementia (AGREED); Medicine, School of Medicine
    Introduction: The development of biomarkers for Alzheimer's disease (AD) has allowed researchers to increase sample homogeneity and test candidate treatments earlier in the disease. The integration of biomarker "screening" criteria should be met with a parallel implementation of standardized methods to disclose biomarker testing results to research participants; however, the extent to which protocolized disclosure occurs in trials is unknown. Methods: We reviewed the literature to identify prodromal AD trials published in the past 10 years. From these, we quantified the frequency of biomarker disclosure reporting and the depth of descriptions provided. Results: Of 30 published trials using positron emission tomography or cerebrospinal fluid-based amyloid positivity as an eligibility criterion, only one mentioned disclosure, with no details on methods. Discussion: Possible reasons for and implications of this information gap are discussed. Recommendations are provided for trialists considering biomarker screening as part of intervention trials focused on prodromal AD. Highlights: Few prodromal Alzheimer's disease (AD) trial papers discuss biomarker disclosure. Disclosure has implications for participants, family members, and trial success. Disclosure must be consistently integrated and reported in prodromal AD trials. Best practice guidelines and training resources for disclosure are needed.
  • Thumbnail Image
    Item
    Disclosure of individual research results at federally funded Alzheimer's Disease Research Centers
    (Wiley, 2021-10-14) Roberts, J. Scott; Ferber, Rebecca; Blacker, Deborah; Rumbaugh, Malia; Grill, Joshua D.; Medical and Molecular Genetics, School of Medicine
    Introduction: This study describes practices for disclosing individual research results to participants in Alzheimer's disease research. Methods: An online survey of clinical core leaders at National Institutes of Health-funded Alzheimer's Disease Research Centers in the United States (response rate: 30/31, 97%) examined return of results practices across nine different types of research results. Results: Most centers had returned consensus research diagnoses (83%) and neuropsychological test results (73%), with fewer having shared amyloid positron emission tomography (43%), tau imaging (10%), or apolipoprotein E (APOE) genotype (7%) results. Centers reported having disclosed a mean of 3.1 types of results (standard deviation = 2.1; range 0-8). The most commonly cited reason for disclosure was to inform participants' medical decision-making (88%). Disclosure involved multiple professionals and modalities, with neurologists (87%) and in-person visits (85%) most commonplace. Discussion: Centers varied widely as to whether and how they disclosed research results. Diagnostic and cognitive test results were more commonly returned than genetic or biomarker results.
  • Thumbnail Image
    Item
    The Advisory Group on Risk Evidence Education for Dementia: Multidisciplinary and Open to All
    (IOS Press, 2022) Rosen, Allyson C.; Arias, Jalayne J.; Ashford, J. Wesson; Blacker, Deborah; Chhatwal, Jasmeer P.; Chin, Nathan A.; Clark, Lindsay; Denny, Sharon S.; Goldman, Jill S.; Gleason, Carey E.; Grill, Joshua D.; Heidebrink, Judith L.; Henderson, Victor W.; Lavacot, James A.; Lingler, Jennifer H.; Menon, Malavika; Nosheny, Rachel L.; Oliveira, Fabricio F.; Parker, Monica W.; Rahman-Filipiak, Annalise; Revoori, Anwita; Rumbaugh, Malia C.; Sanchez, Danurys L.; Schindler, Suzanne E.; Schwarz, Christopher G.; Toy, Leslie; Tyrone, Jamie; Walter, Sarah; Wang, Li-san; Wijsman, Ellen M.; Zallen, Doris T.; Aggarwal, Neelum T.; Medical and Molecular Genetics, School of Medicine
    The brain changes of Alzheimer’s disease and other degenerative dementias begin long before cognitive dysfunction develops, and in people with subtle cognitive complaints, clinicians often struggle to predict who will develop dementia. The public increasingly sees benefits to accessing dementia risk evidence (DRE) such as biomarkers, predictive algorithms, and genetic information, particularly as this information moves from research to demonstrated usefulness in guiding diagnosis and clinical management. For example, the knowledge that one has high levels of amyloid in the brain may lead one to seek amyloid reducing medications, plan for disability, or engage in health promoting behaviors to fight cognitive decline. Researchers often hesitate to share DRE data, either because they are insufficiently validated or reliable for use in individuals, or there are concerns about assuring responsible use and ensuring adequate understanding of potential problems when one’s biomarker status is known. Concerns include warning people receiving DRE about situations in which they might be compelled to disclose their risk status potentially leading to discrimination or stigma. The Advisory Group on Risk Evidence Education for Dementia (AGREEDementia) welcomes all concerned with how best to share and use DRE. Supporting understanding in clinicians, stakeholders, and people with or at risk for dementia and clearly delineating risks, benefits, and gaps in knowledge is vital. This brief overview describes elements that made this group effective as a model for other health conditions where there is interest in unfettered collaboration to discuss diagnostic uncertainty and the appropriate use and communication of health-related risk information.