Browsing by Author "Miller, David S."

Now showing 1 - 3 of 3
  • 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
    Diagnostic criteria for apathy in neurocognitive disorders
    (Wiley, 2021) Miller, David S.; Robert, Philippe; Ereshefsky, Larry; Adler, Lawrence; Bateman, Daniel; Cummings, Jeff; DeKosky, Steven T.; Fischer, Corinne E.; Husain, Masud; Ismail, Zahinoor; Jaeger, Judith; Lerner, Alan J.; Li, Abby; Lyketsos, Constantine G.; Manera, Valeria; Mintzer, Jacobo; Moebius, Hans J.; Mortby, Moyra; Meulien, Didier; Pollentier, Stephane; Porsteinsson, Anton; Rasmussen, Jill; Rosenberg, Paul B.; Ruthirakuhan, Myuri T.; Sano, Mary; Zucchero Sarracini, Carla; Lanctôt, Krista L.; Psychiatry, School of Medicine
    Introduction: Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed. Methods: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019. Results: The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change from the patient's usual behavior, and including one of the following: diminished initiative, diminished interest, or diminished emotional expression/responsiveness; causing significant functional impairment and not exclusively explained by other etiologies. Discussion: These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research.
  • Thumbnail Image
    Item
    Is age a prognostic biomarker for survival among women with locally advanced cervical cancer treated with chemoradiation? An NRG Oncology/Gynecologic Oncology Group ancillary data analysis
    (Elsevier, 2016-11) Moore, Kathleen N.; Java, James J.; Slaughter, Katrina N.; Rose, Peter G.; Lanciano, Rachelle; DiSilvestro, Paul A.; Thigpen, J. Tate; Lee, Yi-Chun; Tewari, Krishnansu S.; Chino, Junzo; Seward, Shelly M.; Miller, David S.; Salani, Ritu; Moore, David H.; Stehman, Frederick B.; Obstetrics and Gynecology, School of Medicine
    Objective To determine the effect of age on completion of and toxicities following treatment of local regionally advanced cervical cancer (LACC) on Gynecologic Oncology Group (GOG) Phase I–III trials. Methods An ancillary data analysis of GOG protocols 113, 120, 165, 219 data was performed. Wilcoxon, Pearson, and Kruskal-Wallis tests were used for univariate and multivariate analysis. Log rank tests were used to compare survival lengths. Results One-thousand-three-hundred-nineteen women were included; 60.7% were Caucasian, 15% were age 60–70 years and an additional 5% were >70; 87% had squamous histology, 55% had stage IIB disease and 34% had IIIB disease. Performance status declined with age (p = 0.006). Histology and tumor stage did not significantly differ., Number of cycles of chemotherapy received, radiation treatment time, nor dose modifications varied with age. Notably, radiation protocol deviations and failure to complete brachytherapy (BT) did increase with age (p = 0.022 and p < 0.001 respectively)., Only all grade lymphatic (p = 0.006) and grade ≥3 cardiovascular toxicities (p= 0.019) were found to vary with age., A 2% increase in the risk of death for every year increase >50 for all-cause mortality (HR 1.02; 95% CI, 1.01–1.04) was found, but no association between age and disease specific mortality was found. Conclusion This represents a large analysis of patients treated for LACC with chemo/radiation, approximately 20% of whom were >60 years of age. Older patients, had higher rates of incomplete brachytherapy which is not explained by collected toxicity data. Age did not adversely impact completion of chemotherapy and radiation or toxicities.