Over 200 publications, including the composite endpoints regulators now recognize. We publish our methodology in the open so reviewers meet it before your submission does.
Alzheimer's Association International Conference (AAIC) · 2024:Poster Tue-17 · Hendrix, Dickson et al.
Companies recently identified clinical study sites engaging in fraudulent practices, reducing success in Alzheimer's disease (AD) clinical trials. Successful trials are reliable…
When the sample size a conventional design demands is larger than the trial you can run, a Global Statistical Test lets the clinical-endpoint hypotheses be tested anyway. The paper sets out when GST applies, how it is pre-specified, and how it has been received in review.
11 publications
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2023 · Am J Pharm Educ
Wassom, Mitchell
Objective: This study aimed to determine whether postgraduate year 1 (PGY-1) pharmacy residents felt more prepared for residency training after having completed a Longitudinal Advanced Pharmacy Practice Experience (LAPPE) program during pharmacy school. Methods: This was a multicenter, two-arm, cross-sectional study among PGY-1 pharmacy residents. The primary outcome was self-reported residency preparedness. Secondary outcomes included self-reported competency in key indicators for success during early residency and matching with a preferred residency program. A survey was developed to obtain these data and was sent via email to all residency program directors of qualifying programs, who then redistributed it to PGY-1 residents in their respective programs. Results: A total of 960 PGY-1 residents were included in the study. Of these, 180 (19%) reported prior participation in a LAPPE program. Longitudinal Advanced Pharmacy Practice Experience participants reported increased preparedness for residency training as compared to nonparticipants (mean 6.18 vs 5.72 on a 7-point Likert scale; difference 0.46, 95% CI 0.309-0.618). Longitudinal Advanced Pharmacy Practice Experience participation was also associated with greater self-reported clinical knowledge and skills (mean 5.18 vs 4.95, difference 0.23, 95% CI 0.093-0.372). Self-reported matching with a preferred residency program was common and similar between cohorts. Conclusion: Postgraduate year 1 residents who had completed a LAPPE felt better prepared for residency than those who had not completed a LAPPE. Prior LAPPE participation was also associated with greater self-reported clinical knowledge and skills at the start of residency training.
2023 · EBioMedicine
Dickson, Samuel · Hendrix, Suzanne
Background: Anti-amyloid vaccines may offer a convenient, affordable, and accessible means of preventing and treating Alzheimer's disease. UB-311 is an anti-amyloid-β active immunotherapeutic vaccine shown to be well-tolerated and to have a durable antibody response in a phase 1 trial. This phase 2a study assessed the safety, immunogenicity, and preliminary efficacy of UB-311 in participants with mild Alzheimer's disease. Methods: A 78-week, randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 2a study was conducted in Taiwan. Participants were randomised in a 1:1:1 ratio to receive seven intramuscular injections of UB-311 (Q3M arm), or five doses of U311 with two doses of placebo (Q6M arm), or seven doses of placebo (placebo arm). The primary endpoints were safety, tolerability, and immunogenicity of UB-311. Safety was assessed in all participants who received at least one dose of investigational product. This study was registered at ClinicalTrials.gov (NCT02551809). Findings: Between 7 December 2015 and 28 August 2018, 43 participants were randomised. UB-311 was safe, well-tolerated, and generated a robust immune response. The three treatment-emergent adverse events (TEAEs) with the highest incidence were injection-site pain (14 TEAEs in seven [16%] participants), amyloid-related imaging abnormality with microhaemorrhages and haemosiderin deposits (12 TEAEs in six [14%] participants), and diarrhoea (five TEAEs in five [12%] participants). A 97% antibody response rate was observed and maintained at 93% by the end of the study across both UB-311 arms. Interpretation: These results support the continued development of UB-311.
2023 · Alzheimers Res Ther
Dickson, Samuel · Hennessey, Sean · Nicodemus-Johnson, Jessie · Knowlton, Newman · Hendrix, Suzanne
Key points of disagreement between the aducanumab FDA statistical review, which had primarily negative conclusions, and the clinical review, which had primarily positive conclusions, were investigated. Results from secondary endpoints in positive Study 302 were significant and these endpoints provided meaningful additional information. Findings indicate the statistical review of the aducanumab data was incorrect in a number of key areas. Greater placebo decline was not responsible for the significant results in Study 302. Correlations did exist between reduction in β-amyloid and clinical outcomes. Missing data and functional unblinding did not likely bias results. In contrast, the clinical review went too far in saying the negative results in Study 301 did not detract from the positive results in Study 302, as all clinical data should be considered in the evaluation, and the clinical review accepted the company's explanation for divergence of the results between the studies although much of the divergence remained unexplained. Interestingly, both the statistical review and the clinical review considered the available efficacy evidence despite both studies being terminated early. Implications of these findings include that the divergence in results seen in the two phase 3 aducanumab studies can be expected in other studies with similar design and analysis. Therefore, further research is needed to determine if analysis methods other than MMRM and/or optimized outcomes will provide more consistent results across studies.
2023 · The Journal of Infectious Diseases
2023 · The Journal of Prevention of Alzheimer's Disease
2023 · The Journal of Prevention of Alzheimer's Disease
2023 · medRxiv
Nicodemus-Johnson, Jessie · Hendrix, Suzanne
Alzheimer’s Disease (AD) is a multifactorial, progressive neurodegenerative disease that disrupts cognitive function through maladaptive misfolded proteins, abnormal neuroimmune responses, and disordered neuronal network activities. Despite continued scientific advances in the understanding of AD biology, there remains an unmet need for safe and effective disease-modifying treatments. Sensory stimulation is an emerging therapeutic approach which has demonstrated disease-modifying effects in preclinical transgenic models of AD. This randomized, sham-controlled, clinical trial (OVERTURE; NCT03556280) evaluated the feasibility and safety of 40Hz auditory and visual stimulation with the CogTx-001 medical device in 70 participants with mild to moderate AD, administered as daily, 1-hour active stimulation (as compared to sham stimulation) over a 6-month period. Primary endpoints of the therapy showed that it was well-tolerated, showed high adherence and demonstrated a favorable safety profile. Secondary outcomes included exploratory outcomes measures such as ADCS-ADL and MMSE scores, which demonstrated significant effects on functional and cognitive abilities. Additionally, sensory stimulation also showed a significant reduction in brain volume loss and cortical thinning, without changes in amyloid PET signal in active versus sham groups. These encouraging results justify further development of 40Hz sensory stimulation as a safe and potentially disease-modifying therapy for AD patients.
2023 · The Journal of Prevention of Alzheimer's Disease
2023 · The Journal of Prevention of Alzheimer's Disease
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