Expectations and clinical meaningfulness of randomized controlled trials

Petersen, Ronald C.; Aisen, Paul S.; Andrews, Jeffrey Scott; Atri, Alireza; Matthews, Brandy R.; Rentz, Dorene M.; Siemers, Eric; Weber, Christopher J.; Carrillo, María C.

doi:10.1002/alz.12959

Cited by 39 publications

(43 citation statements)

References 42 publications

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“…Treatment may be discontinued due to AEs or if the patient transitions to moderate AD dementia or a more severe stage. The aligns with the guidance and recommendations of the Alzheimer's Association working group, which consists of experienced and internationally recognized clinicians and researchers [44]. The group aimed to reassess the definition of a significant and meaningful benefit or slowing of ADs, while prioritizing the needs of patients and their families.…”

Section: Discussionmentioning

confidence: 97%

“…According to the working group, if treatments are continued long-term-longer than the 18 months of a typical Phase III Alzheimer's trial-and sustain their effectiveness at the same modest levels as in the clinical trial, they would be expected to show cumulative benefits that become larger, more readily apparent, and more meaningful over time. [44] Given that treatment effect expanded with time on therapy over the 18-month trial duration in the CLARITY AD, our modeling assumption may have been conservative.…”

Section: Discussionmentioning

confidence: 99%

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Estimated Societal Value of Lecanemab in Patients with Early Alzheimer’s Disease Using Simulation Modeling

Monfared

Ye²,

Sardesai³

et al. 2023

Neurol Ther

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Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with memory, cognitive, and behavioral deficits, and brings significant economic burden on caregivers and healthcare systems. This study aims to estimate the long-term societal value of lecanemab plus standard of care (SoC) versus SoC alone, corresponding to a range of willingness-to-pay (WTP) thresholds based on the phase III CLARITY AD trial readouts from both the US payer and societal perspectives. Methods: An evidence-based model was developed to simulate the effects of lecanemab on disease progression in early AD using interconnected predictive equations based on longitudinal clinical and biomarker data derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The model was informed with the results of the phase III CLARITY AD trial and published literature. Key model outcomes included patient life-years (LYs), quality-adjusted life-years (QALYs), and total costs of both the direct and indirect costs of patients and caregivers over a lifetime horizon. Results: Patients treated with lecanemab plus SoC gained an additional 0.62 years of life versus SoC alone (6.23 years vs. 5.61 years). The mean time on lecanemab was 3.91 years, and the treatment was associated with an increase in patient QALYs of 0.61 and an increase in total QALYs of 0.64 when both patient and caregiver utilities were considered. The model estimated that the annual value of lecanemab for the US payer perspective was US$18,678 ($19,351 for societal perspective) at the WTP threshold of $100,000-200,000 per QALY gained, respectively. Scenario analyses of patient subgroups, time horizon, input sources, treatment stopping rules, and treatment dosing were conducted to explore the impact of alternative assumptions on the model results. Conclusion:The economic study suggested that lecanemab plus SoC would improve health and humanistic (quality of life) outcomes and reduce economic burden for patients and caregivers in early AD.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Estimated Societal Value of Lecanemab in Patients with Early Alzheimer’s Disease Using Simulation Modeling

Monfared

Ye²,

Sardesai³

et al. 2023

Neurol Ther

View full text Add to dashboard Cite

show abstract

“…The magnitude of the response is modest and the lack of improvement above baseline will be make it difficult for patients, families, and clinicians to perceive the benefit [13]. This degree of slowing equates to extending the mild cognitive impairment phase of AD by approximately 7.5 months [14]. Simulation modeling suggests that treatment with lecanemab will extend the mild phases of AD dementia by approximately 2.5 years with substantial cost savings [15,16].…”

Section: Mabs Are Disease-modifying Therapiesmentioning

confidence: 99%

Anti-Amyloid Monoclonal Antibodies are Transformative Treatments that Redefine Alzheimer's Disease Therapeutics

Cummings

2023

Drugs

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Two anti-amyloid monoclonal antibodies (MABs)-lecanemab (Leqembi ® ) and aducanumab (Aduhelm ® )-have been approved in the USA for the treatment of Alzheimer's disease (AD). Anti-amyloid monoclonal antibodies are the first disease-modifying therapies for AD that achieve slowing of clinical decline by intervening in the basic biological processes of the disease. These are breakthrough agents that can slow the inevitable progression of AD into more severe cognitive impairment. The results of trials of anti-amyloid MABs support the amyloid hypothesis and amyloid as a target for AD drug development. The success of MABs reflects a relentless application of neuroscience knowledge to solving major challenges facing humankind. The success of these transformative agents will foster the development of more anti-amyloid MABs, other types of anti-amyloid therapies, treatments of other targets of AD biology, and new approaches to therapies for an array of neurodegenerative disorders. Monoclonal antibodies have side effects and, during the period of treatment initiation, patients must be closely monitored for the occurrence of amyloid-related imaging abnormalities (ARIA) and infusion reactions. A successful first step in the development of disease-modifying therapy for AD defines desirable features for the next phase of therapeutic development including less frequent ARIA, more convenient administration, and greater efficacy. Unprecedented agents make new demands on patients and care partners, clinicians, payers, and health care systems. Collaboration among stakeholders is essential to take advantage of the therapeutic benefits offered by these agents and to make them widely available. Monoclonal antibodies usher in a new era in AD therapy and define a new landscape of what is possible for therapeutic development for neurodegenerative disorders.

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“…The authors should be commended for clarifying recently that their study was intended only to identify thresholds of meaningful withinpatient progression and should not be used for determining meaningful group-level differences in clinical trials. 7 However, they should still acknowledge their error, as it pertains to estimating meaningful within-patient decline.…”

Section: Disease Severity and Minimal Clinically Important Difference...mentioning

confidence: 99%

Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials

Dyck

O’Dell

Mecca

2023

A&D Transl Res & Clin Interv

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Expectations and clinical meaningfulness of randomized controlled trials

Cited by 39 publications

References 42 publications

Estimated Societal Value of Lecanemab in Patients with Early Alzheimer’s Disease Using Simulation Modeling

Estimated Societal Value of Lecanemab in Patients with Early Alzheimer’s Disease Using Simulation Modeling

Anti-Amyloid Monoclonal Antibodies are Transformative Treatments that Redefine Alzheimer's Disease Therapeutics

Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials

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