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Clinical research designs for emerging treatments for Alzheimer disease: moving beyond placebo-controlled trials
1Department of Neurology, University of Minnesota, Minneapolis 55455, USA.
Abstract:
The design of clinical trials must evolve as new therapies become available. The demonstrated efficacy and clinical use of donepezil and vitamin E for Alzheimer disease (AD) has shifted the options for AD research design. There is now a compelling case for alternatives to trials that include a treatment arm with no active therapy (ie, a placebo control). With an existing therapy, such as donepezil or vitamin E, new drugs that are clearly superior to those drugs should be sought. Combination therapy is a likely strategy for the future, implying that clinical trials, if possible, should replicate actual practice. The long duration of future AD trials also will make placebo-controlled trials more difficult to justify and more difficult to recruit for. Add-on or active-control designs represent the alternative approaches. We believe that definitive clinical trials of new AD drugs that use one or the other of these designs would be more likely to bring about therapeutic advances than would comparisons with inactive treatments. Our argument is not a general rejection of placebo-control designs. Our recommendations apply only to the circumstances in which the field of AD drug therapy now finds itself.
Insights
Clinical trial designs for Alzheimer disease (AD) need updating. Given existing treatments like donepezil, future trials should use active controls instead of placebo controls for better therapeutic advances.
Area of Science:
- Neurology
- Clinical Trial Design
- Pharmacology
Background:
- Established therapies like donepezil and vitamin E for Alzheimer disease (AD) impact clinical trial design.
- The availability of effective treatments necessitates a reevaluation of traditional placebo-controlled trials.
Purpose of the Study:
- To advocate for alternative clinical trial designs in Alzheimer disease research.
- To propose the adoption of add-on or active-control designs over placebo controls for new AD drug development.
Main Methods:
- The study presents a conceptual argument based on the current landscape of AD therapeutics.
- It analyzes the limitations of placebo-controlled trials in the context of existing treatments and future combination therapies.
Main Results:
- Active-control or add-on designs are more appropriate for evaluating new Alzheimer disease drugs in the current therapeutic environment.
- These designs are more likely to yield significant therapeutic advances compared to placebo-controlled trials.
Conclusions:
- The evolution of Alzheimer disease therapy justifies a shift away from placebo-controlled trials.
- Implementing active-control or add-on designs will better reflect clinical practice and accelerate the development of superior treatments for Alzheimer disease.