Background: A practicing clinician will often be confronted with the results of a new clinical trial in their relevant field and will be faced with the dilemma of determining whether these results are clinically relevant to their own work. This chapter aims to describe the concepts of statistical significance in randomized clinical trials from a mainly classical statistical inference perspective. This chapter describes approaches to assess clinical significance and illustrates these approaches with examples from the contemporary neurological literature.
Results: There are several approaches that have been described in the research literature to assess the clinical significance including the minimal important clinical difference, the fragility index, Bayesian approaches, and a graphical approach. Unfortunately none of these methods have been widely used in the neurological research literature. Examples are provided to illustrate how these methods can be applied to the contemporary neurological literature in order to provide the clinician with some guidance on their use.
Conclusions: How the trial is designed can affect the external validity of the results and subsequently the clinical relevance of a randomized clinical trial. Large-scale streamlined clinical trials with inclusion criteria that are not too restrictive can improve the generalizability of trial results. Even highly statistically significant treatment effects can be unreliable if they are based on a small number of events. The approaches described in this chapter should provide the practicing clinician with a starting point in order to determine whether the reported statistically significant results are indeed clinically relevant.
Background: Neurological disorders are heterogeneous clinical conditions with variable course and outcome.
Summary: The basic aspects of the commonest neurological disorders are addressed along with the proposed structure of randomized clinical trials (RCTs). Dementing disorders, including Alzheimer's disease (AD), are clinical conditions in which altered cognitive functions are associated with behavioral and personality changes. Parkinson's disease (PD) is a multisystem disorder characterized by motor dysfunction associated with dysautonomia, sleep and olfactory disturbances, cognitive changes, and depression. Amyotrophic lateral sclerosis (ALS) is an invariably fatal clinical condition involving motor neurons. The available treatments are purely symptomatic for PD but virtually ineffective for AD and ALS. Headache disorders, multiple sclerosis, and epilepsy, three diseases characterized by recurrent symptoms and chronic or episodic course, can be fairly easily controlled by current treatments, but cannot be prevented nor cured. The objectives of treatments of neurodegenerative disorders include primary prevention, slowing or arrest of disease progression, and control of symptoms. Stroke is an acute clinical condition causing frequent disability and death, with only one approved treatment. There are many challenges to acute stroke clinical trials; among them, the very short therapeutic window and the issue of stroke heterogeneity. In this chapter, only the core elements of the study designs are outlined.
Key messages: The design of an RCT must be adapted to the basic characteristics of each clinical condition.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：