A novel adaptive design strategy increases the efficiency of clinical trials in secondary progressive multiple sclerosis

Chataway, Jeremy; Nicholas, Richard; Todd, Susan; Miller, David H.; Parsons, Nicholas R.; Valdès-Márquez, Elsa; Stallard, Nigel; Friede, Tim

doi:10.1177/1352458510382129

Cited by 48 publications

(43 citation statements)

References 23 publications

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“…So we have entered a new era of RCT in MS: since patients are enrolled in trials which are more and more benign and the use of placebo has become ethically questionable 2 new design strategies are required to handle this evolution, and a large effort is devoted to study, among other strategies, the validation of surrogate outcomes 3,4 and the application of adaptive designs. 5,6 Therefore, after about 20 years of RCT history in MS, the aim of this paper is to review the quality of RCT in MS reports from 1993 to 2010. In this last decade, the quality of RCT reporting has in general constantly improved, with many journals having statistical refereeing and clearer guidelines to authors.…”

Section: Introductionmentioning

confidence: 99%

The quality of reports of randomized trials in multiple sclerosis: a review

2012

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Randomized clinical trials (RCT) in multiple sclerosis (MS) have a recent tradition, but their number has been exponentially increasing since the first study detecting the efficacy of a disease modifying drug in MS. To examine the methodological details of reports of RCT in MS, we extracted from five leading journals all the reports of RCT published between 1993 and 2010. Trial reports were compared for different periods (1993-2001, 2002-2006, 2007-2010) for a set of indicator variables reflecting methodological quality (including details about randomization and blinding, statistical methods, results reporting, subgroup analyses). Fifty-three reports were included in the analysis. All of the methodological items indicated an improvement over time in the quality of reporting, the main weaknesses being frequent and inappropriate use of significance testing for assessing baseline imbalances and the statistical approach to subgroup analysis. A complete and transparent reporting of trial methodology is becoming even more important in an era when new design strategies are required for the feasibility of future trials in MS.

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Section: Introductionmentioning

confidence: 99%

The quality of reports of randomized trials in multiple sclerosis: a review

2012

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“…Dragalin (2011) discusses the potential for the use of adaptive designs in all phases of development, including discussion of phase II/III trials, in central nervous system studies. Chataway et al (2011) and Friede et al (2011) propose a phase II/III seamless adaptive design for use in secondary progressive multiple sclerosis trials.…”

Section: Introductionmentioning

confidence: 99%

A Comparison of Methods for Treatment Selection in Seamless Phase II/III Clinical Trials Incorporating Information on Short-Term Endpoints

Kunz

Friede

Parsons

et al. 2015

Journal of Biopharmaceutical Statistics

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In an adaptive seamless phase II/III clinical trial interim analysis, data are used for treatment selection, enabling resources to be focused on comparison of more effective treatment(s) with a control. In this paper, we compare two methods recently proposed to enable use of short-term endpoint data for decision-making at the interim analysis. The comparison focuses on the power and the probability of correctly identifying the most promising treatment. We show that the choice of method depends on how well short-term data predict the best treatment, which may be measured by the correlation between treatment effects on short-and long-term endpoints.

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“…For example, MRI outcomes could guide the interim decision, while clinical disability would be the phase III primary outcome. This strategy has the capacity to reduce both the duration and magnitude of SPMS trials compared with conventional designs [149].…”

Section: Trial Designmentioning

confidence: 99%

“…A number of alternative trial designs have been proposed in order to overcome this problem. Adaptive seamless trial designs combine phase II and phase III trials, and may simultaneously test multiple drugs, using interim markers to define which treatments should be taken into phase III [149,150]. For example, MRI outcomes could guide the interim decision, while clinical disability would be the phase III primary outcome.…”

Section: Trial Designmentioning

confidence: 99%

Secondary Progressive Multiple Sclerosis: Definition and Measurement

et al. 2016

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Secondary progressive multiple sclerosis (SPMS) is diagnosed retrospectively and involves a clinical course characterized by a progressive accumulation of neurological disability, independent of relapses, following an initial relapsing-remitting (RR) phase. Our incomplete understanding of the pathological mechanisms underlying neurodegeneration in multiple sclerosis (MS) may explain why, to date, there is no definitive imaging or laboratory test that is able to inform us when the disease is clearly entering into a progressive phase and why the vast majority of clinical trials testing immunosuppressant and immunomodulating drugs in SPMS patients has so far yielded disappointing or mixed results. Here we discuss the definition(s) of SPMS and how it may vary, outcome measurements (current and emerging) and modern trial design.

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A novel adaptive design strategy increases the efficiency of clinical trials in secondary progressive multiple sclerosis

Abstract: Although more complex in design, ASDs have the potential to be more efficient and more powerful than conventional designs.

Cited by 48 publications

References 23 publications

The quality of reports of randomized trials in multiple sclerosis: a review

The quality of reports of randomized trials in multiple sclerosis: a review

A Comparison of Methods for Treatment Selection in Seamless Phase II/III Clinical Trials Incorporating Information on Short-Term Endpoints

Secondary Progressive Multiple Sclerosis: Definition and Measurement

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