Treatment Comparisons in Clinical Trials

2010 ◽  
pp. 55-80
Keyword(s):  
Clinical Trials ◽  
Treatment Comparisons

scholarly journals A simple solution to the inadequacy of asymptotic likelihood-based inference for response-adaptive clinical trials

2021 ◽  
Author(s):  
Alessandro Baldi Antognini ◽  
Marco Novelli ◽  
Maroussa Zagoraiou
Keyword(s):  
Clinical Trials ◽  
Primary Outcome ◽  
Wald Test ◽  
Simple Solution ◽  
Nuisance Parameters ◽  
Simulation Studies ◽  
Fundamental Properties ◽  
Adaptive Clinical Trials ◽  
Treatment Comparisons ◽  
Practical Recommendations

AbstractThe present paper discusses drawbacks and limitations of likelihood-based inference in sequential clinical trials for treatment comparisons managed via Response-Adaptive Randomization. Taking into account the most common statistical models for the primary outcome—namely binary, Poisson, exponential and normal data—we derive the conditions under which (i) the classical confidence intervals degenerate and (ii) the Wald test becomes inconsistent and strongly affected by the nuisance parameters, also displaying a non monotonic power. To overcome these drawbacks, we provide a very simple solution that could preserve the fundamental properties of likelihood-based inference. Several illustrative examples and simulation studies are presented in order to confirm the relevance of our results and provide some practical recommendations.

Extracorporeal Membrane Oxygenation and the Play the Winner Rule

PEDIATRICS ◽  
1985 ◽  
Vol 76 (4) ◽  
pp. 622-623
Author(s):  
NIGEL PANETH ◽  
SYLVAN WALLENSTEIN
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Extracorporeal Membrane Oxygenation ◽  
Randomized Clinical Trial ◽  
Conventional Treatment ◽  
Randomized Clinical Trials ◽  
Ethical Problem ◽  
Therapeutic Trial ◽  
Membrane Oxygenation ◽  
Treatment Comparisons

The therapeutic trial comparing extracorporeal membrane oxygenation with conventional treatment in neonatal respiratory failure reported by Bartlett et al (Pediatrics 1985;76:479-487) uses a method of comparing treatments unlikely to be familiar to most pediatricians. Known as the "randomized play the winner" method, it has thus far been little used in clinical research. Most clinical investigators consider the conventional randomized clinical trial to be the last word in treatment comparisons. But randomized clinical trials are costly, cumbersome, and to some observers less than ideal ethically. The ethical problem arises from the fact that during a "successful" randomized clinical trial (ie, one that demonstrates a significant advantage to one treatment) about half of the trial subjects will receive a treatment which, at the end of the trial, will be known to be inferior.

Remission Control of Pre-Post Treatment Comparisons by Two-Sample Symmetry Testing

1986 ◽  
Vol 25 (02) ◽  
pp. 116-122 ◽  
Author(s):  
T. Havránek ◽  
G. A. Lienert
Keyword(s):  
Clinical Trials ◽  
Contingency Tables ◽  
Psychotherapy Research ◽  
Spontaneous Remission ◽  
Post Treatment ◽  
Omnibus Test ◽  
Global Improvement ◽  
Treatment Comparisons ◽  
Symmetry Tests

SummaryStarting from one-sample symmetry testing in pre-post treatment square contingency tables, two-sample symmetry tests were constructed and suggested for control of spontaneous remission in clinical trials. The fourfold tests presented are sensitive to the alternatives of specified improvement effects, global improvement effects and differential improvement effects in subgroups of patients and include a composite fourfold omnibus test which is rather insensitive to many alternatives. The application of two-sample symmetry testing is illustrated numerically by an example from controlled psychotherapy research.

Clinical trials with new oral anticoagulants

2013 ◽  
Vol 33 (01) ◽  
pp. 62-70 ◽  
Author(s):  
C. Weiss ◽  
J. Harenberg
Keyword(s):  
Clinical Trials ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
New Oral Anticoagulants ◽  
Replacement Surgery ◽  
Hip Replacement Surgery ◽  
Mixed Treatment ◽  
Total Knee ◽  
Treatment Comparisons ◽  
Mixed Treatment Comparisons

SummaryTo compare the efficacy and safety of the new oral anticoagulants (NOAC), ideally head-to-head clinical trials should be performed. Given the expense of such an undertaking, it is highly unlikely that such a comparison would be performed. Therefore, there is a need for an unbiased comparative assessment of the benefits and risks of the NOACs, based on the available trial data. Indirect or mixed treatment comparisons may be an useful tool to overcome these limitations also known as network meta-analysis (NMA).The aim of this paper is to give an overview on published NMAs for dabigatran, rivaroxaban and apixaban, each assessed against warfarin in patients with atrial fibrillation, and against enoxaparin in patients undergoing total knee and total hip replacement surgery, in order to obtain insights into the comparability of the adopted methodological techniques.

scholarly journals Optimal designs for testing hypothesis in multiarm clinical trials

2018 ◽  
Vol 28 (10-11) ◽  
pp. 3242-3259 ◽  
Author(s):  
Alessandro Baldi Antognini ◽  
Marco Novelli ◽  
Maroussa Zagoraiou
Keyword(s):  
Clinical Trials ◽  
Treatment Effects ◽  
Optimal Allocation ◽  
Statistical Tests ◽  
Optimal Solution ◽  
Binary Outcomes ◽  
Model Parameters ◽  
Statistical Efficiency ◽  
Power Of The Test ◽  
Treatment Comparisons

The present paper deals with the problem of designing randomized multiarm clinical trials for treatment comparisons in order to achieve a suitable trade-off among inferential precision and ethical concerns. Although the large majority of the literature is focused on the estimation of the treatment effects, in particular for the case of two treatments with binary outcomes, the present paper takes into account the inferential goal of maximizing the power of statistical tests to detect correct conclusions about the treatment effects for normally response trials. After discussing the allocation optimizing the power of the classical multivariate test of homogeneity, we suggest a multipurpose design methodology, based on constrained optimization, which maximizes the power of the test under a suitable ethical constraint reflecting the effectiveness of the treatments. The ensuing optimal allocation depends in general on the unknown model parameters but, contrary to the unconstrained optimal solution or to some targets proposed in the literature, it is a non-degenerate continuous function of the treatment contrasts, and therefore it can be approached by standard response-adaptive randomization procedures. The properties of this constrained optimal allocation are described both theoretically and through suitable examples, showing good performances both in terms of ethical gain and statistical efficiency, taking into account estimation precision as well.

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