Subject Selection and Characterization in Clinical Trials in Children with Autism

CNS Spectrums ◽  
2004 ◽  
Vol 9 (1) ◽  
pp. 22-32 ◽  
Author(s):  
Lawrence Scahill ◽  
Catherine Lord
Keyword(s):  
Clinical Trials ◽  
Sample Size ◽  
Effect Size ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Primary Outcome Measure ◽  
Expected Improvement ◽  
Measure Data ◽  
Subject Selection ◽  
Study Results

ABSTRACTThe goal of psychopharmacohgic research in autism is to provide guidance to clinicians and families on the risks and benefits of specific interventions. Careful subject selection and subject characterization in clinical trials are necessary for replication, to inform clinicians about the sample, and to elucidate the type of patients who might benefit from, the treatment. At minimum, subject characterization includes demographic information, diagnosis (autism, Åsperger's syndrome, or pervasive developmental disorder-not otherwise specified), intellectual functioning, adaptive functioning, symptom severity, general behavioral profile, health status, pertinent clinical laboratory measures, height, weight, current treatments, and educational placements. Subject selection, sample size, and choice of the primary outcome measure are closely interrelated and linked to the study hypothesis. The magnitude of expected improvement on the primary outcome measure, which can be expressed by effect size, has direct implications for sample size. Large sample sizes are required to detect small effect sizes. To facilitate interpretation of study results, research reports should provide descriptive characteristics of the sample as well as the mean change and standard deviation on the primary outcome measure data to permit calculation of the effect size.

Statistical analysis, trial design and duration in Alzheimer's disease clinical trials: a review

2011 ◽  
Vol 24 (5) ◽  
pp. 689-697 ◽  
Author(s):  
P. A. Thompson ◽  
D. E. Wright ◽  
C. E. Counsell ◽  
J. Zajicek
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Statistical Analysis ◽  
Statistical Methods ◽  
Outcome Measures ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Primary Outcome Measure ◽  
Primary Analysis

ABSTRACTBackground: The social and economic burden of Alzheimer's disease (AD) and its increasing prevalence has led to much work on new treatment strategies and clinical trials. The search for surrogate markers of disease progression continues but traditional parallel group trial designs that use well-established, but often insensitive, clinical outcome measures predominate.Methods: We performed a systematic search across the Cochrane Library and PubMed abstracts published between January 2004 and August 2009. Information regarding the clinical trial methodology, outcome measures, intervention type and primary statistical analysis techniques was extracted and categorized, according to a standard protocol.Results: We identified 149 papers describing results from clinical trials in AD containing sufficient detail for our purposes. The largest proportion (38%) presented results of trials based on tests of cognition as the primary outcome measure. The primary analysis in most papers (85%) was a univariate significance test of a single primary outcome measure.Conclusions: The majority of trials reported a comparison of baseline and end-point assessment over relatively short patient follow-up periods, using univariate statistical methods to compare differences between intervention and control groups in the primary analysis. There is considerable scope to introduce newer statistical methods and trial designs in treatment evaluations in AD.

scholarly journals Reporting of statistical sample size calculations in publications of trials on age-related macular degeneration, glaucoma and cataract

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252640
Author(s):  
Sabrina Tulka ◽  
Stephanie Knippschild ◽  
Sina Funck ◽  
Isabelle Goetjes ◽  
Yasmin Uluk ◽  
...  
Keyword(s):  
Sample Size ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Sample Size Calculation ◽  
Primary Outcome Measure ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Number Of Patients ◽  
Sample Size Calculations ◽  
Statistical Sample

Background Transparent and complete publications of randomised controlled trials (RCT) ought to comply with the guidelines of the CONSORT Statement, which stipulates sample size calculation as an important aspect of trial planning. The objective of this study was to analyse and compare the reporting of statistical sample size calculations in RCT papers on the treatment of age-related macular degeneration (AMD), glaucoma and cataract published in 2018. Material and methods This study comprises a total of 113 RCT papers (RCT-P) published in 2018 (AMD: 14, glaucoma: 28, cataract: 71), in English or German, and identified through an internet-based literature search in PubMed and EMBASE. The primary outcome measure of the study was the number of trials providing a complete description of the underlying sample case calculation on the basis of the variables required (significance level, expected outcomes, power, and resulting sample size). Results Of the RCTs reviewed, 64% (AMD), 61% (glaucoma) and 31% (cataract) provided a justification of the number of patients included. A complete description of the described studies’ sample size calculation including all the necessary values (primary outcome measure of this study) was described by 21% of the AMD, 29% of the cataract and 18% of the glaucoma RCT publications (in total: 24 of 113 (21%) at a confidence interval of 95%: [13%; 29%]). Conclusion All three treatment areas analysed lacked reporting quality regarding the justification of the number of patients included in a clinical trial based on a sample size calculation required for ethical reasons. More than half of all RCT publications reviewed did not provide all of the required information on statistical sample size calculation, and thus lacked transparency and completeness. It is therefore urgently required to involve methodologists in a study’s planning and publishing processes to ensure that methodology descriptions are transparent and of high quality.

Rationale for use of the Clinical Dementia Rating Sum of Boxes as a primary outcome measure for Alzheimer's disease clinical trials

2012 ◽  
Vol 9 (1S) ◽  
pp. S45-S55 ◽  
Author(s):  
Jesse M. Cedarbaum ◽  
Mark Jaros ◽  
Chito Hernandez ◽  
Nicola Coley ◽  
Sandrine Andrieu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Primary Outcome Measure ◽  
Clinical Dementia Rating

scholarly journals Timed walk as primary outcome measure of treatment response in clinical trials for HTLV-1-associated myelopathy: a feasibility study

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Fabiola Martin ◽  
Eisuke Inoue ◽  
Irene C. M. Cortese ◽  
Ramon de Almeida Kruschewsky ◽  
Adine Adonis ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Response ◽  
Feasibility Study ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Primary Outcome Measure

The role of MRI as a surrogate outcome measure in multiple sclerosis

2002 ◽  
Vol 8 (1_suppl) ◽  
pp. 40-51 ◽  
Author(s):  
HF McFarland ◽  
F. Barkhof ◽  
J. Antel ◽  
DH Miller
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Imaging Techniques ◽  
Primary Outcome Measure ◽  
New Therapies ◽  
Surrogate Outcome ◽  
Underlying Pathology ◽  
Surrogate Outcome Measure

The need for more specific and more sensitive outcome measures for use in testing new therapies in multiple sclerosis (MS) is generally accepted. This need has been accentuated by the realization that the ability to conduct large placebo-controlled trials will be limited in the future. From the first use of magnetic resonance imaging (MRI) to study MS, the ability of this imaging technique to identify areas of the central nervous system damage by the disease process in MS has been impressive. Thus, the possibility that MRI could serve as a surrogate outcome measure in clinical trials in MS has been attractive. The use of MRI as a surrogate outcome measure has been examined by an international group of investigators with expertise in clinical aspects of MS, the use of MRI in MS, and in experimental therapeutics. The group agreed that MRI does not represent a validated surrogate in any clinical form of MS. It was also agreed, however, that MRI does provide a reflection of the underlying pathology in the disease, but no single MRI measurement in isolation was seen as sufficient to monitor disease. The use for multiple imaging techniques, especially new, emerging techniques that may better reflect the underlying pathology, was seen as particularly important in monitoring studies of patients with either secondary or primary progressive MS. The choice of MRI techniques used to monitor new therapies needs to be consistent with the proposed mechanisms of the new therapy and phase of the disease. It was also noted, however, that additional validation is required for nonconventional imaging techniques. Finally, the participants noted that clinical trials using MRI as a primary outcome measure may fail to fully identify the effects of the therapy on clinical measures and that the risk and cost-benefit ratio of the treatment might be unresolved. Thus, before MRI is used as a primary outcome measure, new approaches to trial design must be given careful consideration. Multiple Sclerosis (2002)8, 40-51

Lesional magnetization transfer ratio: a feasible outcome for remyelinating treatment trials in multiple sclerosis

2010 ◽  
Vol 16 (6) ◽  
pp. 660-669 ◽  
Author(s):  
IJ van den Elskamp ◽  
DL Knol ◽  
H. Vrenken ◽  
G. Karas ◽  
A. Meijerman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Magnetization Transfer ◽  
Primary Outcome Measure ◽  
Magnetization Transfer Ratio ◽  
Power Calculations ◽  
Transfer Ratio ◽  
Feasible Outcome

Magnetization transfer ratio (MTR) is a sensitive parameter to quantify the integrity of myelinated white matter in patients with multiple sclerosis. Lesional MTR decreases in the acute phase due to demyelination, and subsequently shows recovery depending on the degree of remyelination in the absence of axonal loss. Recovery of average lesion MTR therefore might prove a viable outcome measure to assess the effect of remyelinating agents. Our objective was to determine the required sample size for phase II multicentre clinical trials using the recovery of average lesion MTR as primary outcome measure. With 7-monthly MRI scans, the MTR evolution of 349 new enhancing lesions before and after enhancement was assessed in 32 MS patients from 5 centres. Multilevel models were fitted to the data yielding estimates for the variance components, which were applied in power calculations. Sample sizes were determined for placebo-controlled, multicentre trials using lesional MTR recovery post-enhancement as primary outcome measure. Average lesion MTR decreased slightly in the build-up to enhancement, decreased dramatically during enhancement and showed recovery in the period after cessation. The power calculations showed that for a power of 80%, approximately 136 patients per trial (mean number of 6 lesions per patient) are required to detect a 30% increase in lesional MTR post-enhancement compared with placebo, whereas 48 subjects are required to detect a 50% increase in lesional MTR compared with placebo. Recovery of lesion MTR is a feasible outcome measure for future multicentre clinical trials measuring the effect of remyelinating agents.

Comparison of Percentage of Syllables Stuttered With Parent-Reported Severity Ratings as a Primary Outcome Measure in Clinical Trials of Early Stuttering Treatment

2018 ◽  
Vol 61 (4) ◽  
pp. 811-819 ◽  
Author(s):  
Mark Onslow ◽  
Mark Jones ◽  
Sue O'Brian ◽  
Ann Packman ◽  
Ross Menzies ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Trials ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Primary Outcome Measure ◽  
Analysis Of Covariance ◽  
Data Sets ◽  
Randomized Controlled ◽  
Absolute Agreement

Purpose This report investigates whether parent-reported stuttering severity ratings (SRs) provide similar estimates of effect size as percentage of syllables stuttered (%SS) for randomized trials of early stuttering treatment with preschool children. Method Data sets from 3 randomized controlled trials of an early stuttering intervention were selected for analyses. Analyses included median changes and 95% confidence intervals per treatment group, Bland–Altman plots, analysis of covariance, and Spearman rho correlations. Results Both SRs and %SS showed large effect sizes from pretreatment to follow-up, although correlations between the 2 measures were moderate at best. Absolute agreement between the 2 measures improved as percentage reduction of stuttering frequency and severity increased, probably due to innate measurement limitations for participants with low baseline severity. Analysis of covariance for the 3 trials showed consistent results. Conclusion There is no statistical reason to favor %SS over parent-reported stuttering SRs as primary outcomes for clinical trials of early stuttering treatment. However, there are logistical reasons to favor parent-reported stuttering SRs. We conclude that parent-reported rating of the child's typical stuttering severity for the week or month prior to each assessment is a justifiable alternative to %SS as a primary outcome measure in clinical trials of early stuttering treatment.

The role of MRI as a surrogate outcome measure in multiple sclerosis

2002 ◽  
Vol 8 (1) ◽  
pp. 40-51 ◽  
Author(s):  
H F McFarland ◽  
F Barkhof ◽  
J Antel ◽  
D H Miller
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Imaging Techniques ◽  
Primary Outcome Measure ◽  
New Therapies ◽  
Surrogate Outcome ◽  
Underlying Pathology ◽  
Surrogate Outcome Measure

The need for more specific and more sensitive outcome measures for use in testing new therapies in multiple sclerosis (MS) is generally accepted. This need has been accentuated by the realization that the ability to conduct large placebo-controlled trials will be limited in the future. From the first use of magnetic resonance imaging (MRI) to study MS, the ability of this imaging technique to identify areas of the central nervous system damage by the disease process in MS has been impressive. Thus, the possibility that MRI could serve as a surrogate outcome measure in clinical trials in MS has been attractive. The use of MRI as a surrogate outcome measure has been examined by an international group of investigators with expertise in clinical aspects of MS, the use of MRI in MS, and in experimental therapeutics. The group agreed that MRI does not represent a validated surrogate in any clinical form of MS. It was also agreed, however, that MRI does provide a reflection of the underlying pathology in the disease, but no single MRI measurement in isolation was seen as sufficient to monitor disease. The use for multiple imaging techniques, especially new, emerging techniques that may better reflect the underlying pathology, was seen as particularly important in monitoring studies of patients with either secondary or primary progressive MS. The choice of MRI techniques used to monitor new therapies needs to be consistent with the proposed mechanisms of the new therapy and phase of the disease. It was also noted, however, that additional validation is required for nonconventional imaging techniques. Finally, the participants noted that clinical trials using MRI as a primary outcome measure may fail to fully identify the effects of the therapy on clinical measures and that the risk and cost-benefit ratio of the treatment might be unresolved. Thus, before MRI is used as a primary outcome measure, new approaches to trial design must be given careful consideration.

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