scholarly journals Fall Incidence as the Primary Outcome in Multiple Sclerosis Falls-Prevention Trials

2014 ◽  
Vol 16 (4) ◽  
pp. 178-184 ◽  
Author(s):  
Susan Coote ◽  
Jacob J. Sosnoff ◽  
Hilary Gunn
Keyword(s):  
Multiple Sclerosis ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Primary Outcome Measure ◽  
Falls Prevention ◽  
Research Network ◽  
Prevention Research ◽  
Prevention Interventions ◽  
Prevention Trials ◽  
Definition Of

The aim of this article is to provide recommendations on behalf of the International MS Falls Prevention Research Network (IMSFPRN) for the primary outcome measure for multiple sclerosis (MS) falls-prevention interventions. The article will consider the definition of a fall, methods of measuring falls, and the elements of falls that should be recorded, as well as how these elements should be presented and analyzed. While this information can be used to inform the content of falls-prevention programs, the primary aim of the article is to make recommendations on how the outcome of these programs should be captured.

scholarly journals Targeting Dynamic Balance in Falls-Prevention Interventions in Multiple Sclerosis

2014 ◽  
Vol 16 (4) ◽  
pp. 198-202 ◽  
Author(s):  
Davide Cattaneo ◽  
Johanna Jonsdottir ◽  
Susan Coote
Keyword(s):  
Multiple Sclerosis ◽  
Daily Living ◽  
Outcome Measure ◽  
Dynamic Balance ◽  
Falls Prevention ◽  
Research Network ◽  
Inclusion Criteria ◽  
Prevention Interventions ◽  
Balance Deficits ◽  
Prevention Trials

Balance deficits are common in people with multiple sclerosis (MS) and are associated with past and future falls. People with MS tend to fall during activities of daily living and recreation that involve transitions between body positions and during walking and turning. The evident deficits in dynamic balance may be partly due to impairment in the collection or integration of sensory inputs or the execution of appropriate movements in moments of distraction. There is growing evidence that dynamic balance is modifiable and that improvements in dynamic balance are associated with reduction in falls. Consequently, it is imperative that balance measures be appropriate to capture changes in components of dynamic balance. There are numerous ways to measure dynamic balance. When selecting the appropriate dynamic balance measure for an MS falls-prevention trial, the inclusion criteria and content of intervention will inform the choice of measure. The International MS Falls Prevention Research Network (IMSFPRN) suggests that measures of dynamic balance be included as an outcome measure for use in falls-prevention trials.

scholarly journals Whom to Target for Falls-Prevention Trials

2014 ◽  
Vol 16 (4) ◽  
pp. 203-207 ◽  
Author(s):  
Michelle Cameron ◽  
Susan Coote ◽  
Jacob J. Sosnoff
Keyword(s):  
Falls Prevention ◽  
Research Network ◽  
Assistive Device ◽  
Prevention Research ◽  
Inaugural Meeting ◽  
Prevention Interventions ◽  
History Of ◽  
Prevention Trials ◽  
Review Reports ◽  
Device Use

Effective falls-prevention approaches for people with multiple sclerosis (MS) are needed. A significant challenge in studying falls-prevention programs for people with MS is deciding whom to include in trials. This article presents and discusses potential criteria for selecting participants for trials of falls-prevention interventions in MS. This narrative review reports on the inaugural meeting of the International MS Falls Prevention Research Network (IMSFPRN), which was held in March 2014 in Kingston, Ontario, Canada. Criteria considered were age, assistive device use, cognition, and fall history. The IMSFPRN reached consensus agreement to recommend that participants of all ages with varying levels of cognitive ability who are able to ambulate with or without assistance and who have a history of falling should be included in their future falls-prevention trials.

Change in quality of life in patients with relapsing–remitting multiple sclerosis over 2 years in relation to other clinical parameters: results from a trial of intramuscular interferon β-1a

2011 ◽  
Vol 17 (6) ◽  
pp. 734-742 ◽  
Author(s):  
DM Miller ◽  
B Weinstock-Guttman ◽  
D Bourdette ◽  
X You ◽  
P Foulds ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Primary Outcome Measure ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: A randomized, placebo-controlled, multicenter study of weekly intramuscular injections of interferon beta-1a (IFNβ-1a) in relapsing–remitting multiple sclerosis included the Sickness Impact Profile (SIP), a validated measure of patient-reported quality of life (QoL). Objective: To demonstrate the impact of moderate to severe SIP disability at baseline and change in QoL as measured by SIP over 2 years in relation to other study parameters. Methods: In 158 patients, SIP scores were determined at baseline and 2 years. Scores were correlated with disease progression and treatment. Results: Patients who experienced disability progression, as defined by Expanded Disability Status Scale (EDSS) and annualized relapse rate, during the study demonstrated significant worsening in Physical SIP scores compared with patients who did not progress ( p = 0.031). In patients with low SIP scores, indicating moderate or severe disability at baseline, treatment with IFNβ-1a significantly improved Physical SIP subscores. Conclusions: Patients with disability progression defined using EDSS, the physician-derived primary outcome measure, had Physical SIP scores indicating worsening disability, validating the physician-derived primary outcome measure using patient self-report. Treatment with IFNβ-1a had beneficial effects on QoL in patients with worse SIP scores at baseline.

Persistent T1 hypointensity as an MRI marker for treatment efficacy in multiple sclerosis

2008 ◽  
Vol 14 (6) ◽  
pp. 764-769 ◽  
Author(s):  
IJ van den Elskamp ◽  
J Lembcke ◽  
V Dattola ◽  
K Beckmann ◽  
C Pohl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Black Hole ◽  
Phase Ii ◽  
Primary Outcome ◽  
Negative Binomial ◽  
Outcome Measure ◽  
Primary Outcome Measure ◽  
Cumulative Number ◽  
Sample Sizes ◽  
Simulation Procedure

Background MRI is often used as primary outcome measure in phase II clinical trials in multiple sclerosis (MS). Since persistent T1 hypointense lesions are a surrogate parameter for axonal damage and demyelination, they may serve as a marker for monitoring the efficacy of neuroprotective drugs. At present, a power analysis using black hole (BH) evolution as primary outcome measure has not been performed. Objective To assess the feasibility of using BH evolution on serial brain MR images as primary outcome measure in proof of concept studies in MS. Methods MRI-data obtained from 169 active RRMS patients were analysed for BH evolution by determining the cumulative number of contrast enhancing lesions (CEL) evolving into a persistent black hole (PBH) after 3 months. With a parametric simulation procedure, based on a statistical distribution fitting the data, sample sizes were calculated. Results 21.2% of the total number of CELs observed during the study period evolved into a PBH. Ring enhancing lesions evolved most frequently into a PBH (59.4%), followed by lesions larger than 10 mm (57.4%) and periventricular CELs (30.6%). The simulation procedure, based on the statistical negative binomial (NB) model resulted in a sample sizes between 200 subjects and 30 subjects per arm, for treatment effects ranging from 50% to 90% reduction of the number of CELs evolving into a PBH, respectively. Conclusion To perform a MRI monitored phase II clinical trial with a feasible sample size, using the evolution of CELs into PBHs as primary outcome parameter, a potent drug is required to obtain sufficient power.

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.

scholarly journals Applying the RE-AIM Framework to Inform the Development of a Multiple Sclerosis Falls-Prevention Intervention

2014 ◽  
Vol 16 (4) ◽  
pp. 192-197 ◽  
Author(s):  
Marcia Finlayson ◽  
Davide Cattaneo ◽  
Michelle Cameron ◽  
Susan Coote ◽  
Patricia N. Matsuda ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Group Discussion ◽  
Practice Change ◽  
Falls Prevention ◽  
Research Network ◽  
Prevention Intervention ◽  
Prevention Interventions ◽  
Research Findings ◽  
Large Group Discussion ◽  
Widespread Dissemination

Successfully addressing the problem of falls among people with multiple sclerosis (MS) will require the translation of research findings into practice change. This process is not easy but can be facilitated by using frameworks such as RE-AIM during the process of planning, implementing, and evaluating MS falls-prevention interventions. RE-AIM stands for Reach, Effectiveness, Adoption, Implementation, and Maintenance. Since its initial publication in 1999, the RE-AIM framework has become widely recognized across a range of disciplines as a valuable tool to guide thinking about the development and evaluation of interventions intended for widespread dissemination. For this reason, it was selected by the International MS Falls Prevention Research Network to structure initial discussions with clinicians, people with MS, and representatives of professional and MS societies about the factors we need to consider in the development of an MS falls-prevention intervention for multisite testing that we hope will someday be disseminated widely. Through a combination of small-group work and large-group discussion, participants discussed four of the five RE-AIM elements. A total of 17 recommendations were made to maximize the reach (n = 3), adoption (n = 5), implementation (n = 4), and maintenance (n = 5) of the intervention the Network is developing. These recommendations are likely to be useful for any MS rehabilitation researcher who is developing and testing interventions that he or she hopes will be widely disseminated.

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.

scholarly journals Clinical impact of left and right axis deviations with narrow QRS complex on 3-year outcomes in a hospital-based population in Japan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuta Seko ◽  
Takao Kato ◽  
Yuhei Yamaji ◽  
Yoshisumi Haruna ◽  
Eisaku Nakane ◽  
...  
Keyword(s):  
Cardiovascular Events ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Conduction Block ◽  
Primary Outcome Measure ◽  
Excess Risk ◽  
Major Adverse Cardiovascular Events ◽  
Prognostic Impact ◽  
Axis Deviation ◽  
The Right

AbstractWhile the prognostic impact of QRS axis deviation has been assessed, it has never been investigated in patients without conduction block. Thus, we evaluated the prognostic impact of QRS-axis deviation in patients without conduction block. We retrospectively analyzed 3353 patients who had undergone both scheduled transthoracic echocardiography and electrocardiography in 2013 in a hospital-based population, after excluding patients with a QRS duration of ≥ 110 ms, pacemaker placement, and an QRS-axis − 90° to − 180° (northwest axis). The study population was categorized into three groups depending on the mean frontal plane QRS axis as follows: patients with left axis deviation (N = 171), those with right axis deviation (N = 94), and those with normal axis (N = 3088). The primary outcome was a composite of all-cause death and major adverse cardiovascular events. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the left axis deviation group (26.4% in the left axis deviation, 22.7% in the right axis deviation, and 18.4% in the normal axis groups, log-rank P = 0.004). After adjusting for confounders, the excess risk of primary outcome measure remained significant in the left axis deviation group (hazard ratio [HR] 1.44; 95% confidence interval [CI] 1.07–1.95; P = 0.02), while the excess risk of primary outcome measure was not significant in the right axis deviation group (HR 1.22; 95% CI 0.76–1.96; P = 0.41). Left axis deviation was associated with a higher risk of a composite of all-cause death and major adverse cardiovascular events in hospital-based patients without conduction block in Japan.

scholarly journals Computerised cognitive–behavioural therapy for adults with intellectual disability: randomised controlled trial

2017 ◽  
Vol 211 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Patricia Cooney ◽  
Catherine Jackman ◽  
David Coyle ◽  
Gary O'Reilly
Keyword(s):  
Intellectual Disability ◽  
Randomised Controlled Trial ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Controlled Trial ◽  
Behavioural Therapy ◽  
Primary Outcome Measure ◽  
Cognitive Behavioural ◽  
Randomised Controlled

BackgroundDespite the evidence base for computer-assisted cognitive–behavioural therapy (CBT) in the general population, it has not yet been adapted for use with adults who have an intellectual disability.AimsTo evaluate the utility of a CBT computer game for adults who have an intellectual disability.MethodA 2 × 3 (group × time) randomised controlled trial design was used. Fifty-two adults with mild to moderate intellectual disability and anxiety or depression were randomly allocated to two groups: computerised CBT (cCBT) or psychiatric treatment as usual (TAU), and assessed at pre-treatment, post-treatment and 3-month follow-up. Forty-nine participants were included in the final analysis.ResultsA significant group x time interaction was observed on the primary outcome measure of anxiety (Glasgow Anxiety Scale for people with an Intellectual Disability), favouring cCBT over TAU, but not on the primary outcome measure of depression (Glasgow Depression Scale for people with a Learning Disability). A medium effect size for anxiety symptoms was observed at post-treatment and a large effect size was observed after follow-up. Reliability of Change Indices indicated that the intervention produced clinically significant change in the cCBT group in comparison with TAU.ConclusionsAs the first application of cCBT for adults with intellectual disability, this intervention appears to be a useful treatment option to reduce anxiety symptoms in this population.

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