Standardized Nomenclature for Modified Rankin Scale Global Disability Outcomes: Consensus Recommendations From Stroke Therapy Academic Industry Roundtable XI

Stroke ◽  
2021 ◽  
Author(s):  
Jeffrey L. Saver ◽  
Napasri Chaisinanunkul ◽  
Bruce C.V. Campbell ◽  
James C. Grotta ◽  
Michael D. Hill ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Statistical Analysis ◽  
Health State ◽  
Modified Rankin Scale ◽  
Stroke Therapy ◽  
Subsequent Work ◽  
Consensus Recommendations ◽  
Weighted Analysis ◽  
Scale Scores

The modified Rankin Scale (mRS), a 7-level, clinician-reported, measure of global disability, is the most widely employed outcome scale in acute stroke trials. The scale’s original development preceded the advent of modern clinimetrics, but substantial subsequent work has been performed to enable the mRS to meet robust contemporary scale standards. Prior research and consensus recommendations have focused on modernizing 2 aspects of the mRS: operationalized assignment of scale scores and statistical analysis of scale distributions. Another important characteristic of the mRS still requiring elaboration and specification to contemporary clinimetric standards is the Naming of scale outcomes. Recent clinical trials have used a bewildering variety, often mutually contradictory, of rubrics to describe scale states. Understanding of the meaning of mRS outcomes by clinicians, patients, and other clinical trial stakeholders would be greatly enhanced by use of a harmonized, uniform set of labels for the distinctive mRS outcomes that would be used consistently across trials. This statement advances such recommended rubrics, developed by the Stroke Therapy Academic Industry Roundtable collaboration using an iterative, mixed-methods process. Specific guidance is provided for health state terms (eg, Symptomatic but Nondisabled for mRS score 1; requires constant care for mRS score 5) and valence terms (eg, excellent for mRS score 1; very poor for mRS score 5) to employ for 23 distinct numeric mRS outcomes, including: all individual 7 mRS levels; all 12 positive and negative dichotomized mRS ranges, positive and negative sliding dichotomies; and utility-weighted analysis of the mRS.

Statistical analysis plan for evaluating different intensities of blood pressure control in the ENhanced Control of Hypertension And Thrombolysis strokE stuDy

2018 ◽  
Vol 14 (5) ◽  
pp. 555-558 ◽  
Author(s):  
Craig S Anderson ◽  
Mark Woodward ◽  
Hisatomi Arima ◽  
Xiaoying Chen ◽  
Richard I Lindley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Body Weight ◽  
Statistical Analysis ◽  
Lower Risk ◽  
Standard Dose ◽  
Statistical Analysis Plan ◽  
Symptomatic Intracerebral Hemorrhage ◽  
Stroke Study

Background The ENhanced Control of Hypertension And Thrombolysis strokE study (ENCHANTED) trial was initiated as a 2 × 2 partial-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial to evaluate in thrombolysis-eligible acute ischemic stroke (AIS) patients whether: (1) Arm A – low-dose (0.6 mg/kg body weight) intravenous (iv) alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage (sICH) compared with standard-dose (0.9 mg/kg body weight) iv alteplase; and (2) Arm B – early intensive blood pressure (BP) lowering (systolic target 130–140 mmHg) has superior efficacy and lower risk of ICH compared with guideline-recommended BP control (systolic target <180 mmHg). Arm A was completed in 2016; Arm B is now concluding. Objective To outline in detail and make public the predetermined statistical analysis plan (SAP) for the ‘BP control’ arm of this study. Methods All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be outlined, and for each item, statistically relevant descriptive elements will be described. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described. Results A SAP was developed for the results of the BP control arm of this study that is transparent, available to the public, verifiable, and predetermined before completion of data collection. Conclusions We have developed a predetermined SAP for the ENCHANTED BP control arm to be followed to avoid analysis bias arising from prior knowledge of the study findings. Clinical trial registration ClinicalTrials.gov (NCT01422616); ISRCTN Register (ISRCTN82387104); Australian New Zealand Clinical Trial Registry (ACTRN12611000236998); EU Clinical Trials Register (2011-005545-12); and Clinical Trials Registry – India (REF/2017/05/014334).

Abstract WP257: Accuracy of Pre-enrollment Last Known Well Time in a Large Prehospital Stroke Clinical Trial

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Nerses Sanossian ◽  
Emma Balouzian ◽  
Lucas Ramirez ◽  
David S Liebeskind ◽  
Sidney Starkman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Routine Practice ◽  
Stroke Therapy ◽  
Screening Criteria ◽  
Intervention Evaluation ◽  
Treatment Start ◽  
Tiered System ◽  
Telephone Screening ◽  
Entry Window

Background: Clinical trials of stroke therapies require accurate documentation of last known well time (LKWT) to account for injury accumulation prior to treatment start. For prehospital studies, this requirement is particularly challenging, as paramedic-determined and final-determined LKWTs in routine practice are concordant (within 15 mins) in only half of cases. We sought to determine the accuracy of LKWT obtained in the field by a two-tier enrollment system of study-trained paramedics and cellphone-connected physician-investigators. Methods: Paramedics screened consecutive transports for participation in the NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) clinical trial. Paramedic screening criteria included LKWT <2 hours. Physician-investigators by cellphone confirmed or refined the LKWT after conversation with paramedics and patients or legally authorized representative. Prehospital LKWT was compared with post-arrival LKWT determined by trained study nurses after ED arrival by speaking with patients, family and other sources. We describe the number of enrollment calls with inaccurate LKWT at the paramedic-screening level and at the post paramedic plus physician-investigator telephone screening level. Results: A total of 4458 post-screening enrollment calls were made by paramedics from January 2005 to December 2012 of which 539 (12%) were determined by physician-instigators to have inaccurate LKWT leading to non-enrollment. Of the remaining 3919 calls, 1700 led to enrollments in the study and 2219 were not enrolled for a reason other than inaccurate LKWT. Among enrolled cases, exact congruence between prehospital and post-arrival LKWTs occurred 72% (n=1220), concordance within 15 minutes in 87%, within 30 minutes in 93%, and within 1 hour in 97%. Among enrolled cases, final-determined LKWT was within the study entry window of 2h in 96.3%. Conclusions: A 2-tiered system of paramedic screening followed by physician-investigator cellphone assessment led to high congruence between prehospital-determined and post-arrival-determined of LKWT. This system can be used in future trials of prehospital, paramedic-in initiated stroke therapy when accuracy of LKWT is important for intervention evaluation.

scholarly journals Rate of patient’s Recruitment and Recruitment Derivatives from the Perspectives of Internal factors - Protocol Study Nosology, Experience of Investigators and Potential Patient’s Pool of Sites

2021 ◽  
Vol 2 (2) ◽  
pp. 1-6
Author(s):  
Svyatoslav Milovanov
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Statistical Analysis ◽  
Retrospective Analysis ◽  
Analysis Data ◽  
Recruitment Rate ◽  
Internal Factor ◽  
Internal Factors ◽  
Study Recruitment ◽  
Protocol Study

The recruitment as a process found by many authors to be undergoing of many factors. There is a factors which are decreasing the recruitment and last data is reporting up to 80% trials failed due to law or even absence of recruitment on level of sites. But the factors are differently changing the recruitment. The final number of recruitment is static figure very well known, there is also known speed of recruitment which is calculating in the start of the study and these parameters along with others is quantitative evaluation of recruitment. We investigated the rate of recruitment in the light of some factors using parameters reflecting the recruitment progress of recruitment. Materials and Methods: Retrospective analysis of data of four clinical trials II-III phases in oncology and hematology, conducted since 2007 to 2017 years. Study objectives: to investigate the study recruitment rate using different parameters and its changes along with acting of internal factors; to develop new parameters which could be sensitive for evaluation of factor’s action. Statistical analysis: data had been collected from feasibility questionnaires, open statistical sources. Results: It was determined rate of recruitment and its derivatives where was acting an internal factor. Discussion: Recruitment been undergone the internal factors. The way of action is multidirectional and could boost the recruitment and in opposite to decrease one and knowing it is important in success of recruitment and clinical trial itself eventually

Study protocol and statistical analysis plan for the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial

2020 ◽  
Vol 22 (2) ◽  
pp. 133-141
Author(s):  
Alexis P Poole ◽  
◽  
Mark E Finnis ◽  
James Anstey ◽  
Rinaldo Bellomo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Intensive Care ◽  
Blood Glucose ◽  
Statistical Analysis ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Statistical Analysis Plan

BACKGROUND: Contemporary glucose management of intensive care unit (ICU) patients with type 2 diabetes is based on trial data derived predominantly from patients without type 2 diabetes. This is despite the recognition that patients with type 2 diabetes may be relatively more tolerant of hyperglycaemia and more susceptible to hypoglycaemia. It is uncertain whether glucose targets should be more liberal in patients with type 2 diabetes. OBJECTIVE: To detail the protocol, analysis and reporting plans for a randomised clinical trial — the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial — which will evaluate the risks and benefits of targeting a higher blood glucose range in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A multicentre, parallel group, open label phase 2B randomised controlled clinical trial of 450 critically ill patients with type 2 diabetes. Patients will be randomised 1:1 to liberal blood glucose (target 10.0–14.0 mmol/L) or usual care (target 6.0–10.0 mmol/L). MAIN OUTCOME MEASURES: The primary endpoint is incident hypoglycaemia (< 4.0 mmol/L) during the study intervention. Secondary endpoints include biochemical and feasibility outcomes. RESULTS AND CONCLUSION: The study protocol and statistical analysis plan described will delineate conduct and analysis of the trial, such that analytical and reporting bias are minimised. TRIAL REGISTRATION: This trial has been registered on the Australian New Zealand Clinical Trials Registry (ACTRN No. 12616001135404) and has been endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.

scholarly journals Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4691-4695 ◽  
Author(s):  
S. Vincent Rajkumar ◽  
Jean-Luc Harousseau ◽  
Brian Durie ◽  
Kenneth C. Anderson ◽  
Meletios Dimopoulos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Response Criteria ◽  
Current Response ◽  
Consensus Panel ◽  
Consensus Recommendations ◽  
Clinical Trial Results

Abstract It is essential that there be consistency in the conduct, analysis, and reporting of clinical trial results in myeloma. The goal of the International Myeloma Workshop Consensus Panel 1 was to develop a set of guidelines for the uniform reporting of clinical trial results in myeloma. This paper provides a summary of the current response criteria in myeloma, detailed definitions for patient populations, lines of therapy, and specific endpoints. We propose that future clinical trials in myeloma follow the guidelines for reporting results proposed in this manuscript.

scholarly journals Calculation of Recruitment Which Were Proposed by Clinical Sites on Stage of Feasibility to Clinical Trial of II – III Phases

2021 ◽  
Vol 2 (1) ◽  
pp. 1-07
Author(s):  
Svyatoslav Milovanov
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Statistical Analysis ◽  
Retrospective Analysis ◽  
Analysis Data ◽  
Integral Approach

Many of clinical trials failed due to absence of needed per protocol recruitment of patients. Recruitment of patients in centralized trials is announcing by PI of clinical sites during the feasibility stage. This is subjective decision of investigator based on integral approach like experience, incidence of disease and many other parameters. The objective approach like calculation is apparently needed for calculation of proposed recruitment on the stage of feasibility. Materials and methods: retrospective analysis data of four clinical trials II-III phases, conducted since 2007 to 2017 years. Aim: to find out the approach for calculation of proposed by sites the recruitment on particular study on the stage of feasibility. Statistical analysis: data had been collected from feasibility questionnaires, open statistical sources. Results: It was proposed the formula for calculation of proposed recruitment of patients on the stage of feasibility. Discussion: Recruitment of patients might be calculated which will decrease the number of failed clinical trials. We called the calculation “Calculated proposed recruitment of patients” - CPRP».

scholarly journals DEBATE-statistical analysis plans for observational studies

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Bart Hiemstra ◽  
Frederik Keus ◽  
Jørn Wetterslev ◽  
Christian Gluud ◽  
Iwan C. C. van der Horst
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Statistical Analysis ◽  
Observational Study ◽  
Observational Studies ◽  
Data Driven ◽  
Study Power ◽  
Definition Of ◽  
Main Message ◽  
New Item

Abstract Background All clinical research benefits from transparency and validity. Transparency and validity of studies may increase by prospective registration of protocols and by publication of statistical analysis plans (SAPs) before data have been accessed to discern data-driven analyses from pre-planned analyses. Main message Like clinical trials, recommendations for SAPs for observational studies increase the transparency and validity of findings. We appraised the applicability of recently developed guidelines for the content of SAPs for clinical trials to SAPs for observational studies. Of the 32 items recommended for a SAP for a clinical trial, 30 items (94%) were identically applicable to a SAP for our observational study. Power estimations and adjustments for multiplicity are equally important in observational studies and clinical trials as both types of studies usually address multiple hypotheses. Only two clinical trial items (6%) regarding issues of randomisation and definition of adherence to the intervention did not seem applicable to observational studies. We suggest to include one new item specifically applicable to observational studies to be addressed in a SAP, describing how adjustment for possible confounders will be handled in the analyses. Conclusion With only few amendments, the guidelines for SAP of a clinical trial can be applied to a SAP for an observational study. We suggest SAPs should be equally required for observational studies and clinical trials to increase their transparency and validity.

Statistical Analysis of a Clinical Trial in Orthostatic Hypotension -a Nonparametric Approach

1987 ◽  
Vol 26 (01) ◽  
pp. 47-52
Author(s):  
R. Haux ◽  
H. Immich ◽  
M. Schumacher
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Statistical Analysis ◽  
Mathematical Models ◽  
Orthostatic Hypotension ◽  
Nonparametric Tests ◽  
Trial Methodology ◽  
Clinical Trial Methodology ◽  
Nonparametric Approach ◽  
Serial Measurements

SummarySome basic problems and considerations of analyzing clinical trials, in which a large amount of data is recorded on very few patients - mostly in the form of serial measurements -, are highlighted within the framework of a clinical trial in orthostatic hypotension. The method suggested to analyze these kinds of trials renounces the use of complex mathematical models and complicated statistical methods. It is simply based on the derivation of relevant aspects of the patient’s profiles and the use of well-known nonparametric tests and requires only a very simple study design. With this procedure, however, it is possible to satisfy at least the basic requirements of clinical trial methodology.

Availability of study protocols for randomized trials published in high-impact medical journals: A cross-sectional analysis

2019 ◽  
Vol 17 (1) ◽  
pp. 99-105 ◽  
Author(s):  
O’Mareen Spence ◽  
Kyungwan Hong ◽  
Richie Onwuchekwa Uba ◽  
Peter Doshi
Keyword(s):  
Internal Medicine ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Statistical Analysis ◽  
Random Sample ◽  
Randomized Clinical Trials ◽  
A Priori ◽  
Research Integrity ◽  
Clinical Trial Registry ◽  
Study Protocols

Background: To improve reporting transparency and research integrity, some journals have begun publishing study protocols and statistical analysis plans alongside trial publications. We sought to assess the overall availability and characteristics of protocols and statistical analysis plans of randomized clinical trials published in the top five (by impact factor) general medicine journals. Methods: All randomized clinical trials published in Annals of Internal Medicine, BMJ, JAMA, Lancet, and NEJM in 2016 were identified. For each randomized clinical trial, we searched for protocols and statistical analysis plans on journal websites (including supplementary material) and in the article, for example, a referenced publication or link to trial or institutional website. Characteristics of randomized clinical trials were extracted from the publication and clinical trial registry. A detailed assessment of protocols and statistical analysis plans was conducted in a 20% random sample of randomized clinical trials. Results: Protocols were available for 299 (82%) trials, ranging from 50% in BMJ to >95% in NEJM and JAMA. Statistical analysis plans were available for 182 (50%) trials and varied from <10% for Annals of Internal Medicine, BMJ, and Lancet to 92% for NEJM. Of the 76 randomized clinical trials in the 20% random sample, 63 (83%) had a protocol but less than half (31; 44%) included an a priori (dated prior to patient enrollment) version of the protocol. Statistical analysis plans were available for 35 (46%) trials, and only 5 (7%) included an a priori version. Conclusion: Protocols and statistical analysis plans are publicly available for the majority of trials. However, the a priori versions of these documents are only available for a minority of trials. More attention must be paid to ensuring the public availability of a priori versions.

Planning the Size of Clinical Trials with Allowance for Patient Noncompliance

1990 ◽  
Vol 29 (03) ◽  
pp. 243-246 ◽  
Author(s):  
M. A. A. Moussa
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Sample Size ◽  
Event Rate ◽  
Survival Functions ◽  
Time Intervals ◽  
Patient Noncompliance ◽  
Event Rates ◽  
Larger Sample

AbstractVarious approaches are considered for adjustment of clinical trial size for patient noncompliance. Such approaches either model the effect of noncompliance through comparison of two survival distributions or two simple proportions. Models that allow for variation of noncompliance and event rates between time intervals are also considered. The approach that models the noncompliance adjustment on the basis of survival functions is conservative and hence requires larger sample size. The model to be selected for noncompliance adjustment depends upon available estimates of noncompliance and event rate patterns.

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