Prediction and Outcome Analyses in Acute Neurological Diseases

Most treatments and interventions in health care are aimed at optimizing clinical outcomes. Ischemic stroke, aneurysmal subarachnoid hemorrhage (aSAH) and traumatic brain injury (TBI) are acute neurological diseases with a heterogeneous disease course that are often associated with poor functional outcomes and reduced quality of life. This stimulates measurement of clinical outcomes in terms of prognosis, variation across settings and new assessment methods. The overall aim of this thesis is to identify patients at high risk for poor outcome after acute neurological diseases (Part II) and to enhance knowledge on outcome variation and statistical efficiency of new outcome measures (Part III). Specific research questions are: 1. What characteristics are associated with poor outcome after acute neurological diseases? 2. What is the methodological quality of existing prognostic models in acute neurological diseases? 3. Do these models provide reliable predictions for patients in specific clinical settings? 4. What are the differences in clinical outcomes between patients with aSAH in a range of international hospitals, and can these differences be explained by variation in case-mix? 5. What is the statistical efficiency of new outcome measures for acute neurological diseases

Validation of prognostic models: challenges and opportunities

Multivariable prognostic models combine several characteristics to provide predictions for individual patients. Prognostic models can be applied in research and clinical practice, for instance to assist clinicians with decisions regarding treatment choices or informing patients and family members on prognosis (1). Before application in clinical practice, prognostic models should be validated to judge their generalizability. Although guidelines have been proposed to improve development and reporting of prognostic models, a majority of the published models is not thoroughly validated (1,2). In this viewpoint, we focus on design and analysis of validation

National Institutes of Health Stroke Scale: An Alternative Primary Outcome Measure for Trials of Acute Treatment for Ischemic Stroke

Background and Purpose- The modified Rankin Scale (mRS) at 3 months is the most commonly used primary outcome measure in stroke treatment trials, but it lacks specificity and requires long-term follow-up interviews, which consume time and resources. An alternative may be the National Institutes of Health Stroke Scale (NIHSS), early after stroke. Our aim was to evaluate whether the NIHSS assessed within 1 week after treatment could serve as a primary outcome measure for trials of acute treatment for ischemic stroke. Methods- We used data from 2 randomized controlled trials of endovascular treatment for ischemic stroke: the positive MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; N=500) and the neutral IMS (Interventional Management of Stroke) III trial (N=656). We used a causal mediation model, with linear and ordinal logistic regression adjusted for confounders, to evaluate the NIHSS 24 hours and 5 to 7 days after endovascular treatment as primary outcome measures (instead of the mRS at 3 months) in both trials. Patients who had died before the NIHSS was assessed received the maximum score of 42. NIHSS+1 was then log10-transformed. Results- In both trials, there was a significant correlation between the NIHSS at 24 hours and 5 to 7 days and the mRS. In MR CLEAN, we found a significant effect of endovascular treatment on the mRS and on the NIHSS at 24 hours and 5 to 7 days. After adjustment for NIHSS at 24 hours and 5 to 7 days, the effect of endovascular treatment on the mRS decreased from common odds ratio 1.68 (95% CI, 1.22-2.32) to respectively 1.36 (95% CI, 0.97-1.91) and 1.24 (95% CI, 0.87-1.79), indicating that treatment effect on the mRS is in large part mediated by the NIHSS. In the IMS III trial there was no treatment effect on the NIHSS at 24 hours and 5 to 7 days, corresponding with the absence of a treatment effect on the mRS. Conclusions- The NIHSS within 1 week satisfies the requirements for a surrogate end point and may be used as a primary outcome measure in trials of acute treatment for ischemic stroke, particularly in phase II(b) trials. This could reduce stroke-outcome assessment to its essentials (ie, neurological deficit), and reduce trial duration and costs. Whether and under which conditions it could be used in phase III trials requires a debate in the field with all parties. Clinical Trial Registration- URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758; https://www.clinicaltrials.gov. Unique identifier: NCT00359424

Letter by Dijkland et al Regarding Article, "Development and Validation of a Predictive Model for Functional Outcome After Stroke Rehabilitation: The Maugeri Model"

_To the Editor:_ With great interest, we read the study by Scrutinio et al, which describes the development and validation of the Maugeri model that predicts functional outcome after inpatient stroke rehabilitation based on easily obtainable clinical characteristics. We agree with the authors that prediction of functional outcome after stroke rehabilitation is important to inform patients and relatives on prognosis and to identify rehabilitation goals. The authors performed external validation of the model, which is crucial to evaluate generalizability. However, we noted opportunities for methodological improvement in the development and validation of the Maugeri

Between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage in the subarachnoid hemorrhage international trialists (SAHIT) repository

OBJECTIVE Differences in clinical outcomes between centers and countries may reflect variation in patient characteristics, diagnostic and therapeutic policies, or quality of care. The purpose of this study was to investigate the presence and magnitude of between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS The authors analyzed data from 5972 aSAH patients enrolled in randomized clinical trials of 3 different treatments from the Subarachnoid Hemorrhage International Trialists (SAHIT) repository, including data from 179 centers and 20 countries. They used random effects logistic regression adjusted for patient characteristics and timing of aneurysm treatment to estimate between-center and between-country differences in unfavorable outcome, defined as a Glasgow Outcome Scale score of 1-3 (severe disability, vegetative state, or death) or modified Rankin Scale score of 4-6 (moderately severe disability, severe disability, or death) at 3 months. Between-center and between-country difference