RIGOR Guidelines: Escalating STAIR and STEPS for Effective Translational Research

Abstract

Stroke continues to be a serious and significant health problem in the USA and worldwide. This article will emphasize the need for good laboratory practices, transparent scientific reporting, and the use of translational research models representative of the disease state to develop effective treatments. This will allow for the testing and development of new innovative strategies so that efficacious therapies can be developed to treat ischemic and hemorrhagic stroke. This article recommends guidelines for effective translational research, most importantly, the need for study blinding, study group randomization, power analysis, accurate statistical analysis, and a conflict of interest statement. Additional guidelines to ensure reproducibility of results and confirmation of efficacy in multiple species are discussed.

Translational Stroke Research Opportunities and a Strategy to Develop Effective Cytoprotection

“…This assumes that the level of current research is inadequate and researchers must improve research study design, data handling, and interpretation. This recommendation is consistent with previous recommendations and publications, including STAIR [20], RIGOR [21][22][23][24] and CAMARADES [25,26], guidelines that are now mainstays in the field. However, based upon manuscript submission to this Journal, there is still less than 30% compliance by research laboratories worldwide primarily because high quality fully transparent research can be costly and there is insufficient funding available (see [30]).…”

“…However, based upon manuscript submission to this Journal, there is still less than 30% compliance by research laboratories worldwide primarily because high quality fully transparent research can be costly and there is insufficient funding available (see [30]). For the benefit of the stroke research community worldwide, we must first reiterate the basic recommendations resulting from the 2012 NINDS transparency in research workshop, which were published in the Journal of Neurology and Neurophysiology, Stroke, Translational Stroke Research and Nature among other journals [21][22][23][24].…”

“…& Dr. Malcolm Macleod and colleague, Dr. Emily Sena from the University of Edinburgh, summarized the CAMARADES effort and emphasized that researchers need to define the method of randomization, conduct power analysis and conduct studies blinded [see RIGOR guidelines above [21][22][23][24]. & Committee members recommended that aged animals be used for stroke research, comorbid conditions need to be represented (see [31,32,33]), chronic stroke models (months of survival) should be developed because rodents display adaptive plasticity, and stroke studies should incorporate atrial fibrillation, hypoperfusion, transient ischemic attack (TIA), and white matter damage.…”

To Improve Translational Research in Subarachnoid Hemorrhage

“…Animal studies also offer a wider range of possibilities for example such as examining toxicity of a specific treatment or studying the underlying mechanisms of diseases. However, because most of new therapies shown to be effective in animal studies have been ineffective in clinical trials, some guidelines including the Stroke Therapy Academic Industry Roundtable (STAIR) were proposed to improve the quality and reproducibility of individual animal studies evaluating neuroprotective drugs in ischemic stroke [1][2][3]. Recent special issues BChallenges and Controversies in Translational Stroke Research, Part 1 and 2^in this journal provide an excellent overview as to the innate biological variability and the methodological challenges that are needed to address bias in preclinical research for the successful translation of experimental therapies to clinical stroke treatments.…”

“…The proposed standards include (1) clinical relevance of animal models (detailed information on animals used (species, strain, age, weight, gender, etc. ), selection of anesthetics, inclusion and exclusion criteria), (2) sample size calculation and accurate statistical analysis, (3) treatment (randomization, allocation concealment, dose-response determinations, therapeutic time window, blood-brain barrier permeability and tissue drug levels, physiological monitoring), (4) outcome (blinded assessment, at least two outcome measures (morphology and function), covering both acute (1-3 days) and longterm (7-30 days) endpoints), and (5) reporting of animals excluded from analysis, potential conflicts of interest, and study funding [1][2][3][4][5][6][7]. In addition, several challenges exist to successfully translate the outcomes from animal research to humans in a clinical setting.…”