Editorial - Clinical Investigation (2022) Volume 12, Issue 10

Clinical TBI studies have statistical problems.

Corresponding Author:
Yasmin Nizar
Editorial Office, Journal of Clinical Investigation, London
E-mail: hawraj5@hotmail.com

Received: 2 -Oct -2022, Manuscript No. fmci-22-81871; Editor assigned: 7- Oct-2022, PreQC No. fmci-22-81871 (PQ); Reviewed: 15- Oct-2022, QC No. fmci-22-81871 (Q); Revised: 20- Oct-2022, Manuscript No. fmci-22-81871 (R); Published: 28- Oct-2022; DOI: 10.37532/2041-6792.2022.12(10). 175-177


There are various difficulties in identifying and assessing traumatic brain injury over time. The search for quantitative physiological indicators that can be used to define traumatic brain damage is garnering more attention because these lesions can have subtle effects. The findings of this study need to be carefully reviewed. This paper presents six arguments for cautious assessment. The concerns mentioned here are all old ones. The technical literature that addresses the mathematical analysis of clinical data typically includes these as standard components. The goal of this publication is to bring these difficulties to light since doctors must take them into account when determining the value of this research. These issues are occasionally shown by simulation studies of diagnostic procedures. The explicit description of the mathematical techniques utilised to arrive at these results is taken into consideration as an extra objective. The appendices contain this information. The ensuing observations are made: A successful diagnostic technique is not always ensured by a statistically significant separation of a symptomatic population from a control population. Increasing the number of factors in a diagnostic discrimination may reduce classification accuracy in some cases. When the approach is used on a broader neuropsychiatric population, having good sensitivity and specificity in TBI versus control group categorization does not guarantee successful diagnostic outcomes. Assessments of treatment effectiveness must take into account the fact that a damaged central nervous system exhibits significant levels of variability and that either disease progression or spontaneous recovery can skew the results. Large pre-treatment versus posttreatment effect sizes alone do not prove a treatment was effective. It takes at least a two-step inquiry to distinguish between treatment responders and non-responders. This process needs a way to distinguish between those who respond to the treatment, people who respond to the placebo, and people who heal spontaneously. These techniques can be used to look for prodrome of neuropsychiatric diseases after traumatic brain injury.


Traumatic Brain Injury ∙ Doxorubicin


Here, we look at four processes that are connected with statistical problems that are seen in clinical trials. They are diagnosis, treatment evaluation, treatment efficacy assessment, and the detection of psychiatric illness prodrome. Though traumatic brain injury is the focus, the conclusions apply to other illnesses as well. In terms of mathematics, diagnosis is a process of classification. What is the likelihood that a particular patient, given a set of measurements taken from them, will belong to previously defined and characterised populations, including a set of suitably matched healthy controls? Currently, clinical populations are defined in accordance with traditional diagnostic frameworks, such as those for schizophrenia, PTSD, major depressive disorder, and similar conditions. A mental health diagnosis Although the diagnostic standards may alter, the statistical problems that must be resolved in their application do not [1,2].

In the restricted sense that it involves calculations of the probability that the patient is a member of a clinical group identified in the diagnosis, which should decrease over the course of treatment, and the calculation of the probability that the patient is a member of an appropriately matched healthy control group, which should increase longitudinally, longitudinal assessment and the evaluation of treatment effectiveness is a classification problem. These membership probabilities can be calculated to provide a general assessment, but they must be supplemented by evaluations of treatment adherence, consistency, inter-rater reliability, and adequately constructed control arms. A significant difference between the pre- and post-treatment effect sizes alone does not indicate a successful treatment [3]

There are significant disparities between the statistical execution of diagnosis and the statistical evaluation of therapy efficacy. In theory, the probability of becoming a member of the control group can be used to determine the effectiveness of the treatment. Without a diagnosis, this can be done. The greatest membership probability calculated across a wide number of clinical groups forms the basis of a statistically based diagnosis. If the measures are not group-specific, the diagnostic process may fail. Low test-retest reliability in the measures can lead to unsuccessful longitudinal assessment. It is important to not undervalue the operational challenges presented by this method of diagnosis and therapy evaluation.

We will use the classification of a control population and a population with traumatic brain injury as an example, but it should be noted that this is done without regard to the clinical group's defining characteristics and without going back to a discussion of the adequacy of treating traumatic brain injury as a diagnostic category. We acknowledge that none of the concepts offered here are novel, as stated in the abstract. Our goal is to state them, back them up with simulations of diagnostic procedures, and provide the key mathematical information in appendices in a clear and succinct manner [4].


The four main objectives of laboratory medicine are, in general, diagnosis; longitudinal monitoring of therapy response or illness progression; prodrome detection; and post-mortem cause of death identification. These goals are fundamentally all categorization issues. With a focus on traumatic brain injury, the first three goals have been taken into account in this contribution. As was already mentioned, severe brain damage poses especially difficult assessment issues. Six findings have been reached in this study

It was demonstrated that a clinical population's statistically substantial separation from a wellmatched healthy comparison group does not guarantee a reliable diagnostic technique. Although necessary, it is insufficient. Although this is well established in the scientific literature, the clinical community does not always acknowledge it.

Clinically, the post-TBI group is diverse. Various injury-related events can set off various pathophysiological processes. Thus, there will never be a single test for traumatic brain injury. A multidimensional analysis is necessary. However, caution must be exercised when adding further measures to a multivariate discriminant. Contrary to popular belief, sometimes adding variables to a classifier can make it perform worse. We gave an example of an EEG classifier where, as measures were removed from the discriminating, the error rate dropped from 65% (really worse than chance) to 27%.

It's important to take into account reports of diagnostic sensitivity and specificity carefully. The increasing evidence suggests that assessment techniques, such as neuropsychological tests and psychological measures like heart rate variability and event-related potentials, are non-specific yet may be sensitive to CNS dysfunction. In a carefully designed clinical trial, a collection of measures might be able to discriminate between healthy controls and TBI patients, but these measures might not be able to distinguish between traumatic brain injury, bipolar disorder, or major depressive disorder on their own. This lack of specificity is more than just an intellectual issue because the clinical reaction will be substantially different. However, this is not adefence of neuropsychological and psychophysiological evaluations in neuropsychiatry. A useful example is body temperature measurement. Despite being a non-specific clinical parameter, body temperature is an essential component of any clinical assessment. We propose that despite their non-specificity, measures of CNS coherence, synchronisation, causal pathways, and network geometry will become more crucial in neuropsychiatric treatment.

The significant level of intra-individual longitudinal variability of biological parameters acquired in neuropsychiatric populations must be taken into consideration while conducting a study on treatment effectiveness. We have claimed that this is especially true for TBI patients. Studies on test-retest reliability that are systematic are crucial. Additionally, the significance of waitlist control groups is established by the high rate of spontaneous recovery from neuropsychiatric illnesses, including TBI. Although a waiting control group is methodologically useful, it is also acknowledged that using one might bring up significant ethical issues. The queue might not be advantageous. There may be severe deterioration depending on the clinical presentation and length of the delay. Devilly and McFarlane advised comparing results with waitlist control data that is already available, but this option is only available for studies that share similar inclusion and exclusion criteria and outcome measures. Ideal statistical design must be given less weight than ethical clinical behaviour, as is the case in every research involving human subjects.

The diversity of these clinical populations also raises the possibility of responder and non-responder subsets in the intake populations for any given medication. If the responder subgroup is small, statistical averaging may obscure a treatment that might be quite successful for that subgroup. However, we cannot adjudge success after the fact by searching among the results for the one we desire. A placebo effect or spontaneous recovery could be to blame for a positive reaction. A two-phase study is necessary, with the first part identifying the respondents' characteristics. The inclusion/exclusion criteria for the second research, which should have a high positive response rate, are then based on these features. There should be a placebo treatment arm in this second study.

The ability to identify incomplete recovery is a benefit of statistically analysing treatment response. P(x Patient|GHealthy) can be used to calculate an individual's responsiveness to therapy even in the absence of a diagnosis. If a diagnosis has been made, the likelihood of being a member of the patient's diagnosis group should decline, albeit it usually remains non-zero. Because symptoms can be present in the definition of more than one diagnostic group, assessments given in reference to a single diagnostic group should be understood carefully. For instance, symptoms of postconcussion syndrome are also prevalent in PTSD, depression, and, most importantly, in populations of healthy controls. In certain studies, endorsement rates in healthy controls were either comparable to or higher than endorsement frequencies in groups with a history of mild TBI, according to a review of the prevalence of post-concussion symptoms in populations without a history of TBI. There is yet another issue to be addressed. Neuropsychiatric illnesses do not have a single causal component. Three subscales were identified in the Potter et al. research on post-concussion symptoms. Similar to how the Pittsburgh Sleep Quality Index has seven subscales, the Beck Depression Index has three. Statistics show that partial recovery can be the consequence of very good responses on some subscales and negative responses on others. These clinically significant findings won't be captured by a naive statistical study that doesn't take this possibility into account

The quest for prodromes of neuropsychiatric illnesses is currently receiving a lot of interest. We've demonstrated that this can be developed as a classification issue using the findings of a longitudinal investigation.

It has been proposed that the use of imaging studies, genomic research, plasma biomarker data, neuropsychological assessments, and psychophysiological measurements might be integrated to create patient-specific, quantitatively informed treatments. It has been demonstrated how useful these measurements are for making betweengroup distinctions, such as for assessing treatment effect size. We are more circumspect in how useful we believe these metrics are for directing individual treatment. Unrestrained optimism regarding these measures' utility at the individual rather than group level is argued against by the heterogeneity of the populations, limited specificity, and low test-retest reliability of these measurements. When crucial and frequently disregarded statistical precautions are implemented, it is discovered that previously reported favourable results are unfounded. Although improvements in the longitudinal quantitative assessment of specific patients are possible, statistical care must be taken.