An item response theory based integrated model of headache, nausea, photophobia, and phonophobia in migraine patients

Abstract

This study developed an integrated model of severity scores of migraine headache and the incidence of nausea, photophobia, and phonophobia to predict the natural time course of migraine symptoms, which are likely to occur by a common disease progression mechanism. Data were acquired from two phase 3 clinical trials conducted during the development of eletriptan. Only the placebo arm was used for analysis. A conventional proportional odds model was compared with an item response theory (IRT) based approach. Results suggested that the IRT based approach led to a better model fit, successfully revealing the difference in relief rates among different symptoms, which was the fastest in phonophobia and the slowest in headache. Simulation with the developed model suggested that using headache scores at 4 h post-dose attained greatest statistical power, yielding sample size of 100 per arm given drug effect of 40%, as compared to that of 200 per arm when 2 h post-dose scores were used as in the original eletriptan protocol. This work demonstrated the usefulness of an IRT based model as applied to analyzing multidimensional migraine symptoms and designing clinical trials. Our model can be similarly applied to analyzing other multiple endpoints sharing a common underlying mechanism.

Integrated Item Response Theory Modeling of Multiple Patient-Reported Outcomes Assessing Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia

“…This overall perspective is lost in a multidimensional IRT setting, since here inference regarding information content can only be made within each scale separately. This may explain why other pharmacometric IRT studies have applied a unidimensional modeling approach to analyze responses from multiple scales ( 18 – 20 ). In the current unidimensional model, the QoL item was found to be the overall most informative, contributing to 17% of the total information content, highlighting the importance of this question for assessing BPH-LUTS.…”

“…Because IRT uses item-level data and quantifies item sensitivity, an integrated IRT model regarding information from the IPSS, QoL, and BII jointly may allow for a powerful approach for assessing BPH-LUTS and detecting drug effects. IRT analyses combining information from different scales have been performed within the therapeutic areas of neonatal pain (18,19) and migraine (20), but, to date, not within BPH-LUTS.…”

Predicting the longitudinal changes of levodopa dose requirements in Parkinson’s disease using item response theory assessment of real‐world Unified Parkinson's Disease Rating Scale

“…Pharmaceutical and medical researchers are increasingly adopting IRT to analyze composite scores used for medical diagnosis, such as the Alzheimer's Disease Assessment Scale-Cognitive subscale 3 and others. [4][5][6][7] It has been successfully applied to modeling UPDRS progression in patients with PD as well. [8][9][10] When used in these contexts, latent ability or trait is often interpreted as latent disease severity.…”

Application of Item Response Theory to Model Disease Progression and Agomelatine Effect in Patients with Major Depressive Disorder

“…It is an important tool in psychometrics and is more and more used in healthcare field. Combined with NLMEM, this methodology was first used in the context of Alzheimer disease [21,24,25,26] and also in other diseases such as multiple sclerosis [27], cognition [28], in mechanically ventilated preterm neonates [29], Parkinson [30], schizophrenia [31], acute ischemic stroke [32] and migraine patients [33]. IRT is a statistical framework aimed at characterising the relation between each component of a scale and an individual ability/disability.…”