Best Practices for the Electronic Implementation and Migration of Patient-Reported Outcome Measures.

While the use of electronic methods to collect patient-reported outcome data in clinical trials continues to increase, it remains the case that many patient-reported outcome measures (PROMs) have originally been developed and validated on paper. Careful consideration during the move from paper PROMs to electronic format is required to preserve the integrity of the measure and ensure a "faithful migration." Relevant literature has long called out the importance of following migration best practices during this process; nevertheless, such best practices are distributed across multiple documents. This article consolidates and builds upon existing electronic PROM implementation best practice recommendations to provide a comprehensive, up-to-date, single point of reference. It reflects the current consensus based on the significant advances in technology capabilities and knowledge gleaned from the growing evidence base on electronic migration and implementation, to balance the need for maintaining the integrity of the measure while optimizing respondent usability. It also specifies whether the practice is rooted in evidence or expert consensus, to enable those using these best practices to make informed and considered decisions when conducting migration.

Spanish and cross-cultural validation of the mind excessively wandering scale.

Introduction: Over the last decade, excessive spontaneous mind wandering (MW) has been consistently associated with emotional disorders. The main aims of the present study were (1) to re-examine the factor structure of the Mind Excessively Wandering Scale (MEWS); (2) to validate the Spanish version of the MEWS; and (3) to conduct a cross-cultural validation of the MEWS in Spanish and UK samples. Methods: A forward/backward translation to Spanish was conducted. Data of 391 Spanish and 713 British non-clinical individuals were analysed. Results: A revised 10-item version of the MEWS (MEWS-v2.0) demonstrated to be a valid instrument to assess MW. A 2-correlated factor structure properly captured the MEWS-v2.0 variance, accounting for two specific but interrelated dimensions (Uncontrolled thoughts and Mental Overactivity). Discussion: The Spanish MEWS-v2.0 showed adequate internal consistency and construct validity, as well as appropriate convergent/divergent validity. Cross-cultural analyses showed that MEWS-v2.0 captured the same construct in both UK and Spanish samples. In conclusion, both Spanish and English MEWS-v2.0 demonstrated to be reliable measures to capture spontaneous MW phenomenon in non-clinical adult populations.

Regulatory Acceptance of Patient-Reported Outcome (PRO) Data from Bring-Your-Own-Device (BYOD) Solutions to Support Medical Product Labeling Claims : Let's Share the Success Stories to Move the Industry Forward.

Bring-your-own-device (BYOD) methods for collecting patient-reported outcome (PRO) data in clinical trials can decrease patient burden and improve data quality. However, adoption of BYOD in clinical trials is limited by the absence of publicly available case studies where BYOD PRO data supported regulatory medical product approvals. Anecdotally, we are aware of multiple examples where efficacy and safety label claims were based on BYOD PRO data; however-except for one-these examples have not been made public. The absence of these case studies can lead sponsors to be hesitant to use BYOD for capturing primary and secondary PRO-based endpoints in their trials. This commentary outlines the context of the issue faced and concludes with a call for sponsor transparency with regard to BYOD use through publicizing where approved labeling claims were based on BYOD data. We suggest how this data could be systematically captured going forward. Sharing this information will benefit the clinical trials enterprise by increasing confidence in the utilization of BYOD and provide opportunities to enhance patient-centricity.

Optimizing electronic capture of patient-reported outcome measures in oncology clinical trials: lessons learned from a qualitative study.

Aim: To understand the impact of anticancer treatment on oncology patients' ability to use electronic solutions for completing patient-reported outcomes (ePRO). Materials & methods: Semi-structured interviews were conducted with seven individuals who had experienced a cancer diagnosis and treatment. Results: Participants reported that the following would impact the ability to interact with an ePRO solution: peripheral neuropathy of the hands (4/7), fatigue and/or concentration and memory issues (6/7), where they are in a treatment cycle (5/7). Approaches to improve usability included: larger, well-spaced buttons to deal with finger numbness, the ability to pause a survey and complete at a later point and presenting the recall period with every question to reduce reliance on memory. Conclusion: Symptoms associated with cancers and anticancer treatments can impact the use of technologies. The recommendations for optimizing the electronic implementation of patient-reported outcome instruments in this population provides the potential to improve data quality in oncology trials and places patient needs at the forefront to ensure 'fit-for-purpose' solutions.

Evaluating a scale of excessive mind wandering among males and females with and without attention-deficit/hyperactivity disorder from a population sample.

Recent studies highlight the role of excessive mind wandering in attention-deficit/hyperactivity disorder (ADHD) and its association with impairment. We believe assessing mind wandering could be especially relevant to individuals, including many females, who present with less externalising manifestations of ADHD. Using a new measure based on ADHD patient reports, the Mind Excessively Wandering Scale (MEWS), we previously found adults with ADHD had elevated levels of mind wandering that contributed to impairment independently of core ADHD symptoms. Using data from an online general population survey, the current study assessed the factor-structure, reliability, validity and measurement invariance of the MEWS. We also investigated sex differences in mind wandering, as well as ADHD symptoms, impairment and wellbeing in those with and without ADHD. The MEWS had a unidimensional structure, was invariant across sex, age and ADHD status, and accounted for unique variance in impairment and wellbeing beyond core ADHD symptoms. Among those with ADHD, we found no evidence for sex differences in mind wandering and among those without ADHD males had higher scores. We also found similar levels of hyperactivity/impulsivity, emotional lability, and impairment in males and females with ADHD, but males reported greater inattention and lower wellbeing. Results suggest the MEWS is a reliable and valid instrument measuring the same construct across sex, age and ADHD status, which could aid diagnosis and monitoring of outcomes.

Sex differences in predicting ADHD clinical diagnosis and pharmacological treatment.

In youth, ADHD is more commonly diagnosed in males than females, but higher male-to-female ratios are found in clinical versus population-based samples, suggesting a sex bias in the process of receiving a clinical diagnosis of ADHD. This study investigated sex differences in the severity and presentation of ADHD symptoms, conduct problems, and learning problems in males and females with and without clinically diagnosed ADHD. We then investigated whether the predictive associations of these symptom domains on being diagnosed and treated for ADHD differed in males and females. Parents of 19,804 twins (50.64% male) from the Swedish population completed dimensional assessments of ADHD symptoms and co-occurring traits (conduct and learning problems) when children were aged 9 years. Children from this population sample were linked to Patient Register data on clinical ADHD diagnosis and medication prescriptions. At the population level, males had higher scores for all symptom domains (inattention, hyperactivity/impulsivity, conduct, and learning problems) compared to females, but similar severity was seen in clinically diagnosed males and females. Symptom severity for all domains increased the likelihood of receiving an ADHD diagnosis in both males and females. Prediction analyses revealed significant sex-by-symptom interactions on diagnostic and treatment status for hyperactivity/impulsivity and conduct problems. In females, these behaviours were stronger predictors of clinical diagnosis (hyperactivity/impulsivity: OR 1.08, 95% CI 1.01, 1.15; conduct: OR 1.43, 95% CI 1.09, 1.87), and prescription of pharmacological treatment (hyperactivity/impulsivity: OR 1.24, 95% CI 1.02, 1.50; conduct: OR 2.20, 95% CI 1.05, 4.63). Females with ADHD may be more easily missed in the ADHD diagnostic process and less likely to be prescribed medication unless they have prominent externalising problems.

Validation of the Mind Excessively Wandering Scale and the Relationship of Mind Wandering to Impairment in Adult ADHD.

OBJECTIVE: This study investigates excessive mind wandering (MW) in adult ADHD using a new scale: the Mind Excessively Wandering Scale (MEWS). METHOD: Data from two studies of adult ADHD was used in assessing the psychometric properties of the MEWS. Case-control differences in MW, the association with ADHD symptoms, and the contribution to functional impairment were investigated. RESULTS: The MEWS functioned well as a brief measure of excessive MW in adult ADHD, showing good internal consistency (α > .9), and high sensitivity (.9) and specificity (.9) for the ADHD diagnosis, comparable with that of existing ADHD symptom rating scales. Elevated levels of MW were found in adults with ADHD, which contributed to impairment independently of core ADHD symptom dimensions. CONCLUSION: Findings suggest excessive MW is a common co-occurring feature of adult ADHD that has specific implications for the functional impairments experienced. The MEWS has potential utility as a screening tool in clinical practice to assist diagnostic assessment.

Catechol-O-methyltransferase val158met genotype determines effect of reboxetine on emotional memory in healthy male volunteers.

BACKGROUND: Catechol-O-methyltransferase (COMT) metabolizes catecholamines in the prefrontal cortex (PFC). A common polymorphism in the COMT gene (COMT val158met) has pleiotropic effects on cognitive and emotional processing. The met allele has been associated with enhanced cognitive processing but impaired emotional processing relative to the val allele. METHODS: We genotyped healthy, white men in relation to the COMT val158met polymorphism. They were given a single 4 mg dose of the selective noradrenaline reuptake inhibitor (NRI) reboxetine or placebo in a randomized, double-blind between-subjects model and then completed an emotional memory task 2 hours later. RESULTS: We included 75 men in the study; 41 received reboxetine and 34 received placebo. In the placebo group, met/met carriers did not demonstrate the usual memory advantage for emotional stimuli that was observed in val carriers. Reboxetine restored this emotional enhancement of memory in met/met carriers, but had no significant effect in val carriers. LIMITATIONS: We studied only men, thus limiting the generalizability of our findings. We also relied on self-reported responses to screening questions to establish healthy volunteer status, and in spite of the double-blind design, participants were significantly better than chance at identifying their intervention allocation. CONCLUSION: Emotional memory is impaired in healthy met homozygotes and selectively improved in this group by reboxetine. This has potential translational implications for the use of reboxetine, which is currently licensed as an antidepressant in several countries, and edivoxetine, a new selective NRI currently in development.

Alpha 2B adrenoceptor genotype moderates effect of reboxetine on negative emotional memory bias in healthy volunteers.

Evidence suggests that emotional memory plays a role in the pathophysiology of depression/anxiety disorders. Noradrenaline crucially modulates emotional memory. Genetic variants involved in noradrenergic signaling contribute to individual differences in emotional memory and vulnerability to psychopathology. A functional deletion polymorphism in the α-2B adrenoceptor gene (ADRA2B) has been linked to emotional memory and post-traumatic stress disorder. The noradrenaline reuptake inhibitor reboxetine attenuates enhanced memory for negative stimuli in healthy and depressed individuals. We examined whether the effect of reboxetine on emotional memory in healthy individuals would be moderated by ADRA2B genotype. ADRA2B deletion carriers demonstrated enhanced emotional memory for negative stimuli compared with deletion noncarriers, consistent with prior studies. Reboxetine attenuated enhanced memory for negative stimuli in deletion noncarriers but had no significant effect in deletion carriers. This is the first demonstration of genetic variation influencing antidepressant drug effects on emotional processing in healthy humans.