Recommendations for the Electronic Migration and Implementation of Clinician-Reported Outcome Assessments in Clinical Trials.

OBJECTIVES: Although best practices from electronic patient-reported outcome (PRO) measures are transferable, the migration of clinician-reported outcome (ClinRO) assessments to electronic modes requires recommendations that address their unique properties, such as the user (eg, clinician), and complexity associated with programming of clinical content. Faithful migration remains essential to ensuring that the content and psychometric properties of the original scale (ie, validated reference) are preserved, such that clinicians completing the ClinRO assessments interpret and respond to the items the same way regardless of data collection mode. The authors present a framework for how to "faithfully" migrate electronic ClinRO assessments for successful deployment in clinical trials. METHODS: Critical Path Institute's Electronic PRO Consortium and PRO Consortium convened a consensus panel of representatives from member firms to develop recommendations for electronic migration and implementation of ClinRO assessments in clinical trials based on industry standards, regulatory guidelines where available, and relevant literature. The recommendations were reviewed and approved by all member firms from both consortia. CONSENSUS RECOMMENDATIONS: Standard, minimal electronic modifications for ClinRO assessments are described. This article also outlines implementation steps, including planning, startup, electronic clinical outcome assessment system development, training, and deployment. The consensus panel proposes that functional clinical testing by a clinician or clinical outcome assessment expert, as well as copyright holder review of screenshots (if possible) are sufficient to support minimal modifications during migration. Additional evidence generation is proposed for modifications that deviate significantly from the validated reference.

Validity and Reliability of the Student Refractive Error and Eyeglasses Questionnaire-Revised Version in Myopic Children.

SIGNIFICANCE: Multiple vision-related quality of life (VRQol) instruments exist, but questionnaires designed specifically for myopic children that are appropriate for assessing the impact of refractive error are rare. PURPOSE: This study aimed to assess the validity and reliability of the Student Refractive Error and Eyeglasses Questionnaire - Revised (SREEQ-R) in school-aged children with myopia in the United Kingdom. METHODS: Community optometrists in the United Kingdom invited children up to the age of 18 years presenting for an eye examination with current or previous reported use of eyeglasses for myopia to complete the SREEQ-R, which consists of 20 specific items divided into two sections each with three response categories. The "without glasses" section relates to perceptions of uncorrected vision/not wearing glasses, and the "with glasses" relates to corrected vision/wearing glasses. Rasch analysis was used to explore the psychometric performance (content, construct validity, and reliability) of the questionnaire items and scale using Winsteps software (Winsteps.com. Portland, OR). RESULTS: A total of 125 eligible children with a mean ± standard deviation age of 12.7 ± 2.9 years completed the SREEQ-R. All items fit the Rasch model and were retained, and the scale was found to be unidimensional. All children and item infit and outfit mean square statistics fell within the recommended fit criteria. As per the Rasch analysis, the person reliability coefficients were 0.84 and 0.91, whereas item reliabilities were 0.99 and 0.80 for the without glasses and with glasses sections, respectively. The internal consistency for the SREEQ-R was good; Cronbach α values were 0.84 for without glasses and 0.91 for with glasses. CONCLUSIONS: The SREEQ-R had satisfactory validity and reliability evidence. Construct validity of the scale was supported to measure the impact of uncorrected and corrected refractive error on vision-related quality of life in myopic school-aged children in the United Kingdom. The SREEQ-R could be used in future studies to evaluate vision-related quality of life in children with myopia.

A Randomized Noninferiority Trial of Wearing Adjustable Glasses versus Standard and Ready-made Spectacles among Chinese Schoolchildren: Wearability and Evaluation of Adjustable Refraction III.

PURPOSE: To compare wear of standard, adjustable, and ready-made glasses among children. DESIGN: Randomized, controlled, open-label, noninferiority trial. PARTICIPANTS: Students aged 11 to 16 years with presenting visual acuity (VA) ≤6/12 in both eyes, correctable to ≥6/7.5, subjective spherical equivalent refractive error (SER) ≤-1.0 diopters (D), astigmatism and anisometropia both <2.00 D, and no other ocular abnormalities. METHODS: Participants were randomly allocated (1:1:1) to standard glasses, ready-made glasses, or adjustable glasses based on self-refraction. We recorded glasses wear on twice-weekly covert evaluation by head teachers (primary outcome), self-reported and investigator-observed wear, best-corrected visual acuity (BCVA) (not prespecified), children's satisfaction, and value attributed to glasses. MAIN OUTCOME MEASURE: Proportion of glasses wear on twice-weekly covert evaluation by head teachers over 2 months. RESULTS: Among 379 eligible participants, 127 were allocated to standard glasses (mean age, 13.7 years; standard deviation [SD], 1.0 years; 54.3% were male), 125 to ready-made (mean age, 13.6; SD, 0.83; 45.6%), and 127 to adjustable (mean age, 13.4 years; SD, 0.85; 54.3%). Mean wear proportion of adjustable glasses was significantly lower than for standard glasses (45% vs. 58%; P = 0.01), although the adjusted difference (90% confidence interval [CI], -19.0% to -3.0%) did not meet the prespecified inferiority threshold of 20%. Self-reported (90.2% vs. 84.8%, P = 0.64) and investigator-observed (44.1% vs. 33.9%, P = 0.89) wear did not differ between standard and adjustable glasses, nor did satisfaction with (P = 0.97) or value attributed to study glasses (P = 0.55) or increase in quality of life (5.53 [SD, 4.47] vs. 5.68 [SD, 4.34] on a 100-point scale, P > 0.30). Best-corrected visual acuity with adjustable glasses was better (P < 0.001) than with standard glasses. Change in power of study lenses at the end of the study (adjustable: 0.65 D, 95% CI, 0.52-0.79; standard, 0.01 D; 95% CI, -0.006 to 0.03, P < 0.001) was greater for adjustable glasses, although interobserver variation in power measurements may explain this. Lens scratches and frame damage were more common with adjustable glasses, whereas lens breakage was less common than for standard glasses. CONCLUSIONS: Proportion of wear was lower with adjustable glasses, although VA was better and measures of satisfaction and quality of life were not inferior to standard glasses.

Selection of and Evidentiary Considerations for Wearable Devices and Their Measurements for Use in Regulatory Decision Making: Recommendations from the ePRO Consortium.

BACKGROUND: Wearable devices offer huge potential to collect rich sources of data to provide insights into the effects of treatment interventions. Despite this, at the time of writing this report, limited regulatory guidance on the use of wearables in clinical trial programs has been published. OBJECTIVES: To present recommendations from the Critical Path Institute's Electronic Patient-Reported Outcome Consortium regarding the selection and evaluation of wearable devices and their measurements for use in regulatory trials and to support labeling claims. METHODS: The evaluation group was composed of Critical Path Institute's clinical outcome assessment (COA) scientists and COA specialists from pharmaceutical trial eCOA solution providers, including COA development and validation specialists. The resulting recommendations were drawn from a broad range of backgrounds, perspectives, and expertise that enriched the development of this report. Recommendations were developed through analysis of existing regulatory guidance relating to COA development and use in clinical trials, medical device certification/clearance regulations, literature-reported best practice, and practical experience of wearable technology application in clinical trials. RESULTS: We identify the essential properties of fit-for-purpose wearables and propose evidence needed to support their use. In addition, we overview the activities required to establish clinical endpoints derived from wearables data. CONCLUSIONS: Using this framework, we believe there is enough current understanding to promote the appropriate use of wearables in study protocols. We hope this will provide a basis for discussion among clinical trial stakeholders and catalyze the development of more robust regulatory guidance.

Rasch analysis of the Student Refractive Error and Eyeglass Questionnaire.

PURPOSE: To evaluate and refine a newly developed instrument, the Student Refractive Error and Eyeglasses Questionnaire (SREEQ), designed to measure the impact of uncorrected and corrected refractive error on vision-related quality of life (VRQoL) in school-aged children. METHODS: A 38-statement instrument consisting of two parts was developed: part A relates to perceptions regarding uncorrected vision and part B relates to perceptions regarding corrected vision and includes other statements regarding VRQoL with spectacle correction. The SREEQ was administered to 200 Native American 6th- through 12th-grade students known to have previously worn and who currently require eyeglasses. Rasch analysis was conducted to evaluate the functioning of the SREEQ. Statements on parts A and B were analyzed to examine the dimensionality and constructs of the questionnaire, how well the items functioned, and the appropriateness of the response scale used. RESULTS: Rasch analysis suggested two items be eliminated and the measurement scale for matching items be reduced from a four-point response scale to a three-point response scale. With these modifications, categorical data were converted to interval-level data to conduct an item and person analysis. A shortened version of the SREEQ was constructed with these modifications, the SREEQ-R, which included the statements that were able to capture changes in VRQoL associated with spectacle wear for those with significant refractive error in our study population. CONCLUSIONS: Although part B of the SREEQ appears to have a less-than-optimal reliability to assess the impact of spectacle correction on VRQoL in our student population, it is able to detect statistically significant differences from pretest to posttest on both the group and individual levels to show that the instrument can assess the impact that glasses have on VRQoL. Further modifications to the questionnaire, such as those included in the SREEQ-R, could enhance its functionality.

Spectacle wear in children given spectacles through a school-based program.

PURPOSE: To investigate factors associated with spectacle wear in a group of primarily Native-American children provided spectacles free of charge through a school-based vision program. METHODS: Spectacle wear was studied in 247 participants provided two pairs of spectacles the previous year. Univariate and multivariate logistic regression models assessed whether gender, race, parental education levels, family income, uncorrected distance visual acuity, refractive error, or the children's attitudes and beliefs about their vision and spectacles were associated with spectacle wear. RESULTS: Two thirds of the participants (165/247) were not wearing their spectacles at their annual examination. The most common reasons given for non-wear were lost (44.9%) or broken (35.3%) spectacles. A 1 diopter increase in myopic spherical equivalent was associated with more than a twofold increase in the odds of wearing spectacles [odds ratio (OR) = 2.5, 95% confidence interval (CI) = 1.7 to 3.7]. Among non-myopic participants, increasing amounts of astigmatism in the better- and worse-seeing eye were associated with an increased likelihood of spectacle wear (p ≤ 0.02). In multivariate analysis, only poorer uncorrected acuity in the better-seeing eye (p < 0.001) and shorter acceptance time (p = 0.007) were found to be significantly associated with spectacle wear. For each line of poorer uncorrected acuity in the better-seeing eye, the likelihood that the participant was wearing spectacles increased by 60% (adjusted odds ratio = 1.6; 95% CI = 1.4 to 1.8). Not surprisingly, participants who reported never getting used to their spectacles were less likely to be wearing spectacles than those who reported getting used to wearing glasses in a few days (adjusted OR = 5.7, 95% CI = 1.9 to 17.5). CONCLUSIONS: Despite being provided with two pairs of spectacles, loss and breakage were the most commonly reported reasons for not wearing spectacles. The best predictive factor for determining whether participants were wearing spectacles was their uncorrected acuity.

Predictors of adequate correction following vision screening failure.

PURPOSE: To determine whether compliance with referral 1 year after vision screening failure was associated with care model, demographic, or ocular factors. METHODS: Data were analyzed from 798 children in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study with habitual logMAR visual acuity (VA) ≥0.26 (20/40 + 2 or worse) in either eye due to uncorrected or undercorrected refractive error and who returned the following year. The parents of 492 children failing in TX and CA were sent letters indicating the need for a complete vision examination (screening model), while 306 children seen primarily in AZ and AL received a free complete examination and eyeglasses if needed (complete care model). Presenting to follow-up with adequate correction (logMAR <0.26) in each eye was considered compliant. Logistic regression models for compliance were fit to assess whether care model, ethnicity, sex, age, uncorrected logMAR in the better eye, or parental income, education, or myopia were predictors. RESULTS: Overall compliance was 28%. Age [p = 0.01, odds ratio (OR) = 1.12] and uncorrected logMAR (p < 0.001, OR = 1.13) were associated with compliance but care model, ethnicity, and sex were not. Among the 447 children for whom data on parental factors were available, 27% were compliant. In this model, age, ethnicity, sex, parental income, parental education, and parental myopia were not associated with compliance, but uncorrected logMAR (p = 0.005; OR = 1.13) was predictive. An interaction between unaided VA and care model predicted improved compliance with poorer unaided VA in the complete care model. CONCLUSIONS: Expensive complete care screening programs may not improve compliance over typical notification and referral screening protocols in school-aged children, unless unaided VA is worse than the common 20/40 referral criteria. Unaided VA had less impact on predicted compliance in the screening-only protocol.

Comparability of a provisioned device versus bring your own device for completion of patient-reported outcome measures by participants with chronic obstructive pulmonary disease: qualitative interview findings.

BACKGROUND: There is interest in participants using their own smartphones or tablets ("bring your own device"; BYOD) to complete patient-reported outcome (PRO) measures in clinical studies. Our study aimed to qualitatively evaluate participants' experience using a provisioned device (PD) versus their own smartphone (BYOD) for this purpose. METHODS: Participants with chronic obstructive pulmonary disease (COPD) were recruited for this observational, cross-over study and completed PRO measures daily on one device type for 15 days, then switched to the other device type to complete the same measures for another 15 days. After each 15-day period, semi-structured interviews were conducted about their experience with the device. RESULTS: Of 64 participants enrolled, the final qualitative analysis populations comprised those who participated in an interview without protocol violations. Thus, the qualitative longitudinal population (LP) included n = 57 (89%), while the qualitative cross-sectional population (CSP) included n = 60 (94%). CSP participants found both device types easy to use. Twenty CSP participants (33%) reported missing data entry on at least one day when using PD, and 24 (40%) reported missing at least one day when using BYOD. In the LP, preference for one of the device types was somewhat evenly split; 45.6% (n = 26) preferred PD and 50.9% (n = 29) preferred BYOD. The most common reason for preferring PD was that it was "dedicated" to the study; the "convenience" of carrying a single device was the main reason for preferring BYOD. CONCLUSION: The findings from the interviews demonstrated few differences in participants' experience completing PRO measures on a PD versus BYOD. Our study supports the use of BYOD as a potential addition to PD for collecting PRO data and contributes evidence that BYOD may be employed to collect PRO data in demographically diverse patient populations.

Best Practice Recommendations: User Acceptance Testing for Systems Designed to Collect Clinical Outcome Assessment Data Electronically.

Implementing clinical outcome assessments electronically in clinical studies requires the sponsor and electronic clinical outcome assessment (eCOA) provider to work closely together to implement study-specific requirements and ensure consensus-defined best practices are followed. One of the most important steps is for sponsors to conduct user acceptance testing (UAT) using an eCOA system developed by the eCOA provider. UAT provides the clinical study team including sponsor or designee an opportunity to evaluate actual software performance and ensure that the sponsor's intended requirements were communicated clearly and accurately translated into the system design, and that the system conforms to a sponsor-approved requirements document based on the study protocol. The components of an eCOA system, such as the study-specific application, customization features, study portal, and custom data transfers should be tested during UAT. While the provider will perform their own system validation, the sponsor or designee should also perform their due diligence by conducting UAT. A clear UAT plan including the necessary documentation may be requested by regulatory authorities depending on the country. This paper provides the electronic patient-reported outcome (ePRO) Consortium's and patient-reported outcome (PRO) Consortium's best practice recommendations for clinical study sponsors or their designee for conducting UAT with support from eCOA providers to ensure data quality and enhance operational efficiency of the eCOA system. Following these best practice recommendations and completing UAT in its entirety will support a high quality eCOA system and ensure more reliable and complete data are collected, which are essential to the success of the study.