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.

Measurement Comparability of Electronic and Paper Administration of Visual Analogue Scales: A Review of Published Studies.

BACKGROUND: Visual analogue scales (VASs) are used in a variety of patient-, observer- and clinician-reported outcome measures. While typically included in measures originally developed for pen-and-paper completion, a greater number of clinical trials currently use electronic approaches to their collection. This leads researchers to question whether the measurement properties of the scale have been conserved during the migration to an electronic format, particularly because electronic formats often use a different scale length than the 100 mm paper standard. METHODS: We performed a review of published studies investigating the measurement comparability of paper and electronic formats of the VAS. RESULTS: Our literature search yielded 26 studies published between 1997 and 2018 that reported comparison of paper and electronic formats using the VAS. After excluding 2 publications, 23 of the remaining 24 studies included in this review reported electronic formats of the VAS (eVAS) and paper formats (pVAS) to be equivalent. A further study concluded that eVAS and pVAS were both acceptable but should not be interchanged. eVAS length varied from 21 to 200 mm, indicating that 100 mm length is not a requirement. CONCLUSIONS: The literature supports the hypothesis that eVAS and pVAS provide comparable results regardless of the VAS length. When implementing a VAS on a screen-based electronic mode, we recommend following industry best practices for faithful migration to minimise the likelihood of non-comparability with pVAS.

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.

Association of reading disability on chromosome 6p22 in the Afrikaner population.

The genetic basis of reading disability (RD) has long been established through family and twin studies. More recently genetic linkage studies have identified genomic regions that appear to harbor susceptibility genes for RD. Association studies have been shown to have greater power for detecting genes of modest effect, particularly in genetically isolated populations. Hence, a case control study of RD was undertaken in the Afrikaner population in South Africa. Sixty-eight microsatellite markers in regions where linkages had been reported in previous studies were genotyped on 122 children with reading disability and 112 typically reading controls drawn from the same school population. A single allele of marker D6S299 showed a highly significant association with the RD phenotype (D6S299[229], P-value 0.000014). Other markers on other chromosomes also showed suggestive associations. Of particular interest were markers on chromosomes 1 and 15. These two regions have been implicated in studies of populations that formed the founding population in the Afrikaner population.

Detecting recent positive selection in the human genome from haplotype structure.

The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD and CD40 ligand. At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection.