RESUMEN
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.
Asunto(s)
Electrónica , Medición de Resultados Informados por el Paciente , Ensayos Clínicos como Asunto , Recolección de Datos , Humanos , PsicometríaRESUMEN
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.
Asunto(s)
Papel , Calidad de Vida , Electrónica , Humanos , Dimensión del Dolor/métodos , Escala Visual AnalógicaRESUMEN
Tourette's disorder (TD) frequently co-occurs with attention-deficit/hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). While the relationship between TD and OCD suggests that they share etiological factors, the exact relationship between TD and ADHD is less clear. The goal of the current analyses was to understand better the familial relationship between DSM-IV ADHD and TD. Direct interview diagnostic data from a case-control study of 692 relatives of 75 comorbid TD and ADHD (TD + ADHD), 74 TD without ADHD (TD Only), 41 ADHD without TD (ADHD Only), and 49 control probands were analyzed. Hierarchical loglinear modeling was used to explore association patterns between TD, ADHD, and OCD or sub-clinical OCD (OCD/OCDsub) diagnoses among the 190 affected probands and their 538 relatives. The presence of OCD or OCDsub diagnosis in a proband was associated with a significantly increased risk of comorbid TD + ADHD in his/her relatives. The finding of an association between TD, ADHD and a proband OCD/OCDsub diagnosis was unexpected. The current results suggest that TD, ADHD, and OCD symptoms have overlapping neurobiology when occurring in families of TD and/or ADHD probands.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/psicología , Familia/psicología , Trastorno Obsesivo Compulsivo/psicología , Escalas de Valoración Psiquiátrica , Síndrome de Tourette/psicología , Edad de Inicio , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Estudios de Casos y Controles , Comorbilidad , Susceptibilidad a Enfermedades/psicología , Humanos , Entrevista Psicológica , Trastorno Obsesivo Compulsivo/complicaciones , Factores de Riesgo , Síndrome de Tourette/complicacionesRESUMEN
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.
Asunto(s)
Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto , Registros Electrónicos de Salud , Neoplasias/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Humanos , Evaluación de Resultado en la Atención de Salud , Investigación Cualitativa , Encuestas y CuestionariosRESUMEN
Susceptibility to coronary heart disease (CHD) has long been known to exhibit familial aggregation, with heritability estimated to be greater than 50%. The French Canadian population of the Saguenay-Lac Saint-Jean region of Quebec, Canada is descended from a founder population that settled this region 300-400 years ago and this may provide increased power to detect genes contributing to complex traits such as CHD. Probands with early-onset CHD, defined by angiographically determined coronary stenosis, and their relatives were recruited from this population (average sibship size of 6.4). Linkage analysis was performed following a genome-wide microsatellite marker scan on 42 families with 284 individuals. Nonparametric linkage (NPL) analysis provided suggestive evidence for a CHD susceptibility locus on chromosome 8 with an NPL score of 3.14 (P=0.001) at D8S1106. Linkage to this locus was verified by fine mapping in an enlarged sample of 50 families with 320 individuals. This analysis provided evidence of linkage at D8S552 (NPL score=3.53, P=0.0003), a marker that maps to the same location as D8S1106. Candidate genes in this region, including macrophage scavenger receptor 1, farnesyl-diphosphate farnesyltransferase 1, fibrinogen-like 1, and GATA-binding protein 4, were resequenced in all coding exons in both affected and unaffected individuals. Association studies with variants in these and five other genes did not identify a disease-associated mutation. In conclusion, a genome-wide scan and additional fine mapping provide evidence for a locus on chromosome 8 that contributes to CHD in a French Canadian population.
Asunto(s)
Cromosomas Humanos Par 8/genética , Enfermedad Coronaria/genética , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Mapeo Cromosómico , Estudios de Cohortes , ADN/genética , Femenino , Efecto Fundador , Francia/etnología , Marcadores Genéticos , Genoma Humano , Humanos , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Polimorfismo Genético , QuebecRESUMEN
CONTEXT: Obsessive-compulsive disorder (OCD) is a debilitating familial psychiatric illness with associated brain abnormalities in the white matter. The gene for oligodendrocyte lineage transcription factor 2 (OLIG2) is an essential regulator in the development of cells that produce white matter (myelin). The OLIG2 gene is also highly expressed in brain regions implicated in OCD. OBJECTIVES: To examine OLIG2 as a candidate gene for OCD susceptibility and to explore whether comorbidity subtypes of OCD have distinct associations with OLIG2 and the functionally related OLIG1 gene. It was hypothesized a priori that OLIG2 and OLIG1 were associated with OCD regardless of the presence of comorbid Tourette disorder (TD), but not with TD alone. DESIGN: Family-based association candidate gene study. SETTING: Participants and their family members were recruited from tertiary care OCD and TD specialty clinics. PARTICIPANTS: Families of 66 probands with OCD with and without TD and 31 probands with TD without OCD. MAIN OUTCOME MEASURES: Genotypes of single nucleotide polymorphism markers and related haplotypes. RESULTS: The following 3 single nucleotide polymorphism markers on OLIG2 were associated with the OCD without TD phenotype: rs762178 (minor allele frequency, 35%; P<.001), rs1059004 (minor allele frequency, 44%; P = .005), and rs9653711 (minor allele frequency, 44%; P = .004). A 5-marker haplotype (A/C/T/T/G) constituting these single nucleotide polymorphisms and exonic single nucleotide polymorphisms rs6517137 and rs13046814 was undertransmitted (frequency, 32%; permuted P=.004), whereas the G/A/T/T/C haplotype (frequency, 22%; permuted P=.02) was overtransmitted to probands with OCD alone, with a significant global P value (permuted P=.008). CONCLUSIONS: This is the first study reporting an association between OLIG2 and OCD, specifically when TD comorbidity is absent. The findings support a role for white matter abnormalities in the etiology of the disorder.
Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Familia , Proteínas del Tejido Nervioso/genética , Trastorno Obsesivo Compulsivo/genética , Mapeo Cromosómico , Comorbilidad , Frecuencia de los Genes , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Haplotipos/genética , Humanos , Desequilibrio de Ligamiento , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/epidemiología , Factor de Transcripción 2 de los Oligodendrocitos , Linaje , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Síndrome de Tourette/epidemiología , Síndrome de Tourette/genéticaRESUMEN
In this study, we attempted to confirm genetic linkage to developmental dyslexia and reading-related quantitative traits of loci that have been shown to be associated with dyslexia in previous studies. In our sample of 108 Dutch nuclear families, the categorical trait showed strongest linkage to 1p36 (NPL-LOD = 2.1). LOD scores for quantitative traits word-reading, non-word reading, and rapid naming peaked near the same location as the categorical trait, as well as on chromosome 2. Non-word repetition showed little phenotypic correlation with dyslexia or with the other quantitative traits, and this trait showed linkage peaks on 11p and 15q. No evidence for linkage to 6p22-23 was found for this set of families. Comparison of our results and literature data shows that loci link to different phenotypes in different samples. The mutual connections of these traits and their relation to developmental dyslexia remain elusive.
Asunto(s)
Cromosomas Humanos Par 1 , Cromosomas Humanos Par 2 , Cromosomas Humanos Par 7 , Dislexia/genética , Predisposición Genética a la Enfermedad , Adolescente , Mapeo Cromosómico , Ligamiento Genético , Genotipo , Humanos , Países Bajos , Fenotipo , HermanosRESUMEN
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.
Asunto(s)
Población Negra/genética , Cromosomas Humanos Par 6 , Dislexia/genética , Alelos , Estudios de Casos y Controles , Niño , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 15 , Dislexia/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Genética de Población , Genotipo , Humanos , Masculino , Repeticiones de Microsatélite , Sudáfrica/epidemiologíaRESUMEN
CONTEXT: Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnormalities. Two separate proximal haplotypes in the glutamate transporter gene, SLC1A1, were recently reported to be associated with OCD among males, but replication is required. OBJECTIVES: This study examines SLC1A1 as a candidate gene for OCD and explores gender influences. It was hypothesized that a significant association between SLC1A1 and OCD would be replicated in an independent sample of males but not females. DESIGN: Family-based association candidate gene study. SETTING: Participants were recruited from tertiary care OCD specialty clinics. PARTICIPANTS: OCD probands and their first degree relatives. MAIN OUTCOMES MEASURES: Association of OCD with genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes. RESULTS: Association between OCD and the three-marker haplotype rs12682807/ rs2072657/ rs301430, with overtransmission of A/T/T, was observed in both genders combined (global P = 0.0015) and in males (global P = 0.0031). Single-marker associations with OCD in the region (rs3780412 and rs2228622) demonstrated modest significance (permuted P = 0.045). CONCLUSIONS: This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported.
Asunto(s)
Transportador 3 de Aminoácidos Excitadores/genética , Trastorno Obsesivo Compulsivo/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Distribución por Edad , Edad de Inicio , Niño , Mapeo Cromosómico , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Haplotipos/genética , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Trastorno Obsesivo Compulsivo/diagnóstico , Distribución por SexoRESUMEN
Low levels of high-density lipoprotein cholesterol (HDL-C) are an independent risk factor for cardiovascular disease. To identify novel genetic variants that contribute to HDL-C, we performed genome-wide scans and quantitative association studies in two study samples: a Quebec-wide study consisting of 11 multigenerational families and a study of 61 families from the Saguenay-Lac St-Jean (SLSJ) region of Quebec. The heritability of HDL-C in these study samples was 0.73 and 0.49, respectively. Variance components linkage methods identified a LOD score of 2.61 at 98 cM near the marker D16S515 in Quebec-wide families and an LOD score of 2.96 at 86 cM near the marker D16S2624 in SLSJ families. In the Quebec-wide sample, four families showed segregation over a 25.5-cM (18 Mb) region, which was further reduced to 6.6 Mb with additional markers. The coding regions of all genes within this region were sequenced. A missense variant in CHST6 segregated in four families and, with additional families, we observed a P value of 0.015 for this variant. However, an association study of this single-nucleotide polymorphism (SNP) in unrelated Quebec-wide samples was not significant. We also identified an SNP (rs11646677) in the same region, which was significantly associated with a low HDL-C (P=0.016) in the SLSJ study sample. In addition, RT-PCR results from cultured cells showed a significant difference in the expression of CHST6 and KIAA1576, another gene in the region. Our data constitute additional evidence for a locus on chromosome 16q23-24 that affects HDL-C levels in two independent French-Canadian studies.
Asunto(s)
HDL-Colesterol/genética , Cromosomas Humanos Par 16/genética , Ligamiento Genético , Predisposición Genética a la Enfermedad , Mapeo Físico de Cromosoma , Canadá , Francia , Regulación de la Expresión Génica , Genoma Humano , Humanos , Escala de Lod , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Secuencia de ADNRESUMEN
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.