Considering Sex and Gender in Therapeutics throughout the Product Life Cycle: A Narrative Review and Case Study of Gilteritinib.

Background: Biological sex-related factors influence pharmacokinetic, pharmacodynamic, and disease processes that may affect the predictability of drug dosing and adverse effects, which may in turn have clinical consequences for patients' lives. Nonetheless, sex-related factors are not always taken into account in clinical trial design or clinical decision-making, for multiple reasons, including a paucity of studies that clearly and objectively study and measure sex-disaggregated and sex-related outcomes, as well as gaps in regulatory and policy structures for integrating these considerations. Objectives: To complete a narrative review and use a case study to understand available evidence, inform future research, and provide policy considerations that incorporate information on sex- and gender-related factors into clinician-facing resources. Methods: A comprehensive review of available literature was conducted using a sex- and gender-based analysis plus (SGBA Plus) approach to identify sex- and/or gender-disaggregated information for gilteritinib, a chemotherapeutic agent. Systematic searches were performed in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Wiley), International Pharmaceutical Abstracts (Ovid), Scopus, and ClinicalTrials.gov, from inception to March 18, 2021. The information was then summarized and compared with the Canadian product monograph for this drug. Results: Of 311 records screened, 3 provided SGBA Plus information as a component of outcomes, rather than just as categories or demographic characteristics. Of these, 2 were case studies, and 1 was a clinical trial. No studies from the ClinicalTrials.gov database that were in progress at the time of this review provided details about sex-disaggregated outcomes. The Canadian product monograph did not include sex-disaggregated outcome data. Conclusions: The available evidence from clinical trials, other published literature, and guidance documents does not provide details about sex-disaggregated outcomes for gilteritinib. This paucity of available evidence may create a challenge for clinicians who are making decisions about the efficacy and safety of prescribed therapies in sex-specific populations that have not been well studied.

Contexte: Les facteurs liés au sexe biologique influencent les processus pharmacocinétiques, pharmacodynamiques et pathologiques, qui peuvent avoir une incidence sur la prévisibilité du dosage des médicaments et des effets indésirables. Ceci peut à son tour avoir des conséquences cliniques sur la vie des patients. Néanmoins, les facteurs liés au sexe ne sont pas toujours pris en compte dans la conception des essais cliniques ou la prise de décision clinique, et cela pour de nombreuses raisons ­ notamment le manque d'études qui examinent et mesurent clairement et objectivement les résultats ventilés par sexe et liés au sexe ainsi que les lacunes dans les réglementations et structures politiques pour intégrer ces considérations. Objectifs: Mener un examen narratif et utiliser une étude de cas pour comprendre les preuves disponibles, éclairer les recherches futures et fournir des considérations politiques qui intègrent des informations sur les facteurs liés au sexe et au genre dans les ressources destinées aux cliniciens. Méthodes: Une revue complète de la littérature disponible a été réalisée à l'aide d'une analyse comparative fondée sur le sexe et le genre Plus (ACSG Plus) pour identifier les informations ventilées par sexe et/ou par genre pour le giltéritinib, un agent chimiothérapeutique. Des recherches systématiques ont été effectuées dans MEDLINE (Ovid), Embase (Ovid), CENTRAL (Wiley), International Pharmaceutical Abstracts (Ovid), Scopus et ClinicalTrials.gov, depuis la création de chaque base de données jusqu'au 18 mars 2021. Ces informations ont ensuite été résumées et comparées avec la monographie canadienne de produit pharmaceutique pour ce médicament. Résultats: Sur les 311 documents examinés, 3 ont fourni des informations ACSG Plus en tant que composante des résultats, plutôt que simplement en tant que catégories ou caractéristiques démographiques. Parmi ceux-ci, 2 étaient des études de cas et 1 était un essai clinique. Aucune étude de la base de données ClinicalTrials.gov en cours au moment de cette revue n'a fourni de détails sur les résultats ventilés par sexe. La monographie de produit canadienne ne comprenait pas de données sur les résultats ventilées par sexe. Conclusions: Les preuves disponibles issues d'essais cliniques, d'autres publications et de documents d'orientation ne fournissent pas de détails sur les résultats ventilés par sexe pour le giltéritinib. Ce manque d'éléments probants disponibles peut constituer un défi pour les cliniciens qui prennent des décisions sur l'efficacité et l'innocuité des thérapies prescrites chez des populations sexospécifiques qui n'ont pas été bien étudiées.

Sex, Gender, and the Regulation of Prescription Drugs: Omissions and Opportunities.

The regulation of prescription drugs is an important health, safety, and equity issue. However, regulatory processes do not always consider evidence on sex, gender, and factors such as age and race, omissions that advocates have highlighted for several decades. Assessing the impact of sex-related factors is critical to ensuring drug safety and efficacy for females and males, and for informing clinical product monographs and consumer information. Gender-related factors affect prescribing, access to drugs, needs and desires for specific prescribed therapies. This article draws on a policy-research partnership project that examined the lifecycle management of prescription drugs in Canada using a sex and gender-based analysis plus (SGBA+) lens. In the same time period, Health Canada created a Scientific Advisory Committee on Health Products for Women, in part to examine drug regulation. We report on grey literature and selected regulatory documents to illustrate the extent to which sex and gender-based analysis plus (SGBA+) is utilized in regulation and policy. We identify omissions in the management of prescription drugs, and name opportunities for improvements by integrating SGBA+ into drug sponsor applications, clinical trials development, and pharmacovigilance. We report on recent efforts to incorporate sex disaggregated data and recommend ways that the management of prescription drugs can benefit from more integration of sex, gender, and equity.

Sex, Gender, and Alcohol Use: Implications for Women and Low-Risk Drinking Guidelines.

Alcohol use is coming under increasing scrutiny with respect to its health impacts on the body. In this vein, several high-income countries have issued low-risk drinking guidelines in the past decade, aiming to educate the public on safer levels of alcohol use. Research on the sex-specific health effects of alcohol has indicated higher damage with lower amounts of alcohol for females as well as overall sex differences in the pharmacokinetics of alcohol in male and female bodies. Research on gender-related factors, while culturally dependent, indicates increased susceptibility to sexual assault and intimate partner violence as well as more negative gender norms and stereotypes about alcohol use for women. Sex- and gender-specific guidelines have been issued in some countries, suggesting lower amounts of alcohol consumption for women than men; however, in other countries, sex- and gender-blind advice has been issued. This article reports on a synthesis of the evidence on both sex- and gender-related factors affecting safer levels of drinking alcohol with an emphasis on women's use. We conclude that supporting and expanding the development of sex- and gender-specific low-risk drinking guidelines offers more nuanced and educative information to clinicians and consumers and will particularly benefit women and girls.

A Sex- and Gender-Based Analysis of Adverse Drug Reactions: A Scoping Review of Pharmacovigilance Databases.

Drug-related adverse events or adverse drug reactions (ADRs) are currently partially or substantially under-reported. ADR reporting systems need to expand their focus to include sex- and gender-related factors in order to understand, prevent, or reduce the occurrence of ADRs in all people, particularly women. This scoping review describes adverse drug reactions reported to international pharmacovigilance databases. It identifies the drug classes most commonly associated with ADRs and synthesizes the evidence on ADRs utilizing a sex- and gender-based analysis plus (SGBA+) to assess the differential outcomes reported in the individual studies. We developed a systematic search strategy and applied it to six electronic databases, ultimately including 35 papers. Overall, the evidence shows that women are involved in more ADR reports than men across different countries, although in some cases, men experience more serious ADRs. Most studies were conducted in higher-income countries; the terms adverse drug reactions and adverse drug events are used interchangeably, and there is a lack of standardization between systems. Additional research is needed to identify the relationships between sex- and gender-related factors in the occurrence and reporting of ADRs to adequately detect and prevent ADRs, as well as to tailor and prepare effective reporting for the lifecycle management of drugs.

Influencia del proceso de aculturación en la percepción de riesgos psicosociales en el trabajo / The relationship between the process of acculturation and the perception of psychosocial risks in the workplace

OBJETIVO: Los objetivos del presente estudio son analizar las relaciones existentes entre las estrategias de aculturación y los factores de riesgo psicosocial, el estrés aculturativo y los riesgos psicosociales, y evaluar si existen diferencias en estrés aculturativo dependiendo del sector de actividad. MATERIAL Y MÉTODOS: La muestra estuvo formada por 201 personas trabajadoras migrantes que viven en la Comunidad de Madrid (49%) y procedentes en su mayoría de países de Europa oriental y de América del Sur. Se evaluaron las estrategias de aculturación con el cuestionario Modelo Ampliado de Aculturación Relativa (MAAR), el estrés aculturativo con la escala Barcelona de Estrés del Inmigrante (Barcelona Immigrant Stress Scale [BISS]) y los riesgos psicosociales con el cuestionario DECORE. El diseño fue transversal. RESULTADOS: Los resultados muestran que no existen diferencias estadísticamente significativas en la estrategia utilizada por hombres y mujeres para cada ámbito de aculturación. Los sujetos que utilizan la estrategia de marginación tienen percepción de bajo salario, los que adoptan la estrategia intermedia perciben poco control sobre su trabajo, mientras que los que adoptan la estrategia de integración perciben más demandas laborales (trabajo con más contenido). El estrés aculturativo se muestra como predictor de la percepción adversa del entorno laboral (bajo control, bajas recompensas y poco apoyo social). Por otra parte, las personas trabajadoras de más edad perciben más control sobre su trabajo y los empleados del sector de los servicios para el hogar tienen puntuaciones mayores en nostalgia y estrés psicosocial que los del resto de sectores evaluados. CONCLUSIONES: Se deben poner en marcha dentro de las organizaciones medidas para minimizar el estrés aculturativo, promover la integración de este grupo de personas trabajadoras y mejorar su percepción de los factores de riesgo psicosocial

OBJECTIVE: The objectives of this study were to analyze the relationships between acculturation strategies and psychosocial risk factors, the acculturative stress and the psychosocial risks, and to assess whether there are differences in acculturative stress depending on the activity sector. MATERIAL AND METHODS: The sample consisted of 201 migrant workers living in the Community of Madrid (49%). Most of them were originally from countries from Eastern Europe and South America. Using a cross-sectional design, we applied Relative Acculturation Extended Model (MAAR) questionnaire to measure acculturation strategies; Barcelona Immigrant Stress Scale (BISS) was applied to measure acculturative stress and psychosocial risks were assessed through the DECORE questionnaire. RESULTS: The results showed that there are no statistically significant differences in the strategy used by men and women for each area of acculturation. Participants who used the Marginalization strategy perceived their salary as being low while those who adopted the Intermediate strategy perceived little control over their work. Those who adopted the Integration strategy perceive more work demands (higher job content). Acculturative stress is a predictor of adverse perception of work environment (low control, low rewards and low social support). On the other hand, older workers perceive more control over their work and employees in the home services sector have higher scores in Nostalgia and Psychosocial Stress than those in other sectors. CONCLUSIONS: Within organizations, measures must be put in place to minimize acculturative stress, promote the integration of the workers and improve their perception of psychosocial work factors

Where Sexual Orientation Has No Name: Sexual Orientation Missing Data in the Canadian Community Health Survey (2005-2014).

This study used data from the Canadian Community Health Survey (CCHS) (2005-2014) to analyze the relationships between sexual orientation item nonresponse and interview language, conversation language, migration status (migrant-non-migrant), cultural background, sex, age, education level, and marital status in a cross-sectional sample over 18 (n = 351,713 participants). Item nonresponse rates oscillated between 0.87% in 2007 and 1.4% in 2014. Individuals who self-declared as belonging to cultural groups such as Chinese, South Asian, South East Asian, Arab, Indigenous and Other had higher nonresponse odds compared to people who self-identified as Whites. The results showed significant higher nonresponse odds among immigrants. Women had higher nonresponse rates. The likelihood of non-answer increased with age and decreased with education. French interviews, interviews in other languages and speaking both English and French produced less nonresponse. Contrary to common beliefs, sexual orientation questions are not too controversial. Sexual orientation nonresponse is low and stable over time suggesting that research participants are willing to answer sexual orientation questions. These findings highlight that immigrants and people who self-declare as belonging to different cultural groups may interpret the sexual orientation questions differently.

Sex- and Gender-Based Analysis in Cannabis Treatment Outcomes: A Systematic Review.

There is evidence that sex- and gender-related factors are involved in cannabis patterns of use, health effects and biological mechanisms. Women and men report different cannabis use disorder (CUD) symptoms, with women reporting worse withdrawal symptoms than men. The objective of this systematic review was to examine the effectiveness of cannabis pharmacological interventions for women and men and the uptake of sex- and gender-based analysis in the included studies. Two reviewers performed the full-paper screening, and data was extracted by one researcher. The search yielded 6098 unique records-of which, 68 were full-paper screened. Four articles met the eligibility criteria for inclusion. From the randomized clinical studies of pharmacological interventions, few studies report sex-disaggregated outcomes for women and men. Despite emergent evidence showing the influence of sex and gender factors in cannabis research, sex-disaggregated outcomes in pharmacological interventions is lacking. Sex- and gender-based analysis is incipient in the included articles. Future research should explore more comprehensive inclusion of sex- and gender-related aspects in pharmacological treatments for CUD.

Reliability Generalization as a Seal of Quality of Substantive Meta-Analyses: The Case of the VIA Inventory of Strengths (VIA-IS) and Their Relationships to Life Satisfaction.

Reliable test scores are essential to interpret the results obtained in statistical analyses correctly. In this study, we used the Values in Action Inventory of Strengths (VIA-IS) as an example of a widely applied assessment instrument to analyze its metric quality in what is known as reliability generalization (RG). In addition, we conducted a meta-analysis of the correlations between character strengths and life satisfaction to examine the potential relationship between the reliability of test scores and the intensity of these correlations. The overall variability of alpha coefficients supports the argument that reliability is sample dependent. Indeed, there were statistically significant mean reliability differences for scores across the 24 scales, with the highest level of reliability observed for Creativity and the lowest for scores on Self-regulation. Significant moderators such as the standard deviation of the scores and the sample type contribute to understand the high variability observed in the reliability estimation. The second meta-analysis showed that Zest, Hope, Gratitude, Curiosity, and Love were the character strengths that were highly related to life satisfaction, while Modesty and Prudence were less related to life satisfaction. Furthermore, the high heterogeneity between samples might be an indicator of the relationship between the variability of reliability of character strengths' scores and the intensity of their correlations with life satisfaction. Those character strengths with high-potential RG are related or unrelated to life satisfaction, whereas character strengths with less-potential RG showed unstable correlation patterns. The results of both studies point out the role of the relationship between the reliability of test scores and substantive studies, such as Pearson's correlations meta-analysis.