The GOING-FWD

(Gender Outcomes INternational Group: to

Further Well-being Development)

Project

HOW TO INTEGRATE SEX AND GENDER

IN CLINICAL PRACTICE

September 13, 2019

Valeria Raparelli, Maria Trinidad Herrero, Elizabeth O. Johnson, Alexandra Kautzky-Willer,

Karolina Kublickiene, Colleen M. Norris, Louise Pilote

I DO NOT have any

relevant FINANCIAL relationships to disclose.

Disclosures Statement

20/11/2019 Titolo Presentazione Pagina 3

Raparelli V, Proietti M, Basili S. Heart. 2018 Dec;104(23):1900-01

INTEGRATION OF SEX AND GENDER DIMENSIONS IN CLINICAL

RESEARCH …IS A PRIORITY BUT IT IS CHALLENGING…

Lack of standard

measurement

How can we measure such

psycho-socio-cultural

complexity?

December 2017 December 2018 March 2019

GOOD HEALTH AND WELL-BEING IN NON-COMMUNICABLE

CHRONIC DISEASES: Call for Action

Topic 1.3. SEX, GENDER AND HEALTH

Colleen M. Norris Louise Pilote Valeria Raparelli

Maria Trinidad Herrero

Elizabeth O. Johnson

Alexandra Kautzky-Willer

Karolina Kublickiene

The overarching aims of this large consortium

are to integrate sex and gender dimensions

in applied health research, to evaluate their

impact on clinical cost-sensitive outcomes

and patients reported outcomes (PROMs)

related to quality of life in Non-Communicable

Diseases (NCD)

GOING-FWD AIM

CANADIAN COORDINATION L. Pilote (CAN) C. Norris (CAN)

V. Raparelli (CAN)

(Lead Investigators)

SCIENTIFIC ADVISORY COMMITTEE Vera Regitz-Zagrosek (GER)

Rachel Dreyer (USA) Londa Schiebinger (USA)

Carole Clair (SWI)

Work Package 3 Aim: KT and Dissemination

• K. Kublickiene (SWE) • M. Parry (CAN) • M.T. Herrero (ESP)

Deliverable 1 Gender Variables-derived Database/Gender Scores/Modeling risk

•Publication •Interventions •eHealth App

•Training Modules •Online Tools

Site Principal Investigator Spain

M.T. Herrero

Site Principal Investigator Austria

A. Kautzy-Willer

Site Principal Investigator Sweden

K. Kublickiene

Site Principal Investigator Cyprus

E. Johnson

Site Principal Investigator Canada L. Pilote

Deliverable 2

AVAILABLE DATABASE

(Administrative/Prospective Cohorts)

CARDIOVASCULAR DISEASE

CAN, AUT, SWE, ESP

METABOLIC DISEASE

CAN, AUT, ESP

CHRONIC KIDNEY DISEASE

CAN, AUT, SWE

NEUROLOGICAL DISORDERS

CAN, ESP, CYP

INTERNATIONAL NETWORK RESEARCH MULTIDISCIPLINARY EXPERTISE IN GENDER AND NON COMMUNICABLE CHRONIC DISEASE

Site Investigators Pilote L: Gender Expert, Epidemiology /CVD Collen N: Gender Expert, Epidemiology /CVD Raparelli V: CVD, Endocrinology Humphries K: Women CV Health Parry M: Health Outcomes/Nursing/IT/KT Bacon S: Patient Oriented research/Methodology Sapir-Pichhadze R: Kidney Disease Abrahamowicz M: Biostatistician Fishman J: Biomedical Ethics

Site Investigators Kautzy-Willer: Gender Expert/Endocrinology Etter SB: Methodology, Network Analysis Klimek P: Methodology, Network Analysis Dorner T: Public Health/Social Science Harreiter J: Endocrinology, Pregnancy, Gender Medicine Deischinger C: PhD Student

Site Investigators Kublickiene K: Gender Expert/Gendered KT Innovation Alliance Post-doctoral Program Rashid Qureshi A: Methodology/Biostatistician Stenvinkel P: Kidney Disease Bruchfeld A: Kidney Disease

Site Investigators Johnson E: Neurology/ Psychoneuroendocrinology /Education Johnson E: Neurological Disease Stephanou A: CVD/Knowledge Translation Pantzaris M: Neurology Themistokleous S: Post-Doc

Site Investigators Herrero MT: Neurology/Communication Lozano MLP: Post-doc/MD Fernandez-Villalba E: Neurology Palma Mendez J: Computer Science Fernandez Aleman JL: Computer Science Navarro Noguerra: PhD Psychology Mascarell Llorens: PhD Student

Work Package 2

Aim: Identification of Cost-Sensitive and PROMs

• K. Humphries & Team (CAN) • A. Kautzy-Willer & Team (AUT)

Work Package 1

Aim: Identification GENDER-RELATED VARIABLES

• C. Norris & team (CAN) • E. Johnson & team (CYP)

STEERING COMMITTEE

L. Pilote (CAN) C. Norris (CAN) V. Raparelli (CAN) A.Kautzy-Willer (AUT)

K. Kublickiene (SWE) M.T. Herrero (ESP) E. Johnson (CYP)

Cardiovascular

disease

Metabolic disease -

Diabetes

Chronic Kidney

Disease

Neurological

Disease

Non-communicable Chronic Disease

Gender-Related Factors Gender framework of the Women Health Research Network

Outcomes 1 – Clinical Cost Sensitive

Mortality

Hospitalization

Readmission

Disease-Specific Outcomes

Diabetes Chronic Kidney Disease Coronary Artery Disease

International Consortium for Health Outcomes Measurement

Patient Reported Outcome

Measures (PROMs)

Patient Reported Experience

Measures (PREMs)

Measures impact of an illness or

health condition from the patient’s

perspective

Captures the patient’s view of what

happened during their healthcare visit

(process of healthcare)

Examples:

quality of life, symptom severity,

functional status, health status

Examples:

Communication and trust in staff,

cleanliness, timeliness

Used to monitor the progress of a

health condition or whether a treatment

has been effective by comparing

results over time

Used to evaluate and monitor service

delivery

Measured from the patient’s perspective, usually via questionnaires

Used together to assess quality of care and services from patient’s viewpoint

Outcomes 1 – Patient Related

Sex and Gender Determinants

SEX -Biomedical Factors -Laboratory Biomarkers -Traditional Risk Factors

GENDER

-Roles -Identity -Institutionalized Gender -Relations

Disease/

Conditions

Cardiovascular Disease

Metabolic Syndrome

Chronic Kidney Disease

Neurological Disease

Outcomes

Clinical/ Cost-Sensitive

Outcomes

Patient-Reported Outcome Measures

-Mortality -Hospitalization -Readmission -Disease

Progression

-Patient Surveys -Questionnaires

Conceptual Framework

32 Cohorts

30 Million of patients

30 Investigators

5 Countries

4 main clinical areas

GOING-FWD

NUMBERS

STEP 1 - IDENTIFICATION OF GENDER-RELATED VARIABLES

STEP 2 - DEFINITION OF OUTCOMES

STEP 3 –

BUILDING OF FEASIBLE FINAL VARIABLES LIST

STEP 4 - RETROSPECTIVE DATA HARMONIZATION

STEP 5 - DEFINITION OF DATA STRUCTURE

GOING-FWD METHODOLOGY

MULTISTEP PROCESS

We developed a standard methodology that can be

applied in pre-existing cohort studies for the integration

of gender-related factors in assessing their impact on

health outcomes

Each variable was discussed

at the inaugural meeting

(April 2019, Montreal) of the

GOING-FWD investigators

and consensus was reached

on a final list of “gender-

related” and “outcome”

variables.

STEP 1 and 2 – DEFINITION OF VARIABLE WISH LIST

STEP 1- IDENTIFICATION OF GENDER-RELATED VARIABLES Roles

Primary earner status

Employment Status

Occupation

Paid Work hours per week

Unpaid work hours per week(eg care giver hours)

Full/part time work

Child caregiver responsibilities The individual or others

Adult caregiver responsibilities

Number of hours per week spent on housework

Status of household’s primary responsibility

Number of children

Relations

Marital/Relationship Status

Family or local network (social capital)

Social support

Social support (any recognized social support instrument)

Availability of Caretaker (for self)

Institutionalized variables

Educational Level

SES/Income

Monthly finances

Income (personal, household)

Number of persons living in household

Retirement eligibilities

Perceived Social Standing Questionnaire *McArthur Scale

GII (Gender inequality index) Questionnaire *

Maternity Paternity related variables

Identity

Stress

14-Item Perceived stress scale (PSS) *

Stress level at work (any measure of stress)

Stress level at home (any measure of stress)

Stress management

Personality traits

Emotional intelligence Questionnaire *

Any validated measures of personality (NEO classic 5 personality traits

BEMS (instrument) measurement of gender identity

Depression/Anxiety

Patient Health Questionnaire-9 *

HAD Scale - Hospital Anxiety and Depression Scale*

Anxiety/Depression any scale

Childhood trauma (reported history)

Discrimination

Day-to-day experiences

Perceived bias

Stigmatization

Violence (hx or present)

Intimate partner domestic

Ethnic violence

Sexual orientation

Immigration Status

Behavioral/Lifestyle Risk Factors

European Health Determinants Module

Current smoking

Smoking history

Cigarettes per day

Physical activity

Physical activity (self-reported: PPAQ)

Physical activity (accelerometer)

Food diary - Diet quality index

Alcohol consumption

Substance use (Use of drugs)

Nutrition

Overall diet quality index

Physical activity barriers (fatigue, lack of motivation, etc.)

Nutrition barriers (enpensiveness, lack of motivation, etc.)

Physical activity facilitators (social support, self-motivation, etc.)

Nutrition facilitators (social support, self-motivation, etc.)

WISH

LIST 1

STEP 1- IDENTIFICATION OF GENDER-RELATED VARIABLES

WISH

LIST 1

STEP 1- IDENTIFICATION OF GENDER-RELATED VARIABLES

WISH

LIST 1

STEP 1- IDENTIFICATION OF GENDER-RELATED VARIABLES

WISH

LIST 1

STEP 1- IDENTIFICATION OF GENDER-RELATED VARIABLES

WISH

LIST 1

Each of the cohort data dictionaries were

screened for outcomes of interest outlined in

the GOING FWD proposal

Clinical Outcomes and Patient-Reported

Outcome Measures (specific for disease)

STEP 2 - DEFINITION OF OUTCOMES

International Consortium for Health Outcomes Measurement

WISH

LIST 2

Work Package 2

Aim: Identification of Cost-Sensitive and PROMs

• K. Humphries & Team (CAN) • A. Kautzy-Willer & Team (AUT)

A cross-validation (double blinded) between variables (i.e.

gender-related factors and outcomes) available per database (data

dictionary) was performed.

In case of disagreement or discordant definitions of variables, a

more inclusive approach was pursued for both gender-related

variables and outcomes.

STEP 3 - BUILDING OF FEASIBLE FINAL VARIABLE LIST

Cross-Check

WISH LIST ACTUAL DATA

Finally, a list of harmonized variables will be created using the Maelstrom Research guidelines for rigorous retrospective data harmonization and merging when possible.

STEP 4 - RETROSPECTIVE DATA HARMONIZATION

HARMONIZATION - Process of bringing together data of

varying formats in order to generate one cohesive data set

Vienna – September 11° 2019, 2nd GOING FWD Meeting

STEP 5 – DEFINITION OF DATA STRUCTURE

Summary data meta-analysis

Study-specific data analyses done locally followed by a meta-analysis combining the study-level estimates

Pooled analysis

Data pooled and analyzed in a central location

Federated analysis

Analyses done centrally, but the individual-level participant data can remain on local servers

Sharing of IPD Harmonization: local or

central Analysis: central

Sharing (or not) of IPD Harmonization: local or

central Analysis: central

No sharing of IPD Harmonization: local

Analysis: local

Depending on the type of database, each partner then provided the data management structure and the

analysis plan based on the following options:

• Personalized medicine approach is increasingly appreciated in

clinical research.

• Analysis of already collected data requires a proper definition

of variables and measures included.

• The existing lack of a standardized gender measure poses

challenges which might be mitigated via application of a

systematic multistep approach (5 steps) currently suggested

and currently tested by our multidisciplinary team.

CONCLUSION

• Understanding of how sex and gender-related factors

impact NCDs will help to improve clinical and patient-

related outcomes.

• Potential to identify gender variables (psycho-

social factors) that can be collected prospectively

• Tailor future interventions with a sex- and gender-

specific approach.

CONCLUSION

WHAT’S NEXT?

• Finalize Ethical Approval for Each Country/database

• Starting the harmonization process: evaluate harmonization potential

• Systematic Reviews

• Define the best data analysis plan: traditional vs artificial intelligence approach based on the data and research question

STAY TUNED!!!

https://mcgill.ca/going-fwd4gender/

GOINGFWD2019@outlook.com

Work Package 3 Aim: KT and Dissemination

• K. Kublickiene (SWE) • M. Parry (CAN) • M.T. Herrero (ESP)

THANK YOU TO ALL THE MEMBERS OF

THE GOING-FWD CONSORTIUM