제5차 여성건강포럼 2016. 9. 26 젠더혁신: 의의와 연구사례 백 희 영 여성과총 젠더혁신 연구센터 서울대 명예교수

Science (26.3.2010; Vol 327:1571-2): Between 1997 and 2000, 10 drugs were withdrawn from the U.S. market because of life-threatening health effects —8 of those showed greater severity in women.

Bias in Scientific Research & Product Developments Not Scientifically Valid  Low Quality Research Waste of Research Money & Time Products not suitable for market Causes sufferings and even lives of people

Most researches are done by male researchers in male or unspecified subjects!

M Park, et.al. Am J Physiol. Cell Physiol., 2014

Beery, A., & Zucker, I. (2011). Sex Bias in Neuroscience and Biomedical Research. Neuroscience and Biobehavioral Reviews, 35 (3), 565-572.

Percentage of women in clinical trials vs. real world

NIH Revitalization Act of 1993 Guidelines to include women and minority in Phase III Clinical Studies Historically women were excluded if of reproductive age (ages 18-45) Fear of harm to potential unborn child In essence, excluded MAJORITY of women New guidelines eliminates this stipulation

Nature, Vol. 509 (15 May, 2014), 282-283 미국 NIH 또한 2014년 10월부터 동물과 세포를 사용하는 모든 임상전 연구에서 성별 균형을 요구할 계획임.

Sex as a biological variable NIH Grant applicants are required to address consideration of sex as a biological variable in the Research Strategy section of the application for studies in vertebrate animals and humans. For applications proposing to study only one sex, strong justification from the scientific literature, preliminary data, or other relevant considerations, must be provided . Review criteria will include evaluation of the adequacy of the research plan with regard to consideration of sex as a biological variable. These changes will go into effect for research grant applications due January 25, 2016, and beyond, to all NIH funded research programs.

http://grants.nih.gov/grants/guide/pa-files/PA-16-066.html

http://genderedinnovations.stanford.edu/

Gendered Innovations… harness the creative power of sex and gender analysis to discover new things. provide researchers with the tools to integrate sex and gender analysis into science and engineering research. 1) develop state-of-the-art Methods of sex and gender analysis 2) provide Case Studies to illustrate how gender analysis leads to innovative science and technology.

용어정의 성(Sex): 생물학적 특성에 따라 결정됨 male/female/intersexed 젠더(Gender): 사회적, 문화적으로 형성된 태도와 행동 남성적(masculine) 여성적(feminine) 성분석 (Sex Analysis): 성별에 따른 연구계획과 자료 분석 젠더분석 (Gender Analysis): 모든 연구와 실험단계에서 젠더 특성이 미치는 영향을 고려하여 시행. (Schiebinger, 2013)

Methods Rethinking Research Priorities and Outcomes Rethinking Concepts and Theories Formulating Research Questions Analyzing Sex Analyzing Gender Analyzing how Sex and Gender Interact Analyzing Factors Intersecting with Sex and Gender Engineering Innovation Processes Designing Health & Biomedical Research Participatory Research and Design Rethinking Standards and Reference Models Rethinking Language and Visual Representations

4. Analyzing Sex Reporting the sex of research subjects or users. Recognizing differences that exist within groups of females and males/women and men. Collecting and reporting data on factors intersecting with sex in study subjects or users/consumers. Analyzing and reporting results by sex. Reporting null findings. Meta-Analysis. 175cm, 70 kg men

(Politzer, 2014)

5. Analyzing Gender What are the researchers' or engineers’ gendered assumptions and behaviors that affect the proposed research? What are the research subjects' and users’ gender needs, assumptions, or behaviors as they affect the proposed research? How do #1 & #2 interact? How do the genders of the researcher and the genders of the subject/user interact?

6. Analyzing How Sex and Gender Interact "Sex" and "gender" are distinguished for analytical purposes. In reality, sex and gender interact To form individual bodies, cognitive abilities, and disease patterns To shape the ways engineers design objects, buildings, cities, etc. For social factors, age, SES, …

7. Analyzing Factors Intersecting with Sex and Gender Examining how other factors intersect with sex and gender Genetics, Age, Sex Hormones, Reproductive Status, Body Composition, Comorbidities, Body Size, Socioeconomic Status, Education, Religion, Lifestyle, Family, Environment … Identifying relevant factors or variables. Defining factors or variables. Identifying intersections

9. Designing Health & Biomedical Research Sex and gender should be considered in All biomedical researches Basic Applied Translational Wide range of study designs Survey Experimental Clinical Trials Field trials …..

http://genderedinnovations.stanford.edu/

5 4 3 2 1 여성과총 젠더혁신 연구사업 연혁 첫 연구사업 (한국사례연구) Pilot Project 확산과 발전 GS 6 – AP 주도적 참여 Oct. '13 Nov. '13 – Feb. '14 Mar. '14- July '15 Aug. '15 Feb. '16 4 젠더혁신 연구센터설립 5 27

Gender Analysis in Dietary Assessment in Diet and Health Studies Example of case study Fresh Food Gender Analysis in Dietary Assessment in Diet and Health Studies Source: H. Lee, et al. British Journal of Nutrition (2016) 115:666-71

What is FFQ? Food Frequency Questionnaire: Used in most cohort studies on diet and disease Aims to estimate usual dietary intake 2) 3) FFQ Development 1) 1) Food Items 2) Frequency 3) Portion Size 첫번째로 연구배경 및 목적입니다. 식품섭취빈도 조사법은 FFQ라고도 불리며 장기간의 식이섭취 정보를 얻을 수 있는 식이섭취 조사 도구입니다. 비용이 저렴하고 수행과정이 간편하여 주로 식이요인과 질병과의 상관관계를 연구하는 대규모 코호트 연구에서 사용됩니다. FFQ는 식품목록, 섭취빈도, 섭취분량 이렇게 세 부분으로 구성됩니다. 대규모 코흐트연구에서는 대상 집단에 대해 사전조사를 실시하여 이 구성요소들을 개발하기도 하고, 국가단위의 식사조사 자료를 이용하기도 합니다. 개발된 후에는 대상 집단의 식생활을 잘 반영하고 있는지 확인하기 위해 24시간 회상법과 같은 레퍼런스 방법과 비교하여 타당도를 검증하게 됩니다. FFQ Validation Diet-Health Studies

Challenges Dietary intake estimation determined by food items and portion size on FFQ Food items and PS usually determined using prior dietary data Failure to reflect gender difference will result in incorrect FFQ Leading to incorrect diet-disease relatioship

Study Objective To examine whether FFQs validated up to present time have considered gender differences in developing FFQs To compare the performances of FFQs developed with or without gender consideration in validation studies diet-disease studies (meat intake and colon cancer)

Study Design Validation Study Diet-Disease Study - Only one sex - Not for healthy adult - Review articles - Not relevant - Original article not found - Not written in English - Duplications Web search (PubMed) of FFQ validation articles 2290 Excluded FFQ validation articles for healthy adult & both sex 246 FFQ development studies 196 FFQ Development articles Gender considered in development stage? Yes No Gender-Specific Food Frequency Questionnaire (GS-FFQ) Not gender-specific Food Frequency Questionnaire (NGF-FFQ) 먼저 펍메드에서 키워드 조합을 통해 일차적으로 2290개의 논문을 검색하였고, 초록과 본문 검토를 통해 건강한 성인 남녀를 대상으로 하는 246편의 FFQ 타당도 논문을 최종 선정하였습니다. 246편에서 타당도를 검증한 198편의 FFQ 개발논문을 검색하여 개발과정에서 성별에 따른 차이가 반영되었는 지 여부로 GS FFQ, NGS FFQ로 분류하였습니다. 그 다음 이 두 그룹간 타당도 검증결과, 코호트 연구결과를 비교하였습니다. Compare performance Validation Study Diet-Disease Study (Meat intake and colon cancer) Selected from WCRF Report

Methods 1. Classification of FFQ 2. Performance in Validation Studies - FFQ classified by whether gender was considered in development Food Item Selection ? Determining portion size? Yes for either question No for both questions Gender-sensitive (GS) FFQ Not Gender-sensitive (NGS) FFQ 2. Performance in Validation Studies Classify 246 validation studied by FFQs used (GS vs. NGS) Compare results of nutrient intakes by FFQ / ref method of each study Ratiostudy = (Intake by FFQ) / (Intake by Ref. method) Mean ratio = (Sum of Ratiostudy) / Number of studies - Statistical test on differences in mean ratios of GS vs. NGS 성별을 고려했는지 여부를 어떻게 판단했는지 그 예시입니다. 왼쪽을 보시면 해당 FFQ는 식품 목록 선정 시에 국가단위 식이섭취 조사 자료를 가지고 연령, 인종, 성별 특이적인 영양소별 급원 식품을 구하여 특정 집단이 주로 섭취하는 식품이 FFQ를 개발할 때 제외되지 않도록 하였습니다. 오른쪽은 섭취 분량을 선정할 때 국가 단위 식이섭취 조사 자료를 이용하여 연령 및 성별 특이적인 평균 분량을 구하여 FFQ에서 제시한 경우입니다.

3. Performance in Diet-Disease Studies: Meta-analysis of studies on meat intake and colon cancer Selection of Studies: - Cohort studies used in WCRF Report on Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective, Continuous Update Project. Colorectal Cancer 2011 - Studies done with both men and women - Have results for red meat and/or processed meat intakes Classification of Studies: - Selected studies are classified by the FFQs used in the study GS vs. NGS Meta-analysis of Studies - Meta-analysis of study results for red meat intake - Meta-analysis of study results for processed meat intkae - Statistical analysis by STATA/SE 13.1

Results Gender- specific (GS) FFQ Not gender-specific (NGS) FFQ Table 1. Classification of FFQs Development Category No. (%) Gender Considered Food item only 4 (2.0%) Portion size only 10 (5.1%) Food item + Portion size 1 (0.5%) Single sex (female only) 6 (3.1%) Gender Not Considered None 175 (89.3%) Total 196 (100.0%) Gender- specific (GS) FFQ Not gender-specific (NGS) FFQ 젠더 고려 여부에 따른 FFQ 분류 결과 입니다. 198편 중에서 젠더를 고려한 10.6%, 21편이 Gender specific FFQ로 분류되었습니다. FFQ의 구성요소인 식품목록과 섭취분량 중에서는 섭취분량을 선정할 때 더 자주 젠더를 고려하는 것으로 보입니다.

Results GS group NGS group Total Table 2. Results Presentation in Validation Studies Results GS group NGS group Total By gender 18 (40.0%) 44 (21.9%) 62 (25.2%) Total & by gender 3 (6.6%) 25 (12.4%) 28 (11.4%) Total only 24 (53.3%) 132 (65.7%) 156 (63.4%) 45 (100.0%) 201 (100.0%) 246 (100.0%) 246편의 타당도 검증 문헌에서 결과를 표시할 때 젠더를 나누어 표시하는 지 알아보았습니다. 63.4%의 문헌이 젠더를 구분하지 않고 결과를 표시하는 것으로 나타났습니다. 선행연구에 따르면 연학연구 에서 대상자 수가 충분하지 않을 경우 연구의 유의성을 얻기 위해 남녀를 구분하지 않고 분석하는 경우가 많다고 밝힌 바 있습니다. GS: Gender-specific; NGS: Not gender-specific

Table 3-1. Ratio of nutrient takes in validation studies of GS vs. NGS FFQs in men Nutrients No. of Studies GS Group NGS Group Intake Levels GS NGS Reference (A) FFQ (B) Ratio (B/A) Energy (kcal) 9 21 2333.7 2150.5 0.92† 2298.4 2336.9 1.02 Carbohydrate (g) 7 17 251.7 255.2 1.01 302.1 311.2 1.03 Protein (g) 90.7 79.6 0.88† 87.9 83.1 0.95 Fat (g) 8 19 91.1 77.6 0.85‡ 70.7 71.5 Cholesterol (mg) 4 16 391.7 325.8 0.83 304.8 289 Fiber (g) 5 14 21.2 22.4 1.06 22 1.05 Calcium (mg) 6 1065.2 1044.3 0.98 778.4 797.4 Vitamin C (mg) 13 88.5 101.8 1.15 116.9 141.4 1.21† Median   (Vit C excluded) 0.92 타당도를 검증한 논문에서 FFQ로 측정한 섭취량과 레퍼런스 방법으로 측정한 섭취량을 구해서 그 비율을 구해보았습니다. 이 표는 응답자가 남성일 경우인데요, 보시면 NGS group에서는 비율이 1을 보이고 있습니다. Gs group에서는 이 비율이 0.95인데 이것은 레퍼런스 방법보다 FFQ로 측정했을 때 섭취량이 높게 나온다는 것을 의미합니다.

Table 3-2. Ratio of nutrient takes in validation studies of GS vs. NGS FFQs in women Nutrients No. of Studies GS Group NGS Group Intake Levels GS NGS Reference (A) FFQ (B) Ratio (B/A) Energy (kcal) 9 21 1699.9 1554.3 0.91† 1745.9 1916.2 1.10† Carbohydrate (g) 7 17 192.4 192.1 1 237.2 262.4 1.11† Protein (g) 68.2 60.2 0.88† 67.8 72.9 1.08 Fat (g) 8 19 66.8 54.8 0.82‡ 55.5 62.8 1.13 Cholesterol (mg) 4 16 323.3 285.9 0.88 235.3 246.9 1.05 Fiber (g) 6 14 15.7 17.8 1.14 17.4 20.8 1.21 Calcium (mg) 887 849.8 0.96 669.3 766.6 1.15‡ Vitamin C (mg) 13 92.5 102.9 1.11 110.5 150.3 1.36‡ Median 0.93 1.12 (Vit C excluded) 0.91 응답자가 여성일때 레퍼런스 방법 대비 FFQ 섭취량 비율입니다. 남성과 비교했을 때 여성은 두 그룹 간 비율의 격차가 더 컸는 데요, 성별의 고려 여부에 따라 여성이 더 큰 영향을 받는 것으로 보입니다.특히 여성의 NGS group에서는 7개 영양소 모두 FFQ로 측정했을 때 섭취량을 과대 평가 하는것으로 나타났습니다.

3. Meta-analysis of meat intake and colon cancer Red meat intake (Subject: Combined) 이 표는 WCRF에서 2007년, 2011년에 출간한 보고서에 실린 대장암과 관련된 식이요인들을 보여주고 있습니다. 대장암과 관련된 식이요인 중에서 GS group과 NGS group간 적절한 비교를 위해 해당 연구가 4개 이상인 식이요인 4가지를 선정하였습니다.

Processed meat intake (Subject: Combined) 이 표는 WCRF에서 2007년, 2011년에 출간한 보고서에 실린 대장암과 관련된 식이요인들을 보여주고 있습니다. 대장암과 관련된 식이요인 중에서 GS group과 NGS group간 적절한 비교를 위해 해당 연구가 4개 이상인 식이요인 4가지를 선정하였습니다.

Conclusion of the study Most of FFQs are developed without proper gender consideration. GS-FFQs performed better in validation studies Nutrient intakes in women tend to be overestimated with NGS-FFQs Relationship with red meat intake and colon cancer was detected only in studies which used GS-FFQs Gender considerations will provide knowledge applicable for all population

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