International audience ; Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers.Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.
International audience ; Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers.Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.
International audience ; Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers.Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.
Background: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. Methods: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. Findings: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75–84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28–4·7) and 7·0% (1·2–13·0). Interpretation: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. Funding: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.
Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). Methods: Participants were 30,785 dementia-free individuals aged 55–103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.
BACKGROUND: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). METHODS: Participants were 30,785 dementia-free individuals aged 55–103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. RESULTS: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. CONCLUSION: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.
Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). Methods: Participants were 30, 785 dementia-free individuals aged 55–103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.
Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
Researchers increasingly use meta-analysis to synthesize the results of several studies in order to estimate a common effect. When the outcome variable is continuous, standard meta-analytic approaches assume that the primary studies report the sample mean and standard deviation of the outcome. However, when the outcome is skewed, authors sometimes summarize the data by reporting the sample median and one or both of (i) the minimum and maximum values and (ii) the first and third quartiles, but do not report the mean or standard deviation. To include these studies in meta-analysis, several methods have been developed to estimate the sample mean and standard deviation from the reported summary data. A major limitation of these widely used methods is that they assume that the outcome distribution is normal, which is unlikely to be tenable for studies reporting medians. We propose two novel approaches to estimate the sample mean and standard deviation when data are suspected to be non-normal. Our simulation results and empirical assessments show that the proposed methods often perform better than the existing methods when applied to non-normal data. ; anadian Institutes of Health Research (CIHR) KRS-134297 Fonds de recherche du Quebec -Sante (FRQS) Canadian Institutes of Health Research (CIHR) Canadian Institutes of Health Research (CIHR) FRQS Masters Training Awards Vanier Canada Graduate Scholarship FRQS Postdoctoral Training Fellowship Research Institute of the McGill University Health Centre G.R. Caverhill Fellowship from the Faculty of Medicine, McGill University Cumming School of Medicine, University of Calgary Alberta Health Services through the Calgary Health Trust Hotchkiss Brain Institute Senior Health Scholar award from Alberta Innovates Health Solutions Health Research Council of New Zealand Lundbeck International Tehran University of Medical Sciences M-288 Department of Education, National Institute on Disability and Rehabilitation Research, Spinal Cord Injury Model Systems: University of Washington H133N060033 Baylor College of Medicine H133N060003 University of Michigan System H133N060032 National Health and Medical Research Council of Australia 1002160 Safe Work Australia Australian Research Council FT130101444 European Foundation for Study of Diabetes Chinese Diabetes Society Lilly Foundation Asia Diabetes Foundation Liao Wun Yuk Diabetes Memorial Fund United States National Institute of Mental Health (NIMH) grant 5F30MH096664 United States Department of Health & Human Services National Institutes of Health (NIH) - USA United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH Fogarty International Center (FIC) United States Department of Health & Human Services National Institutes of Health (NIH) - USA National Cancer Center United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) NIH Office of Research for Women's Health through the Fogarty Global Health Fellows Program Consortium 1R25TW00934001 American Recovery and Reinvestment Act United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) R24MH071604 / R34 MH072925/ K02 MH65919 / P30 DK50456 / R24 MH56858 / RO1 MH073687 /RO1-MH069666 / R34MH084673 /R24 MH071604 United States Department of Health & Human Services Centers for Disease Control & Prevention - USA R49 CE002093 St Anne's Community Services, Leeds, UK US National Center for Medical Rehabilitation Research RO1 HD39415 Federal Ministry of Education & Research (BMBF) 01GY1150 United States Department of Health & Human Services National Institutes of Health (NIH) - USA T37 MD001449 / T32 GM07356 Ohio Board of Regents Research and Development Administration Office, University of Macau MYRG2015-00109-FSS Federal Ministry of Education & Research (BMBF) 01 GD 9802/4 ; 01 GD 0101 Federation of German Pension Insurance Institute Federal Ministry of Education & Research (BMBF) Perpetual Trustees Flora and Frank Leith Charitable Trust Jack Brockhoff Foundation Grosvenor Settlement Sunshine Foundation Danks Trust Canadian Institutes of Health Research (CIHR) FRN 83518 Scleroderma Society of Canada Scleroderma Society of Ontario Scleroderma Society of Saskatchewan Sclerodermie Quebec Cure Scleroderma Foundation Inova Diagnostics Inc Euroimmun FRQS Canadian Arthritis Network Lady Davis Institute of Medical Research of the Jewish General Hospital, Montreal, QC FRQS Senior Investigator Award National Strategic Reference Framework European Union (EU) Greek Ministry of Education, Lifelong Learning and Religious Affairs (ARISTEIA-ABREVIATE) 1259 Ministry of Health, Labour and Welfare, Japan UK National Institute for Health Research under its Programme Grants for Applied Research Programme RP-PG-0606-1142 Canada Research Chair in Neurological Health Services Research AIHS Population Health Investigator Award National Health and Medical Research Council of Australia 1088313 Netherlands Organization for Health Research and Development 945-03-047 National Health Research Institutes - Taiwan NHRI-EX97-9706PI Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 49086 Reitoria de Pesquisa da Universidade de Sao Paulo 09.1.01689.17.7 Banco Santander 10.1.01232.17.9 Pfizer medical faculty of the University of Heidelberg, Germany 121/2000 Research University Grant Scheme from Universiti Putra Malaysia, Malaysia Postgraduate Research Student Support Accounts of the University of Auckland, New Zealand National Program for Centers of Excellence (PRONEX/FAPERGS/CNPq, Brazil) Pfizer US Pharmaceutical Inc. PQ-CNPq-2 301321/2016-7 Belgian Ministry of Public Health and Social Affairs Pfizer Ministry of Health, Italy UK National Health Service Lothian Neuro-Oncology Endowment Fund Universiti Sains Malaysia United States Department of Health & Human Services United States Health Resources & Service Administration (HRSA) R40MC07840 United States Department of Health & Human Services Agency for Healthcare Research & Quality R36 HS018246 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Center for Research Resources (NCRR) TL1 RR024135 University of Melbourne Hunter Medical Research Institute Innovatiefonds Zorgverzekeraars Netherlands Organization for Health Research and Development (ZonMw) Mental Health Program 100.003.005 100.002.021 Academic Medical Center/University of Amsterdam Fund for Innovation and Competitiveness of the Chilean Ministry of Economy, Development and Tourism, through the Millennium Scientific Initiative IS130005 US Department of Veteran Affairs US Department of Veteran Affairs United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) R01 HL079235 American Federation for Ageing Research Robert Wood Johnson Foundation (RWJF) Ischemia Research and Education Foundation
In: De Leoz , M L A , Duewer , D L , Fung , A , Liu , L , Yau , H K , Potter , O , Staples , G O , Furuki , K , Frenkel , R , Hu , Y , Sosic , Z , Zhang , P , Altmann , F , Gru Nwald-Grube , C , Shao , C , Zaia , J , Evers , W , Pengelley , S , Suckau , D , Wiechmann , A , Resemann , A , Jabs , W , Beck , A , Froehlich , J W , Huang , C , Li , Y , Liu , Y , Sun , S , Wang , Y , Seo , Y , An , H J , Reichardt , N C , Ruiz , J E , Archer-Hartmann , S , Azadi , P , Bell , L , Lakos , Z , An , Y , Cipollo , J F , Pucic-Bakovic , M , Štambuk , J , Lauc , G , Li , X , Wang , P G , Bock , A , Hennig , R , Rapp , E , Creskey , M , Cyr , T D , Nakano , M , Sugiyama , T , Leung , P K A , Link-Lenczowski , P , Jaworek , J , Yang , S , Zhang , H , Kelly , T , Klapoetke , S , Cao , R , Kim , J Y , Lee , H K , Lee , J Y , Yoo , J S , Kim , S R , Suh , S K , de Haan , N , Falck , D , Lageveen-Kammeijer , G S M , Wuhrer , M , Emery , R J , Kozak , R P , Liew , L P , Royle , L , Urbanowicz , P A , Packer , N H , Song , X , Everest-Dass , A , Lattová , E , Cajic , S , Alagesan , K , Kolarich , D , Kasali , T , Lindo , V , Chen , Y , Goswami , K , Gau , B , Amunugama , R , Jones , R , Stroop , C J M , Kato , K , Yagi , H , Kondo , S , Yuen , C T , Harazono , A , Shi , X , Magnelli , P E , Kasper , B T , Mahal , L , Harvey , D J , O'Flaherty , R , Rudd , P M , Saldova , R , Hecht , E S , Muddiman , D C , Kang , J , Bhoskar , P , Menard , D , Saati , A , Merle , C , Mast , S , Tep , S , Truong , J , Nishikaze , T , Sekiya , S , Shafer , A , Funaoka , S , Toyoda , M , de Vreugd , P , Caron , C , Pradhan , P , Tan , N C , Mechref , Y , Patil , S , Rohrer , J S , Chakrabarti , R , Dadke , D , Lahori , M , Zou , C , Cairo , C , Reiz , B , Whittal , R M , Lebrilla , C B , Wu , L , Guttman , A , Szigeti , M , Kremkow , B G , Lee , K H , Sihlbom , C , Adamczyk , B , Jin , C , Karlsson , N G , Örnros , J , Larson , G , Nilsson , J , Meyer , B , Wiegandt , A , Komatsu , E , Perreault , H , Bodnar , E D , Said , N , Francois , Y N , Leize-Wagner , E , Maier , S , Zeck , A , Heck , A J R , Yang , Y , Haselberg , R , Yu , Y Q , Alley , W , Leone , J W , Yuan , H & Stein , S E 2020 , ' NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies : Comparison of Results from Diverse Analytical Methods ' , MCP : Molecular & cellular proteomics , vol. 19 , no. 1 , pp. 11-30 . https://doi.org/10.1074/mcp.RA119.001677
Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
Glycosylation is a topic of intense current interest in the development of biopharmaceuticals since it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.