Alfonso Iorio, MD, PhD; Jeffrey S. Stonebraker, PhD; Hervé Chambost, MD; Michael Makris, MD; Donna Coffin, MSc; Christine Herr, MPH; Federico Germini, MD, MSc; for the Data and Demographics Committee of the World Federation of Hemophilia *
Note: This work did not receive any financial support. All authors are members of the Data and Demographics Committee of the World Federation of Hemophilia or work for the agency. None of them declared any conflict of interest in relation to the present work. The findings and conclusions in this report are those of the authors.
Acknowledgment: The authors thank the members of the Data and Demographics Committee and the Medical Advisory Board of the World Federation of Hemophilia for their comments; they also thank Ben Palmer (United Kingdom Haemophilia Centre Doctors' Organisation) for kindly providing prevalence-at-birth data for the United Kingdom.
Disclosures: Drs. Iorio and Germini report that their institution, McMaster University, has received in the past 3 years project-based funding via research or service agreements with Bayer, CSL, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Sobi, and Takeda/Shire (formerly Baxter and Baxalta). Dr. Iorio is or has been the local principal investigator for clinical research studies in the patients with hemophilia sponsored by Octapharma, Pfizer, and Roche. Neither Dr. Iorio nor Dr. Germini received any personal honorarium or compensation for any of the aforementioned activities. Dr. Makris reports personal fees from Novo Nordisk, Pfizer, Shire, Freeline, Bioverativ, Catalyst, and Spark. He is project lead for the European Haemophilia Safety Surveillance scheme, which receives funding from Bayer, Biotest, BPL, CSL Behring, Grifols, Novo Nordisk, Pfizer, Roche, Sobi, Shire (Takeda), Kedrion, and Octapharma; this is outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-1208.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement: Study protocol: Not applicable. Statistical code: Available on request from Dr. Germini (e-mail, firstname.lastname@example.org). Data set: Available on request and signature of a confidentiality agreement (email@example.com).
Corresponding Author: Jeffrey S. Stonebraker, PhD, North Carolina State University, Department of Business Management, Poole College of Management, Raleigh, NC 27695; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Iorio: Department of Health Research Methods, Evidence, and Impact, McMaster University, CRL 140, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
Dr. Stonebraker: North Carolina State University, Department of Business Management, Poole College of Management, Raleigh, NC 27695.
Dr. Chambost: Hôpital de la Timone, 278 Rue Saint-Pierre, 13005 Marseille, France.
Dr. Makris: Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom.
Dr. Coffin and Ms. Herr: World Federation of Hemophilia, 1425 Boulevard René-Lévesque Ouest, Bureau 1200, Montréal, Québec H3G 1T7, Canada.
Dr. Germini: Department of Health Research Methods, Evidence, and Impact, McMaster University, CRL 125, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
Author Contributions: Conception and design: A. Iorio, J.S. Stonebraker, M. Makris.
Analysis and interpretation of the data: A. Iorio, J.S. Stonebraker, H. Chambost, F. Germini.
Drafting of the article: A. Iorio, J.S. Stonebraker, M. Makris.
Critical revision of the article for important intellectual content: J.S. Stonebraker, H. Chambost, M. Makris, D. Coffin, F. Germini.
Final approval of the article: A. Iorio, J.S. Stonebraker, H. Chambost, M. Makris, D. Coffin, C. Herr, F. Germini.
Provision of study materials or patients: M. Makris.
Statistical expertise: A. Iorio, J.S. Stonebraker, F. Germini.
Administrative, technical, or logistic support: J.S. Stonebraker, D. Coffin, C. Herr.
Collection and assembly of data: A. Iorio, J.S. Stonebraker, M. Makris, D. Coffin, C. Herr.
The large observed variability in hemophilia prevalence prevents robust estimation of burden of disease.
To estimate the prevalence and prevalence at birth of hemophilia and the associated life expectancy disadvantage.
Random-effects meta-analysis of registry data.
Australia, Canada, France, Italy, New Zealand, and the United Kingdom.
Male patients with hemophilia A or B.
Prevalence of hemophilia as a proportion of cases to the male population, prevalence of hemophilia at birth as a proportion of cases to live male births by year of birth, life expectancy disadvantage as a 1 − ratio of prevalence to prevalence at birth, and expected number of patients worldwide based on prevalence in high-income countries and prevalence at birth.
Prevalence (per 100 000 males) is 17.1 cases for all severities of hemophilia A, 6.0 cases for severe hemophilia A, 3.8 cases for all severities of hemophilia B, and 1.1 cases for severe hemophilia B. Prevalence at birth (per 100 000 males) is 24.6 cases for all severities of hemophilia A, 9.5 cases for severe hemophilia A, 5.0 cases for all severities of hemophilia B, and 1.5 cases for severe hemophilia B. The life expectancy disadvantage for high-income countries is 30% for hemophilia A, 37% for severe hemophilia A, 24% for hemophilia B, and 27% for severe hemophilia B. The expected number of patients with hemophilia worldwide is 1 125 000, of whom 418 000 should have severe hemophilia.
Details were insufficient to adjust for comorbid conditions and ethnicity.
The prevalence of hemophilia is higher than previously estimated. Patients with hemophilia still have a life expectancy disadvantage. Establishing prevalence at birth is a milestone toward assessing years of life lost, years of life with disability, and burden of disease.
Iorio A, Stonebraker JS, Chambost H, et al, for the Data and Demographics Committee of the World Federation of Hemophilia. Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries. Ann Intern Med. 2019;171:540–546. [Epub ahead of print 10 September 2019]. doi: https://doi.org/10.7326/M19-1208
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Published: Ann Intern Med. 2019;171(8):540-546.
Published at www.annals.org on 10 September 2019
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