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Figure.  Prevalence of Inappropriate Intramuscular Vitamin B12 Prescribing in Ontario From January 1, 2011, to September 30, 2015
Prevalence of Inappropriate Intramuscular Vitamin B12 Prescribing in Ontario From January 1, 2011, to September 30, 2015
Table.  Characteristics of Patients Who Received an Intramuscular Vitamin B12 Prescriptiona
Characteristics of Patients Who Received an Intramuscular Vitamin B12 Prescriptiona
1.
Chan  CQH, Low  LL, Lee  KH.  Oral vitamin B12 replacement for the treatment of pernicious anemia.  Front Med (Lausanne). 2016;3(38):38.PubMedGoogle Scholar
2.
van Walraven  CG, Naylor  CD.  Use of vitamin B12 injections among elderly patients by primary care practitioners in Ontario.  CMAJ. 1999;161(2):146-149.PubMedGoogle Scholar
3.
Graham  ID, Jette  N, Tetroe  J, Robinson  N, Milne  S, Mitchell  SL.  Oral cobalamin remains medicine’s best kept secret.  Arch Gerontol Geriatr. 2007;44(1):49-59. doi:10.1016/j.archger.2006.02.003PubMedGoogle ScholarCrossref
4.
Tilburt  JC, Wynia  MK, Sheeler  RD,  et al.  Views of US physicians about controlling health care costs.  JAMA. 2013;310(4):380-388. doi:10.1001/jama.2013.8278PubMedGoogle ScholarCrossref
5.
Devalia  V, Hamilton  MS, Molloy  AM; British Committee for Standards in Haematology.  Guidelines for the diagnosis and treatment of cobalamin and folate disorders.  Br J Haematol. 2014;166(4):496-513. doi:10.1111/bjh.12959PubMedGoogle ScholarCrossref
6.
Kwong  JC, Carr  D, Dhalla  IA, Tom-Kun  D, Upshur  RE.  Oral vitamin B12 therapy in the primary care setting: a qualitative and quantitative study of patient perspectives.  BMC Fam Pract. 2005;6(1):8. doi:10.1186/1471-2296-6-8PubMedGoogle ScholarCrossref
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    Research Letter
    July 15, 2019

    Prevalence of Inappropriateness of Parenteral Vitamin B12 Administration in Ontario, Canada

    Author Affiliations
    • 1Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    • 2Division of Medical Oncology & Hematology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
    • 3Department of Laboratory Medicine & Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
    • 4Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    • 5ICES, Toronto, Ontario, Canada
    JAMA Intern Med. 2019;179(10):1434-1436. doi:10.1001/jamainternmed.2019.1859

    Randomized clinical trials demonstrate that treating vitamin B12 (cobalamin, or hereinafter B12) deficiency with oral supplementation substantially increases serum B12 levels compared with intramuscular injections, with no difference in hematologic or neuropsychiatric outcomes.1 Despite this, some primary care physicians still inappropriately administer B12 injections to elderly patients.2 To our knowledge, there is no published literature characterizing prescribing patterns of intramuscular B12 using laboratory data to document patient serum levels. In this study, we assessed the prevalence of inappropriate B12 supplementation using population-based databases and estimated the associated cost.

    Methods

    We performed a population-based, retrospective cohort study using health system administrative databases within ICES, formerly the Institute for Clinical Evaluative Sciences, in Ontario, Canada. Data sets were linked using unique, encoded identifiers and analyzed at ICES. All persons 65 years or older who received at least 1 intramuscular B12 prescription from January 1, 2011, to September 30, 2015 (data on B12 levels were not available until January 1, 2010), were included. Data were analyzed from July 26, 2018, to November 22, 2018. The primary outcome was the proportion of inappropriate B12 supplementation, defined as persons with either a normal serum B12 level (≥ 221 pmol/L), or without a documented B12 level in the 12 months prior to their first intramuscular B12 prescription. Vitamin B12 supplementation was considered appropriate when persons had at least 1 documented level of marginal B12 deficiency (≤ 221 pmol/L) in the year prior to receiving their first B12 injection. Annual cost of inappropriate, once-monthly injections was estimated in Canadian dollars using the amount paid for a physician visit ($33.70), intramuscular injection ($3.89), and prescription cost ($6.74). Sunnybrook Health Sciences Centre’s research ethics board approved this study and waived patient written informed consent for deidentified data.

    Results

    A total of 405 469 intramuscular B12 prescriptions were dispensed to 146 850 persons (Table); the majority (63.7%; n = 93 615) of these were inappropriate (Figure). In the year preceding persons’ first intramuscular B12 injection, 25.5% (n = 37 487) had a normal B12 level, whereas 38.2% (n = 56 128) did not have a B12 level documented. Findings were similar over a 24-month look-back period (data not shown). Only 43.1% (n = 24 175) of the 56 128 people without a B12 level documented in the year preceding their first B12 prescription had ever had one measured. This was performed a mean (SD) 1033.5 (488.1) days prior to their first prescription (range, 366-2801 days). Only 35.3% (n = 8539) of these 24 175 persons had marginally deficient B12 levels. The estimated annual cost of inappropriate B12 prescribing was $45.6 million, assuming a 64% inappropriate prescription rate. Finally, only 1.7% (n = 2498) of persons prescribed intramuscular B12 demonstrated any deficiency with a malabsorptive indication.

    Discussion

    Most parenteral B12 in Ontario was prescribed to persons without evidence of deficiency in the year preceding their first B12 prescription. Potential drivers of this include patient demands and poor physician awareness of the evidence informing B12 supplementation.3,4 It is also questionable whether parenteral supplementation is required over oral supplementation because oral B12 raises B12 serum levels and improves sequelae of deficiency as well as, if not better than, intramuscular B12, even for pernicious anemia.1 Plausible reasons why physicians prefer parenteral B12 include low quality of evidence supporting oral B12, society guidelines recommending intramuscular B12 for all patients, poor physician understanding of how to prescribe oral B12, and physician misperception that patients prefer parenteral over oral B12.1,3,5,6

    Our study’s limitations include only looking 2 years before a person’s first documented prescription; using this abridged period might have misclassified persons undergoing treatment for chronic B12 deficiency, and so with normal B12 levels, as receiving inappropriate supplementation. We were also unable to access information on oral B12, and could not understand why B12 was prescribed without laboratory evidence of deficiency. Further studies should examine this issue, to inform quality improvement initiatives aimed at reducing this unnecessary care.

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    Article Information

    Accepted for Publication: April 20, 2019.

    Published Online: July 15, 2019. doi:10.1001/jamainternmed.2019.1859

    Correction: This article was corrected on August 26, 2019, to fix errors in the dates of data analysis in the Methods section.

    Corresponding Author: William K. Silverstein, MD, Core Internal Medicine, Faculty of Medicine, University of Toronto, Department of Medicine, University Health Network, 200 Elizabeth St, Eaton Building 14-217, Toronto, Ontario M5G 2C4, Canada (william.silverstein@mail.utoronto.ca).

    Author Contributions: Drs Cheung, Croxford, and Dharma had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Lin and Cheung contributed equally as co–senior authors to this study.

    Study concept and design: Silverstein, Lin, Dharma, Cheung.

    Acquisition, analysis, or interpretation of data: Lin, Dharma, Croxford, Earle, Cheung.

    Drafting of the manuscript: Silverstein, Cheung.

    Critical revision of the manuscript for important intellectual content: Lin, Dharma, Croxford, Earle, Cheung.

    Statistical analysis: Dharma, Croxford, Cheung.

    Obtained funding: Cheung.

    Administrative, technical, or material support: Silverstein, Dharma, Cheung.

    Study supervision: Lin, Cheung.

    Conflict of Interest Disclosures: Dr Lin reported that she was a consultant for Pfizer and that she was on the advisory board of Amgen. No other disclosures were reported.

    Funding/Support: This study was supported by research funding from the Sunnybrook Hospital Foundation. This study was also supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC).

    Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Disclaimer: No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this material are based on data and information compiled and provided by the Canadian Institute for Health Information (CIHI). The opinions, results and, conclusions reported in this article are those of the authors and are independent from the funding sources and CIHI.

    Additional Contributions: We thank IMS Brogan Inc for use of their Drug Information Database. No contributors received compensation for their assistance.

    References
    1.
    Chan  CQH, Low  LL, Lee  KH.  Oral vitamin B12 replacement for the treatment of pernicious anemia.  Front Med (Lausanne). 2016;3(38):38.PubMedGoogle Scholar
    2.
    van Walraven  CG, Naylor  CD.  Use of vitamin B12 injections among elderly patients by primary care practitioners in Ontario.  CMAJ. 1999;161(2):146-149.PubMedGoogle Scholar
    3.
    Graham  ID, Jette  N, Tetroe  J, Robinson  N, Milne  S, Mitchell  SL.  Oral cobalamin remains medicine’s best kept secret.  Arch Gerontol Geriatr. 2007;44(1):49-59. doi:10.1016/j.archger.2006.02.003PubMedGoogle ScholarCrossref
    4.
    Tilburt  JC, Wynia  MK, Sheeler  RD,  et al.  Views of US physicians about controlling health care costs.  JAMA. 2013;310(4):380-388. doi:10.1001/jama.2013.8278PubMedGoogle ScholarCrossref
    5.
    Devalia  V, Hamilton  MS, Molloy  AM; British Committee for Standards in Haematology.  Guidelines for the diagnosis and treatment of cobalamin and folate disorders.  Br J Haematol. 2014;166(4):496-513. doi:10.1111/bjh.12959PubMedGoogle ScholarCrossref
    6.
    Kwong  JC, Carr  D, Dhalla  IA, Tom-Kun  D, Upshur  RE.  Oral vitamin B12 therapy in the primary care setting: a qualitative and quantitative study of patient perspectives.  BMC Fam Pract. 2005;6(1):8. doi:10.1186/1471-2296-6-8PubMedGoogle ScholarCrossref
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