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

Abstract

This population-based cohort study evaluated how often intramuscular vitamin B₁₂ was prescribed to Canadian elderly patients when not medically necessary.

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.

Table. Characteristics of Patients Who Received an Intramuscular Vitamin B₁₂ Prescription^a.

Characteristics	Patients, No. (%) (n = 146 850)
Age, y
Mean (SD)	76.5 (8.1)
Median (IQR) [range]	76 (14.0) [65-110]
Age categorized, y
65-69	36 866 (25.1)
70-74	28 196 (19.2)
75-79	28 014 (19.1)
80-84	26 055 (17.7)
85-89	18 384 (12.5)
≥ 90	9335 (6.4)
Sex
Male	60 037 (40.9)
Female	86 813 (59.1)
Location of residence
Rural	12 692 (8.6)
Urban	124 359 (84.7)
Neighborhood income quintile
Q1 (lowest)	32 905 (22.4)
Q2	32 230 (22.0)
Q3	29 828 (20.3)
Q4	27 679 (18.9)
Q5 (highest)	23 573 (16.1)
Comorbidities
Crohn disease, ulcerative colitis, and malabsorption	9309 (6.3)
Pernicious anemia	40 908 (27.9)
ADG comorbidity classification scheme
Low scores (0-5)	24 135 (16.4)
Moderate scores (6-9)	51 920 (35.4)
High scores (≥ 10)	70 795 (48.2)
Dementia	14 844 (10.1)
Neuropathy	2471 (1.7)

Abbreviations: ADG, Aggregated Diagnosis Group; IQR, interquartile range.

^a Some totals may not add up owing to missing data.

Figure. Prevalence of Inappropriate Intramuscular Vitamin B₁₂ Prescribing in Ontario From January 1, 2011, to September 30, 2015.

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.