Comparing costs of intramuscular and oral vitamin B₁₂ administration in primary care: A cost-minimization analysis

Abstract

Objective: To establish whether savings could be made by changing patients from intramuscular to high doses of oral vitamin B₁₂ in primary care without compromising their wellbeing. Methods: Cost-minimization analysis from a UK perspective, using secondary data obtained from the literature available and expert opinion. Results: The cost of the resources used to treat patients with vitamin B₁₂ deficiency with intramuscular vitamin B₁₂ was calculated as between £55.99 (€83.1) and £99.99 (€148.5) per year. The cost of treating patients with high doses of oral vitamin B₁₂ during the first year was between £125.55 (€186.5) and £248.55 (€369.1). However, once patients receiving intramuscular treatment had been converted to oral treatment, or in new patients treated orally from the outset, the cost was £35.55 per year (€52.8). One variable, home visits, had a high impact on the calculations.

Conclusion: Switching patients with vitamin B₁₂ deficiency from intramuscular to high-dose oral therapy and treating patients newly diagnosed with vitamin B₁₂ deficiency with oral vitamin B₁₂ from the outset could save resources in the medium and long term, and in newly diagnosed patients. Savings would come particularly in the form of nursing time.

• Cobalamin
• cost minimization
• pernicious anaemia
• vitamin B12

Introduction

Vitamin B₁₂ (cobalamin) was first isolated in 1948 [1], [2] and has since been widely used for the treatment of vitamin B₁₂ deficiency. The true prevalence of vitamin B₁₂ deficiency in the general population is unknown, but the condition is common, especially amongst the elderly, where prevalences as high as 13% have been reported [3], [4]. During the last half century, most vitamin B₁₂-deficient individuals in the UK and other countries have been managed with intramuscular vitamin B₁₂, despite several case-control and case-series studies that have since demonstrated the efficacy and effectiveness of the oral route [5–10]. Intramuscular injections are a “considerable source of work” for healthcare professionals [11]. Intramuscular administration often involves a special trip to a health facility or a home visit by a health professional, with the associated costs that this entails [12]. Archie Cochrane, working in South Wales, was one of the first to identify that substantial financial savings could be made from more evidence-based prescribing of vitamin B₁₂. His focus was on excessive prescription of intramuscular vitamin B₁₂[13]. More recently, a Canadian study estimated that converting patients aged over 65 years from intramuscular vitamin B₁₂ to an oral form could save between $2.9 (£1.26, €1.9) and $17.6 (£7.65, €11.4) million over 5 years in Ontario alone [14]. We conducted an economic evaluation, using cost-minimization analysis, to determine whether any saving could be made by switching patients from intramuscular to high doses of oral vitamin B₁₂. We investigated implications in the UK using secondary data obtained from the current literature available and expert opinion.

Methods

Health economic analysis was used to identify, measure and value the resources used with the current treatment of vitamin B₁₂ deficiency with intramuscular vitamin B₁₂. How those resources might change if patients were to be treated with high doses of oral vitamin B₁₂ was examined, to establish whether switching to the oral regime could make savings.

A cost-minimization analysis approach was selected because we identified evidence from a systematic review we conducted that the effectiveness of both intramuscular and oral vitamin B₁₂ treatments is similar, and they have similar consequences, adverse effects and compliance [15]. We calculated costs using pounds sterling and a discount rate of 3.5%.

Data collection

Secondary data obtained from a literature review and expert opinion were used to determine the quantity of resources required in the treatment with intramuscular vitamin B₁₂.

Cost specifications

Two types of resources were identified: direct and indirect. Direct resources are the resources directly involved in the administration of intramuscular vitamin B₁₂. They include the cost of the drug (costs of the medication, the costs of laboratory monitoring and the costs of the syringe, needle and needle disposal) and the costs of drug administration (mainly the costs of nursing time, which in many cases will involve a home visit). Indirect resources are resources not directly attributable to the administration of intramuscular vitamin B₁₂. These resources include building maintenance, computer maintenance, gas and electricity, telephone and medical insurance. Other indirect resources more difficult to evaluate are the costs of productivity and production losses incurred by the patient and society, including time lost from work and lost wages, loss of leisure time, and time lost in travelling to the surgery.

Analysis

The cost of medication (intramuscular and oral vitamin B₁₂) was obtained from the British National Formulary [16] and prices in health shops and on the Internet. Opportunity costs of general practitioners’ (family physicians’), practice nurses’ and district nurses’ time were examined to calculate the costs of the consultations needed to administer intramuscular vitamin B₁₂. Income was used as a proxy for the value of general practitioners’ time, wages as proxy for the value of ancillary staff time, and market values as a proxy for costs of overheads [17]. Home visits were included as part of the costs of consultations (general practitioners’ and nursing time). Also taken into account were the initial extra costs likely to be incurred in converting patients from the intramuscular to the oral regime during the first year. This was considered to be a one-off spend that would involve physician visits (home visits when necessary) and laboratory tests: full blood count and serum vitamin B₁₂ levels. A cautious approach was adopted in assuming that three extra general practitioner visits and laboratory tests would be needed during the conversion period. Extra training for physicians may be required.

Small resources associated with the administration of intramuscular vitamin B₁₂ were excluded, e.g. needle disposal, room maintenance, electricity, heating. These resources are very difficult to disentangle from the overall costs of the normal running of a practice in primary care and would be very similar if patients take oral vitamin B₁₂. Other resources that were also excluded because we had no reason to presume they would differ between both modes of administering vitamin B₁₂ were costs for the patients and society, cost of managing adverse events, costs of non-compliance with tablets or injections, and cost of incomplete medical treatment.

For our sensitivity analysis, a combination of one-way sensitivity analysis and the extreme-scenario analysis was used. The variable thought to have the biggest impact on the study, i.e. generating the best and worse scenario (home visits), was given particular attention. The assumption was made that each patient on intramuscular vitamin B₁₂ would receive four injections of vitamin B₁₂ a year, as recommended by the British National Formulary, and each patient on oral treatment would take one tablet a day of oral vitamin B₁₂.

Results

The total costs for the UK for a year of intramuscular vitamin B₁₂ treatment were calculated as £9.84 (€14.6) per patient, and the theoretical cost to the National Health Service (NHS) for a year of high-dose oral vitamin B₁₂ treatment as £25.55 (€33.5) per patient. The cost of the consultations required to administer intramuscular vitamin B₁₂ was about £20 (€29.7), if done by a practice nurse, district nurse or general practitioner. If the consultation required a home visit, the consultation was much more expensive, ranging from £20 (€29.7) if done by a district nurse to £61 (€90.6) when performed by a general practitioner. The laboratory costs of monitoring patients on high doses of oral vitamin B₁₂ were the same as monitoring those on the intramuscular regime. The UK laboratory costs of the tests needed for this were £3 (€4.4) for a full blood count and £7 (€10.4) for measuring serum vitamin B₁₂ levels. These tests are usually requested once a year. When converting patients from intramuscular to oral vitamin B₁₂, the same monitoring tests would be necessary in the long term. However, during the first year, closer monitoring would be required to ensure compliance and response to the treatment. Assuming that three extra batches of blood tests would be necessary during the first year, the laboratory costs of converting patients would be £30 (€44.5) in the first year. The conversion costs would also include the costs of physician consultations. The consultations necessary in order to convert patients from intramuscular to high doses of oral vitamin B₁₂ would be carried out by general practitioners who would probably need to see these patients an extra three times a year. This would mean a cost of £60 (€89.1) a year if no home visits were involved and £183 (€271.8) if home visits were required on all three occasions.

During the first year of conversion from intramuscular to high doses of oral vitamin B₁₂, the oral regime was considerably more expensive. This was mainly due to the initial conversion costs required during this period. During the second year, once the conversion period had ended, the oral regime was cheaper than intramuscular treatment. This was mainly due to the decreased need for nursing and general practitioners’ time. These calculations were also valid for newly diagnosed patients with B₁₂ deficiency started on oral vitamin B₁₂ from the outset, as no conversion would be required (see Table I).

Table I.  Cost of vitamin B₁₂ replacement: first and second year.

Cost per year in £ (and €)	First year		Second year
	Intramuscular	Oral	Intramuscular	Oral
Medication	9.84 (14.6)	25.55 (37.9)	9.84 (14.6)	25.55 (37.9)
GP/nursing time	36–80 (53.5–118.8)	Included in conversion costs	36–80 (53.5–118.8)	—
Syringe and needle	0.15 (0.2)	—	0.15 (0.2)	—
Conversion costs	—	90–213 (133.7–316.3)	—	—
Laboratory monitoring	10 (14.8)	10 (14.8)	10 (14.8)	10 (14.8)
Total	55.99–99.99 (83.1–148.5)	125.55–248.55 (186.5–369.1)	55.99–99.99 (83.1–148.5)	35.55 (52.8)

The sensitivity analysis focused mainly on the cost of the home visits, as this had the biggest impact on the calculations. If it was assumed that all intramuscular injections were administered by a practice nurse in the primary-care premises, the cost in terms of nursing time would be £36 (€53.5) a year. If home visits by district nurses were required, the costs would increase to £80 (€118.8) a year. With oral treatment, home visits also had a big impact, but these were centred on the conversion period. If home visits were not required during the conversion period, the total cost per patient using oral vitamin B₁₂ in the first year would be £125.55 (€186.5). However, if home visits were required, this cost would increase to £248.55 (€391.1). In the second year, no home visits would be required in patients using the oral regime (see Table II).

Table II.  Costs of intramuscular and oral vitamin B₁₂ in the first and second year depending on whether home visits are required.

Cost per year in £ (and €)	First year			Second year
	Intramuscular	Oral	Difference	Intramuscular	Oral	Difference
No home visit	55.99 (83.1)	125.55 (186.5€)	69.56 (103.3)	55.99 (83.1)	35.55 (52.8)	−20.44 (30.3)
Home visit	99.99 (148.5)	248.55 (369.1€)	148.56 (220.6)	99.99 (148.5)	n.a. ^a	−64.44 (95.7)

^a No home visits required in the second year with oral vitamin B₁₂ treatment.

The costs of oral and intramuscular vitamin B₁₂ treatments were calculated in both cases at 1 and 2 years’ duration, making no difference when analysing the results taking discounting into account.

Discussion

This cost-minimization analysis suggests that changing the route of treatment of patients with vitamin B₁₂ deficiency from intramuscular to oral could save resources to the NHS. These savings would come mainly in the form of nursing time. The nursing time that could be freed by using the oral regime could be used in providing other services.

Initial conversion costs considerably increased the cost of switching patients to high-dose oral vitamin B₁₂. These costs were estimated to be between £90 (€133.7) and £213 (€316.3), but they are only applicable during the first year, and are not necessary in newly diagnosed patients started on oral treatment from the outset. The savings obtained by changing patients from intramuscular to oral vitamin B₁₂ would be obtained in the medium to long term. In the short term (2–3 years), because of the high conversion costs, oral vitamin B₁₂ would be more expensive than the intramuscular regime.

For newly diagnosed patients with vitamin B₁₂ deficiency, it would be considerably cheaper to use high doses of oral vitamin B₁₂ rather than intramuscular vitamin B₁₂.

The cost of the resources used to treat patients with vitamin B₁₂ deficiency with intramuscular vitamin B₁₂ was calculated as between £55.99 (€83.1) and £99.99 (€148.5) per year. The cost of treating patients with high doses of oral vitamin B₁₂ once they had been converted, or in new patients, was £35.55 (€52.8) per year.

Sensitivity analysis showed that the variable “home visit” had a higher impact on the oral regime because the initial conversion period required switching patients from intramuscular to oral vitamin B₁₂. After the initial conversion period, home visits only had an impact on the intramuscular regime. In this last scenario, even when we removed the costs of the home visits that could be associated with the intramuscular treatment, the oral treatment was still cheaper than the intramuscular (£35.55 [€52.8] versus £55.99 [€83.1]) because there is less need for nursing time.

It was assumed that three extra sets of blood tests and visits would be necessary during the first year to monitor conversion to oral vitamin B₁₂, but it could be argued that the efficacy of the oral regime has already been established, and the conversion from intramuscular to high doses of oral vitamin B₁₂ would not need this extra monitoring. This was a cautious approach, and, if fewer blood tests and visits, particularly home visits, were required, it would considerably reduce the costs of the oral treatment during the first year, making an even clearer case for the use of oral vitamin B₁₂.

In an attempt to minimize the limitations of this study, a sensitivity analysis was performed. However, a number of limitations still need to be recognized. Despite having apparently robust evidence though a systematic review and several case-control studies that the effectiveness of both intramuscular and oral vitamin B₁₂ treatments is for all intents and purposes clinically equivalent, the systematic review included just two randomized controlled trials [15]. The resource use was estimated using the authors’ experience in clinical practice, data obtained from experts in the field of vitamin B₁₂ deficiency, and the findings of our literature review. A health system perspective was adopted without taking into consideration patient-borne costs and the cost for society. It could be argued that, by switching to oral medication, the health service would be shifting costs to the patient. For example, not using a patient perspective has led to an underestimation of the cost savings made by using high doses of oral vitamin B₁₂ because, after the initial conversion period, fewer visits to the nurse (and therefore less travel and time) would be required with oral therapy. Another point open for discussion is the risk of non-compliance with the oral regime. It could be argued that with intramuscular injections it is easier to ensure compliance because nurses give the injections; with oral treatment, the compliance may decrease, as it is known that some patients do not take the tablets prescribed by their doctors. However, similarly, patients may not go to a health facility to receive their injections or they may receive the injection more often than required. Early studies of oral vitamin B₁₂ reported good compliance with the treatment, very similar to the intramuscular regime [10].

These findings could have widespread implications for service delivery in the UK and in Europe, as many primary-care practices manage vitamin B₁₂ replacement for a number of their patients. However, it is essential that the change in route of administration is acceptable to the patients receiving the treatment and their views are taken into account in making treatment choices and changes. We can learn from the Swedish experience where, in the last 40 years, a spontaneous change in prescription habits has occurred, and most patients requiring vitamin B₁₂ therapy are now routinely started on oral vitamin B₁₂[18], [19].

Conflict of interest

We have not received any commercial sponsorship for this study.