Mbs reviews vitamin b12 testing report february 2014 table of contents section Page

Purpose of the review

This Review Report outlines the rationale behind conducting the review of the MBS items relevant to vitamin B12 testing services (refer to Appendix 3 for MBS item descriptor) and the process undertaken to identify and appraise the available information on the MBS item to ensure that it reflects contemporary evidence, improves health outcomes for patients, and represents value for money.

Vitamin B12 testing

Vitamin B12, also called cobalamin, is a water soluble vitamin that plays a fundamental role in the normal functioning of the brain and nervous system, and for the formation of blood. Vitamin B12 deficiency can be the result of nutritional deficiency, increased requirements, impaired absorption, or other gastrointestinal causes. Deficiency is associated with a wide spectrum of haematologic, neurologic and psychiatric disorders that can often be reversed by early diagnosis and prompt treatment. The diagnosis of vitamin B12 deficiency has traditionally been based on measuring total serum levels of vitamin B12.

Concerns about vitamin B12 testing

Concerns raised with vitamin B12 testing relate to the increase in the number of claims and benefits paid for MBS item numbers 66599 and 66602. Given the widespread testing of vitamin B12/folate by general practitioners, this review is focused on identifying appropriate clinical indications for medically necessary vitamin B12 testing, and determining whether testing should be limited to certain high risk groups.

Review methodology

The review methodology comprised of consulting with key stakeholders; developing a review protocol, which outlined the detailed review methodology (including specifying the key clinical/research questions for the systematic review, preparing the clinical flowcharts, and documenting the economic analysis strategy); analysing secondary data sources (Medicare Australia); conducting an evidence-based systematic literature review on vitamin B12; and undertaking an assessment and analysis of the evidence to draw conclusions in relation to the clinical/research questions.

Stakeholder consultation

Stakeholder engagement is a pivotal part of the MBS Reviews process, particularly as feedback helps inform Review Reports. During the review process, stakeholders were informed of the progress of the MBS items being considered. This included ensuring that relevant documents were released for public consultation at the appropriate time and that comments were incorporated into the review process.
As part of the MBS Review process, the Department established a Review Consultation Committee (RCC). The RCC is a time-limited committee of nominated representatives, established to provide advice to the Department. A list of RCC members is found at Appendix 2.

Summary of findings

Current usage of vitamin B12 and/or folate testing services in Australia

Over the past 10 years, the number of claims for MBS item 66599 has more than doubled (+119%) from 282,531 in 2003/04 to 618,744 in 2012/13. Over the same timeframe the number of claims for MBS item 66602 has had an even greater increase (+307%) from 522,980 to 2,129,051. The increase in benefits paid for both items reflects the increase in claims (+120% for item 66599 and +309% for item 66602). While total benefits increased significantly, the proportion of benefits paid to each state and territory remained relatively constant over the ten-year period. The highest proportion of benefits paid over the past ten years was in New South Wales (34% and 38% of total benefits for 66599 and 66602, respectively), followed by Victoria (30% for 66599 and 28% for 66602).
An analysis was conducted of the number of services per capita (i.e. per 100,000 population). Across Australia, there were 2,666 claims for item 66599 per 100,000 people enrolled in Medicare in 2012/13 and 9,172 claims per 100,000 for item 66602. South Australia had the highest per capita rate of claiming for item 66599, while the Northern Territory had the lowest. For item 66602, the highest number of claims per capita was for NSW and Victoria, while Tasmania had the lowest.
MBS item numbers 66599 and 66602 are claimed by both males and females; however, females had a higher number of tests at all ages, except in the youngest age category (< 5 years). Females also had a steeper increase in testing volume than males, with the largest difference between genders in the 15-24 and 25-34 year age groups. For item 66599, the number of tests being performed in people aged 45 years and over was 76% for males and 64% for females. For item 66602, 71% of claims for males were aged 45 years and over versus 60% for females.
For both MBS items, there was an increase in the overall number of patients tested between 2008/09 and 2012/13. However, there was very little change in the proportion of patients receiving either one test per year (approximately 91%), two tests per year (approximately 8%), or three or more tests per year (approximately 1%). These data suggest that the majority of vitamin B12/folate testing services are being undertaken for the purposes of screening/testing rather than monitoring.
Over the five-year time period from 2008/09 to 2012/13, there were no material changes in the pattern of requesting providers. General practitioners and other medical practitioners accounted for approximately 71% and 67% of all providers requesting item 66599 and item 66602, respectively. Approximately 14% of providers requesting vitamin B12/folate testing were internal medicine consultant physicians. There was a large variety of other providers requesting services, but they each accounted for less than 4% of provider counts.
For both items, there was an increase over the period 2008/09 to 2012/13 in the overall number of providers requesting vitamin B12/folate testing. The majority of providers (97% and 88% for item 66599 and 66602, respectively) requested 100 or fewer tests per year. There were a small number of providers that requested more than 400 tests per year (601 providers in 2012/13).

Clinical guidance on vitamin B12 testing

The MBS data indicates that the majority of requests for vitamin B12 testing are initiated by general practitioners and other medical practitioners. However, no relevant Australian guidelines were identified in the literature search. Four international guidelines on diagnosing vitamin B12 deficiency were identified (two from the UK and two from Canada), with limited evidence supporting the recommendations. One 2012 guideline from the British Columbia Medical Association and Ministry of Health, Canada, concluded that routine screening for vitamin B12 deficiency is not recommended. No other guidelines made recommendations relating to routine screening.
Several guidelines recommend that patients with symptoms or signs of vitamin B12 deficiency anaemia (macrocytic anaemia or macrocytosis) and patients with suspected neuropsychiatric abnormalities should be tested for vitamin B12 deficiency. Other populations where testing could be considered include the elderly, long-term vegans, people on drugs that interfere with vitamin absorption (long-term H2 receptor antagonists or proton pump inhibitors or metformin) and patients with inflammatory bowel disease, gastric or small intestine resection.
The frequency with which patients should be tested was not addressed in the guidelines. However, a 2005 best practice review from the UK stated that there is no obvious merit in repeating vitamin B12 measurements in patients with macrocytic anaemia, macrocytosis, or patients with specific neuropsychiatric abnormalities, unless lack of compliance is suspected or anaemia recurs.
Only one guideline specified a methodology for vitamin B12 measurement. A practice parameter, published by the American Academy of Neurology recommended using serum vitamin B12 level with metabolites (MMA and Hcy) in the evaluation of vitamin B12 deficiency in all patients with distal symmetric neuropathy. None of the guidelines advised on the diagnostic accuracy of the different tests used to assess vitamin B12 deficiency or advised on which metabolite is the best indicator of vitamin B12 status. This may be attributed to the lack of a gold reference standard for vitamin B12.
In July 2013, Health Quality Ontario released recommendations on a variety of common clinical tests, including vitamin B12. On the basis of their rapid review which found that serum vitamin B12 test has low diagnostic accuracy, it was recommended that vitamin B12 testing is removed from the Ontario laboratory requisition form.

Relationship between testing for vitamin B12 levels and health outcomes

No definitive conclusions can be drawn about the effectiveness of vitamin B12 testing since no prospective comparative trials have been conducted to directly assess the impact of testing on health outcomes in healthy populations or in patients with chronic disease associated with vitamin B12 deficiency.
No trials designed to directly measure the risks or harms associated with vitamin B12 testing were identified. However, vitamin B12 testing relies on a blood draw, which is a safe procedure. Vitamin B12 supplements are generally considered safe when taken in amounts that are not higher than the recommended dietary allowance. Thus, it is likely that the consequences of inaccurate or inappropriately interpreted serum vitamin B12 test results, such as a false positive, are relatively small.
It is unknown whether measurement of vitamin B12 levels is cost-effective. No costing studies or economic analyses relating to vitamin B12 testing were identified.

Diagnostic performance of vitamin B12 tests

There is currently no consensus on the best method to estimate vitamin B12 deficiency and vitamin B12 status. A 2011 systematic review evaluated the diagnostic accuracy of serum B12 tests using MMA, Hcy and holoTC as reference standards. The review noted that measurement of total serum vitamin B12 is widely used as a standard screening test; however, the evidence base for the diagnostic accuracy of this test is low, due to the lack of a gold reference standard. From the available evidence, diagnosis of conditions amenable to vitamin B12 supplementation on the basis of serum vitamin B12 levels alone cannot be considered a reliable approach to investigating suspected vitamin B12 deficiency. Across clinical indications, practice settings and different methodologies, the authors of the review found low levels of test sensitivity and, to a lesser extent, specificity. The authors of the review also demonstrated that the transition from older assay methods to newer technologies, such as chemiluminescence, was not associated with improved diagnostic accuracy. The lack of a gold standard also hampers the ability to compare the various markers of B12 deficiency (MMA, Hcy, and holoTC) with each other.
There is some evidence that holoTC has comparable or better diagnostic accuracy to that of total serum vitamin B12. However, there is insufficient evidence to establish holoTC testing as an alternative to either total serum vitamin B12, or levels of MMA or homocysteine in the diagnosis of vitamin B12 deficiency.