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

1.2 The clinical flowcharts

The clinical decision pathway that determines whether vitamin B12 testing should be undertaken is provided in Figure 1.3.

Figure 1.3: Clinical flow chart for vitamin B12 testing

2 REVIEW METHODOLOGY

The review methodology comprises an analysis of secondary data (e.g. MBS claims), a guideline concordance analysis, and a systematic literature review for clinical and economic evidence. This Chapter presents clinical research questions and the methodology used for each of these review components.

2.1 Secondary data analysis

Data from Medicare Australia were analysed to determine whether the existing MBS item numbers for vitamin B12 testing (66599 and 66602) are appropriate.

2.1.1 The research questions for the MBS analysis

The MBS data were examined to determine:

1. 
   Whether the existing MBS items for service (66599 and 66602), including the associated explanatory notes, are appropriate
   

1. 
   How frequent are the MBS item numbers under review claimed?
   
2. 
   Are there any age, sex, temporal or geographic trends associated with usage of these item numbers?
   
3. 
   Are the Medicare claims data consistent with trends in the incidence/prevalence of the conditions/diseases being addressed by the services?
   
4. 
   What is the frequency of vitamin B12 testing per patient?
   
5. 
   What is the frequency of vitamin B12 testing by referring clinician?
   
6. 
   What is the profile of referring clinician for vitamin B12 testing?
   

2.1.2 Methods for analysis of MBS data

MBS data relates to private medical services (provided in- or out-of-hospital), where the services are provided to patients regardless of whether or not they have private health cover. MBS in-hospital services are mainly provided in private hospitals and day surgery clinics, but patients can elect to be treated as a private patient in a public hospital.
MBS data were analysed by patient gender, age group, patterns of use and discipline of provider requesting the test.
Results of the analysis of the MBS data is presented in Chapter 3.

2.2 Guideline concordance

2.2.1 The research questions for the guideline concordance analysis

The research questions addressed as part of the Review using guideline concordance analysis are:

1. 
   Are the existing MBS items for service consistent with evidence-based (or in the absence of evidence, consensus-based) recommendations provided in relevant clinical practice guidelines?
   
2. 
   What are the appropriate clinical indications for vitamin B12 testing?
   
3. 
   How frequently should vitamin B12 levels be tested?
   

1. 
   in apparently healthy populations (including pregnant women, elderly, vegetarians)?
   
2. 
   in patients with chronic disease linked to vitamin B12 deficiency (e.g. infants with metabolic disease; patients with anaemia or haematologic , neurologic, psychiatric, gastrointestinal and malabsorption disorders)?
   

2.2.2 Methods for guideline concordance analysis

Searches of guidelines databases² and relevant discipline websites were undertaken to locate any existing guidelines relevant to vitamin B12 testing. Analysis of MBS item numbers 66599 and 66602 was undertaken relative to ‘best practice’, as recommended in relevant Australian clinical practice guidelines. Where Australian clinical practice guidelines do not exist, other guidelines in operation in comparable health systems overseas were included. Where guidelines existed, they were assessed for quality using the AGREE II instrument⁽⁶⁹⁾. Differences in the purpose and intended audience of any such guidelines were considered, documented and acknowledged.
See Chapter 4 for results of the concordance analysis for vitamin B12 testing.

2.3 Systematic literature review for clinical evidence

2.3.1 The clinical questions for the systematic literature review

The clinical questions that were the focus of the literature review are:

1. 
   What are the appropriate clinical indications for vitamin B12 testing?
   
2. 
   Is there evidence that testing for vitamin B12 levels improves health outcomes?
   

1. 
   in apparently healthy populations (including pregnant women, elderly, vegetarians)?
   
2. 
   in patients with chronic disease linked to vitamin B12 deficiency?
   

3. 
   Are there risks/harms associated with vitamin B12 testing?
   
4. 
   Does quality of testing vary according to testing platform?
   

2.3.2 Search strategy

A comprehensive search of peer-reviewed scientific literature was conducted to identify relevant studies addressing the key questions. Electronic databases were searched for original research papers including systematic reviews as shown in Table 2.1. Searches were restricted to studies published in the English language between January 2006 and September 2013. Databases maintained by Health Technology Assessment (HTA) agencies were searched to identify existing assessments of vitamin B12 testing.
Table 2.1: Databases searched

Database	Search period
MEDLINE	2006 – September 2013
PubMed	2006 – September 2013
The Cochrane Library (includes Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment, Cochrane Methodology Register)	2006 – September 2013
Relevant HTA websites and databases^3	Up to September 2013

Reference lists of systematic, semi-systematic and selected narrative reviews were also reviewed. In addition, during the consultation process clinicians were asked if they were aware of any relevant clinical guidelines, unpublished studies or reviews relevant to this review of vitamin B12 testing.

2.3.3 Eligibility criteria for studies

The PICO (Population, Intervention, Comparator, Outcomes) criteria⁽⁷⁰⁾ was used to develop well-defined questions for the search of published literature. This involved focusing the question on four elements:

the target population for the intervention;

the intervention being considered;

the comparator for the existing MBS service (where relevant); and

the clinical outcomes that are most relevant to assess safety and effectiveness.
The PICO criteria were determined on the basis of information provided in the literature, as well as clinical advice. The PICO criteria for the review of vitamin B12 testing are shown in Table 2.2.
Table 2.2: PICO criteria for the vitamin B12 testing items under review

Population	Intervention	Comparator	Outcomes
Patients at risk of vitamin B12 deficiency, including (but not limited to): Pregnant women Elderly Alcoholics Vegans Patients with gastrointestinal and malabsorption disorders Infants with metabolic disease Patients with anaemia and haematologic diseases Patients with neurologic disease Patients with psychiatric disorders	Vitamin B12 testing	No testing	Effectiveness Physical health outcomes as a consequence of vitamin B12 testing (e.g. all-cause mortality, anaemia, NTDs, CVD, neuropathy, depression and dementia). Safety Complications associated with vitamin B12 testing (e.g. infection, needle injuries)

The detailed search strategy and terms used is presented in Appendix 4.

Studies were excluded on the basis of citation information and/or abstract, where it was obvious that they did not meet the inclusion criteria. Where there was any doubt about any reference based on the title and/or abstract, the full paper was retrieved and evaluated. Table 2.3 lists the pre-specified inclusion and exclusion criteria.
Table 2.3: Inclusion/exclusion criteria for identification of relevant studies

Characteristic	Criteria
Search period	2006 – 2013 Should there be limited data available during this period, the search will be extended back in five year increments until sufficient data are sourced.
Publication type	Clinical studies included. Non-systematic reviews, letters, editorials, animal, in vitro and laboratory studies excluded. Systematic reviews Systematic reviews that have been superseded were excluded Primary studies Primary studies published during the search period of included systematic reviews were excluded Effectiveness studies included if: prospective, comparative trial >20 patients Safety studies included if: >50 patients
Intervention	Vitamin B12 testing
Comparator	No vitamin B12 testing
Outcome	Studies must report on at least one of the following outcomes: Patient outcomes: morbidity, mortality, quality of life Safety: adverse physical health outcomes or complications associated with testing
Language	Non-English language articles excluded

2.3.4 Process for classifying the evidence

All eligible studies were assessed according to the National Health and Medical Research Council (NHMRC) Dimensions of Evidence (refer to Appendix 5). There are three main domains: strength of the evidence, size of the effect, and relevance of the evidence. One aspect of the ‘strength of the evidence’ domain is the level of evidence, which is assigned using the NHMRC Levels of Evidence (Appendix 5). For any eligible publications, study quality was evaluated and reported using the NHMRC Quality Criteria (Appendix 5) for randomised controlled trials (RCTs), cohort studies, case-control studies and systematic reviews.
The results of the review of clinical evidence for vitamin B12 testing are presented in Chapter 5.