1.Avoid Routine Multiple Daily Self-Glucose Monitoring in Adults with Stable Type 2 Diabetes

1.Avoid routine multiple daily self-glucose monitoring in adults with stable type 2 diabetes on agents that do not cause hypoglycaemia

Once target control is achieved and the results of self-monitoring become quite predictable, there is little gained in most individuals from repeatedly confirming. There are many exceptions, such as for acute illness, when new medications are added, when weight fluctuates significantly, when A1c targets drift off course and in individuals who need monitoring to maintain targets. Self-monitoring is beneficial as long as one is learning and adjusting therapy based on the result of the monitoring.

Materiality/usage patterns

Total utilisation of blood glucose test strips is growing at a rate of approximately 6.3% per annum.Approximately 35% of all blood glucose test strips dispensed are for people with type 2 diabetes not using insulin.[1] In 2011-12, the Australian Government spent approximately $143.5 million subsidising glucose test strips for people living with diabetes, through both the PBS ($17 million) (Medicare Australia 2012) and the NDSS ($126.5 million).[2]

Figure 1: Total Prescriptions (and NDSS equivalent supplies) for blood glucose test strips

Source: Department of Health and Ageing 2012, ‘Pharmaceutical Benefits Scheme Products Used in the Treatment of Diabetes’, Report to the Pharmaceutical Benefits Advisory Committee

Lessons from research and guidelines

While self-monitoring of blood glucose (SMBG) can improve glycaemic control, the clinically meaningful effects are negligible to small, particularly over the longer term. It is only recommended when there is appropriate education and willingness to self-adjust drug treatments based on readings. This makes the benefits of multiple daily tests even more questionable, particularly for those not using insulin.

Paper / Approach / Conclusions / Consistent with inclusion?
Malanda et al 2012[3] / Systematic reviews of RCTs, 12 included / When diabetes duration is over one year, the overall effect of self-monitoring of blood glucose on glycaemic control in patients with type 2 diabetes who are not using insulin is small up to six months after initiation and subsides after 12 months. Furthermore, based on a best-evidence synthesis, there is no evidence that SMBG affects patient satisfaction, general well-being or general health-related quality of life / Y
Farmer et al 2012[4] / Meta-analysis based on individual participant data of RCTs published since 2000 with at least 80 participants / Not convincing for a clinically meaningful effect compared with management without self-monitoring, although the difference in HbA(1c) level between groups was statistically significant / Y
Department of Health and Ageing and University of South Australia 2012[5] / Literature review / Studies and other recent evidence suggest that there is some initial benefit gained from blood glucose monitoring when a person is first diagnosed with type 2 diabetes. However, over time, that benefit is reduced as a person’s diabetes stabilises. Further, while regular testing may assist in identifying hyperglycaemia, regular engagement with healthcare professionals and periodic testing of a patient’s
HbA1c is of greater benefit for patients not using insulin / Y
Clar et al 2010[6] / Systematic review from 1996 to April 2009, 30 RCTs identified / SMBG is of limited clinical effectiveness in improving glycaemic control in people with T2DM on oral agents, or diet alone, and is therefore unlikely to be cost-effective. SMBG may lead to improved glycaemic control only in the context of appropriate education and if patients are able to self-adjust drug treatment. / Y
McIntosh et al 2010[7] / Systematic review from January 1990 to March 2009 included RCTs and observational studies, 25 selected. / Associated with a modest, statistically significant reduction in haemoglobin A1c concentrations, regardless of whether patients were provided with education. Did not demonstrate consistent benefits in terms of quality of life, patient satisfaction, prevention of hypoglycemia or long-term complications of diabetes, or reduction of mortality. / Y
International Diabetes Federation 2009[8] / Guidelines / SMBG should be used only when individuals with diabetes (and/or their care-givers) and/or their healthcare providers have the knowledge, skills and willingness to incorporate SMBG monitoring and therapy adjustment into their diabetes care plan in order to attain agreed treatment goal / Y
Allemann et al 2009[9] / Systematic review and meta-analysis to 2009, 15 trials included. / SMBG compared with non-SMBG is associated with a significantly improved glycaemic control in non-insulin treated patients with type 2 diabetes. The added value of more frequent SMBG compared with less intensive SMBG remains uncertain / N

2.Don’t routinely order a thyroid ultrasound in patients with abnormal thyroid function tests if there is no palpable abnormality of the thyroid gland

Thyroid ultrasound is used to identify and characterize thyroid nodules, and is not part of the routine evaluation of abnormal thyroid function tests (over- or underactive thyroid function) unless the patient also has a palpably large goitre or a nodular thyroid. Incidentally discovered thyroid nodules on ultrasound are common. Overzealous use of ultrasound will frequently identify nodules, which are unrelated to the abnormal thyroid function, and may divert the clinical evaluation to assess the nodules, rather than the thyroid dysfunction, may lead to further unnecessary investigation, unwarranted patient anxiety and increased costs. Imaging may be needed in thyrotoxic patients; when needed, a radionuclide thyroid scan, not an ultrasound, is used to assess the aetiology of the thyrotoxicosis and the possibility of focal autonomy in a thyroid nodule or nodules.

Materiality/usage patterns

There is no specific MBS item for thyroid ultrasounds. Instead it is covered by the MBS items for neck ultrasounds. While not allneck ultrasounds ordered by endocrinologists will be thyroid scans (some will be assessing parathyroids), Figure 2 below shows the usage of neck ultrasounds ordered by all medical practitioners over the 2004 to 2014 financial year period while Figure 3 shows similar usage patterns just for endocrinologists over the shorter time period for which such specialised data is available over 2010 to 2014.

Note that the data has not been separated out into data on the number of tests ordered as a first test by endocrinologists compared with those that need to be ordered as a follow up – which could better reveal the extent to which inappropriately ordered ‘first tests’ lead to additional follow up tests. We have requested customised data on this from the Department of Health but the data has not been received in time for the finalisation of this document.

Bearing these caveats in mind, the figures show that there has been a significant increase in the number of neck ultrasounds ordered. For all tests over the 2004 to 2014 period the compounded growth rate has been 9.3% p.a. while the growth rate for the number of such tests ordered by endocrinologists has been more than 12.5% p.a.

Total benefits paid out for these tests amounted to $9.8 million in 2004 but had grown to almost $28.3 million by 2014 which is an annual growth rate of more than 11%. This growth if anything may underestimate the opportunity costs from inappropriate testing as it does not include the costs for specialty consultations, subsequent surgery and other activity based on the initial inappropriate investigation. Nor have costs in terms of mental health burdens and anxieties caused by false positive results been taken into account.

Figure 2: No. of services - MBS items 55032, 55033, 55011, 55013

Source: MBS website data

Figure 3: No. of services ordered by endocrinologists - MBS items 55032, 55033, 55011, 55013

Source: MBS website data

Lessons from research and guidelines

There is insufficient evidence to evaluate the comparative benefit of a thyroid ultrasound for use beyond the boundaries of established indications, frequency, intensity, or dosage. Guidelines recommend that thyroid ultrasounds are useful in detection of nodules and cancer but not in the absence of any palpable abnormalities. There is also evidence that inappropriate thyroid investigations leads to the over detection and treatment of thyroid cancers including the lack of benefits from the use of RAIs for small papillary cancers.

Paper / Approach / Conclusions / Consistent with inclusion?
Ahn et al 2014[10] / Observational study / In 2011, the rate of thyroid-cancer diagnoses in the Republic of Korea was 15 times that observed in 1993, yet thyroid-cancer mortality remains stable — a combination that suggests that the problem is overdiagnosis attributable to widespread thyroid-cancer screening. / Y
Brito et al 2012[11] / Clinical review / New imaging methods allow the detection and biopsy of thyroid nodules as small as 2 mm.There is an expanding gap between the incidence of thyroid cancer and stable death rates from papillary thyroid cancer which is evidence of overdiagnosis.Patients having thyroidectomy experience physical complications, financial and psychosocial burdens, and need lifelong thyroid replacement therapy. One caveat is that thisinference about overdiagnosis of thyroid cancer is based on epidemiological and observational evidence. / Y
Bahn et al 2011[12] / Guidelines / The use of thyroid ultrasonography in all patients with GD (Graves’ Disease) has been shown to identify more nodules and cancer than does palpation and 123I scintigraphy. However, since most of these cancers are papillary microcarcinomas with minimal clinical impact, further study is required before routine ultrasound (and therefore surgery) can be recommended’ / Y

3.Don’t routinely measure 1,25-dihydroxyvitamin D unless the patient has hypercalcemia or decreased kidney function

Serum levels of 1,25-dihyroxyvitamin D have little or no relationship to vitamin D stores but rather are regulated primarily by parathyroid hormone levels, which in turn are regulated by calcium and/or vitamin D. In vitamin D deficiency, 1,25-dihydroxyvitamin D levels go up, not down.

Unregulated production of 1,25-dihydroxyvitamin D is an uncommon cause of hypercalcemia; this should be suspected if blood calcium levels are high and parathyroid hormone levels are low and confirmed by measurement of 1,25-dihydroxyvitamin D. The enzyme that activates vitamin D is produced in the kidney, so blood levels of 1,25-dihydroxyvitamin D are sometimes of interest in patients on dialysis or with end-stage kidney disease. There are few other circumstances, if any, where 1,25-dihydroxyvitamin D testing would be helpful.

Materiality/usage patterns

As MBS restrictions have only recently (in October 2014) been introduced which break out a separate 1,25-dihyroxyvitamin D testing item, there is no useful dataset yet on long term usage patterns for this test item.

Lessons from research and guidelines

Guidelines recommend against using the serum 1,25-dihydroxyvitamin D (as opposed to the 25-hydroxyvitamin D) test for testing for vitamin D deficiency. The former test can be inaccurate because those with vitamin D deficiency can exhibit normal or even elevated levels of serum 1,25-dihydroxyvitamin D.

Paper / Approach / Conclusions / Consistent with inclusion?
Holick et al 2011[13] / Guideline / Recommends using the 25(OH)D] level to evaluate vitamin D status in patients who are at risk for vitamin D deficiency. Recommends against using 1,25(OH)2D assay for this purpose and are in favour of using it only in monitoring certain conditions, such as acquired and inherited disorders of vitamin D and phosphate metabolism.
Serum 1,25(OH)2D does not reflect vitamin D reserves, and its measurement is not useful for monitoring the vitamin D status of patients. Serum 1,25(OH)2D is frequently either normal or even elevated in those with vitamin D deficiency, due to secondary hyperparathyroidism. / Y
Holick et al 2007[14] / Review article / Since the kidneys
tightly regulate the production of 1,25-dihydroxyvitamin
D, serum levels do not rise in response to
increased exposure to sunlight or increased intake
of vitamin D.1-3 Furthermore, in a vitamin D–
insufficient state, 1,25-dihydroxyvitamin D levels
are often normal or even elevated / Y

4.Don’t order a total or free T3 level when assessing thyroxine dose in hypothyroid patients

T4 is converted into T3 at the cellular level in virtually all organs. Intracellular T3 levels regulate pituitary secretion and blood levels of thyroid-stimulating hormone (TSH), as well as the effects of thyroid hormone in multiple organs; a normal TSH indicates an adequate T4 dose. Conversion of T4 to T3 at the cellular level may not be reflected in the T3 level in the blood. Compared to patients with intact thyroid glands, patients taking T4 may have higher blood T4 and lower blood T3 levels. Thus the blood level of total or free T3 may be misleading (low normal or slightly low); in most patients a normal TSH indicates a correct dose of T4.

Materiality/usage patterns

Figure 5: No. of services - MBS item 66719 (2004 to 2014)

Source: MBS website data

MBS data (which does not include services provided to public patients in public hospitals or services that qualify for a benefit from the Department of Veterans' Affairs) shows an increase in the number of T3 level tests ordered over the 2004 to 2014 period. This has been at an average rate of 8.4% p.a. A breakdown is not available for the number of these tests ordered for hypothyroid patients. Nonetheless, the increase suggests there is a prima facie case for better selectivity in use of the ordering of these tests.

In 2004 the total cost of these tests was more than $28 million. This had grown to almost $62.7 million in 2014 which is an annual average growth rate of around 8%.

The variation in usage per capita is noticeable but not significant ranging from 5351 per 100,000 in NT to 10,685 per 100,000 in Queensland.

Lessons from research and guidelines

Guidelines states that the serum T3 measurement has limited utility in assessing hypothyroidism and can lead to both false positives and false negatives.

Paper / Approach / Conclusions / Consistent with inclusion?
Garber et al 2012[15] / Guidelines / Serum T3 measurement, whether total or free, has limited utility in hypothyroidism because levels are often normal due to hyperstimulation of the remaining functioning thyroid tissue by elevated TSH and to up-regulation of type 2 iodothyronine deiodinase. Moreover, levels of T3 are low in the absence of thyroid disease in patients with severe illness because of reduced peripheral conversion of T4 to T3 and increased inactivation of thyroid hormone. / Y

5.Don’t prescribe testosterone therapy unless there is evidence of proven testosterone deficiency

Many of the symptoms attributed to male hypogonadism are commonly seen in normal male aging or in the presence of comorbid conditions. Testosterone therapy has the potential for serious side effects and represents a significant expense. It is therefore important to confirm the clinical suspicion of hypogonadism with biochemical testing. Current guidelines recommend the use of a total testosterone level obtained in the morning. A low level should be confirmed on a different day, again measuring the total testosterone. In some situations, for example conditions in which sex hormone-binding globulin concentrations are altered,a calculated free or bioavailable testosterone may be of additional value.

Materiality/usage patterns

Over two decades, total annual expenditure on testosterone products increased ninefold to $12.7 million according to PBS data and fivefold to $16.3 million according to IMS, a source of commercial pharmaceutical data. When adjusted for inflation and population growth, total annual expenditure on testosterone products increased 4.5-fold according to PBS data and 2.5-fold according to datafrom January 1992 to December 2010. Differences in total testosterone prescribed per capita between the states and territories with the highest and lowest rates of prescribing were roughly twofold at the beginning and at the end of this period.[1]

Figure 6: No. of scripts – testosterone products (2005 to 2011)

Source: Australian Statistics on Medicines, various years, PBS

PBS statistics show that there has been a steep increase in number of scripts written for testosterone products which increased by 5.23% p.a. between 2001 and 2011 (with the steeper increases starting from around 2005). The increase in injections and transdermal prescriptions has more than made up for declines in number of scripts written for other testosterone products.

Lessons from research and guidelines

Guidelines recommend that testosterone therapy should be considered in men who are androgen deficient. There is ongoing controversy over potential adverse effects associated with use of this therapy.Treatment should be preceded by consideration of the benefits versus risks in individuals.

Research

Paper / Approach / Conclusions / Consistent with inclusion?
Corona et al 2014[16] / An up to date meta-analysis of randomised controlled trials involving 75 studies with 3,016 men treated with T and 2,448 with placebo for a mean duration of 34 weeks. / Testosterone is not related to any increase in CV risk, even when composite or single adverse events were considered. In RCTs performed in subjects with metabolic derangements a protective effect of TS on CV risk was observed / N
Finkle et al 2014[17] / Cohort study of the risk of acute non-fatal myocardial infarction (MI) following an initial testosterone prescription (n = 55,593). / In older men, and in younger men with pre-existing heart disease, the risk of non-fatal MI was higher in the 90 days following prescription of testosterone compared with the preceding period.. / Y
Baillargeon et al 2014[18] / Case-control study of men 66 years of age and older in which testosterone therapy was not associated with risk of myocardial infarction. / In men at the highest risk, testosterone therapy was associated with lower incidence of MI / N
Vigen et al 2013[19] / Retrospective national cohort study of men with low testosterone levels who underwent coronary angiography (8709 participants) / Among a cohort of men who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. / Y
Xu et al 2013[20] / Systematic review and meta-analysis of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events.(27 trials included) / Testosterone therapy increased risk of a cardiovascular-related event. In trials not funded by the pharmaceutical industry the risk of a cardiovascular-related event on testosterone therapy was greater than in pharmaceutical industry funded trials. / Y
Shores et al 2012[21] / Cohort study in male US veterans with an initial low measured T concentration. / Testosterone therapy was associated with reduced mortality, compared with no testosterone therapy / N
Bhasin et al 2010[22] / Clinical practice guideline / ‘Our proposed diagnostic strategy reflects our preference to avoid labeling men with low testosterone
levels due to S HBG abnormalities, natural variations in testosterone levels, or transient disorders as requiring testosterone therapy. Our strategy also
reflects our preference to avoid treatment in men
without unequivocally low testosterone levels and
symptoms in whom the benefits and risks of testosterone therapy remain unclear.’
‘It is important to confirm low testosterone concentrations
in men with an initial testosterone level in the
mildly hypogonadal range, because 30% of such men
may have a normal testosterone level on repeat
measurement.’
The Task Force recommends against a general policy of offering testosterone therapy to all older men with low testosterone levels. (1 | +OOO)
The Task Force suggests that clinicians consider offering testosterone therapy on an individualized basis to older men with low testosterone levels on more than one occasion and clinically significant symptoms of androgen deficiency, after explicit discussion of the uncertainty about the risks and benefits of testosterone therapy. / Y
Fernández-Balsells et al 2010[23] / Systematic review of studies from 2003 through August 2008, included 51 studies / Adverse effects of testosterone therapy include an increase in haemoglobin and haematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about safety of testosterone treatment in men in terms of patient-important outcomes is of low quality. / Y

6.Don’t screen for gestational diabetes at 26-28 weeks using fasting plasma glucose, random blood glucose, glucose challenge test or urinalysis for glucose

The oral glucose tolerance test (OGTT) is currently the gold standard for the diagnosis of diabetes including gestational diabetes. If a woman has had gestational diabetes, a repeat OGTT is recommended at 6–8 weeks after delivery. If the results are normal, repeat testing is recommended between 1 and 3 years depending on the clinical circumstances.