Pharmaceutical Benefits Scheme Criteria Research Articles

Comparing PCSK9 inhibitor prescription rates within high-risk populations: diabetes mellitus, multi-territory vascular disease, multivessel and recurrent coronary artery disease

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are subsidised in Australia for treatment of hypercholesterolemia in particularly high-risk patients with atherosclerotic cardiovascular disease (ASCVD). These high-risk groups are defined as: diabetes mellitus (with age≥60, Aboriginal or Torres Strait Islander origin or microalbuminuria), recurrent ASCVD (≥2 events within 5 years), multivessel coronary disease (≥50% stenosis in ≥2 large vessels) and multi-territory vascular disease (concurrent cerebrovascular or peripheral vascular disease). Methods A retrospective observational analysis was conducted on high-risk patients with LDL>2.6 admitted to a quaternary hospital with ASCVD between 2020-2022. Australian Pharmaceutical Benefits Scheme (PBS) criteria was applied to assess and compare PCSK9 inhibitor eligibility and prescription rates within high-risk populations. Results In total, 477 ASCVD patients with LDL>2.6 were included. This was further categorised into: multivessel coronary disease (n=239, 50.1%), diabetes mellitus (n=60, 12.6%), recurrent ASCVD (n=55, 11.5%) and multi-territory vascular disease (n=32, 6.7%), p<0.001. When 2020 PBS criteria was applied, the number of eligible patients were 16/239 (6.7%), 5/60 (8.3%), 13/55 (23.6%) and 4/32 (12.5%) respectively, p=0.002. Of PBS eligible patients, the number prescribed PCSK9 inhibitors were: 7/16 (43.8%) for multi-vessel coronary disease, 1/5 (20%) for diabetes mellitus, 4/13 (30.8%) for recurrent ASCVD and 1/4 (25%) for multi-territory vascular disease patients (p=0.73). Conclusion Although there was a significantly higher prevalence and proportion of eligible multivessel coronary disease patients, prescribing rates for PCSK9 inhibitor therapy remain low amongst all high-risk eligible groups including diabetes mellitus, multi-territory vascular disease, multivessel and recurrent coronary artery disease.

Tocilizumab use in giant cell arteritis: comparing Pharmaceutical Benefits Scheme eligible and ineligible cases in South Australia.

Tocilizumab (TCZ) is increasingly used as a steroid-sparing agent in giant cell arteritis (GCA), but there are strict Pharmaceutical Benefits Scheme (PBS) restrictions for its use in Australia. Patients who do not meet the PBS criteria can obtain TCZ through public hospital individual patient use (IPU) schemes which may not be universally accessible. We compared patients receiving IPU-approved TCZ with patients receiving PBS-subsidised TCZ and found IPU approvals were granted mainly for visual loss, a serious complication of GCA, in patients who otherwise failed to meet PBS criteria. Further studies demonstrating that TCZ is comparatively more effective than prednisolone monotherapy, as well as cost-effective, are needed to substantiate the rationale for expanding PBS approval criteria.

Pharmacoepidemiology of testosterone: Impact of reimbursement policy on curbing off-label prescribing.

To estimate the impact on testosterone prescribing over 3 years following the 2015 tightening of Pharmaceutical Benefits Scheme (PBS) criteria. Analysis of testosterone prescribing data from PBS and private (non-PBS) sources between 2012 and 2018 covering 2015 change in PBS prescribing criteria. New and total PBS testosterone prescriptions estimating usage by quarter analyzed by product type, patient age-group, indication and prescriber type. Total national testosterone prescriptions (private plus PBS) was verified from an independent data supplier (IQVIA). PBS usage peaked in 2014 declining by 30% in 2017-8 with PBS prescribing covering a fall from 97.6% by usage in 2014 to 74% in 2017-18 of all testosterone prescribing. The tighter 2015 PBS restrictions sustained the selective reduction in GP initiation of prescriptions for middle-aged men without pathological hypogonadism whereas specialist initiations and prescription for adult hypogonadism or pediatric/prepubertal indications were largely unaffected. The tightening of PBS criteria from 1 April 2015 to curb off-label prescribing remained effective and selective over 3 years yet total national testosterone prescribing continued with little change, reflecting a shift to private prescriptions. The continuation of off-label testosterone prescribing for unproven indications suggests that long-term androgen dependence is created in men without pathological hypogonadism who commence testosterone. This highlights the need to avoid prescribing testosterone to men without pathological hypogonadism in the absence of sound evidence of efficacy and safety, the latter including the little unrecognized risks of long-term androgen dependency when trying to quit.

Prevalence of minimal disease activity in Australian patients with Psoriatic Arthritis: Assessing the outcome of national funding criteria for biologic disease-modifying antirheumatic drug prescribing.

Discrepancies exist between international treatment guidelines and current Australian Pharmaceutical Benefits Scheme (PBS) criteria for funding biologic disease-modifying antirheumatic drug (bDMARD) prescribing in psoriatic arthritis (PsA). We aimed to determine the prevalence of minimal disease activity (MDA) achievement and differences in inflammatory marker levels between PsA patients who have and have not met the Australian PBS criteria for bDMARDs. Consecutive participants diagnosed with PsA were assessed for MDA components and serum inflammatory markers. For those on bDMARDs, joint counts and inflammatory markers at the time of bDMARD qualification were compared with matched rheumatoid arthritis (RA) controls. Minimal disease activity was achieved by 56/105 participants overall. There were no differences in inflammatory marker levels or involved joint count patterns between the PsA and RA groups at the time of bDMARD qualification. Seventy-three percent of the 53 PsA patients on bDMARD achieved MDA, vs 33% in the non-bDMARD group (P<0.001). More bDMARD than non-bDMARD patients achieved four out of seven MDA components. Of those with any enthesitis, its prevalence was higher in the non-bDMARD group (22 vs 10, P=0.009). Regardless of treatment, there was no difference in inflammatory marker levels between those who did and did not achieve MDA. The Australian PBS criteria, funding bDMARD prescribing for PsA, select well for MDA achievers. A high prevalence of MDA non-achievement remains in patients ineligible for bDMARD funding, and enthesitis in this population is more common. Inflammatory markers were not discriminators between treatment or MDA achievement groups.

Pharmacoepidemiology of testosterone: Curbing off-label prescribing.

To estimate the impact of the first year of new Pharmaceutical Benefits Scheme (PBS) prescribing criteria that dictate eligibility for national health scheme subsidy of testosterone prescribing. Analysis of cumulative PBS data. Retrospective analysis of testosterone prescribing from PBS data. Nil MAIN OUTCOME MEASURES: PBS expenditure analysed by total expenditure, by state, and by product type as well as the age, indication, and prescriber type for new testosterone treatment. Total PBS expenditure continued to exceed $20 million in 2014 before declining from 2015 with changes that were uniform by state and product type. Prior to 2015, over 80% were for men aged over 40years of age for low circulating testosterone in the absence of reproductive system disorders ("Low T") initiated by GPs. From 2015, these features were markedly reduced without changing the numbers of new prescriptions for pathological reproductive disorders or specialist initiations. The short-term impact of 2015 PBS criteria showed highly effective and well-targeted curbing of off-label testosterone prescribing. The findings indicate that the main driver for the recent upsurge in testosterone prescribing was treatment of middle-aged men for "Low T" initiated by GPs.

Prevalence and treatment of osteoporosis in older Australian men: findings from the CHAMP study

To determine the proportion of older Australian men who meet the Pharmaceutical Benefits Scheme (PBS) criteria for osteoporosis treatment and are receiving effective treatment. A population-based, cross-sectional analysis of the baseline phase of the Concord Health and Ageing in Men Project (CHAMP), a large epidemiological study focusing on the health of older men. Data were collected through questionnaires and clinical assessments. Bone mineral density (BMD) of the hip and spine was measured by dual x-ray absorptiometry (DXA). Vertebral deformities were identified from DXA lateral vertebral fracture assessment images. The study was conducted at Concord Hospital, Sydney, between January 2005 and May 2007. 1705 community-dwelling men aged 70 years or over from a defined geographical region around Concord Hospital. Prevalence of vertebral deformities; previous minimal trauma fractures; BMD T-scores ≤ - 3; falls in the previous 12 months; use of bisphosphonates and calcium and vitamin D supplements. Of the 1705 men seen at baseline, 1626 completed all DXA scans and 401 (25%) met one or more of the PBS criteria for osteoporosis treatment. Ninety per cent of the men who met the PBS criteria were unaware they had osteoporosis. Of the men eligible for PBS-subsidised treatment, 39 (10%) reported use of a bisphosphonate, 56 (14%) had taken calcium supplements, and 28 (7%) had taken vitamin D supplements. Only three men had taken calcium, vitamin D and bisphosphonates in combination. Despite a high prevalence of osteoporosis in elderly Australian men, awareness, diagnosis and treatment of the condition remain very low.

Anti‐tumour necrosis factor‐α treatment for perianal Crohn's disease in Australia

To examine the prevalence of perianal Crohn's disease (PCD) and the eligibility of PCD patients to access anti-tumour necrosis factor-alpha (anti-TNFalpha) treatment under current Australian Pharmaceutical Benefits Scheme (PBS) guidelines. A retrospective study of patients with Crohn's disease (CD) and PCD attending four large adult inflammatory bowel disease (IBD) centres in Australia between January 2004 and May 2008. Patients for whom anti-TNFalpha therapy was clinically indicated were assessed to determine whether they satisfied PBS criteria for subsidised medication. Prevalence of CD and PCD in patients attending different IBD centres; eligibility of PCD patients for PBS-subsidised anti-TNFalpha medication. Data were available on 3589 patients, representing about 6% of all patients with IBD in Australia. Of the 1815 patients with CD, 310 (17%) had PCD. Anti-TNFalpha therapy was deemed clinically indicated for 166 patients with PCD (54%), of whom 49 (30%) did not qualify for PBS-funded therapy. Thirty per cent of patients with clinically significant PCD currently do not have access to PBS-subsidised optimal medical treatment. We believe that PBS criteria should be extended to include this subgroup of IBD patients.

Clopidogrel Prescribing and Concordance with the Pharmaceutical Benefits Scheme in Hospital Patients

ABSTRACTBackgroundClopidogrel is used for the secondary prevention of cerebrovascular and cardiovascular events. Clopidogrel has a similar safety profile to low‐dose aspirin but is considerably more expensive. Clopidogrel is subsidised for restricted indications via the Pharmaceutical Benefits Scheme (PBS).AimTo examine clopidogrel prescribing in hospital; and to identify patients discharged on clopidogrel according to PBS criteria.MethodCross‐sectional evaluation of patients started on clopidogrel (July 2006 to June 2007) at the Royal Darwin and Royal Hobart Hospitals. Clopidogrel prescribing was examined and the indication for discharge on clopidogrel was documented. The primary outcome was concordance between clopidogrel use and PBS criteria.ResultsData were collected for 385 patients. 54% of patients from the Royal Darwin Hospital and 39% of patients from the Royal Hobart Hospital discharged on clopidogrel met PBS criteria. The main reason for noncompliance with the PBS was absence of a history of cardiovascular or cerebrovascular events while on low‐dose aspirin and an absence of contraindications to aspirin at the time of clopidogrel prescribing.ConclusionAlthough clopidogrel prescribing at the hospitals was often not in accordance with PBS criteria, in most cases prescribing was based on the available evidence.

Lipid treatment guidelines and cardiovascular risk for Aboriginal people in Central Australia

To evaluate the extent to which the current Pharmaceutical Benefits Scheme (PBS) guidelines for patient eligibility for lipid-lowering medication are applicable to Aboriginal people in Central Australia. A 10-year cohort study of 659 Aboriginal people who participated in population-based cardiovascular disease (CVD) risk factor surveys in 1995 and who were free of CVD at baseline, for the period from 1995 to 2004-2005 or until first CVD event. Evidence of atherosclerotic CVD (ischaemic heart disease, ischaemic stroke, and peripheral vascular disease) was sought from hospital, primary health care and death records. PBS eligibility was assigned according to the current PBS criteria, which were amended in 2006 to include Aboriginal-specific criteria, using participants' baseline (1995) and 10-year follow-up data. Proportions of PBS-eligible and PBS-ineligible participants who had CVD events during the study period; sensitivity and specificity of the criteria. Of 42 participants who had CVD events during the study period, 35 were PBS-eligible (incidence, 1130/100 000 person-years; relative risk compared with PBS-ineligible population, 4.87 [95% CI, 2.19-10.80]) and seven were PBS-ineligible. PBS eligibility was associated with older mean age (37 v 32 years) and male sex (48% v 37%), with 50.7% of participants (334/659) meeting eligibility criteria. The mean high-density lipoprotein cholesterol level at baseline was very low in both groups (0.81 v 0.87 mmol/L). The current PBS guidelines have low specificity (52%) in this population, which was found to improve (to 71%-82%) by incorporating additional non-lipid criteria (age and multiple non-lipid risk factors). The current PBS lipid treatment criteria, which include any Aboriginal person with diabetes and less stringent cholesterol thresholds than the previous version, identify a group at very high risk of CVD. Global risk assessment may better identify those at risk.

How do the Australian guidelines for lipid‐lowering drugs perform in practice? Cardiovascular disease risk in the AusDiab Study, 1999–2000

To determine how well the current Pharmaceutical Benefits Scheme (PBS) eligibility criteria for subsidy of lipid-lowering drugs compare with current national guidelines for determining the population at high risk of developing cardiovascular disease (CVD). Analyses of the population-based, cross-sectional Australian Diabetes, Obesity and Lifestyle (AusDiab) study, conducted in 1999-2000. The 1991 Framingham risk prediction equation was used to compute 5-year risk of developing first-time CVD in 8286 participants aged 30-74 years with neither CVD nor diabetes. Based on the National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand guidelines, people with either 5-year CVD risk > or = 15% or with 5-year CVD risk of 10%-< 15% and the metabolic syndrome were defined as having estimated high absolute CVD risk. 5-year CVD risk; estimated population with high CVD risk. Among participants without prevalent CVD or diabetes, 7.9% of men and 1.5% of women had a 5-year CVD risk > or = 15%. Of the estimated residential Australian population in 2000 aged 30-74 years without CVD or diabetes, 717 000 people were considered to be at high absolute CVD risk. Among the high-risk AusDiab participants without CVD or diabetes, only 16.9% of men and 15.4% of women were being treated with lipid-lowering drugs. Of the 9.6% of participants free of CVD and diabetes who were untreated but eligible for subsidy under PBS criteria, only 27.4% had an estimated high absolute CVD risk. Strategies for CVD prevention using lipid-lowering medications can be improved by adoption of the absolute-risk approach.

Has the use of disease‐modifying anti‐rheumatic drugs changed as a consequence of controlled access to high‐cost biological agents through the Pharmaceutical Benefits Scheme?

A prerequisite for access to biological agents for the treatment of rheumatoid arthritis under Australia's Pharmaceutical Benefits Scheme (PBS) is evidence of an adequate trial of conventional disease-modifying anti-rheumatic drugs (DMARDs). The aim of this study was to examine whether there were changes in prescribing DMARDs since the introduction of the PBS criteria for access to biologicals in August 2003. A retrospective study was undertaken of the national use of DMARDs in the period before and after the introduction of biologicals under the PBS. Dispensing data were analysed for changes in patterns of DMARD prescription rates (2000-2005). There were 2 887 746 prescriptions for DMARDs between August 2000 and June 2005. PBS prescriptions accounted for 95% of these. Government expenditure for the DMARDs was $A156m. Trends in the use of DMARDs remained relatively steady over the study period without a significant change around the time the PBS criteria for biologicals were introduced. Use of hydroxychloroquine and leflunomide increased steadily, use of methotrexate and sulfasalazine was stable and use of gold preparations and penicillamine was considerably lower during this 5-year period. Introduction of PBS criteria for access to biologicals did not alter the trends in use of DMARDs based on national dispensing data. This study emphasized the value that would accrue from availability of more comprehensive, de-identified, individual patient data that would enable more detailed examination of the use of medicines. These data are available, but cannot be easily accessed. It is time to make the data available for approved, ethical research in the interests of better outcomes from medicines supplied under PBS.

Pharmaceutical Benefits Scheme criteria for the use of tumour necrosis factor‐α inhibitors in the treatment of ankylosing spondylitis in Australia: are they evidence based?

In 2004, the Pharmaceutical Benefits Scheme (PBS) listed infliximab as a subsidised treatment for ankylosing spondylitis (AS). Eligibility to receive this treatment for AS involved fulfilling several criteria. To examine the medical literature concerning response to tumor necrosis factor (TNF)-alpha inhibitors in AS and compare with the PBS criteria for these agents. Review of published studies and analysis of the PBS criteria for the prescription of TNF inhibitors for the treatment of AS to assess whether the published criteria are evidence based. The published findings on the prediction of response to TNF inhibitors in the treatment of AS suggest that age, duration of disease, disease activity, functional status at the time of commencement of TNF inhibitors and, possibly, level of acute phase reactants predict the outcome of treatment with TNF inhibitors in AS. The PBS criteria do not reflect the published findings on predictors of response to TNF inhibitors. The current PBS criteria that need to be fulfilled for patients to receive subsidised treatment with TNF inhibitors for AS are not evidence based and will lead to the selection of patients with established disease while excluding patients with early disease.

Cost‐effectiveness of prescribing statins according to Pharmaceutical Benefits Scheme criteria

(i) To analyse how well Pharmaceutical Benefits Scheme (PBS) criteria for prescribing lipid-lowering therapy identify people most at risk of coronary heart disease (CHD); and (ii) to determine the cost-effectiveness of primary prevention therapy with pravastatin according to these criteria in Australia. (i) Analysis of targeting of CHD risk according to PBS criteria; (ii) cost-effectiveness analysis for pravastatin as primary preventive therapy (40 mg/day), with a 20-year projection from 1999. (i) Men and women aged 25-69 years from the 1989 National Heart Foundation Risk Factor Prevalence Survey; (ii) Australian men and women, aged 25-85 years, excluding those with diabetes and existing CHD. (i) Proportion eligible for lipid lowering treatment according to PBS criteria within 15-year risk of CHD mortality groups; (ii) average net cost in Australian dollars ($) per year of life saved (YOLS), with 80% uncertainty ranges (UR). (i) PBS criteria do not adequately identify those most at risk of CHD, as only 61% of Australians (aged 25-69 years) with a greater than 10% 15-year risk of CHD mortality were eligible for treatment; and 11% of those at low risk of CHD mortality (< 2.5% over 15 years) were eligible for treatment. (ii) Cost-effectiveness of treatment according to PBS criteria was estimated at $110,000 (80% UR, $96,000-$150,000) per YOLS for men and $87,000 (80% UR, $80,000-$130,000) per YOLS for women. As an indicator of the likely recurrent annual costs, total first-year treatment costs (excluding the costs of non-compliers) were estimated at $940 million. Assuming compliance of 50%, cost-effectiveness of treatment was markedly improved using 32.5% 15-year risk of CHD mortality as a cut-off, with ratios of $31,000 (80% UR, $27,000-$40,000) per YOLS for men and $39,000 (80% UR, $33,000-$53,000) per YOLS for women. First-year treatment costs of $940 million were the same as treating according to PBS criteria, but absolute health impact in terms of deaths averted and years of life saved was more than doubled. While PBS criteria do target patients at risk of CHD, there is room for improvement in identifying those most at risk of CHD, and treatment according to PBS criteria is not likely to be the most cost-effective. For optimal cost-effectiveness, targeting of therapy for primary CHD prevention needs to be based on population-specific, multivariable risk.

Concordance between use of proton pump inhibitors and prescribing guidelines.

To determine (i) the relationship between prescriptions for proton pump inhibitors (PPIs) and upper gastrointestinal conditions, and (ii) compliance with Pharmaceutical Benefits Scheme (PBS) prescribing guidelines for PPIs. Drug utilisation evaluation. 800-bed metropolitan teaching hospital. 253 patients dispensed PPIs from the hospital pharmacy over five consecutive weeks (11 January to 15 February 1999). Recorded gastrointestinal conditions; previous trial of H2-antagonist therapy; compliance with PBS criteria for prescribing PPIs. Seventy patients (27.7%) had no appropriate upper gastrointestinal tract investigations, and 62 patients (24%) did not receive an adequate trial of H2-antagonist therapy before the commencement of a PPI. The major indications for use of PPIs in investigated patients were gastro-oesophageal reflux in 99 (54%) and peptic ulcer disease in 30 (16.4%). In only 57 patients (22.5%) did PPI prescriptions comply with PBS prescribing guidelines. Clinical indications that failed to meet prescribing criteria included milder forms of gastro-oesophageal reflux, gastritis/duodenitis, and non-specific dyspepsia with normal endoscopy results. Drug utilisation data indicate widespread use of PPIs outside current prescribing guidelines. Many patients have not had relevant investigations and/or an adequate trial of H2-antagonist therapy. These findings explain the considerable hospital expenditure on PPIs.