Use of non-formulary high-cost medicines in an Australian public hospital

Abstract

Background Clinicians prescribe high-cost medicines for rare diseases and nonapproved indications when conventional therapies have failed. Objective To examine the use of non-formulary high-cost medicines at an Australian public hospital. Methods Retrospective audit of individual patient use applications for nonformulary medicines costing more than $5000 AUD per year at a large tertiary referral hospital in Adelaide, South Australia over a 12-month study period from January 2015 to December 2015. Main outcome measures Total cost of non-formulary high-cost medicines, medication class, indications for use, level of supporting evidence and proposed monitoring outcomes. Results Eighty-seven individual patient use applications were examined. All except one were approved, at a total cost of $1,339,203 AUD. The most common drug classes were anti-CD20 (n = 33, 38%), combined antiretrovirals (n = 10, 11%) and TNF-alpha antagonists (n = 10, 11%). There were 56 indications for these medicines with the majority being inflammatory conditions (n = 52, 60%), followed by infections (n = 14, 16%) and malignancies (n = 14, 16%). Of the first-time individual patient use applications (n = 63), there were 25 applications (40%) that provided a case series as supporting evidence. Approximately half of new individual patient use applications (n = 32) proposed an objective monitoring outcome, but few (n = 13, 21%) contained sufficient information to allow a third party to determine efficacy of the medication. Conclusions Non-formulary high-cost medicines are being used for a broad range of indications based largely on low levels of evidence. Prospective definition of an adequate response to treatment and reporting of these outcomes is required to improve the evidence-base and to aid decision-making for subsequent treatment courses.

Appendices

Appendix A

Appendix B: Complete list of indications for non-formulary high-cost medicines

Indication	Applications for use (N)
Human immunodeficiency virus	10 (11%)
Focal segmental glomerulosclerosis	4 (5%)
Myasthenia gravis	3 (3%)
Membranous glomerulonephritis	3 (3%)
Systemic lupus erythematosus	3 (3%)
Hidradenitis suppurativa	3 (3%)
Thyroid cancer	2 (2%)
Thrombotic thrombocytopenic purpura	2 (2%)
Sarcoidosis	2 (2%)
Pyoderma grangrenosum	2 (2%)
Myelodysplastic syndrome	2 (2%)
Idiopathic thrombocytopaenia purpura	2 (2%)
Graft-versus-host disease	2 (2%)
Gout	2 (2%)
Chronic inflammatory demyelinating polyneuropathy	2 (2%)
Breast cancer	2 (2%)
Acute myeloid leukaemia	2 (2%)
Systemic sclerosis	1 (1%)
Peripheral neuropathy	1 (1%)
Pemphigus vulgaris	1 (1%)
Osteosarcoma	1 (1%)
Neurosarcoid	1 (1%)
Nephrotic syndrome	1 (1%)
Multiple sclerosis	1 (1%)
Mucormycosis	1 (1%)
Melanoma	1 (1%)
Malignant otitis exterma	1 (1%)
Inflammatory myositis	1 (1%)
IgM paraproteinemic polyneuropathy	1 (1%)
Idiopathic inflammatory myelopathy	1 (1%)
Hyperparathyroidism	1 (1%)
Hereditary angioedema	1 (1%)
Hepatitis B virus	1 (1%)
Haemophilia A	1 (1%)
Haemolytic anaemia	1 (1%)
Deep vein thrombosis	1 (1%)
Chronic myeloid leukaemia	1 (1%)
Castleman disease	1 (1%)
Blau syndrome	1 (1%)
Bechet’s disease	1 (1%)
Autoimmune-mediated necrotising myopathy	1 (1%)
Autoimmune encephalitis	1 (1%)
Autoimmune autonomic neuropathy	1 (1%)
Aspergullus fumigatus	1 (1%)
Antibody-mediated rejection	1 (1%)
Angiodysplasia	1 (1%)
Amylodosis	1 (1%)
Essential thrombocytosis	1 (1%)
Chronic idiopathic urticaria	1 (1%)
Acute lymphoblastic leukaemia	1 (1%)
Neuromyelitis optica spectrum disorder	1 (1%)
Cystic fibrosis	1 (1%)
Grave’s orbitopathy	1 (1%)
Bronchiectasis	1 (1%)
Antibody-mediated rejection	1 (1%)
Hodgkin’s lymphoma	1 (1%)

Appendix C: NHMRC evidence hierarchy

Level	Intervention
I	A systematic review of level II studies
II	A randomised controlled trial
III-1	A pseudorandomised controlled trial
III-2	Comparative study with concurrent control
	Non-randomised, experimental trial
	Cohort study
	Case–control study
	Interrupted time series with a control group
III-3	Comparative study without concurrent controls
	Historical control study
	Two or more single arm study
	Interrupted time series without a parallel control group
IV	Case series with either post-test or pre-test/post-test outcomes

1. NHMRC National health and medical research council