Cavenagh, John D

Currow, David Christopher

Good, Phillip D

Ravenscroft, Peter J

Tuffin, Penelope H

Woods, David A

Flinders Academic Commons

Archived at the Flinders Academic Commons:  http://dspace.flinders.edu.au/dspace/  This is the publisher’s copyrighted version of this article.  The original can be found at: http://www.racgp.org.au/afp/200604/200604good.pdf © 2006 Australian Family Physician www.afp.org.au Copyright to Australian Family Physician. Reproduced with permission. Permission to reproduce must be sought from the publisher, The Royal Australian College of General Practitioners. Reprinted from Australian Family Physician Vol. 35, No. 4, April 2006  261Many palliative care doctors feel that patients receiving palliative care in the community are disadvantaged in accessing drugs because the Pharmaceutical Benefits Scheme (PBS) constrains them. Members of the Australian and New Zealand Society for Palliative Medicine (ANZSPM) started to advocate to redress this. Barriers to changing the PBS regulations were: some drugs on the list require Therapeutics Goods Administration approval for palliative care indications; others needed evidence of effectiveness, cost effectiveness and clinical place in therapy for PBS listing; and these drugs would require an industry sponsor to fund and take on responsibility for the application and subsequent use, as required by Australian law – a problem as many drugs were out of patent. 	As	 a	 way	 forward,	 a	 Joint	Therapeutics	 Committee	of	 Palliative	 Care	Australia,	 ANZSPM,	 and	 the	 Clinical	Oncological	Society	of	Australia	 formed	 to	generate	a	 list	of	 essential	 drugs	 for	 palliative	 care.	One	had	 previously	been	generated	 from	a	world	survey	sent	 to	50	palliative	care	doctors	 in	25	different	countries	 (including	Australia),	and	a	 list	of	what	was	 thought	 the	 ‘20	essential	drugs	 in	palliative	care’	published.1		 We	decided	to	survey	palliative	care	doctors	in	Australia	to	 compile	 a	 similar	 list	 of	 essential	 drugs,	 and	 also	 to	assess	 the	 level	 of	 evidence	 for	 them,	 setting	out	which	were	available	through	the	PBS.MethodWe	 surveyed	members	 of	ANZSPM,	 asking	 them	what	they	 thought	 were	 essential	 drugs	 for	 palliative	 care.	The	 questionnaire	 used	 a	 list	 of	 the	 22	most	 frequently	encountered	 symptoms	derived	 from	 the	 literature,	 ‘pain’	occupying	 three	 of	 these.	 Respondents	 could	 list	 up	 to	five	 individual	drugs	 for	each	symptom,	 together	with	 their	estimated	 level	of	evidence	 for	 the	drug	 for	 that	 indication,	using	a	 ranking	of	 the	evidence	 (Table 1).	This	differs	 from	BACKGROUNDThere is a disparity of availability and cost of drugs in the community for palliative care patients through the Pharmaceutical Benefits Scheme (PBS) compared to those available to inpatients in public hospitals.METHODSThe Joint Therapeutics Committee of the Australian and New Zealand Society of Palliative Medicine, Palliative Care Australia and the Clinical Oncological Society of Australia surveyed palliative care practitioners in Australia to compile  a list of drugs they considered essential.RESULTS Drugs nominated generally had good levels of evidence for use in palliative care, although many practitioners still used some without evidence of benefit.DISCUSSIONWe are now working with the Commonwealth Department of Health and Ageing to agree on a list of drugs for specific palliative care indications. As a result, the first ever section in the PBS for a specific patient population has been created. There is a need for high quality studies in palliative care to determine the best drugs to add to the list. What are the essential medications in palliative care? A survey of Australian palliative care doctorsPhillip D GoodMBBS, FRACP, is Staff Specialist, Newcastle Mater Misericordiae Hospital, New South Wales. phillip.good@mater.health.nsw.gov.au John D CavenaghMBBS, FAChPM, is Senior Staff Specialist, Newcastle Mater Misericordiae Hospital, New South Wales.David C CurrowBMed, MPH, FRACP, is Professor of Palliative and Supportive Services, Flinders University, South Australia.David A WoodsMBBS, FACRRM, FAChPM, is Medical Specialist, Tasmanian Palliative Care Service (North), Tasmania.Penelope H TuffinBPharm, PGDip, HospPharm, is a clinical pharmacist, Cancer Council of WA Cottage Hospice, Western Australia.Peter J RavenscroftMBBS, FRACP, MD, FFPMANZCA, FAChPM, is Professor of Palliative Care, University of Newcastle, New South Wales. RESEARCHTable 1. Levels of evidence used in the questionnaireLevel 1	 	Evidence	from	systematic	review	of	all	relevant	randomised	controlled	trialsLevel 2	 	Evidence	from	at	least	one	properly	designed	randomised	controlled	trialLevel 3	 	Evidence	from	nonrandomised	controlled	trials,	cohort	studies,	case	control	studies	Level 4	 	Evidence	from	case	reports/expert	opinion	Level 5	 Unknown	to	respondent	what	level	of	evidence	exists	What are the essential medications in palliative care? – a survey of Australian palliative care doctorsRESEARCH262  Reprinted from Australian Family Physician Vol. 35, No. 4, April 2006current	National	Health	 and	Medical	 Research	Council	 (NHMRC)	 guidelines2	 in	 retaining	 the	expert	 opinion	 no	 longer	 included	 in	NHMRC	guidelines.	While	 these	 levels	 have	 been	used	throughout	the	article	for	consistency,	where	the	only	evidence	available	 is	expert	opinion,	 that	 is	denoted	‘4E’.		 The	 questionnaire	was	 hand	 delivered	 to	registrants	 at	 a	 biennial	 scientific	 committee	of	ANZSPM	held	in	Geelong	(Victoria)	in	September	2000	 and	 in	 addition,	 mailed	 to	 all	 other	members	not	present.		 The	Hunter	Area	Research	Ethics	Committee	gave	ethics	approval	for	this	study.	ResultsOut	of	 350	questionnaires,	 102	were	 returned.	Two	were	 excluded	 because	 the	 address	was	unknown,	 giving	 a	 response	 rate	 of	 100/350	(29%).	Median	age	was	46	years	 (range	28–70),	and	median	 time	since	graduation	was	21	years	(range	5–49).	Most	respondent's	(58%)	main	area	of	practice	was	palliative	medicine,	while	the	rest	were	mostly	general	practitioners	with	experience	in	palliative	care.	 The	first	ranked	drug	for	selected	symptoms,	PBS	 availability,	 and	 level	 of	 evidence	 at	 the	Table 2. Palliative symptoms, with the drug nominated as ‘essential’ for that symptom, by symptom control, PBS subsidy, and perceived  and actual evidence of benefit    PBS subsidy     	 	 	 	 at time of Level of  	 	 	 % of respondents survey evidence   nominating this (September nominated by % Level ofPalliative symptom  Drug drug as first rank 2000) respondents responding evidence ReferencePain	using	opioid	analgesics	 Morphine	 98	 Yes		 1	 43	 2	 4	 		 	 	 	 	 2	 12	 		 	 	 	 	 3	 9	 		 	 	 	 	 4	 9	 	 	 	 	 5	 27Pain	using	nonopioid	analgesics	 Paracetamol	 88	 Yes	 1	 43	 1	 5	 	 	 	 	 2		 5	 	 	 	 	 3	 11	 	 	 	 	 4	 9	 	 	 	 	 5	 32Pain	using	adjuvant	analgesics	 Valproate	 61	 Yes	 1	 8	 1	 6	 	 	 	 	 2	 18	 	 	 	 	 3	 22	 	 	 	 	 4	 12	 	 	 	 	 5	 40Dyspnoea	 Morphine	 94	 No	 1	 9	 2	 7	 	 	 	 	 2	 18	 	 	 	 	 3	 26	 	 	 	 	 4	 15	 	 	 	 	 5	 31End	stage	respiratory		 Hyoscine		 86	 No	 1	 4	 4	 8reflexes	(grunting,	secretions)	 Hydrobromide	 	 	 2	 6	 	 	 	 	 3	 22	 	 	 	 	 4	 31	 	 	 	 	 5	 37Terminal	restlessness	 Midazolam	 81	 No	 1	 5	 4	 9	 	 	 	 	 2	 8	 	 	 	 	 3	 15	 	 	 	 	 4	 31	 	 	 	 	 5	 41Anorexia	 Dexamethasone	 69	 Yes		 1	 6	 2	 10	 	 	 	 	 2	 20	 	 	 	 	 3	 20	 	 	 	 	 4	 19	 	 	 	 	 5	 35Nausea	 Metoclopramide	 86	 Yes		 1	 19	 3	 11	 	 	 	 	 2	 14	 	 	 	 	 3	 12	 	 	 	 	 4	 11	 	 	 	 	 5	 45What are the essential medications in palliative care? – a survey of Australian palliative care doctors RESEARCHReprinted from Australian Family Physician Vol. 35, No. 4, April 2006  263time	of	 the	survey	are	 listed	 in	Table 2.	Table 2	shows	a	60%	agreement	between	 respondents	in	regards	to	the	number	one	medication	used	in	each	category,	apart	from	anxiety,	depression,	dry	mouth,	and	constipation.		 The	20	most	frequently	nominated	drugs	and	level	of	evidence	are	shown	in	Table 3.1Discussion The	response	rate	of	the	survey	was	low,	therefore	we	 cannot	 be	 sure	 this	 represents	Australian	palliative	 care	 doctors.	 Nevertheless,	 a	 broad	spectrum	of	 palliative	 care	 doctors	 responded	and	our	 findings	were	similar	 to	 the	 international	survey.1	There	were	 differences	 among	 the	 20	essential	drugs	with	only	10	common	to	both	lists	(the	top	eight,	followed	by	diazepam	and	fentanyl).	There	are	many	possible	explanations,	 including	different	 availability	 and	 formulations,	 costs	 and	different	preferences	 (perhaps	based	on	 clinical	experience	 rather	 than	evidence).	Laxatives	such	as	lactulose	are	commonly	prescribed	worldwide,	while	 in	Australia,	 docusate	 and	 senna	 is	most	commonly	prescribed.	There	 is	no	evidence	 that	adding	docusate	 to	senna	provides	benefit.	Any	difference	between	lactulose	and	senna	appears	to	be	minimal	in	the	small	amount	of	data	available.3	 There	 seems	 to	 be	 a	 relatively	 low	 level	 of	evidence	 for	 some	 important	 medications	 in	palliative	care	(eg.	midazolam)	although	the	majority	of	first	ranked	drugs	have	at	least	level	2	evidence.	Apart	from	the	most	frequently	used	medications,	there	 was	 a	 large	 discrepancy	 between	 the	respondents’	belief	about	the	available	evidence	and	what	is	actually	available.	For	example	paracetamol	for	pain,	where	 level	1	evidence	 is	available,	but	the	majority	 of	 respondents	 rated	 evidence	 as	levels	3–5,	while	more	 than	one	 in	3	 respondents	thought	morphine	only	had	level	4	or	5	evidence	for	analgesia,	whereas	 the	evidence	 is	 level	2.	About	a	 third	 thought	 there	was	 level	1–3	evidence	 for	hyoscine	hydrobromide	 (level	 4)	 and	midazolam	(level	4).	 We	have	used	these	lists	to	facilitate	a	process	to	 increase	 their	PBS	 listing	with	a	group	made	up	of	the	medical	profession	and	the	Rural	Health	and	 Palliative	 Care	Branch	 of	 the	Department	of	 Health	 and	Ageing	 in	 association	with	 the	Australian	government.	This	has	lead	to	a	section	in	 the	PBS	specifically	 for	palliative	care	with	an	initial	list	of	approved	drugs.		 For	many	widely	used	drugs	the	best	level	of	evidence	is	not	sufficient	to	justify	further	subsidy.	Reasons	may	be	 that	studies	have	not	yet	been	undertaken	–	we	should	address	this.Implications for general practice•	Access	to	drugs	for	palliative	care	is	harder	in	 the	 community	 (through	 the	PBS)	 than	in	hospital.•	A	survey	of	palliative	care	doctors	produced	a	list	of	drugs	they	thought	essential.•	Their	perception	of	the	evidence	for	their	use	was	variable.•	Collaborative	work	has	led	to	the	creation	of	the	first	ever	section	in	the	PBS	for	a	specific	patient	population.	•	There	 is	 a	 need	 for	 high	quality	 studies	 to	justify	PBS	listing	of	palliative	care	drugs.Table 2. (continued) Palliative symptoms, with the drug nominated as ‘essential’ for that symptom, by symptom control, PBS subsidy,  and perceived and actual evidence of benefit    PBS subsidy     	 	 	 	 at time of Level of  	 	 	 % of respondents survey evidence   nominating this (September nominated by % Level ofPalliative symptom  Drug drug as first rank 2000) respondents responding evidence ReferenceConstipation	 Docusate		 58	 No	 1	 9	 4E	 12	 	 and	senna	 	 	 2	 12	 	 	 	 	 3	 14	 	 	 	 	 4	 17	 	 	 	 	 5	 48Dry	mouth	 Artificial		 39	 No	 1	 –	 2	 13	 	 saliva	 	 	 2	 9	 	 	 	 	 3	 15	 	 	 	 	 4	 6	 	 	 	 	 5	 70Delirium	 Haloperidol	 84	 Yes		 1	 21	 2	 14	 	 	 	 	 2	 16	 	 	 	 	 3	 13	 	 	 	 	 4	 11	 	 	 	 	 5	 39Depression	 Sertraline	 40	 Yes	 1	 25	 2	 15	 	 	 	 	 2	 17	 	 	 	 	 3	 7	 	 	 	 	 4	 3	 	 	 	 	 5	 48Anxiety	 Diazepam	 52	 Yes		 1	 23	 2	 16	 	 	 	 	 2	 11	 	 	 	 	 3	 6	 	 	 	 	 4	 6	 	 	 	 	 5	 54What are the essential medications in palliative care? – a survey of Australian palliative care doctorsRESEARCH264  Reprinted from Australian Family Physician Vol. 35, No. 4, April 2006Conflict	of	 interest:	David	Woods	–	speaker	 fees	and	travel	assistance	to	attend	meetings	has	been	paid	for	by	Mundipharma	and	Janssen-Cilag.	AcknowledgmentsThanks to the Australian and New Zealand Society of Palliative Medicine and Palliative Care Australia for funding, to Mary Brooksbank for research assistance, and the Department of Health and Ageing (National Cancer Strategies Group and A/Prof Rosemary Knight) for support.References1. Dickerson D. The 20 essential drugs in palliative care. European Journal of  Palliative Care 1999;6:130–5.2. National Health and Medical Research Council. Guide to the development implementation and evaluation of clinical practice guidelines. Available at www.health.gov.au/nhmrc/publications/pdf/cp30.pdf Accessed 13 January 2005. 3. Agra Y, Sacristan A, Gonzalez M, Ferrari M, Portugues A, Calvo MJ. Efficacy of senna versus lactulose in terminal cancer patients treated with opioids. J Pain Symptom Manage 1998;15:1–7.4. Boureau F, Saudubray F, d’Arnoux C, et al. A comparative study of controlled release morphine (CRM) suspension and CRM tablets in chronic cancer pain. J Pain Symptom Manage 1992;7:393–9.5. de Craen AJ, Di Giulio G, Lampe-Schoenmaeckers JE, Kessels AG, Kleijnen J. Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review. BMJ 1996;313:321–5.6. McQuay H, Carroll D, Jadad AR, Wiffen P, Moore A. Anticonvulsant drugs for management of pain: a systematic review. BMJ 1995;311:1047–52.7. Bruera E, MacEachern T, Ripamonti C, Hanson J. Subcutaneous morphine for dyspnea in cancer patients. Ann Intern Med 1993;119:906–7.8. Bennett MI. Death rattle: an audit of hyoscine (scopolamine) use and review of management. J Pain Symptom Manage 1996;12:229–33.9. Burke AL, Diamond PL, Hulbert J, Yeatman J, Farr EA. Terminal restlessness: its management and the role of midazolam. Med J Aust 1991;155:485–7.10. Loprinzi CL, Kugler JW, Sloan JA, et al. Randomised com-parison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. 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Alprazolam and diazepam in the treatment of generalized anxiety. J Clin Psychopharmacol 1984;4:125–9.17. Wiffen PJ, Edwards JE, Barden J, McQuay HJ. Oral morphine for cancer pain. Cochrane Database Syst Rev 2003;CD003868.18. Glare P, Pereira G, Kristjanson LJ, Stockler M, Tattersall M. Systematic review of the efficacy of antiemetics in the treatment of nausea in patients with far advanced cancer. Support Care Cancer 2004;12:432–40.19. McQuay HJ, Tramer M, Nye BA, Carroll D, Wiffen PJ, Moore RA. A systematic review of antidepressants in neu-ropathic pain. Pain 1996;68:217–27.20. Purohit OP, Radstone CR, Anthony C, Kanis JA, Coleman RE. A randomised double blind comparison of intrave-nous pamidronate and clodronate in the hypercalcaemia of malignancy. Br J Cancer 1995;72:1289–93.21. Back IN, Jenkins K, Blower A, Beckhelling J. A study comparing hyoscine hydrobromide and glycopyrrolate in the treatment of death rattle. Palliat Med 2001;15:329–36.22. 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Gastroenterology 1992;103:1302–6.Table 3. Ranking of ‘essential’ drug, compared with those of a previous world surveyRank Drug Main palliative Rank number of a  Highest level Current PBS listing   care indication previous (world) of evidence (December 2005)    survey11	 Morphine	 Pain	 1,*	5*	 1		17	 Yes2	 Haloperidol	 Delirium	 2	 2		14	 Yes3	 Dexamethasone	 Anorexia/cachexia	 4	 2		10	 Yes4	 Midazolam	 Terminal	restlessness	 7	 4		9	 No5	 Metoclopramide	 Nausea/vomiting	 3	 1		18	 Yes6	 Clonazepam	 Terminal	restlessness	 15	 4E	 12	 Yes7	 Paracetamol	 Pain	 9	 1		5	 Yes8	 Amitryptiline	 Neuropathic	pain	 6	 1		19	 Yes9	 Pamidronate	 Hypercalcaemia	 	 2		20	 Yes10	 Cyclizine	 Nausea/vomiting	 	 4E		12	 No11	 Hyoscine	hydrobromide	 Excess	oropharyngeal	secretions	 	 3		21	 No12	 Diazepam	 Anxiety	 17	 2		16	 Yes13	 Lorazepam	 Anxiety	 	 2		22	 No14	 Omeprazole	 Dyspepsia	 	 1		23	 Yes15	 Chlorpromazine	 Delirium	 	 2		14	 Yes16	 Fentanyla	 Pain	 12	 1		24	 Yes17	 Spironolactone	 Ascites	 	 4		25	 Yes18	 Ranitidine	 Dyspepsia	 	 1		26	 Yes19	 Promethazine	 Nausea/itch	 	 4E		12	 Yes20	 Frusemide	 Ascites	 	 4		27	 Yesa	=	injectable	fentanyl	not	available	on	the	PBS		*	=	normal	release		+	=	sustained	releaseCORRESPONDENCE email: afp@racgp.org.au

What are the essential medications in palliative
            care? - A survey of Australian palliative care doctors

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What are the essential medications in palliative care? - A survey of Australian palliative care doctors

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