June 2003 PBAC Outcomes - "Subsequent" Decisions not to Recommend

"Subsequent" Decisions not to recommend, made by the Pharmaceutical Benefits Advisory Committee (PBAC) in June 2003

Drug and Form	TGA Indication	Current PBS Listing	Listing requested by Sponsor	PBAC Recommendation
Anagrelide hydrochloride capsule 500 µg, Agrylin® Orphan Australia Pty Ltd	Treatment of essential thrombocythaemia.	Not PBS listed		PBAC rejected the re-submission because of the clinical and economic uncertainties.
			Section 100 (Highly Specialised Drug) Private Hospital Authority Required for: Initial treatment of essential thrombocythaemia in patients 60 years of age or less who satisfy the following criteria: platelet count of not less than 1,000 x 109 per L or who have had a prior thrombotic event. Treatment of symptomatic essential thrombocythaemia in patients over 60 years of age, who initially had a platelet count of not less than 1,000 x 109 per L or who have had a prior thrombotic event, and who have failed to control platelet counts satisfactorily or failed to be tolerated or where such therapy is contraindicated as defined in the approved Product Information for the agent. Continuing treatment of essential thrombocythaemia where the patient has previously been issued with this drug under section 100 and the patient has demonstrated a response to treatment as manifested by a decrease in platelet count to less than 600 x 109 after 3 months and then a maintenance of this reduction is observed every 6 months thereafter.	PBAC noted that anagrelide reduces the platelet count and symptom rate to a similar level regardless of baseline platelet count. Additionally, the baseline rate of symptomatic events does not consistently increase with increases in the baseline platelet count. Thus, the platelet count thresholds for initiating and continuing anagrelide may not be justified.
			Comparator: Standard care	Accepted.
			Clinical Claim: Anagrelide is significantly more effective than standard care, but has more toxicity.	Rejected. PBAC found that there were several clinical uncertainties over the nature and extent of clinical benefit in the studies related to deficiencies in the measures taken to minimise bias.
			Economic Claim: A cost-effectiveness analysis was presented.	Rejected. PBAC concluded that there was uncertainty over interpretation of the cost-effectiveness ratios related primarily to the clinical uncertainty and the interpretation of the clinical outcome measure used in the ratios.
				Sponsor's comments: The sponsor will be considering its position regarding any future course of action.

Table containing subsequent decisions not to recommend, made by the PBAC in June 200
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Drug and Form	TGA Indication	Current PBS Listing	Listing requested by Sponsor	PBAC Recommendation
Bosentan tablets 62.5 mg and 125 mg, Tracleer® Actelion Pharmaceuticals Australia Pty Limited	For treatment of primary pulmonary arterial hypertension or pulmonary arterial hypertension associated with scleroderma with WHO Class 3 or 4 symptoms.	Not PBS listed		PBAC rejected the re-submission because of uncertainty in the clinical benefit, in terms of a gain in survival, and uncertain and inadequate cost-effectiveness.
			Section 100 listing for treatment of primary pulmonary arterial hypertension or pulmonary arterial hypertension associated with scleroderma with WHO Class 3 or 4 symptoms to improve exercise ability and symptoms, and decrease the rate of clinical worsening.	Accepted
			Comparator: Placebo for usual care without bosentan.	Accepted
			Clinical Claim: Bosentan is significantly more effective than usual care and has similar or less toxicity.	Rejected. PBAC considered that bosentan treatment resulted in an improvement in walking distance and improved functional class, but the trial provided did not demonstrate a difference in mortality.
			Economic Claim: A cost-effectiveness analysis was presented.	The economic model was rejected because it assumes a survival advantage even though no survival advantage was demonstrated in the trial.
				Sponsor's comments: The sponsor intends to lodge a re-submission.

Drug and Form	TGA Indication	Current PBS Listing	Listing requested by Sponsor	PBAC Recommendation
Nicotine, transdermal delivery system, 15 mg per 16 hours, Nicorette® Patch Pharmacia Australia Pty Limited	Treatment of nicotine dependence, as an aid to smoking cessation. It is intended to be used as part of an effective behavioural program in an overall strategy for smoking cessation. Therapy should be confined to short-term use (16 weeks) and be initiated after appropriate medical assessment.	Not PBS listed		PBAC rejected the re-submission as previously because the direct evidence indicates that nicotine transdermal patch is less effective than bupropion and because of uncertain cost-effectiveness.
			Authority required listing for use within an available treatment program, as short-term adjunctive therapy for nicotine dependence with the goal of maintaining abstinence. NOTE: Only one application per year with no increased maximum quantity or repeats will be authorised.	PBAC preferred a clearer wording that required patients to return to the doctor for their second supply of nicotine transdermal patch.
			Comparator: Bupropion	Accepted.
			Clinical Claim: Nicotine transdermal patch has similar effectiveness to bupropion, but has less toxicity.	Rejected. PBAC found the Bayesian approach is consistent with the results of the head-to-head randomised trial in confirming a therapeutic advantage for bupropion over nicotine transdermal patch, particularly with reference to sustained abstinence at 12 months. Thus, as previously, PBAC concluded that nicotine transdermal patch is less effective, but safer, than bupropion.
			Economic Claim: A cost-minimisation analysis and two cost-effectiveness analyses were presented.	Rejected. Given the conclusion that nicotine transdermal patch is less effective than bupropion, a model is required to address the longer-term health and economic impacts.
				Sponsor's comments: Pharmacia and Pfizer disagree with the decision. Please refer to the following website for further information. Weblink: www.nicorette.com.au