Samuel R. Saks

Translating safety, efficacy and compliance into economic value for controlled release dosage forms.

SummaryAdvanced controlled release (CR) dosage forms are relative newcomers to pharmaceutical markets, and few studies relate their efficacy, safety or compliance benefits to economic value. This literature review was undertaken to assess the cost effectiveness of CR dosage forms using such measures as purchase costs, total treatment costs, and economic value of improved therapeutic outcomes compared with those with non-CR dosage forms. Three therapeutic areas were examined: cardiovascular therapy, pain management and estrogen replacement therapy.In cardiovascular therapy, prescription costs of sustained re lease (SR) verapamil were significantly higher than for conventional release verapamil. However, these were more than offset by lower physician, hospital and laboratory expenditures for the SR group, in whom compliance was superior. Similarly, patients receiving SR diltiazem had better prescription refill compliance than those using a conventional formulation of the drug, as well as significantly lower aggregate healthcare costs during a 1-year study period. These lower costs with both SR verapamil and diltiazem may relate to better compliance.CR nifedipine has lower daily acquisition costs than the conventional form, simplifies the dosage regimen to once daily, extends the indications of the drug to hypertension as well as angina, and reduces vasodilatory adverse effects by reducing peak plasma drug concentrations and the postdose rate of increase in concentration.Compared with oral clonidine given twice daily, transdermal clonidine, given once weekly, had higher purchase costs, but was associated with improved compliance, reduced adverse effects (due to control of plasma concentrations), and lower nondrug health costs, such as physician, hospital and laboratory costs. Lower costs were also found for once daily oral formulations of various antihypertensives, suggesting that the economics of both types of CR dosage forms related to compliance.CR metoprolol 50 or 100mg and conventional release atenolol 50mg, each given once daily, provided effective β1-adrenoceptor blockade. The conventional formulation caused deterioration in the sense of well-being that was temporally associated with sharp peaking of its plasma concentrations. Such peaking did not occur with either dose of CR metoprolol, nor did any deterioration in the sense of well-being.Transdermal nitroglycerin (glyceryl trinitrate), compared with long-acting oral nitrates, improved quality of life (QOL) [despite a higher incidence of some adverse effects, such as headache, dizziness and skin irritation]. Furthermore, in some studies, this formulation reduced angina attacks, sublingual nitroglycerin use, and hospitalisation or emergency room use. Cost comparisons between transdermal products favoured those that have superior adhesion.In pain management, CR oral morphine and transdermal fentanyl have higher acquisition costs than short-acting tablets or injectable agents, but lower total administration costs may outweigh the higher purchase price. The long-acting products also alleviate many pain management problems, including inadequate or mistimed dosage, labour intensiveness, lack of patient acceptance, and adverse effects on QOL. Transdermal fentanyl is comparable in price to CR morphine, but is administered every 3 days versus twice daily for CR morphine. The transdermal formulation can be used by patients unable to take oral medication.Transdermal estrogen has a higher acquisition cost than oral estrogen, but is effective in lower doses. Furthermore, the transdermal formulation does not cause an increase in renin substrate or other hepatic proteins, and is not associated with adverse hepatobiliary changes, while providing physiological estrogen levels. It is applied twice weekly, reducing noncompliance due to adverse effects or forgetfulness.In conclusion, some CR dosage forms add economic value to drug products by simplifying administration regimens, with resultant enhanced compliance, and by controlling drug input, which prevents super- or subtherapeutic plasma drug concentrations. The subsequent improvements in efficacy, adverse effect profile and QOL can decrease the costs associated with diagnosing and treating toxic effects of drugs. In addition, the need for costly re-evaluation to adjust dose, change medications or escalate therapy is minimised. Thus, overall care costs, not solely drug purchase costs, should be the criteria for assessing the economic value of drug products.

The pharmacoeconomic value of controlled-release dosage forms

Abstract In recent years the health care industry has been increasingly charged with establishing the economic “value” of new pharmaceutical products. Controlled-release dosage forms have a significant potential to provide economic value by enhancing efficacy and decreasing treatment costs. In this article we review basic pharmacoeconomic concepts as they apply to controlled-release dosage forms, give an overview of strategies for economic assessment of new drug therapies, summarize selected published stidies that have evaluated the cost effectiveness of controlled-release products, and present examples of three types of pharmacoeconomic analyses that have been considered recently at ALZA Corporation. We conclude by noting the particular value provided by obtaining timely information about a products costs, benefits and relative cost-effectiveness from prospective clinicoeconomic studies.