The use of pharmacoeconomic evidence to support formulary decision making in Saudi Arabia: Methodological recommendations

In pharmacoeconomics the costs and consequences of alternative medications are compared. Many countries have begun to use pharmacoeconomic evidence to support decisions on licensing, pricing, reimbursement, or addition to the formulary. In Saudi Arabia, it is not mandatory to submit cost effectiveness evidence to support licensing or addition to the formulary decisions however, data will be considered if submitted. Previous evidence suggests that the use of pharmacoeconomic evidence by Saudi Pharmacy and Therapeutic (P&T) committee members in formulary decisions making process is limited mainly because of lack of expertise and lack of resources. This paper intended to provide Saudi P&T decision makers with a clear set of best practice methodological recommendations to help in increasing the utilisation of pharmacoeconomic evidence in the formulary decisions making process.     

An integrated pharmacoeconomic approach to antimicrobial formulary decision-making.

PURPOSE: The utility of a novel interdisciplinary approach to antimicrobial formulary decision-making was studied. METHODS: Pseudomonas aeruginosa minimum inhibitory concentration (MIC) distribution data for cefepime and ceftazidime were retrieved from nonrepeat isolates obtained from November 2002 to October 2003. Unbound drug exposures were simulated for 5000 patients using the Monte Carlo method. Weighted target attainment rates (TARs) were calculated for cefepime and ceftazidime 1 g every 8 hours and 1 g every 12 hours (infused over 0.5, 2, and 4 hours), using three representative pharmacodynamic targets (percentage of time above the MIC of 67%, 100%, and 400%). RESULTS: MIC data for 1230 nonrepeat P. aeruginosa were analyzed. The MIC at which 90% of the P. aeruginosa isolates were inhibited was 16 and 32 mg/L for cefepime and ceftazidime, respectively. Drug acquisition cost was the highest with cefepime 1 g given every 8 hours (37.56 dollars/day), followed by cefepime 1 g every 12 hours (25.04 dollars/day) and ceftazidime 1 g every 8 hours (22.26 dollars/day). When infused over 0.5 hour, the highest TAR was achieved with cefepime 1 g every 8 hours (82%), followed by ceftazidime 1 g every 8 hours (77%) and cefepime 1 g every 12 hours (66%); ceftazidime 1 g every 8 hours was 70% more cost-effective than cefepime 1 g every 8 hours. Cefepime 1 g every 12 hours, infused over 4 hours, increased the TAR to 89% and was similar in cost-effectiveness to ceftazidime 1 g every 8 hours infused over 0.5 hour. CONCLUSION: An integrated pharmacoeconomic approach to antimicrobial formulary decision-making addressed local resistance patterns, population pharmacokinetics, pharmacodynamics, dosing regimens, and drug acquisition costs. This method appeared to be more realistic and objective than the conventional approach of considering only drug acquisition costs, especially for agents in a similar structural or functional class.     

Use of centrally developed pharmacoeconomic assessments for local formulary decisions.

PURPOSE: The distribution, content, timeliness, use, and influence of pharmacoeconomic assessments (PEAs) of drugs in New Zealand public hospitals were examined. METHODS: In April 2005, a questionnaire-based, cross-sectional survey was sent to chief pharmacists at all 29 New Zealand hospitals employing a pharmacist. The questionnaire asked pharmacists about the use and influence of PEAs in their hospitals' formulary decision-making process. Answers were given using a scale of 1 to 6, with 1 being the most positive response. RESULTS: Of the 29 surveys mailed, 24 (83%) were completed. Data on 12 PEAs were analyzed. Assessments were seen and summaries read in most hospitals (median, 77% and 65%, respectively). Full documents were read in fewer hospitals (35%). In general, the PEAs were considered moderately easy to understand, provided a concise summary, and contained adequate detail of the methodology. Of the 24 respondent hospitals, 21 had assessment processes for new medicines; hence, a total of 252 hospital evaluations of Pharmaceutical Management Agency (PHARMAC)-assessed drugs were possible. A total of 132 possible evaluations (52%) were undertaken. More evaluations (106 [42%]) took place before PHARMAC's PEAs were distributed and fewer (26 [10%]) after distribution. Where used, the PEAs appeared to have a modest effect on hospital decisions. CONCLUSION: The provision of 12 PEAS by PHARMAC to hospitals in New Zealand had only a modest influence on their formulary decision-making process, mostly due to the lack of timeliness of the PEAs. The timely delivery of centrally developed PEAs may be essential to generating a greater effect on the formulary decisions at a wider level.     

Institutional formularies: the relevance of pharmacoeconomic analysis to formulary decisions

Formularies, in one form or another, have been in existence for nearly 100 years. Beginning simply as a list of available agents, the formulary has evolved into a complex system which acts as a guide to prescribing practices. As the importance of the formulary has increased, so has the need for formulary managers to make an appropriate decision about each drug's formulary status. Several systematic approaches to drug evaluations have been developed to aid in the decision process. However, while some reviews of drug utilisation contain fairly rigorous analyses of their clinical efficacy, very few include an economic evaluation that goes beyond the cost of drug acquisition, preparation, distribution and administration. This is surprising, since formulary managers rank economic data second only to clinical data when making formulary decisions. In the past this apparent oversight has been due, in part, to the absence of a sophisticated model which can both approximate a drug's true economic impact and express cost and quality in similar terms. The explosion of new and very expensive biotechnology drugs into the market has the potential to improve patient care significantly. Such drugs also have the potential to increase institutional pharmacy budgets significantly; with some analysts predicting a spending of $US60 million yearly for these drugs by the year 2000, critical evaluation will be mandatory. Fortunately, advances in the relatively new science of pharmacoeconomics have made it possible to conduct appropriate estimates of the true economic impact of new drug therapies. Pharmacoeconomic studies can be very useful in evaluating drugs for formulary inclusion and in assessing the effects of formulary changes on institutional budgets. Cost-effectiveness and cost-benefit analyses, utilising decision analysis models and/or data gathered from clinical studies, are used most frequently. Relatively simple models can be used to evaluate drugs within the same class if sufficient published data on their clinical efficacy and safety are available. More complex analyses are necessary when comparing dissimilar agents or when comparing agents with non-drug therapy. Pharmacoeconomic studies have frequently been used to demonstrate that very substantial direct costs of drug therapy are often offset by equal or greater reductions in other institutional direct and indirect patient care costs. Pharmacoeconomic studies have also been used to calculate the relative cost-effectiveness of drug therapies for different disease states, although such evaluations are more useful to governmental and regulatory agencies than to individual institutions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Relationship between practice guidelines, formulary management, and pharmacoeconomic studies

Pharmacy and therapeutics committees can use pharmacoeconomic and outcome studies as tools to evaluate and implement clinical guidelines for patient care. Results of studies help optimize the clinical effects and control the costs of drug therapy. Such data also assist in positioning products in competitive environments. A four-part classification of research studies is offered as an aid to strategic research planning.     

Interpreting pharmacoeconomic and quality-of-life clinical trial data for use in therapeutics

Interpretation of quality-of-life (QOL) and pharmacoeconomic data for therapeutic decision making and therapeutic policy planning requires a basic understanding of the methods, assumptions and limitations of the data and associated methods of analysis. Measures of the effectiveness of different pharmaceutical agents can be modified by including functions which involve assessment of the treated individual's quality of life. These quality-adjusted effectiveness measures will alter conclusions concerning clinical decisions as well as the cost-effectiveness of the comparative agents under consideration. To provide a conceptual and analytical framework for understanding the relationship between QOL assessment and pharmacoeconomic modelling, interpretations of the quality-adjusted analyses are reviewed, conceptual and analytical models are proposed, and recommendations for using QOL data in pharmacoeconomic models are outlined. Techniques for incorporating QOL measures in pharmacoeconomic models are examined using a hypothetical model involving therapeutic assessments of antiviral treatments for individuals with HIV disease. Adjustments of effectiveness measures based upon QOL-related functions are then globally addressed using stochastic compartmental models. Three specific methods for adjustment used in therapeutic trials are reviewed. Applications of these techniques to 3 studies involving the treatment of HIV disease and hypertension are critically reviewed. Issues relevant to choosing or estimating measures of quality of life for use in pharmacoeconomic models are summarised, and research guidelines are proposed.     

Obtaining pharmacoeconomic data in health care organizations

The article illustrates the process and techniques of obtaining or collecting pharmacoeconomic data in various health care organizations, focusing on hospitals, physicians' offices, and pharmacies as the research settings. The role that pharmacoeconomic data have in the decision-making process as well as the perspective of the decision maker are also discussed. The three primary components needed to conduct a complete pharmacoeconomic analysis (clinical outcomes, humanistic outcomes, and economic outcomes) are described in relation to the health care organization. The strengths, weaknesses, advantages, and disadvantages of such data are discussed. Various databases that are accessible within each organization are also outlined.     

Pharmacoeconomic series: Part 3. Applying pharmacoeconomic and quality-of-life measures to the formulary management process

P & T Committees were established as an institution's primary organizational tool for the development and maintenance of the formulary. Traditionally, P & T Committees have focused on the safety, efficacy, and acquisition cost of medications to be considered for formulary approval. Today, the impact of pharmaceuticals on patients' quality-of-life and total health care expenditures are increasingly important considerations to be weighed by P & T Committees. Pharmacoeconomic analyses and quality-of-life outcomes represent valuable contributions to the formulary decision-making and management process.     

The pharmacoeconomic impact of amlodipine use on coronary artery disease.

The most frequent cause of mortality and morbidity in industrialized countries is coronary artery disease (CAD), which in Europe alone is responsible for around two million deaths per year. In 2001 it accounted for about 260,000 hospital discharges in Italy. The costs of CAD treatment in Italy--which were borne by the Italian state, the third-party payer--amounted to 800 million euros. We propose to assess the pharmacoeconomic implications of using amlodipine besylate treatment in Italy for patients with coronary artery disease. The study is based on a post-hoc cost-effectiveness analysis that compared standard care supplemented by amlodipine besylate with ordinary standard care over a 36-month time horizon. The clinical outcome data were based on the prospective randomized evaluation of vascular effect of norvasc trial (PREVENT). Direct medical costs referred to the purchase costs of amlodipine besylate and the cost of National Health Service (NHS) hospitalization. The costs were discounted back at an annual rate of 5%. Patients administered amlodipine besylate exhibited a significant risk reduction with respect to any major vascular event or procedure when compared to the placebo group. The reduction mainly referred to unstable angina events and revascularization procedures. We estimated that the total cost of adding amlodipine besylate to standard care amounted to 139,050 euros per 1000 patients treated for 36 months. This represents a cost of 1780 euros per patient remaining free of any vascular event. Results were sensitive to both clinical and economic variables. The incremental costs of the alternative therapy ranged from 296 euros to 5066 per patient free of any event in, respectively, the best and worst scenario. Amlodipine besylate therapy can be a cost-effective strategy for CAD treatment in Italy. Our economic evaluation demonstrated, first, that by reducing vascular events and the need for revascularization procedures savings were achieved in hospital expenditure, and, second, that such savings could significantly offset drug costs.     

The effect of formulary restriction in the use of antibiotics in an Italian hospital

OBJECTIVE: To compare the expenditure and usage of antibiotics at the San Martino Teaching Hospital, a 2500-bed hospital in Genoa, Italy, before and after the implementation of an antibiotic control program that streamlined the hospital formulary and the creation of a restricted group of antibiotics requiring approval before use. METHODS: Usage and expenditure data for all antibiotics were collected from 1996 to 1998. Antibiotic usage was standardised by defined daily doses (DDDs) per 100/patient-days. Cost data were expressed in Euros. Changes in antibiotic usage was determined by comparing the mean usage during 1996 and 1997, the period before the implementation of the antibiotic control program, to 1998 when the streamlined formulary and restricted group of antibiotics, controlled by the Infectious Disease Team (IDT). were initiated. The Wilcoxon rank sign test was used to determine statistical significance of the changes in overall antibiotic use; a P value of less than 0.05 was considered significant. RESULTS: After the implementation of the antibiotic control program, overall antibiotic usage decreased by 8.5%, 28.00 DDD/100 patient-days during 1996-1997 to 25.62 DDD/100 patient-days during 1998. The control program resulted in overall savings of 342,927 Euros after the first year of implementation. The usage and expenditure in the restricted group of antibiotics decreased by 78.5% and 53.5%, respectively, (P=0.03). Restricting the use of ceftazidime and imipenem accounted for the majority of the decreased usage and savings. In the non-restricted group of antibiotics, usage increased only by 32.6% resulting in a net reduction of 46.3% in all antibiotic use. CONCLUSION: Although antibiotic control programs have been successful in other countries, this represents the first attempt at successful antibiotic control in a large Italian teaching hospital. Streamlining the formulary to control antibiotic choices and the creation of a restriction program using the expertise of infectious disease physicians resulted in significant reductions in the use of and expenditure for antibiotics.     

Sertraline. A pharmacoeconomic evaluation of its use in depression

Depression is a common condition that is often unrecognised, misdiagnosed and/or undertreated. It is associated with substantial direct, indirect and intangible costs. The indirect costs of lost earnings/productivity and premature death account for the majority of these costs; drug costs account for only about 1 to 2% of total costs and about 10 to 12% of direct costs. Thus, better recognition and appropriate treatment of depression would increase the direct costs associated with this illness, but would also have the potential to greatly reduce indirect costs and consequently the overall cost of depression. Because of their higher acquisition costs relative to tricyclic antidepressants (TCAs), there has been much debate about whether the use of sertraline or other selective serotonin reuptake inhibitors (SSRIs) for first-line treatment of depression can be justified. While these agents have similar efficacy to TCAs, they are better tolerated and have a lower risk of death on overdosage. Despite the large economic burden of depression on society, pharmacoeconomic data on sertraline and antidepressant drugs in general are scarce. Most of the available studies on sertraline are limited to considerations of direct costs and do not assess costs from a societal perspective. In addition, a number of studies have significant methodological problems which limit determination of meaningful conclusions. Nonetheless, data from 2 more recent studies with fewer methodological problems than earlier studies indicated that sertraline was more cost-effective than TCAs because of fewer psychiatrist consultations, and less costly than fluoxetine because of fewer absences from work and fewer medical consultations. The cost-utility ratio of maintenance therapy of depression with sertraline appears to fall within the range of accepted cost-utility ratios of common healthcare interventions. Thus, studies to date have generally shown that overall treatment costs with sertraline and other SSRIs are no greater than those for TCAs; this is despite the lower acquisition costs of the latter agents. Therefore, it is clear from these data that it is misleading to classify antidepressant agents as expensive or inexpensive based solely on their acquisition costs. Sertraline, therefore, can be considered as a first-line alternative to TCAs and other SSRIs for the treatment of depression on both clinical and pharmacoeconomic grounds.     

Mirtazapine. A pharmacoeconomic review of its use in depression

Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA). The antidepressant efficacy of mirtazapine has been established in randomised, double-blind comparative studies. Mirtazapine has generally shown similar efficacy to other antidepressants. There is evidence for a faster onset of action with mirtazapine than with the selective serotonin (5-hydroxytryptamine; 5-HT) re-uptake inhibitors (SSRIs) on the basis of mean depression rating scale scores. Data from a long term (mean 240 days) clinical trial that was subsequently used in pharmacoeconomic analyses showed that mirtazapine was associated with significantly higher sustained remission rates and rates of discontinuation because of improvement than amitriptyline and placebo. Although differences were not statistically significant, mirtazapine had higher response rates at 6 weeks than the SSRI fluoxetine in an analysis that was also used as the basis of pharmacoeconomic studies. Mirtazapine improved quality of life to a similar extent to fluoxetine, citalopram and paroxetine in unpublished studies of 6 and 8 weeks' duration. Pooled analyses suggest that mirtazapine may be associated with greater improvement than fluoxetine and citalopram in quality of life after 2 and 4 weeks, although confirmation is required. In a decision analytical model of approximately 6 months' duration, mirtazapine was associated with a higher proportion of successfully treated patients and lower total direct costs than amitriptyline. The direct cost per successfully treated patient with mirtazapine was lower than that with amitriptyline by 33,112 Austrian schillings (S; year of costing not stated), 24,212 French francs (FF; 1995/1996 values), 13,851 Swedish kronor (SEK; 1997 values) and 553 Pounds (1997/1998 values) in Austrian, French, Swedish and UK analyses, respectively. Compared with fluoxetine, mirtazapine was associated with higher per-patient costs in all 4 countries but a higher proportion of successfully treated patients. Mirtazapine was more cost effective than fluoxetine: the direct cost per successfully treated patient was lower by S32,046 in Austria, FF25,914 in France, SEK9796 in Sweden and 327 Pounds in the UK. The additional cost of mirtazapine versus fluoxetine for each additional successfully treated patient at 6 months was S11,732, SEK17,229, 750 Pounds and FF3342 in the Austrian, Swedish, UK and French analyses, respectively. Mirtazapine was generally associated with lower indirect costs (for lost productivity of employed patients) than amitriptyline and similar indirect costs to fluoxetine in the analyses. CONCLUSIONS: Available data suggest that mirtazapine is a cost-effective alternative to amitriptyline and fluoxetine for the treatment of depression. Mirtazapine also has similar effects to SSRIs on quality of life with possibly a shorter time to onset of action, although published trial results are required to confirm these preliminary data.     

Paroxetine. A pharmacoeconomic evaluation of its use in depression

There has been intense debate about whether the use of paroxetine or other selective serotonin reuptake inhibitors (SSRIs) as alternatives to tricyclic antidepressants for first-line treatment of depression can be justified, considering their higher acquisition costs. The rationale for using paroxetine in the treatment of depression lies in its more favourable tolerability profile than tricyclic antidepressants and its lower risk of death on overdosage. Depression is one of the most common psychiatric disorders and is associated with substantial direct, indirect and intangible costs. Indirect costs account for the majority of costs associated with depression, while drug costs account for only 9 to 25% of direct costs. Therefore, increased recognition and treatment of depression has the potential to greatly reduce the overall cost of this disease. Pharmacoeconomic data on paroxetine and other SSRIs in the treatment of depression are scarce. Available studies are limited to considerations of direct costs alone and are primarily based on retrospective data from clinical trials. Nevertheless, in terms of costs per successfully-treated patient, available data suggest that the treatment costs associated with paroxetine are similar to those of amitriptyline and possibly less than those of imipramine. Paroxetine treatment costs also appear to be similar to those of amitriptyline and imipramine in terms of expected costs per patient. While one group of investigators suggested that the overall cost of administering paroxetine may also be less than that for fluoxetine and sertraline when drug costs and labour costs associated with dosage adjustment are taken into account, more data are required before conclusions on the relative pharmacoeconomic merits of SSRIs can be made. Despite the lower risk of death from overdosage with SSRIs, switching from an established tricyclic antidepressant to a newer tricyclic or related antidepressant in an attempt to avoid suicide appears to be more cost effective than switching to an SSRI. Thus, evidence available to date indicate that despite higher acquisition costs paroxetine and other SSRIs are no more costly than tricyclic antidepressants when total costs per successfully treated patient or expected costs per patient are considered. With its favourable tolerability profile and low risk of death on overdosage, paroxetine should therefore be considered as an effective alternative to tricyclic antidepressant agents as a first-line treatment of depression.(ABSTRACT TRUNCATED AT 400 WORDS)     

Escitalopram: a pharmacoeconomic review of its use in depression

Escitalopram (Cipralex), a new highly selective serotonin reuptake inhibitor (SSRI), is the active S-enantiomer of RS-citalopram. It is effective in the treatment of patients with major depressive disorder (MDD) and may have a faster onset of therapeutic effect than citalopram. It has also been shown to lead to improvements in measures of QOL. Escitalopram is generally well tolerated, with nausea being the most common adverse event associated with its use. Modelled pharmacoeconomic analyses found escitalopram to have a cost-effectiveness and cost-utility advantage over other SSRIs, including generic citalopram and fluoxetine and branded sertraline, and also over the serotonin-noradrenaline reuptake inhibitor (SNRI) venlafaxine extended-release (XR). These studies used a decision-analytic approach with a 6-month time horizon and were performed in Western Europe (year of costing 2000 or 2001). Cost-effectiveness ratios for escitalopram, in terms of cost per successfully treated patient over 6 months, ranged from Euro 871 to Euro 2598 in different countries, based on direct costs and remission rates, and were consistently lower (i.e. more favourable) than the ratios for comparators (Euro 970 to Euro 3472). Outcomes similarly favoured escitalopram when indirect costs (represented by those associated with sick leave and loss of productivity) were included. The results of comparisons with citalopram, fluoxetine and sertraline were not markedly affected by changes to assumptions in sensitivity analyses, although comparisons with venlafaxine XR were sensitive to changes in the remission rate. The mean number of QALYs gained during the 6-month period was similar for all drugs evaluated, but direct costs were lower with escitalopram, leading to lower cost-utility ratios than for comparators. Incremental analyses performed in two of the studies confirmed the cost-effectiveness and cost-utility advantage of escitalopram. A prospective, 8-week comparative pharmacoeconomic analysis found that escitalopram achieved similar efficacy to venlafaxine XR, but was associated with 40% lower direct costs (Euro 85 vs Euro 142 per patient over 8 weeks; 2001 costs), although this difference did not reach statistical significance. In both the modelled and prospective analyses, the differences in overall direct costs were mainly due to lower secondary care costs (in particular those related to hospitalisation) with escitalopram. In the prospective analysis, escitalopram had lower estimated drug acquisition costs than venlafaxine XR. CONCLUSION: Escitalopram, the S-enantiomer of RS-citalopram and a highly selective SSRI, is an effective antidepressant in patients with MDD, has a favourable tolerability profile, and, on the basis of available data, appears to have a rapid onset of therapeutic effect. Modelled pharmacoeconomic analyses from Western Europe suggest that it may be a cost-effective alternative to generic citalopram, generic fluoxetine and sertraline. Although the available data are less conclusive in comparison with venlafaxine XR, escitalopram is at least as cost effective as the SNRI based on a prospective study, and potentially more cost effective based on modelled analyses. Overall, clinical and pharmacoeconomic data support the use of escitalopram as first-line therapy in patients with MDD.