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Proton pump inhibitors for acid suppression in the intensive care unit: formulary considerations.

PURPOSE: The rationale for limiting the proton pump inhibitor (PPI) products included in an institutional formulary, factors to consider when making formulary decisions about PPI products, the results and limitations of cost-effectiveness analyses of PPI therapy in critically ill patients, the role of clinical practice guidelines in improving PPI use in the intensive care setting, and how these guidelines can be developed are discussed. SUMMARY: Therapeutic interchange may make it possible to limit the number of PPI products included in the formulary and reduce costs without compromising the efficacy or safety of drug therapy. The results of studies comparing the pharmacokinetics, pharmacodynamics, and efficacy of different PPI dosage forms and routes of administration; practical considerations; safety; and costs are among the factors to consider when making formulary decisions. Some of the newer oral PPI products offer advantages over older ones in improved palatability and ease of preparation, storage, and administration. The cost-effectiveness of intravenous (i.v.) PPIs for preventing the recurrence of peptic ulcer bleeding has been demonstrated, but the cost-effectiveness of oral therapy for this indication and both oral and i.v. therapy for preventing stress-related mucosal bleeding has not been well established. CONCLUSION: Intravenous PPIs are cost-effective for patients at risk for the recurrence of peptic ulcer bleeding. The introduction of new oral PPI products that can be administered as a suspension has expanded the therapeutic options for critically ill patients. The use of clinical practice guidelines can optimize the use of PPIs in the intensive care setting.

Cost-Benefit Analysis↗

Formularies, therapeutics, and outcomes: new opportunities.

The increasing prominence of drug therapies in health care and their rapidly rising costs have led to a dramatic escalation of interest in the use of outcomes data for therapeutics and formulary decisions. The expanded use of formulary submission dossiers, effectiveness data, health outcomes analysis, and pharmacoeconomic modeling has created an urgent need for outcomes research to investigate topics especially relevant for health plan drug therapy coverage decisions. This article examines the evolving use of outcomes data on drug formulary and other therapeutic decisions, and outlines several priority areas for outcomes research. These include research into surrogate measures of long-term health and economic outcomes, evaluations of new formulary submission programs, and research on the impact of pharmaceutical cost-sharing arrangements on health outcomes. The article also discusses the importance of evaluating patient compliance and health outcomes after implementation of a Medicare prescription drug benefit, and the need for new types of clinical trials that can respond to changing demands of pharmacy and therapeutics committees and providers

Adolescent↗

Using interrupted time series analysis to assess associations of fluoroquinolone formulary changes with susceptibility of gram-negative pathogens and isolation rates of methicillin-resistant Staphylococcus aureus.

The use of fluoroquinolones has been linked to increasing bacterial resistance and infection and/or colonization with already resistant pathogens both as a risk factor and based on volume of use. Changes in individual fluoroquinolones used in an institution may also be related to these clinical problems. Interrupted time series analysis, which allows for assessment of the associations of an outcome attributable to a specific event in time, was used to study the effect of changes in our hospital's fluoroquinolone formulary on fluoroquinolone susceptibility rates in select gram-negative pathogens and the methicillin-resistant Staphylococcus aureus (MRSA) isolation rate. Susceptibility rates to ciprofloxacin were considered for the period of 1993 through 2004, while the MRSA isolation rate was assessed from 1995 through 2004. Levofloxacin was added to the formulary in 1999, and gatifloxacin was substituted for levofloxacin in 2001. Statistically significant changes in the already declining rates of susceptibility of Pseudomonas aeruginosa (P, 0.042) and Escherichia coli (P, 0.004) to ciprofloxacin and in the already rising MRSA isolation rate (P, 0.001) were associated with the addition of levofloxacin to the formulary. Substitution of gatifloxacin for levofloxacin on the formulary was associated with reversals in the downward trend in E. coli susceptibility to ciprofloxacin and the upward trend in MRSA isolation rate. No associations were detected on susceptibility of Klebsiella pneumoniae or Proteus mirabilis to ciprofloxacin. These findings suggest that potential changes in susceptibility to fluoroquinolones and isolation of MRSA may vary by both drug and organism.

Anti-Bacterial Agents↗

The use of drug formularies in managed care.

As a way of controlling the rising costs of health care, most managed care companies have implemented drug formularies. A drug formulary is generally defined as a listing of medications the health plan will cover for reimbursement. Some medications may need authorization from the health plan before they will be dispensed. This paper argues that drug formularies contain cost while causing no physical harm to the patient. The method of research used is descriptive. The paper will examine the issue from the side of the physician, the health plan and the patient. The research includes personal interviews, anecdotal records and reviews of available literature. The findings will show that patients still have access to a wide range of therapeutic medications and do not suffer physical harm as a result of a drug formulary.

Cost Control↗

Do open formularies increase access to clinically useful drugs?

Before 1990 many state Medicaid programs maintained "restrictive" formularies, which denied reimbursement for unlisted prescription drugs. This type of formulary has been criticized for denying important medications to poor, medically needy persons. As part of the Omnibus Budget Reconciliation Act of 1990, restrictive formularies in Medicaid programs were disallowed. Based on research into the 200 top-selling prescription drugs in the United States, we conclude that eliminating Medicaid restrictive formularies improved access to a subset of the 200 best sellers, but that the majority of these products offered only questionable or no additional therapeutic benefit.

Drug Costs↗

The impact of a national prescription drug formulary on prices, market share, and spending: lessons for Medicare?

Several recent bills in Congress to add a Medicare prescription drug benefit would allow the use of formularies to control costs. However, there is little empirical evidence of the impact of formularies among elderly and disabled populations. We assess the effect of a closed formulary implemented by the Veterans Health Administration (VHA) in 1997 on drug prices, market share, and drug spending. We find that the VHA National Formulary was effective at shifting prescribing behavior toward the selected drugs, achieving sizable price reductions from manufacturers, and greatly decreasing drug spending.

Aged↗

Formulary management.

The hospital formulary is not only a list of drugs, but also a policy that involves several complex processes and activities. Formularies are developed based on cost-effectiveness evaluation, but maintaining cost-effectiveness requires educational strategies. The clinical pharmacist plays an active role in formulary processes. These processes are discussed in this paper. There is a need for studies on the cost-effectiveness of clinical pharmacy services in support of the hospital formulary.

Clinical Trials as Topic↗

Alternate financial incentives in multi-tiered formulary systems to improve accountability for outcomes.

BACKGROUND: Drug manufacturer rebates paid to health plans and pharmacy benefit management companies have come under increased public scrutiny. Over the past several years, numerous articles have appeared in the literature encouraging a shift to a more quality-based decision-making process for health plan drug formularies. OBJECTIVE: To propose a new basis for formulary placement decisions that would include consideration of health-plan-specific measures (clinical outcomes, total cost, adherence, and appropriateness of care) and align incentives for health plans, physicians, pharmacists, and pharmaceutical companies to promote high-quality care. SUMMARY: The proposed approach builds on key components of the Pharmacy's Framework for Drug Therapy Management in the 21st Century and the Academy of Managed Care Pharmacy's Format for Formulary Submission, including a focus on patient outcomes and evidence-based decision making. The proposed approach would lessen the influence of drug manufacturer rebates on formulary placement by shifting the focus to appropriateness of care, clinical outcomes, patient adherence, and total cost of care. Pharmaceutical manufacturers would benefit from the focus on adherence to drug therapy and total cost of care. Health plans and pharmacy benefit management companies would gain in that they may be able to reduce efforts in drug utilization review as pharmaceutical manufacturers are given incentives to market their drugs more appropriately. Physicians and pharmacists would benefit because the rebate money would be used to provide quality-based financial incentives related to adherence and appropriate use of drugs. CONCLUSION: The implementation of this approach would be difficult and require cooperation from employers, pharmacists, pharmaceutical manufacturers, health plans, and pharmacy benefit management companies. Aspects of this approach could be incorporated into existing pharmacy benefit management processes to encourage the delivery of high-quality health care.

Cyclooxygenase Inhibitors↗

Clinical monograph for drug formulary review: systemic agents for psoriasis/psoriatic arthritis.

BACKGROUND: Significant advances in the pharmacologic treatment of psoriasis, most notably the introduction of the biologic agents efalizumab and alefacept, have occurred recently. In addition, another biologic agent, etanercept, was recently approved for the treatment of psoriasis and psoriatic arthritis, thus adding to the list of biologic agents approved for the treatment of these disease states. A review was conducted by the Drug Information Service of a pharmacy benefits manager (PBM) to determine the relative merits and place in therapy of commonly used systemic agents for the treatment of psoriasis and psoriatic arthritis. OBJECTIVE: To provide readers with a comprehensive clinical monograph on psoriasis and psoriatic arthritis agents, written with a managed care perspective, as used in actual drug formulary decision making by a PBM. METHODS: The drug formulary of this PBM is designed to provide health plans with an evidence-based review of drugs, therapeutic classes, and disease states with a managed care focus. For each therapeutic class or disease review, an extensive and thorough literature search of MEDLINE is conducted for efficacy, safety, effectiveness, and humanistic and economic data. Drug/disease-state databases (UpToDate online, MICROMEDEX), U.S. Food and Drug Administration clinical reviews, key Internet sites, medical/pharmacy-related news sites, clinical guidelines, and AMCP dossiers are also reviewed. Formulary drug monographs produced by the Drug Information Service of the PBM include a critical analysis and summary of disease-oriented and patient-oriented clinical outcomes, effectiveness, and humanistic data. Additional data considered and included in the formulary review process are clinical attributes, patent expirations/generic competition, off-label or pending indications, and pharmacoeconomic data. RESULTS: The biologic agents do not appear to be as efficacious as traditional systemic therapies but are associated with fewer long-term toxicities that often limit treatment duration with traditional systemic agents. Although no head-to-head comparisons between alefacept and efalizumab exist, efalizumab appears to offer slightly higher efficacy rates, while alefacept has a longer duration of action. Etanercept at the higher approved dose appears more efficacious compared with efalizumab or alefacept for the treatment of psoriasis, and it is the only biologic currently approved for the treatment of psoriatic arthritis. Efalizumab and alefacept are generally well tolerated, but rebound flare of psoriasis is associated with efalizumab, thus requiring continuous treatment to avoid a flare in disease. Efalizumab and etanercept can be self-administered by the patient, while alefacept and infliximab require administration by a health care professional. CONCLUSIONS: Systemic therapy is reserved for patients with moderate-to-severe psoriasis or patients with psoriatic arthritis. The biologic agents are not as efficacious as traditional therapies but, due to better tolerability, are gaining acceptance in the treatment of psoriasis and psoriatic arthritis. The biologic agents differ in efficacy rates and are generally well tolerated. Clinical attributes, overall efficacy, and economic costs associated with the biologic agents will be significant factors in selecting agents for the treatment of psoriasis and psoriatic arthritis.

Arthritis, Psoriatic↗

Clinical monograph for drug formulary review: erectile dysfunction agents.

BACKGROUND: Significant advances in the pharmacologic treatment of erectile dysfunction (ERD) have occurred in recent years, most notably the introduction of sildenafil, the first oral selective phosphodiesterase type 5 (PDE5) inhibitor, in 1998. Sildenafil quickly gained acceptance by the medical community and the public because of its broad efficacy for different types of ERD and its ease of use. Two PDE5 inhibitors, vardenafil and tadalafil, have since joined sildenafil to compete in the ERD market. A review was conducted by the Drug Information Service of a pharmacy benefits manager (PBM) to determine the relative merits and place in therapy of commonly used ERD drugs as part of drug formulary management process and decision making by the Pharmacy & Therapeutics (P&T) committee. OBJECTIVE: To provide readers with a comprehensive clinical monograph on ERD drugs written from a managed care perspective. METHODS: The PBM clinical monograph is designed to provide health plans with an evidence-based review of drugs, therapeutic classes, and disease states with a managed care focus. For each therapeutic class or disease review, an extensive and thorough literature search of MEDLINE is conducted for efficacy, safety, effectiveness, and humanistic and economic data. Drug/disease-state databases (UptoDate online, MICROMEDEX), U.S. Food and Drug Administration clinical reviews, key Internet sites, medical/pharmacy-related news sites, clinical guidelines, and AMCP dossiers are also reviewed. Formulary drug monographs prepared by the Drug Information Service of the PBM include a critical analysis and summary of disease-oriented and patient-oriented clinical outcomes, effectiveness, and humanistic data. Additional data considered and included in the formulary review process are clinical attributes, patent expirations/generic competition, off-label or pending indications, and pharmacoeconomic data. RESULTS: Despite the lack of head-to-head comparative studies, all 3 PDE5 inhibitors appear to have equivalent efficacy in the treatment of general ERD and ERD associated with diabetes and postprostatectomy. Sildenafil has additional efficacy data in the management of ERD associated with spinal cord injury and antidepressant medications. Tadalafil has the longest duration of action (up to 36 hours); this feature can be both beneficial (greater sexual spontaneity) or possibly detrimental (greater exposure to drug, delayed adverse events). All 3 PDE5 inhibitors appear to be generally well tolerated and have similar contraindications and warnings. However, vardenafil is the only PDE5 inhibitor with a cardiac conduction precaution. Alprostadil products are recommended in current ERD guidelines as second-line therapy for those who have not responded or cannot take the oral PDE5 inhibitors. Overall, higher clinical efficacy rates are achieved with intracavernous than with transurethral administration. CONCLUSION: A large amount of clinical efficacy and safety data has been published since the market launch of sildenafil in 1998. Sildenafil has the greatest body of efficacy and safety evidence. No comparative studies have been conducted with any of the PDE5 inhibitors. Differences in study populations, primary end points, and measurement tools make comparisons difficult. However, all PDE5 inhibitors appear to be roughly equivalent in efficacy, with minor differences in adverse event profiles. Until more comparative data are available, economic considerations will be a significant factor in choosing ERD products for formulary inclusion.

Carbolines↗

US Medicaid drug formularies: do they work?

Does the use of a restricted drug formulary achieve cost savings within state Medicaid programmes? Restricted formularies are often justified by putting forth the attributes of a perfectly operating and implicitly costless policy. Analysis suggests, however, that the operation of 'actual' restricted formularies produce realised effects that are substantially at odds with the desired effects. Although the implementation of a restricted formulary can reduce a state's drug expenditures, service substitution causes expenditures to increase elsewhere in the system. Furthermore, direct savings in the drug budget are completely offset by these spillover effects.

Cost Savings↗

A review of limited lists and formularies: are they cost-effective?

The 'limited list' or 'formulary' concept has been used to promote rational use of drugs and to set standards for drug use. Recently the concept has been aimed more toward containment of drug costs. Effective hospital formulary systems assist in purchasing and inventory management. Application of the formulary concept has resulted in savings within specific classes of drugs and in total hospital drug costs. Key features which promote effectiveness are development of policies by prescriber consensus and continued education along with feedback on drug usage. The formulary concept also provides a foundation for appropriate use of drugs in hospitals. In the community setting, limited lists can achieve cost savings and can assist in the rational use of drugs. National limited lists have been less successful in controlling overall drug costs, probably because they have focused on economic effects, rather than education, feedback or user participation. Properly organised drug rationalisation policies embracing the limited list concept can improve health outcomes by promoting rational drug use. They can also contain or reduce drug costs.

Australia↗

Formulary restriction of selective serotonin reuptake inhibitors for depression: potential pitfalls.

The American healthcare market is currently estimated at more than 900 billion US dollars with double digit rising costs per year. Psychotropic agent costs have more than kept pace with market increases. Medication acquisition costs are an obvious focus for limiting costs in various care systems. Restrictive formularies are a common method of attempting to limit costs. To support our opinion that a single agent is ill advised, we explored the available evidence on the intended and unintended consequences of having a single or exclusive selective serotonin reuptake inhibitor (SSRI) on a formulary. Central to this position is an assumption of the interchangeability of SSRIs; we examined the evidence for and against this through a model to determine the probability of interchangeability. We conclude that the practice of having a single SSRI on the formulary for a healthcare plan seems ill founded. Patients who switch antidepressants remain in treatment 50% longer and cost approximately 50% more to treat in a more costly treatment setting. Giving the primary care physician several antidepressant choices can provide more options to continue treatment of his or her patient in the less expensive primary care setting. In terms of cost containment, formulary restrictions are far more likely to have the opposite effect.

Depressive Disorder↗

P & T Committee perspectives: maintaining a successful formulary system in a private community hospital.

Institution of an effective formulary and P & T Committee is a difficult but critical task for many private hospitals. In this exclusive Hospital Formulary interview, Drs. Benner, Mykita, and Brown, members of Sutter Memorial Hospital's Pharmacy, Formulary, and Therapeutic Review Committee (their name for the P & T Committee) emphasize the need for a sound formulary system in order to survive the current changes in health care. Sutter Memorial is sophisticated in its delivery of healthcare services, which include advanced neonatology and state-of-the-art heart transplantation. Although good patient care remains the foremost concern, these committee members acknowledge that care must be affordable as well as therapeutically sound. Key to their committee's success is the cooperative effort among the pharmacy, nursing, and medical staff. They foresee the issue of rational therapeutics as a major challenge in the 1990s.

California↗

Operation, formulary decision-making activities of a P & T Committee in a managed care setting.

Managing drug benefits in a Health Maintenance Organization (HMO) is perhaps best accomplished through a formulary, as demonstrated by Kaiser Permanente of Colorado. According to Dr. Jim Adams and Ms. Jackie Richardson, the Chairman and Secretary, respectively, of Kaiser Permanente's P & T Committee, since the advent of their formulary only a few years ago, the cost of drugs has been kept well under control, without jeopardizing the quality of care. Both physician and patient education are critical to the success of a formulary in a managed care system--both monumental tasks for Kaiser Permanente of Colorado considering that prescribers exceed 300 and the number of patients they treat approaches 250,000. What is clear in this exclusive Hospital Formulary interview is that HMOs--long recognized for their ability to control costs--can also provide quality health care for patients who use their facilities.

Colorado↗

Reducing costs with formulary limitation of H2-receptor antagonists in a community hospital.

Cost containment has become a major issue for all hospital pharmacies. At Carney Hospital, a 366-bed community hospital, where H2-receptor antagonists accounted for 10% of a $1.5 million total drug budget, the search for cost savings led to a move from an open to a limited formulary for the H2-receptor antagonists. Cimetidine and ranitidine, the two most widely used agents of this class, are considered equivalent in terms of safety and efficacy. Prior to formulary limitations, however, most H2-receptor antagonist orders were written for ranitidine, the more expensive agent. Carney Hospital, a member of the Daughters of Charity hospital purchasing group, was able to participate in an advantageous H2-receptor antagonist cost agreement by limiting its formulary to cimetidine. After the first 9 months of the closed formulary program, Carney had realized cost savings of $33,220. At that time, cimetidine accounted for 96% of all parenteral H2-receptor antagonist orders, testifying to physician satisfaction with this agent. Finally, 85% of the parenteral cimetidine orders were written q8h, which was essential to the success of the cost savings program.

Boston↗

Formulary: what it is and how it works.

Estimates for healthcare expenditures in 1993 exceeded $900 billion, approaching 15% of GNP. Of this, approximately 7.5% ($62 billion) was spent on drugs. More recently, costs show that the US spends over $3,000 per person per year on healthcare. Although no one disputes that the cost of healthcare is rising, generally the rate at which it rises is not as rapid in a managed care environment compared to a fee-for-service one. Because of this, the boundaries of managed care and pharmacy benefits management (PBM) continue to expand. Outpatient drug benefits, for instance, are being carved out of the medical benefit offered by several types of insurance programs. This is mainly a result of point-of-sale claims processing and enhanced information system data base reporting making the drug portion easier to identify and separate from other medical claims. Self-funded employers are now actively seeking PBM companies to contract with for this type of service. The services being offered by PBM companies include: Pharmacy networks in which plan members fill prescriptions at a discounted or contracted rates. Disease state management. Drug utilization review. Financial reporting. Formulary management. The main component of formulary management is the development and distribution of a drug formulary. This article discusses what a drug formulary is and how it works.

Cost-Benefit Analysis↗

Incorporating quality of life data into managed care formulary decisions: a case study with salmeterol.

Pharmacy and Therapeutics committees of managed care organizations have traditionally developed formularies by limiting the numbers and kinds of pharmaceuticals they purchase, with the goal of cutting costs. These attempts to manage pharmaceutical costs do not take into account the interrelationship of the costs of various components of care; thus, drug costs may decrease, but expenditures for utilization of other resources may increase. Cost-minimization and basic cost-effectiveness studies, on which many prior- authorization and formulary programs are based, only evaluate only the cost of the drug and its effectiveness. However, with the heightened competition in the healthcare market, emphasis is increasingly being laid on patient satisfaction and outcomes. Cost-utility analysis is a potentially superior pharmacoeconomic tool because it evaluate the effect of drug therapy on quality of life; however, data from such analyses are seldom readily available to the committees that evaluate a drug's potential effects on the entire healthcare system. The purpose of this review is to stress the importance of approaching formulary management from a wider perspective and to emphasize that the results of cost-utility studies should be proactively evaluated and incorporated into decisions regarding formularies. This is especially important for symptom-intensive diseases, such as asthma, in which the quality of life can be notably impaired. Cost-utility analyses should be conducted for all newer therapies, such as salmeterol, which are highly effective and which have a positive impact on quality of life, to determine the overall effect on the managed care plan's budget.

Albuterol↗