Evaluation of conflicting literature and application to formulary decisions.

PURPOSE: Guidelines were developed for grading the quality, quantity, and consistency of drug literature in support of formulary recommendations. METHODS: Four developmental steps were taken to create a comprehensive literature evaluation system. The first step identified the attributes of a body of literature that were most reflective of its applicability to patient care. The next step defined each domain (quality, quantity, consistency), as determined by the Agency of Healthcare Research and Quality (AHRQ), in terms of the specific qualities to be assessed; a value was assigned to those qualities. Also, a literature search was conducted to identify strategies for evaluating bodies of literature employed in published assessment tools. Following the analysis of previously published systems, which were evaluated with respect to their inclusion of the AHRQ-identified domains, the next step was the development of specific domains and definitions to get a composite grade (with "better" evidence earning more points) for formulary recommendations. The final step was the creation of a system that aggregated the final score for the recommendation. The recommendation was categorized according to quality, quantity, and consistency of supporting evidence, and the total number of points was calculated and the recommendation given letter and numerical grades. RESULTS: The guidelines that were developed allow the user to accurately, consistently, and easily determine the strength of recommendations for a body of literature that may be conflicting. The addition of criteria for quantity and consistency to previously-published grading systems has made the guidelines more objective. CONCLUSION: A system that accounts for the quality, quantity, and consistency of drug literature was developed to assist in making formulary decisions.     

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)     

Controversies in antimicrobial therapy: formulary decisions on third-generation cephalosporins

Factors affecting the admission of antimicrobial agents to hospital formularies are discussed, using third-generation cephalosporins as examples. Inappropriate antimicrobial therapy is costly in terms of wasted drugs, ineffective therapy, and drug toxicity. In 1984, 10 of the top 15 drug products (in sales to hospitals) were antimicrobial agents; these accounted for $1 billion in sales. Since third-generation cephalosporins are very similar in terms of spectra, clinical efficacy, and safety, they are useful in illustrating the process a hospital might use in deciding which individual agent to admit to a formulary. Five factors should be considered in formulary evaluations of antimicrobial agents: in vitro activity, pharmacokinetic disposition, adverse effects, clinical efficacy, and total economic impact. As applied to third-generation cephalosporins, this decision analysis leads to the conclusion that these agents should be considered therapeutic alternates. The decision would then rest solely on the institution-specific factors of microbial susceptibility patterns, patient case-mix, and acquisition costs. Antimicrobial agents account for the largest financial expenditure among hospital drug products; a set of these agents should be selected carefully to meet the needs of the individual institution.     

Using economic evaluations to make formulary coverage decisions. So much for guidelines

BACKGROUND: It is mandatory for drug manufacturers requesting formulary inclusion under the British Columbia (BC) provincial drug plan to submit a pharmacoeconomic analysis according to published guidelines. These submissions are reviewed by the Pharmacoeconomic Initiative (PI) of BC. OBJECTIVE: To assess the compliance of submitted studies with specific criteria outlined in the guidelines, to assess the methodological quality of individual submissions, and to demonstrate the importance of submitting guidelines-compliant pharmacoeconomic analyses. DATA AND METHODS: All submissions between January 1996 and April 1999 assessed by the PI of BC were included. Submissions were reviewed according to a checklist to establish compliance with respect to choice of comparator drug, study perspective, sensitivity analysis, analytical horizon and discounting. Submissions were examined for association between analytical technique and author, and between source of submission and compliance. Association between compliance and recommendation for approval was also examined. RESULTS: 95 applications were reviewed. Seven submitted no analyses. There were 25 cost-comparison/consequence, 14 cost-effectiveness, 11 cost-minimisation, 9 cost-utility/benefit and 29 budget-impact analyses. 65 of these 88 submissions failed to comply with guidelines. Of these, 45% used an inappropriate comparator drug, 61% lacked a sensitivity analysis, 73% used a third-party payer and excluded a societal perspective, 66% did not provide a long term evaluation and 25% did not specify any time horizon. 80% of noncompliant studies were cost-comparison/consequence or budget-impact analyses (p < 0.001, Fisher's Exact). Of 25 cost-comparison/consequence and 29 budget-impact analyses, 19 (76%) and 24 (83%), respectively, were industry-conducted, whereas cost-effectiveness (11 of 14) and cost-utility/benefit (6 of 9) analyses were mostly subcontracted to private consultants or academics (p < 0.001, Fisher's Exact). 74% of all submissions (compliant and noncompliant) were not recommended by the PI for listing as a provincial drug plan benefit, 16% received approval for restricted benefit and 9% were recommended as full benefit. 80% of the noncompliant submissions were not recommended (p = 0.06, Fisher's Exact test). Moreover, a strong association between type of analysis and type of recommendation was found (p = 0.03, Fisher's Exact test). Cost-comparison/consequence and budget-impact analyses were less likely to be recommended. IMPLICATIONS OF FINDINGS: Our findings show poor compliance with guidelines, especially among industry-conducted studies. Possible explanations are lack of expertise in pharmacoeconomics and/or scepticism regarding the importance of guidelines and submission quality in decision making. As corroborated by the strong associations between type of recommendation and compliance, and between type of recommendation and type of analysis, these 2 characteristics have a significant impact on decision making.     

Institution-specific versus published in vitro antimicrobial susceptibility data in making formulary decisions

The results of susceptibility testing of 549 isolates of gram-negative organisms to 17 antimicrobial agents were compared with published reports of the sensitivity of those organisms to those agents. All gram-negative bacilli isolated from cultures obtained from hospitalized patients during a three-month period were preserved for antimicrobial sensitivity testing. Standard Kirby-Bauer disk diffusion susceptibility tests were performed using 17 broad-spectrum antimicrobial agents that either were included in the hospital formulary or were being considered for inclusion. Organisms were recorded as being sensitive or resistant to each drug, and the results were compared with the published results of in vitro sensitivity studies. When the results of actual antimicrobial sensitivity testing varied from published results, the discordant results were assigned a ranking of 1 to 4 based on the percentage difference. In 34 of 77 drug-organism pairs tested, the results of susceptibility testing differed by more than 10% cumulative susceptibility from published values; 26 of these represented instances in which the results of actual testing were at least 10% less than published values. For seven of the antimicrobial agents that were being considered for inclusion in the hospital formulary, results indicating unexpectedly suboptimal activity against institutional pathogens were a determinant in eliminating the agents from further consideration. In vitro testing of antimicrobial susceptibility of local pathogens can be a better method of predicting the susceptibility of such pathogens to new antimicrobial agents than relying on published susceptibility data. Pharmacy and therapeutics committees should consider testing prevalent institutional pathogens for susceptibility to all antimicrobial agents that are proposed additions to the formulary.     

Application of economic analyses in U.S. managed care formulary decisions: a private payer's experience

BACKGROUND: Promoting use of pharmaco-economic models by formulary reviewers is a goal of the Academy of Managed Care Pharmacy (AMCP) Format for Formulary Submissions, but relatively few decision makers use such models, and many doubt that they provide meaningful input. OBJECTIVE: To demonstrate how sophisticated disease-based pharmaco-economic models can aid formulary decision makers when long-term outcomes data are lacking. METHODS: The Center for Outcomes Research (CORE) Diabetes Model (CDM), a published, validated Markov pharmaco-economic model that projects clinical and economic endpoints, was used to model the cost-effectiveness of exenatide, a new injectable antidiabetic agent that enhances glucose-dependent insulin secretion, in a standard cohort of type 2 diabetes patients (mean body mass index [BMI] = 27.5 3 kg/m2), compared with a modified obese cohort (mean BMI = 35 3 kg/m2) that was otherwise demographically identical at baseline to the standard cohort. The standard cohort was assumed to maintain baseline weight during treatment, and the modified obese cohort was assumed to experience weight loss of approximately 9% (mean = 3 kg/m2), with corresponding improvements in blood pressure, low density lipoprotein cholesterol, and triglycerides. We selected a 30-year time horizon because it was the time interval during which the CDM predicted most of the subjects would have died, and the costs obtained thus reasonably projected lifetime total direct medical costs for these cohorts. While treatment options certainly will change over a 30-year period, our goal was to estimate the incremental effect of exenatide over other available therapies. RESULTS: The model predicted reduced long-term treatment costs in obese patients, driven by an 11% decrease in cardiovascular disease burden and derived from the presumed weight loss. The incremental cost-effectiveness ratio (ICER) for adding exenatide over 3 years was 35,000 dollars/quality-adjusted life-year (QALY). Using a 30-year horizon, ICER values were 13,000 dollars/QALY versus insulin, 32,000 dollars versus generic glyburide, and 16,000 dollars versus no additional treatment. Exenatide dominated pioglitazone. By comparison, the 30-year ICER for exenatide versus insulin in the nonobese cohort was 33,000 dollars. These results were presented to the pharmacy and therapeutics (P&T) committee and influenced its decision to add exenatide to the drug formulary. While our modeling assumed certain patient characteristics (e.g., obesity, need of further A1c reduction at baseline, motivation to lose weight), the P&T committee imposed only a step-therapy requirement to try either metformin or a sulfonylurea before trying exenatide and did adopt a nonspecific requirement for physician reauthorization of refills before the fourth pharmacy claim for exenatide. CONCLUSIONS: Disease-based pharmaco-economic models may help third party payers project costs and be particularly useful when only data from short-term clinical trials are available. In the present case, the pharmacy staff of a health plan used a pharmaco-economic model for drug treatment of type 2 diabetes provided by the manufacturer as part of the AMCP Format dossier process to project cost outcomes for exenatide, adjunct injectable therapy for patients taking metformin and/or sulfonylurea. The P&T committee approved the drug for inclusion in the drug formulary based in part on the results of the pharmaco-economic model produced from the cost inputs entered into the model by the health plan pharmacists.     

The role of cost-effectiveness analysis in managed-care decisions

This article considers the role of cost-effectiveness studies in the formulary and disease-state management decisions of managed-care entities. In a recently published symposium volume [Soc Sci Med 1997; 45 (4): 505-647], US managed-care entities were found to be among the leaders in applying cost-effectiveness studies to healthcare decisions. At the same time, a number of barriers were identified that hinder their wider usage in the managed-care sector. These factors are analysed in this paper along with the prospects for future changes. The potential roles for government policy in this area are also discussed in the final section of the article.     

Issues in developing multivariable molecular signatures for guiding clinical care decisions

ABSTRACT

Omics technologies that generate a large amount of molecular data characterizing biospecimens have the potential to provide information about patients’ disease characteristics above and beyond standard clinical features. By combining information from a large number of features into a multivariable model, called a biomarker signature, there is the opportunity to identify distinct subgroups of patients for whom treatment decisions can be personalized. The key challenge is to derive a signature with good performance and appropriately characterize its performance. We summarize the key statistical issues and methods for developing and validating biomarker signatures, using examples from the literature for illustration.     

The role of pharmacoeconomics in formulary decision making in different hospitals in Riyadh,Saudi Arabia

Objective

To assess the trend of using pharmacoeconomic information by Pharmacy and Therapeutics (P&T) committees when making formulary decisions.

Design

A cross-sectional study conducted in 2007, using structured survey questionnaires which were distributed to members of the P&T committees in 11 different hospitals in Riyadh, Saudi Arabia.

Results

A total of 100 survey questionnaires were sent to head of pharmacy departments of 11 different hospitals in Riyadh, Saudi Arabia. Out of these, 48 questionnaires were completed and returned. Of the total respondents participated in the study, 64.58% were medical doctors and 16.66% were pharmacists and 75% of the respondents said they have applied pharmacoeconomic evaluations in their decision making process. More than 80% of the respondents perceived that they had a fair knowledge of pharmacoeconomics. Approximately 80% of respondents expressed some degree of agreement that pharmacoeconomics should be applied as a decision making tool. The majority of decision-makers (95%) expressed the interest in attending workshops on pharmacoeconomics.

Conclusion

The study showed that pharmacoeconomics can play an important role in the P&T committee formulary decisions. However, more education to health care professionals and to hospital administrators should be conducted to facilitate the use of such a tool. Also, hospitals should recruit health care professionals with pharmacoeconomic expertise to manage limited health resources in the best way available.     

N端脑利钠肽前体在肺部感染患者机械通气中的指导作用

目的 研究N端脑利钠肽前体(NT-PROBNP)对患者采用机械通气及脱机治疗时机的指导意义.方法 选取使用呼吸机的肺部感染患者48例,测定患者使用呼吸机前、使用呼吸机时、成功撤机后的动脉血NT-PROBNP浓度及相对应的患者心衰分级,观察并比较患者血液中NT-PROBNP浓度的变化及心衰程度的改变.结果 患者使用呼吸机前的NT-PROBNP浓度及心衰分级小于使用呼吸机时的NT-PROBNP浓度及心衰分级 (P<0.001);成功撤机后的NT-PROBNP浓度及心衰分级小于使用呼吸机时的NT-PROBNP浓度及心衰分级 (P<0.001).结论 NT-PROBNP对肺部感染患者是否采用机械通气及脱机治疗具有指导意义.     

The role of public opinion in drug resource allocation decisions

Drug resource allocation decisions have a very real and direct impact on the public, due to cost and availability constraints resulting from these decisions. This presents an opportunity for public opinion to play an important role in influencing decisions that have far-reaching effects. Public opinion regarding pharmaceutical issues is influenced by drug companies, special interest groups, researchers and others. Since these groups often have conflicting goals, they may send contradictory messages to the public. In this article, we examine the issues of who comprises the public, how public opinion is influenced and what impact public opinion does and should have on drug resource allocation decisions. We emphasise that, for appropriate resource allocation decisions to be made, there is a continuing need to conduct high quality outcomes research and to continue the trend of increasing interest in how drugs are used rather than how much is sold or how much they cost. There is also a major role for pharmacoeconomic research to play in this issue, with a real need to make such research accessible and understandable by the public, including patients, physicians, pharmacists and policy makers, so that policy decisions can be based on such research.     

The role of laboratory tests in alcoholism treatment

Although assessment in the field of alcoholism treatment is generally verbal in nature, biological tests can also provide counselors and program evaluators useful and unique information. Five such laboratory measures are briefly described, with particular emphasis on carbohydrate deficient transferrin, a biomarker recently approved by the FDA. Applications for laboratory tests in alcohol screening, motivating patients, and monitoring treatment progress are also proposed.