Comparison of length of hospital stay for patients with known or suspected methicillin-resistant Staphylococcus species infections treated with linezolid or vancomycin: a randomized, multicenter trial.

STUDY OBJECTIVE: To compare hospital length of stay (LOS), weekly discharges, and days of antibiotic treatment with linezolid (intravenous with oral follow-up) and vancomycin (intravenous only). DESIGN: Multinational, randomized, phase III trial. SETTINGS: Hospitals in North America, Latin America, and Europe. PATIENTS: Four hundred sixty hospitalized patients with infections of known or suspected methicillin-resistant Staphylococcus species. INTERVENTION: Administration of linezolid or vancomycin. MEASUREMENTS AND MAIN RESULTS: For linezolid recipients, median LOS was 5 and 8 days shorter (p=0.05 and 0.003) in the complicated skin and soft tissue infection intent-to-treat (230 patients) and clinically evaluable (144) samples, and slightly but not significantly shorter in the overall intent-to-treat (460) and clinically evaluable (254) samples. In all samples, linezolid recipients had more discharges in the first week of treatment and fewer days of intravenous therapy than vancomycin recipients. CONCLUSION: Our results support linezolid's ability to reduce medical resource use.

An economic evaluation of levofloxacin versus cefuroxime axetil in the outpatient treatment of adults with community-acquired pneumonia.

OBJECTIVE: To examine treatment costs of community-acquired pneumonia (CAP) in adult outpatients given oral (p.o.) levofloxacin or cefuroxime axetil as initial therapy. STUDY DESIGN: Patients with a primary diagnosis of CAP were enrolled in a multicenter, prospective, randomized, open-label, active-controlled Phase III clinical trial. Both inpatients and outpatients were assigned to 1 of 2 treatment groups: (1) intravenous (i.v.) or p.o. levofloxacin; or (2) i.v. ceftriaxone and/or p.o. cefuroxime axetil. METHODS: To make legitimate and meaningful cost comparisons between similar types of patients receiving drugs via the same route of administration (i.e., orally), this outpatient economic study examined the resource utilization of the 211 patients enrolled as outpatients who received oral formulations as initial treatment (levofloxacin, 103 patients; cefuroxime axetil, 108 patients). Resource utilization data and clinical trial data were collected concurrently. To generate cost estimates, Medicare cost estimates for resources were multiplied by the resource units used by patients in each treatment arm. RESULTS: Cost estimates indicated a total cost difference that favored the levofloxacin group (base case: $169; sensitivity analysis: $223 [P = .008]). The results for the base case were not significant (P = .094). In addition, within the cost categories, there was a statistically significant study drug cost differential favoring levofloxacin ($86; P = .0001 for both the base case and sensitivity analysis). CONCLUSION: Oral levofloxacin is less costly than oral cefuroxime axetil in the outpatient treatment of adults with CAP.

At what price significance? The effect of price estimates on statistical inference in economic evaluation.

Because data on resource utilization are now collected in many comparative trials of health interventions, statistical analysis of between-group differences in mean costs has become common. Statistical analyses of costs are generally performed conditional on a set of resource prices (or unit costs), thereby suppressing any uncertainty associated with those price estimates. Results presented here demonstrate that varying price estimates can have a non-negligible effect on statistical inference regarding between-group cost differences. Depending on the relative prices used in an analysis, between-group differences in total costs per patient may be either statistically significant or insignificant, regardless of whether differences in utilization of the underlying resources are statistically significant. These results highlight the importance of recognizing that evaluations based on patient-level economic data may be sensitive to assumptions regarding the values of unobserved variables, such as the relative prices of resources. Traditional methods of sensitivity analysis remain a valuable tool for analysing the implications of uncertainty around estimates of those unobserved variables.

An economic evaluation of pain therapy after hysterectomy. Patient-controlled analgesia versus regular intramuscular opioid therapy.

OBJECTIVES: To assess the economics of patient-controlled analgesia (PCA) treatment versus regular intramuscular (i.m.) injections of opioid analgesia for pain management after hysterectomy. METHODS: Cost-minimization analysis was used based on the comparable pain control results achieved in the two treatment groups. Observations were taken of treatment-related events with personnel (mostly nursing) time implications during the trial. Times were then associated with these events in an independent study of personnel activity. Costs were linked by using average wage rates for the various personnel for the Montreal area during the time of the study. Drug and material costs were hospital acquisition costs for all items. The cost of the PCA pump itself was not included in the analysis. Several analyses were performed to test the sensitivity of the results to various assumptions. RESULTS: The results for total costs of the two therapies generally showed PCA to be more costly than regular i.m. injections despite no costs of the pump being included in the analyses. These results were robust with respect to changes in assumptions. Even when intentionally biasing the analysis against i.m. therapy, it was difficult to obtain results that favored PCA. CONCLUSIONS: Based upon the institutions and assumptions in this analysis, PCA offers no cost advantages over regular i.m. therapy in the pain management after hysterectomy. Regular i.m. injections provided less costly analgesia.

Efficacy and costs of patient-controlled analgesia versus regularly administered intramuscular opioid therapy.

BACKGROUND: Many studies have shown the efficacy of patient-controlled analgesia (PCA). However, it is not clear whether PCA has clinical or economic benefits in addition to efficient analgesia. The current study was designed to evaluate these issues by comparing PCA with regularly administered intramuscular injections of opioids after hysterectomy. METHODS: This prospective study included 126 patients who underwent abdominal hysterectomy and were randomly assigned to receive PCA or regularly timed intramuscular injections of morphine during a period of 48 h. Doses were adjusted to provide satisfactory analgesia in both treatment groups. Pain at rest and with movement, functional recovery, drug side effects, and patient satisfaction were measured using rating scales and questionnaires. The costs of PCA and intramuscular therapy were calculated based on personnel time and drug and material requirements. RESULTS: Comparable analgesia was observed with the two treatment methods, with no significant differences in the incidence of side effects or patient satisfaction. The medication dosage had to be adjusted significantly more frequently in the intramuscular group than in the PCA patients. The PCA did not favor a faster recuperation time compared with intramuscular therapy in terms of times to ambulation, resumption of liquid and solid diet, passage of bowel gas, or hospital discharge. The results of the economic evaluation, which used a cost-minimization model and sensitivity analyses, showed that PCA was more costly than regular intramuscular injections despite the fact that no costs for the pump were included in the analyses. Cost differences in nursing time favoring PCA were offset by drug and material costs associated with this type of treatment. CONCLUSIONS: Compared with regularly scheduled intramuscular dosing, PCA is more costly and does not have clinical advantages for pain management after hysterectomy. Because of the comparable outcomes, the general use of PCA in similar patients should be questioned.

Exorcising protocol-induced spirits: making the clinical trial relevant for economics.

Economic evaluation frequently depends on estimates from clinical trials of both effectiveness of treatment and resource utilization accompanying it. Protocol-driven events in the trial among other influences often imply that both estimates will be inaccurate. This paper indicates how one may supplement a trial with additional data to connect the artificial trial to the real world of clinical practice. It also shows that data required for this model may be estimated from other sources (via Bayesian modeling) if they are not directly available. The required data include (for example) the proportion of patients with disease who would have presented with clinical signs if they had not been part of a trial that allowed early detection and treatment based on subclinical testing mandated by trial protocol. Those presenting with clinical signs would use additional resources for treatment and/or confirmatory diagnostics. Those with subclinical disease either 1) would never use resources in the case where they never developed clinical manifestations or 2) would use resources of a different type or intensity and perhaps have different outcomes by virtue of their disease's being discovered at a later point in time. Basing resource use and ultimate effectiveness on this revised measure of outcome rather than the one in the trial should lead to more accurate predictions for economic purposes.

Healthy years equivalents versus time trade-off. Ambiguity on certainty and uncertainty.

Preference assessment literature has debated the equivalence of the healthy years equivalents (HYE) and time trade-off (TTO) methods. The central issue is whether the HYE measures preferences under uncertainty. This work shows that the two stages of the HYE first add and then remove the element of uncertainty so that ultimately the technique doses not measure preferences under uncertainty. This makes the HYE, at best, a cumbersome equivalent of the TTO.

Respondent-specific information from the randomized response interview: compliance assessment.

In situations in which researchers ask potentially embarrassing questions, respondents may feel uncomfortable with revealing certain behavior. Consequently, response rates or accuracy may be low. The "randomized response interview" (RRI) was developed to enable researchers to better elicit responses to such questions. The technique has clear potential in estimating population proportions engaging in embarrassing behavior. It does not appear to have been recognized that one may also obtain more respondent-specific information from the application of the RRI. This article indicates that while still only probabilistic, respondent-specific information is obtainable from the RRI.

A novel compliance assessment technique. The randomized response interview.

Changing compliance with medication directives can greatly affect health outcomes. To assess programs that influence compliance, accurate measurement of compliance is essential. All currently available methods are imperfect. This paper suggests a new method-the "randomized response interview"-along with a strategy for its implementation.

The relevance of searching for effects under a clinical-trial lamppost: a key issue.

In economic evaluations of new medical technologies, analysts often need to use data from randomized controlled trials. Trials are designed to achieve high internal validity; however, their selected populations and often highly artificial environments may imply low external validity. Thus, the use of trial data in an economic evaluation may bias the results, since economic evaluation is concerned not with theoretical capability in a trial but with likely performance in the practice environment. This paper indicates both the probable bias of one aspect of artificiality in the trial environment--selected populations--and a method of adjusting the analysis so that results will be more likely to reflect actual practice. The judicious use of extra-trial information can be used to correct the biases of clinical trials.

Potential inconsistencies between cost-effectiveness and cost-utility analyses. An upstairs/downstairs socioeconomic distinction.

This paper indicates that certain economic evaluation methods (cost-effectiveness and cost-utility analyses) may yield inconsistent results. Along with the lack of formal grounding of these methods in economic "first principles," this finding suggests the possible benefit of greater reliance on the more formally developed method of cost-benefit analysis.

Economic incentives and disincentives for efficient prescribing.

Efficient prescribing is a controversial concept when defined in economic terms. Such terms imply that neither the best nor the cheapest drug may be efficient. Efficiency depends on patient evaluations of outcomes--an essential, yet still underdeveloped, field of inquiry. Encouraging prescribing efficiency (once it is clear what efficient treatments are) may require the use of incentives, (economic and otherwise). Although physicians do react to economic incentives, encouraging them to also act as good economists rather than only as good healthcare providers may be difficult since economic efficiency goals may conflict with pure medical goals. While it is conceptually reasonable to assume that economic incentives will accomplish behavioural change, other (noneconomic) incentive mechanisms may appear less controversial. Since it is the result, not the process, that is important, a mix of incentives to achieve efficient solutions is suggested. However, further investigation into both health and economic outcomes research and debate on proper efficiency goals should precede the discussion of optimal incentives.

Community pharmacists as immunization advocates. Cost-effectiveness of a cue to influenza vaccination.

To assess the cost-effectiveness of a cue to influenza vaccination provided by community pharmacists, a decision tree was constructed of the consequences of implementing a pharmacy-based vaccine-advocacy program, based on experience gained in an experiment involving three community pharmacies in Durham County, North Carolina. The model used morbidity and mortality assumptions derived from the infectious-disease literature and cost assumptions based on 1990-91 Medicare Part A and Part B reimbursement costs. This analysis suggests that if Medicare reimbursed pharmacists for advising 100,000 patients at risk to accept influenza vaccine through vaccine-advocacy messages, for an apparent expenditure of $110,000, the increased rate of influenza vaccinations would avert 139 hospitalizations and 63 deaths, and actually yield Medicare a net savings of $280,588. These calculations probably underestimate the benefit to society of a pharmacy-based vaccine-advocacy program, because only direct costs to the single government agency were computed and no cost was attributed to death or lost earnings.