Economic consequences of alterations in platelet transfusion dose: analysis of a prospective, randomized, double-blind trial.

BACKGROUND: In recent years, decreasing financial resources led to the use of lower-dose platelet components. However, the economic consequences of the use of such components have not been carefully studied. STUDY DESIGN AND METHODS: A formal economic analysis was conducted of a recently reported, prospective, randomized, double-blind study examining the platelet dose-response relationship in nonrefractory patients. The economic analysis used a decision analysis model, conducted from the hospital's perspective and based directly on the observed clinical data and on institutional cost structures. RESULTS: The decision analysis model estimated that a 38-percent reduction in mean platelet dose, within the commonly prescribed dose range, would result in the average patient's requiring approximately 60 percent more transfusions in the posttransplant period (8 vs. 5; p = 0.05), which would result in an estimated 60-percent increase in the median cost to the hospital ($4486/patient vs. $2804/patient [in 1996 US dollars], p = 0.05). CONCLUSION: Efforts to decrease costs by utilizing lower-dose single-donor platelet transfusions are predicted to result in a disproportionate increase in the number of transfusions per patient, with a corresponding increase in overall hospital transfusion costs.

Clinical consequences of alterations in platelet transfusion dose: a prospective, randomized, double-blind trial.

BACKGROUND: The dose-response relationship for platelet transfusion has become increasingly important as the use of platelet transfusion has grown. STUDY DESIGN AND METHODS: One hundred fifty-eight prophylactic apheresis platelet transfusions were administered to 46 patients undergoing high-dose therapy followed by hematopoietic progenitor cell transplantation in a prospective, randomized, double-blind, multiple-crossover study. Transfusions were administered in pairs, differing only in platelet content. Each pair consisted of a lower-dose platelet component (LDP) and a higher-dose platelet component (HDP) administered in random order to the same patient. LDPs contained a mean of 3.1 x 10(11) platelets (range, 2.3-3.5 x 10(11)), and HDPs contained a mean of 5.0 x 10(11) platelets (range, 4.5-6.1 x 10(11)). Patients with active bleeding and those who were refractory to platelet transfusions were excluded. RESULTS: The mean posttransfusion platelet count increment with LDP was 17,010 per microL, and that with HDP was 31,057 per microL (p<0.0001). Only 37 percent of LDPs resulted in platelet count increments of at least 20,000 per microL, whereas 81 percent of HDPs resulted in increments above this level (p<0.0001). The mean transfusion-free interval with LDP was 2.16 days, whereas that with HDP was 3.03 days (p<0.01). Administration of LDPs was associated with a 39 to 82 percent increase in the relative risk (per day) of requiring subsequent platelet transfusions (p<0.0001). CONCLUSION: As compared to the administration of HDPs, the administration of LDPs for prophylactic transfusion in hematopoietic progenitor cell transplant patients results in a lower platelet count increment, a lower likelihood of obtaining a posttransfusion platelet increment >20,000 per microL, a shorter transfusion-free interval, and a greater relative risk per day of requiring additional transfusions.

Pharmacoeconomic analysis of 3 treatment strategies for cytomegalovirus retinitis in patients with AIDS.

A decision-analytical simulation model was constructed to perform a pharmacoeconomic analysis of the following 3 treatment strategies for previously untreated cytomegalovirus (CMV) retinitis in patients with AIDS: (i) intravenous foscarnet (IVF) for induction and maintenance therapy; (ii) intravenous ganciclovir (IVG) for induction and maintenance therapy; and (iii) intravenous ganciclovir for induction therapy, followed by oral ganciclovir for maintenance therapy (IVG-ORG). Patients who experienced significant adverse effects during, or who failed, initial therapy were switched once to one of the other 2 treatments. The model was used to estimate the direct medical cost (from the perspective of a public payer), survival, and survival adjusted for disutility because of lost vision, for each strategy in the first year following treatment initiation. The expected first-year costs of treatment initiated with IVF, IVG and IVG-ORG were $US47,918, $US38,817 and $US32,036 (1994 values), respectively, while expected first-year survival was 41 weeks, 35 weeks and 35 weeks, respectively. The incremental cost per incremental year of survival using IVF was $US78,000 versus IVG and $US138,000 versus IVG-ORG before adjustment for lost vision, and $US93,000 versus IVG and $US166,000 versus IVG-ORG after adjustment for lost vision. About 23% of the cost of the IVG treatment strategy was attributable to treatment-related adverse events, compared with 14% of the cost of IVF and 16% of the cost of IVG-ORG. Because of the high failure rate with IVG-ORG, initial treatment with IVG-ORG frequently led to switching to another treatment. Only 27% of the costs associated with the IVG-ORG treatment strategy were in fact attributable to the cost of induction and maintenance therapy prior to a switch to alternative treatment. In this analysis, initial treatment with IVG-ORG was the least costly approach for treating CMV retinitis in patients with AIDS. Initial treatment with IVF resulted in slightly longer survival adjusted for vision-related quality of life. New treatments for AIDS may reduce the survival benefit of initial treatment with IVF.

Reimbursement and pharmacoeconomic perspectives in biotechnology.

Problems associated with reimbursement for biotechnology agents and strategies for solving these problems are reviewed. Because of the many different insurers in the U.S. health care system, a variety of reimbursement strategies have been developed for the biotechnology drugs that are now reaching the market. These strategies can vary by insurer, contract, treatment setting, and patient condition. With the advent of high-cost biotechnology drugs, pharmacists have taken on the additional roles of institutional educators and reimbursement specialists. Case studies involving three biotechnology agents illustrate how insurers deal with reimbursement for these drugs. Thrombolytic agents are reimbursed under Medicare, but the diagnosis-related-group (DRG) payment for myocardial infarction was not changed until two years after alteplase was marketed. Septic shock therapies potentially face similar reimbursement problems, which are compounded because the drugs can be lifesaving--leading to longer hospital stays. When filgrastim is administered, the amount reimbursed depends on the treatment setting. When claims for biotechnology agents are denied, the institution or provider should contact the payer to provide the needed information (in the case of missing information) or to discuss payer policies that may need review. Through proper case management, pharmacists and other institutional personnel can ensure reimbursement for these lifesaving biotechnology therapies.

Cost-effectiveness analyses in a changing health care environment: new issues and challenges.

Rising health care expenditures have fuelled the demand for more information about the impact of new medical products on costs and outcomes. Cost-effectiveness analysis (CEA) is one technique used to inform health care decisionmakers. Recent analyses show an increase in the number of CEAs published annually, although study quality remains unchanged. While advances in CEA methodology have been significant, further progress will require changes in the way we conduct basic clinical research, and a greater commitment by groups not usually involved in these analyses.

Adjunctive medications in patients receiving thrombolytic therapy: a multicenter prospective assessment. The Virginia Multicenter Thrombolytic Study Group.

OBJECTIVE: To describe the use of adjunctive therapies in patients with acute myocardial infarction receiving thrombolytic agents. DESIGN: Data were collected prospectively by the study-site investigator or the emergency department physician caring for the patient. Study participation did not influence thrombolytic regimen selection or the adjunctive therapies ordered. SETTING: Thirteen Virginia hospitals representing a cross-section of hospitals in the state. Eleven are urban medical centers; four have graduate medical education programs. PARTICIPANTS: Patients were included in the study if the decision to administer thrombolytic therapy was made in the emergency department. MAIN OUTCOME MEASURES: Concomitant medications administered during the first six hours after initiation of thrombolytic therapy. RESULTS: Two hundred ten patients (aged 57 +/- 14.1 y) were evaluated. Ninety-five percent of these patients were treated with tissue plasminogen activator, 3 percent received anisoylated plasminogen streptokinase activator complex, and 2 percent received streptokinase. Ninety-one percent of the patients also received heparin, the most commonly used adjunctive medication; 77 percent concomitantly received lidocaine; 62 percent received aspirin; and only 19 percent received a beta-blocker. CONCLUSIONS: Our data provide a reference point for future studies to determine factors that influence the selection of adjunctive agents for treating patients with acute myocardial infarction receiving thrombolytics.

Hospital delays and problems with thrombolytic administration in patients receiving thrombolytic therapy: a multicenter prospective assessment. Virginia Thrombolytic Study Group.

STUDY OBJECTIVES: To assess the timing of key decisions and clinical events in the treatment of acute myocardial infarction with thrombolytic therapy. DESIGN: Prospective study of emergency department patients. SETTING: EDs in 11 urban and two rural hospitals. TYPES OF PARTICIPANTS: Patients with presumed acute myocardial infarction for whom a decision was made in the ED to administer thrombolytic therapy. MEASUREMENTS AND MAIN RESULTS: Statistical analyses included determination of frequency of response, cross tabulation analysis, and Wilcoxon rank sum tests. In 210 thrombolytic-treated patients (mean age, 57 +/- 14.1 years), a median time of 155 minutes elapsed between pain onset and therapy; 67% of the delay was pre-ED arrival. The median time between ED arrival and the initial ECG was six minutes. The median time required for physicians to make a treatment decision was 20 minutes, followed by another median time of 20 minutes for staff to begin drug infusion. The median total hospital (door-to-needle) time was 50 minutes. Significantly shorter delays occurred in urban, teaching, and high-volume hospitals; when thrombolytics were stocked and/or started in the ED; and when emergency physicians treated without involving private attending physicians. Although 95% of patients received tissue plasminogen activator, six patients treated with anisoylated plasminogen-streptokinase activator complex experienced a significantly faster door-to-needle time (P less than .05). CONCLUSION: Thrombolytics should be stocked and started in the ED. Emergency physicians should generally make the decision to administer thrombolytic therapy with reference to accepted protocols without awaiting an ED consultation from either private attendings or cardiologists.

Blood transfusion costs: a multicenter study.

The cost of delivering a unit of blood (whole blood or red cells) to a hospitalized patient was examined in 19 United States teaching hospitals. The average hospital acquisition cost was calculated by using the prices charged by regional blood centers for blood products. To this cost was added an estimate of costs incurred by hospitals for handling, testing, and administering blood. Across study sites, the average hospital cost per unit transfused was $155 and the average charge to the patient was $219. Acquisition cost, the price that hospitals pay for blood, was 37 percent of the total cost to the hospital; the other 63 percent of the hospital cost included costs for blood bank handling (13%), laboratory tests (43%), and blood administration (7%). Significant variations in blood transfusion cost were found within our sample. Most of the variability can be attributed to geographic location of the blood supply source, type of red cell product transfused, prices charged by blood transfusion services, and the frequency of laboratory tests. The results of this transfusion cost study may be helpful in determining the costs of health care delivery, especially when blood transfusions are indicated.

Sequences controlling histone H4 mRNA abundance.

The post-transcriptional regulation of histone mRNA abundance is manifest both by accumulation of histone mRNA during the S phase, and by the rapid degradation of mature histone mRNA following the inhibition of DNA synthesis. We have constructed a comprehensive series of substitution mutants within a human H4 histone gene, introduced them into the mouse L cell genome, and analyzed their effects on the post-transcriptional control of the H4 mRNA. Our results demonstrate that most of the H4 mRNA is dispensable for proper regulation of histone mRNA abundance. However, recognition of the 3' terminus of the mature H4 mRNA is critically important for regulating its cytoplasmic half-life. Thus, this region of the mRNA functions both in the nucleus as a signal for proper processing of the mRNA terminus, and in the cytoplasm as an essential element in the control of mRNA stability.

Identification of promoter elements necessary for transcriptional regulation of a human histone H4 gene in vitro.

We have examined the nucleotide sequences necessary for transcription of a human histone H4 gene in vitro. Maximal transcription of the H4 promoter requires, in addition to the TATA box and cap site, promoter elements between 70 and 110 nucleotides upstream from the transcription initiation site. These distal promoter elements are recognized preferentially in extracts from synchronized S-phase HeLa cells. The inability of non-S-phase nuclear extracts to recognize the H4 upstream sequences reflects a specific lack of a transcription factor which interacts with those sequences. These results indicate that the cell cycle regulation of human histone gene expression involves both a specific transcription factor and distal transcription signals in the H4 promoter.