Cost-effectiveness of Oral Versus Intravenous Ibuprofen Therapy in Preterm Infants With Patent Ductus Arteriosus in the Neonatal Intensive Care Setting: A Cohort-based Study.

PURPOSE: Use of ibuprofen for the patent ductus arteriosus (PDA) has become increasingly common. This study aimed to evaluate the clinical and economic impact of oral ibuprofen versus intravenous ibuprofen for PDA among preterm infants. METHODS: This retrospective, cohort-based pilot study examined the clinical and economic associations of oral versus intravenous ibuprofen for PDA. A decision-analytic model was constructed, from the hospital perspective, to follow the oral versus intravenous administrations of ibuprofen for PDA and their clinical and economic consequences. The course regimen of either formulation was an initial 10 mg/kg followed by 5 mg/kg at 24- and 48-h intervals. Clinical and resource utilization data were extracted from Cerner medical database, from 2014 through 2018, at the tertiary neonatal intensive care unit setting in Qatar. The primary outcome measures were the rate of successful closure based on the ductal diameter measure after the first course of treatment and the overall direct medical cost of PDA management. A population of 118 neonates was required for results with 80% power and 0.05 significance. Sensitivity analyses involving unit costs and a subgroup analysis based on gestational age and birth weight, added to a second-order probabilistic analysis of all model inputs, were performed. FINDINGS: Forty infants were available for inclusion in the oral ibuprofen study group, not achieving the desired sample size, with successful PDA closure reported in 64% of cases compared with a reduced success of 36% with intravenous ibuprofen (n = 59) (risk ratio = 0.56; 95% CI, 0.32-0.97; P = 0.04), which was associated with economic advantage to oral ibuprofen. The probabilistic analysis illustrated that oral ibuprofen costs less than intravenous ibuprofen in 72% of patient cases, with QAR 48,751 (US $13,356) (95% CI, QAR 47,500-50,000, US $13,014-$13,699) in mean savings. Sensitivity analyses confirmed the robustness of study conclusions and found that the rate of closure success versus failure was the most influential on results, followed by the occurrence of adverse drug events with both intravenous and oral ibuprofen. Although both ibuprofen formulations had similar safety profiles (P = 0.16), the intravenous formulation was associated with a larger number of adverse drug effects. IMPLICATIONS: This is the first cost-effectiveness evaluation of oral versus intravenous formulations of ibuprofen among infants with PDA. The oral ibuprofen might be associated with an enhanced ductal closure at a considerably lower cost. The study results support recent trends in neonatal intensive care unit practices in favor of the oral administration of ibuprofen.

Aspirin-exacerbated respiratory disease: burden of disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by adult onset of asthma, chronic rhinosinusitis (CRS), nasal polyposis, and aspirin sensitivity. In this syndrome, each disease component has deleterious effects on the patient's health and quality of life. Latest figures from the Centers for Disease Control indicate 8.2% of the U.S. population has asthma and among adult asthmatic patients, up to 9% have AERD. Approximately 13% of the population suffers from CRS and 15% of patients with CRS with nasal polyposis have AERD. A review of the impact that each component of AERD has on patients will delineate the considerable burden of AERD, especially when considering the cumulative effects of the tetrad.

A randomized, controlled clinical trial of ketoprofen for sickle-cell disease vaso-occlusive crises in adults.

Vaso-occlusive crisis (VOC) is the primary cause of hospitalization of patients with sickle-cell disease. Treatment mainly consists of intravenous morphine, which has many dose-related side effects. Nonsteroidal antiinflammatory drugs have been proposed to provide pain relief and decrease the need for opioids. Nevertheless, only a few underpowered trials of nonsteroidal antiinflammatory drugs for sickle-cell VOC have been conducted, and conflicting results were reported. We conducted a phase 3, double-blind, randomized, placebo-controlled trial with ketoprofen (300 mg/day for 5 days), a nonselective cyclooxygenase inhibitor, for severe VOC in adults. A total of 66 VOC episodes were included. The primary efficacy outcome was VOC duration. The secondary end points were morphine consumption, pain relief, and treatment failure. Seven VOC episodes in each group were excluded from the analysis because of treatment failures. No significant between-group differences were observed for the primary outcome or the secondary end points. Thus, although ketoprofen was well-tolerated, it had no significant efficacy as treatment of VOC requiring hospitalization. These findings argue against its systematic use in this setting.

A randomized, multicentre, double-blind, parallel-group study to assess the adverse event-related discontinuation rate with celecoxib and diclofenac in elderly patients with osteoarthritis.

OBJECTIVE: To compare the adverse event (AE)-related discontinuation rate with celecoxib vs. diclofenac when given to reduce joint pain associated with knee or hip osteoarthritis (OA) in elderly patients. METHODS: This was a double-blind, randomized, multicentre, parallel-group, 1-year comparison of celecoxib 200 mg once daily and diclofenac 50 mg twice daily in 925 patients with OA aged > or = 60 years. Study visits were at baseline and at 4, 13, 26, 39, and 52 weeks. At each visit, the Patient's and Physician's Global Assessment of Arthritis (PaGAA, PhGAA), the Patient's Assessment of Arthritis Pain--Visual Analogue Scale (PAAP-VAS), and AEs were assessed. A concomitant health economic analysis was conducted throughout. RESULTS: The rate of study discontinuation due to AEs, laboratory abnormalities, and deaths was 27% for celecoxib and 31% for diclofenac (p = 0.22). The results of the arthritis/pain efficacy assessments were similar for celecoxib and diclofenac. Significantly fewer patients in the celecoxib group than the diclofenac group experienced cardiovascular/renal AEs (70/458 vs. 95/458, p = 0.039) or hepatic AEs (10/458 vs. 39/458, p<0.0001). Medication costs were higher for celecoxib than diclofenac but mean total treatment cost was slightly higher in the diclofenac group. CONCLUSION: Treatment with celecoxib 200 mg once daily and diclofenac 50 mg twice daily resulted in similar rates of AE-related study discontinuation in elderly patients with OA. Celecoxib and diclofenac demonstrated comparable efficacy in relieving the signs and symptoms of OA. However, the proportion of patients with cardiorenal and hepatic AEs was significantly lower in the celecoxib group than the diclofenac group.

[Cost study of NSAID use in rheumatoid arthritis based on recent therapeutic protocols]. / NSAID szerek költség-ertékelése rheumatoid arthritisben az ervényben 1évo terápiás protokoll alapján.

In today's health care beside the medical perspective, economic aspects should also be taken into consideration. Because of the significant opportunity-cost, only the most cost-effective techniques should be subsidized, which result the highest net-benefit for the society. This paper focuses on the economic aspects of the chronic NSAID use in rheumatoid arthritis. Based on recent therapeutic protocols a cost study (partial economic evaluation) was carried out. Our results indicate that for patients with an average GI-risk retard diclofenac could be a possible good choice. For patients with moderate to severe GI risk, retard diclofenac + pantoprazole combination therapy should be prescribed. COX-2 inhibitors are advised only for a limited group of patients with specific conditions; because of their higher price and side effect profile (severe CV adverse effect and uncertain GI benefits). We would also highlight the importance of individual therapy. In complex our purpose was to evaluate current therapeutic guidelines from a pharmacoeconomic perspective.

The payer side: patient outcomes and cost.

Payers and clinicians share a commitment to successful clinical outcomes in patients with acute or chronic pain. However, there are several issues that concern payers and managed care plans, including the cost of therapy and the cost of treating side effects. This article reviews the economic implications of pain management and the need to provide care in a clinically and economically responsible way. The article also addresses the value of medications to patients, the need for more judicious use of very expensive medications, and the use of evidence-based treatment guidelines.

Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of ankylosing spondylitis in the UK.

OBJECTIVES: To evaluate the cost-effectiveness of etoricoxib, a cyclooxygenase (COX)-2 selective inhibitor, versus non-selective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in the treatment of ankylosing spondylitis (AS). METHODS: The cost-effectiveness of etoricoxib versus nsNSAIDs was evaluated from the UK National Health Service (NHS) and society perspective with a decision-analytic model. Patients stayed on initial therapy throughout 52 weeks unless they experienced an adverse event (AE) or lacked efficacy, in which case they switched to another nsNSAID or a tumor necrosis factor alpha antagonist. Efficacy data were obtained from a 1-year etoricoxib clinical trial in AS. Bath AS Functional Index (BASFI) data were translated into Quality Adjusted Life Year (QALY) weights using a published data on the relation between BASFI and Short-form (SF) 36 Quality of life scores, as well as the relation between SF-36 and utility. Safety data were based on meta-analyses of etoricoxib trials. Information on treatment pathways, resource consumption, and absenteeism from work was obtained from literature and experts. Model outcomes included QALYs, perforations, ulcers, or bleeds, cardiovascular events, and costs. RESULTS: Etoricoxib was cost-effective compared to nsNSAIDs in terms of cost per QALY saved ( pound5611). Probabilistic sensitivity analysis found a 77% probability of the incremental cost per QALY saved being within a threshold for cost-effectiveness of pound20 000. The expected direct costs over the 52-week period were pound1.23 (95% uncertainty distribution pound1.10; pound1.39) and pound1.13 per day ( pound0.78; pound1.55) for patients starting with etoricoxib and nsNSAIDs, respectively. When costs related to absenteeism were taken into account, the cost per QALY saved was pound281. CONCLUSIONS: Given the underlying assumptions and data used, this economic evaluation demonstrated that, compared to nsNSAIDs, etoricoxib is a cost-effective therapy for AS patients in the UK.

Injustifiable use of gastroprotection in advanced cancer patients.

The aim of this survey was to prospectively collect data about gastroprotector prescription at admission of an acute pain relief and palliative care unit. An observational survey was performed on three-hundred consecutive patients. Reasons for admission, concomitant treatment and use of drugs were recorded at admission. About 60.6% patients had been prescribed proton pump inhibitors or anti-H2 receptors agents. Of these patients, possible risk factors were nonsteroidal anti-inflammatory drugs (41, 22.5%), corticosteroids (43, 23.6%), age > 75 years (27, 14.8%). In only 25 admissions (13.7%) prescription corresponded to Italian drug agency recommendations with an odds ratio of an off-label prescription of 7.28. In a relatively high percentage of admissions (55%), patients receiving gastroprotectors were on chemotherapy, with an odds ratio of 1.42. This survey showed that gastroprotectors are often prescribed regardless of Health Care System regulations, as only a minority of patients satisfied the requirements of an appropriate and refundable prescription. The attitudes of oncologists who prescribe gastroprotectors for a putative protective effects are not supported by evidence. Health Care Service in Italy should be aware of these problems to improve the strategies of budgeting the drug expense in a better way or providing further guidelines based on studies able to demonstrate the real cost-benefit ratio of this class of drugs.

Cost analysis applied to postoperative analgesia regimens: a comparison between parecoxib and propacetamol.

BACKGROUND: Postoperative pain management represents a significant part of perioperative costs. Non-opioid analgesics are often used in combination with opiates to improve pain relief and reduce opioid-related side effects. OBJECTIVE: To assess the costs and cost efficacy of intravenous (i.v.) parecoxib versus i.v. propacetamol in postoperative pain. METHODS: A prospective, randomised, double-blind, clinical evaluation was performed to compare the efficacy of a single bolus injection of 40 mg parecoxib and 2 g propacetamol, administered twice within 12 h following surgical repair of inguinal hernia. Resources for each arm of treatment were collected, and total costs were determined, including costs of drug acquisition, devices and labour for preparation of the two analgesic drugs. Cost-efficacy analysis was performed as the cost to achieve complete satisfaction with analgesia. Incremental cost efficacy was determined as the ratio between the differential costs and the differential patient satisfaction. The analysis was performed from an institutional perspective over a 12 h time frame. RESULTS: A total of 182 patients was evaluated. Pain at rest and morphine consumption were observed to be reduced in the parecoxib group. The percentages of patients totally satisfied with their pain management 12 h after surgery were 87% in the parecoxib-treated group and 70% in the propacetamol-treated group (P < 0.01). The average cost per patient was higher in the parecoxib group, 6.65 euros vs 5.28 euros in the propacetamol group). Cost per patient satisfied was calculated at a mean value of 7.64 euros for parecoxib and 7.54 euros for propacetamol. Incremental cost per additional patient satisfied was 8.02 euros in the parecoxib-treated group when preparation costs were included. Sensitivity analysis (+/-15%), including a bootstrap method applied to costs and efficacy, did not modify these conclusions. CONCLUSION: Parecoxib exhibits higher cost and greater patient satisfaction than does propacetamol. From a cost-efficacy approach, incremental cost per additional patient satisfied for parecoxib treatment must be analysed in light of overall perioperative pharmaceutical cost.

Utilization and cost comparison of current and optimal prescribing of nonsteroidal antiinflammatory drugs in Quebec, Canada.

OBJECTIVE: Clinical practice guidelines recommend prophylactic use of gastroprotective agents (GPA) with nonselective nonsteroidal antiinflammatory drugs (nsNSAID) for patients at risk of gastrointestinal (GI) complications. We estimated the costs of cyclooxygenase-2 selective inhibitors, nsNSAID, and concurrent GPA prescribed in 2002 in Quebec, Canada, and compared these to estimated costs if prescribing followed guideline recommendations. METHODS: We used the Quebec government medical and pharmaceutical claims database (RAMQ). All prescriptions for NSAID and concurrent GPA dispensed between January 1 and December 31, 2002, were evaluated for continuously covered beneficiaries 18 years of age or older. Prescriptions were stratified by patient GI risk factors determined at the dispensing date of each prescription into low-, moderate-, elevated-, and high-risk categories. Five scenarios of "appropriate" NSAID therapy were identified using clinical practice guidelines. The potential effect on the prescription drug budget of implementing each of these scenarios was estimated. RESULTS: In total, 503,671 patients filled 1,863,171 prescriptions for NSAID, representing 41.1 million days of treatment with total expenditures of about dollar 94 million CDN for NSAID and concurrent GPA. Average actual daily costs for coxibs (rofecoxib and celecoxib), celecoxib, nsNSAID, and concurrent GPA were dollar 1.94, dollar 2.06, dollar 1.19, and dollar 2.30, respectively. Prescribing nsNSAID with GPA to all patients at moderate and elevated risks while prescribing NSAID without GPA to patients at low risk, and celecoxib with a GPA to patients at very high risk would have cost dollar 36.4 million more, mainly due to the additional cost of GPA. CONCLUSION: Compared to actual prescribing patterns, a prescribing strategy consistent with clinical practice guidelines can increase drug acquisition costs to the healthcare payer.

[Pharmaco-economic analysis of NSAID usage in Gastroenterology Department of Tuzla Clinic]. / Farmakoekonomska analiza primjene nesteroidnih antireumatika na odjelu za gastroenterologiju Klinickog centra u Tuzli.

Pharmacoeconomics is young rapidly developing science that uses economic, clinical and epidemiologic methods. It studies adequate use of therapeutics giving guidelines towards rational utilization of the resources in health care. Pharmacoeconomics indentifies estimates and compares costs and clinical outcomes of different strategies giving the best solution: optimal cost/benefit ratio. These studies can be used to estimate existing programs and plan the new ones. The aim of this paper was to carry out pharmacoeconomic study on the non-steroid anti-inflamatory drugs (NSAID) use in canton Tuzla, to compare costs of medication with highly selective cyclooxygenase 2 (COX-2) inhibitors and nonselective NSAIDs and to calculate medication costs of the bleeding from upper parts of gastrointestinal tract. Study covers period from January to April 2004. Meta-analysis of selected clinical studies on safe and efficiency of NSAIDs was simultaneously conducted. Our results show that hospital treatment costs of the high-risk patients group significantly exceeds their potential medication costs with highly selective COX-2 inhibitors. Simultaneous use of non-selective NSAIDs with antacids has justification only in the low-risk group with mild gastrointestinal disturbances.

Medical and pharmacy expenditures after implementation of a cyclooxygenase-2 inhibitor prior authorization program.

STUDY OBJECTIVE: To evaluate the effects of a cyclooxygenase (COX)-2 inhibitor prior authorization (PA) program on direct medical and pharmacy costs. DESIGN: Prospective, pre- and postimplementation cohort study with reference group. SETTING: Large corporation in the Midwest. PATIENTS: Of 26,375 continuously enrolled members, 737 used a COX-2 inhibitor in the 3 months before January 1, 2003, when the PA program was implemented. MEASUREMENT AND MAIN RESULTS: The PA program limits coverage for a COX-2 inhibitor to members with a documented risk for a nonselective nonsteroidal antiinflammatory drug (NSAID)-induced gastrointestinal adverse event. All pharmacy and medical claims and costs were analyzed from the payer's perspective for a 15-month period. Separate pharmacy cost comparisons and medical cost comparisons were made between the 3-month quarter before PA program implementation and each follow-up quarter after PA program implementation. In the 3 months after PA program implementation, 620 (84.1%) of 737 members had no claims for a COX-2 inhibitor, and during this period their pharmacy and medical costs initially declined 40.0% (p < 0.001) and 18.7% (p < 0.001), respectively, and remained significantly lower. Among a subgroup of 156 members who tried to fill a COX-2 inhibitor prescription but were denied coverage, pharmacy and medical costs initially declined, 48.1% (p < 0.001) and 10.3% (p < 0.001), respectively, with pharmacy costs remaining significantly lower; however, overall medical expenditures increased, then returned to baseline. No change was noted in physician outpatient encounters, and two members had an emergency department visit for abdominal pain with no gastrointestinal ulcerations or bleeds during the 12-month follow-up. CONCLUSION: Among members denied coverage for a COX-2 inhibitor after implementation of a PA program, pharmacy costs declined without a medical cost increase associated with gastrointestinal diagnoses.