Meloxicam versus Celecoxib for Postoperative Analgesia after Total Knee Arthroplasty: Safety, Efficacy and Cost.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as part of multimodal analgesia in total knee arthroplasty (TKA). Selective cyclooxygenase (COX)-2 inhibitors (e.g., celecoxib) are believed to have fewer gastrointestinal (GI) adverse effects than nonselective NSAIDS. Meloxicam is less selective for COX-2 than celecoxib is and partially inhibits COX-1 at higher doses. Nonetheless, some surgeons prefer using nonselective NSAIDs because of their lower expense. METHODS: Four thousand nine hundred ninety-four patients who underwent TKA between January 2015 and February 2020 and took either celecoxib (n = 3,174), meloxicam 15 mg/d (n = 1,819), or meloxicam 7.5 mg/d (n = 451) were studied. Mutlimodal postoperative analgesia protocols were otherwise similar. GI bleeding and wound complication incidence were determined, as well as average 30-day prescription costs. RESULTS: GI bleeding incidence was similar in the three cohorts (P = 0.4). The incidence of wound complications did not significantly differ between the groups: 0.06%, 0.07%, and 0.22% in the celecoxib, meloxicam 15 mg/d, and meloxicam 7.5 mg/d groups, respectively (P = 0.06). Subsituting meloxicam for celecoxib results in an average savings of $183 per prescription. DISCUSSION: Meloxicam used at higher doses (15 mg/d) does not markedly increase the risk of GI or wound complications associated with COX-1 inhibition and is less costly for multimodal analgesia after TKA.

The Headache Pipeline: Excitement and Uncertainty.

There are many new treatment options available for migraine and more are coming. Three calcitonin gene-related peptide (CGRP) antagonist monoclonal antibodies have been approved and a 4th is due in early 2020. Small molecule CGRP receptor-blocking oral compounds, both for acute care and prevention, are also coming. Four neurostimulators are available, with others on the way. New acute treatments coming soon include the 5HT1F agonist lasmiditan, a zolmitriptan intradermal micro-needle patch, and a nasal mist sumatriptan with a permeability enhancer. Farther out, three novel dihydroergotamine delivery systems, and a liquid-filled capsule of celecoxib show early promise. A new, safer form of methysergide is in the works, as is a longer-duration onabotulinumtoxinA. As always with new products, questions regarding safety, tolerability, cost, and insurance coverage will need to be addressed. Despite these concerns and uncertainties, a robust headache treatment pipeline is good for patients who are not satisfied with the results of their treatment and/or cannot tolerate existing treatments.

Exposure to cox-2 inhibitors (coxibs) during the first trimester and pregnancy outcome: a prospective observational cohort study.

PURPOSE: Cox-2-inhibitors (coxibs) are not recommended in pregnancy but early exposure may occur, for instance in unplanned pregnancies. Experience in pregnancy is limited leading to concerns in patients and their health care providers. Therefore, further data on coxibs and their effects on embryogenesis are needed. METHODS: This observational cohort study evaluates pregnancies ascertained in Germany during the study period from January 2000 to January 2016. A cohort of 174 women exposed to coxibs in the first trimester was compared to a randomly selected cohort of 521 women without exposure to coxibs, other nonsteroidal anti-inflammatory drugs or known teratogens. RESULTS: The overall rate of major birth defects was not significantly increased in the study cohort (2.9 vs. 2.7%, OR 1.08, 95% CI 0.34-3.42; OR adjusted 0.96, 95% CI 0.28-3.26). The cumulative incidence of spontaneous abortions was nonsignificantly lower in the exposed cohort (14.3 vs. 20.0%; HR, 0.90, 95% CI 0.51-1.58; HR adjusted, 0.87; 95% CI, 0.49-1.56). Elective terminations of pregnancies (ETOP), mainly for 'social' reasons, were more frequent in the coxib cohort (17.5 vs. 7.0%, HR, 2.31; 95% CI, 1.26-4.24; HR adjusted 2.12, 95% CI 1.13-3.97). CONCLUSIONS: Our study results support the assumption that coxibs are not major teratogens. Considering the still limited evidence basis on coxib exposure during pregnancy, well-established alternatives should be preferred.

Acute Liver Failure Due to Etodolac, a Selective Cycloxygenase- 2 (COX -2) Inhibitor Non-Steroidal Anti-Inflammatory Drug Established by RUCAM-Based Causality Assessment.

Drug induced liver injury is a common cause of acute liver failure (ALF). While most of these cases are due to dose dependent hepatotoxicity with acetaminophen, idiosyncratic drug-induced liver injury (DILI) is responsible for about 15% cases of ALF. Antibiotics are the most common cause of idiosyncratic DILI as well as DILI induced ALF. Etodolac is a selective cycloxygenase- 2 (COX -2) inhibitor non-steroidal anti-inflammatory drug used as an analgesic and anti-inflammatory in musculoskeletal diseases. Severe liver impairment is extremely rare. Till date, only 3 cases of ALF related to etodolac have been reported in the literature. Here we report two cases with a unique presentation of ALF occurring due to DILI caused by etodolac, as diagnosed by Roussel Uclaf Causality Assessment Method (RUCAM).

Assessment of a prognostic model, PSA metrics and toxicities in metastatic castrate resistant prostate cancer using data from Project Data Sphere (PDS).

BACKGROUND: Prognostic models in metastatic castrate resistant prostate cancer (mCRPC) may have clinical utility. Using data from PDS, we aimed to 1) validate a contemporary prognostic model (Templeton et al., 2014) 2) evaluate prognostic impact of concomitant medications and PSA decrease 3) evaluate factors associated with docetaxel toxicity. METHODS: We accessed data on 2,449 mCRPC patients in PDS. The existing model was validated with a continuous risk score, time-dependent receiver operating characteristic (ROC) curves, and corresponding time-dependent Area under the Curve (tAUC). The prognostic effects of concomitant medications and PSA response were assessed by Cox proportional hazards models. One year tAUC was calculated for multivariable prognostic model optimized to our data. Conditional logistic regression models were used to assess associations with grade 3/4 adverse events (G3/4 AE) at baseline and after cycle 1 of treatment. RESULTS: Despite limitations of the PDS data set, the existing model was validated; one year AUC, was 0.68 (95% CI 95% CI, .66 to .71) to 0.78 (95%CI, .74 to .81) depending on the subset of datasets used. A new model was constructed with an AUC of .74 (.72 to .77). Concomitant medications low molecular weight heparin and warfarin were associated with poorer survival, Metformin and Cox2 inhibitors were associated with better outcome. PSA response was associated with survival, the effect of which was greatest early in follow-up. Age was associated with baseline risk of G3/4 AE. The odds of experiencing G3/4 AE later on in treatment were significantly greater for subjects who experienced a G3/4 AE in their first cycle (OR 3.53, 95% CI 2.53-4.91, p < .0001). CONCLUSION: Despite heterogeneous data collection protocols, PDS provides access to large datasets for novel outcomes analysis. In this paper, we demonstrate its utility for validating existing models and novel model generation including the utility of concomitant medications in outcome analyses, as well as the effect of PSA response on survival and toxicity prediction.

Chemoprevention of colorectal neoplasia.

BACKGROUND: Colorectal cancer is a common and often fatal malignancy. Currently, the modifications that alter disease outcome include early symptom recognition, population screening as well as improved surgical and adjuvant treatments. Preventative strategies have been limited with little evidence that lifestyle changes significantly alter risk. There is however a growing awareness of a potential role for chemoprevention in some patient groups. This study aimed to review the literature associated with chemoprevention in colorectal cancer. METHODS: An electronic literature search of MEDLINE and Embase databases was performed on PubMed for studies detailing the use of chemoprevention agents in colon and rectal cancer. The search was limited to clinical trials on adult humans (>16 years of age) published in English since 1990. RESULTS: The strongest evidence is for non-steroidal anti-inflammatory drugs slowing polyp progression, notably Sulindac and aspirin in patients with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, respectively. There is also increasing evidence that continuing use of low-dose aspirin reduces long-term incidence of colorectal cancers. Cyclooxygenase 2 inhibitors also have a potential role but cardiac toxicity currently limits their use. Folic acid, statins, antioxidants, calcium and 5-aminosalicylic acid lack evidence to support their use at present. CONCLUSIONS: Currently, there is not enough evidence to support the implementation of a chemopreventative agent for general use. However, there appears to be a role for aspirin in selected subgroups.

Comparison of Calipers for Matching on the Disease Risk Score.

Previous studies have compared calipers for propensity score (PS) matching, but none have considered calipers for matching on the disease risk score (DRS). We used Medicare claims data to perform 3 cohort studies of medication initiators: a study of raloxifene versus alendronate in 1-year nonvertebral fracture risk, a study of cyclooxygenase 2 inhibitors versus nonselective nonsteroidal antiinflammatory medications in 6-month gastrointestinal bleeding, and a study of simvastatin + ezetimibe versus simvastatin alone in 6-month cardiovascular outcomes. The study periods for each cohort were 1998 through 2005, 1999 through 2002, and 2004 through 2005, respectively. In each cohort, we calculated 1) a DRS, 2) a prognostic PS which included the DRS as the independent variable in a PS model, and 3) the PS for each patient. We then nearest-neighbor matched on each score in a variable ratio and a fixed ratio within 8 calipers based on the standard deviation of the logit and the natural score scale. When variable ratio matching on the DRS, a caliper of 0.05 on the natural scale performed poorly when the outcome was rare. The prognostic PS did not appear to offer any consistent practical benefits over matching on the DRS directly. In general, logit-based calipers or calipers smaller than 0.05 on the natural scale performed well when DRS matching in all examples.

[Cost-effectiveness analysis of celecoxib versus non-selective non-steroidal anti-inflammatory drug therapy for the treatment of osteoarthritis in Spain: A current perspective]. / Análisis coste-efectividad de celecoxib frente a antiinflamatorios no esteroideos no selectivos en el tratamiento de la artrosis en España: una perspectiva actual.

OBJECTIVE: To assess the cost-effectiveness of celecoxib and non-selective non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis in clinical practice in Spain. METHODS: A decision-tree model using distribution, doses, treatment duration and incidence of GI and CV events observed in the pragmatic PROBE-designed «GI-Reasons¼ trial was used for cost-effectiveness. Effectiveness was expressed in terms of event averted and quality-adjusted life-years (QALY) gained. QALY were calculated based on utility decrement in case of any adverse events reported in GI-Reasons trial. The National Health System perspective in Spain was applied; cost calculations included current prices of drugs plus cost of adverse events occurred. The analysis was expressed as an incremental cost-effectiveness ratio per QALY gained and per event averted. One-way and probabilistic analyses were performed. RESULTS: Compared with non-selective non-steroidal anti-inflammatory drugs, at current prices, celecoxib treatment had higher overall treatment costs €201 and €157, respectively. However, celecoxib was associated with a slight increase in QALY gain and significantly lower incidence of gastrointestinal events (p<.001), with mean incremental cost-effectiveness ratio of €13,286 per QALY gained and €4,471 per event averted. Sensitivity analyses were robust, and confirmed the results of the base case. CONCLUSION: Celecoxib at current price may be considered as a cost-effective alternative vs. non-selective non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis in daily practice in the Spanish NHS.

Gastroprotective agent underuse in high-risk older daily nonsteroidal anti-inflammatory drug users over time.

OBJECTIVES: To examine whether older adults taking nonsteroidal anti-inflammatory drugs (NSAIDs) decreased the underuse of gastroprotective agents over time. DESIGN: Before-and-after study. SETTING: Health, Aging and Body Composition Study. PARTICIPANTS: Daily users of a NSAID (prescription and over the counter (OTC)) at visits in 2002-03 (preperiod; n = 404) and 2006-07 (postperiod; n = 172). The sample had a mean ± standard deviation age of 78.2 ± 2.7 at the preperiod visit and 81.9 ± 2.7 at the postperiod visit. The majority were white and female and had 12 or more years of education. MEASUREMENTS: Underusers were defined as persons taking nonselective NSAIDs who were at risk of peptic ulcer disease (PUD; because of current warfarin or glucocorticoid use or history of PUD) and not using a proton pump inhibitor (PPI) or persons taking cyclooxygenase 2 (COX-2) selective NSAIDs and aspirin who were at risk of PUD (having at least one risk factor) and not using a PPI. RESULTS: Daily NSAID use decreased from 17.6% to 11.3% (P < .001), and gastroprotective agent underuse decreased from 23.5% to 15.1% (P = .008). Controlling for important covariates, having prescription insurance was somewhat protective against underuse in the preperiod (adjusted odds ratio (AOR) = 0.78, 95% confidence interval (CI) = 0.46-1.34; P = .37), but more so and significantly in the postperiod (AOR = 0.41, 95% CI = 0.18-0.93; P = .03). Having prescription insurance was more protective in the post- than in the preperiod (less gastroprotective agent underuse; adjusted ratio of OR = 0.53, 95% CI = 0.22-1.29; P = .16), but this increased protection was not statistically significant. CONCLUSION: In older daily NSAID users at high risk of PUD, having prescription insurance and adequate gastroprotective use was more common in the post- than in the preperiod.

"First-wave" bias when conducting active safety monitoring of newly marketed medications with outcome-indexed self-controlled designs.

Large health care databases are used extensively for pharmacoepidemiologic studies. Unique methodological issues arise when applying self-controlled designs (i.e., using within-person comparisons) for active surveillance of newly marketed drugs. We use 3 examples to illustrate bias related to population-level exposure time trends when using outcome-indexed self-controlled (i.e., case-crossover) designs for active surveillance and evaluate the ability of the case-time-control design to adjust for bias from population-level exposure time trends. We mimicked active surveillance by conducting sequential analyses after market entry for 3 medications and outcomes (valdecoxib for myocardial infarction (MI), aripiprazole for MI, and telithromycin for acute liver failure) using Medicaid Analytic eXtracts (from all 50 US states, 2000-2006). The case-crossover exposure odds ratio (EOR) in the months immediately following valdecoxib market entry implausibly suggested a 12-fold higher risk of MI during exposed time relative to unexposed time; among age-, sex-, and time-matched controls, the corresponding EOR of 4.5 indicated strong population-level exposure time trends. Over subsequent monitoring periods, case-crossover EORs rapidly dropped to 1.4. Adjustment for bias from population-level exposure time trends with the case-time-control analysis resulted in more consistent associations between valdecoxib and MI across sequential monitoring periods. Similar results were observed in each example. Strong population-level exposure time trends can bias case-crossover studies conducted among "first-wave" users of newly marketed medications. Suggested strategies can help assess and adjust for population-level exposure time trends.

Gastroprotective strategies in chronic NSAID users: a cost-effectiveness analysis comparing single-tablet formulations with individual components.

OBJECTIVES: To evaluate the cost-effectiveness of competing gastroprotective strategies, including single-tablet formulations, in the prevention of gastrointestinal (GI) complications in patients with chronic arthritis taking nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: We performed a cost-utility analysis to compare eight gastroprotective strategies including NSAIDs, cyclooxygenase-2 inhibitors, proton pump inhibitors (PPIs), histamine-2 receptor antagonists, misoprostol, and single-tablet formulations. We derived estimates for outcomes and costs from medical literature. The primary outcome was incremental cost per quality-adjusted life-year gained. We performed sensitivity analyses to assess the effect of GI complications, compliance rates, and drug costs. RESULTS: For average-risk patients, NSAID + PPI cotherapy was most cost-effective. The NSAID/PPI single-tablet formulation became cost-effective only when its price decreased from €0.78 to €0.56 per tablet, or when PPI compliance fell below 51% in the NSAID + PPI strategy. All other strategies were more costly and less effective. The model was highly sensitive to the GI complication risk, costs of PPI and NSAID/PPI single-tablet formulation, and compliance to PPI. In patients with a threefold higher risk of GI complications, both NSAID + PPI cotherapy and single-tablet formulation were cost-effective. CONCLUSIONS: NSAID + PPI cotherapy is the most cost-effective strategy in all patients with chronic arthritis irrespective of their risk for GI complications. For patients with increased GI risk, the NSAID/PPI single-tablet formulation is also cost-effective.

[Drug-related claims in the Norwegian system of compensation to patients]. / Legemiddelsaker i Norsk pasientskadeerstatning.

BACKGROUND: Patients subjected to drug-related injuries can, in accordance with Norwegian legislation, seek compensation from the Norwegian System of Patient Injury Compensation (NPE). The aim of this study was to examine what drugs and injuries instigate claims against NPE, and how these cases are resolved. MATERIAL AND METHODS: We have assessed anonymised summaries of 992 consecutive indemnity applications received and evaluated by NPE over the period 2003-2009. We recorded the age and gender of applicants, treatment diagnosis, drugs implicated, outcome, and NPE's decision in each case. RESULTS: A total of 964 claims were included. The most commonly implicated drugs were those affecting the nervous system (34.6%) and the musculoskeletal system (26.1%). Rofecoxib at 18.9% was the predominant single drug implicated. In two-thirds of the cases, adverse effects were given as the reason for the claim, whereas the last one-third consisted of claims for medication errors. The most common injuries were related to cardiovascular diseases (28.7%) or non-specific conditions (17.5%). 8.4% of the cases related to fatalities. In all, 26.3% of the claims resulted in compensations. INTERPRETATION: Few patients made use of the NPE. Most of the compensation claims in the years 2003-2009 involved rofecoxib and psychoactive drugs, and the majority of claims were rejected.

Quantifying the impact of NSAID-associated adverse events.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used among patients experiencing many different types of pain, including inflammatory, acute pain (eg, injury, low back pain, headache, postoperative pain), and chronic pain (eg, rheumatoid arthritis, osteoarthritis). However, both traditional NSAIDs and second-generation NSAIDs (cyclooxygenase-2 inhibitors) can lead to very expensive and serious adverse events. Gastrointestinal, cardiovascular, and renal complications associated with NSAIDs have been shown to be dose-dependent. In 2005, to help minimize these risks, the US Food and Drug Administration issued a public health advisory stating that "NSAIDs should be administered at the lowest effective dose for the shortest duration consistent with individual patient treatment goals." This article reviews the undue clinical and economic burden associated with NSAID-related serious adverse events.

The cost-effectiveness of celecoxib vs diclofenac in the treatment of osteoarthritis in the UK; an update to the NICE model using data from the CONDOR trial.

OBJECTIVES: The National Institute for Health and Clinical Excellence (NICE) health economic model for assessing the cost-effectiveness of celecoxib plus a proton pump inhibitor (PPI) compared to diclofenac plus PPI in the treatment of osteoarthritis has been updated using new adverse event (AE) risks from the CONDOR trial. In light of this new information, this study aimed to evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus PPI compared to diclofenac plus PPI. METHODS: NICE developed a health economic model as part of their 2008 multiple technology assessment of treatments for osteoarthritis. The model was adapted for this study to update the relative risks of adverse events, using data from the CONDOR trial. RESULTS: Using the AE data from the CLASS trial alone, celecoxib plus PPI has an ICER of £9538 per QALY when compared to diclofenac plus PPI. When the AE data from CONDOR alone is used, this ICER decreases to £4773 per QALY. Using the pooled data from both trials, celecoxib plus PPI has an ICER of £9377 per QALY compared to diclofenac plus PPI. DISCUSSION: The results suggest that when new AE risks are used, celecoxib plus PPI remains a cost-effective treatment for OA when compared to diclofenac plus PPI. However, this analysis is limited by the short time horizon, and additional AEs that have not been considered.

Comparative impact on prostanoid biosynthesis of celecoxib and the novel nonsteroidal anti-inflammatory drug CG100649.

Nonsteroidal anti-inflammatory drugs (NSAIDs) elevate cardiovascular risk by disrupting cyclooxygenase-2 (COX-2)-dependent biosynthesis of prostacyclin (PGI(2)). CG100649 is a novel NSAID proposed to inhibit both COX-2 and carbonic anhydrase (CA)-I/-II. We compared its impact on prostanoid biosynthesis with that of celecoxib, an NSAID purposefully designed to selectively inhibit COX-2. In a controlled, double-blind randomized trial, single oral doses of 2 or 8 mg CG100649, 200 mg celecoxib, or placebo were well tolerated by healthy volunteers (n = 23). Both CG100649 and celecoxib had the effect of depressing urinary excretion of 2,3-dinor-6-keto-PGF(1α) (PGI-M); the effect of CG100649 was dose-dependent and more sustained (up to 240 h after the dose) than that of celecoxib. Neither CG100649 nor celecoxib significantly inhibited COX-1-dependent prostanoid formation. CA inhibition was not detected after administration of CG100649, despite its partitioning asymmetrically into erythrocytes. CG100649 and celecoxib are both relatively selective inhibitors of COX-2, but they differ in duration of action. Whether they have similar impact on cardiovascular events remains to be determined.

[Bringing evidence to practice: obstacles and barriers]. / Evidenztransfer in die praxis - hindernisse und barrieren.

Translating clinical research findings into daily medical practice is a complex procedure and subject to multiple impacts. Studies sponsored by drug manufacturers produce positive results more frequently than would be expected by chance alone; positive studies have a better chance to be published than negative ones. There is a lack of effective implementation strategies for medical guidelines. The mismatch of study population and own patients renders the generalizability of study results difficult. Other confounding factors in head-to-head studies are drug comparisons that do not conform to the gold standard, non-equivalent dosages and study duration. To solve these problems clinical research must pick up questions and problems from daily medical care. Studies independent of drug companies should be funded with public money, and health care research needs public support. Access to study protocols and data must be open to the public.

Further assessment of the clinically effective dose range of etoricoxib: a randomized, double-blinded, placebo-controlled trial in rheumatoid arthritis.

OBJECTIVE: To further assess the clinically active dose range of etoricoxib, a COX-2 selective inhibitor, in rheumatoid arthritis (RA). METHODS: RA patients were randomized to etoricoxib 10, 30, 60, or 90 mg or placebo in a double-blind, 12-week study. DMARDs (methotrexate, biologics) or low-dose corticosteroids were allowed in stable doses. The primary endpoint was the proportion of patients completing the study and achieving an American College of Rheumatology 20% (ACR20) response. Secondary endpoints included individual components of the ACR index and Patient Global Assessment of Pain. Safety was assessed by physical exam and adverse experiences (AEs) occurrences. RESULTS: Etoricoxib 90 mg was the only dose to reach a statistically significant difference from placebo (p < 0.001) on the primary endpoint; etoricoxib 60 mg approached significance (p = 0.057). Significant pain improvement vs. placebo was observed with etoricoxib 90 mg (p < 0.001), 60 mg (p = 0.018), and 30 mg (p = 0.017). Despite the use of background biologics and corticosteroids, a dose response was still apparent. A higher proportion of etoricoxib 60 and 90 mg patients had renovascular AEs (i.e., edema and hypertension) compared with placebo, although discontinuations for renovascular AEs were rare. Etoricoxib 90 mg had a higher incidence of serious AEs (n = 5; 1 was considered drug-related) versus placebo (n = 0). LIMITATIONS: The present study was not powered to detect differences in cardiovascular or gastrointestinal safety by dose. Additionally, further research is needed to clarify the role of doses less than the etoricoxib 90 mg dose for pain management in RA patients. CONCLUSION: Etoricoxib 90 mg demonstrated statistically superior efficacy (ACR20) compared with placebo and numerical superiority over the other doses of etoricoxib studied. Etoricoxib 30 and 60 mg demonstrated significant pain improvement versus placebo, suggesting utility for some patients.

Prescription pattern of NSAIDs and the prevalence of NSAID-induced gastrointestinal risk factors of orthopaedic patients in clinical practice in Korea.

This is a cross-sectional observational study undertaken to explore the current prescription pattern of non-steroidal anti-inflammatory drugs (NSAIDs) and the prevalence of NSAID-induced gastrointestinal (GI) risk factors of orthopaedic patients in real clinical practice in Korea. Study cohort included 3,140 orthopaedic outpatients at 131 hospitals and clinics between January 2008 and August 2008. A self-administered questionnaire was completed by each patient and physician. A simplified risk scoring scale (the Standardized Calculator of Risk for Events; SCORE) was used to measure patients' risk for GI complications. The pattern of NSAIDs prescription was identified from medical recordings. Forty-five percent of the patients belonged to high risk or very high risk groups for GI complications. The cyclooxygenase-2 enzyme (COX-2) selective NSAID showed a propensity to be prescribed more commonly for high/very high GI risk groups, but the rate was still as low as 51%. In conclusion, physician's considerate prescription of NSAIDs with well-understanding of each patient's GI risk factors is strongly encouraged in order to maximize cost effectiveness and to prevent serious GI complications in Korea. Other strategic efforts such as medical association-led education programs and application of Korean electronic SCORE system to hospital order communication system (OCS) should also be accompanied in a way to promote physician's attention.

Value of information in the osteoarthritis setting: cost effectiveness of COX-2 selective inhibitors, traditional NSAIDs and proton pump inhibitors.

BACKGROUND: Recent National Institute for Health and Clinical Excellence (NICE) guidance recommended that when traditional NSAIDs or cyclo-oxygenase (COX)-2 selective inhibitors are used by people with osteoarthritis (OA), they should be prescribed along with a proton pump inhibitor (PPI). However, specific recommendations about the type of NSAID or COX-2 could not be made due to high levels of uncertainty in the economic evaluation. OBJECTIVE: To investigate the value of obtaining further evidence to inform the economic evaluation of NSAIDs, COX-2s and PPIs for people with OA. METHODS: An economic evaluation with an expected value of perfect information (EVPI) analysis was conducted, using a Markov model with data identified from a systematic review. The base-case model used adverse event data from the three largest randomized trials of COX-2 inhibitors, and we repeated the analysis using observational adverse event data. The model was run for a hypothetical population of people with OA, and subgroup analyses were conducted for people with raised gastrointestinal (GI) and cardiovascular (CV) risk. The EVPI was based upon the OA population in England - approximately 2.8 million people. Of these, 50% were assumed to use NSAIDs or COX-2 selective inhibitors for 3 months per year and 56% of these were assumed to be patients with raised GI and CV risk. RESULTS: The value of further information for this decision problem was very high. Population-level EVPI was £85.1 million in the low-risk group and £179.5 million in the high-risk group (2007-8 values). Expected value of partial perfect information (EVPPI) analysis showed that the groups of parameters for which further evidence was likely to be of most value were CV adverse event risks and all adverse event rates associated with the specific drugs celecoxib and ibuprofen. The value of perfect information remained high even when observational adverse event data were used. CONCLUSIONS: There is a very high value associated with obtaining further information on uncertain parameters for the economic evaluation of NSAIDs, COX-2 selective inhibitors and PPIs for people with OA. Obtaining further randomized or observational information on CV risks is likely to be particularly cost effective.