Actions following adverse drug events - how do these influence uptake and utilisation of newer and/or similar medications?

BACKGROUND: Over the last decade, actions following some adverse drug events received major publicity. This study investigated changes in usage patterns of medications in Australia following two examples - rofecoxib market withdrawal (2004) and warnings about jaw necrosis following bisphosphonates (2007). METHODS: Dispensing data for COX-2 inhibitors (2000-2008) and anti-osteoporosis medications (2003-2012) were obtained from the Australian Pharmaceutical Benefits Scheme database. For bisphosphonates, data on Australian marketing expenditures were purchased from Cegedim(R). RESULTS: For COX-2 inhibitors, celecoxib dispensing halved after rofecoxib withdrawal, but meloxicam dispensing increased by 60 %. When lumiracoxib was introduced (2006) there was uptake of prescribing at a faster rate than meloxicam in 2002, its first year of use. For bisphosphonates, alendronate had highest use at the time of the warnings (8.3 DDD/1000/day), dropping to 4.9 DDD/1000/day by 2012. In contrast, risedronate use rose 2007-2012 from 4.1 to 4.9 DDD/1000/day. There was 49 % increase in reported annual expenditure on detailing for risedronate from 2007 to 2008 (to AUD$7.3 million) and only 29 % increase for alendronate (to AUD$3.1 million). CONCLUSIONS: The rapid uptake of prescribing of lumiracoxib and increased use of meloxicam flagged a concern, especially after rofecoxib withdrawal due to safety issues. Bisphosphonates are useful drugs, however the dramatic rise in expenditure on detailing, followed by a rise in utilisation of risedronate could suggest that adverse publicity triggered a marketing response. These examples highlight the importance of tracking utilisation of medication classes in real time, using different data as needed, to ensure that due caution is exercised (and quick intervention provided if needed) for medications in the same class.

[Financial cost of early rheumatoid arthritis in the first year of medical attention: three clinical scenarios in a third-tier university hospital in Colombia]. / Costos directos de la artritis reumatoide temprana en el primer año de atención: simulación de tres situaciones clínicas en un hospital universitario de tercer nivel en Colombia.

INTRODUCTION: In Colombia, the cost burden of chronic diseases is not well known, either globally or in localized areas of the health system. Rheumatoid arthritis is one of most common chronic diseases, and represents a high cost for the health system. OBJECTIVE: The direct medical costs were estimated for rheumatoid arthritis patients in the in the first year of diagnosis at a level 3 university hospital in Colombia. MATERIALS AND METHODS: Three therapy settings for early rheumatoid arthritis patients were established in the first year of diagnosis according to national and international guidelines. Each setting included treatment with disease-modifying anti-rheumatic drugs or biologic therapy based on disease severity as measured by Disease Activity Score 28. All direct medical costs were included: specialized medical care, diagnostic tests and drugs. Cost information was obtained from the Central Military Hospital finance department in Bogotá and the national manual of drug prices based on the "Farmaprecios" 2007 guide, a reference in general use by health institutions. Results. The average of cost of medical care in patients with mild, moderate and severe disease was US $1689, $1805 and $23,441 respectively. The recommended retail prices of the medicines published in "Farmaprecios" was US $1418, $1821 and $31,931. When the charges levied by several major health institutions were compared, substantial increases were noted, US $4936, $7716 and $123,661, respectively. Drug costs represented 86% of total cost, laboratory costs were 10% and medical attention was only 4%. CONCLUSIONS: Drugs costs were the principal component of the total direct medical cost, and it increased 40 times when a biological therapy is used. Complete economic evaluation studies are necesary to estimate the viability and clinical relevance of biological therapy for early rheumatoid arthritis.

Costs and persistence of brimonidine versus brinzolamide in everyday glaucoma care: an analysis conducted on the UK General Practitioner Research Database.

OBJECTIVE: To compare the persistence and costs of brimonidine versus brinzolamide therapy according to data collected by the UK General Practitioner Research Database (GPRD). METHODS: Patients with diagnoses of ocular hypertension or glaucoma, or treated for glaucoma by surgery or laser therapy were identified. Selected patients were prescribed either brimonidine or brinzolamide as monotherapy. Treatment failure was defined as a glaucoma prescription change (adding, removing or replacing a drug, or initiating surgery or laser therapy). Times to treatment failure were compared with an adjusted Cox model using a propensity score method. RESULTS: A total of 2,172 patients received brimonidine and 485 brinzolamide. Mean age was 69.5 years and 46.4% were male. Age and gender did not differ significantly whereas disease duration was longer with brinzolamide. Treatment failure at 1 year was experienced by 47.7% of patients given brinzolamide and by 55.9% given brimonidine (p<0.001). The hazard ratio for failure was less with brinzolamide (0.79: p<0.001) compared to brimonidine, after adjusting for age, gender, comorbidities and duration of follow-up. Adjusted annual costs of glaucoma management (in pound2005) were significantly (p<0.0042) lower with brinzolamide (pound196) than brimonidine (pound230). CONCLUSIONS: According to data from everyday practice collected by the UK GPRD, brinzolamide was found to be more persistent than brimonidine when given as glaucoma monotherapy. Patients continued longer with brinzolamide treatment at a lower cost.

Modelling therapeutic strategies in the treatment of osteoarthritis: an economic evaluation of meloxicam versus diclofenac and piroxicam.

OBJECTIVE: To assess the economic efficiency of meloxicam, a cyclo-oxygenase (COX)-2 selective inhibitor, versus diclofenac and piroxicam in the UK for the treatment of patients with osteoarthritis and the impact on the NHS budget of substituting nonselective NSAIDs with meloxicam. Methods and perspective: A decision analytical model was used to compare the effects of 4 weeks' treatment of osteoarthritis with meloxicam (7.5 mg/day), diclofenac (100 mg/day) and piroxicam (20 mg/day). The decision tree was derived by combining best practice and clinical reality. Analysis was from the NHS perspective. The study considered only the direct costs. These included costs for drug acquisition and management of all adverse events, both serious gastrointestinal events requiring hospitalisation, and non-serious events that required maintenance. Resource use and treatment costs were obtained from local and published sources. A range of sensitivity analyses was carried out. RESULTS: Based on two 4-week large-scale trials, the Meloxicam Large-scale International Study Safety Assessment (MELISSA) and Safety and Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) trials, and a decision analytical model, the findings suggested that meloxicam had the lowest cost per patient ( pound 30 versus pound 35 for piroxicam and pound 51 for diclofenac [costs presented as 1998 values except for drug costs which were in 2000 values]). The results of the Monte Carlo probabilistic sensitivity analysis, using 4000 samples, suggested that meloxicam was the optimal strategy in the drug treatment of patients with osteoarthritis compared with nonselective NSAIDs both individually and as a group. The cost savings were due to lower levels of serious adverse events accompanied by fewer days in intensive care units and shorter overall duration of hospital stay observed with meloxicam compared with diclofenac and piroxicam in the 4-week trials. CONCLUSIONS: Based on the 4-week trial period, meloxicam was predicted to be the lowest cost drug therapy, and thus the optimal drug therapy, in the management of patients with osteoarthritis compared with nonselective NSAIDs such as diclofenac and piroxicam. Applying the cost savings per patient derived from the model, switching patients from piroxicam and diclofenac to meloxicam would indicate a cost saving of over pound 25 million per annum. Models such as this can facilitate better clinical guidance and is a useful way of assessing treatment outcomes.

Cost-minimisation study of dorzolamide versus brinzolamide in the treatment of ocular hypertension and primary open-angle glaucoma: in four European countries.

OBJECTIVE: Cost is an issue when prescribing two drugs with equivalent efficacy. We compared the direct medical costs of topical brinzolamide 1% (twice a day or three times daily) with topical dorzolamide 2% (twice a day or three times daily) in France, Italy, Portugal and Spain in patients with ocular hypertension or primary open-angle glaucoma. DESIGN AND SETTING: Three double-blind, controlled, randomised trials (with a study duration of 3 months) compared the response rate of brinzolamide twice a day or three times daily versus dorzolamide three times daily, and the response rate of brinzolamide-timolol twice a day versus a dorzolamide-timolol combination twice a day. A fourth double-blind randomised trial (with a duration of 12 months) compared brinzolamide twice a day and three times daily with timolol monotherapy. Local tolerance was compared in two dedicated studies. Rates of switching to a new medication regimen were evaluated through a US health maintenance organisation database. In case of treatment failure, the patients were treated with latanoprost. A model was developed to value direct medical costs over 3 months. The economic perspective was that of the third-party payer and the patient, and included direct medical costs (reimbursed part plus co-payment). PATIENTS: Patients with ocular hypertension and/or primary open-angle glaucoma who had not responded to or could not tolerate beta-blocker therapy. OUTCOME MEASURE: The daily direct medical costs of therapy with the two drugs. RESULTS: As monotherapy, brinzolamide twice daily and three times daily was found to be as efficacious as dorzolamide three times a day. Brinzolamide twice daily plus timolol was also as efficacious as a combination of dorzolamide and timolol twice a day. Stinging of the eye upon instillation with brinzolamide was experienced by fewer patients than with dorzolamide (p < 0.0001). The likelihood of patients treated with dorzolamide changing therapy was 1.28 times greater than that for those treated with brinzolamide. The size of the brinzolamide drop is 18.7% smaller than that of dorzolamide allowing seven more therapy days per bottle with brinzolamide twice daily than with dorzolamide monotherapy, and five more days when brinzolamide is used three times a day. The direct medical costs for patients treated with brinzolamide were lower in all four European countries when drop size was taken into account than for those treated with dorzolamide. Sensitivity analyses confirmed the robustness of our findings. CONCLUSION: Because brinzolamide can be prescribed twice daily in monotherapy and because fewer patients treated with brinzolamide switch therapy due to local intolerance, our model suggests that brinzolamide is a cost-saving alternative to dorzolamide.

Developing a managed care-pharmaceutical research partnership.

Increasingly, MCOs ask pharmaceutical companies for evidence of a new product's cost effectiveness before adding it to the formulary. This article examines a research partnership between a pharmaceutical company and 14 MCOs to assess the cost effectiveness of a new medication for osteoarthritis. The research partnership, a study protocol, and research activities are discussed.