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PubMed2004

Review of health economics modelling in rheumatoid arthritis.

As the cost of drug treatment for rheumatoid arthritis (RA) constitutes only a small proportion of total costs of the disease to individuals and society, therapeutic interventions have the potential for significant economic benefit. To take advantage of this potential, clinicians need to gain a global, long-term perspective on patient care. Economic evaluations of RA therapies are critically important in influencing decisions regarding the role of costly, but highly effective new therapies, particularly in settings where there are financial constraints on healthcare provisions. Such evaluations, therefore, need to be methodologically similar with valid results to enhance their value to clinicians and policy decision-makers. This requires the use of appropriate elements in the numerator (i.e. total number of dollars spent on healthcare as a result of the intervention) and the denominator (net health effectiveness) components of the cost-effectiveness equation. Other important design factors also need to be managed properly to ensure validity of the evaluation. In this regard, the guidelines proposed by the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Task Force represent a useful approach to help create common standards for economic evaluations in RA. Recently, the development of a number of decision analysis models in RA has helped predict the likely cost-effectiveness of new interventions such as the anti-tumour necrosis factor (TNF)-alpha agents, etanercept and infliximab, both of which have been found to be cost-effective relative to other disease-modifying anti-rheumatic drugs (DMARDs) using short-term efficacy endpoints. In comparisons of these two agents in patients with DMARD-resistant RA, etanercept has been shown to be more cost-effective than the combination of methotrexate and infliximab, administered in various dosages, over a period of 1 year using American College of Rheumatology (ACR) response rates as the primary efficacy measure. However, the criteria for determining clinical efficacy is paramount and other studies that use radiographic progression as a measure of clinical effectiveness show no difference between etanercept and infliximab in clinical efficacy. Important issues that need to be considered in developing economic models in RA include consideration of the connection between the prevention of radiographic progression and downstream economic consequences, and the need to employ lifetime models wherever possible because a long time period is necessary to determine the true cost-effectiveness of agents that modify radiographic progression of RA, such as etanercept, infliximab, and adalimumab. In doing so, it is hoped that such studies will provide optimal information to facilitate important decisions on resource allocation.

Antirheumatic Agents↗
PubMedDate not supplied

An economic model for nurse manpower planning in the Caribbean--Part 1: The issues.

Below is a noneconomist's view on economic issues impacting on nurse manpower development in the Commonwealth Caribbean. The issues however are of an international nature and are therefore pertinent to all those interested in nurse manpower development. The main objective is to present a model for economic analysis and planning.

Economics, Nursing↗
PubMed2004

Economic consequences of the adverse reactions related with antipsychotics: an economic model comparing tolerability of ziprasidone, olanzapine, risperidone, and haloperidol in Spain.

Frequency of adverse reactions (ARs) related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. The purpose of this study was to model the economic consequences of ARs related with ziprasidone, olanzapine, risperidone, and haloperidol in Spain, by means of a cost-effectiveness model developed using a Markov modeling approach. The model simulated treatment of a cohort of 1000 schizophrenics for 12 months, initiating treatment with one of four antipsychotic drugs; haloperidol, risperidone, olanzapine and ziprasidone. Conditional probabilities of developing any of four adverse events were calculated. Treatment was modified (decrease dose, switch medication) according to incidence of ARs and physician judgments, obtained from a local cross-sectional study and clinical trials previously published. The analysis was conducted in year 2002 from a third party payer perspective. Results are shown as annual cost per month with psychotic symptoms controlled and included univariate sensitivity analysis. The therapeutic strategy starting with ziprasidone showed the lower costs and the greater number of months with symptoms controlled in most scenarios evaluated versus the other options considered, although the differences were weak: 9.6, 9.3, 9.5 and 9.5 controlled months per patient in base scenario, with annual cost per patient per month with symptoms controlled of 1035 Euros, 1084 Euros, 1087 Euros and 1090 Euros for ziprasidone, haloperidol, risperidone and olanzapine, respectively. Results were robust to one-way sensitivity analysis. Despite the unlike drug prices of antipsychotics, a considerable economic impact due to adverse reactions was seen in our setting. These results should be taken into account by health decision makers and clinicians in the management of patients with schizophrenia.

Antipsychotic Agents↗
PubMed2006

Clinical effectiveness and cost-effectiveness of tests for the diagnosis and investigation of urinary tract infection in children: a systematic review and economic model.

OBJECTIVES: To determine the diagnostic accuracy of tests for detecting urinary tract infection (UTI) in children under 5 years of age and to evaluate the effectiveness of tests used to investigate further children with confirmed UTI. Also, to evaluate the effectiveness of following up children with UTI and the cost-effectiveness of diagnostic and imaging tests for the diagnosis and follow-up of UTI in children under 5. An additional objective was to develop a preliminary diagnostic algorithm for healthcare professionals. DATA SOURCES: Electronic databases were searched up to the end of 2002/early 2003. Consultation with experts in the field. REVIEW METHODS: A systematic review was undertaken using published guidelines and results were analysed according to test grouping: diagnosis of UTI and further investigation of UTI. The cost-effectiveness results from existing evaluations were synthesised. A separate cost-effectiveness model was developed using the best available evidence, in part derived from the results of the systematic review, to illustrate the potential cost-effectiveness of some alternative management strategies in a UK setting. The results of the systematic review were used to propose diagnostic algorithms for the diagnosis and further investigation of UTI in children. Economic analyses did not contribute directly to the development of these algorithms. RESULTS: The studies included in the review provided very little data on the accuracy of clinical investigations for the diagnosis of UTI, and criteria for clinical suspicion of UTI were not further defined. The majority of studies included in the review found that clean voided midstream urine (CVU) samples had similar accuracy to suprapubic aspiration (SPA) samples when cultured with the advantage of being a non-invasive collection method that can be used in the GP's surgery. Pad, nappy or bag specimens may be appropriate methods for obtaining a urine sample in non-toilet-trained children, although only limited data were available. Although the glucose test was reported to have the highest accuracy in terms of both ruling in and ruling out disease, only a limited number of studies of this test were included and these were conducted over 30 years ago. Dipstick tests are easy to perform in the GP's surgery, give an immediate result and are relatively cheap. The results of the systematic review showed that a dipstick for leucocyte esterase (LE) and nitrite, where both test results are interpreted in combination, was a good test both for ruling in (both positive) and ruling out (both negative) a UTI. A dipstick positive for either LE or nitrite and negative for the other provides inconclusive diagnostic information and further testing is therefore required in these patients. Microscopy is more time consuming and expensive to perform than a dipstick test, but potentially quicker and cheaper than culture. As with dipstick tests, a combination of microscopy for pyuria and bacteriuria can be used accurately to rule in and rule out a UTI. An indeterminate test result is again obtained if microscopy is positive for either pyuria or bacteriuria, and negative for the other. Confirmatory culture is required in these patients. In patients considered to have a UTI, further culture to determine antibiotic sensitivities may be an option to inform treatment decisions. Only one study satisfied the inclusion criteria of the economic review and the review highlighted a number of potential limitations of this study for NHS decision-making. A separate decision-analytic model was therefore developed to provide a more reliable estimate of the optimal strategy regarding the diagnosis and further investigation of children under 5 with suspected UTI from the perspective of the NHS. The economic model found that the optimal diagnostic strategy for children presenting with symptoms suggestive of UTI depends on a number of key factors. These included the relevant subgroup of children concerned, in terms of gender and age, and the health service's maximum willingness to pay for an additional quality-adjusted life-year. CONCLUSIONS: The results of the systematic review were used to derive an algorithm for the diagnosis of UTI in children under 5. This algorithm represents the conclusions of the review in terms of effective practice. There were insufficient data to propose an algorithm for the further investigation of UTI in children under 5. The quality assessment highlighted several areas that could be improved upon in future diagnostic accuracy studies.

Algorithms↗
PubMed2005

Economic modeling comparing trauma and general surgery reimbursement.

BACKGROUND: The viability of trauma care as a surgical subspecialty is continually challenged by economic pressures related to reimbursement and opportunity costs. METHODS: The literature was examined for articles focused on economic implications of a trauma focused surgical practice. Economic forecasting techniques were applied using a recalculating spreadsheet to examine charge and revenue generation comparing the effects of numerous variables affecting a trauma or general surgical service. RESULTS: Elective general surgery practices derive the majority of revenues from procedural services, whereas trauma practices derive the majority of revenues from evaluation and management. Only centers with high admission volume can expect trauma surgeons to cover salary and expenses, predictably in association with high opportunity costs. CONCLUSION: The differences in time, effort, and patient volume required for a trauma surgeon to generate revenues comparable to an elective practice are dramatic. The current system creates disincentives for surgeons to participate in trauma care.

Elective Surgical Procedures↗
PubMed2006

Economic models of antiretroviral therapy: searching for the optimal strategy.

The diffusion of protease inhibitors and non-nucleoside reverse transcriptase inhibitors in the US in 1996 and 1997 reduced the number of deaths attributable to HIV disease and changed the way we think about the illness. Today, HIV disease may be deemed a fairly expensive chronic condition rather than an intolerably expensive fatal illness. Although most studies have found that patients receiving new drug therapies are hospitalised less frequently than patients who received early drug therapies, it is unclear whether the diffusion of new drug therapies has increased or decreased the annual cost of care. However, it is evident that the diffusion of new drug therapies has increased the lifetime cost of care. Analysts rely on models to simulate the course and cost of HIV disease. This study reviews the evolution of these models, paying particular attention to how these models estimate the cost of care. The primary findings of this review are that the economic data used in these models are often too imprecise to accurately identify the cost of each disease stage and are almost always outdated. Moreover, it was found that estimates of drug costs in these models may not accurately reflect actual expenditures.

Anti-Retroviral Agents↗
PubMed2003

Systematic review of isolation policies in the hospital management of methicillin-resistant Staphylococcus aureus: a review of the literature with epidemiological and economic modelling.

OBJECTIVE: To review the evidence for the effectiveness of different isolation policies and screening practices in reducing the incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonisation and infection in hospital in-patients. To develop transmission models to study the effectiveness and cost-effectiveness of isolation policies in controlling MRSA. DATA SOURCES: MEDLINE, EMBASE, CINAHL, The Cochrane Library and SIGLE (1966-2000). Hand-searching key journals. No language restrictions. REVIEW METHODS: Key data were extracted from articles reporting MRSA-related outcomes and describing an isolation policy in a hospital with epidemic or endemic MRSA. No quality restrictions were imposed on studies using isolation wards (IW) or nurse cohorting (NC). Other studies were included if they were prospective or employed planned comparisons of retrospective data. Stochastic and deterministic models investigated long-term transmission dynamics, studying the effect of a fixed capacity IW, producing economic evaluations using local cost data. RESULTS: A total of 46 studies were accepted: 18 IWs, 9 NC, 19 other isolation policies. Most were interrupted time series, with few planned formal prospective studies. All but one reported multiple interventions. Consideration of potential confounders, measures to prevent bias, and appropriate statistical analysis were mostly lacking. No conclusions could be drawn in a third of studies. Most others provided evidence consistent with reduction of MRSA acquisition. Six long interrupted time series provided the strongest evidence. Four of these provided evidence that intensive control measures which included patient isolation were effective in controlling MRSA. In two others IW use failed to prevent endemic MRSA. There was no robust economic evaluation. Models showed that improving the detection rate or ensuring adequate isolation capacity reduced endemic levels, with substantial savings achievable. CONCLUSIONS: Major methodological weaknesses and inadequate reporting in published research mean that many plausible alternative explanations for reductions in MRSA acquisition associated with interventions cannot be excluded. No well-designed studies allow the role of isolation measures alone to be assessed. Nonetheless, there is evidence that concerted efforts that include isolation can reduce MRSA even when endemic. Little evidence was found to suggest that current isolation measures recommended in the UK are ineffective, and these should continue to be applied until further research establishes otherwise. The studies with the strongest evidence, together with the results of the modelling, provide testable hypotheses for future research. Guidelines to facilitate design of future research are produced.

Cost-Benefit Analysis↗
PubMedDate not supplied

Towards an economic model of the Dutch health care sector.

This paper describes the construction of a model of the Dutch health care sector. It discusses the behaviour of patients, general practitioners, medical specialists and hospital managers. It also analyses the various ways the actors interact, such as general practitioners supplying the services demanded by patients, specialists dispatching referrals made by general practitioners or hospital managers boosting output to match an increasing amount of specialist services. Numerical simulations illustrate the various mechanisms in the model.

Computer Simulation↗
PubMed2006

A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling.

OBJECTIVES: To assess the relative effectiveness, patient acceptability, costs and cost-effectiveness of four strategies for the prevention of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastrointestinal (GI) toxicity: (1) Cox-1 NSAIDs plus histamine-2 receptor antagonist (H2RA), (2) Cox-1 NSAIDs plus proton pump inhibitors (PPIs), (3) Cox-1 NSAIDs plus misoprostol, and (4) Cox-2 NSAIDs (later expanded to 4a Cox-2 coxibNSAIDs and 4b Cox-2 preferential NSAIDs). DATA SOURCES: Electronic databases up to May 2002. REVIEW METHODS: Relevant studies were selected, assessed and analysed. Pooled relative risk ratios (RR) from the systematic review were combined with up-to-date UK resource use and unit costs data in an incremental economic analysis. A probabilistic decision-analytic model was designed and populated with data to carry out incremental economic analysis. Incremental cost-effectiveness ratios (ICERs) were generated for the outcome measure, endoscopic ulcer or serious GI event averted, against total cost, and non-parametric bootstrapping was used to simulate variance of these ICERs. RESULTS: Of 118 selected trials, including 125 relevant comparisons (which included 76,322 participants) only 138 deaths and 248 serious GI events were reported. Seven comparisons were judged to be at low risk of bias. Comparing the gastroprotective strategies against placebo, there was no evidence of effectiveness of H2RAs against any primary outcomes (few events reported), PPIs may reduce the risk of symptomatic ulcers [RR 0.09, 95% confidence interval (CI) 0.02 to 0.47], misoprostol reduces the risk of serious GI complications (RR 0.57, 95% CI 0.36 to 0.91) and symptomatic ulcers (RR 0.36, 95% CI 0.20 to 0.67), Cox-2 'preferentials' reduce the risk of symptomatic ulcers (RR 0.41, 95% CI 0.26 to 0.65) and Cox-2 'coxibs' reduce the risk of symptomatic ulcers (RR 0.49, 95% CI 0.38 to 0.62) and possibly serious GI events (RR 0.55, 95% CI 0.38 to 0.80). All strategies except Cox-2 'preferentials' reduce the risk of endoscopic ulcers. There were only 12 direct comparisons between gastroprotective strategies. All they suggest is that Cox-2 preferentials are better than misoprostol for preventing GI complications. Indirect comparisons suggested that PPIs may prevent symptomatic ulcers better than Cox-2 coxibs, but this is very weak evidence. For prevention of endoscopic ulcers PPIs and misoprostol appear more successful than H2RAs and misoprostol is better than Cox-2 preferentials. There were no UK head-to-head published economic analyses with regard to the main gastroprotective strategies. There were generally insufficient data with regards to cardiac or renal outcomes, serious GI outcomes or life-years gained to populate the mode. Mean (2.5th and 97.5th percentile) costs per endoscopic ulcer averted compared with Cox-1 NSAIDs alone were as follows: Cox-1 plus H2RAs, -186 pounds (-555 to 804); Cox-1 plus PPIs, 454 pounds (251 to 877); Cox-1 plus misoprostol, 54 pounds (-112 to 238); Cox-2 selective NSAIDs, 263 pounds (-570 to 1280), or Cox-2 specific NSAIDs, 301 pounds (189 to 418). With regard to the prevention of endoscopic ulcers, Cox-1 NSAID plus H2RA is a dominant option. Cost-effectiveness acceptability analysis showed a 95% probability that this combination was less costly and more effective. Cost-effectiveness acceptability frontiers showed that if the decision-maker is willing to pay up to 750 pounds to avoid an endoscopic ulcer, then Cox-1 plus H2RA is the optimal strategy. If the decision-maker is willing to pay over 750 pounds, the optimal strategy is NSAID plus misoprostol. Between 1900 pounds and 3750 pounds, Cox-2 selective inhibitors are optimal, and over 3750 pounds, Cox-2 specific inhibitors become optimal. NSAID plus PPI is never the optimal strategy. Sensitivity and subgroup analyses suggest that Cox-1 NSAID plus H2RA and Cox-1 NSAID plus misoprostol become more cost-effective in the older age group. Some conclusions were associated with high levels of uncertainty. CONCLUSIONS: Although there is a very large body of evidence comparing Cox-2 NSAIDs with Cox-1 NSAIDs, this is not matched by studies of the other types of gastroprotectors or by studies directly comparing active gastroprotective strategies. This lack of direct comparisons led to the use of indirect comparisons to help understand the relative efficacy of these strategies. Indirect evidence in itself is weak and was also hampered by lack of evidence in the underlying studies (where the gastroprotectors were compared with placebo). Economic modelling suggests that Cox-1 NSAID plus H2RA or Cox-1 NSAID plus PPI are the most cost-effective strategies for avoiding endoscopic ulcers in patients requiring long-term NSAID therapy. All strategies other than Cox-2 selective inhibitors reduce the rate of endoscopic ulcer compared with Cox-1 alone. The economic analysis suggests that there may be a case for prescribing H2RAs in all patients requiring NSAIDs. Misoprostol is more effective, but is associated with a greater cost and GI side-effects which may be unacceptable for patients. However, when assessing serious GI events, the economic analysis is sufficiently weakened by the data available as to render clear practice recommendations impossible. Further large, independent RCTs directly comparing various gastroprotective strategies are needed. These should report items such as major outcomes, primary data, adverse events, assessment of practice and patient preference.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

An economic model of 2-hour post-dose ciclosporin monitoring in renal transplantation.

BACKGROUND: Monitoring of microemulsion ciclosporin (cyclosporine; Neoral) by 2-hour post-dose drug concentrations (C2) is an accurate measure of ciclosporin absorption efficiency and exposure, and appears superior to trough (C0) monitoring for prediction of rejection risk. A predictive decision model was used to determine if this approach also reduces total treatment costs in the first 12 months after renal transplantation. METHODS: Parameter estimates for key clinical events were derived from the literature and from prospective pharmacokinetic studies comprising 234 adult HLA-non-identical renal graft recipients at seven Canadian centres. Patients were treated with microemulsion ciclosporin (Neoral), corticosteroids and azathioprine or mycophenolate mofetil. Using the perspective of the Canadian healthcare provider, total treatment costs for the C2 versus the C0 strategy were modelled over 12 months, and then remodelled using conservative estimates to extend the timeframe to 5 years. Health resources were valued in 1999 Canadian dollars. RESULTS: The incidence of acute rejection was estimated to be 25% at 1 year in patients monitored by C0 and 18% in those monitored by C2. Patient survival was considered to be independent of monitoring strategy, and graft loss was predicted to be 1.4% lower in the C2 group. The studies suggested no important differences in comorbidity and the costs of C0 and C2 monitoring and ambulatory-based adverse events were held equivalent. Using these inputs, the average cost per patient for the first year post-transplant was Can dollars 46,857 for C0 monitoring and Can dollars 45,306 for C2 monitoring, rising to Can dollars 146,879 and Can dollars 142,569 after 5 years. The predicted cost for initial hospitalisation was Can dollars 11,280 for C0 and Can dollars 10,806 for C2 monitoring. The cost of maintenance immunosuppressive drug use, graft loss and dialysis was Can dollars 19,098 in the C0 group and Can dollars 18,612 in the C2 group, while acute rejection treatment costs were Can dollars 2169 and Can dollars 1577, respectively. An additional Can dollars 14,310 was consumed by other events, including repeat hospitalisation, for each group. Sensitivity analysis indicated that the most influential parameters affecting savings due to C2 monitoring were a reduction in the duration of initial and follow-up hospitalisations and reduced risks of acute rejection and subsequent graft loss. CONCLUSIONS: Compared with traditional trough concentration monitoring, ciclosporin monitoring at 2 hours post-dose produced a predicted saving of Can dollars 1551 during the first year after renal transplant. Although modelling assumptions become more restrictive over time, this projection allows a preliminary assessment of the long-term economic impact of the routine use of C2 monitoring.

Adult↗
PubMed1999

The cost-effectiveness of isotretinoin in the treatment of acne. Part 3. A cost-minimisation pharmaco-economic model.

OBJECTIVES: The cost-effectiveness of systemic isotretinoin therapy in the treatment of moderate to severe acne was assessed in a comparative cost-minimisation analysis. Systemic isotretinoin at the recommended daily dose of 1 mg/kg (cumulative dose of 120 mg/kg) was compared with: (i) oral antibiotics taken as chronic medication; (ii) a combination of chronic oral antibiotics and anti-androgen therapy; and (iii) isotretinoin prescribed only after two failed courses of oral antibiotics, as per South African guidelines. The perspective taken was that of the funder of health care, and the resources used were funder charges as a proxy for costs. METHODOLOGY: Statistical and epidemiological data as well as relevant costs from the previously reported meta-analysis and profiling study for acne therapy were used as the clinical basis for the construction of a cost-minimisation model. Additional costs were sourced from published pharmaceutical retail prices and professional rates. The South African treatment guidelines were used to define the frequencies associated with physician visits and pathology testing. Standard statistical methods were applied, as appropriate. From the above, a modified Markov process was used to model the costs associated with the four comparator treatment regimens over a period of 120 months. Suitable clinical and economic endpoints were defined so that comparison could be made between regimens. RESULTS: Assuming a relapse rate of 21.45%, it was found that isotretinoin therapy compares favourably with the other regimens. After 50 and 35 months, systemic isotretinoin cumulative costs were less than those incurred in oral antibiotic and oral antibiotic/anti-androgen therapy, respectively. For the stepped therapy of oral antibiotics followed by systemic isotretinoin, these break-even periods were 56 and 39 months, respectively. The cost per successfully treated patient receiving isotretinoin was R8941. This compares well with the cost for those patients receiving chronic oral antibiotics, which after 5 years amounted to R10 428 per patient. Sensitivity analyses proved these findings to be robust to variations in the isotretinoin relapse rate, and the cost of oral antibiotic therapy and the concomitant use of topical therapies. CONCLUSION: From the cost-minimisation model it is clear that where systemic isotretinoin is clinically indicated, the sooner such therapy is initiated the more cost-effective the outcome will be. If isotretinoin is prescribed on diagnosis of moderate to severe acne, then the cost of treatment is significantly reduced in the long term when compared with standard chronic oral antibiotic therapy.

Acne Vulgaris↗
PubMed2005

A modeled economic analysis of a digital tele-ophthalmology system as used by three federal health care agencies for detecting proliferative diabetic retinopathy.

The objective of this study was to compare, using a 12-month time frame, the cost-effectiveness of a non-mydriatic digital tele-ophthalmology system (Joslin Vision Network) versus traditional clinic-based ophthalmoscopy examinations with pupil dilation to detect proliferative diabetic retinopathy and its consequences. Decision analysis techniques, including Monte Carlo simulation, were used to model the use of the Joslin Vision Network versus conventional clinic-based ophthalmoscopy among the entire diabetic populations served by the Indian Health Service, the Department of Veterans Affairs, and the active duty Department of Defense. The economic perspective analyzed was that of each federal agency. Data sources for costs and outcomes included the published literature, epidemiologic data, administrative data, market prices, and expert opinion. Outcome measures included the number of true positive cases of proliferative diabetic retinopathy detected, the number of patients treated with panretinal laser photocoagulation, and the number of cases of severe vision loss averted. In the base-case analyses, the Joslin Vision Network was the dominant strategy in all but two of the nine modeled scenarios, meaning that it was both less costly and more effective. In the active duty Department of Defense population, the Joslin Vision Network would be more effective but cost an extra 1,618 dollars per additional patient treated with panretinal laser photo-coagulation and an additional 13,748 dollars per severe vision loss event averted. Based on our economic model, the Joslin Vision Network has the potential to be more effective than clinic-based ophthalmoscopy for detecting proliferative diabetic retinopathy and averting cases of severe vision loss, and may do so at lower cost.

Cost-Benefit Analysis↗
PubMed2000

Health economic models: a question of balance--summary of an open discussion on the pharmacoeconomic evaluation of non-steroidal anti-inflammatory drugs.

Pharmacoeconomics and pharmacoeconomic models are increasingly being used to guide health care decisions. In designing and using these models, an appropriate balance must be struck between scientific rigour and model transparency. It is therefore important to consider carefully how the various model components, such as model perspective, internal and external validity, and choice of comparators and outcomes, should be integrated into the model. These factors are discussed in relation to the pharmacoeconomic evaluation of non-steroidal anti-inflammatory drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents.

OBJECTIVES: To assess the clinical and cost-effectiveness of oral methylphenidate hydrochloride (MPH), dexamfetaminesulphate (DEX) and atomoxetine (ATX) in children and adolescents (<18 years of age) diagnosed with attention deficit hyperactivity disorder (ADHD) (including hyperkinetic disorder). DATA SOURCES: Electronic databases covering 1999--July 2004 for MPH, 1997--July 2004 for DEX and 1981--July 2004 for ATX. REVIEW METHODS: Selected studies were assessed using modified criteria based on CRD Report No. 4. Clinical effectiveness data were reported separately for each drug and by the type of comparison. Data for MPH were also analysed separately based on whether it was administered as an immediate release (IR) or extended release (ER) formulation. For all drugs, the data were examined by dose. Data for the core outcomes of hyperactivity (using any scale), Clinical Global Impression [as a proxy of quality of life (QoL)] and adverse events were reported. For crossover studies, the mean and standard deviation (SD) for each outcome were data extracted for end of trial data (i.e. baseline data were not considered). For parallel studies, change scores were reported where given, otherwise means and SDs were presented for end of trial data. In addition, mean differences with 95% confidence intervals were calculated for each study. For adverse events, self-ratings were reported when used, otherwise, parent reports were utilised. Percentages of participants reporting adverse events were used to calculate numbers of events in each treatment arm. All the clinical effectiveness data and economic evaluations (including accompanying models) included in the company submissions were assessed. A new model was developed to assess the cost-effectiveness of the alternative treatments in terms of cost per quality-adjusted life-year. To achieve this, a mixed treatment comparison model was used to estimate the differential mean response rates. Monte Carlo simulation was used to reflect uncertainty in the cost-effectiveness results. RESULTS: In total, 65 papers met the inclusion criteria. The results suggest that MPH and DEX are effective at reducing hyperactivity and improving QoL (as determined by Clinical Global Impression) in children, although the reliability of the MPH study results is not known and there were only a small number of DEX studies. There was consistent evidence that ATX was superior to placebo for hyperactivity and Clinical Global Impression. Studies on ATX more often reported the study methodology well, and the results were likely to be reliable. Very few studies made direct head-to-head comparisons between the drugs or examined a non-drug intervention in combination with MPH, DEX or ATX. Adequate and informative data regarding the potential adverse effects of the drugs were also lacking. The results of the economic evaluation clearly identified an optimal treatment strategy of DEX first-line, followed by IR-MPH for treatment failures, followed by ATX for repeat treatment failures. Where DEX is unsuitable as a first-line therapy, the optimal strategy is IR-MPH first-line, followed by DEX and then ATX. For patients contraindicated to stimulants, ATX is preferred to no treatment. For patients in whom a midday dose of medication is unworkable, ER-MPH is preferred to ATX, and ER-MPH12 appears more cost-effective than ER-MPH8. As identified in the clinical effectiveness review, the reporting of studies was poor, therefore this should be borne in mind when interpreting the model results. CONCLUSIONS: Drug therapy seems to be superior to no drug therapy, no significant differences between the various drugs in terms of efficacy or side effects were found, mainly owing to lack of evidence, and the additional benefits from behavioural therapy (in combination with drug therapy) are uncertain. Given the lack of evidence for any differences in effectiveness between the drugs, the economic model tended to be driven by drug costs, which differed considerably. Future trials examining MPH, DEX and ATX should include the assessment of tolerability and safety as a priority. Longer term follow-up of individuals participating in trials could further inform policy makers and health professionals. Such data could potentially distinguish between these drugs in a clinically useful way. In addition, research examining whether somatic complaints are actually related to drug treatment or to the disorder itself would be informative.

Adolescent↗
PubMed2001

An economic model for determining the costs and consequences of using various treatment alternatives for the management of arthritis in Canada.

OBJECTIVE: To construct a decision analytical model to compare the costs and clinical consequences of treating patients with celecoxib or various nonsteroidal anti-inflammatory drug (NSAID)/gastrointestinal (GI) co-therapy regimens for the management of osteoarthritis and rheumatoid arthritis. The model quantified the number of patients expected to experience any GI complication commonly associated with NSAID therapy. DESIGN: Resource use for the treatment of each GI complication in the model was estimated after consulting Canadian experts. Standard unit costs from Ontario were applied to resources to calculate the cost of each complication. MAIN OUTCOME MEASURES AND RESULTS: The model revealed that the NSAID-alone regimen was associated with the lowest cost [$262 Canadian dollars ($Can) per patient per 6 months] followed by the celecoxib regimen ($Can273), diclofenac/misoprostol ($Can365), NSAID + histamine H2 receptor antagonist ($Can413), NSAID + misoprostol ($Can421), and NSAID + proton pump inhibitor ($Can731). A break-even analysis showed that up to 80% of the study cohort could be treated with celecoxib instead of the NSAID-alone regimen without increasing the health system's overall budget. Celecoxib was associated with the fewest GI-related deaths, hospitalised events; symptomatic ulcers, and cases of anaemia. The celecoxib regimen was also associated with the fewest cases of upper GI distress. Sensitivity analyses revealed that the model was most sensitive to the distribution of GI risk in the population and to the ingredient costs of the treatment alternatives. CONCLUSIONS: This model indicates that the use of celecoxib could lead to the avoidance of a significant number of NSAID-attributable GI adverse events, and the incremental cost of using celecoxib for arthritis patients > or = 65 years of age in place of current treatment alternatives would not impose an excessive incremental impact on a Canadian provincial healthcare budget.

Aged↗