Claude Le Pen

Economic Evaluation of Pharmaceuticals

SummaryIn recent years there has been a large increase in the number of economic evaluations of pharmaceuticals. Many of these studies have been commissioned by individual pharmaceutical companies, in support of new or existing products. In 2 countries, Australia and Canada (in the province of Ontario), draft guidelines issued by the government have outlined the requirements for economic evaluations to be submitted in support of requests for reimbursement (government subsidy) of particular products. One consequence of the guidelines is that they clarify what is required, and in specifying the procedure for submission of dossiers, identify a clear audience for the economic evaluation.In contrast, the situation in Europe is diverse. A wide range of healthcare systems exist, including national health services and more liberal systems, involving a wide range of insurers and providers. European countries also differ widely in their approach to the pricing and reimbursement of pharmaceuticals. Because of this diversity, the nature, conduct and impact of economic evaluation in Europe is not clear. It is therefore difficult for pharmaceutical companies to develop appropriate strategies for economic evaluation and for analysts to decide on appropriate study methodology.This article reviews the nature of any official guidance or requirements for economic evaluation, the potential for use of economic evaluation, the range of studies carried out and the identifiable impacts. There is currently no official guidance in any country, although some countries are considering issuing guidelines. In some countries there is official encouragement to pharmaceutical companies to undertake studies, and where economic data have been presented they have been considered by the relevant committees.The potential uses of economic evaluation vary widely from country to country. These can be classified in terms of a potential role in undertaking national price negotiations, deciding on reimbursement status or copayment level, deciding on inclusion in local formularies or in treatment guidelines, or in improving prescribing decisions.Approximately 80 economic evaluations of pharmaceutical products have been conducted to date in Europe, covering a wide range of clinical areas. There are relatively few examples of identifiable effects of such studies. In part this is because it is often difficult to assess the part played by various items of data. Nevertheless, the overriding conclusion is that economic evaluation of medicines is likely to be more relevant in Europe in the future. The problem for the pharmaceutical industry is in determining when and how.

Impact of irritable bowel syndrome (IBS) on health-related quality of life (HRQOL)

AIMS To assess the impact of irritable bowel syndrome (IBS) on patient-reported health-related quality of life (HRQOL). METHODS Two HRQOL instruments were administered by telephone interviews to a sample of 253 IBS French patients recruited from the general population. IBS was diagnosed according to the Manning, Rome I and Rome II criteria. Patients with organic diseases were excluded from the study. A generic instrument, the Short Form 36 (SF-36), and an IBS disease-specific instrument, the IBSQOL, were used. RESULTS Patients with IBS had statistically significant (P<0.05) lower scores for all SF-36 QOL domains compared with the general French population. Women (N=192) reported significantly (P<0.05) poorer HRQOL on both the SF-36 and the IBSQOL scores than men (N=61) for all domains except energy on the SF36 and the sleep on the IBSQOL. HRQOL deteriorated with time since onset of IBS symptoms for some domains such as diet. For both instruments, a positive correlation was observed between low scores and intensity of pain and discomfort. IBS patients with a predominance of diarrhea (N=72) exhibited significantly greater impairment of HRQOL in the emotional domain than IBS persons with constipation predominance (N=65) (P<or=0.05). CONCLUSION IBS has a significant impact on HRQOL of patients. In addition, specific characteristics such as gender, symptom severity and time since onset of symptoms are predictive of more impaired health-related quality of life.

Cost effectiveness of rituximab maintenance therapy in follicular lymphoma: long-term economic evaluation.

Background: Rituximab maintenance therapy was shown to significantly extend overall survival (OS) and progression-free survival (PFS) in relapsed/refractory follicular lymphoma (FL) in the pivotal EORTC 20981 trial.Objective: To assess the long-term costs and cost effectiveness of rituximab maintenance therapy after induction therapy versus current standard practice (observation) from the French National Health Service perspective.Methods: A lifetime transition model was developed comparing rituximab maintenance with observation. PFS and OS were obtained from the EORTC 20981 trial with a median follow-up of 28 months and extrapolated from 2-year Kaplan-Meier curves using a Weibull distribution. PFS and OS benefits of rituximab were conservatively assumed to last only 5 years. Utility data were obtained from a multicentre observational study using the EQ-5D questionnaire. Direct medical costs were obtained from French official sources. All costs are reported in €, year 2006 values.Results: The EORTC 20981 study demonstrated that rituximab maintenance was effective in the management of relapsed/refractory FL. The model results showed that life expectancy and QALYs were increased by 22% and 28%, respectively, in patients treated with rituximab. The incremental cost-effectiveness ratios (ICERs) were €7612 per life-year gained and €8729 per QALY gained. In a oneway sensitivity analysis,most of the ICERs fell within the range of €7000–12 000.Conclusion: The results tend to show that rituximab maintenance therapy may be a cost-effective strategy in the management of relapsed/refractory FL in France, with ICERs below those observed for other therapies in the oncology field. The cost of rituximab was partly offset by the lower cost of relapse due to a longer time in the disease-free health state for patients in the rituximab arm.

Effectiveness of a lumbar belt in subacute low back pain: an open, multicentric, and randomized clinical study.

Study Design. Multicentric, randomized, and controlled study of clinical evaluation of medical device in subacute low back pain. Objective. To evaluate the effects of an elastic lumbar belt on functional capacity, pain intensity in low back pain treatment, and the benefice on medical cost. Summary of Background Data. There is limited evidence of efficiency of lumbar supports for treatment of low back pain. There is also a lack of the methodology in the studies reported on the efficiency of this device. Methods. This study is randomized, multicentric, and controlled with 2 groups: a patient group treated with a lumbar belt (BWG) and a control group (CG). The main criteria of clinical evaluation were the physical restoration assessed with the EIFEL scale, the pain assessed by a visual analogic scale, the main economical criteria was the overall cost of associated medical treatments. Results. One hundred ninety-seven patients have participated. The results show a higher decrease in EIFEL score in BWG than CG between days 0 and 90 (7.6 ± 4.4 vs. de 6.1 ± 4.7;P = 0.023). Respectively significant reduction in visual analogic scale was also noticed (41.5 ± 21.4 vs. 32.0 ± 20; P = 0.002). Pharmacologic consumption decreased at D90 (the proportion of patients who did not take any medication in BWG is 60.8% vs. 40% in CG;P = 0.029). Conclusion. Lumbar belt wearing is consequent in subacute low back pain to improve significantly the functional status, the pain level, and the pharmacologic consumption. This study may be useful to underline the interest of lumbar support as a complementary and nonpharmacologic treatment beside the classic medication use in low back pain treatment.

Cost-Minimisation Study of Dorzolamide versus Brinzolamide in the Treatment of Ocular Hypertension and Primary Open-Angle Glaucoma In Four European Countries

AbstractObjective: 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 β-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.

Public health and budget impact of probiotics on common respiratory tract infections: a modelling study.

Objectives Two recent meta-analyses by the York Health Economics Consortium (YHEC) and Cochrane demonstrated probiotic efficacy in reducing the duration and number of common respiratory tract infections (CRTI) and associated antibiotic prescriptions. A health-economic analysis was undertaken to estimate the public health and budget consequences of a generalized probiotic consumption in France. Methods A virtual age- and gender-standardized population was generated using a Markov microsimulation model. CRTI risk factors incorporated into this model were age, active/passive smoking and living in a community setting. Incidence rates and resource utilization were based on the 2011-2012 flu season and retrieved from the French GPs Sentinelles network. Results of both meta-analyses were independently applied to the French population to estimate CRTI events, assuming a generalized probiotic use compared to no probiotics during winter months: -0.77 days/CRTI episode (YHEC scenario) or odds-ratio 0.58 for ≥1 CRTI episode (Cochrane scenario) with vs. without probiotics. Economic perspectives were National Health System (NHS), society, family. Outcomes included cost savings related to the reduced numbers of CRTI episodes, days of illness, number of antibiotic courses, sick leave days, medical and indirect costs. Results For France, generalized probiotic use would save 2.4 million CRTI-days, 291,000 antibiotic courses and 581,000 sick leave days, based on YHEC data. Applying the Cochrane data, reductions were 6.6 million CRTI days, 473,000 antibiotic courses and 1.5 million sick days. From the NHS perspective, probiotics’ economic impact was about €14.6 million saved according to YHEC and €37.7 million according to Cochrane. Higher savings were observed in children, active smokers and people with more frequent human contacts. Conclusions Public health and budget impact of probiotics are substantial, whether they reduce CRTI episodes frequency or duration. Noteworthy, the 2011-12 winter CRTI incidence was low and this analysis focused on the fraction of CRTI patients consulting a practitioner.

Economic Evaluation of Nimesulide versus Diclofenac in the Treatment of Osteoarthritis in France, Italy and Spain

ObjectiveTo assess and compare the incremental costs of the 15-day treatment of osteoarthritis (OA) with nimesulide vs that with diclofenac in France, Italy and Spain.DesignA cost-minimisation analysis was performed through a decision tree, assuming the National Health System perspective. A meta-analysis was performed to assess the incidence of gastrointestinal adverse events (GIAEs) in patients with OA treated with nimesulide or diclofenac.ResultsThree studies were included in the meta-analysis, which included a sample size of 484 patients in total. The incidence of GIAEs is higher in patients treated with diclofenac than in those treated with nimesulide. Nimesulide is cost-saving in all three countries: treatment costs are reduced by Euro dollars (EUR) 1.5 per case in France, EUR2 in Italy and EUR3.6 in Spain. Final results are not sensitive to variation of incidence rates of gastric and intestinal events and to changes in the resource consumption: nimesulide always remains cost-saving.ConclusionsThis is the first economic analysis carried out in three different countries on original epidemiological data comparing nimesulide and diclofenac directly. Projecting our results to the estimated OA prevalence in the entire population of the three countries, the expected savings to the NHS would vary from a minimum of EUR17 500 000 in France to a maximum of EUR30 000 000 in Spain. It can be stated that these findings can provide support for clinicians and policy-makers for the adoption of this cost-saving treatment strategy in patients with OA.

Drug Pricing and Reimbursement in France

SummaryThe pharmaceutical market in France is characterised by low prices and high sales volumes. Despite these advantageous market conditions, the French pharmaceutical industry has in general been an underperformer in the global context. Acknowledgement of the contributory role made by state regulation of drug expenditures in creating this situation has resulted in a number of attempts to correct problems within the market. At best, these have achieved only temporary improvements.Since 1993, however, a new drug policy, which emphasises voluntary moderation by physicians of their own prescribing activities rather than the use of budgetary means to cut expenditures, has been in operation in France. This ‘medicalised strategy’ involves 2 main instruments, viz., a list of guidelines for clinical practice (Références Médicales Opposables) and a set of ‘industrial conventions’ (agreed between each drug company and the government) for determining drug prices. While it is too early at this stage to determine whether these new approaches will be beneficial in the long term, some changes in drug prescribing have already been observed, and it is clear that the new policy has also encouraged more healthy relationships between policymakers, the medical profession, and the pharmaceutical industry in France.

Cost-effectiveness and cost-utility analysis of travoprost versus latanoprost and timolol in the treatment of advanced glaucoma in five European countries: Austria, France, Germany, The Netherlands and the United Kingdom

Summary This study compares the cost and effectiveness of timolol, latanoprost and travoprost in Austria, France, Germany, The Netherlands and the UK in patients with advanced glaucoma. A Markov model was constructed to assess the incremental cost-effectiveness ratio. Health states were stable and progressive patients. Transition probabilities were derived from daily intraocular pressure means and variances using two discriminant functions. Costs refer to a specific survey in France, to the General Practice Research Database in the UK, and to expert interviews in the other countries. Utilities were derived from a French survey and from the literature. The time horizon was 5 years (Stewart survey). A payer perspective was adopted. Time without a visual field defect (VFD) was 3.417 years with travoprost, 3.285 years with latanoprost and 2.812 years with timolol. Travoprost economically dominated latanoprost in Austria, Germany, the UK and The Netherlands. The incremental cost-utility ratio of travoprost against both latanoprost and timolol was always less than 50,000 Euro per quality-adjusted life-year. Travoprost is a cost-effective alternative to latanoprost and timolol. A larger prospective study should confirm these findings.

Effect of HAART on Health Status and Hospital Costs of Severe HIV-Infected Patients: A Modeling Approach

Abstract Purpose: The purpose of this study was to assess the impact of highly active antiretroviral therapy (HAART) on health status and hospital costs in severe HIV-infected patients who were followed in a French hospital. Method: The first 500 patients who received HAART, with CD4 + cell count below 250/mm3, were considered. Evolution of the distribution of patients among different health states, including death, was modeled through a continuous time Markov model. Hospital financial charges and antiretroviral treatment costs were computed. Health states defined by both CD4 counts and viral load were used to show clinical changes in the patient population over a 14-month period after HAART initiation. The economic impact of HAART initiation was assessed using a simplified model based on CD4 counts only over two 14-month periods, before and after initiation. Results: Between day 0 and month 14, the proportion of patients in the least severe state (CD4 + >100/mm3 and viral load<500 copies/mL) increased from 1% to 50%, and the proportion with more than 100 CD4 + cells/mm3 increased from 17% to 80%. Antiretroviral treatments amounted to Fr 2,141 per patient-month before HAART initiation and to Fr 3,093 after. Conversely, hospital charges fell from Fr 5,138 per patient-month to Fr 3,136. Conclusion: Our model gives a representation of the effect of HAART on (1) the improvement of patients’ health status, (2) the increase of treatment costs, and (3) the reduction of hospital financial charge. Important savings in hospital charges can compensate for the extra cost associated with the initiation of HAART.