Psychometric properties of a questionnaire (HEMO-FISS-QoL) to evaluate the burden associated with haemorrhoidal disease and anal fissures.

AIM: Current questionnaires designed to evaluate the burden of haemorrhoidal disease ignore symptoms such as bleeding, pain and itching. A specific questionnaire is needed to evaluate the global impact of anal disorders on patients' daily lives. METHOD: We developed a questionnaire (HEMO-FISS-QoL) to assess the symptom burden of anal disorders and administered it to 256 patients (mean age 46.2 years; men 60.4%) with haemorrhoidal disease (67.2%), anal fissure (29.3%) or both (3.5%). Psychometric properties were evaluated by testing the acceptability, construct validity and reliability of the questionnaire. Principal components and multi-trait analyses were used to identify dimensions and to assess construct validity. Backward Cronbach alpha curves and a graded response model were used to reduce the number of items and modalities. External validity was evaluated against SF-12 and the Psychological Global Well-Being Index (PGWBI) using Spearman's correlation coefficient. RESULTS: Principal component analysis defined four dimensions: physical disorders, psychology, defaecation and sexuality. The number of questions was reduced from 38 to 23. The HEMO-FISS-QoL scores correlated well with those of the SF-12 and PGWBI (P < 0.001). Cronbach's coefficients (all > 0.7) reflected good internal reliability of the different dimensions. The total score increased with the severity of the anal disorders and with their consequences (days off work and personal spending related to the disease). CONCLUSION: The HEMO-FISS-QoL questionnaire reliably evaluates the global impact of haemorrhoids and anal fissures on patients' daily lives. This simple tool may prove useful for treatment evaluation in clinical trials and daily practice.

Lifetime costs and effectiveness of ReSTOR compared with a monofocal IOL and Array-SA40 in the Netherlands.

PURPOSE: To estimate the lifetime cost consequences for society and the National Health Service (NHS) of bilateral monofocal (SI40NB) or multifocal (ReSTOR or Array-SA40) intraocular lense (IOL) implantation after cataract surgery. SETTING: Public hospital in the Netherlands. METHODS: A Markov model simulated three cohorts of patients followed 69 until 100 years of age, or death. Spectacle independence rates for each IOL were adjusted to the results of a randomized clinical trial that compared monofocal and multifocal Array-SA40 IOL implants, together with a prospective cohort of patients implanted with ReSTOR. Adjustment was performed using the propensity score method in a multivariate analysis. Resource consumption was estimated from a dedicated Dutch survey. Dutch unit costs were applied to spectacles, cataract surgery, IOLs, visits to ophthalmologists, optometrists, transport, and spectacle cleaning materials. Cost discounted at 4% and undiscounted economic results were calculated. RESULTS: Spectacle independence rates were 86.0% for ReSTOR, 8.7% for monofocal IOLs, and 8.5% for Array-SA40. Patients lived without needing spectacles for 12.9 years after ReSTOR, for 1.4 years after monofocal IOLs, and 1.3 years after Array-SA40. ReSTOR patients bought 6.4 fewer pairs of spectacles than monofocal patients. Lifetime discounted cost consequences for the society were ReSTOR euro3969, monofocal IOLs euro4123, and Array-SA40 euro5326. Corresponding costs for the NHS were euro2415, euro2555, and euro2556, respectively. CONCLUSIONS: ReSTOR IOLs provided higher levels of spectacle independence than monofocal SI40NB or multifocal Array-SA40 IOLs resulting in savings, compared to a monofocal, over the period modelled of euro315 for society and euro140 for the NHS.

Modelling lifetime cost consequences of toric compared with standard IOLs in cataract surgery of astigmatic patients in four European countries.

OBJECTIVE: To compare the lifetime costs of freeing astigmatic patients from spectacles after bilateral cataract surgery implanting toric intraocular lenses (IOLs: i.e., Acrysof Toric) versus monofocal IOLs, in France, Italy, Germany and Spain. METHODS: A Markov model followed patient cohorts from cataract surgery until death. Prevalence rates of patients not needing spectacles and the types of spectacles prescribed for those requiring them were obtained from clinical trials and national surveys. The economic perspective was societal. Mortality rates were incorporated into the model. Discount rates were applied. A sensitivity analysis was performed on non-discounted costs. RESULTS: Fewer patients with toric IOLs needed spectacles for distance vision than patients with monofocal IOLs. With monofocal IOLs more than 66% of patients needed complex spectacles compared to less than 25% implanted with toric IOLs. In France and Italy, toric IOLs reduced overall costs relative to otherwise high spectacle costs after cataract surgery. Savings were 897.0 euros (France), 822.5 euros (Germany), 895.8 euros (Italy) and 391.6 euros (Spain), without discounting. On applying a 3% discount rate the costs became 691.7 euros, 646.4 euros, 693.9 euros and 308.2 euros, respectively. CONCLUSIONS: Bilateral toric IOL implants in astigmatic patients decreased spectacle dependence for distance vision and the need for complex spectacles. The economic consequences for patients depended on the national spectacle costs usually incurred after cataract surgery.

Modelling lifetime cost consequences of ReSTOR for presbyopia in four European countries.

AIMS: To compare the lifetime cost consequences, in France, Italy, Germany and Spain, of liberating presbyopic patients from spectacles by implanting the multifocal intraocular lens ReSTOR. METHODS: A Markov model was created to compare a patient cohort implanted with ReSTOR at age 45 years, with a cohort using spectacles, until death or age 100 years. Prevalence rates of patients not requiring spectacles after surgery were obtained from clinical trials. Resource utilisation included implant surgery, spectacles, visits to ophthalmologists and optic centres, transport and time lost by patients. Economic perspectives were those of society and sickness funds. Mortality rates were introduced into the model. Cataract surgery was allowed just for the spectacles-only cohort. RESULTS: Rate of spectacle independence was fixed at 80% for ReSTOR. When time spent to care for refraction was not taken into account, lifelong ReSTOR cost was higher than spectacles in all countries (293 euro; 1013 euro), according to the societal perspective. When time was included, cost saving was observed in Italy (136 euro) and the incremental cost to be free of spectacles comprised between \[euro]11 and \[euro]816. According to the NHS perspective, ReSTOR is a cost saving strategy (-274 euro; -605 euro). CONCLUSIONS: At a 3% discount rate, savings achieved by liberating patients from spectacles counterbalanced partially the initially higher cost of ReSTOR according to the society perspective. ReSTOR could be considered as cost-effective in the four countries provided that the willingness to pay of patients to be free of spectacles would be lower than 23.65 euro/year.

Costs and persistence of carbonic anhydrase inhibitor versus alpha-2 agonists, associated with beta-blockers, in glaucoma and ocular hypertension: an analysis of the UK-GPRD database.

OBJECTIVE: To compare the effectiveness and associated costs of carbonic anhydrase inhibitors + beta-blocker versus alpha-2 adrenergic agonists + beta-blocker in glaucoma therapy, as documented by The United Kingdom General Practitioner Research Database (UK-GPRD). RESEARCH DESIGN: Patient chart analysis. METHODS: Patient records were screened for diagnoses of ocular hypertension or glaucoma, and for surgery, laser therapy or medication specific to glaucoma. Selected patients were those prescribed either carbonic anhydrase inhibitors + beta-blocker or alpha-2 adrenergic agonists + beta-blocker. Treatment failure was defined as a glaucoma prescription change, i.e. addition, cessation or replacement of medication, surgery or laser therapy. Times to treatment failure were compared with an adjusted Cox model. MAIN OUTCOME MEASURES: Treatment persistence and cost. RESULTS: Included patients were those treated with either carbonic anhydrase inhibitors + beta-blocker (n = 5581) or alpha-2 adrenergic agonists + beta-blocker (n = 1164). The average age at diagnosis was 68.1 years and 48.2% were male. Treatment failure at one year was significantly (p < 0.001) less frequent after carbonic anhydrase inhibitors + beta-blocker (57% of patients) than after alpha-2 adrenergic agonists + beta-blocker (64.3%). The hazard ratio for failure was lower (0.82: p < 0.0001) with carbonic anhydrase inhibitors + beta-blocker following adjustment for age, gender, comorbidities and duration of follow-up. Adjusted annual costs of glaucoma management were pound 348.04 for carbonic anhydrase inhibitors + beta-blocker and pound 356.80 for alpha-2 adrenergic agonists + beta-blocker. CONCLUSIONS: According to UK-GPRD information, glaucoma therapy with carbonic anhydrase inhibitors + beta-blocker is more persistent than with alpha-2 adrenergic agonists + beta-blocker at a similar cost.

Costs and effectiveness of travoprost versus a dorzolamide + timolol fixed combination in first-line treatment of glaucoma: analysis conducted on the United Kingdom General Practitioner Research Database.

OBJECTIVE: To compare the effectiveness and associated costs of travoprost versus a fixed combination of dorzolamide + timolol as first-line therapy for glaucoma according to data collected by the United Kingdom General Practitioner Research Database (UK-GPRD). METHODS: Patients with a diagnosis of ocular hypertension, glaucoma, or who had been treated topically by surgery or laser therapy were selected. Patients starting first-line treatment with travoprost or a fixed dorzolamide + timolol combination were included. Times to treatment failure were compared with an adjusted Cox model. MAIN OUTCOME MEASURES: Cost and treatment failure defined as a prescription change (adding or removing a topical treatment, or initiating laser therapy or surgery). RESULTS: 56 612 patients were extracted from the database and 39 808 patients received at least one topical prescription for IOP-lowering (intraocular pressure) therapy. Of these, 639 were treated with travoprost and 387 with dorzolamide + timolol, as first-line therapies. No significant difference was found between patient characteristics. Patients were aged 70.0 years and 48.5% were male. At 1 year, treatment failure was experienced by 30.4% of patients receiving travoprost and 49.4% receiving dorzolamide + timolol (p < 0.001). The hazard ratio for failure was 0.79 (p < 0.03) less with travoprost, after adjusting on age, gender, comorbidities and duration of follow-up. Adjusted annual costs of glaucoma management were significantly (p < 0.001) lower with travoprost ( pound198.31) than with dorzolamide + timolol ( pound312.21). CONCLUSION: This retrospective costs and consequences analysis study showed that travoprost is more efficient than dorzolamide + timolol as first-line therapy for glaucoma patients. Patients continued longer with first-line treatment when prescribed travoprost at a lower cost.

Effects of dyskinesias in Parkinson's disease on quality of life and health-related costs: a prospective European study.

The treatment of Parkinson's disease (PD) with l-DOPA leads to involuntary movements (dyskinesias). This 6-month observational study in three European countries in PD patients with various degrees of motor complications examined the effects of dyskinesias on the quality of life (QoL) of patients and health care costs. Retrospective and prospective health economic data were collected, and QoL of patients was measured using the Short Form-36 (SF-36) and the PD Quality of Life (PDQL) Scale. Regression analysis was used to estimate the adjusted effects of dyskinesias on QoL and costs, whilst accounting for the potentially confounding effects of disease progression, motor fluctuations and country. Increasing dyskinesia scores on either the Unified PD Rating Scale or the Goetz Dyskinesia Rating Scale were associated with significant reductions in QoL scores on the SF-36 and PDQL Scale. Increasing dyskinesia severity was also associated with increased depression scores on the Montgomery-Asberg Depression Rating Scale along with significant increases in health care costs. The effects of dyskinesia on QoL, depression and costs decreased but remained significant after adjustment for the confounding effects of disease progression and motor fluctuations. In conclusion, dyskinesias may adversely affect QoL and increase health care costs in patients with PD. Future studies should evaluate the potentially beneficial effects in terms of QoL and health care costs of strategies to delay the onset of, or the treatment of, dyskinesias.

Socioeconomic aspects of laser in situ keratomileusis, eyeglasses, and contact lenses in mild to moderate myopia.

PURPOSE: To compare the societal costs and consequences of 3 strategies to correct mild to moderate myopia: laser in situ keratomileusis (LASIK), eyeglasses, and contact lenses (CLs). SETTING: Instituto Oftalmológico de Alicante, Alicante, Spain. METHODS: A Markov model was set up to compare the present value of LASIK, eyeglasses, and CLs. A structured questionnaire was administered to 40 consecutive patients with mild to moderate myopia to collect resource information including direct medical and nonmedical costs as well as indirect costs (transportation, time spent, hotel, eyeglasses, CLs, LASIK, cleaning products, visits to ophthalmologist/optometrist/optical center, and adverse events linked to LASIK and CLs). The time period ranged from 10 to 30 years with a 5% discount rate. The Spanish population was used as the basis for the economic data. Full sensitivity analyses were conducted. RESULTS: Based on the time period, LASIK saved from 18 to 278 km in distance to care centers compared with eyeglasses and from 405 to 1436 km compared with CLs. The time to care for visual acuity was similar between LASIK and CLs, but up to 1180 additional hours were spent by CL users. Laser in situ keratomileusis saved from 4.69 to 12.07 eyeglasses and from 28 to 84 eyeglass cleaning packs. With LASIK, there were 18 to 50 visits to the optical center compared with 41 to 117 visits with CLs. Laser in situ keratomileusis saved 4.7 to 12.2 visits to correct visual acuity compared with eyeglasses and CLs. It prevented 95 to 295 per 10 000 cases of CL-related keratitis. Contact lenses were always more costly than LASIK, which was always more costly than eyeglasses. The 2 sensitivity parameters were time period and discount rate. CONCLUSIONS: Laser in situ keratomileusis was less costly than CLs and more expensive than eyeglasses, although the potential nonmonetary benefit of LASIK over eyeglasses was not taken into account.

The epidemiology, economics and quality of life burden of age-related macular degeneration in France, Germany, Italy and the United Kingdom.

Age-related macular degeneration (AMD) is a major public health issue, but little is known about the economics of the disease. This contribution describes the epidemiology and the economics of AMD in four European countries: France, Germany, Italy and the United Kingdom (UK). We reviewed published information on AMD, including guidelines, official statistics, and local literature and interviewed AMD experts. All available health-related quality of life studies (HRQoL) on AMD were also reviewed. Data collection focused on epidemiology, medical management and resource use (both medical and non-medical items). Prevalence of AMD among persons older than 65 years is 8% and increases with age. There are two forms of the disease: atrophic (80-85% of AMD cases) and exudative, which is characterised by choroidal neovascularisation (CNV; 15-20% of AMD cases). No treatment for the atrophic form is available. Laser photocoagulation is the mainstay of treatment for CNV, although less than 30% of persons with CNV can benefit from it. Photodynamic therapy (PDT), a new treatment for CNV, reduces the risk of vision loss in forms with predominantly visible lesions. Several other new procedures are also under development. Rehabilitation and low-vision aids are useful palliative interventions when there is a residual visual acuity. The yearly budget impact of AMD was found to be between 51.3 and 101.1 million euros in the four countries studied. Information on social services and resource use was scant and little is reported on the impact of AMD on HRQoL. Economic studies of AMD should be conducted in order to assist public health decision making.

Cost effectiveness of emedastine versus levocabastine in the treatment of allergic conjunctivitis in 7 European countries.

OBJECTIVE: To assess the cost effectiveness of emedastine, a new antihistamine, versus levocabastine in the treatment of acute allergic conjunctivitis (AAC) in Belgium, France, Germany, The Netherlands, Norway, Portugal and Sweden. DESIGN AND SETTING: Randomised double-blind multicountry clinical trial followed by economic modelling from the treatment provider perspective. PATIENTS: A total of 221 patients (109 emedastine, 112 levocabastine) with AAC were included. METHODS: The clinical trial compared the efficacy and safety of emedastine 0.05% and levocabastine 0.05%, both twice daily, for 42 days, using ocular redness, itching, days without symptoms and clinical failure as outcome measures. The cost of first-line treatment failure, including visits, drugs and laboratory examinations, was established in each country from a panel of ophthalmologists and general practitioners. Full sensitivity analyses were conducted. RESULTS: From day 7 to 42, patients treated with emedastine had less itching (p < 0.001) and less redness (p < 0.001). The failure rate was 10% less (p < 0.02) with emedastine and patients treated with emedastine had an incremental 8.5 days (p < 0.01) without symptoms. Emedastine and levocabastine were equally well tolerated. In all European countries, the cost of failure was lower with emedastine. Emedastine was found to be economically dominant relative to levocabastine, i.e. more effective and less expensive, in Belgium, Germany, Portugal and Sweden; in France, The Netherlands and Norway the incremental cost was low (less than 1 euro per additional symptom-free day). CONCLUSION: Through a model based on a randomised clinical trial and cost estimates of treatment failure derived from practitioner interviews, emedastine is a cost-effective treatment of AAC.

Diagnosis related group costs in a regulated environment. A note about their economic interpretation.

The availability of the Diagnosis Related Group (DRG) system for determining hospital costs in some European countries has encouraged its use in pharmacoeconomic evaluations. The DRG system was developed in the US to provide data for prospective payments for hospitals. However, the financing of hospitals in some European countries is still based on the so-called 'global budget' approach. Therefore, results of pharmacoeconomic studies involving hospitals financed by the 'global-budget' approach in which DRG costs have been used require careful consideration. The main points to consider are: (i) that most of the cost components constituting the DRGs are in fact charges fixed by the government. This cost-charge ratio varies significantly across different DRGs, altering economic consequences when cost-shifting between DRGs; (ii) that there is rarely a perfect concordance between attributable cost (as proposed by the DRGs) and the definition of variable cost (as defined in economic evaluations); (iii) from the Sickness Fund's point of view, the way DRGs could be interpreted is rather unclear: financing or bench-marking?; and (iv) the perspective of DRG cost is a mixed patient-hospital perspective which is neither the societal nor the health insurance perspective generally used in pharmacoeconomic evaluations. In conclusion, the use of DRG costs is a major improvement for pharmacoeconomic evaluation. However, many hypotheses still need to be made in these studies, depending on the economic perspective of the study. Therefore, the results of pharmacoeconomic studies should be considered and discussed in line with the national financing system of the hospitals involved.

[Epidemiology and economics of chemotherapy combinations in the treatment of advanced breast cancer]. / Epidémiologie et économie des associations de chimiothérapies dans le traitement du cancer du sein métastasé.

125 oncologists, taken at random from a French professional list, followed up a cohort of 836 patients suffering from advanced breast cancer and treated by chemotherapy. The following data were collected prospectively: socio-demographics of patients and practitioners, disease history, characteristics of one chemotherapy cycle (type, utility and cost). A total of 89 chemotherapy combinations were described during the first-line treatment, independently of doses, eight combinations representing 70 per cent of all the prescriptions. No statistically significant differences were found when comparing the utility of the most often used combinations. Chemotherapy was the main cost driver of administration, rising to 90 per cent of the total cost when using taxans, followed by CSF. The cost price of taxan administration was twice to three times that of FEC or vinorelbine associations. These differences were poorly taken into account by the French budget allocation system as based on Diagnosis Related Groups.

Economic assessment of a maintenance treatment strategy in prevention of recurrent depressive disorder.

OBJECTIVE: To compare the 12-month cost-effectiveness of milnacipran in maintenance treatment of depression to that of medical follow-up without antidepressant. METHOD: A Markov model with transition probabilities from a double blind clinical trial demonstrating the prophylactic efficacy of milnacipran was used. Other parameters were obtained from published sources. RESULTS: Base-case incremental cost for preventive treatment was 1,191 FF. It was reduced to 685 FF when using a 25% hospitalization rate in case of recurrence. Patients with a high initial response had extra cost of 191 FF and cost-utility was estimated to be 23,875 FF per QALY gained. For those patients, using a 25% hospitalization rate in case of recurrence, costs were lower at 1,174 FF and preventive strategy was dominating. CONCLUSION: Cost of maintenance therapy is partially balanced by the gain from recurrence prevention. It should be focused on patients with few residual symptoms or a high probability of hospitalization in case of recurrence.

[Clinico-economic assessment of milnacipran in the prevention of depressive episodes]. / Evaluation médico-économique de milnacipran dans la prévention des épisodes dépressifs.

The objective of this study was to evaluate, for patients at risk of a new depressive episode, the net cost of maintenance therapy with milnacipran compared with a symptomatic treatment of further episodes. Using clinical decision analysis techniques, a Markov-state transition was constructed to estimate the 12 months direct costs of the two therapeutic strategies. Model construction and probabilities for performing the analysis were primarily based on a controlled phase III clinical trial demonstrating the prophylactic efficacy of milnacipran compared to placebo. Others parameters and unit costs were obtained from published sources. For each group (maintenance and episodic treatment groups), the model simulated the clinical evolution of patients on 6 successive 2-months cycles. Costs were affected for each health state period (remission, depression, abandonment of health care, suicide). The baseline analysis showed the mean costs per patient and year were 627 FF (105 US$) higher for maintenance treatment. Sensitivity analysis suggested that costs were equal under a 25% rate of hospitalization hypothesis for a depressive episode. Maintenance costs were 1,587 FF (265 US$) lower than episodic treatment costs for depressed subjects with a good initial response to milnacipran (HDRS-21 score at remission < 5); this economic benefit remained under a lower rate of hospitalization hypothesis (12%). Based on the study assumptions, maintenance treatment with milnacipran appears to be clinically and economically justified for patients at high risk of hospitalization when having a recurrence, and even more for patients with an excellent initial acute response.

Comparison of the cost-effectiveness of milnacipran (a SNRI) with TCAs and SSRIs: a modeling approach.

A simulation model based on the theory of clinical decision analysis was used to compare outcomes and costs when treating patients with major depressive episodes using either a selective serotonin re-uptake inhibitor (SSRI) or a tricyclic antidepressant (TCA), in comparison with milnacipran (a serotonin), and a norepinephrine re-uptake inhibitor (SNRI). The clinical data used were taken from published meta-analyses. This analysis supports: (1) a comparable efficacy of milnacipran and TCA with a better tolerance; and, (2) an advantage of milnacipran over SSRI for efficacy with a comparable tolerance. Based on these findings, a decision tree was constructed with the assistance of a panel of psychiatrists in order to provide a model of usual clinical practice. Estimates not available from clinical studies were obtained either from literature analysis or from the panel. Economic appraisal was performed according to the viewpoint of the French national sickness fund (sécurité sociale), and expenditure assessment was limited to direct costs (hospitalizations, antidepressant medications, visits, and laboratory tests). The results suggest that milnacipran is a cost-effective alternative: the expected cost of treatment per depressive episode is lower than either a French representative panel of TCAs (a saving of 288 FF), or SSRIs (a savings of 961 FF). The expected length of clinical remission is slightly higher than comparators. The robustness of these findings was supported by sensitivity analyses.

Use of diagnostic clusters to assess the economic consequences of rhinopharyngitis in children in Italy and France during the winter. Rhinitis Survey Group.

To determine how practitioners diagnose rhinopharyngitis (RP), we conducted a longitudinal, multicenter study of a cohort of 900 children, collecting medical and economic data without interfering with usual medical practice during the winter of 1996-1997 in France and Italy. All ear, nose, and throat (ENT) infections were described clinically; data on the consumption of medical items (physician visits, drug treatment, hospitalization, physiotherapy, preventive treatment, laboratory tests, roentgenograms, and outpatient procedures) were collected to estimate the cost of caring for patients with RP. The mean age of the children was 28.0 months, and the ratio of males to females was approximately 5 to 4. Patients had had a mean 4.1 episodes of RP the previous year and 1.4 episodes of acute otitis media (AOM). There were no marked differences in the children's characteristics between France and Italy. During the winter of the study, this population experienced 4.26 episodes of ENT infection, of which 73.5% were documented at the study sites. Seven homogeneous groups of RP were found, 2 of them each representing <4% of the overall population. One group presented with otalgia, although the diagnosis of AOM was not recorded by the physician. In 4 groups, the presence of nasal discharge plus cough (without otalgia) was used to make the diagnosis. Medical item consumption varied by country and by group of RP, mainly in the prevailing choice of antibiotics. The difference in duration of treatment was not statistically significant. As a consequence, the costs of caring for patients with RP varied greatly, RP with AOM being the most costly. Last, prognostic factors for costly episodes of infectious ENT were identified. The population at risk included young children who had had AOM episodes during the previous winter, had a first episode of AOM before 6 months of age, had a history of AOM associated with effusion, or attended a community-based child care facility. Therefore, clinical trials aimed at demonstrating cost-effectiveness of prophylaxis should focus on this population.

Cost effectiveness of immunoprophylaxis in the prevention of recurrent infectious rhinitis in adults.

OBJECTIVE: Recurrent infectious rhinitis (RIR) is a frequent disease among adults and constitutes an economic burden for National Sickness Funds (NSF) that might be prevented by immunostimulant therapy. Cost effectiveness of preventive methods should be documented. The aim of this study was to determine whether the cost of treating patients with ribosomal vaccine (Ribomunyl), an immunostimulant therapy, could be offset by the savings associated with avoided RIR episodes. DESIGN AND SETTING: Using a 'piggy-back' approach, an economic analysis was conducted based on a placebo-controlled clinical trial of 327 patients with at least 3 episodes of RIR in the past year. Patients were recruited during September and October 1994 through 50 French and 2 Belgian specialists (ear, nose and throat; ENT) and were randomised to receive ribosomal vaccine or placebo for a 6-month period covering the entire winter season. Two economic perspectives were analysed: (i) the French NSF; and (ii) the patient (i.e., considering copayments which are not reimbursed by the NSF). MAIN OUTCOME MEASURES AND RESULTS: The placebo-controlled clinical trial demonstrated a significant decrease (p < 0.001) of more than 30% in the cumulative number of RIR episodes with ribosomal vaccine during the 6-month study period. In general, patients receiving the active treatment tolerated it well. Data were collected on the use of medical services (e.g. number of physician visits), antibacterial and other drug courses, as well as the number of sick-leave days for the study participant. Patients treated with ribosomal vaccine visited their general practitioner (GP) less frequently (mean reduction of 33%), had fewer days of antibacterial use (mean reduction of 3.5 days) and took fewer sick-leave days (mean reduction of 6.3%). CONCLUSIONS: Overall, the cost of prevention with ribosomal vaccine was offset by the savings to both the French NSF and to patients (in terms of out-of-pocket expense). Indeed, ribosomal vaccine was deemed to be a cost-saving agent in the prevention of RIR in the French healthcare setting, provided that it is prescribed only for patients who are expected to develop at least 2 episodes of RIR in the coming year.