Aqueous intradermal low-dose house dust mite immunotherapy in tropical settings: a valid cost-effective approach for developing nations?

INTRODUCTION: Aqueous allergen injections, an effective and century-old technique, is considered a second-line approach in daily clinical practice. Inconveniences still surround conventional subcutaneous immunotherapy (SCIT) administration, such as a need for frequent injections, prolonged up-dosing schedules, elevated costs, and the unlikely possibility of a systemic reaction. The intradermal immunotherapy route (IDR) might favorably impact many of the aforementioned issues (Table 1). House dust mite (HDM) allergens are the main perennial sensitizers in the tropics, and as such, are solely employed in immunotherapy treatments. METHODS: We carried out a year-long real-life study in 25 perennial allergic rhinitis children, symptomatic on exposure to house dust, employing an intradermal low-dose allergen mix consisting of 50 ng of Dermatophagoides pteronyssinus/Dermatophagoides farinae and 120 ng of Blomia tropicalis, under a unique cost-wise protocol. Basal symptoms/signs and face Visual Analog Scale (fVAS) scores were recorded for 2 weeks and later compared with those registered throughout the 1-year treatment. Serum-specific IgG4 and IL-10 levels were employed in the assessment of the immune responses. RESULTS: Symptoms/signs and fVAS scores were significantly reduced from days 42 and 49, respectively, and remained so until treatment completion. Increases in specific IgG4's and IL-10 levels reflected significant immune responses. Injections were well tolerated and families reported improved health status (quality of life, QoL). CONCLUSIONS: A unique cost-effective immunotherapy alternative for deprived allergic communities in tropical settings is depicted; further research is needed.

Providing cost-effective care for food allergy.

OBJECTIVE: To review the cost-effectiveness of food allergy management strategies. DATA SOURCES AND STUDY SELECTIONS: A narrative review and synthesis of literature identified using a PubMed search of relevant articles describing cost-effectiveness evaluations of food allergy management. RESULTS: Screening at-risk infants for peanut allergy carries risk of overdiagnosis and is not cost-effective. Evidence suggests that cost-effective care could be better optimized by minimizing delay in oral food challenges for eligible patients, clarifying the role of precautionary allergen labeling, incorporating patient-preference sensitive care in activation of emergency medical services for resolved allergic reactions, and considering value-based pricing and school-supply models for epinephrine. Finally, the annual value-based cost (willingness to pay [WTP] $100,000/quality-adjusted life years [QALY]) of peanut immunotherapy has been estimated to be between $1568 and $6568 for epicutaneous immunotherapy (EPIT) and between $1235 and $5235 for probiotic with peanut oil immunotherapy (POIT), with each therapy showing more favorable cost-effectiveness with greater improvements in health utility, particularly if sustained unresponsiveness can be achieved. CONCLUSION: Many aspects of food allergy management are not cost-effective, and recent evaluations suggest a greater role for incorporating patient and family preferences into guideline-based and traditionally reflexive management decisions. Caregiver understanding of food allergy screening tradeoffs is critical, given that screening children before allergen exposure has significant costs and results in overdiagnosis, especially when oral food challenges are omitted from diagnostic algorithms. Cost-effectiveness analysis can help to identify important decision levers in patient management across a wide range of topics. Further research is needed to better understand health state utilities of specific patient populations.

Non-adherence to subcutaneous allergen immunotherapy: inadequate health insurance coverage is the leading cause.

BACKGROUND: To sustain the long-lasting beneficial effects of subcutaneous allergen immunotherapy, the recommended duration of treatment is 3 to 5 years. Nevertheless, many patients discontinue allergy injections prematurely and therefore might not appreciate the full therapeutic benefit. OBJECTIVE: To examine factors leading to premature discontinuation of subcutaneous allergen immunotherapy (cessation before completion of the recommended duration). METHODS: Patients who discontinued immunotherapy before the completion of the prescribed duration and received their final injection from January 2008 through September 2013 were contacted to identify the reason for stopping the allergy injections. Phase of treatment (escalation or maintenance) was used to measure the duration of treatment at the time of cessation and patients were grouped accordingly. RESULTS: The study population consisted of 555 patients with allergic rhinitis and/or asthma who terminated immunotherapy prematurely. Two hundred thirteen (38%) were men and 342 (62%) were women. The following reasons were cited by patients for non-adherence to immunotherapy: requirement of copayment for allergy injections and/or payment for allergen extract by their health insurer (40%); inconvenience of travel (15%); change of residence (8%); concurrent health problems (5%); patient-perceived ineffectiveness (4%); patient-perceived lack of need to continue immunotherapy (2%); adverse effects from injection (local reaction 1%; systemic allergic reaction 0.5%); and trial of alternative medicine (0.1%). The remaining 24.4% did not provide a reason for discontinuation. CONCLUSION: Of the various factors, inadequate reimbursement for allergen extract and allergy injections by health insurers is the most common reason cited for non-adherence to subcutaneous allergen immunotherapy.

Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects. OBJECTIVE: Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation. METHODS: We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate. RESULTS: Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were €3800, an amount that was largely misspent. CONCLUSION: Real-life persistence is better in SCIT users than in SLIT users, although it is low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance.

Treating allergic rhinitis by sublingual immunotherapy: a review.

OBJECTIVE: Allergic rhinitis (AR) is a disease with high and increasing prevalence. The management of AR includes allergen avoidance, anti-allergic drugs, and allergen specific immunotherapy (AIT), but only the latter works on the causes of allergy and, due to its mechanisms of action, modifies the natural history of the disease. Sublingual immunotherapy (SLIT) was proposed in the 1990s as an option to traditional, subcutaneous immunotherapy. MATERIAL AND METHODS: We reviewed all the available controlled trials on the efficacy and safety of SLIT. RESULTS AND CONCLUSION: Thus far, more than 60 trials, globally evaluated in 6 meta-analyses, showed that SLIT is an effective and safe treatment for AR. However, it must be noted that to expect clinical efficacy in the current practice SLIT has to be performed following the indications from controlled trials, that is, sufficiently high doses to be regularly administered for at least 3 consecutive years.

Cost effectiveness analysis of immunotherapy in patients with grass pollen allergic rhinoconjunctivitis in Germany.

OBJECTIVES: An economic evaluation was conducted to assess the outcomes and costs as well as cost-effectiveness of the following grass-pollen immunotherapies: OA (Oralair; Stallergenes S.A., Antony, France) vs GRZ (Grazax; ALK-Abelló, Hørsholm, Denmark), and ALD (Alk Depot SQ; ALK-Abelló) (immunotherapy agents alongside symptomatic medication) and symptomatic treatment alone for grass pollen allergic rhinoconjunctivitis. METHODS: The costs and outcomes of 3-year treatment were assessed for a period of 9 years using a Markov model. Treatment efficacy was estimated using an indirect comparison of available clinical trials with placebo as a common comparator. Estimates for immunotherapy discontinuation, occurrence of asthma, health state utilities, drug costs, resource use, and healthcare costs were derived from published sources. The analysis was conducted from the insurant's perspective including public and private health insurance payments and co-payments by insurants. Outcomes were reported as quality-adjusted life years (QALYs) and symptom-free days. The uncertainty around incremental model results was tested by means of extensive deterministic univariate and probabilistic multivariate sensitivity analyses. RESULTS: In the base case analysis the model predicted a cost-utility ratio of OA vs symptomatic treatment of €14,728 per QALY; incremental costs were €1356 (95%CI: €1230; €1484) and incremental QALYs 0.092 (95%CI: 0.052; 0.140). OA was the dominant strategy compared to GRZ and ALD, with estimated incremental costs of -€1142 (95%CI: -€1255; -€1038) and -€54 (95%CI: -€188; €85) and incremental QALYs of 0.015 (95%CI: -0.025; 0.056) and 0.027 (95%CI: -0.022; 0.075), respectively. At a willingness-to-pay threshold of €20,000, the probability of OA being the most cost-effective treatment was predicted to be 79%. Univariate sensitivity analyses show that incremental outcomes were moderately sensitive to changes in efficacy estimates. The main study limitation was the requirement of an indirect comparison involving several steps to assess relative treatment effects. CONCLUSION: The analysis suggests OA to be cost-effective compared to GRZ and ALD, and a symptomatic treatment. Sensitivity analyses showed that uncertainty surrounding treatment efficacy estimates affected the model outcomes.

[Role of allergen-specific immunotherapy (desensitization) for the treatment of allergies in Germany. Current situation]. / Die spezifische Immuntherapie (Hyposensibilisierung) mit Allergenen zwischen wissenschaftlichem Fortschritt und medizinischer Versorgungsrealität. Eine Standortbestimmung.

Allergen-specific immunotherapy (SIT, desensitization) is applied monthly with subcutaneous injections (SCIT) or sublingually (SLIT) with droplets or tablets on a daily basis. Numerous immunological changes during SIT induce long-lasting tolerance. Efficacy has been demonstrated by a number of controlled studies for insect venom hypersensitivity (SCIT), allergic rhinoconjunctivitis (SCIT, SLIT particularly in grass pollen allergy), and allergic asthma (SCIT > SLIT). SIT is indicated in children and adults with severe allergic reactions from insect venoms (e.g., bee, wasp) or cumbersome symptoms from pollen, house dust mites or mold allergens and proven immediated-type allergy. Contraindications must be considered individually. SIT is performed for 3 years, in case of venom allergy 3-5 years. Severe systemic reactions are rare after SCIT. After SLIT rather local allergic symptoms of short duration occur in the mouth and throat. At present, the number prescriptions for SIT has decreased due to inadequate reimbursement of allergy-related services (diagnostics, therapies, monitoring). In the future, inferior medical care of allergic patients in Germany is expected, who until now have benefited from the preventive effects of SIT (reduced risk of developing asthma and new allergic sensitizations).

[Basis to modify the immunotherapy regimen at the Allergy Service, General Hospital of Mexico]. / Fundamentos para modificar el esquema de la inmunoterapia en el servicio de Alergia del Hospital General de México.

BACKGROUND: In Mexico, the way allergen immunotherapy is performed has remained without changes for many years. Here we present the modifications that have been performed in the General Hospital of Mexico to make immunotherapy more effective. OBJECTIVE: To show the changes implemented to make immunotherapy faster and more effective by changing the volume of allergy vaccines from 5 or 10 mL to 3 mL, and the theoretical and practical support for the change. MATERIAL AND METHOD: The amount of protein delivered in each immunotherapy shot was computed to show how they change along the treatment. Results for schedules for 3, 5 and 10 mL were compared. RESULTS: Results showed serial rises and falls in protein amount injected every time a new vaccine flask starts to be used. However, in the case for 3 mL vaccines schedules, those changes are less pronounced. CONCLUSIONS: Due to these results we suggest a schedule of immunotherapy with 3 mL vaccines that allow getting the maintenance doses in a shorter time and at lower cost.

Cost-effectiveness of specific immunotherapy with Grazax in allergic rhinitis co-existing with asthma.

BACKGROUND: In the United Kingdom, approximately 10.8 million people suffer from asthma, placing an economic burden on the society of more than 2 billion pounds sterling per year. For allergic asthma, treatment options consist of allergen avoidance, symptomatic treatment and allergen-specific immunotherapy (SIT). Only SIT addresses the underlying cause of the disease, reducing symptoms and offering the potential for long-term improvement. Grazax--the first tablet-based SIT--is indicated for the treatment of patients with grass pollen-induced rhinoconjunctivitis, including those with co-existing asthma. OBJECTIVE: To assess the cost-effectiveness of Grazax in patients with rhinoconjunctivitis and co-existing asthma. METHODS: A prospective pharmacoeconomic analysis was carried out as part of a multinational clinical trial assessing the efficacy of Grazax (n = 79) compared with placebo (n = 72). Both groups had access to symptomatic medication; thus the placebo group represented current standard care. Pooled data on health resource use, productivity loss because of absence from work and quality of life (Quality Adjusted Life Years, QALYs) were collected in the trial. Reduced productivity at work was estimated from the literature. A societal perspective was adopted with a 9-year time horizon. The NHS price of Grazax of 2.25 pounds sterling per tablet was used. RESULTS: The QALY gain was significantly higher for patients treated with Grazax than the placebo group receiving symptomatic medication alone (0.197 discounted QALYs gained 9 years into the future - equal to an extra 72 days of perfect health over 9 years). The levels of resource use and productivity loss were higher for the placebo group. As a result, the cost per QALY gained with Grazax was 4319 pounds sterling , which is highly cost-effective. Price sensitivity analyses demonstrated that Grazax remained cost-effective up to a tablet price of 5.07 pounds sterling . CONCLUSION: SIT with Grazax is a cost-effective strategy compared with standard management of patients with rhinoconjunctivitis and co-existing asthma.

Economic evaluation of sublingual vs subcutaneous allergen immunotherapy.

BACKGROUND: Sublingual allergen immunotherapy (SLIT) is a commonly used alternative route of administration to standard subcutaneous immunotherapy (SCIT) in Europe. Despite its wide use, the cost-effectiveness of SLIT vs SCIT has not been well established. OBJECTIVE: To evaluate the cost and effectiveness of SLIT compared with SCIT in patients with allergic rhinoconjunctivitis during a 3-year specific allergen immunotherapy (SIT) from a third-party payer's, a patient's, and society's perspectives. METHODS: We performed an open-label randomized clinical trial of patients receiving SLIT (n = 19), patients receiving SCIT (n = 23), and a control group (n = 22). The outcome measures were Rhinoconjunctivitis Quality of Life Questionnaire score, visual analog scale score, symptomatic medication reduction, and direct and indirect costs. RESULTS: SLIT offered clinical benefits to patients comparable to those provided by SCIT. From the perspective of a third-party payer, the total average direct medical cost per patient of 3-year SIT was estimated at Euro 416 vs Euro 482 in the SLIT and SCIT groups, respectively. A patient who received SLIT paid less than a patient who received SCIT for all out-of-pocket costs (Euro176 for SLIT vs Euro 255 for SCIT) but more for sole allergen extracts (Euro 72 for SLIT vs Euro 55 for SCIT). When both direct and indirect costs were considered, the 3-year SIT expenditures per patient reached Euro 684 vs Euro 1,004 in the SLIT and SCIT groups, respectively. CONCLUSIONS: SLIT represents a less expensive alternative relative to subcutaneous administration from all perspectives. However, from a patient's perspective, SCIT offers a less expensive alternative for patients who do not experience loss of income and travel costs associated with treatment.

[Influence of the difference in the pollen count on medical costs in an allergen-specific immunotherapy for Japanese cedar pollinosis].

BACKGROUND: We studied medical economic efficacy and influence by the different number of pollen scattering in patients treated with allergen-specific immunotherapy for Japanese cedar pollinosis. METHODS: We calculated medical treatment costs and the medicine expense from medical records in eighteen cedar pollinosis patients treated with allergen-specific immunotherapy (IT-G) and with medications (M-G). We examined with the same patients for three years of different pollen scattering, mass scattering year (2005), moderate scattering year (2003), a few scattering year (2004). Furthermore, satisfaction of treatment and symptom score measured by visual analog scale in both subjects was studied in a mass scattering year. RESULTS: Total medical costs at hospital was cheaper in IT-G than in M-G. The result was depended on prescribed medical costs. In addition, prescribed medicine agents and total medical costs did not increase by the mass scattering year of pollen. Satisfaction of treatment and symptom score in IT-G was better than that in M-G. CONCLUSION: Immunotherapy had a benefit on a medical economy.

Grazax: an oral vaccine for the treatment of grass pollen allergy (hay fever).

Grazax is a self-administered, once-daily, tablet-based vaccine that offers an alternative to allergy shots for adults with grass pollen allergy (hay fever). (2) Evidence from three randomized controlled trials indicates modest improvements in hay fever symptoms, with reduced use of medication to control symptoms (rescue medication use) in adults who took Grazax compared with placebo. No studies have compared Grazax with injection-based allergen immunotherapy. (3) It is not yet known if patients treated with Grazax will have a sustained tolerance to grass pollen following treatment discontinuation. (4) Adverse effects of Grazax are generally mild to moderate local allergic reactions of short duration, and include itching and swelling of the mouth, and throat irritation. (5) If Grazax becomes widely prescribed and is covered by provincial drug plans, the costs to the Canadian health care system and the impact on allergy specialist services could be substantial.

Cost-effectiveness of GRAZAX for prevention of grass pollen induced rhinoconjunctivitis in Southern Europe.

BACKGROUND: Allergic rhinoconjunctivitis is a global health problem. Around 14 million people in Spain, France, Italy, and Austria suffer from grass pollen induced allergic rhinitis. Standard care only provides symptoms relief, while allergen specific immunotherapy (SIT) treats the underlying cause of the disease. Grazax from ALK-Abelló is a new, tablet-based, effective route of SIT for home treatment. The objective was to assess the cost-effectiveness of Grazax in four Southern European countries. METHODS: A prospective pharmacoeconomic analyses was carried out alongside a multinational, clinical trial measuring the efficacy of Grazax. Pooled data on resource use and health outcomes were collected. A societal perspective was adopted, and the analysis had a nine-year time horizon. The primary outcome measure was quality adjusted life years (QALYs). RESULTS: Grazax was superior to standard care for all efficacy endpoints, including QALYs gained, and resulted in significantly less use of rescue medication and fewer hours missed from work. Grazax was cost-effective for all countries for an annual price in the range of 1500 euros - 1900 euros. The result was improved by inclusion of future costs of asthma and exclusion of Spanish trial centers which experienced an exceptionally low pollen season. CONCLUSION: The analysis illustrates that allergen SIT with Grazax for grass pollen induced rhinoconjunctivitis is a cost-effective intervention in Southern Europe.

A cost-effectiveness analysis of immunotherapy with SQ allergen extract for patients with seasonal allergic rhinoconjunctivitis in selected European countries.

BACKGROUND: Seasonal allergic rhinoconjunctivitis can, for some people, reduce quality of life and the ability to cope with everyday tasks. SCOPE: In this paper we investigate the cost-effectiveness of immunization therapy with Alutard SQ (ASQ) and compare the cost-effectiveness in countries where the therapy has been in use in order to assess the impact of national therapeutic practices on the results of health economic assessments. Data are obtained from a clinical trial carried out in 2001-2002. To evaluate the cost-effectiveness of immunization we have added data on resource use in Austria, Denmark, Finland, Germany, The Netherlands, and Sweden. FINDINGS: The computations result in cost-effectiveness ratios for allergen immunization between 10,000 euros and 20,000 euros per QALY even without provision for indirect costs, and achieving dominance in most countries where indirect costs have also been taken into account. The country comparisons show that the direct cost of administrating the up-dosing and maintenance differs considerably between countries, and that the cost of medical staff is substantial, constituting in most cases more than half of the direct costs of the immunization therapy. CONCLUSION: The study shows that immunotherapy with SQ allergen extract is cost-effective in a wide range of national environments, and that cost-effectiveness differences by country are largely a result of different practices in the up-dosing phase.

Pharmacoeconomics of allergen immunotherapy compared with symptomatic drug treatment in patients with allergic rhinitis and asthma.

Only a few studies analyzed the pharmacoeconomics of allergen immunotherapy compared with drug treatment in subjects with allergic rhinitis and asthma. This study was aimed at evaluating whether allergen immunotherapy has an economic advantage on standard antiallergic drugs in patients with pollen-induced rhinitis and asthma. Thirty patients with rhinitis and asthma caused by Parietaria pollen were included in the study, 20 (11 men and 9 women; mean age, 35.45 +/- 10.45 years) were treated with subcutaneous immunotherapy by a Parietaria judaica extract (Alustal, Stallergénes, Antony, France) by a conventional build-up schedule in 12 weeks and a maintenance treatment every 4 weeks for 3 years, and 10 (6 men and 4 women; mean age, 31.90 +/- 10.97 years) were treated with antiallergic drugs. Each patient was evaluated before starting the treatment and annually for 6 years in the pollen period of Parietaria by means of nose, eyes, and lung symptom scores, along with drug consumption registered in diary cards. In other specifically designated cards general practitioner's or specialist's visits, the number of desensitizing injections and the number of boxes of antiallergic drugs were registered. A significant difference in favor of immunotherapy plus drug treatment versus drug treatment alone was observed, reaching a cost reduction of approximately 15% the second year and 48% the third year, with a highly statistical significance that was maintained up to the sixth year, i.e., 3 years after stopping immunotherapy, when an 80% reduction was found. The net saving for each patient at the final evaluation corresponded to euros 623 (dollars 830)/year. These findings confirm some previous observations in studies from Germany and the United States that subcutaneous immunotherapy has significant economic advantages over antiallergic drug treatment in the long term.

Health-economic analyses of subcutaneous specific immunotherapy for grass pollen and mite allergy.

OBJECTIVE: To investigate the health and monetary consequences of treating allergy with specific immunotherapy (SIT) compared with symptomatic treatment/standard care among patients with grass pollen or mite allergy. METHODS: We performed an economic analysis based on 253 grass- and/or mite allergic patients who started SIT from 1.1.1996 to 1.1.2002 at the Allergy Unit, Aarhus University Hospital and at a specialist practice in Aarhus. Relevant data were collected before, during and after SIT treatment from the national health service based on each patient's personal identification number and medical records and from a specifically designed questionnaire. A cost-benefit analysis including direct and indirect costs before, during and after SIT was performed. In addition direct costs were related to the clinical effect (improvement in well-being) in the form of a cost-effectiveness analysis. RESULTS: The direct cost per patient/year before SIT (equivalent to standard care) was DKK 2,580. The investment in SIT was DKK 27,545 (in present values) per patient over a 4-year period. After SIT the cost was reduced to DKK 1,072 per patient/year. In the long term, prospective introduction of SIT incurred additional present-value direct costs of DKK 13,676 per patient treated and DKK 2,784 per patient/year of improved well-being. However, when indirect costs were included in the economic evaluation SIT was shown to be net beneficial. CONCLUSION: This study reveals that SIT is associated with initial resource investments and subsequent resource savings in the long term compared with standard care. When all consequences are measured in monetary terms, and assuming that sick days are associated with a loss of productivity, this analysis suggests that SIT increases societal welfare. This conclusion also holds if there is no loss of productivity.

Health-Economic analyses of subcutaneous specific immunotherapy for grass pollen and mite allergy

Objective: To investigate the health and monetary consequences of treating allergy with specific immunotherapy (SIT) compared with symptomatic treatment/standard care among patients with grass pollen or mite allergy. Methods: We performed an economic analysis based on 253 grass- and/or mite allergic patients who started SIT from 1.1.1996 to 1.1.2002 at the Allergy Unit, Aarhus University Hospital and at a specialist practice in Aarhus. Relevant data were collected before, during and after SIT treatment from the national health service based on each patient's personal identification number and medical records and from a specifically designed questionnaire. A cost-benefit analysis including direct and indirect costs before, during and after SIT was performed. In addition direct costs were related to the clinical effect (improvement in well-being) in the form of a cost-effectiveness analysis. Results: The direct cost per patient/year before SIT (equivalent to standard care) was DKK 2,580. The investment in SIT was DKK 27,545 (in present values) per patient over a 4-year period. After SIT the cost was reduced to DKK 1,072 per patient/year. In the long term, prospective introduction of SIT incurred additional present-value direct costs of DKK 13,676 per patient treated and DKK 2,784 per patient/year of improved well-being. However, when indirect costs were included in the economic evaluation SIT was shown to be net beneficial. Conclusion: This study reveals that SIT is associated with initial resource investments and subsequent resource savings in the long term compared with standard care. When all consequences are measured in monetary terms, and assuming that sick days are associated with a loss of productivity, this analysis suggests that SIT increases societal welfare. This conclusion also holds if there is no loss of productivity

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